Cellular immune deficiency with autoimmune hemolytic anemia in purine nucleoside phosphorylase deficiency. Immunologic and metabolic abnormalities were studied in a five year old boy with 0.07 per cent of normal erythrocyte purine nucleoside phosphorylase activity. The clinical course is characterized by severe autoimmune hemolytic anemia, a transient neurologic disorder with tremor and ataxia, and minor infectious illnesses. There is severe lymphopenia with decreased absolute numbers of T and B lymphocytes. Mitogen-stimulated blastogenesis is reduced, but response to allogeneic lymphocytes is normal. A monoclonal IgG protein is present. There is hypouricemia, elevated plasma inosine level, hypouricosuria and an increase in the urinary concentration of inosine and guanosine. The pattern of heterozygote distribution in the patient's family is compatible with an autosomal recessive trait in which heterozygotes are identifiable. In addition, the unusual laboratory and clinical manifestations of this patient illustrate the heterogeneity of the clinical syndrome associated with purine nucleoside phosphorylase deficiency.


Calcium binding by a myeloma protein.

Calcium binding by a myeloma protein. We describe a patient with immunoglobulin G (IgG)-kappa myeloma and severe, long-standing, asymptomatic hypercalcemia. Serum nonprotein-bound calcium concentration was 5.2 mg/dl (normal 4.2 to 5.0 mg/dl) at a time when total serum calcium concentration was 17.8 mg/dl. The patient's myeloma protein, IgGCAB, and Fab fragments of IgGCAB migrated more anodally when agarose gel electrophoresis was performed in the absence of calcium ion than when electrophoresis was performed in the presence of calcium ion; 60 other myeloma proteins did not demonstrate such behavior. Purified IgGCAB bound 1.5 calcium ions with a single dissociation constant of 1.2 X 10(-4) M. We speculate that the rare syndrome of myeloma and high protein-bound calcium is due to binding of calcium to variable regions of the myeloma antibody molecules.


Effect of dexamethasone on prolactin secretion in late pregnancy. It is established that PRL secretion is regulated by estrogens. Glucocorticoids, on the other hand, suppress estrogen secretion during pregnancy and may also inhibit PRL by direct hypothalamopituitary action. In this study PRL and estradiol were determined with specific radioimmunoassays in 14 women during gestational weeks 28 to 34 prior to, during, and following short-term intramuscular dexamethasone administration (12, 8, and 4 mg on three consecutive days) used for prophylaxis of RDS in preterm infants. There were no significant alterations in PRL serum concentrations; estradiol showed a significant drop (P less than 0.001) during all 3 days of treatment, returning to the pretreatment level on posttreatment day 1. The PRL and TSH responses to 200 micrograms of intravenous TRH on day 2 or 3 of dexamethasone treatment in six women during late pregnancy were not inhibited. Short-term dexamethasone treatment with pharmacologic doses does not suppress the physiologic secretion and release of PRL or the release induced by TRH during late pregnancy.


Pregnancy-associated ovarian refractoriness to gonadotropin: a myth. Ovulation was induced in three of five rhesus monkeys during midpregnancy using human menopausal gonadotropin/human chorionic gonadotropin therapy. No evidence of ovarian refractoriness to gonadotropic stimulation was found. It is concluded that cyclic ovarian function in these primates is suspended during gestation and into the puerperium because pituitary gonadotropin secretion is insufficient to support folliculogenesis.


Deposition of IgA in renal glomeruli of mink affected with Aleutian disease. The glomerular deposition of immunoglobulin (Ig) was studied in sapphire mink affected with terminal Aleutian disease (AD). Fluorescein conjugated Ig-class specific antiserums were used to evaluate and identify the glomerular Ig. Kidneys of all 28 mink with documented AD had deposits of IgA and beta 1 C in a capillary and mesangial distribution. Only 7 of 28 mink had demonstrable glomerular IgG and/or IgM. In addition, interstitial plasma cell infiltrates in 17 of 19 kidneys stained exclusively with anti-IgA. All antiserums used in this study were evaluated for Ig-class specificity by both gel diffusion and agarose-bead techniques. The striking Ig class restriction demonstrated for glomerular Ig deposition in AD is discussed in light of current knowledge of the pathogenesis of AD glomerulopathy.


The volar skin of primates: its frictional characteristics and their functional significance. Friction of volar skin on wood is not proportional to load in human beings and prosimians, but to load raised to a fractional power. This meets theoretical expectations for the frictional characteristics of convex elastic surfaces. Although this enables small clawless primates to cling to steeper slopes and larger vertical supports than would otherwise be possible, the magnitude of the effect is not great enough to overcome the disadvantages of clawlessness in climbing vertical or steeply-sloping tree trunks and branches. In human subjects, friction appears to be more nearly proportional to load than in small prosimians used as experimental subjects. It is suggested that this is due to the fact that the small animals have discrete, elevated volar pads. Pad coalescence in large primates may be an adaptation for increasing the power to which load must be raised to become proportional to friction; increasing this exponent yields more friction per unit of adduction force on supports that are small relative to the animals' dimensions and weights.


Case report. An autonomously functioning thyroid adenoma in a male with thyroxine-binding globulin excess. A male with thyroxine-binding globulin (TBG) excess and an autonomously functioning thyroid adenoma is presented. The problem of diagnosing hyperthyroidism in the presence of TBG excess is discussed. The utility of the thyrotropin-releasing hormone test (TRH) is emphasized.


Sexual activity of male rhesus monkeys introduced into a heterosexual group. Unfamiliar males were introduced during the breeding season to a stable heterosexual group of rhesus monkeys to determine how the presence of more dominant resident males affected their mating activity and how their entry was received by resident females. Initially, new males were allowed access to females under controlled conditions both in the presence and absence of resident males, simulating situations which may occur under natural conditions. Results indicated that the sexual activity, including ejaculation rate, of the new males was initially inhibited by the presence of more dominant, resident males, but these inhibiting properties did not carry over to periods when the resident males were absent and were diminished with time. Group females preferentially directed their behavior towards the new males throughout the study. These data suggest that although entry of new males into a stable group is at low rank, their subsequent reproductive success may not be reduced and that the association with resident females may facilitate male rhesus transfer between groups observed during the breeding season.


On the adaptive pattern of "Ramapithecus". A reconstruction of the adaptive pattern of the Miocene hominoid "Ramapithecus," supported by comparative data and morphological comparisons, is presented. It is based upon the completely known dentition, inferior portion of the face, and on the paleoecology and geographic distribution of "Ramapithecus" bearing deposits. The known adaptive and morphological patterns of the "Ramapithecus" species are almost indistinguishable from those of the contemporary species of Sivapithecus, which has taxonomic priority. The "Ramapithecus" species are therefore referred to Sivapithecus, a dryopithecine genus which apparently radiated throughout Eurasia and Africa during the Middle Miocene.


Correlates between locomotor anatomy and behavior in two sympatric of Lemur. Sympatric populations of Lemur catta and Lemur fulvus show major differences in their occupation of canopy forest levels. Lemur catta is usually found in the lowest levels of the forest, and uses the ground for travel over 65% of the time. Lemur fulvus uses the upper levels of the canopy forest and is observed on the ground in less than 2% of all observations. Comparison of hindlimb musculoskeletal anatomy show statistically significant differences in the lengths of the long bones and the height of the talus. Differences also occur in ranges of tibio-talar and mid-talar joint mobility. The details of insertion of the biceps femoris muscle are distinct in the two species as is the relative mass of muscle associated with flexion of the pedal digits, and flexion of th tibio-talar joint. The metric and morphological differences in the hindlimb anatomy of Lemur catta and Lemur fulvus are consistent with differences in habitat and substrate utilization.


Studies on the condition and structure of bone of the Saldanha fossil cranium. The external surface of the Saldanha cranium shows extensive exfoliation and cracking. In a few places remnants of the probable original bone surfaces can be observed. These are orange-brown in color, contrasting with the nearly white color of exposed deeper layers, and are subdivided into small segments with pits in their centers. Causes of the color differences are uncertain but merit investigation. The surface cracking and exfoliation probably result from weathering before fossilization. This conclusion is based on the observation that the endocranial surfaces show no such effects, despite the scattering of the cranial fragments at the time of discovery. A depressed fracture in the frontal bone indicates a heavy blow at or shortly after the time of death. This blow probably created some of the fragments, but there are also incomplete fracture cracks which may have resulted from the blow. Unresolved taphonomic problems include the manner in which the cranium held together after decay of soft tissues allowed weathering, and the manner in which the fragments were subsequently scattered. Chips from the cranial vault indicate that the outer table was very thick, tending to support recent proposals that the specimen and assoicated fauna and tools are from a considerably earlier time period than originally believed. The surface damage to the brow ridges gives information on the structure of deeper layers. These are lacking orientation, supporting the hypothesis that hominid brow ridges are not primarily a response to masticatory forces, but may afford protection for the eyes.


On a new australopithecine partial endocast. A newly discovered right parietal/temporal/frontal fragment from an australopithecine natural endocast is described and compared to other australopithecine endocasts. This specimen shows that the central sulcus was arched, rather than straight as previously believed, and reveals frontal lobe convolutions not preserved in other australopithecine endocasts.


Effect of ethanol on disaccharidases of hamster jejunal brush border membrane. This study was undertaken to investigate the effect of alcohol on the activity of jejunal disaccharidases (DS). The activity of DS in a preparation of purified brush border membrane of hamster jejunum was measured in the absence and in the presence (0.8 to 6.4% wt/vol) of ethanol. To compare the effect of alcohol on DS with its action on a brush border enzyme of a different group, we also measured the activity of alkaline phosphatase (AP) under similar conditions. Ethanol depressed the activity of sucrase, maltase, and lactase in a dose-dependent and time-dependent manner, but it stimulated the activity of AP. The ethanol-induced inhibition of DS was completely reversible. Kinetic studies indicate that ethanol depressed the Vmax and increased the Km of sucrase and lactase. The Vmax of maltase also decreased, but the Km of this hydrolase was not affected by ethanol. From the results of this study it would appear that acute exposure of the jejunal brush border to ethanol depresses the DS activity of the membrane and that (because the AP was not depressed) the ethanol-induced inhibition of DS is not the result of a general inhibition of all enzymes of the brush border.


Somatostatin effects on lower esophageal sphincter function. The effect of somatostatin (GH-RIH) infusion (2 microgram/min) on lower esophageal sphincter pressure (LESP) responses to various stimuli was evaluated in adult male baboons. GH-RIH infusion did not affect basal LESP, but did cause a significant suppression of mean immunoreactive insulin (IRI) to 5.8% of basal values (P less than 0.05). Pentagastrin IV caused dose-related increases in LESP that were unaffected by GH-RIH. Abdominal compression caused a threefold rise in LESP (P less than 0.005) both without and with GH-RIH. However, atropine (20 microgram/kg iv bolus) completely blocked this cholinergic LES pressure response. Intragastric alkali as well as intragastric glycine caused significant increases in LESP (P less than 0.05). These LESP responses to alkali and to glycine were totally abolished by GH-RIH. In conclusion, GH-RIH infusion in the baboon does not affect basal LESP, LES smooth muscle response to exogenous stimulation, nor a cholinergically mediated LES response. GH-RIH does inhibit the response of LESP both to intragastric alkali and to glycine by the apparent suppression of a hormonally mediated mechanism.


Vasopressin release and drinking induced by intracranial injection of angiotensin II in monkey. The effects of intracerebral injection of angiotensin II (AII) on both water intake and arginine-vasopressin (AVP) release were tested on unanesthetized rhesus monkeys (Macaca mulatta). Injection of 10(-10) mol of peptide was administered with a cannula microinjection system stereotaxically implanted into different diencephalic structures. The preoptic area, anterior part of third ventricle, caudate nucleus, and septum appeared to be the injection sites most effective in eliciting both drinking behavior and AVP release when the animal did not have access to water. On the contrary, when water was presented, AVP release was blocked after AII microinjections in the preoptic area and the third ventricle. No drinking was observed after microinjection in the supraopticus nucleus although AVP release was stimulated. These data suggest that AII might be effective in the regulation of water balance by centrally controlling both the input (drinking) and the output (ADH secretion) of water.


Interaction of acetylcholine and cholecystokinin with dispersed smooth muscle cells. Isolated gastric smooth muscle cells were prepared from the stomach of Bufo marinus by successive incubation in collagenase without added trypsin. Contraction was determined by image-splitting micrometry and expressed as the mean percentage decrease in cell length from control. Peak contractile response was attained within 30 s. Dose-response curves constructed from peak responses showed that the maximal responses to CCK-OP (37.2 +/- 3.8%), acetylcholine (35.3 +/- 2.5%), and Ca2+ (42.3 +/- 0.9%) were similar. The D50s for octapeptide of cholecystokinin (CCK-OP) and acetylcholine were around 10(-12) M and 10(-11) M, respectively. The response to a combination of submaximal concentrations of acetylcholine and CCK-OP exceeded the individual responses but did not exceed the maximal response to either agent alone. A low concentration of atropine (5 X 10(-10) M) inhibited specifically the maximal response to acetylcholine. A high concentration of atropine (5 X 10(-8) M) inhibited partially the maximal response to CCK-OP but had no effect on the maximal response to Ca2+. It was concluded that 1) dispersed gastric smooth muscle cells are highly sensitive to stimulation; 2) CCK-OP has a direct (myogenic) contractile effect on gastric smooth muscle; and 3) the effect of CCK-OP and acetylcholine are mediated by separate receptors.


Amphotericin B and K+ transport across excised toad urinary bladder. The transmural electric PD of bladders bathed by Na2SO4 Ringer was not affected by amphotericin (5 x 10(-6) M, mucosal) but the PD followed the direction for K+ diffusion in the presence of a transmural K+ gradient. Increases in bathing solution K+ increased conductance. Ouabain pretreatment did not affect drug-induced changes in PD or conductance. Unidirectional fluxes of radiolabeled Na+ and K+ but not SO42- across the short-circuited bladder were increased by amphotericin. Ninety percent of the rise in the serosal-to-mucosal flow of Na+ disappeared when mucosal Na+ was replaced by choline. Amphotericin induced a 20-fold increase in mucosal-to-serosal K+ flux but K+ serosal-to-mucosal flow increased 200-fold. This flux asymmetry persisted for 110 min, was abolished by pre- or posttreatment with ouabain, and was immeasurable when bathing solution K+ was increased from 2.4 to 59 meq/liter. With 2.4 meq K+/liter the ratio of active Na+ reabsorption to K+ secretion was 8 to 1, but K+ secretion was not closely linked to Na+ transport. The results suggest that amphotericin induces a paracellular K+-selective path, Na+ isotope exchange, and K+ secretion.


Auxotonic contractions in cardiac muscle segments. The dynamics of segment shortening have been measured in the central regions of isolated papillary muscles during muscle isometric and after-loaded isotonic contractions. Segment lengths are inferred from muscle cross-sectional area using an assumption that the segments remain isovolumic. Area is assessed with a magnetic induction technique. Infused microspheres have been used as visual markers to corroborate the segment length measurement. The results confirm the existence of major segmental shortening during muscle isometric conditions. However, the time course of shortening is not the same as that of force development. Rather, the segments remain shortened until after force has fallen significantly from its peak value. This behavior appears in the force-segment length plane as counterclockwise loops. The relationship of peak force to segment length has been determined and found to depend on the mechanical conditions under which the muscle is equilibrated. These results demonstrate the utility of the new technique and indicate central segment behavior that is substantially different from that observed for the whole muscle.


Light and electron microstructure of a Sarcocystis sp. from the Malaysian long-tailed monkey, Macaca fascicularis. The ultrastructure of the cyst wall and zoites of a species of Sarcocystis from the skeletal muscles of a naturally-infected Malaysian long-tailed monkey, Macaca fascicularis, is described in detail. The wavy, electron-dense primary cyst wall is thin (55 nm) and invaginated. Cytophaneres are absent. The ground substance contains electron-dense granules and bundles of parallel, fibrillar elements in some areas. Thin trabeculae are present. The zoites measure 1.2 X 4.7 microns and have an interior conoid, 22 subpellicular microtubules, 50-60 micronemes, 4-6 rhoptries, and a posteriorly situated nucleus. Some ultrastructural aspects of the cyst wall and the zoites of this parasite resemble those of Sarcocystis species of the moonrat, rhesus monkey, tamarin, and baboon. The light microscopic appearance of this species from M. fascicularis also bears some resemblance to that of parasites from the four cases of human Sarcocystis reported in Malaysia. The cyst in all these human cases were thin-walled, with no cytophaners. Although the final hosts of these species of Sarcocystis are not known, it is quite possible that man, monkeys, and perhaps the moonrat (an insectivore) may serve as common intermediate hosts for one or several species of Sarcocystis.


Improvements in routine xenodiagnosis with first instar Dipetalogaster maximus (Uhler 1894) (Triatominae). First instar Dipetalogaster maximus proved as effective as third instar Triatoma infestans in detecting circulating Trypanosoma cruzi in patients with chronic infections examined in a routine xenodiagnostic laboratory. Since rearing costs are diminished, D. maximus has now replaced T. infestans as the xenodiagnostic agent in our laboratory. However, further work is needed to define the optimal conditions necessary when using this species in xenodiagnosis.


Coagulation abnormalities induced by Russell's viper venom in the rhesus monkey. Coagulation studies were carried out in a group of non-human primates (rhesus monkeys) following envenomation with lethal and sublethal doses of Russell's viper venom. The envenomated animals showed significant fibrinogenopenia in association with or without disseminated intravascular coagulation. The findings offer a rational explanation for the bleeding manifestations seen in clinical cases of Russell's viper bite.


Acute complications of jejuno-ileal pseudodiverticulosis: surgical implications and management. Acute inflammatory complications of jejuno-ileal pseudodiverticulosis that necessitate surgical intervention are attended by excessive mortality rates of 20 to 40 per cent primarily because of delay in diagnosis. Early diagnosis is confused by the frequent coexistence of other gastrointestinal pathology, most commonly perforated gastric or duodenal ulcers, colonic pseudodiverticulitis, and acute appendicitis with rupture. Resection of pseudodiverticula-containing segments with primary reanastomosis is the preferred method of surgical management for perforation, bleeding, and obstruction. Recommendations are made for more accurate and earlier detection and management.


Fine structural demonstration of tyrosinase activity in the retinal pigment epithelium of normal and PTU-treated chick embryos. The effect of phenylthiourea (PTU) on the retinal pigment epithelium of chick embryo was studied by using electron microscopy and electron-microscopic histochemistry. In the retinal pigment epithelium of PTU-treated, 10-day-old chick embryo, there is an abundance of premelanosomes and relative increases in the smooth endoplasmic reticulum (ER), and in the smooth-surfaced anastomosing tubular channels. Reaction products resulting from electron-microscopic histochemistry are first observed in some cisternae of the distal or active face of the Golgi apparatus and occasionally in small vesicles in the 5-day-old embryo, and these reactions become more intense with time. PTU treatment blocks melanin synthesis in the premelanosomes of 10-day-old chick embryo. Electron-microscopic histochemistry is completely inhibited by PTU treatment. Removal of PTU allows a weak positive reaction to histochemistry in some elements of the Golgi apparatus and in some small vesicles.


Structure of the soft palate and composition of the oral mucous membrane in monkeys. The soft palate of monkeys (M. irus, mulatta, fasciculata; 2.3 +/- 0.4 kg in weight) was studied morphologically and stereologically. After fixation by perfusion, the tissue was disected free, divided in halves and the halves into 5 segments each, and processed for light, transmission- and scanning electron microscopy. Morphometric techniques and a newly developed computer program for automatic data processing (Mumana) were employed in order to estimate, at the light microscopic level, the volumetric composition of the oral soft palate mucosa. The latter showed a different composition in anterior and uvular segments, without significant differences between male and female animals, but with slight changes possibly due to age. The main constituents of the oral soft palate mucosa were glandular and connective tissue, and lymph follicles, the latter being associated with the glandular duct system. The epithelial lining of the oral and nasal aspects were described, and taste buds embedded in island of orthokeratinizing stratified epithelium were demonstrated. The association between lymph follicles and the glandular duct system was discussed in relation to similar structures in man, and in relation to the hypothesis that they are concerned in local antigen recognition.


A fine structural analysis of the myelin sheath in rat spinal roots. The present study is concerned with the fine structure of the myelin sheath in rat and monkey spinal roots. Pictures are obtained that show that the intraperiod gap of the myelin sheath is continuous and opens into both the internal and external mesaxons, which in turn open into the periaxonal and endoneurial extracellular spaces. These results are compatible with the idea that the intraperiod gap is a cleft that traverses the thickness of the myelin sheath and links the periaxonal and endoneurial extracellular spaces.


Lens extraction with anterior chamber lens implantation in the macaque. Three macaques (Macaca arctoides) had anterior chamber implantations with the Choyce Mark VIII lenses in 5 eyes. The eyes were monitored clinically and histologically for approximately 2 years. Histologic sections verified that these lenses were well tolerated in the eyes of the macaques.


Recovery of alveolar macrophages from rhesus and cynomolgus macaques by lung lavage. A lung lavage technique was developed to recover alveolar macrophages from rhesus and cynomolgus macaques. Sterile saline solution was injected through an endotracheal tube in anesthetized macaques; lung wash fluids containing leukocytes were withdrawn. The lung wash fluids from each animal routinely contained more than 16 x 10(6) leukocytes. The predominant cell type was the alveolar macrophage; lung wash fluids contained more than 53% and 80% alveolar macrophages from rhesus and cynomolgus macaques, respectively. Lung lavage was performed each week for 6 weeks in both species with no ill effects. This technique has many applications in the study of infection and of pulmonary defense mechanisms.


[Acute meningococcal infection (author's transl)]. Authors report 49 patients bacteriologicallyly diagnosed of acute meningococcal infection collected during a 12 months period out of a series of 76 cases diagnosed on clinical grounds. "N. meningitidis" was found in 18 blood and 43 CSF cultures. 31 cases were of the B-group, one was A-group and 17 were not typed. All of them were sulphamide resistant. Hyperthermia with vomiting, cephalea, arthralgia and seizures were the initial symptoms. All patients showed pettechiae, purpura and/or ecchymoses. Endotoxic shock was diagnosed in 26,5% of the cases. In them systolic blood pressures were under p-5. Overall mortality was 14%, and that of endotoxic patients 53%. Therapeutic routines and chemoprophylaxis are reviewed.


IgA antibasement membrane nephritis with pulmonary hemorrhage. Goodpasture's syndrome has characteristically been described as being mediated by IgG antibodies. We have recently seen a 55-year-old man who developed renal failure and hemoptysis; a renal biopsy showed linear deposits of IgA and C3 involving glomerular and tubular basement membrane. Serologic tests for detecting (IgG) antiglomerular basement membrane antibodies were negative. Elution studies of kidney and lung showed the presence of an IgA antibasement membrane antibody only. The patient's serum contained IgA, but not IgG, antibodies reactive with glomerular and tubular basement membrane of normal human kidney and alveolar basement membrane of normal human lung. Attempts to transfer disease with the patient's IgA antibody to a monkey and to Lewis and Brown-Norway rats were unsuccessful. Immunoglobulin A antibasement membrane antibody must be considered in the design of immunoserologic procedures for the diagnosis of Goodpasture's syndrome.


Safety of changing intravenous delivery systems at longer than 24-hour intervals. Routinely changing the intravenous delivery system (fluid containers and administration set) every 24 h is widely practiced in American hospitals to reduce the risk of septicemia caused by contaminated infusate. We did a prospective clinical study to ascertain whether changing at longer intervals could be justified. At the conclusion of infusion therapy through one system, both the cannula and an aliquot of remaining fluid were cultured quantitatively. Of 790 infusions, contaminated infusate was detected in one (0.39%) of 258 discontinued and sampled after 1 to 24 h of continuous use, three (0.84%) of 259 after 25 to 48 h, and one (0.58%) of 173 after 49 to 71 h; none of these five contaminated systems produced septicemia. However, five cannula-related septicemias were identified during the study, none associated with concordant contamination of infusate. Routinely replacing the delivery system every 48 h seems to be justified and could result in considerable savings to hospitals. Infection of the cannula wound and contamination of infusate seem to be unrelated.


Hyperamylasemia in diabetic ketoacidosis: sources and significance. The origins and clinical significance of hyperamylasemia during diabetic ketoacidosis are unclear. We have therefore correlated important clinical and laboratory indices of diabetic ketoacidosis with sequential determinations of serum and urine amylase concentrations, amylase/creatinine clearance ratios, and specific amylase isozyme types. Hyperamylasemia occurred in 79% of our patients with diabetic ketoacidosis, often after admission to the hospital. Among these patients, 48% had pancreatic-type, 36% salivary-type, and 16% mixed-type (pancreatic and salivary) hyperamylasemia. There were no correlations between the presence, degree, or isozyme type of hyperamylasemia and most laboratory or clinical characteristics, including gastrointestinal symptoms. Patients with pancreatic-type hyperamylasemia tended to have higher amylase/creatinine clearance ratios, but it was not possible to unequivocably diagnose acute pancreatitis during diabetic ketoacidosis with current routine clinical or laboratory procedures.


Amino acid deficiency and the skin rash associated with glucagonoma. A 47-year-old white man had a malignant glucagonoma and severe necrolytic migratory erythema. His plasma glucagon levels were markedly elevated at 50 ng/mL and plasma amino acids diminished to 45% of normal. To test the hypothesis that the skin rash associated with a glucagonoma is secondary to an amino acid deficiency, we obtained 2 d of fasting baseline laboratory data from the patient while he consumed his usual diet. He was then given 3 L/d of supplemental intravenous amino acids for 3 d. His plasma amino acid levels increased slightly, and there was some improvement in his skin rash. Immediately thereafter, total parenteral nutrition was administered for 3 d without added zinc or fatty acids. During total parenteral nutrition, 14 of 17 plasma amino acids became normal, and the patient's skin rash rapidly disappeared. These findings suggest that the skin rash associated with a glucagonoma is most likely due to an amino acid deficiency and can be reversed by parenteral nutrition.


Hemoperfusion to treat intoxications.

Hemoperfusion to treat intoxications. Hemoperfusion is being increasingly proposed and used for the treatment of a large variety of exogenous intoxications. This procedure has been shown to achieve high clearance rates of most common intoxicants, and case reports have claimed that its application has been, on occasion, life-saving. We tabulated our experience in the treatment of 94 consecutive patients with severe intoxications who were treated with supportive management only; this group constituted 25% of all patients admitted with a diagnosis of drug overdose. Of the 94 patients only one died; all others were discharged without sequelae resulting from the intoxication or its complications; only 21% required more than a 48-hour stay in the intensive care unit. We propose that supportive management must remain the mainstay of therapy even in severely intoxicated patients; with few exceptions, hemoperfusion must be considered an as yet unproven form of therapy; further controlled studies are necessary to establish its range of indications, potential benefits, and cost effectiveness.


An evaluation of serum thyroxine binding globulin as a routine test of thyroid function. Serum thyroxine binding globulin (TBG) values were correlated with other thyroid function test results and with the clinical condition in 680 patients. The estimation of serum TBG was helpful in the evaluation of thyroid status only in those patients who were either acutely ill, were taking the contraceptive pill, or were pregnant. Further, the derived index, thyroxine: TBG ratio, proved to be a better diagnostic index than the thyroxine:tri-iodothyronine uptake ratio and in many cases would have avoided the use of more expensive and time-consuming tests.


Serological and chemical studies of latent allotypes in the rabbit. Genetic data has shown that antigenic variants or allotypes of variable and constant regions of the heavy and light chains of immunoglobulins represent products of allelic structural genes. New findings in several animal systems have demonstrated the non-allelic behavior of immunoglobulin allotypes. In the present study we report the results of our efforts to confirm the presence of latent allotypes in rabbit sera. Varying amounts of latent allotypes for groups a and b markers were detected in 95% of all normal and immune sera tested. Several rabbits expressed high levels of latent a and b allotypes (in excess of 200 micrograms/ml of serum). By gel diffusion and radioimmune inhibition analysis, the latent b4 marker from one b6b6 rabbit, B240, was identical to the nominal b4 allotype. Also, the L chains bearing the latent b4 marker were isolated from B240 IgG and analyzed chemically by taking advantage of an acid-labile aspartic acid-proline bond at positions 109 and 110, which is unique for b4 and b9 kappa L chains.


Expression of latent allotypes in SJL mice. SJL mice (CH allogroup Igb) were immunized against immunoglobulins from strain BALB/c (allogroup Iga). We used either animals purchased directly from the Jackson Institute, or Jackson-derived mice which had been inbred further in our laboratory. In some mice from three independent immunization series we observed, contrary to expectation, the expression of molecules carrying allotypic determinants of Iga instead of the expected production of antibodies against these determinants. Various types of breeding experiments were carried out with parents being either "orthodox" SJL mice, or animals expressing the "wrong" allotype. Among the progeny, as analyzed so far, we again found animals which changed their allotype after antiallotypic immunization. The data do not appear to be compatible with a single-gene, dominant mendelian inheritance of allotypic determinants in this stock of mice.


A hypothetical explanation of saccadic oscillations. Eye movements in a patient with saccadic oscillations (ocular flutter) were recorded and analyzed. Findings were related to recent microelectrode studies in the monkey pontine reticular formation which have identified three types of premotor neurons related to saccadic eye movements: burst, tonic, and pause cells. We incorporated these cell types into a hypothetical circuit that generates saccades by rapidly driving the eye to a designated orbital position rather than preprogramming a distance for movement. Physiological measurements suggest that this neural network is unstable and that the burst neurons must be tonically inhibited to prevent saccadic oscillations during periods of fixation. Pause cells, which discharge tonically except during saccades, when they pause, appear to inhibit burst cells and prevent such saccadic oscillations. Analysis of our patient's behavior indicates that many types of saccadic oscillations can be explained and classified by assuming an abnormality of pause cell control over saccadic burst neurons.


Regeneration of the magnocellular system of the rhesus monkey following hypothalamic lesions. The hypothalamic magnocellular system of the rhesus monkey was studied with specific immunocytochemical techniques in animals that had undergone hypothalamic lesions. The results indicate that this system maintains a regenerative capacity even when its tracts are interrupted within the hypothalamus. New neurohemal units are reconstituted from newly formed vessels within the scar as well as from preexistent blood vessels, such as perforating and pial arterioles, and the vessels of the pars tuberalis of the pituitary gland, which normally do not contain neurosecretory terminals.


[Gentamycin activity in combination with etonium in relation to Pseudomonas aeruginosa]. Gentamicin is one of the most effective drugs for treatment of infections caused by Ps. aeruginosa. However, isolation of the strains resistant to the antibiotics was not infrequent. It was shown in the experiments with 40 cultures that the activity of gentamicin against Ps. aeruginosa increased approximately 20 times when it was used in combination with ethonium, a derivative of bis-quaternary ammonium compounds.


Immunoglobulin allotypy of allophenic rabbits. We obtained two allophenic rabbits formed by the manipulation of blastocysts from strains which differed by their coat colour and their immunoglobulin allotypic specificities. The phenotype of these two rabbits was a1,a2,a3,b4. They were chimeras for their lymphocytic system but not for their coat colour as they had the homogeneous brown coat colour of one of their parental strain. The IgG concentration in the serum of these allophenic rabbits was of the same order of magnitude as the IgG concentration in the serum of normal rabbits of the same age. Twenty-five weeks after birth, one of the allophenic rabbits expressed predominantly the a1 allotypic specificity (around 70% a1, 5% a2, 20% a3) which came from its brown parents, while the second one expressed predominantly the a3 allotypic specificity (around 2% a1, 20% a2, 60% a3) which came from its white parents. Each allotypically different IgG produced by these allophenic rabbits possessed the whole set of allotypic determinants found on IgG carrying the same specificity and produced by normal rabbits. We did not find significant signs of genetic information transfers from the cells of one parental strain to the cells of the other parental strain, or of eventual perturbations of the functional haploidy of the immunoglobulin-producing cells. As these allophenic rabbits only had different a series allotypic specificities, the probability of finding such signs was certainly low as they would have implied hybrid IgG molecules with two allotypically different heavy chains. We now have allophenic rabbits in which different a and b series allotypic specificities are involved and with which we will look for hybrid IgG molecules with heavy chains from one parental strain and light chains from the other parental strain. With these two rabbits we observed the "chimeric drift", namely the slow disappearance of constituants (here one allotypic specificity) coming from one parental strain. The first progeny tests carried out with these allophenic rabbits indicated that they did not seem to be chimeras at the germinal cell level. All their first offspring which were homogeneously brown and homozygous a1,b4 expressed the whole set of variants and determinants of the a1 or the b4 allotypic specificity.


Evolutionary conservation of a gene which controls the VH regions of an anti-hapten antibody (NP). Wild mice of eight types were immunized with hapten NP, and the occurrence of a genetically controlled idiotype NP-b in their sera was studied. Five of the mouse types were subspecies of Mus musculus, the others were M. cervicolor, M. dunni and M. caroli. An idiotype indistinguishable from NP-b was the prediminant anti-NP antibody in M. m. molossinus, the other seven types of mice did not have this antibody population. Lack of the idiotype in these mice does not show that they do not have the VH gene controlling its expression since the idiotypic population must have the lambda light chain, and the seven types of mice either have little of lambda immunoglobulin or have lambda chains different from the lambda chains of the laboratory mice.


In vitro activity of piperacillin compared with that of carbenicillin, ticarcillin, ampicillin, cephalothin, and cefamandole against Pseudomonas aeruginosa and Enterobacteriaceae. Piperacillin (T-1220), a semisynthetic derivative of aminobenzylpenicillin, was more active than either carbenicillin or ticarcillin against Pseudomonas aeruginosa; over 60% of isolates were inhibited at a concentration of 6.3 mug/ml. Piperacillin was bactericidal for 84% of Pseudomonas strains at 100 mug/ml, carbenicillin killed 60%, and ticarcillin killed 68% at that concentration. Piperacillin was also more active than the other penicillins against isolates of Escherichia coli, Enterobacter, and Proteus mirabilis. The combination of piperacillin and tobramycin, demonstrating synergistic inhibition of 87% of strains of P. aeruginosa, was the most active of the penicillin-aminoglycoside combinations tested for synergism.


Comparative study of anti-pseudomonas activity of azlocillin, mezlocillin, and ticarcillin. The anti-pseudomonas activities of azlocillin and mezlocillin were compared with that of ticarcillin. We measured the minimal inhibitory and minimal bactericidal concentrations of the three drugs against 20 different strains of Pseudomonas aeruginosa and found significantly lower values for azlocillin than for the other two drugs. We then infused 5 g of each drug into 10 volunteers on three consecutive days and determined the serum levels of the three antibiotics at 1-h intervals from 1 to 6 h after injection. The levels of azlocillin were significantly higher than those of mezlocillin and ticarcillin (at 1 h: 236.55 mug/ml +/- 12.9 for azlocillin, 192.45 mug/ml +/- 28.8 for mezlocillin, and 131.5 mug/ml +/- 10.9 for ticarcillin). The inhibitory and bactericidal activities of the sera obtained 1 and 6 h after the injection against the same 20 strains of P. aeruginosa demonstrated a significantly greater anti-pseudomonas activity of azlocillin when compared with mezlocillin and ticarcillin; mezlocillin and ticarcillin had approximately the same activity. The mean values for bactericidal activity against the strains tested were 1/32 for azlocillin, 1/8 for mezlocillin, and 1/8 for ticarcillin. Azlocillin thus appears to be a promising anti-pseudomonas drug and should be tested in clinical trials.


Dihydrofolate reductase from Neisseria sp. Members of the genus Neisseria are relatively nonsusceptible to trimethoprim, an inhibitor of dihydrofolate reductase. For example, the minimal inhibitory concentration (MIC) of trimethoprim for N. gonorrhoeae ranges from 2 to 70 mug/ml, whereas the MIC for Escherichia coli is 0.2 mug/ml or less. In an effort to understand this difference, dihydrofolate reductase was partially purified from five Neisseria species and compared with the enzyme from E. coli. N. gonorrhoeae dihydrofolate reductase was similar to that from E. coli in molecular weight (18,000) and affinity for the substrates reduced nicotinamide adenine dinucleotide phosphate and dihydrofolate (K(m) = 13 and 8 muM, respectively). However, the gonococcal enzyme had a decreased affinity for trimethoprim, with an apparent K(i) of 45 x 10(-9) M, some 30-fold greater than the E. coli value of 1.2 x 10(-9) M. These enzymes also differed in their isoelectric points and pH activity profiles. Within the genus Neisseria, the dihydrofolate reductase isolated from N. meningitidis and N. lactamica resembled the N. gonorrhoeae enzyme, and only small differences were detected for the N. flavescens and Branhamella catarrhalis dihydrofolate reductases. These data indicate that the relatively poor affinity of trimethoprim for the dihydrofolate reductase from these organisms may be largely responsible for the relative nonsusceptibility of Neisseria sp. to trimethoprim. The contribution of other resistance mechanisms to the overall nonsusceptibility was assessed. Strains of N. gonorrhoeae with altered cell envelope permeability had MIC values less than twofold different from those of isogenic wild-type strains. Also, a direct relationship was observed between the affinity of trimethoprim analogs for gonococcal dihydrofolate reductase and the MIC of these compounds for the gonococcus. These observations suggest that the cell envelope of N. gonorrhoeae is not impermeable to trimethoprim. Changes in the amount of dihydrofolate reductase activity could cause alterations in the susceptibility of the gonococcus to trimethoprim, as demonstrated with N. gonorrhoeae strains selected for trimethoprim resistance after chemical mutagenesis. However, the level of dihydrofolate reductase activity in wild-type N. gonorrhoeae was similar to that of E. coli, indicating that the difference in the susceptibility of these organisms is not due to greater amounts of enzyme in N. gonorrhoeae.


In vitro activity of HR 756, a new cephalosporin, against Neisseria gonorrhoeae. The in vitro activity of HR 756 was compared with penicillin, cefamandole, cefoxitin, and tetracycline against Neisseria gonorrhoeae. A total of 192 randomly selected isolates (of which 23 had minimal inhibitory concentrations of >/=0.5 mug/ml for penicillin) and three beta-lactamase-producing isolates were tested. HR 756 was the most active antibiotic tested, with more than 90% of the isolates inhibited by 0.008 mug/ml and all inhibited by 0.25 mug/ml.


Peptidoglycan transpeptidase inhibition in Pseudomonas aeruginosa and Escherichia coli by Penicillins and Cephalosporins. Peptidoglycan transpeptidase activity has been studied in cells of Escherichia coli 146 and Pseudomonas aeruginosa 56 made permeable to exogenous, nucleotide-sugar peptidoglycan precursors by ether treatment. Transpeptidase activity was inhibited, in both organisms, by a range of penicillins and cephalosporins, the Pseudomonas enzyme being more sensitive to inhibition in each case. Conversely, growth of E. coli 146 was more susceptible to these antibiotics than growth of P. aeruginosa 56. Furthermore, similar transpeptidase inhibition values were ob-obtained for the four penicillins examined against the Pseudomonas enzyme, although only two of these (carbenicillin and pirbenicillin) inhibited the growth of this organism. We therefore conclude that the high resistance of P. aeruginosa 56 to growth inhibition by most beta-lactam antibiotics cannot be due to an insensitive peptidoglycan transpeptidase.


Conditional antifolate resistance in Bacillus subtilis thyA. Resistance to antifolates in Bacillus subtilis strains results from the presence of an antifolate resistance mutation (afo). Strains which are thyA(+)afo are unconditionally resistant to antifolates. The conditional resistance of thyA afo strains is hypothesized to be due to the thyB(+) gene product (thymidylate synthetase B) having a high K(m) for the folate substrate, thus leading to thymineless death in the presence of antifolates. An alternative model for conditional antifolate resistance was shown to be incorrect by analysis of folate metabolism in methotrexate-treated cells. Genetic analysis and studies of the response of afo(+) cells to methotrexate suggested that most, if not all, B. subtilis thymine-requiring mutants are afo. Analysis of dihydrofolate reductase from afo cells did not reveal an obvious mechanism for antifolate resistance in those cells.


Antibiotic susceptibility of Neisseria gonorrhoeae strains from Europe and Africa. The in vitro activities of 16 antimicrobial agents were tested by a plate dilution method against 268 unselected isolates of Neisseria gonorrhoeae from Belgium, Rwanda, Swaziland, and Zaire. Fifteen beta-lactamase-producing strains isolated in Europe from various origins were also tested. There were significant regional variations in antimicrobial agent susceptibility, even among the African isolates, with the Rwandan and Zairean strains being most resistant. Benzylpenicillin and ampicillin were equally active in all but the beta-lactamase-producing strains. Among the cephalosporins, cefotaxime was by far the most active, followed by cefuroxime, cefamandole, cefoxitin, and cefaclor, in that order. All strains were susceptible to spectinomycin, thiamphenicol, kanamycin, and rifampin, with the exception of one highly rifampin-resistant isolate and a moderately thiamphenicol-resistant strain. Twenty-six percent of the isolates were highly resistant to streptomycin. Six percent of the gonococci had a minimal inhibitory concentration for tetracycline greater than 2 mug/ml. Clavulanic acid inhibited the beta-lactamase activity of the gonococci tested and improved markedly the activities of ampicillin and amoxicillin against beta-lactamase-producing strains.


Comparative in vitro activity of azlocillin, ampicillin, mezlocillin, piperacillin, and ticarcillin, alone and in combination with an aminoglycoside. The in vitro activities of the newer semisynthetic penicillins azlocillin, mezlocillin, and piperacillin were compared with those of ampicillin and ticarcillin by using 290 clinical laboratory isolates. Piperacillin and mezlocillin were the most active against Escherichia coli, Proteus mirabilis, Klebsiella spp., and Enterobacter spp. When Pseudomonas aeruginosa was tested, piperacillin and azlocillin were more active than either mezlocillin or ticarcillin. Streptococcus pneumoniae and Haemophilus influenzae species were highly susceptible to all of the penicillins tested. Ticarcillin had relatively poor activity against enterococci. The rate of bacterial killing with multiples of the minimal inhibitory concentration of azlocillin, ampicillin, or ticarcillin was tested for E. coli, P. mirabilis, P. aeruginosa, and Klebsiella spp. Increasing concentrations increased the bactericidal effect. The effect of combining azlocillin, ampicillin, or ticarcillin with an aminoglycoside was studied by using both killing curves and checkerboards. The isobolograms constructed from the checkerboards showed a synergistic pattern for the organisms tested, which included E. coli, P. aeruginosa, Klebsiella spp., P. mirabilis, and enterococci. However, the rate of killing was increased by the combination only for P. aeruginosa and enterococci.


Comparative susceptibility of penicillinase-positive and -negative Neisseria gonorrhoeae to 30 antibiotics. The minimal inhibitory concentrations of 30 antibiotics were determined by the agar dilution method for 17 penicillinase-positive and 50 penicillinase-negative strains of Neisseria gonorrhoeae. The latter included 42 strains that were penicillin susceptible (pen S) (minimal inhibitory concentration, <0.125 mug/ml) and 8 strains with intermediate resistance to penicillin (pen I; minimal inhibitory concentration, 0.125 to 0.5 mug/ml). Two penicillinase-resistant penicillins (methicillin and nafcillin) were inhibitory for penicillin-resistant (pen R) strains. Three new cephalosporins (cefuroxime, cefamandole, cefaclor) and a cephamycin (cefoxitin) were bacteriostatic (minimal inhibitory concentration </=0.8 mug/ml) for 90% of pen S, pen I, and pen R strains. Pen I strains were more resistant than pen R strains to 6 of 13 cephalosporins. Rifampin, erythromycin, spectinomycin, chloramphenicol, and the tetracyclines were inhibitory for both pen S and pen R strains. The minimal bactericidal concentrations of cefuroxime, cefamandole, cefaclor, and cefoxitin were measured for 17 pen R strains and eight pen I strains by serial dilution of the antibiotics in Trypticase soy broth supplemented with 1% Iso VitaleX and 1% hemoglobin. All tubes were subcultured after overnight incubation at 37 degrees C. Cefuroxime and cefoxitin were bactericidal at low concentrations (minimal bactericidal concentration, </=1.0 mug/ml) for 16 of 17 pen R strains and 6 of 8 pen I strains.


Dermopathic changes in hypozincemia.

Dermopathic changes in hypozincemia. In seven patients with chronic debilitating gastrointestinal disease who were being given total parenteral nutrition using L-amino acids and concentrated dextrose solution, severe hypozincemia (less than 60 micrograms/dL) developed with characteristic skin lesions and alopecia. The lesions were similar to seborrheic dermatitis, and they occurred in areas of high sebaceous gland concentration. Hyperkeratotic lesions were also seen on the extensor surfaces of large joints. The skin lesions and alopecia disappeared when serum zinc values were raised to levels above 60 micrograms/dL, with appropriate zinc sulfate replacement. A hypothesis on the etiology and clinical manifestations is presented.


Thiotepa-induced leukoderma.

Thiotepa-induced leukoderma. Periorbital depigmentation developed in a black man approximately six months after the application of an ophthalmic solution containing thiotepa. The drug was used postoperatively to prevent revascularization after removal of a pterygium. By light and electron microscopy, melanocytes were apparently absent in the depigmented area. The list of medications and chemicals that can cause cutaneous depigmentation is growing. An appropriate history may be of considerable value in the evaluation of vitiligo-like conditions.


[Daily bath and its effect on the normal human skin flora quantitative and qualitative investigations of the aerobic skin flora (author's transl)]. The behaviour of the aerobic skin flora of the flexor sides of the forearm, under a daily repeated bath during 21 days, using two marketable bath-supplements, was investigated in 24 volunteers for its quantitative and qualitative aspects. The combined scrubbing-washing-method was used as described by Burtenshaw with Ringer's solution. After the daily baths, using Wilcoxon-test, statistically no significant changes in the total number of microorganizations and in the number of the single groups of bacteria were found in the areas investigated by intermittent samplings of the skin flora. In the analysis of the composition of the normal aerobic skin flora, however, changes were obvious in 4 volunteers. There were no clinical changes of the skin surface in any of the volunteers.


[Pyocin typing of 111 strains of Pseudomonas aeruginosa isolated in Tuscany, using the Gillies and Govan method]. Pseudomonas aeruginosa strains from Tuscany have been typed for pyocine production against Govan and Gillies' extended set of indicator strains; results have been expressed following a binary code. Among 111 strains only 6 could not be typed; the remaining 105 strains (94.6%) presented 59 different patterns, 44 of which were represented by one isolate only. The most commonly encountered pattern (n. 8045, corresponding to Govan and Gillies' subtype 1e) was shared by 13 strains. Isolates from outpatients or from the environment tended to a uniform distribution of pyocine patterns; those from two different hospitals tended to group into distinct subtypes.


[Sensitivity to antibiotics of the "Neisseria meningitidis" strains isolated among healthy subjects (author's transl)]. In 1977, from March through April, 16 strains of N. meningitidis were isolated among 400 healthy subjects: 334 school-children 6-11 years of age and 66 adults, with a carrier rate of 3.85% and 4.5% respectively. The serological identification carried out by slide agglutination showed: 1 strain belonging to serogroup A; 4 strains to serogroup B; 1 strain to serogroup C; 1 strain to serogroup Y; 3 strains were autoagglutinable and 5 nonagglutinable. Minimum inhibiting concentrations of sulfamethoxypyrazine and some antibiotics (penicillin, streptomycin, rifampicin, chloramphenicol, chlortetracyclin) were determined for 12 strains. All the isolates were inhibited by a concentration of rifampicin of 0.2 microgram/ml, whereas 2 strains were resistant, respectively, to 0.8 UI/ml of penicillin (M.I.C. greater than 0.8 less than or equal to 1 UI/ml) and to 4 UI/ml (M.I.C. greater than 4 less than or equal to 6 UI/ml). Various levels of resistance to sulfamethoxypyrazine and other antibiotics were also noted.


Influence of increasing carbohydrate intake on glucose kinetics in injured patients. The metabolic and hormonal effect of glucose loads, ranging from 125 to 504 g/70 kg/day, were studied in severely injured patients. There was little or no correlation of glucose intake with nitrogen balance, plasma glucose, fatty acid concentrations, or epinephrine excretion. Increased norepinephrine excretion correlated with and may have resulted from increased glucose intake. Serum glucagon concentrations averaged 320 pg/ml and were not depressed by glucose intake. Insulin concentrations rose with glucose intake but were low for the level of plasma glucose. Glucose oxidation and non-oxidative metabolism, including glycogen deposition, correlated well with glucose intake. Gluconeogenesis from alanine was much higher than normal but was completely suppressed at very high intakes. The data imply that cycling of glucose, with glycerol, glycogen, or both, increased with increasing glucose intake.


Nondialysis uses for vascular access procedures. Chemotherapeutic agents, blood products and hyperalimentation solutions have been administered and recurrent diabetic ketoacidosis has been treated via vascular access procedures in 13 patients during the period from 1972 through 1977. Bovine heterograft, saphenous vein graft and the direct arteriovenous fistulae have been successfully utilized in the construction of arteriovenous fistulae in patients requiring vascular access for nonhemodialysis purposes. Operative techniques and therapeutic usefulness are discussed.


[Reiterant contaminations by "pseudomonas aeruginosa" on culture cell lines in a hospital virology service (author's transl)]. The selection of antibiotic resistant Pseudomonas aeruginosa strains by an indiscriminate administration of antibiotics has been observed. The consequences induced by Ps. aeruginosa on the tissue culture cell lines (both primary and continuos) are harmful, velding a sharp pH drop from a slight initial increase, followed by the destruction of the cell layer. Sometimes the cells succeed in growing up for some passages since antibiotics are usually present in the growth medium. Tissue culture contamination can be avoided by carrying out drastic disinfection treatments. A profilatic measure would amply to keep the Virology laboratories separated from the rest of the hospital in which Ps. aeruginosa is often present.


Effect of protein depletion and repletion on liver structures, nitrogen content and serum proteins. The data presented in this paper demonstrate that a liver which has been severely damaged by protein malnutrition can be restored to normal composition, anatomy and functional capability by central venous feeding. An atypical serum protein electrophoretic pattern characterizes protein malnutrition. TPN repletion restores all of the protein fractions back to normal except for the gamma globulin levels. Liver nitrogen is a very sensitive index of both protein malnutrition and TPN repletion. The liver is dramatically effected by protein malnutrition and its return toward normal can be achieved by TPN support as demonstrated in this paper.


Major complications of small bowel diverticula. Complications of diverticula of the duodenum, jejunum and ileum, exclusive of Meckel's diverticula are extremely rare but can produce major diagnostic and therapeutic problems. Major reported complications include hemorrhage, perforation, biliary and pancreatic obstruction, and inflammation with intestinal obstruction. The mortality of complicated duodenal diverticula is reported from 33 to 48%. Our experience with some of these complications is reported. This experience and a review of other reported cases have led to the following recommendations for surgical treatment. 1) Massively bleeding duodenal diverticulum. Precise localization of the bleeding point by endoscopy and/or arteriography is highly desirable. Excision or partial excision of the diverticulum with suture ligation of the bleeding point is necessary. 2) Perforated duodenal diverticulum. Excision or partial excision, secure closure and drainage are necessary. If peri-Vaterian, a probe should be passed through the ampulla of Vater via the common duct. Unless an entirely satisfactory closure is achieved, complete diversion of the enteric stream from the duodenum by vagotomy, antrectomy with closure of duodenal stump, and Billroth II anastomosis is recommended. 3) Choledochal obstruction due to duodenal diverticulum. Choledocho-duodenostomy. 4) Perforation, bleeding, or obstruction due to jejunal or ileal diverticulum. In rare cases, local excision of the diverticulum is feasible. Usually, resection of the involved segment with primary anastomosis is indicated.


Review of 404 patients with gastrointestinal fistulas. Impact of parenteral nutrition. This paper represents an extensive review, spanning 30 years of experience with 404 patients with gastrointestinal fistulas. It includes the first period (1945-1960) during the introduction of antibiotics, the second period (1960-1970) which saw rapid improvements in parasurgical care including, respiratory support, perfection of antibiotics, some introduction of nutritional support and improved monitoring, and the third period which saw the introduction of parenteral nutrition specifically central venous hyperalimentation using hypertonic glucose and amino acids (1970-1975) in the treatment of patients with fistulas. The principal causes for mortality in the historical sense were malnutrition, sepsis and electrolyte imbalance. Mortality among patients with gastrointestinal cutaneous fistulas decreased between the first and second periods from approximately 48 to 15%. Surprisingly, mortality did not decrease further in the "hyperalimentation period" although spontaneous closure of gastrointestinal fistulase increased. The results suggest that the improvement in mortality in patients with gastrointestinal cutaneous fistulas is mostly due to the introduction of improved parasurgical care. It is acknowledged that nutritional support was practiced in the 1960's although this was generally not in the form of hyperalimentation. The addition of hyperalimentation in large scale to the treatment of gastrointestinal cutaneous fistulas has improved spontaneous closure and is a valuable part of the armamentarium. The decrease in mortality however, cannot be attributed to parenteral nutrition.


Intravascular coagulation and fibrinolysis within primate extremities during tourniquet ischemia. A common although infrequently recognized complication associated with the use of a pneumatic tourniquet is profuse bleeding from the wound after deflation of the tourniquet. The purpose of this study was to determine whether intravascular coagulation and fibrinolysis could be induced in subhuman primates by tourniquet ischemia, and whether this phenomenon could be altered by pretreatment of the animal with heparin. It was shown that, after 2(1/2) hours of tourniquet ischemia, (400 mmHg) to one lower limb, fibrinogen levels were significantly lower (p < .005), antithrombin III levels were significantly lower (p < .05), plasminogen levels were significantly lower (p < .05), fibrin split products significantly higher (p < .025) and fibrinopeptide A levels were significantly higher (p < .02) than values measured simultaneously in the control limbs. After pre-treatment with sodium heparin, 30 units/kg, there was no change in antithrombin III levels or fibrinogen levels, but fibrin split products in the experimental limbs were significantly elevated (p < .05) when compared to control limbs. In both groups the abnormal levels returned to control levels 5-30 minutes after tourniquet deflation. We conclude that intravascular coagulation and fibrinolysis develop within ischemic subhuman primate limbs during tourniquet ischemia. Pretreatment with heparin prevents the consumption of fibrinogen and antithrombin III but does not prevent the increase in fibrin split products which was observed. It is possible that intravascular coagulation and fibrinolysis contribute to post tourniquet bleeding.


Left main coronary artery stenosis: hemodynamic monitoring to reduce mortality. A review of 20 consecutive patients with left main coronary artery stenosis operated on in 1976 indicated a general hemodynamic pattern characterized by systolic hypertension and an increase in heart rate that occurred early during the induction phase of anesthesia. From January through August, 1977, 28 patients with this stenotic condition were operated on with hemodynamic monitoring of left ventricular pressure and cardiac output by a Swan-Ganz catheter inserted before induction of anesthesia. Pharmacological interventions to optimize preload with volume, reduce afterload with nitroprusside or nitroglycerine, control heart rate with propranolol, and improve contractility with dopamine resulted in a decrease in mortality from 20% in Group 1 (1976) to 3.5% in Group 2 (1977). We conclude that control of systemic blood pressure, heart rate, and preload has notably reduced the mortality in this group of patients and that hemodynamic monitoring provides precise guidelines for therapeutic interventions.


[Tolerance and digestibility of Peruvian "common foods" in malnourished infants]. Six diets were prepared based on commonly used Peruvian foods, mainly of vegetable origin, which were offered to eight infants (mean age: 12.8 +/- 8.2 months) recovering from malnutrition. The purpose of this study was to evaluate the acceptability, tolerance and digestibility of the diets in question. Five were prepared with a potato and wheat base (noodle) and the sixth with a quinua-oats base. The acceptability and tolerance was satisfacotry, allowing maintenance of an adequate calorie and protein intake in all patients except one. On the quinua-oats based diet, the mean apparent absorption of nitrogen and fat was significantly lower (P less than 0.05) than in the case of the other diets. The increase in height coefficient (height age/chronological age X 100) and weight/age proved to be adequate during the study, except in the three youngest patients. The authors consider that this type of diets (potato-wheat based) can be recommended for infant feeding after the first year of life, and that the quinua-oats based diet still needs a more thorough evaluation prior to recommending its use.


Factors determining peripheral vein tolerance to amino acid infusions. The tolerance of peripheral veins to intravenous infusions was evaluated. Of 83 infusions studied, 67 contained amino acids. Phlebitis occurred more commonly with the use of solutions that contained the amino acids. The important factors in the production of phlebitis by amino acid solutions were osmolarity, and the amount of potassium infused per day. Phlebitis was universal when osmolarity exceeded 600 mOsm. Other factors that promoted phlebitis were the presence of antibiotics and the size of the vein.


Short term effects of Clophen A 50 and of dichlorobiphenyl in rats. In short term experiments, rats were treated with single oral doses of the polychlorinated biphenyls (PCB's), Clophen A 50 (high chlorinated compound) and dichlorobiphenyl (low chlorinated compound). Clophen A 50 treatment resulted in a marked increase in liver weight and in the activities of GPT, GOT and G1DH in rat serum at 1000 mg/kg similar effects were observed, but to a lesser degree. The levels of the serum lipids, cholesterol and triglycerides were significantly elevated at both dose levels and they remained elevated up to seven days. In contrast, one single oral dose of 1000 mg of dichlorobiphenyl per kg did not cause significant changes in the above mentioned parameters. Histological examination of the liver showed irregularly disseminated droplets of fat in both experiments. These results indicate that Clophen A 50 causes liver damage and alters the lipid metabolism of rats, whereas the low chlorinated dichlorobiphenyl does not exert such effects.


An experimental model for the study of hepatic transport and metabolism of toxic compounds. The usefulness of isolated liver cells for the study of hepatocellular transport and metabolism is demonstrated, using 1-naphthol and 2,2'-dichlorobiphenyl as model compounds. More than 60% of both substances is rapidly taken up by the cells. Naphthol is conjugated with sulphate and with glucuronic acid. These conjugates are released from the cells. Conjugation of dichlorobiphenyl and release of the conjugates is about 25 times slower than that of naphthol.


[Age and thymus morphology of pavian hamadrils]. By different histological methods, 23 thymi have been studied in Papio hamadryas of 5 age groups: fetuses, newborn, one-year-old, mature and old animals. By morphometric methods percentage of quantitative relations of the cortical and medullary substances, as well as their cell composition have been estimated. A rather great similarity in morphogenesis and age histology has been noted in human and monkey thymus. The character of histochemical reactions in thymus corpusculi supports the view on participation of some epithelial structures in the organ's functional activity. Similar supposition is made on the thymus cystic formations.


[Valve of detection of the Du blood group factor in hospital transfusion practice]. Following a description of factor Du, a variant of factor D, a personal series of about 3% is described and the technique using indirect Coombs test is indicated. Identification of factor Du takes on importance in the prophylaxis of post-transfusional isoimmunization as donors of Rh negative blood with Du positive must be considered Rh positive donors.


[Fronto-striate relationships in primate ontogeny]. A comparative investigation on the development of fields in the brain cortical frontal area and in the caudate nucleus was performed in pre- and postnatal life of the monkey and the man. Cyto- and myeloarchitectonics and quantitative methods were applied. Volumes of fields 8, 9, 10, 11, 12, 47, complex of fields 44+45+56 and the caudate nucleus were measured, the size of neuronal bodies was determined. A definite connection in the development of the caudate nucleus and the fields of the frontal area was stated. The development of these formations was found to proceed unevenly: to a definite period, the development of the caudate nucleus dominates (in Macacus ontogenesis--up to a half--one year of life, in human ontogenesis--up to 2-4 years of life). Then the development of the caudate nucleus becomes slower comparing that of the frontal fields.


[Intravenous mogadon in epileptic patients. Clinico-electroencephalographic study]. Mogadon as a parenteral solution was employed for treating status epilepticus (15 cases), intermitent epileptic seizures (10 cases), Lennox syndrome (14 cases), myoclonic seizures (5 cases) and absences (6 cases). The dosage layed between 3,3 mg and 10 mg according to each individual case. Status epilepticus and intermitent seizures disappeared following the injection and so did the irritative EEG alterations. Remission was observed in 10 Lennox cases while the remaining 4 improved. Mogadon abolished myoclonic seizures, in some cases beyond 6 hours. In simple absence improvement was also evident, although more shortlived than in myoclonic seizures. Sleepiness was side-effect, occurring in some cases.


Hypertensive breakdown of cerebral but not of retinal blood vessels in rhesus monkey. Acute hypertension, induced either by intravenous injection of metaraminol bitartrate (Aramine), infusion of isotonic saline into the common carotid artery, or a combination of both procedures did not in the rhesus monkey lead to breakdown of the blood-retinal barrier. Whereas the cerebral vasculature was made permeable to blood-borne dye at carotid pressure above 160 mm Hg, the retinal blood vessels were intact even at pressures as high as 310 mm Hg. Hypertensive blood-brain barrier opening was associated with neurologic defects and brain edema. The results indicate that the retina is more resistant to acute hypertension than is the brain. The greater resistance in the retina may be due to the high number of contractile, perivascular mural cells counteracting increased intravascular hydrostatic pressure. An alternative or supplementary explanation is that choroidal and retinal blood vessels are better protected from surges in blood pressure than are brain blood vessels. Differences between the innervation of brain and ocular blood vessels could account for this.


Scleral buckles and rotation of the ciliary body. Angle closure glaucoma is a well-known complication of scleral buckling and it is of particular interest when it occurs in eyes with previously normal angles. Forward rotation of the ciliary body about the scleral spur has been postulated as one possible mechanism for such angle closure. Large buckles were used in macaque rhesus monkeys and histopathologic examination indicated rotation of the ciliary body about the scleral spur as the cause of angle closure. Pupillary block was not present and large choroidal detachments were not needed to produce the observed closure. The exaggerated buckles used do not allow these monkeys to serve as a clinical model and great caution is stressed in making clinical extrapolations.


Ectropion after blepharoplasty. Experimental and clinical observations. Ectropion, or eversion of the lower lid, is the most common serious complication of blepharoplasty. Although many factors can be related to the production of this phenomenon, excess tension on the suture line has been implicated as a causal factor in the past. Because of the lack of instrumentation for measuring suture line tensions during the performance of blepharoplasty, and the relative difficulty in identifying suitable animal models, there has been little investigation of excess suture line tension as a cause of ectropion. This study was designed to establish a technique for measuring suture line tension during the performance of blepharoplasty and evaluating the effects of excessive suture line tension in the experimental production of ectropion in the stump-tailed monkey. In both monkey and human eyelid excisions, suture line tension is evaluated with the use of a fine-balance dynamometer. Suture line tension is shown to be a measurable parameter, and the technique of measurement is described. Excessive suture line tension has been demonstrated in monkeys and humans to be a causal factor in the production of ectropion following eyelid excisions.


Insulin secretion in non-obese (J-type) diabetics in Papua New Guinea. Nine of ten non-obese non-ketotic diabetics attending Port Moresby General Hospital had detectable C-peptide in plasma. All had received insulin for at least two months at the time of study. It is concluded that many non-obese non-ketotic young diabetics in Papua New Guinea retain pancreatic insulin secretion and so resemble the maturity onset diabetics of "Western" countries.


Abdominal drainage: a clinical review.

Abdominal drainage: a clinical review. A review of the indications for, and technique of, abdominal drainage is presented. An analysis is made of the physical characteristics of the commonly used types of drains. Evidence is presented that abdominal drains, although sometimes life-saving, are potentially harmfully and should be used only when a clear indication is present. When drainage is employed, it should be of the most efficient, closed type, and the drain should be removed at the earliest safe time after operation.


Recent developments in vaccination against bovine brucellosis. Recent research in vaccination against bovine brucellosis has been directed towards reducing the serological response to vaccination and to developing serological tests better able to distinguish vaccinal titres from those resulting from field infection. In the case of strain 19 vaccination, developments such as reducing the dose of vaccine and improving serological tests have so reduced the serological response as to allow adult vaccination to be carried out in combination with eradiction by test and slaughter. B. abortus 45/20 vaccine is being increasingly used as a combined diagnostic aid and protective agent. Progress has been made in identifying antibodies produced in response to this vaccine.


Observations on single brucellosis reactors in large herds. Over a 3 year period specimens were collected from single reacting cattle to the complement fixation test for brucellosis from large herds in north Queensland. Twenty-four such reactors were destroyed for culture, and Brucella abortus was isolated on 3 occasions. The existence of such low levels of Br. abortus in large herds should not be overlooked in the eradication campaign. Explanations were found for 17 of the single reactors, and included introduction of cattle to the herd, exposure to adjoining infected herds or vaccination with Strain 19.


An oesophageal diverticulum in a dog.

An oesophageal diverticulum in a dog. An 11-month-old male Miniature Poodle was found to regurgitate small volumes of fluid and food particles due to a diverticulum in the thoracic oesophagus. The diverticulum was removed surgically. Histologically the wall contained extensive scar tissue. Longterm recovery was uneventful and 5 months after surgery the dog is in good health


Reproductive adaptation in Drosophila exposed to oxygen-enriched atmospheres. Ten successive generations of a Drosophila melanogaster population were exposed to an atmospheric mix of 50% oxygen/50% nitrogen at standard pressure. This atmospheric mix has been shown to be toxic to this species and causes significantly shortened life span. By the fifth generation, survivorship and life span for the first 25-30 days were identical to control populations and total life span was shorter by only a few days. Egg-laying rates were stable in the experimental populations but below those of the controls. Hatching success was identical between experimental and control populations. Even though the egg-laying rates were lower in 50% oxygen, it was concluded that the population had adapted and could maintain a stable population in these conditions. The near-normal life spans, normal hatching rates, and overall population stability, exhibited following five generations of adaptation, were considered sufficient to allow continued reproduction in spite of a reduced egg-laying rate.


Effect of hypoxia on the development of Drosophila melanogaster (Meigen). Specimens of Oregon-R Drosophila melanogaster (Meigen) were bred in a defined sexual ratio in test chambers under different partial pressures of O2. In the gas mixture of 5--7% O2 plus 93--95% N2, the number of ovules dropped to nearly half even in the first generation, the time period of each development stage was considerably extended, and the size of the larvae decreased to a fraction of that of the controls. In the groups kept in a mixture of 10--12% O2 plus 88--90% N2, the same changes took place at a much slower rate, through several generations.


A tissue culture model of cartilage breakdown in rheumatoid arthritis. III. Effects of antirheumatic drugs. The effects of hydrocortisone, indomethacin, and gold thiomalate on proteoglycan release were assessed in bovine nasal cartilage-rheumatoid synovium cocultures. Of the three agents, only hydrocortisone consistently inhibited both basal and synovium-stimulated cartilage breakdown. Hydrocortisone responsivity was a direct function of the degradative capacity of synovial specimens, and this was equally well demonstrated both in patients receiving long-term therapy and those given perioperative glucocorticoid therapy. The data are consistent with significant hydrocortisone inhibition of lysosomal enzyme-mediated degradation of cartilage.


Immunoblastic sarcoma with features of Sjögren's syndrome and systemic lupus erythematosus in a patient with immunoblastic lymphadenopathy. A patient with immunoblastic lymphadenopathy and features of Sjögren's syndrome and systemic lupus erythematosus is presented. Clinical features included generalized lymphadenopathy, rash, alopecia, and synovitis, with associated laboratory abnormalities of a positive antinuclear factor and double-stranded DNA antibodies, positive lupus band test, and hemolytic anemia. Symptoms of Sjögren's syndrome included dry eyes and mouth and swollen parotid gland; biopsy results of the accessory salivary glands were positive. At autopsy immunoblastic sarcoma was found that involved the myocardium, which stained for both kappa and lambda light chains by immunoperoxidase techniques.


[Thyroid function in prophylactic therapy with lithium (author's transl)]. In 62 out-patients under maintenance treatment with lithium, thyroid function was evaluated. 21% of the patients exhibited goiter II0; 34% showed elevated thyrotrophin (TSH) serum levels; in 42% exaggerated TSH response to intravenous thyrotrophin releasing hormone (TRH) was found.


[Preparation of Di3H(9,10)-hydroergot Alkaloids (author's transl)]. In katalytic hydrogenation of native ergot alkaloids with tritium a specific addition of 3H in 9,10 position of the molecules results. The most favourable technique is described in detail on the example of ergotamine/dihydroergotamine.


Some properties of deoxycholate and dodecyl sulphate in relation to macroionic complexes and their biochemical implications. The present communication describes new properties and re-explores some poorly understood characteristics of deoxycholate (DOC, bile salts) and dodecyl sulphate (SDS). These anionic detergents form complexes with basic compounds including drugs and biologically important compounds; the excess of the reagents generally dissolves a complex. A variety of two-component macroionic complexes involving oppositely charged compounds are also dissolved by these reagents. This process implies the dissociation of a complex into its constituent components by DOC/SDS. This would suggest a new attribute of the anionic detergents of breaking up ionic linkages involved in macroionic complexes. This technique makes it possible to obtain quantitative information on the behaviour of binary macroionic complexes. The newly explored characteristics of bile salts might even operate in vivo and thereby explain some of their harmful effects in disorders associated with their elevated levels in vivo. An interference with the action of drugs by bile salts could be another side effect of the latter in the relevant pathological conditions.


Effects of anticalcifying and antifibrobrotic drugs on pre-established atherosclerosis in the rabbit. The effects of the anticalcifying drug, ethane-hydroxydiphosphonate (EHDP) and the inhibitors of collagen biosynthesis, colchicine, penicillamine and azetidine were studied in the rabbit with pre-established atherosclerosis. The drugs were administered with a cholesterol-free diet (regression diet) for 8 weeks following the induction of atherosclerosis by feeding a hypercholesterolemic diet containing 2% cholesterol and 8% peanut oil for 8 weeks. The extent and severity of aortic atherosclerosis, as revealed by the morphological and biochemical findings, increased significantly during the regression period. In rabbits treated with EHDP (5 mg/kg/day) the aorta had fewer gross lesions and contained significantly less cholesterol, collagen and elastin than did the aorta of the rabbits fed the regression diet alone. These changes were associated with a significant reduction in aortic calcium caused by EHDP. The aortic content of cholesterol, collagen and elastin in the EHDP-treated rabbits, although less than that of the rabbits fed the regression diet alone, was about the same as that of the rabbits fed a high cholesterol diet for 8 weeks. Both colchicine (0.2 mg/kg/day) and penicillamine (100 mg/kg/day) had a selective action on the induced plaques in that they suppressed the fibrous proliferation in the lesions without preventing lipid and calcium accumulation in the lesions. Neither colchicine nor penicillamine reduced the extent of aortic atherosclerosis as determined by gross examination of the vessel. Azetidine had no significant effect on the pre-established atherosclerotic lesions. The lipid, fibrous protein and calcium content of the aorta of the azetidine-treated animals was not significantly different from that of the untreated animals. The biochemical findings in the aorta were consistent with the microscopic changes.


The effect of various dietary regimens and cholestyramine on aortic glycosaminoglycans during regression of atherosclerotic lesions in rhesus monkeys. The effect of various diets on the aortic glycosaminoglycan (GAG) composition was studied in rhesus monkeys. Aortas were obtained from monkeys fed diets containing cholesterol and comparative fats including coconut oil--butter and peanut oil and with and without cholestyramine. Additional groups in each experiment were placed on regression diets of low-fat, low-cholesterol with and without cholestyramine. Further, an atherogenic diet of coconut oil--butter was alternated every 2 months with a diet enriched with corn oil. GAG isolated from intima and media--adventitia indicated slight variations in the concentration of total GAG among different dietary groups but major differences in the concentration of individual GAG. The concentrations of hyaluronic acid and heparan sulfate were generally greater in aortas of monkeys fed corn oil diets than in those fed coconut oil--butter or peanut oil diets. The concentration of dermatan suulfate generally decreased during regression of lesions induced by the saturated fat--cholesterol diet. Furthermore, the aortas of monkeys with lesions from feeding peanut oil showed higher levels of dermatan sulfate and lower levels of chondroitin 4-sulfate than the saturated fat-fed groups. The addition of cholestyramine enhanced the effects of regression. These observations show that the composition of GAG of the arterial wall can be influenced by various dietary programs and that GAG play a role in induction and regression of experimental atherosclerotic lesions.


Studies on the disposition of diosgenin in rats, dogs, monkeys and man. Rats, dogs and squirrel monkeys were given a single oral dose of [4-(14)C]diosgenin. Virtually all of the radioactivity was excreted in the feces. All of the absorbed radioactivity was eliminated via the bile. The percent of dose absorbed decreased with increasing dose. The amount of radioactivity in livers of rats given [4-(14)C]diosgenin was less than that after [4-(14)C]cholesterol, but more than after [4-(14)C]beta-sitosterol. Absorbed radioactivity in rats distributed into tissues, most notably the liver, adrenals, and walls of the gastrointestinal tract. No serum diosgenin was detected after a single large dose to rats and dogs. After multiple doses (100 mg/kg/day for 4 weeks) of diosgenin to dogs, up to 15 micrograms/ml of unchanged diosgenin was found in serum. Serum from human subjects receiving 3 g/day of diosgenin for 4 weeks contained less than 1 microgram/ml of unchanged drug. After a single dose of [14C]diosgenin, several metabolites were detected in the bile of rats and dogs; the pattern of metabolites was dissimilar in the two species. No diosgenin or 7-hydroxydiosgenin was found. One of the major biliary metabolites was diosgenin monohydroxylated in the F ring, but the location of the hydroxyl group was different in the two species. Although rat caecal contents were capable of reducing diosgenin to smilagenin in vitro, no smilagenin was present in the feces of rats given chow supplemented with diosgenin. It was concluded that diosgenin is poorly absorbed in the species tested, and that the amount which is absorbed undergoes extensive biotransformation.


[Ossification of the transverse ligament of the atlas. A report on three new cases (author's transl)]. Following the publication of the first two cases reported of ossification of the transverse ligament, the authors describe three recent observations of this lesion. In contrast to the first two cases, in which ossification was reported at the level of the cervico-occipital articulation, which was normal, these three new cases were noted to have associated acquired or congenital abnormalities of the craniovertebral junction.


[Severe protein-calorie malnutrition in the infant]. In fifty infants with early and severe protein-calorie malnutrition, an essentially ambulatory treatment was pursued by a multiprofessional health group from the South-western Area of Santiago attaining nutritional recovery in all of them. The investigation only included malnourished children of primary etiology (low feeding). Babies with birth weight of or under 2,500 g. were excluded. Among them 26, were malnourished of 2nd degree and 24 were 3rd degree malnourished. The following period of these patients was 22 months. Once the nutritional improvement was achieved, the follow-up was continued for 12 months. The last control showed that only 3 infants relapsed in their malnutrition, but in a lower degree. Most of the group was in the same or in a better nutritional state. The socioeconomical status of these infants at the beginning of the study was very poor. A short period of breast feeding was confirmed together with poor conditions of formula preparation and none or low alimentary education in most of the group of mothers. The measurements of these infants at the onset and when they recovered and were discharged are reported including weight for age, length for age and weight for length.


Relationship of natural killer-cell activity to rhesus antigens in man. A number of previous studies have shown that the level of natural killer (NK) cell activity in humans is relatively constant for a given individual but varies widely between individuals. The factors which determine this variability are largely unknown, but genetic factors appear to be involved. In the present study it was found that Rh- normal subjects and melanoma patients had significantly higher natural cytotoxicity to target cells than Rh+ patients. This difference did not appear to be due to sensitization against Rh antigens on the target cell and may indicate that genes determining NK-cell activity are associated with those determining the expression of Rh antigens. Analysis of the survival data for Rh- and Rh+ patients did not reveal any increase in survival attributable to the higher natural cytotoxicity in Rh- patients.


Non-immunological cell death of intravenously injected murine tumour cells. Most DBA mastocytoma and Sarcoma 180 cells trapped in the lungs of mice after i.v. injection died within 7 h.  Rates of cell death were similar for both tumour cell lines. Rates of tumour cell death were unrelated to whether the cells were allogeneic or syngeneic, induced platelet aggregation or not, had different patterns of subsequent tumour growth, or were injected in varying numbers. Cell death was by coagulative necrosis, not apoptosis. Sarcoma 180 tumour cells were quickly localized in the lung and enclosed in platelet aggregates which remained, with degranulation, until the time of tumour cell death. However, platelet aggregation did not appear to play a role in tumour cell killing. The prevention of platelet aggregation by pretreatment of mice with an anticoagulant had little effect on the rate of death of tumour cells in the lung. Mastocytoma tumour cells did not cause platelet aggregation, yet died in the lung at similar rates to Sarcoma 180 cells. The killing of tumour cells in the lung did not appear to be cell-mediated. No mononuclear cells were seen in the vicinity of tumour cells and the type of cell death was not that associated with cell-mediated killing. The tumour cells did not die within 6 h of being injected into the peritoneal cavity. It is suggested that a nonspecific non-immunological process results in the death of intravenously injected tumour cells in the lung. This process was not affected by differing oxygen levels in the inhaled gas.


ADCC (K-cell)lysis of human erythrocytes sensitized with rhesus alloantibodies. I. Investigation of in vitro culture variables. An ADCC system has been developed using anti-D and papainized group O rhesus (D) positive red cells as the targets. Monocyte depleted mononuclear cell suspensions were effective in lysing appropriately sensitized red cells and papainization considerably enhanced the degree of specific lysis. Variation in culture volume and incubation in tubes or microplates were not critical to the degree of specific lysis obtained provided that the number of effector cells and target cells per culture was constant and the anti-D not diluted below the optimal concentration. Cytolytic activity was seen down to levels of 3 ng anti-D per culture. Specificity for lysis resided with the anti-D and not the effector cells. Several sources of anti-D were effective in inducing lysis of D positive red cells although individual variation was noted. Anti-c and anti-E were also shown to be effective in inducing specific lysis of red cells with the appropriate antigens.


ADCC (K-cell) lysis of human erythrocytes sensitized with rhesus alloantibodies. II. Investigation into the mechanism of lysis. The mechanism of lysis of anti-D coated human erythrocytes by human mononuclear K-cells was investigated. Red cell lysis was measurable after 30 min incubation and reached a maximum by 18--20 h. Cell-to-cell contact was necessary for lysis, phagocytosis was not a prerequisite, and intact microfilament function was required. The divalent cations Ca2+ and Mg2+ were both required for lysis to occur. Studies with metabolic inhibitors indicate that some RNA and protein synthesis is required for maximum expression of ADCC and intact microtubule function is essential. In the present system lysis was mediated by IgG1 anti-D antibodies and was significantly inhibited by IgG1 and IgG3 subclasses with some inhibition by IgG2 but not by IgG4, IgA or IgM. This suggests that the K-cell receptor is specific for IgG but that there is major cross-reactivity between IgG1 and IgG3. The inhibiting effect of hydrocortisone suggests that ADCC inhibition may be one mode of action of corticosteroids in ameliorating autoimmune haemolytic anaemia.


Respiratory function in coffee workers.

Respiratory function in coffee workers. Respiratory function was studied in three groups of workers employed in processing coffee. The prevalence of almost all chronic respiratory symptoms was significantly higher in coffee processors than in control workers. In each group during the Monday work shift there was a significant mean acute decrease in the maximum expiratory flow rate at 50% vital capacity (VC), ranging from 4.0% to 8.7%, and at 25% VC, ranging from 6.0% to 18.5%. Acute reductions in FEV1.0 were considerably lower, ranging from 1.3% to 2.8%. On Thursdays the acute ventilatory function changes were somewhat lower than on Mondays. Acute decreases in flow rates at low lung volumes suggest that the bronchoconstrictor effect of the dust acts mostly on smaller airways. Administration of Intal (disodium cromoglycate) before the shift considerably diminished acute reductions in flow rates. A comparison of Monday pre-shift values of ventilatory capacity in coffee workers with those in controls indicates that exposure to dust in green or roasted coffee processing may lead to persistent loss of pulmonary function.


Experimental retinal branch vein occlusion in rhesus monkeys. I. Clinical appearances. Branch and hemisphere vein occlusion were produced in rhesus monkeys by argon laser photocoagulation. The following observations were made: (1) Immediately after occlusion there was venous dilatation, delayed filling of the artery, delayed drainage by the occluded vein, and capillary leakage. (2) Two patterns of evolution were identified within the first week. In some animals the fundus changes resolved and the retina returned to normal, while in others there was progressive retinal capillary closure. (3) Those animals destined to have capillary closure had diffuse or cluster retinal haemorrhages at 24 hours. (4) Capillary closure took place over 1 week and was usually complete over large areas of retina. (5) Retinal atrophy and major vessel changes occurred over several weeks. (6) Retinal revascularisation occurred in those areas of closure, though this was often limited. It was concluded that the early changes mimicked those seen in human retinal vein occlusion, though persistent retinal oedema and preretinal neovascularisation were not identified.


Experimental retinal branch vein occlusion in rhesus monkeys. II. Retinal blood flow studies. Experimental branch vein occlusion by laser photocoagulation in the rhesus monkey leads to early, marked, and lasting reduction of blood flow to the affected retinal region. The radioactive microsphere method demonstrates this reduction of blood flow in both gamma counting and autoradiography. The reduction of flow becomes evident as early as 2 hours after occlusion and persists up to 1 week. The mechanism of the altered flow is discussed.


Experimental retinal branch vein occlusion in rhesus monkeys. III. Histopathological and electron microscopical studies. Experimental retinal vein occlusion in monkeys was followed by an immediate increase in capillary permeability which was accompanied by retinal oedema. This functional capillary change was followed at about 6 hours after occlusion by structural damage to the capillary wall. Thrombus formation occurred in the damaged vessels, and areas of stasis were thus produced with associated retinal haemorrhages. Finally, there was complete loss of the capillary endothelium and pericytes, and the acellular capillaries were invaded by proliferating glial cell processes, so producing permanent capillary closure.


Treatment of amoeboid herpetic ulcers with adenine arabinoside or trifluorothymidine. In previous studies adenine arabinoside and trifluorothymidine were found to be equally effective treatments for dendritic ulcers of the cornea, but a trend emerged which suggested that in amoeboid ulcers trifluorothymidine was more effective. The collection of additional cases confirms the superiority of trifluorothymidine in such cases.


Treatment of experimental herpes simplex keratitis with acycloguanosine. Acycloguanosine, a recently developed compound with high inhibitory activity against viruses belonging to the herpes group, has been evaluated in experimental herpes simplex keratitis in rabbits in comparison with trifluorothymidine and preparations of idoxuridine and vidarabine at present in clinical use. All compunds were used in the form of ophthalmic ointments which were applied 5 times a day at intervals of 2 hours. Treatment began on the third day of infection and was continued for 4 days. Complete cure was obtained with acycloguanosine and idoxurdine; trifluorothymidine and vidarabine were considerably less effective. Acycloguanosine was equally effective when given intravenously in the form of its sodium salt, and could be detected in the tear fluid in inhibitory concentrations when given by mouth. The compound was relatively free from toxicity.