Morphometric analysis of Cartesian coordinates of the human skull. A method for locating the three dimensional coordinates of cranial landmarks with respect to the Frankfort, midsagittal, and coronal planes is presented. Sliding calipers were used to obtain the distances from left and right porion and apex to each landmark, except for a few points where spreading calipers are required. In the present example, 35 landmarks (for a total of 105 measurements) were located for each of 35 Peruvian precolumbian skulls. These distances were entered into a program (SKULL) which calculates the Cartesian coordinates of each landmark. The XYZ coordinates of each landmark contain all the information necessary for calculation of the distances between any two landmarks, and these distances may also be obtained as output from program SKULL, if desired (595 distances if all 35 landmarks are used). Reliability of the location of coordinates was determined by comparing computed distances among selected landmarks from program SKULL with traditional anthropometric measurements. Satisfactory agreements were found. Direct multivariate analysis of the coordinates of the landmarks produced insights not available in traditional multivariate analysis of conventional anthropometric measurements.


Cranial dysraphism mistaken for trephination. Attention is called to a disputed diagnosis of trephination reported for a perforated skull of a prehistoric New England Indian. The perforation, surrounded by a saucer-like depression, is located exactly in the midline just in front of bregma. The finding of a similar lesion in a prehistoric Indian skull from the North Coast of Peru--where, as in New England, good evidence of the practice of trephination is lacking--provides support for a more reasonable diagnosis for both cases: congenital cranial dysraphism, specifically encephalocele. Information about dysraphic states from modern clinical experience is summarized.


Pressure-flow relations in the vessels of the canine aortic arch. Simultaneous measurements of pressure and flow have been made in the vessels of the aortic arch in chloralose-anesthetized dogs under three conditions; control, cardiac sympathetic (SS), and vagal nerve stimulation (VS). The specific sites studied include ascending aorta (AA), descending thoracic aorta (DTA), and brachiocephalic (BCA), left subclavian (LSC), and common carotid arteries (CA). Recorded data were analyzed by Fourier series methods and were used to calculate vascular impedance spectra, pressure and flow propagation characteristics, and hydraulic power. The distribution of cardiac output was found to be 70% to DTA, 22.2% to BCA, and 6.5% to LSC. The fraction of cardiac output to the BCA, LSC, and CA was increased by both SS and VS. The hydraulic power was distributed to the arch vessels nearly the same as the cardiac output. Hydraulic power dissipated in the arch vessels averaged 6% of the total AA hydraulic power and was increased by SS and decreased by VS. The results suggest that viscous losses in the arterial walls represent a considerable portion of the power dissipation. A similarity found in the vascular impedance spectra at the various sites for all three conditions was also observed for the transmission characteristics of pressure and flow harmonics between the sites. The results suggest that major reflections do not occur in the proximal aorta.


Hormone-substrate responses to total fasting in lean and obese mice. The hormone-substrate milieu has been investigated in male fasted lean (C57BL/6-+/+) mice and mutant obese mice of the same strain (C57BL/6-obob). The lean mouse, in winter, mobilized insufficient fat (due to inadequate stores) to permit survival beyong 3 days and was unable to achieve any degree of conservation of vital protein stores. By contrast, in summer, the same animals survived 7 days and showed evidence of greater and more sustained fat mobilization and ketosis and the ability to conserve protein. The insulin, glucagon, and insulin/glucagon molar ratios changed in both groups in a direction consistent with conversion to a catabolic state, and hence were probably largely responsible for the mobilization of substrates and stimulation of gluconeogenesis and ketogenesis. The seasonal difference in response is unexplained. The obob mice, generally employed as a model for obesity, hyperglycemia, and hyperinsulinemia showed these features but also adapted to fasting in a fashion permitting prolonged survival during this state. In a fashion analogous to that known to occur in man, these animals developed fall in glycemia, rise in circulating fat-derived substrates, and marked protein conservation. Profound fall in insulinemia was associated with a fall in glucagonemia, the latter from normal levels. Thus the initial markedly "anabolic" insulin/glucagon molar ratio diminished, but nevertheless remained higher than at any time in the lean mice. Pancreatic contents of insulin showed markedly different changes with fasting in obob compared with lean mice. The ability of the obese mouse to adapt to prolonged fasting in a fashion largely analogous to that of man renders it a useful model for the study of metabolism in this state, with the potential of applicability of findings to man.


Separate lateral hypothalamic pathways for extracellular and intracellular thirst. Small lesions of the midlateral zone of the lateral hypothalamus in rats attentuated water intake elicted by the central microinjection angiotensin or by the peripheral injection of isoproterenol or renin without attenuating drinking to peripherally administered hypertonic saline. Lesions placed further lateral in the hypothalamus, which destroyed the medial aspects of the internal capsule and globus pallidus, produced a marked decrease in water intake induced by  hypertonic saline. Abaltion of the ventromedial nucleus of the hypothalamus increased drinking elicited by angiotension, isoproterenol, or renin. These  results suggest that extracellular and intracellular thirst stimuli are mediated by separate neural pathways at the level of the lateral hypothalamus.


Permeability limitation in estimation of local brain blood flow with [14C]antipyrine. Influence of capillary permeability on local cerebral blood flow (LCBF) estimated by the autoradiograhpic diffusible-indicator method was analyzed by computer simulation. Its influence increases with increasing flow. With normal perfusion rates in gray matter, capillary permeability coefficient x surface area (PS value) must exceed 0.12 cm3-s(-1)-g(-1) for estimated LCBF to attain 95% of true values in all structures. In white matter, with its lower perfusion rates, the PS value must exceed 0.035 cm3-s(-1)-g(-1) for equivalent accuracy. [14C]antipyrine, widely used in the LCBF technique, has a PS value below these values and leads to undersestimation of LCBF. Experimental studies in cats in which LCBF was measured with either [14C]antipyrine or the freely diffusible, radioactive gas, [131I]trifluoroiodomethane, demonstrated consistently lower estimates of LCBF with [14C]antipyrine than with the gas; the deviations in the various cerebral structures approximated those predicted by the theoretical analyses. These results suggest that the uptake of [14C]antipyrine by cerebral tissues is diffusion limited as well as flow limited, and it therefore is not an ideal tracer for the autoradiographic LCBF technique.


Caffeine versus methylphenidate and d-amphetamine in minimal brain dysfunction: a double-blind comparison. The authors compared the efficacy of caffeine, methylphenidate, and d-amphetamine in children with minimal brain dysfunction using a double-blind crossover design. The slight improvement with caffeine was not significantly better than placebo. Both prescription drugs resulted in significant improvement and were significantly superior to caffeine. The authors suggest that the discrepancy between these results and an earlier, more optimistic report mat stem from the use in this study of pure caffeine rather than whole coffee.


Psychotherapy in India: past, present, and future. If psychotherapy is defined as "interpersonal method of mitigating suffering" then many psychotherapeutic systems have existed in India a long time. Unlike Western systems, these have lacked a clinical bias but have provided a more global framework. The future of psychotherapy in both East and West lies in discovering a conceptual framework with universal validity within which ad hoc therapies--for symptom relief, personality development, or interpersonal adjustment--can be developed.


Solitary phalangeal defect in the hand. Report of 2 rare cases. Two unusual causes of bone defect in the finger are described. In one patient, erosion of the proximal phalanx was caused by a ring that eroded its way through the soft tissue and bone after an injury. In the other, a subungual wart caused a defect on the distal phalanx.


The circle system without absorber. Use with controlled ventilation. An investigation is described into the performance of two types of circle system used without a carbon dioxide absorber in both the laboratory and in the operating theatre with controlled ventilation. The newer system was found to be more efficient than the old but in both types of system the tidal volume was found to be very important, a large tidal volume resulted in increased efficiency. The possibility of predicting arterial blood carbon dioxide using this system is briefly discussed, and rules are suggested for the use of the system.


The Retec breathing assistor. An application of fluidics to apparatus for inhalation therapy. The Retec breathing assistor, with its gluidic valve, is an interesting method of providing assisted positive pressure inspiration, a resistive load to expiration and a capability for the administration of drugs by nebuliser. It requires some co-operation but very little training by patients, and is easily cleaned and maintained.


A portable self-inflator-nebuliser.

A portable self-inflator-nebuliser. An inexpensive portable apparatus for the administration of topical nebulisation therapy is described.


The immersion incident.

The immersion incident. The ever increasing participation in aquatic recreational activities is a major factor in the increasing number of deaths due to accidental immersion. Some of these deaths occur while undergoing resuscitative efforts immediately following rescue, on admission to hospital, or even up to 19 days after the immersion incident. Drowning, either acute or its delayed effects, is chiefly responsible for these deaths, but in a number, hypothermia occurring alone or complicating drowning, is the likely explanation. This paper examines the problem and proposes a regime of management.


Some eighteenth century authorities on the resuscitation of the apparently drowned. Attempts to resuscitate the apparently drowned began seriously in the eighteenth century. The theories and methods of resuscitation used or advocated by some of the early European workers have been reviewed. Many of these, including artificial ventilation, chest compression, endotracheal intubation and electrical stimulation of the heart seem to have been forgotten during the nineteenth century and not used again until recent times.


Arterial oxygen tensions during the induction of ether and air anaesthesia with spontaneous respiration. Arterial oxygen tensions were measured during the induction of ether and air anaesthesia with the EMO Inhaler and spontaneous respiration. Severe degrees of anoxia were demonstrated; these were often associated with normal or above normal minute volumes. The danger of anoxia can be alleviated either by supplying oxygen or by the use of relaxants and positive pressure ventilation or both. A choice of priorities has often to be made by those in authority in developing countries where resources of material and manpower are limited and logistic support erratic. Every effort should be made to encourage a supply of oxygen in such circumstances. The training of anaesthetic staff is of paramount importance and it is a great pity that the equivocal attitude of the professions, both medical and nursing, in Britain towards the training of nurses and paramedical personnel in anaesthesia does little to encourage such training in developing countries.


Hyoscine butylbromide: a useful premedicant. The actions of intravenous hyoscine butylbromide (Buscopan) and atropine sulphate on reduction of upper respiratory tract secretions during anaesthesia are compared. Hyoscine butylbromide has a significantly more powerful action.


[Glaucoma, tonometry and anaesthesia (author's transl)]. Definition and classification of glaucomas. Indication of drugs contraindicated in glaucomas. Discussion of the problem of tonometry in anaesthesia in congenital glaucoma suspicion with special regard to factors influencing intraocular pressure. Discussion of correlation between intraocular pressure and systemic blood pressure. Report on own experiences with Ketamine and discussion of advantage and disadvantage of the drug for tonometry in anaesthesia in infants. Explanation of the method of impression--and applanation tonometry with regard to Glaucotest, a new borderline--tonometer suitable for the anaesthesiologist.


Differentiation of sympathicoblasts in cultures of chick ganglia: light and electron microscopic, fluorescence and enzyme histochemical observations. Immature sympathetic ganglia prepared from 5 1/2-or 6-day-old chick embryos were cultured up to one month. The in vitro development was followed by phase microscopy, electron microscopy and using histochemistry for catecholamines, monoamine oxidase and cholinesterases. During the first week of culture extensive plexuses of nerve fibres were formed between and around the clusters of nerve cells. Mature-looking neurons were observed in the cultures by phase microscopy after three weeks, at which age the mean diameter of the perikarya was more than doubled. Varying catecholamine fluorescence was observed in the perikarya during the entire culture period. The nerve fibres showed usually only weak fluorescence, but, in the older cultures, bright varicosities were regularly found in the fibres. Monoamine oxidase activity was demonstrated already at three days of culture and the reaction was maintained positive. Weak or moderate acetyl-cholinesterase activity was demonstrated in the sympathicoblasts and young sympathetic neurons and their processes. The axolemma showed acetylcholinesterase activity also around the nerve terminals containing small dense cored vesicles. Reactions for the non-specific cholinesterases were negative. Electron microscopy of the 30-day-old cultures revealed that the clusters of nerve cells consisted of mature sympathetic neurons, which contained large (60-200 nm) and small (35-60 nm) granular catecholamine-storing vesicles. Glial cells were almost totally lacking. Large numbers of nerve terminals containing both large and small granular vesicles were observed in the clusters, often in synaptic contact with the sympathetic neurons. It is concluded that the primitive sympathicoblasts are, in favourable conditions, capable of differentiation in culture up to mature sympathetic neurons.


Electron microscopic localization of calcium in vascular smooth muscle. Potassium pyroantimonate has been employed in this study to localize calcium in the vascular smooth muscle of the thoracic aorta of the rabbit. The pyroantimonate ion precipitates sodium, magnesium and calcium. Incubation of theisolated thoracic aorta in a high potassium bathing medium which does not contain sodium, magnesium or calcium depletes the tissue of sodium. Addition of 10.8 mM CaC12 to the incubation medium results in well-localized depositions of reaction product, presumably that of calcium pyroantimonate, in mitochondria, sarcoplasmic reticulum, and at the plasma membrane. Some or all of these organelles may, therefore, play a vital role in the contraction-relaxation cycle of vascular smooth muscle.


New advances in pulmonary gas exchange.

New advances in pulmonary gas exchange. Unevenness of ventilation and blood flow within the lung is of great clinical importance because this mechanism is the commonest cause of hypoxemia and respiratory failure. In spite of this, little is known about the distribution of ventilation-perfusion ratios in disease. A new technic for determining these distributions is described and examples are given. An important finding is instability of areas with low ventilation-perfusion ratios during oxygen breathing.


Effects of intraoperative PEEP on postoperative arterial oxygenation. Previous studies have suggested that early postoperative hypozemia may be due to a reduction of functional residual capacity (FRC) during anesthesia and surgery. Positive end-expiratory pressure (PEEP) has been recommended as a means of maintaining FRC and improving arterial oxygenation. Fifteen selected patients undergoing peripheral surgical procedures were anesthetized with one of three types of ventilatory patterns: (1) spontaneous respiration; (2) controlled ventilation; and (3) controlled ventilation with 10 cm. of water PEEP. Pao2 were sampled at selected preoperative, intraoperative, and postoperative periods. Patients receiving PEEP maintained the highest mean Pao2 intraoperatively. However, the beneficial effect of intraoperative PEEP was not sustained in the recovery room, where all patients experienced the same degree of arterial hypoxemia.


Antazoline phosphate and naphazoline hydrochloride, singly and in combination for the treatment of allergic conjunctivitis-a controlled, double-blind clinical trial. A controlled, double-blind comparison of naphalzoline hydrochloride 0.05%, antazoline phosphate 0.5%, a combination of both components and a placebo was performed on 51 ragweed sensitive patients presenting allergic conjunctivitis. Evaluation of response at various times after instillation of medication for lacrimation, conjunctival inflammation, pruritus, photophobia and pain showed naphazoline hydrochloride, antazoline phosphate and the combination product superior to placebo. The combination product was statistically significantly superior for conjunctival inflammation and photophobia. The need for post-challenge treatment with epinephrine hydrochloride was significantly less in those eyes treated with the combination product. demonstrating prophylactic efficacy.


Pyridoxine treatment of childhood bronchial asthma. Urinary xanthurenic and kynurenic acid levels were measured in five patients while they were receiving 50 mg and 100 mg of pyridoxine. The levels of tryptophane metabolite decreased progressively as the dose was increased but remained above basal levels. There was marked clinical improvement in these patients while receiving the higher dose only. The double-blind study with 76 asthmatic children followed for five months indicated significant improvement in asthma following pyridoxine therapy (200 mg daily) and reduction in dosage of bronchodilators and cortisone. The data suggest that these children with severe bronchial asthma had a metabolic block in tryptophane metabolism, which was benefitted by long-term treatment with large doses of pyridoxine.


Protection against neonatal enteric colibacillosis in pigs suckling orally vaccinated sows. Pregnant swine were vaccinated with 1 of 2 enteropathogenic strains of Escherichia coli, and their pigs were challenge inoculated with the homologous strain 1.5 hours after the entire litter was born. Seventeen sows were vaccinated orally by feeding viable cultures on 3 consecutive days, 6 sows were given 2 intramuscular (IM) injections of viable cultures at 10- to 14-day intervals, 6 sows were given 2 IM injections fo formolized cultures at 10- to 14-day intervals, and 12 sows were not vaccinated. The pigs from sows which had been orally vaccinated with viable cultures were protected during the 10-day observation period against diarrhea, as well as against death, when the newborn pigs were challenge inoculated with the homologous strain. Most of the pigs from sows which had been vaccinated IM were protected against death, but few neonates were protected against the diarrheal effects of challenge exposure with the homologous strain. Challenge-inoculated pigs suckling nonvaccinated sows had diarrhea and became dehydrated, and many died. Fewer viable E coli were usually recovered from the homogenized intestinal contents or intestinal segments of newborn pigs which did not have diarrhea than from similar specimens of diarrheal pigs. Microscopic examination of segments of the small intestine revealed that large numbers of E coli were closely associated with the ileal mucosa of newborn pigs killed in the acute phase of neonatal enteric colibacillosis caused by either strain, but organisms were not detected in this location in the pigs which remained normal after challenge exposure. It is concluded that swine which have been vaccinated by feeding large numbers of viable E coli late in gestation can provide good protection to their suckling pigs against the effects of challenge inoculation with the homologous enteropathogenic strain.


Anesthesia and subarachnoid intracranial pressure. Intracranial pressure (ICP) was continuously monitored by the Richmond technic of Vries and Becker in 17 patients undergoing elective craniotomy. This method entails the placement, underlocal anesthesia, of a hollow screw through the cranium into the subarachnoid space. The screw was connected to a Statham P23Db pressure transducer with heavy vinyl tubing and with pressures recorded on a Beckman Dynograph. The effects of 3 anesthetic technice-halothane, enflurane, and nitrous oxide-narcotic-relaxant-on ICP during induction and maintenance were compared with preinduction control pressures. Control ICP in awake, lightly premedicated patients was 15 plus or minus 10 torr. Mask inductions with halothane and enflurane consistently caused significant increases in ICP from preinduction levels in the absence of excitement or airway obstruction. Induction with nitrous oxide-narcotic-relaxant did not increase ICP. Decreases in ICP following barbiturate administration were noted. Addition of halothane and enflurane to the inspired mixture of patients controlled and hyperventilated with nitrous oxide and oxygen caused consistent increases in ICP. With control hyperventilation (Paco2 25 plus or minus 5 torr), the ICP did not return toward preinduction values within 5 minutes with enflurane and halothane.


Enteric colibacillosis: evaluation of strains of Escherichia coli utilizing the ligated loop technique in gnotobiotic swine. The enteropathogenicity of 6 strains of Escherichia coli was evaluated via the ligated loop technique in 15 gnotobiotic swine 3 to 4 weeks old. Strain enteropathogenicity in gnotobiotic swine, as determined on the basis of visual loop distention and light microscopic evaluation of intestinal sections, compared favorably with that reported in conventional swine, except that jejunal loops of gnotobiotic swine may be somewhat less sensitive to certain strains. In addition, postoperative mortality rate among gnotobiotic pigs was greater than that reported in conventional pigs. Two types of aberrant loop reactions were observed during the experiment. The 1st, and the more commonly encountered type, was due to the leakage of enteropathogenic organisms or enterotoxin from one loop to another; this was considered to be a true false-positive reaction. The 2nd type of unexpected positive reaction occurred in 2 sacs inoculated with the nonenteropathogenic strain 115. This latter reaction may have represented either a reversion of the organism to its previous enteropathogenic state or a unique reaction of the gnotobiotic intestine to this strain. False-positive loops were not identified in any other sacs, whether inoculated or not. Results of these experiments support the hypothesis that false-positive loops originate from naturally occurring infection.


Enzootic occurrence of chloramphenicol-resistant Salmonella typhimurium var copenhagen in calf population. Chloramphenicol (CP)-resistant Salmonella typhimurium var copenhagen was frequently isolated (44.1 to 76.7%) from dead, diseased, and healthy calves on 3 farms in 1973 in northern Japan. On 2 of the farms, CP-resistant salmonella appeared suddenly during an epizootic of salmonella infection, and persisted. Of 87 CP-resistant to tetracycline (TC), streptomycin (SM), and sulfonamides (SA), and the remaining 13 isolates from dead calves on a farm were resistant to TC, SM, SA, and kanamycin (KM). Resistance patterns of all CP-resistant isolates were transferred completely.


Concentration of lactoferrin in milk of normal lactating cows and changes occurring during mastitis. The mean lactoferrin (Lf) concentration determined by electroimmunodiffusion (EID) assay of whey preparations from 80 quarters of 20 normal lactating cows was 0.35 mg/ml. The mean alpha-lactalbumin (alpha-LAC) and bovine serum albumin (BSA) concentrations were 2.01 mg/ml and 0.29 mg/ml, respectively. The mean was significantly related to cell count (P smaller than 0.01), BSA (P smaller than 0.05), stage of lactation (P smaller than 0.05), and milk production (P smaller than 0.05). The Lf-milk production relationship was the only negative correlation. In 11 cows with mastitis, there was a significant (P smaller than 0.01) increase in mean Lf concentration in infected quarters from 0.55 mg/ml on day 1 of the infection to 1.89 mg/ml by day 3. By day 15 clinical signs had subsided and mean Lf concentrations had decreased to near day 1 values. On day 3 quarters infected with coliform bacteria (clinical mastitis generally more severe) had mean Lf values more than twofold greater than those quarters infected with species of Staphylococcus or Streptococcus (milder clinical signs). Noninfected (control) quarters of cows having coliform bacteria-infected quarters had slightly increased mean Lf concentrations, where Lf concentration in contral quarters of cows having quarters infected with gram-positive organisms remained unchanged.


Subacute staphylococcal pneumonia in a renal transplant recipient. A patient is reported who developed subacute staphylococcal pneumonia 17 months after renal transplantation. Although the illness was modified by oral antimicrobial drugs, a remarkably benign course was observed, leading to a presumptive diagnosis of opportunistic fungal infection. Thus, staphylococcal pneumonia may complicate the differential diagnosis of pulmonary infection in transplant recipients.


Disseminated mycobacterium kansasii infection presenting as cellulitis in a recipient of a renal homograft. A recipient of a renal homograft developed disseminated infection caused by Mycobacterium kansaii. He initially presented with cellulitis and abscesses in one foot, and was thought to have a pyogenic bacterial infection. The daily administration of prednisone and azathioprine appears to have prevented the typical cell-mediated granulomatous reaction to mycobacterial infection and to have contributed to the patient's atypical inflammatory response. A switch to alternate-day prednisone combined with antimycobacterial medication resulted in rapid healing without rejection of the homograft.


The pulmonary response to a bacteremic challenge. The pulmonary response to a bacteremic challenge was studied in a mouse model. The distribution of intravenously injected radiotracer-labeled Proteus mirabilis and Staphylococcus aureus in the lungs, liver, spleen, kidney, and blood was examined at 0, 5 30, 60, and 240 min. Pulmonary killing of these organisms was studied at 0, 30, and 240 min; 0.8 plus or minus 0.1 per cent of the P. mirabilis and 1.5 plus or minus 0.2 per cent of the S. aureus remained within the lungs after 4 hours. Although only 2.2 plus or minus 0.2 per cent of the P. mirabilis organisms were alive, 33.8 plus or minus 8.8 per cent of the staphylococci remained viable after this period. Light and electron micographs verified that polymorphonuclear leukocytes phagocytized these bacteria. The defense mechanisms of the lung against bloodborne and airborne bacterial infection are functionally, as well as morphologically, distinct.


Learning pulmonary function interpretation: deductive versus inductive methods. Volunteer undergraduate medical students were randomly divided into 2 groups. One group were given pulmonary function data and the correct diagnoses from 18 patients. They were told to try to derive the rules by which the diagnoses were made. The other group were given the data from the same 18 patients, but were required to use a computer-assisted instructional program to arrive at the diagnoses in a deductive fashion. Both groups were pre- and post-tested. The deductive method provided higher post-test results. The inductive method took longer and produced more dropouts from the study.


Health hazards of bivalve-mollusk ingestion. Bivalve mollusks (oysters, clans, and mussels) filter large quantities of water unselectively and thereby may concentrate a variety of aquatic contaminants pathogenic for man within edible shellfish viscera. The recognized bacterial disease associated with ingestion of contaminated bivalves include typhoid fever (not presently a public health problem), Vibrio parahemolyticus gastroenteritis, and Vibrio chloerae infection. The major known shellfish-associated viral diseases are viral hepatitis and possibly viral gastroenteritis. The ingestion of bivalves that have fed on the toxic species of dinoflagellates that produce red tides may be responsible for an uncommon and very rarely fatal illness, paralytic shellfish poisoning. Outbreaks of airborne respiratory irritation in populations exposed to red tides may be the most common public health problem associated with red tides. The health hazards resulting from industrial, agricultural, and oil pollution of bivalves in coastal waters and the hazard from improper handling of bacterially contaminated mollusks remain to be defined.


The monoclonal nature of lymphocytes in multiple myeloma. Effects of therapy. Despite the increased amounts of serum immumoglobulins (Ig) in multiple myeloma, the percentage of bone marrow-dependent (B) cells carrying surface Ig in the peripheral blood compartment were decreased, when compared with that in control patients with polyclonal gammopathy or with that in normals (5 plus or minus 2% in patients with multiple myeloma and 19 plus or minus 5% or 22 plus or minus 7% in controls). Most circulating B cells in patients with multiple myeloma were shown to carry individually specific idiotypic Ig. The monoclonal idiotypic nature of the surface Ig was shown by using antiserums raised against the monoclonal Ig. The idiotypic antiserum was capable of actively binding to and stimulating the idiotypic lymphocytes to divide in vitro. Commercial anti-Ig antiserums raised against normal Ig did not bind to the myeloma lymphocytes. After chemotherapy, lymphocytes carrying the idiotypic Ig decreased in numbers, and this correlated with other variables of clinical improvements. Its role in the pathogenesis of myeloma and its importance for diagnosis and follow-up of patients with myeloma are discussed.


The immunofluorescent "band" test in mixed connective tissue disease. Skin biopsy specimens from normal subjects and patients with mixed connective tissue disease, systemic lupus erythematosus, and rheumatoid arthritis were examined for the presence of a "band" of immunoglobulins and complement at the dermal-epidermal junction, using immunofluorescent techniques. A positive immunofluorescent band test was found in the clinically uninvolved skin in three of six patients with mixed connective tissue disease, five of six patients with systemic lupus erythematosus, and none of the patients with rheumatoid arthritis or normal subjects. Although a positive immunofluorescent band test in uninvolved skin has been considered to be fairly specific for the diagnosis of systemic lupus erythematosus, our results suggest that this test cannot be used to distinguish mixed connective tissue disease from systemic lupus erythematosus.


[Surgical malabsortion (author's transl)]. Two interesting aspects should be considered in intestinal malabsortion from the Surgical point of view. First, this sindrome may be caused by subobstructive lesions of the gut, which may be able of surgical correction. Second, malabsortion may follow certain operations performed in the gastrointestinal tract. Many of this problems are connected with alterations of the intestinal flora, and or a diminution in the obstructive intestinal surface. The clinical picture is not clear due to the pathological and surgical implications. The experience of the last 10 years is reviewed and conected with the following items, whem accompanied by not infectious diarrhea: a) Hiatus hernia and vaguectomy; b) Gastrointestinal by-pass; c) Intestinal atresia and stenosis; d) Small gut resections-Short bowel sindrome; e) Incompetence of the ileocecal valve.


Renal vein thrombosis and nephrotic syndrome. A prospective study of 36 adult patients. During 2 years we studied 36 of 41 consecutive patients with nephrotic syndrome. Twelve (Group 1) had renal vein thrombosis; the renal pathology was membranous glomerulonephritis in 10 and membranoproliferative glomerulonephritis in 2. Eighteen without renal vein thrombosis (Group 2) had either membranous (10 patients) or membranoproliferative (8 patients) glomerulonephritis. Clinical presentation, laboratory data, renal function, renal histology, and immunopathology were similar in both groups; thromboembolic phenomena were frequent. Ten of 12 patients with renal vein thrombosis were given oral anticoagulants and followed for 4 to 24 months. None died or had thromboembolic episodes. The results show that one third of the patients with nephrotic syndrome associated with either membranous or membranoproliferative glomerulonephritis had renal vein thrombosis, and there were no clinical, laboratory, histological, or immunopathological finding(s) diagnostic of renal vein thrombosis. Our data indicate that renal vein thrombosis is a frequent complication in nephrotic syndrome and membranous or membranoproliferative glomerulonephritis.


Long-term therapy for chronic bacteriuria in men. U.S. Public Health Service cooperative study. Response to therapy, renal function, and mortality were analyzed in a prospective study of 249 men with bacteriuria followed for up to 10 years. All patients received initial organism-specific antibiotic therapy followed by 2 years of continuous treatment with sulfamethizole, nitrofurantoin, methenamine mandelate, or placebo. Continuous therapy with active drugs delayed recurrence of bacteriuria and reduced acute clinical exacerbations of infection. Patients with pure Escherichia coli bacteriuria, normal intravenous pyelogram, no previous therapy, and a normal prostate had a good prognosis with short-term antibiotic therapy alone. The presence of prostatic or upper urinary tract calculi, pyelonephritic scars, or mixed or enterococcal infections predicted a poor bacteriologic prognosis. In the absence of severe urologic disease or concomitant noninfectious renal disease no patients with persistent bacteriuria developed renal failure. Continuous antibiotic therapy is of value in selected male patients with bacteriuria in reducing recurrence and acute clinical exacerbations of urinary tract infection.


Cardiac response to repeated doses of isoproterenol aerosol. We studied 18 patients with moderate to severe asthma for cardiac response to repeated doses of isoproterenol aerosol. In only 1 patient was there a significant increase in heart rate immediately after inhalation of isoproterenol aerosol, and it lasted only for 1 minute. In 2 patients increased heart rate was either due to breathholding or to the propellant in the aerosol. There was no cumulative effect on heart rate. Arrhythmias did not develop at any time despite repeated doses of aerosol every 5 to 20 minutes. Peak expiratory flow rate increased 5 minutes after the first dose, and it increased even further after repeated doses; at no time did it decrease after repeated doses.


Spindle microtubules: thermodynamics of in vivo assembly and role in chromosome movement. In this paper I have presented results of experiments in which spindle microtubules were depolymerized by hydrostatic pressure, in order to examine the Inoué dynamic equilibrium concept of spindle assembly and the possible role of microtubule depolymerization-polymerization in the movement of chromosomes. Using a newly developed optical hydrostatic pressure chamber, I investigated with polarization microscopy the quantitative effects of pressure on the polymerization of spindle microtubules and, with phase contrast microscopy, the relationship of pressure-induced spindle microtubule depolymerization to chromosome movement in living cells. From results of earlier experiments, principally those of Inoué et al. with low temperature and colchicine as microtubule-depolymerizing agents, and from results of my own research, I have concluded that: (1) spindle fiber microtubules are sensitive to depolymerization by pressure (3000-7000 psi), spindle microtubules do exist in a labile equilibrium with a pool of subunits, and the Inoué simple equilibrium model does predict changes in spindle microtubule assembly at metaphase induced by pressure; (2) the stability of microtubules depends on the number of "attached ends;" (3) the longest interpolar microtubules and the longest chromosomal fiber microtubules regulate the spindle interpolar length and the chromosome-to-pole positions; (4) chromosome velocity is independent of the number of spindle microtubules, as well as of the drag force of the chromosomes; (5) the chromosomal fiber microtubules transmit the forces between the poles and between the chromosomes and the poles; and (6) polymerization of microtubules does produce pushing forces and, if controlled microtubule depolymerization does not actually produce pulling forces, at least it governs the velocity of chromosome-to-pole movement.


Photokeratoscopy in the fitting of soft contact lenses. Our ultimate goal is to develop a photokeratoscopic system that will enable the fitter to select an initial lens of the proper design and power to fit a given eye and with reasonable assurance that further fitting will rarely be required. Our studies in this direction have carried us through to a prefitting screening system for the Bausch and Lomb Soflens that greatly increases the probability of successful fitting (and which demonstrates the importance of corneal shape in the successful fit of this lens) to a highly promising experimental system that is applicable to larger lenses with spherical base curves. The development of this computer-assisted fitting system is highly desirable. It will make the fitting a much simpler and efficient process with much less trauma to the eye and a marked reduction in the risk of accidental infection than with trial lens fitting. But, a second desirable effect that is not readily apparent is the use of the computer to drive fabrication equipment to manufacture lenses on a custom-fit basis to obtain the maximum in physiological tolerance that these lenses are capable of delivering. In either case, the patient is the ultimate beneficiary and that should always be our major goal.


A revised Fasanella-Servat ptosis operation. The Fasanella-Servat operation for ptosis has had several modifications of suture placement. The present method utilized 5-0 nylon which traverses the cut edges as a running mattress suture. The ends of the suture are fixed on the skin surface with rubber bolsters. The suture is removed in 10 days. The advantages are: (1) no suture knots on the corneal surface; (2) ease of placement; (3) minimal tissue reaction; (4) the suture is removed; and (5) ease of suture removal.


Levator tuck: a simplified blepharoptosis procedure. A simplified technique for tucking the levator palpebrae superioris aponeurosis and muscle in the correction of blepharoptosis is described. The anterior (skin) approach is used and no special instruments are required. The advantages of this procedure are discussed, including preservation of the normal anatomy as much as possible, minimum dissection and minimum edema. A preliminary number of cases are reported. It is believed that this technique is useful in cases of acquired blepharoptosis and in congenital blepharoptosis with good levator function.


Choledochal cysts. A review of the cystic anomalies of the biliary tree. Congenital cysts of the biliary tree, although uncommon, are being reported in increasing numbers. The widely accepted classification would seem to warrant modification in the light of recent observations. The clinical spectrum of the condition is reviewed, together with the surgical approach to treatment and its indications and complications.


Anesthesia in the Yom Kippur war.

Anesthesia in the Yom Kippur war. The role of the anesthetist in the treatment of battle casualties is discussed in the light of personal experience in a field hospital and in the rear during the Yom Kippur War of October 1973. Resuscitation and intensive care both before and after evacuation play an important part in reducing mortality, and the importance of providing adequate facilities for these functions in the battle area as well as at the base is emphasized.


Scanning techniques to assess thyroid nodules. Despite its nonspecificity, the thyroid scan remains an important diagnostic aid in the evaluation of the patient with a solitary thyroid nodule. Dual radionuclide thyroid imaging using 99m-Tc pertechnetate and 123-I offers useful information than either alone. The role of complementary diagnostic modalities using ultransonography and thermography looks promising but is as yet unclear.


Selective distal splenorenal shunt for bleeding esophageal varices. The selective distal splenorenal shunt has been shown to be equally as effective as total portal-systemic shunting procedures in the control of variceal hemorrhage and it can now be performed with an equivalent operative mortality. It is superior to other shunts in metabolic aspects and results in a markedly decreased incidence of postoperative hepatic encephalopathy. Massive ascites constitutes a definite contraindication to the selective distal splenorenal anastomosis, but for all other suitable patients this procedure appears to be the optimal method of surgical management at this time.


Low renin hypertension.

Low renin hypertension. Low renin hypertension comprises a spectrum of disorders ranging from primary aldosteronism to obvious disorders of other mineralocorticoids, as well as a variety of miscellaneous disorders. The largest group of patients with low renin hypertension have no clear abnormality in mineralocorticoid production. However, many lines of evidence suggest the critical role of volume excess in the pathogenesis of hypertension in these patients. More detailed physiological studies must be performed in order to totally understand the spectrum of pathophysiology in low renin hypertension. However, while such studies are in progress the evidence from the literature suggests that these patients must be treated and that in most of these patients diuretic administration, either spironolactone or the thiazide group of diuretics, is usually effective in achieving a reduction of blood pressure to normal.


The steal syndromes.

The steal syndromes. Blood can be stolen from almost any vascular bed and redistributed. The external carotid artery can steal from cerebral structures when occlusion of the common carotid artery proximal to the bifurcation causes reversal of flow through the internal carotid artery (13, 45, 46). The external carotid artery has also been shown to steal blood flow from the vertebral artery distribution (13, 74). Double steals involving both the subclavian and external carotid arteries are seen in 1 to 2% of patients (13, 46). There is also the "triple steal syndrome" wherein both subclavian arteries and one external carotid artery are involved (14).


Von Willebrand's disease.

Von Willebrand's disease. The common inheritable hemorrhagic disorder, von Willebrand's disease, has been known for only about 50 yr. During these years it has been well established that the cause of the disease is a deficiency of a plasma protein with remarkable biological properties. Future research should focus on details of the molecular structure of this protein. It is hoped that basic science will help to elucidate those aspects of von Willebrand's disease that are not yet properly understood.


The autinglobulin test in autoimmune hemolytic anemia. The foregoing summarizes what can be learned from a carefully performed antiglobulin test using specific antisera. Clinical syndromes can be more easily considered, and mechanisms of destruction can be more certainly discerned.


Metabolic response to infection.

Metabolic response to infection. A generalized infectious process leads to a broad and complex array of metabolic responses within the host. Certain of these responses have a direct causal relationship to the interactions of body cells with invading  microorganisms or their products, or to specific host defensive mechanisms. Other host metabolic responses have less clearly defined roles although they involve many tissues and seem to be initiated and regulated by certain hormones-like endogenous mediators. These latter responses contribute to the maintenance of body homeostasis, the provision of metabolizable energy to meet increased body needs, and the synthesis of the acute phase reactant serum proteins.


Effects of drugs on uric acid in man.

Effects of drugs on uric acid in man. In this review the drugs capable of increasing or lowering the serum urate concentration are considered with regard to mechanism of action and significance of the effect, where known.  Several hypouricemic agents, probenecid, sulfinpyrazone, and allopurinol, are considered in further detail because of their major clinical importance.  No effort has been made, however, to summarize the relative clinical indications for each agent.  In addition, in those cases where specific details could not be included because of limitation of space, the appropiate reference has been given.


Oral contraceptives: relations to mammary cancer, benign breast lesions, and cervical cancer. The results of experimental studies on the relationship of estrogens and oral contraceptives to mammary lesions demonstrate that the type of response obtained depends largely on the species and strain of animal that is employed. A variety of clinical studies has failed to demonstrate that estrogen can cause mammary cancer, this lack of effort correlates with the results obtained in various studies in animals. Similar relationships exist for oral contraceptives, and the clinical data show good agreement in demonstrating that the contraceptive steroids do not have a tumorigenic effect on the human mammary gland.  Estrogen can increase the occurrence of cervical cancer in certain strains of mice, but apparently this effect is not observed in other species of animals, including man.  The preponderance of data shows that oral contraceptives do not adversely affect the occurence of abnormal Papanicolaou smears, cervical dysplasia, cervical cancer in situ, or invasive cervical cancer.


Antibiotic resistance patterns of clinical isolates of Serratia marcescens. Antimicrobial susceptibility patterns of 102 clinical isolates of Serratia marcescens from three medical centers were studied by using disk sensitivity and agar dilution methods. The least resistance was demonstrated against gentamicin, nalidixic acid, chloramphenicol, and sulfisoxazole, all of which inhibited more than 80% of the strains. Cephalothin was completely ineffective, and more than 90% of strains were resistant to ampicillin and tetracycline. As demonstrated by the agar dilution method, the minimal inhibitory concentration of nalidixic acid, gentamicin, tobramycin, and chloramphenicol for most strains fell within therapeutically attainable concentrations. The prevalence of resistance to ampicillin, cephalothin, and tetracycline was nearly the same at all three medical centers, whereas there appeared to be patterns characteristic for each center with regard to the other drugs used. Eleven of the isolates produced pigment and exhibited patterns similar but not identical to those of the nonpigmented strains, all 11 being resistant to between three and six drugs. Half of the strains were resistant to five or more antibiotics, indicating that some Serratia exhibit resistance to an unusually broad range of therapeutic agents.


Comparative efficacy of cephalexin and ampicillin for shigellosis and other types of acute diarrhea in infants and children. Most ampicillin-resistant Shigella are susceptible to cephalexin. Randomized treatment with cephalexin or ampicillin was given to 154 infants and children with acute diarrhea. Rectal swab cultures revealed Shigella in 42%, Salmonella in 6%, enteropathogenic Escherichia coli in 2%, and no pathogen in 50%. Cephalexin failed to eradicate Shigella after 5 days of treatment in 76% of patients as contrasted with 28% of ampicillin-treated patients with susceptible organisms. Shigella persisted in 78% of ampicillin-treated patients with resistant organisms. Diarrhea lasted more than 5 days in 43% of cephalexin-treated patients, in 56% of the ampicillin group with resistant organisms, but in only 9% of ampicillin-treated patients with susceptible organisms. The failure of cephalexin was due to the relatively high minimal inhibitory concentrations and minimal bacterial concentrations of 5 or 10 mug/ml and, although serum concentrations were twice the minimal bacterial concentration, they were not sufficient to demonstrate killing by the serum dilution method. In vitro susceptibility or resistance of Shigella to ampicillin correlated with clinical success or failure. Cephalexin is not a suitable drug for treatment of shigellosis in patients with ampicillin-resistant organisms.


Rapid, simple bioassay for 5-fluorocytosine in the presence of amphotericin B. It is important that serum levels of 5-fluorocytosine (5FC) be measured to insure therapeutic levels while avoiding toxicity. This is particularly true in patients with renal insufficiency. The concurrent use of amphotericin B and 5FC complicates the measurement of 5FC in the serum, since fungi used in conventional bioassay systems are uniformly susceptible to amphotericin B. This paper describes the development of a simple, reliable, 6-h bioassay for 5FC in the presence of amphotericin B. The assay is based upon the fact that 5FC diffuses readily through yeast nitrogen base agar, whereas amphotericin B apparently does not. This assay allows rapid adjustments in therapy of patients receiving both 5FC and amphotericin B and has permitted us to maintain 5FC serum levels between limits of 25 and 120 mug/ml in patients with altered renal function.


Inhibition by levorphanol and related drugs of amino acid transport by isolated membrane vesicles from Escherichia coli. Levorphanol inhibits the transport of the amino acids proline and lysine by cytoplasmic membrane vesicles derived from Escherichia coli. The degree of inhibition increases with increasing levorphanol concentration and ranges from 26% at 10(-6) M levorphanol to 92% at 10(-3) M levorphanol. The effect is independent of the energy source, since levorphanol inhibits proline uptake to the same extent in the presence of 20 mM d-lactate or 20 mM succinate and in the absence of an exogenous energy source. Levorphanol does not irreversibly alter the ability of membrane vesicles to transport proline, since incubation of membrane vesicles for 15 min in the presence of 0.25 mM levorphanol, a concentration which inhibits proline transport by more than 75%, has no effect on the rate of proline transport by these vesicles once the drug is removed. Both the maximum velocity and the K(m) of proline transport are modified by levorphanol, hence, the type of inhibition produced by levorphanol is mixed. The inhibitor constant (K(i)) for levorphanol inhibition of proline transport is approximately 3 x 10(-4) M. Membrane vesicles incubated in the presence of levorphanol accumulate much less proline at the steady state than do control vesicles. Furthermore, the addition of levorphanol to membrane vesicles preloaded to the steady state with proline produces a marked net efflux of proline. Levorphanol does not block either temperature-induced efflux or exchange of external proline with [(14)C]proline present in the intravesicular pool. Dextrorphan, the enantiomorph of levorphanol, and levallorphan, the N-allyl analogue of levorphanol, inhibit proline and lysine transport in a similar manner. Possible mechanisms of the effects of these drugs on cell membranes are discussed.


Inactivation of Treponema pallidum by silver sulfadiazine. Silver sulfadiazine, an anti-infectious agent for the prevention and treatment of burn sepsis, has been found to possess antitreponemal activity against Treponema pallidum. At 28 C, complete inactivation of the organism was produced by exposure of the organism to a concentration of 50 mug of the drug per ml for 1 to 5 min, 12 to 25 mug/ml for 10 to 15 min, and 6.2 mug/ml for 30 min. At 37 C, the amounts of silver sulfadiazine required for inactivation were two- to fourfold less.


Effect of protein concentration and binding on antibiotic assays. ASSAY CURVES, USING A DISK DIFFUSION METHOD FOR THE ANTIBIOTICS GENTAMICIN AND CEFAZOLIN, WERE PREPARED WITH: saline, saline plus 10% serum, and ascitic, synovial, cerebrospinal, and pleural fluids. The curves were compared with a standard curve prepared with pooled human serum. The pH, total protein, glucose, blood urea nitrogen, sodium, potassium, calcium, phosphorus, chloride, CO(2) content, uric acid, cholesterol, bilirubin, serum glutamic oxalacetic transaminase, CPK, LDH, and alkaline phosphatase were determined and compared for all fluids. Measurements for cefazolin levels were falsely elevated in those fluids with low protein content when serum was used as a reference standard. There was a linear inverse relationship between the protein content of the fluids and the cefazolin level with serum as the standard for the assay of this highly protein-bound antibiotic. No discrepancies were observed in the assay curves for gentamicin, an antibiotic known not to be bound by serum proteins.


Recovery of polysome function of T4-infected Escherichia coli after brief treatment with chloramphenicol and rifampin. T4-infected Escherichia coli cells briefly exposed to rifampin, or to rifampin plus chloramphenicol, were capable of protein synthesis for some time after removal of the antibiotics, although ribonucleic acid synthesis was irreversibly inhibited. Partially completed peptides trapped on polysomes by high levels of chloramphenicol were eventually completed after removal of the drug, as demonstrated by subjecting labeled peptides from appropriate polysome regions to polyacrylamide disc gel electrophoresis. Thus, the effect of the drug appears to be reversible on the molecular as well as the cellular level.


Stimulation of enzyme synthesis by sublethal concentrations of chloramphenicol is not mediated by ribonucleotide pools. Growth of Salmonella typhimurium LT-2 strain pyrA81 in minimal medium containing 0.8 mug of chloramphenicol (CAP) per ml resulted in a 50 to 100% increase in the steady-state nucleotide pools in the cells. When such a culture was starved for uracil, the pyrimidine nucleotide pools decayed much more slowly in CAP-treated cells than in controls. An attempt was made to determine whether this effect of CAP on nucleotide pools could account for enhanced enzyme derepression observed under the same conditions (8). Treatment with low levels of puromycin also resulted in elevation of nucleotide pools but did not lead to enhanced enzyme synthesis. CAP treatment during arginine starvation has been shown to enhance enzyme synthesis, but nucleotide pools were not significantly affected by CAP nor was the stringent response relieved under these conditions. Thus, the effects of CAP on enzyme synthesis cannot be the result of effects of the antibiotic on nucleotide pools in all cases. The elevation of nucleotide pools was shown not to be due to enhanced conversion of exogeneous uracil into nucleotides, but to result from the enhanced turnover of ribonucleic acid in CAP-treated cells.


Effect of tetracycline on puromycin-induced polysome degradation: influence of magnesium and polyamines. Puromycin-induced polysome degradation has been shown to require G factor, guanosine 5'-triphosphate, and the presence of a ribosome release factor (Hirashima and Kaji, 1972, 1973). Tetracycline, which does not inhibit formation of peptidyl-puromycin (Gottesman, 1967; Sarkar and Thach, 1968) nor the guanosine 5'-triphosphate hydrolysis mediated by elongation factor Tu (Ono et al., 1969), inhibits polysome degradation. The tetracycline inhibition requires Mg(2+) at concentrations above 8 mM, which are inhibitory to protein synthesis in vitro. At concentrations of Mg(2+) below 8 mM, polysome degradation is insensitive to tetracycline, but not to fusidic acid. Addition of spermidine, but not of other polyamines, enables the tetracycline inhibition to occur at concentrations of Mg(2+) as low as 2 mM. The inhibition by tetracycline and by fusidic acid suggests that ribosome movement may be essential for the function of ribosome release factor, or that these antibiotics may directly affect its action.


Incorporation of L-2,5-dihydrophenylalanine into cell proteins of Escherichia coli and sarcoma 180. l-2,5-Dihydrophenylalanine is extensively incorporated as a phenylalanine analogue into cell proteins. Phenylalanine-requiring Escherichia coli ATCC 9723f and sarcoma 180 grow at normal rates initially with the analogue and maximally replace 65 and 33%, respectively, of phenylalanine in the peptide residues of their cell protein without death. With the analogue alone growth of E. coli becomes non-steady-state and asymptotically inhibited. In mixtures of the analogue and phenylalanine, growth eventually becomes steady state or logarithmic. The logarithmic rate is inversely proportional to the extent of incorporation of this analogue or of p-fluorophenylalanine, and the projected maximal replacement is the same as that obtained asymptotically with the analogue alone. Thus, the toxicities in steady-state and non-steady-state growth are closely related. Moreover, it is proposed that single salient protein defects may determine the extent of growth rate reduction.


Empiric therapy for cancer patients: comparative study of ticarcillin-tobramycin, ticarcillin-cephalothin, and cephalothin-tobramycin. Three combinations of antibiotics (cephalothin-tobramycin, cephalothin-ticarcillin, and ticarcillin-tobramycin) were administered empirically to 186 patients with cancer who were suspected of having a life-threatening infection. In approximately one-half of these patients, gram-negative infection was documented bacteriologically and consisted of septicemia in 50% of these patients. The three antimicrobial regimens were similarly effective and resulted in a favorable clinical response in approximately 55% of the patients. The administration of the cephalothin-tobramycin combination was associated with a significantly higher frequency of nephrotoxicity than that of the other two regimens.


Treatment of anaerobic infections with metronidazole. The results of treatment of 10 patients with anaerobic infections with metronidazole are presented. Six patients were cured, three showed initial good response but circumstances required a change to another drug, and one patient did not respond. The unique spectrum of the drug, its pharmacology, and limitations are discussed. The results indicate that further clinical trials to determine the efficacy of metronidazole in the treatment of anerobic infections are indicated.


Antibacterial activity of cinoxacin in vitro. Cinoxacin is a new synthetic compound similar chemically and in antimicrobial activity to oxolonic acid and nalidixic acid. It is most effective against Escherichia coli and Proteus mirabilis, but at concentrations expected in the urine it is inhibitory for all species of Enterobacteriaceae. Relative to nalidixic acid, cinoxacin has slightly greater inhibitory and bactericidal activity, less inoculum effect probably due to less heterogeneity in the susceptibility of bacterial cells, and less inhibition by high concentrations of serum protein. Both drugs are more active in an acid than an alkaline medium. Glucose can specifically antagonize the inhibitory effect against P. mirabilis. In urine the bactericidal rate and effect are decreased. Resistance to cinoxacin can be developed quickly by serial transfers in vitro. Some nonresistant organisms remained viable in bactericidal drug concentrations. The in vivo importance of the favorable features of cinoxacin must be determined by clinical trials.


Scanning electron microscopy of Candida albicans after in vitro treatment with miconazole. A study was made on the in vitro action of the antimycotic miconazole on Candida albicans yeast cells with scanning electron microscopy, and the effects were compared with those seen on the yeast cells by means of transmission electron microscopy. It was found that cells exposed to fungistatic and minimal fungicidal doses of miconazole (10(-7) M and 10(-6) M) presented rough surfaces and had multiple, desoriented buds and bud scars. Whereas in control cultures the cells were well separated, the treated ones formed small clusters of interconnected cells. After exposure to a fungicidal concentration (10(-4) M) of the drug, most of the remaining cells showed smooth surfaces and were covered with numerous vesicular structures probably representing cytoplasmic remnants derived from broken cells. This has been substantiated by the presence of abundant fragments of cell walls and confirmed by examination of similarly treated cultures in the transmission electron microscope. Moreover, the cells with an apparently intact surface when examined with scanning electron microscopy were shown with transmission electron microscopical examination to be completely necrotic inside.


Pfizer selective enterococcus agar overlay method for the enumeration of fecal streptococci by membrane filtration. The use of Pfizer selective enterococcus (PSE) agar with the membrane filter technique for the enumeration of fecal streptococci is limited due to the inability of the characteristic black precipitate, indicative of esculin hydrolysis, to diffuse from the medium through the membrane. A modification of the membrane filter technique that consisted of placing the membrane on PSE agar and overlaying it with tempered PSE agar was evaluated by comparing recovery, selectivity, and other parameters with M-enterococcus and KF-streptococcus agars, two selective media routinely used with the membrane filter technique for the enumeration of fecal streptococci in water and wastewater. No statistically significant differences could be demonstrated in the recovery capabilities of the three media. Inasmuch as the PSE overlay technique requires only 24 h of incubation as opposed to 48 h for the other two media, this modification may have some merit in water pollution monitoring programs.


Occurrence of Klebisiella pneumoniae in surface waters. The occurrence of Klebsiella pneumoniae in surface waters was not found to be ubiquitous. When it was isolated, Escherichia coli could also be found. The fecal coliform to fecal streptococci ratio suggest that its origin could be human, animal, or mixed sources.


Inhibition of microbial growth by fatty amine catalysts from polyurethane foam test tube plugs. When polyurethane foam test tube plugs are autoclaved, they release volatile fatty amines that inhibit the growth of some microorganisms. The chemical structures of these amines were determined by the use of a gas chromatograph-mass spectrometer. They are catalysts used to produce the foam. The problem of contaminating growth media with toxic substances released from polymeric materials is discussed.


Isolation and characterization of Vibrio parahaemolyticus from Cape Cod soft-shell clams (Mya arenaria). Vibrio parahaemolyticus was isolated from soft-shell clams (Mya arenaria) taken from 10 different clamming areas on Cape Cod, Mass., during July and August 1972. Direct plating on thiosulfate-citrate-bile salts-sucrose agar was found to be superior to either direct plating on Vanderzant modified salt starch agar or enrichment with Trypticase soy broth containing 7% salt for isolation from clam samples. Morphological and biochemical characteristics of 33 isolates from 30 samples generally conform to those described for this organism in the literature, except for the production of acid from sucrose, lactose, and sorbitol. Six of the isolates were hemolytic on human blood agar plates, whereas all showed a negative Kanagawa phenomenon. Twenty of the 33 isolates reacted with pooled antisera to the K antigen; 15 of these reacted with 9 different specific K antisera, leaving 5 untypable. Ten of these 15 reacted with 4 different O antisera.


Qualitative and quantitative assay of trichothecin: a mycotoxin produced by Trichothecium roseum. A method for quantitative determination of trichothecin in crude culture filtrates was presented. The method utilized an agar diffusion bioassay against Candida albicans, a colorimetric test involving a halochromatic reaction with sulfuric acid, and subsequent formation of blue color with methanol, and thin-layer chromatography of trichothecin and its dinitrophenylhydrazine derivative. A positive result in all three systems confirmed the presence of trichothecin. Quantitative results were generally in close agreement.


Effect of dichlorodifluoromethane on the appearance, viability, and integrity of Escherichia coli. Cultures of Escherichia coli H52 were treated with liquid dichlorodifluoromethane (fluorocarbon-12 [f-12]) for 2 h at 22 C and then examined microscopically. Treated cells tended to clump, and their cytoplasms were generally less dense and less uniform in appearance than those of control cells. E. coli ML30 was exposed to f-12 at a concentration of 1.25 X saturation for times up to 1,200 min at 22 C. Cells were examined for changes in viability (plate count), permeability (as measured by exit of alpha-[14-C]methylglucoside or uptake of omicron-nitrophenyl-beta-D-galactopyranoside), release of compounds absorbing at 260 nm, and lysis (changes in absorbance at 420 nm). Large losses of alpha-methylglucoside and of percentage of viability occurred after brief exposure to f-12. Release of compounds absorbing at 260 nm occurred more slowly than the aforementioned events, possibly because these molecules are larger than alpha-methylglucoside. During 1,200-min exposure to f-12, the number of survivors decreased from 10-9 to 10-4 organisms/ml, the loss of compounds absorbing at 260 nm amounted to 50 percent, and 32 percent lysis occurred. Most of these changes occurred during the first 300 min of treatment. Loss of alpha-methylglucoside was almost complete after 1-min exposure to f-12. These results suggest that death of the cell involves several stages, with a change of permeability, occurring first, followed by leakage of compounds of increasing size and, finally, lysis.


Sequential growth of bacteria on crude oil. By modification of the enrichment culture procedure three bacterial strains capable of degrading crude oil in sea water were isolated in pure culture, UP-2, UP-3, and UP-4. Strain UP-2 appears to be highly specialized for growth on crude oil in sea water since it showed strong preference for oil or oil degradation products as substrates for growth, converted 66% of the oil into a form no longer extractable by organic solvents, quantitatively degraded the paraffinic fraction (gas chromatographic analysis), emulsified the oil during exponential growth, and produced 1.6 x 10-8 cells per mg of oil. After exhaustive growth of UP-2 on crude oil the residual oil supported the growth of UP-3 and UP-4, but not a previously isolated oil-degrading bacterium, RAG-1. Strains UP-2, UP-3, and UP-4 grew on RAG-1-degraded oil (specifically depleted of n-alkanes). The growth of UP-3 and UP-4 on UP-2 and RAG-1-degraded oil resulted in the production of new paraffinic compounds as revealed by gas chromatography. When the four strains were grown either together in a mixed culture or sequentially, there was over 75% oil conversion. By plating on selective media, growth of the individual strains was measured kinetically in the reconstituted mixed culture, revealing competition for common growth substances (UP-2 and RAG-1), emhanced die-off (UP-2), and stabilization (UP-4) during the stationary phase.


Production of cellulose microfibrils by Rhizobium. Electron microscope examination of Rhizobium spp. revealed microfibrils produced by flocculating strains but not by nonflocculating strains. The microfibrils from R. trifolii (NA30) were isolated and identified as cellulose by enzymatic, X-ray diffraction, and infrared spectral analyses. Both infective and noninfective strains of R. trifolii flocculated and produced microfibrils. More infection threads were observed in clover root hairs growing in the presence of flocs in comparison with root hairs where single bacterial cells predominated.


Fluorescent-antibody study of natural finger-like zoogloeae. Fluorescent-antibody techniques using Zoogloea ramigera 106 antiserum were used to study fresh activated sludge flocs and finger-like zoogloeae in the microbial film that developed over stored samples of activated sludge. Few cells in fresh activated sludge reacted positively with the fluorescein-labeled antiserum. Finger-like zoogloeae containing reactive cells were readily observed in the microbial film layer over stored activated sludge. Certain of the naturel finger-like projections were entirely composed of cells that reacted positively to the labeled Z. ramigera 106 antiserum, whereas other projections were devoid of reactive cells.


Effect of aflatoxin on phagocytosis of Aspergillus fumigatus spores by rabbit alveolar macrophages. Rabbits were given dialy doses of aflatoxin B1 equivalents of 0.03, 0.05, 0.07, and 0.09 mg for a 2-week period. Macrophages were harvested at the end of the experimental period, and in vitro phagocytosis experiments were conducted using Aspergillus fumigatus spores as ingestion particles. Alveolar macrophages from rabbits given the above doses of aflatoxin had reduced phagocytic activity when compared with macrophages from control rabbits. Incorporation of serum from the aflatoxin-treated rabbits in the in vitro culture system resulted in less stimulation of phagocytosis by macrophages from control rabbits when compared with the same system incorporating control serum. Stimulation of phagocytosis by macrophages was least when both serum and macrophages from aflatoxin-treated rabbits were used in the in vitro system.


Microbiological characteristics of Dungeness crab (Cancer magister). Aerobic, heterotropic microorganisms of Dungeness crab (Cancer magister) were isolated from raw crab, cooked crab, crab meats obtained during commercial processing, and from retail crab meat samples. Each microbial isolate was then identified to the genus level employing the revised replica plating procedure. Microbial groups most commonly isolated from crab meat were, in the order of predominance, Moraxella, Pseudomonas, Acinetobacter, Arthrobacter, Micrococcus, Flavobacterium-Cytophaga, and Bacillus sp. Proteus, Staphylococcus, yeasts, Vibrio, and Lactobacillus sp. were found less frequetly in some samples. Distribution patterns of microbial flora in crab meat revealed the presence of three classes of microorganisms. Microorganisms that originated from the raw crab and gained predominance by growth during refrigerated storage were Moraxella, Pseudomonas, Acinetobacter, and Flavobacterium-Cytophaga sp. Those that originated from the crab but did not grow in meat were Arthrobacter and Bacillus sp. Micrococcus, Staphylococcus, and Proteus sp. were introduced during processing, but they did not grow in the refrigerated crab meat.


Application of the deoxyribonucleic acid/ribonucleic acid hybridization technique in Bdellovibrio as a model for studying ribonucleic acid turnover in host-parasite systems. The kinetics of host ribonucleic acid (RNA) degradation and its resynthesis into Bdellovibrio-specific polyribonucleotides has been studied. The kinetics of RNA turnover was followed during a one-step synchronous growth cycle of Bdellovibrio growing within 32-po4-Labeled Escherichia coli host cells. The species of labeled RNA present at any given time was ascertained through the specificity of the deoxyribonuclei acid (DNA)/RNA hybridization technique. At nearsaturating levels of RNA and at zero time, 7% of the host DNA sequences and only 0.04% of the Bdellovibrio DNA became hybridized with 32-P-labeled host cell RNA (greater than 99% host specific). At the end of the burst, 98% of the labeled RNA sequences were specific for Bdellovibrio DNA. About 74% of the initial labeled host cell RNA became turned over into Bdellovibrio-specific sequences. We provide data indicating that host cell ribosomal RNA is assimilated by Bdellovibri. Degradation of host cell RNA occurs in a gradual fashion over most of the Bdellovibrio developmental growth cycle. This application of the DNA/RNA hybridization technique and its general concept should be of value in elucidating the kinetics of nucleic acid turnover in other types of host-parasite systems.


Use of immunofluorescence staining in kerion. We describe two cases of kerion caused by Trichophyton rebrum and Microsporum gypseum. In the histological sections, a PAS stain revealed a small number of hypha-like rods and spore-like round bodies in the dermis of patient 1. Except for some clusters of PAS-positive materials, no definite fungal elements were observed in the dermis of patient 1, whereas a considerable number of hyphae were demonstrated within a hair shaft. Immunofluorescence staining, using fluorescein-labeled T mentagrophytes antiserum, disclosed the presence of fungal antigens, not only within a hair shaft, but also in the inflammatory infiltrate in the dermis of both patients.


Agar in the management of hyperbilirubinaemia in the premature baby. Eighty low birthweight infants (1500 to 2500 g) were randomly assigned to a group given oral agar and a control group. The study was first performed in 24 agar-fed babies and 24 control babies. The treated infants received a daily total amount of 600 mg/kg of agar beginning at 12 hours of age, for 7 days. In the later stage of the trial, 16 agar-fed babies and 16 control babies were investigated. The total daily amount of agar was raised to 700 mg/kg, beginning at 6 hours of age for 7 days. No complications were observed with the administration of agar. Serum bilirubin levels were not significantly lower in the agar-fed infants. We conclude that agar supplemented feeding is not indicated in the management of hyperbilirubinaemia in low birthweight newborn infants.


Familial opsonization defect associated with fatal infantile dermatitis, infections, and histiocytosis. Members of four generations of a family had a defect of serum opsonization for yeast phagocytosis consistent with dominant inheritance. 2 were healthy, one had chronic osteomyelitis, and the fourth developed a fatal illness in infancy characterized by exfoliative dermatitis, diarrhoea, multiple bacterial infections, and failure to thrive, which resembled the two prevously reported cases with this opsonization defect. At necropsy the infant also had lymphoid depletion, which was possibly secondary, and massive histiocytic infiltration.


"Added lactose" and "added sucrose" cow's milk formulae in nutrition of low birthweight babies. During the manufacture of dried milks for infant feeding the composition of cow's milk may be modified by the addition of extra carbohydrate powder to lower the relative proportions of protein and minerals, and in practice various carbohydrates are used in a largely empirical manner. In other circumstances it is known that the quality of dietary carbohydrate affects intestinal tolerance, deposition of body fat (in rats), and concentrations of plasma lipids (in man). Therefore, in this study the effects of feeding newborn infants on added lactose formula and added sucrose formula have been investigated. 29 low birthweight babies were observed throughout the first 3 months of life. The added carbohydrate achieved a satisfactory composition in terms of mineral and protein concentration of the reconstituted milk, but the "added lactose" group experienced more diarrhoea and a greater degree of metabolic acidosis during the first week of life. The added lactose group was slightly fatter and the plasma triglyceride concentration slightly higher than in the "added sucrose" group. Despite teleological evidence in favour of lactose, we found no objective contraindication to the addition of sucrose to cow's milk in the manufacture of infant feeding formulae. Both milks contained only small quantities of linoleic acid and the polyunsaturated fatty acid content of the plasma and adipose tissue lipids fell to low levels, but no clinical evidence of "essential fatty acid deficiency" was found.


Autoantibodies in childhood connective tissue diseases and in normal children. The prevalence of nine serum autoantibodies has been studied in 117 children with various connective tissue disorders and in 134 normal controls. In juvenile rheumatoid arthritis rheumatoid factor was present in 5%, and antinuclear factor in 4%, compared with an incidence of 4% and 0% respectively in controls. In Henoch-Schönlein purpura there was little evidence of associated autoimmune disorder. Gastric parietal cell and thyroid microsomal antibodies were found in 9% and 10% of our control population, but the significance of this is not clear. It is concluded that in children the presence or absence of autoantibodies as diagnostic criteria should be interpreted with the greatest caution.


Isosorbide in treatment of infantile hydrocephalus. This paper reports the experiences of the second clinical trial in the use of isosorbide in the treatment of 34 selected cases of infantile hydrocephalus of all types. Subject to careful biochemical monitoring of serum electrolyte, urea, and acid-base balance, treatment with 2 g/kg body weight 6-hourly is safe. Side effects are immediately eliminated by interrupting therapy. With lower dosage, prolonged maintenance therapy was possible, for as long as 11 months, without side effects and with need for much less frequent biochemical monitoring. Isosorbide effectively prevented the need for shunt therapy in 10 of 34 patients, including 3 infants with uncomplicated congenital hydrocephalus of moderate degree and infants whose hydrocephalus was associated with spina bifida and whose cerebral mantle was between 20 to 25 mm. In posthaemorrhagic and postmeningitic hydrocephalus valuable time was gained before shunt therapy until the infant and his CSF were fit for operation.


Pneumothorax in the newborn. Changing pattern. The clinical course of pneumothorax and its allied conditions was studied in 34 newborn infants who presented over a 2 1/2-year period. We found an overall incidence of 3/1000 live births. 11 term infants without obvious pulmonary pathology presented early (9 within minutes of birth); 6 of these had aspirated meconium or blood. The remaining 23 were preterm infants with hyaline membrane disease (HMD) and accounted for 68% of the infants in this series. In contrast, they presented late (mean 45 hours) and 16 were on continuous distending pressure (CDP) or intermittent positive pressure ventilation (IPPV) at the onset of pneumothorax. 15% of all infants with HMD who required CDP/IPPV developed pneumothorax; this increased incidence was most evident in infants who received CDP only. All except 2 of the 11 term infants in the first group were managed conservatively and all survived. Wehn pneumothorax occurred as a complication of HMD in preterm infants, 14 of the 16 infants required intrapleural drainage. Persistence or recurrence of pneumothorax occurred in 9 infants, 7 of whom were receiving CDP/IPPV at the time. Lung expansion was affected only after replacement with a patent chest drain through the same incision or insertion of a second drain on the same side of the chest. All 5 deaths occurred in the group of preterm infants with HMD. 3 resulted directly form respiratory failure due to severe HMD complicated by pneumothorax. We emphasize the increasing importance of pneumothorax as a complication of HMD in preterm infants, particularly in those receiving CDP. Successful management depends on prompt diagnosis and treatment of pneumothorax, which may occur as unexplained sudden deterioration at any time during the course of illness in this group of high risk infants.


Prevalence of atopy and exercise-induced bronchial lability in relatives of patients with cystic fibrosis. Skin tests and exercise tests were performed on children with cystic fibrosis (CF) and first-degree relatives of CF children. Positive skin tests were found in 56% of patients and 19% of relatives, but the prevalence of atopy in CF patients bore no relationship to its prevalence in their relatives. Increased 0ronchial lability, mainly due to bronchoconstriction, was present in 54% of patients and 27% of relatives. The results showed that increased prevalence of bronchial lability, but not atopy, is found in first-degree relatives of CF children, and that the abnormal lability and atopy found in CF children does not indicate a familial allergic background.


The removable buried retention suture: a new technique. Through-and-through retention sutures are inherently inefficient and prone to produce skin and subcutaneous damage. Most surgeons are reluctant to permanently bury non-absorbable retention sutures. This new technique uses tube conduits to bring the retention sutures from deep fascial level to above the skin-surface, where they are available for removal. Thus, the sutures do not cross the skin and subcutaneous tissue, and they exert maximal efficiency at the deep fascial layers. This method has been used in over 60 cases without deep-wound separation, and complications have been minimal.


Central nervous systen alpha-adrenergic mechanisms and cardiovascular regulation in rats. Noradrenaline (NA) induced a decrease in blood pressure and heart rate when injected into specific areas in either the medulla oblongata or the hypothalamus. In the medulla the area of the nucleus tractus solitarius was specifically sensitive to NA; in the hypothalamus depressor effects were obtained only after NA injections into the anterior hypothalamic/preoptic region. The cardiovascular effects induced by NA (3-40 nmol) in these areas consisted of an immediate decrease in both arterial pressure and heart rate. Size and duration of these effects depended upon the dose of NA injected. Alpha-methylNA (5-15 nmol) induced a long lasting decrease in blood pressure and heart rate when injected into the anterior hypothalamic/preoptic region. These data are discussed in view of the existence of at least two sites within the central nervous system (CNS) from which interference with noradrenergic mechanisms can cause changes in the cardiovascular system.


Treatment of fungal infections with flucytosine. Treatment with flucytosine of 20 patients with fungal infections gave favorable results in four patients with crytococcal infections, two of four patients with disseminated candidiasis, eight of ten patients with urinary tract infections due to Candida albicans and Torulopsis glabrata, and tow of three patients with miscellaneous infections due to Calbicans. Two patients with crytococcal meningitis and altered host resistance and one patient with an aorto femoral graft infection due to C albicans were treated with flucytosine and smphotericin B. The infection was eradicated in one of the patients with meningitis, and cultures from an infected arterial graft became negative. Adverse side effects of flucytosine included mild leukopenia and thrombocytopenia, a transient increase in alkaline phosphatase and glutamic oxaloacetic transaminase, and nausea and diarrhea.


Malignant hypertension. Recovery of kidney function after renal allograft failure. A 28-year old patient with malignant hypertension developed endstage renal failure necessitating chronic maintenance hemodialysis for seven months and transplantation of a renal allograft that was rejected within a month. After this, with continued control of the hypertension, the patient's own kidneys gradually resumed function and achieved anendogenous creatinine clearance of 30 ml/min. She has not required further dialysis for more than nine months. Recovery of sufficient renal function to maintain homeostasis, one year after onset of uremia, indicates the prolonged antihypertensive treatment period that may be necessary to reverse the renal arteriolar changes associated with malignant hypertension. This experience further underlines the necessity of moderation in the use of nephrectomy in the management of severe hypertension.


Effect of edeine on primary immunologic response in mice. The effect of edeine on primary immune response against sheep erythrocytes in mice was studied. The response intensity was evaluated on the cellular and humoral level. The results showed significant decrease in the number of spleen cells capable of synthesizing hemolysins, and the decrease in serum level of these antibodies.


Adsorption of pneumocins and aerocins on bacterial cells. Adsorption of aerocins 1a-E26, 1b-E47, 1b-E43, 2-E26, 2-E47 and pneumocins A-114 and A-902 was found to be dependent on the presence of specific receptors on the surface of sensitive bacteria. Resistant mutants, selected by these bacteriocins, were incapable of adsorption owing to loss or altered structure of receptors. Maximal numbers of Killing Units of pneumocins and aerocins adsorbed by one bacterial cell of sensitive strains were determined. Kinetics of adsorption and degree of killing of bacteria in relation to concentration of bacteriocins were studied. The lethal effect on bacteria was of the "single hit" type, i. e. one particle of aerocin respectively pneumocin killed one bacterial cell.


Variability of effect of positive end expiratory pressure. Mechanical ventilation with positive end expiratory pressure (PEEP) has been reported to produce prompt improvement in oxygeneration when used to treat acute respiratory failure. Reports of the effect of PEEP on cardiac output have been conflicting. We studied 14 patients and found that, although mean values of arterial oxygen tension (PaO2) increased as PEEP increased, on eight occasions in the acute studies and three in the elective studies, it fell as PEEP was increased. On five occasions the fall in PaO2 was associated with an increased shunt. Arterial pressure did not, on the average, change at any level of PEEP, but in 13 of 30 measurements it fell by more than 20% and necessitated curtailment of the study at blood pressure levels of less than 50 torr. Since these effects of PEEP cannot be predicted, careful patient monitoring is essential when ventilation with PEEP is utilized.


A chemosterilized antigen-extracted autodigested alloimplant for bone banks. Limited chemical extraction of hydrophobic glycopeptides and subtotal autodigestion of the donor's cells and plasma membranes in undemineralized cortical bone in vitro reduces the putative quantity of haptenic substances absorbed by the recipient. Iodoacetic acid and sodium azide or other sulfhydryl group enzyme inhibitors added to the buffer solutions during in vitro autodigestion and estraction of intracellular alloantigens protects the bone matrix morphogenetic property against enzymatic degradation. The delayed hypersensitivity reaction induced by aseptically collected freeze-dried bone and the destruction of the bone morphogenetic property caused by radiation-sterilization is avoidable by sequential chemodigestion and chemosterilization of bone that preserves the maximum morphogenetic potential while transferring a minimum quantity of alloantigen.


Blowhold cecostomy for cecal decompression. Blowhole cecostomy is a method for achieving decompression of the distended cecum. Emphasis is placed on a McBurney-type incision, a watertight suture line joining bowel to muscle, and avoidance of opening the cecum until the suturing is done.


Mutagenic activity of cyclophosphamide, ifosfamide, and trofosfamide in different genes of escherichia coli and salmonella typhimurium after biotransformation through extracts of rodent liver. Experiments are performed to compare the mutagenic properties of the three phosphamide esters of nitrogen mustard, cyclophosphamide (CP), ifosfamide (IF), and trofosfamide (TF), in different bacterial systems. The systems include forward mutations leading to resistance against 5-methyltryptophan (MTR) and from galR-s18 to gal-+ in Escherichia coli 343/113, back mutations from arg56 to arg-+ in Escherichia coli 343/113 and back mutations from hisG46 to his-+ in Salmonella typhimurium TA1535. CP, IF, and TF are not mutagenic per se. After biotransformation through isolated rodent liver homogenates (S-9 fraction) all three compounds exhibit mutagenic activity in the order CP smaller than IF smaller than TF. Specific activating potential of mouse liver extracts is higher than that of rat liver. Except for back mutations in S. typhimurium TA1535, all mutation systems tested show a similar pattern of induction after treatment with CP, IF, and TF. However, because gal-+ mutations are not induced by CP under conditions where arg-+ and MTR are induced, it is suggested that more than one mutational system be used in routine mutagenicity testing.


Interlamellar corneal grafts in rats. Effect of histocompatibility. A technique of interlamellar keratoplasty was employed to evaluate the influence of difference in histocompatibility on the results of corneal transplantation in highly inbred rats. The degree of corneal clarity and vascularity and the incidence of rejection of relatively conpatible ("weak") and incompatible ("strong") allografts were recorded blindly in recipients with normal and vascularized corneas and in recipients sensitized with donor tissue either before or after corneal grafting. In contrast to the well-known effects of histocompatibility on skin and organ allografts, there was no substantial effect whatsoever of histocompatibility on either the severity of corneal allograft reactions orthe incidence of rejection. Consequently, the results of this experimental investigation suggest that tissue typing may have little or no value in clinical keratoplasty.


Corneal epithelial preservation.

Corneal epithelial preservation. While clinical experience has demonstrated that current storage techniques are adequate for the preservation of human endothelial cells, increased use of donor epithelium in cases of severe disturbance to epithelial and stromal integrity requires a reexamination of storage effects on the epithelial layer. Measurement of human and rabbit metabolite levels in stored corneas indicates that the epithelium is maintained in a normal state only if the eye is cooled promptly. If cold storage is delayed for as little as one hour after death, glucose levels in the stroma and aqueous fall below levels known to be required for preservation of epithelial integrity. The fundamental time of interest in preservation of donor corneal tissue is in the interval between death and cooling of the eye. If prompt enucleation is not possible, ice should be applied to maintain viability of the epithelium.


[Studies on soft tissue reactions to implantation of glass ceramics (author's transl)]. This report describes the implantation of glass and glass-ceramics into soft tissues. These experiments revealed that our new glass and glass-ceramic materials are well compatible with soft tissues. The fibrous membrane surrounding such an implantat consists of normal dense collageneous connective tissue. The cells are fibroblasts and fibrocyt-like cells without any abnormal morphology. Macrophages could not be detected. However, the degree of implants solubility must be chosen with care, because high solubility of the implant increases the reaction of the surrounding soft tissues. The described materials are also compatible with osseous tissues. In our previous experiments we have already pointed out, that bonding developed between glass material and bone. Few weeks after implatation we have seen mature lamellar homegeneously mineralized bone opposed to the implant. There was no fibrous membrane between implant and bone. Longtime studies show that hitherto the described bonding exists about 2 years.


Acupuncture for sensorineural hearing loss. Forty children, aged 9 to 16 years, with severe and profound sensorineural hearing loss received acupuncture five times weekly for three out of four weeks for a period of six months.  The children had weekly audiometric evaluations.  There were no clinically important differences during and post acupuncture.


Effect of the high potassium medium on cultured cochlear epithelial cells. 1. A high potassium and low sodium culture medium does not produce morphological change in cochlear epithelial cells such as sulcus cell, Deiters' cell, Hensen's cell, Claudius' cell and Raissner's membrane cell. 2. Interdental cells of spiral limbus are affected by a high potassium medium but the change is to a moderate degree. 3. Outer hair cells degenerate quickly in a high potassium and low sodium medium. The onset and the grade of the degeneration is in a parallel with the potassium concentration, and a concentration of more than 46.4 mEq/l produces an acute and severe degeneration of outer hair cells.


Temporal and masking phenomena in persons with sensorineural hearing loss. Relatively few experimental investigations have studied backward or forward masking, masking level differences, or differential frequency effects in simultaneous masking among persons with hearing impairment. This is regrettable since such efforts may lead to important new understandings of auditory processes. This paper reviews available data, discusses some precautions of experimental procedure, and offers suggestions for future research directions.


Masking level difference: a measure of auditory processing capability. MLDs are evidence of the superiority of the binaural auditory system. Cochlear lesions do not necessarily impair the MLD and persons with cortical lesions are also able to produce normal MLDs. The evidence for intermediate level auditory pathway lesions is more equivocal. The MLD is not the only measure of binaural hearing and binaural hearing is itself only one measure of a number of complex auditory processes. In this experiment measures of MLDs, localization, temporal integration, central masking and difference limen for intensity were made on 11 persons with normal hearing. Correlational analyses including factor analysis indicated that the MLD is a fairly independent measure but that central masking, brief tone audiometry and difference limen for intensity represent related auditory tasks. The relationship of localization tasks in this picture is unclear.


Auditory localization and its clinical applications. Factors of significance in the localization of sound are considered. The ability of hearing-impaired subjects to localize noise in the horizontal plane was examined with and without hearing aids, and also compared with the results for normally hearing subjects. The directional hearing was not found to be improved by the hearing aids used. The ability to localize sound has been used by several investigators as a diagnostic tool: poor directional hearing may be expected in patients with lesions of the cochlear nerve or the pontine region. However, other factors are also of significance and may impair the localization of sound. These problems are discussed.


Some effects of prestimulus activity and length of prestimulus observation on judgments of newborns' responses to sounds. Previous work on the effects of prestimulus state on newborn auditory response is briefly reviewed. Subjectively assessed responses of nine newborns by five observers were studied as a function of (1) prestimulus activity level and (2) duration of prestimulus observation period. Response assessment was significantly affected for the former but not by the latter. For sounds which elicited a high proportion of responses, the prestimulus activity level had relatively little effect on judgment of response, whereas for sounds (and no-sound "control" trials) to which few responses were ascribed, prestimulus activity tended to be associated with positive ratings of response.


Instrument for the on-line measurement of the slow phase of nystagmus. The on-line measurement of the slow-phase velocity of vestibular nystagmus, induced or spontaneous, has considerable practical advantages. An instrument for this purpose, developed around simple operational amplifiers, is described. Typical applications of the system are given in respect of nystagmus induced by optokinetic, rotational, and caloric stimuli.


Relationship between virus multiplication and culture cells synchronized by excess thymidine treatment. V. Effect of chikungunya virus infection upon the host cell cycle. The cell cycle of FL cells infected with chikungunya virus was examined using cultures synchronized with excess thymidine. Viral growth at the cellular level was demonstrated by the presence of viral antigen and viral RNA synthesis. It was found that cells which had been infected with virus before the S phase, could enter the S phase. Furthermore,, cells infected in the phase before the M phase could enter the M phase. However, infected cells showed abrupt karyorrhexis after a certain period of infection. This contrasts with studies on pox virus-infected cells, where the cell cycle dose not proceed once viral-DNA synthesis is initiated at any phase of the cell cycle.