[Memories and reflexions of a psychiatrist of former times]. After 64 years as a psychiatrist, the author relates his experiences in psychiatric centers and in official practice as an expert. In this way, he comments on the evolution of psychiatry spanning three quarters of a century. In particular, he recalls the various methods of treatment used successively, their success and failure and the resulting accidents. He also describes the development of help given and the increasing tendency to reduce obstacles to the freedom of movements of those suffering from mental illness. Mention is also made of the changing working conditions found in psychiatric hospitals and the conception to which has the practicien himself of his role. With regard to the official practice as an expert, different objectives and approaches to the problem have been observed in the past and others are to be hoped in the future.


[Survival of microorganisms frozen on solid medium (author's transl)]. Different freezing methods have been studied for 12 microorganisms. This study has been carried out on solid support in the conditions near the freezing of foods. The survival rates are on relation with species and freezing methods. The survival of some microorganisms during a storage at -20 degrees C has been studied.


Corneal foreign bodies of coconut origin. Corneal foreign bodies of varied nature have been reported, however, vegetable foreign bodies in the cornea have seldom been described. A case is reported of a male from the Marshall Islands in the Pacific who retained a number of deep corneal foreign bodies after being struck in the eye by a piece of a coconut shell. The foreign bodies caused considerable inflammation which ceased after they were exposed and removed by means of a centrally based lamellar corneal flap. The patient's eye has remained quiet for 4 months following removal of the foreign bodies.


Endogenous Nocardia endophthalmitis: report of a case in a patient treated for lymphocytic lymphoma. A patient with pulmonary, cerebral, and intraocular nocardiosis is reported. The intraocular disease was first recognized at autopsy. Only 7 patients with intraocular nocardiosis have been described previously. The intraocular lesions were central and paracentral, and the distribution resembled those described in 5 of the previous patients with metastatic intraocular disease. The ocular histology differed from those cases previously reported in that a granulomatous reaction accompanied the suppurative component. Malignant lymphoma treated with radiation therapy, cytotoxic drugs, and steroids formed the background against which the disease occurred in this patient.


Enzyme multiplied immunoassay of phenobarbital by LKB reaction Rate Analyser: a comparison with analysis by gas-liquid chromatography. A procedure for the enzyme multiplied immunoassay of phenobarbital using the LKB Reaction Rate Analyser is described. The temperature optimum, linearity, specificity, and precision of the assay are reported. A highly significant correlation coefficient is obtained when the technique is compared with gas-liquid chromatography by analysing human sera containing a range of phenobarbital levels.


Determination of the anticonvulsant drug--dipropyl acetate (Epilim) in human plasma by gas chromatography. A relatively simple gas chromatographic procedure is proposed for the analysis of the drug dipropylacetic acid in plasma. The compound is chromatographed, as the free acid after ether extraction. Prior to concentration of the solvent the acid is converted to its potassium salt, then regenerated to the free acid immediately before analysis.


A review of the metabolism and toxicology of nickel. Although nickel is an essential element for animal nutrition, the physiological role of nickel is not yet established. Pathological alterations of nickel metabolism are recognized in several human diseases. The diverse clinical manifestations of nickel toxicology include: (1) acute pneumonitis from inhalation of nickel carbonyl, (2) chronic rhinitis and sinusitis from inhalation of nickel aerosols, (3) cancers of nasal cavities and lungs in nickel workers, and (4) dermatitis and other hypersensitive reactions from cutaneous and parenteral exposures to nickel alloys. The toxicity, carcinogenicity and embryotoxicity of nickel compounds in experimental animals are reviewed in this article, and consideration is given to the therapeutic use of chelating drugs in nickel poisoning.


[Immuno-reactive somatostatin in acetic extracts of duodenal, antral and fundic biopsies (author's transl)]. The concentration of immunoreactive somatostatin in acetic extracts of duodenal, antral and fundic biopsies was estimated in 11 subjects with no gastric or duodenal abnormality and 21 duodenal ulcer patients by using a specific and reproducible radioimmunoassay. Somatostatin was detected in the duodenal, antral and fundic mucosa in normal subjects. As compared to the values in the control group, the concentrations in the duodenal ulcer patients were comparable in the antrum and duodenal bulb, and significantly higher in the fundus.


Bacteriostatic inhibition of Klebsiella pneumoniae by three human transferrins. Three human transferrin variants verified by rivanol precipitation were separated using vertical block polyacrylamide gel electrophoresis followed by elution convection. A bacteriostatic inhibition measurement in vitro of the three transferrins was made. The data indicate that human transferrin variants exhibit different degrees of inhibition on Klebsiella pneumoniae.


Rapid development of glomerular crescents in epinephrine-infused dogs. A serendipitous finding in the kidneys examined by light, electron, and immunofluorescence microscopy (LM, EM, and IFM, respectively) in mongrel dogs infused intravenously with epinephrine (4 microgram per kg per min) alone or in combination with therapeutic agents over a six hour period was proliferating epithelial cells in Bowman's space and adhesion to the Bowman's membrane (crescent). This lesion was observed in 10 of 17 dogs. In five, over 50 percent of the glomeruli were involved. In seven additional dogs infused with epinephrine, renal biopsy studies (LM) at 0, 3 and 6 hr periods revealed crescents only in the six hr specimens. By EM, the crescents were composed of actively proliferating epithelial cells with many large mitochondria containing conspicuous intramitochondrial particles. Fibrin was found within glomerular and peritubular capillaries, within tubules but rarely in the crescent. IFM revealed granular deposits of IgG only in the glomerular basement membrane and mesangium. Other changes included necrosis of the tubules in all dogs receiving epinephrine alone and necrosis of arterioles in some of the dogs studied. Dogs receiving normal saline infusions (control) did not reveal any abnormalities in the kidney. This model should prove useful in determining the morphogenesis of crescent formation and in evaluating the effect of therapeutic agents in the prevention of this lesion.


[Hypothalamic LH-RH neuronal modifications after prolactine intraventricular infusion in the guinea pig (author's transl)]. Ovine prolactine injected at doses of either 31,25 to 500 microgram by lateral intraventricular route in male guinea pigs, affects LH-RH hypothalamic neurons within 2 to 24 hours. After this treatment there is an increase of LH-RH immunoreactive material in eminential terminals and in numerous small granules of hypothalamic neuronal cell bodies. This accumulation of immunoactive LH-RH in pericaryon and in terminals can be interpreted as stimulation of LH-RH synthesis. Preliminary results of radioimmunoassayed plasmatic LH level, 2 h after PRL infusion, are in agreement with this hypothesis. The probability that short feed-back by PRL or PIF secretion would simultaneously be able to check LH-RH secretion is discussed.


[Pattern and efferent paths of LHRH neurons in man (author's transl)]. LHRH neurons have been studied by immunofluorescence on slides using rabbit immunosera against unconjugated synthetic LHRH. In Man they form four main groups localized in the medio basal hypothalamus (infundibular nucleus, post-infundibular eminence, premammillary nucleus), the preopticoterminal area, the septum (and pericommissural area), the retromammillary area and the rostral mesencephalon. They give rise, respectively, to the hypothalamo-infundibular LHRH tract, the preoptico-terminal LHRH tract, lastly to various extra-hypophyseal LHRH tracts, ending in the epithalamic area, the telencephalon and the mesencephalon.


[Therapeutical effects of bromocriptine (CB 154) in 10 acromegalic subjects. Study of somatotrophic function and clinical survey (author's transl)]. Plasma GH levels were studied following acute administration of 2.5 mg of bromocriptine (CB 154) in 12 acromegalic patients. In 9 responders, reduction of GH levels was obvious 2 to 4 hours after bromocriptine administration and the lowest values were achieved between 5 and 8 hours following drug absorption. This pattern suggested the use of bromocriptine at a dose of 2.5 mg six-hourly in chronic treatment of acromegaly. Chronic administration of CB-154 in 10 acromegalic patients was followed by a stable reduction of plasma GH levels in seven subjects. No appreciable variation in GH levels were observed in one patient who was unresponsive to acute administration of CB-154 and in two other subjects treated with 2.5 mg 12-hourly. In three patients who had high plasma GH levels inspite of an anterior treatment by hypophyseal surgery and/or physiotherapy, plasma GH values were normalised under bromocriptine therapy. (9 to 24 months). In the four other subjects, high basal plasma GH levels were reduced with at least 50% reduction rate from baseline. Nevertheless, in two subjects from the latter group bromocriptine daily dose was increased to 20 mg divided in four fractions, because of an escape phenomenon to initial dose regimen. Normalisation or reduction of plasma GH levels was associated with considerable clinical improvement. Tolerance of the drug was excellent in all patients but four who experienced nausea and vomiting; these side effects disappeared when treatment was reduced and then increased gradually.


The Quinlan decision: problems and legislative alternatives. In the Quinlan decision, a state supreme court authorized removal of a respirator from a person in a chronic vegetative state provided that the attending physicians and an "ethics committee" agreed there was no reasonable possibility of her regaining cognition or sapience. While the decision involves an unusual factual situation and poses some troublesome technical and doctrinal problems, it underscores the need for formal legal standards to guide physicians and families of severely brain-damaged patients. Legislation seems preferable to a series of court decisions. The legislative process allows the public to express views on controversial ethical and religious questions. It also permits extensive deliberations about medical and scientific data relating to brain damage and its prognosis. Legislative alternatives include expanding the concept of brain death, redefining homicide, allocating to physicians and families legally unreviewable discretion to decide on levels of care, mandating procedures for implementing a desired reduction of care, and approving the use of a "living will" as a means of requiring physicians to withdraw or withhold treatment.


Effect of the alteration of gonadal feed-back on LH and FSH release in men. To observe the influence of gonadal feed-back on FSH and LH release in men we studied the blood levels of both gonadotropins before and after orchiectomy in eight subjects. In four orchiectomized subjects the LH and FSH release induced by LH-RH was also studied. The LH-RH was also administered in eight patients with primary gonadal diseases. Our findings clearly show that FSH is more increased than LH by orchiectomy. The LH-RH administration in our subjects increased the FSH and LH similarly. These findings suggest that the specificity of pituitary responsiveness to LH-RH is under the influence of gonadal steroids.


Functionally distinct stages in B-lymphocyte maturation. Evidence is reviewed that supports the concept of extrinsic stem cell colonization of inductive micro-environments for B-cell formation in the bursa of Fabricius of chickens and foetal liver of mammals. In these organs, the first distinctive marker of B-lineage differentiation (readily detectable immunoglobulin) is synthesized and displayed on cells which have extensive proliferative and differentiative capacity. The degree of commitment of these cells to the synthesis of trace or large quantities of immunoglobulin of the respective major classes when they colonize peripheral lymphoid tissues and the role of antigen in this process are considered.


Susceptibility to kasugamycin of Escherichia coli carrying conjugative and nonconjugative R plasmids. Ten conjugative and two nonconjugative R plasmids, all of which were naturally isolated, were tested for their ability to confer epistatic susceptibility to kasugamycin upon the host Escherichia coli. All of the conjugative plasmids, which belonged to various incompatibility groups, conferred a plasmid-determined epistatic susceptibility to kasugamycin upon the host cells, whereas the nonconjugative plasmids did not.


Bactericidal activity of the combinations of gentamicin with clindamycin or chloramphenicol against species of Escherichia coli and Bacteroides fragilis. The bactericidal activity of clindamycin, chloramphenicol, and gentamicin alone and of gentamicin plus clindamycin and gentamicin plus chloramphenicol was studied on 8 strains of Escherichia coli and 10 strains of Bacteroides fragilis isolated from clinical material. Gentamicin did not interfere with the activity of clindamycin or chloramphenicol against B. fragilis. The activity of gentamicin against E. coli was not influenced by clindamycin, but chloramphenicol suppressed the rapid bactericidal activity of gentamicin in seven out of eight strains of E. coli examined.


Physiological effects of an antimycotic azasterol on cultures of Saccharomyces cerevisiae. The yeast Saccharomyces cerevisiae has been studied during cultivation with a naturally occurring antimycotic azasterol. At very low concentrations (1.0 to 10.0 ng/ml), where growth retardation is not observed, an unusual sterol, ergosta-8,14-dien-3beta-ol, accumulates in high concentrations. Upon removal of the azasterol from the culture, the 8,14-diene is converted to ergosterol. Much smaller amounts of another 8,14-sterol, but with an additional unsaturation, have also been observed. Total sterol accumulation is higher in cultures containing subinhibitory levels of the antimycotic agent than the amounts of normal sterol accumulation in control cultures. With between 10 and 100 ng of azasterol per ml a transitory cessation of growth is observed from which the culture is able to recover. At much higher concentrations growth inhibition and even cell lysis results. Competitive inhibition of sterol 24(28)methylene reductase is demonstrated.


Anti-Candida activity of clotrimazole in combination with dioctyl sodium sulfosuccinate and other surfactants. Six anionic and five nonionic surfactants were tested for their effect on the fungistatic action of clotrimazole against Candida albicans. All of the anionic agents that did not contain an ethylene oxide group were capable of potentiating the anti-Candida activity of clotrimazole, whereas all five members of the polyoxyethylene surfactant group, including four nonionic agents and one anionic agent, acted in an antagonistic fashion. The combination of clotrimazole and the anionic surfactant dioctyl sodium sulfosuccinate was the most potent in synergy and, thus, more precise studies were made with this combination. Although appropriate combinations of the two drugs showed a potent fungicidal activity against proliferating cultures, none of these combinations tested was lethal when cell growth was restricted by nutritional deficiency. The lethal effect of the combined drugs was partly reversed when growing cultures were treated in the presence of an osmotic stabilizer. Whether cells were treated with moderate and higher concentrations of clotrimazole and dioctyl sodium sulfosuccinate, alone or in combination, there was little change in cell wall content of total protein, carbohydrate, or lipid from that in untreated control cells. However, there was a significant decrease in the cell wall content of phospholipid when moderate concentrations of the two drugs were combined.


Spread of a single plasmid clone to an untreated individual from a person receiving prolonged tetracycline therapy. The aerobic gram-negative intestinal flora of two individuals living in close proximity was followed for 17 months. One of these persons was receiving a prolonged tetracycline treatment for acne vulgaris and was colonized by tetracycline-resistant Escherichia coli strains throughout the survey. The other person studied received no antibiotics during the period in question, but was frequently found to excrete a number of E. coli strains harboring tetracycline-resistant plasmids. The two E. coli strains (O75.H7 and O23.H16) excreted from both persons most frequently were indistinguishable, and so were the R-plasmids they carried. This suggests that R-plasmid-carrying E. coli may spread from individuals under treatment to close relatives that have not been treated.


Rosamicin--a new drug for the treatment of bacterial prostatitis. Rosamicin, a new macrolide substance, was investigated in dogs and humans with regard to its usefulness for the treatment of bacterial prostatitis and compared with the well-known macrolide erythromycin. In dogs with normal and experimentally infected prostates, concentration ratios for rosamicin in prostatic secretion, interstitial fluid (obtained from implanted tissue chambers), and tissue were significantly higher than for erythromycin. The difference was even more pronounced in human prostatic tissue, obtained by transurethral resection. With its broad spectrum against many common urinary pathogens, rosamicin seems to be a promising drug for the treatment of acute and chronic bacterial prostatitis.


Morphological changes in yeasts as a result of the action of 5-fluorocytosine. The mode of action of 5-fluorocytosine on Candida albicans and Saccharomyces cerevisiae was studied with special reference to morphology and ultrastructure. Shortly after contact of yeast cells with 10 mug of 5-fluorocytosine per ml, marked enlargement of the cells occurred. The initial increase in cell size was almost the same with both yeast strains. As incubation proceeded, further increase in cell volume continued with C. albicans, whereas no further change in cell volume was observed with S. cerevisiae. An electron microscope examination of C. albicans cells after exposure to the drug revealed characteristic changes, consisting of an enlarged nucleus and a thin cell wall. The morphological changes were exactly comparable to those reported with inhibitors of deoxyribonucleic acid synthesis in mammalian cells and some bacteria.


Renal transplantation into an ileal conduit. Since the selection criteria for renal transplantation have become less stringent as a consequence of improved graft survival and decreased mortality, patients with severe structural anomalies of the lower urinary tract can now benefit from renal transplantation into an ileal conduit. This is illustrated by two succesful cases. The opertative procedure is discussed, and the possibilities for the future are mentioned.


Rembrandt's anatomy of Dr. Nicolaas Tulp. The bye-laws of the Amsterdam Barber-Surgeon's Guild in the 17th century are mentioned and the rules for instruction in anatomy are discussed. The picture of the lesson given by Dr. Nicolaas Tulp and painted by Rembrandt in 1632 is explained and the accusation of an anatomical mistake is disposed of. Some details of the person and work of Nicolaas Tulp are given.


Topical halcinonide and betamethasone valerate effects on plasma cortisol: acute and subacute usage studies. The effect of topical application of halcinonide cream and betamethasone valerate cream on plasma cortisol was studied in an acute usage study as well as a subacute study, which more closely approximated common clinical usage. In the acute study, halcinonide cream caused a marked decrease in plasma cortisol, both with and without occlusion, in patients with extensive psoriasis, but only with occlusion in normal subjects. Betamethasone valerate cream decreased plasma cortisol levels in patients with extensive psoriasis when applied with occlusion and, to a lesser extent, without occlusion. In a double-blind subacute usage study without occlusion, two of 23 patients treated with halcinonide cream showed decreased plasma cortisol levels during the treatment period, while none of the 21 patients treated with betamethasone valerate cream showed such decreases. Three patients in the halcinonide group developed striae. Clinical response to halcinonide was superior to that with betamethasone valerate cream, but a similar number of patients were resistant to treatment with each medication.


Mycophenolic acid for psoriasis.

Mycophenolic acid for psoriasis. Mycophenolic acid is an antimetabolite used experimentally for the treatment of psoriasis. Thirty-eight patients were treated with mycophenolic acid. A double-blind, placebo-controlled study demonstrated the efficacy of mycophenolic acid (P less than .01). A long-term safety study showed the occurrence of hematologic abnormalities, viral infections, and carcinoma. The position of mycophenolic acid in the therapeutic treatment of psoriasis must await the results of a multicenter cooperative study.


Metastatic basal cell carcinoma: review, pathogenesis, and report of two cases. In 93 reported cases of metastatic basal cell carcinoma (BCC), 76 had spread through lymphatics or blood vessels. Two more cases are presented, bringing the total to 78. Metastasis to regional lymph nodes was the most frequent, followed in frequency by lungs, bones, and other organs. The size of the primary tumor, its site, its resistance to x-ray therapy, and the effects of radiation appeared to contribute to the occurrence of metastasis. However, in an appreciable number of cases, tumor dissemination was related to incomplete excision followed by immediate wound closure, particularly by grafting. It is recommended that wound grafting be delayed for at least six months after excision or large or recurrent BCC in order to assure complete removal.


Septum primum defect repair.

Septum primum defect repair. Two technical maneuvers in septum primum defect repair have resulted in improved mitral valve function and security against heart block. One maneuver, critical to restoring mitral competence, is accurate reconstruction of the leading edge of the mitral valve. A second maneuver, suturing the septal defect patch at its inferior aspect to the mitral valve near the annulus instead of to the inferior septal defect margin or to the tricuspid annulus, eliminates the hazard of atrioventricular node or bundle injury.


Isoniazid chemoprophylaxis. Association with detection and incidence of liver toxicity. The hepatotoxicity of isoniazid was studied in a double blind fashion in 120 adult patients receiving the drug for chemoprophylaxis. The incidence of abnormal SGOT values was significantly higher in those on the drug, 18.3% having elevated values as compared to 6.7% of those on placebo during the three-month study period. There was no statistical difference in the frequency of symptoms suggestive of liver diseases between the isoniazid and placebo groups. Furthermore, there was no significant relationship between symptoms and elevated SGOTs. Therefore, symptomatology would not appear to be a sensitive method for detecting early isoniazid liver toxicity. From available evidence, biochemical monitoring would appear to detect liver toxicity at an earlier and more reversible stage.


Intravenous fructose treatment of acute alcohol intoxication. Effects on alcohol metabolism. This study was designed to determine the efficacy of the intravenous administration of fructose in the treatment of acute alcohol intoxication. The study was prospective and double-blind, with glucose serving as the control. Treatment with glucose and fructose was determined by random selection. Fructose administration did not alter the clinical status or rate of alcohol metabolism as reflected by the decline in serum concentration. In addition, a significant elevation (P less than .05) in serum uric acid and lactate levels occurred in the patients receiving fructose. The results indicate that fructose is of no value in the treatment of acute alcohol intoxication, and produces metabolic abnormalities that could be harmful to the patient.


Disseminated Trichosporon capitatum infection in an immunosuppressed host. Trichosporon is a frequent cause of superficial mycotic infections but has rarely been associated with invasive disease. A patient undergoing bone marrow transplantation who died from disseminated Trichosporon capitatum infection with endocarditis is reported, and the clinical spectrum of human infection caused by fungi of this genus is reviewed. To our knowledge, this is the first reported case of clearly invasive disease caused by this specific organism and emphasizes the expanding spectrum of unusual infections in the severely immunosuppressed patient.


Renal cortical necrosis following Streptococcal infection. Streptococcal infection frequently leads to proliferative glomerulonephritis, and, on rare occasions, to renal cortical necrosis. We report a case in which poststreptococcal proliferative glomerulonephritis and renal cortical necrosis occurred concomitantly.


Diazepam-induced coma with bullae and eccrine sweat gland necrosis. Bullous skin lesions that indicate sweat gland necrosis have been known to occur in drug-induced coma resulting from barbiturates and in carbon monoxide poisoning. To our knowledge, this is the first cases in which diazepam is implicated in causing bullous lesions over pressure points, and the first case showing on biopsy specimen eccrine sweat gland and sweat duct necrosis. Penile and oral lesions are being described here for the first time to our knowledge. The following mechanisms could be responsible for the skin lesions: hypoxia, local pressure, hyperthermia with excessive sweating, and a specific toxic effect on the eccrine gland. With the increasing use of the benzodiazepines, such lesions could be seen more frequently in the future.


[Experimental studies on the pathogenesis of Coli-enterotoxemia in swine. 4. Effect of lipopolysaccharide endotoxin on weaned piglets following parenteral administration]. Ten clinically intact weaned piglets were experimentally intoxicated by intravenous injection of lipoproteide-free lipopolysaccharide endotoxin according to Westphal of E. coli O 127:B8. Severe endotoxin shock with all clinical manifestations of experimental coli-enterotoxaemia was induced in all animals and included circulatory disorder with tachycardia, intermittent pallor and/or cyanosis, symptoms of severe systemic intoxication, neurological symptoms, such as lack of coordination, hindleg staggering, spasm, paresis, paralysis, changes in respiration, such as rise in respiratory frequency and deepened breathing premortal deceleration of respiration and gasping for breath, temperature, variation, including hyperthermia and aggravating hypothermia, gastro-intestinal symptoms, such as temporary vomiting and persistent diarrhoea, leucopenia, eosinopenia, variation of haematocrit, edematisation, increased transudation, congestion, and gastro-intestinal shock lesions. Eight animals died. These experiments quite obviously have confirmed that endotoxin shock is the common pathogenetic principle behind all forms of coli-entertoxaemia (i.e, the forms of edematisation, cardiovascular failure, and gastro-intestinal processes.) Lipopolysaccharide endotoxin alone may be responsible for the development of both edemas and neurotoxic symptoms (edema disease) and diarrhoea (gastro-intestinal form of coli-enterotoxaemia). The pathogenetic relevance of additional toxins (neurotoxin and enterotoxin) is discussed under this aspect.


[Value of the antiglobulin test and indirect immunofluorescence test in the serological diagnosis of bovine brucellosis]. In investigations of 5881 sera from brucella infected herds and 8635 sera from negative herds the antiglobulin test (AgT) because of its high susceptibility was shown to be a valuable method in early diagnosis of brucellosis and clearing of non-specific LA-reactions. However, all infected animals are not detected with the AgT. Therefore it is not adaptable to use in selection controlling, also in combination with other methods. In the final steps of the eradication measures against bovine brucellosis the AgT offers a very valuable serological complementary method. The indirect fluorescence test has no diagnostical advantages in comparison with the AgT and is not recommended for practical brucellosis serology.


[Quantitative analysis of the gastrointestinal flora in the piglet prior and after weaning with special reference to the pathogenesis of Coli-enterotoxemia]. The gastro-intestinal flora of clinically intact piglets on an industrialised sow unit was investigated prior to weaning (n = 12) and after weaning (n = 12). The age of the former group was 23 to 36 days and that of the latter between six and eleven days. While enormous proliferation of haemolysing E. coli was recorded from the anterior portion of the small intestine in the post-weaning group, weaning, quite, generally, was found to have only little impact upon the gastrointestinal flora of piglet. More particularly were there no indicators to the effect that post-weaning proliferation of enteropathogenic strains was favoured by any correlation whatsover between E. coli and other bacterial species or between different types of E. coli. Other factors of possible importance to the pathogenesis of coli-enterotoxaemia are discussed with reference to literature.


Abdominal aortic aneurysmectomy in long-term cardiac transplant survivors. Two thirds of the 114 patients undergoing heart transplantation at Stanford (Calif) Medical Center have had atherosclerotic cardiac disease. Two of these patients have been found in the late posttransplant period to have symptomatic abdominal aortic aneurysms requiring resection. We present the clinical course and successful operative treatment of these two patients, with emphasis on the prophylaxis of infection and maintenance of hemodynamic, metabolic, and immune stability. Close surveillance of the long-term cardiac transplant survivor should be directed towards other manifestations of atheroscleortic disease.


Fixation-induced cyst-like spaced in the brains of rabbit foetuses. During teratologic trials, routine investigations of 4261 brains from rabbit foetuses, fixed in Bouin's solution and sectioned by Wilson's free-hand razor blade technique, revealed cyst-like spaces in the brains of 164 foetuses (3.8%). The cyst-like spaces, characterised by the absence of an epithelial or endothelial lining, were usually solitary and occurred mainly in the massa intermedia of the thalamus. The spaces were found almost as ofter in control foetuses as in those from treated animals. On the basis of histologic examination and different fixation techniques, involving a further 1430 foetuses, these cyst-like spaces, previously interpreted as strain specific brain malformations, can be regarded as fixation artefacts.


[Biochemical methods for the detection of lead poisoning (author's transl)]. After a short description of sources of lead poisoning a review is given of toxicity, absorption, storage and excretion of lead. Afterwards its biochemical affects--especially the influence on the biosynthesis of heme--are treated. Methods for diagnosis of lead poisoning resulting from these affects--determination of coproporphyrine and delta-aminolevulinic acid excretion in urine, erythrocyte delta-aminolevulinic acid dehydratase activity and erythrocyte protoporphyrin--are discussed in detail.


Carcinogenicity of trichloroethylene: fact or artifact? Technical trichloroethylene has been found carcinogenic in mice after high daily doses per os. A GC-MS analysis of this technical sample revealed the presence of considerable amounts of epichlorohydrin and 1.2-epoxibutane as stabilizers. These epoxides are highly mutagenic in the Ames test and are, most probably, responsible for the carcinogenic effect found in mice. The question whether trichloroethylene is carcinogenic or not remains open.


[Comparative morphology of the endocrine portion of the mammalian pancreas]. The endocrinous part of the pancreas in the mammals under investigation (rats, guinea pigs, cattle, cats and man) comprises A-, B- and D-cells always disposed around capillaries were prevailing in all the animals. They excrete the secretory product immediately into the pericapillary gap. A-cells in rodents and man are located in the periphery of the island and often have no contacts with capillaries. The secretion from A- cells having no contacts with capillaries is released into intercapillary clefts into which the cytoplasmic spiculae of the adjacent exocrinous pancreacytes are turned, capable to overlap them and prevent from the entering of the hormone from the intercellular clefts into the pericapillary gap.


[Submicroscopic analysis of the microcirculatory system of the pancreas in several vertebrates]. The metabolic link of the microcirculatory system of the exocrinous part of the pancreas studied electron microscopically in the frog, chicken and rat has a general plan of the structure. It consists of capillaries, pericapillary gap and intercellular clefts of glandular cells connected with it. But in the frog and chicken the adventitional layer was found to be absent from the blood capillary wall, the luminal surface of endothelial cells was increased. The width of the basal layer and intercellular clefts in the rat was less than in other objects. The existence of cytoplasmic spiculae of exocrinous pancreocytes in the pancreas of different vertebrates allows to consider them as an element of the exocrinous part microcirculatory system.


[Proliferative processes in the epithelium of mouse skin allotransplants following cortisone administration]. Proliferative processes were studied in the epithelium of skin grafts from mice of strain CC57 Brown and that of the skin surrounding the grafts in mice of CBA strain. The chart (Fig 1) illustrates cortisone action on normalization of DNA synthesis in the epithelial cells of the allotransplant. Throughout the experiment in operated animals which received no cortisone (Fig. 2, a and 3, a) a high proliferative activity was observed in the recipient's skin epithelium while it was sharply decreased in the epithelium of the allograft. Repeated cortisone injections gave a reverse picture: inhibition of proliferative processes in the recipient's epithelium and their intensification in the epithelium of the allotransplant.


[Aspergillosis of the brain].

[Aspergillosis of the brain]. A case of aspergillosis of the brain in a 49-year old woman is described. In view of the fact that there were no inflammatory changes in other organs, the assumption was put forward that the fungus had penetrated into the brain by the otogenic way, or through the accessory nasal sinuses. The results of experimental infection of laboratory animals aimed at obtaining a model of meningoencephalitis are discussed. It was shown that spores of the Aspergillus fumigatus fungus in low concentrations introduced into the otic veins penetrated into the lungs where they caused an inflammatory process, and then hematogenically entered the brain. The changes in the latter were characterised by endo- and perivasculitis, formation of numerous microabscesses with the presence therein of threads of the fungus mycelium.


[Express method of histological processing of trephined bone marrow]. A method for histological treatment of the trephined bone marrow is suggested; it makes it possible to simplify the manipulation and to shorten the time of treatment of biopsy material by more than 24 hours, thereby enabling the investigator to give the conclusion about the state of the medullar hemopoiesis on the same day. The principle of the method consists in combining the stages of fixation and decalcification and also in acceleration of the final stage of treatment of the trephined bone marrow due to electrodecalcification of the osseous tissue.


[APUD system and neuroendocrine tumors ("apudomas")]. Current concepts of the APUD-system combining neuroendocrinal cells located in different organs are presented. The main feature of these cells is the capacity to accumulate precursors of biogenic amines, to decarboxylate them and to produce biogenic amines or polypeptide hormones. The problem of the development of tumours of these cells is discussed, and their morphological, histochemical and clinical features are described.


[Psychosurgery in behavior disorders].

[Psychosurgery in behavior disorders]. The results obtained in a casuistic of 170 patients with mental diseases and behavior disturbances treated by neurosurgical procedures are reported. The authors call attention to the advantages of the atraumatic stereotaxic psychosurgery over the major surgical procedures on the frontal lobes for the treatment of psychoses and intractable psychoneurosis.


[Creutzfeldt-Jakob disease; clinical, histopathological and electron microscopy study of a case]. The case of a patient 53 years old that had a picture of cortical impairment and pyramidal disfunction, leading in 6 months to acinetic mutism is reported. The histopathology lead to the diagnostic of Creutzeldt-Jakob disease, with neuronal loss, gliosis and status spongiosus. The electron-microscopic examination showed that the status spongiosus was due to cellular processes, some having vesicular bodies sugestive of pre-synaptic vesicles.


Late spontaneous clearing of corneal grafts. Three cases of graft rejection or primary donor failure after penetrating keratoplasty failed to respond to treatment. After cessation of therapy, these edematous corneas all cleared spontaneously in six to 17 months with the return of excellent vision. It is suggested that repeated keratoplasty be delayed up to 18 months in certain instances.


Craniofacial resection for malignant tumors of ethmoid and anterior skull base. A combined craniofacial approach is described for resection of tumors that involve the ethmoid sinuses and adjacent base of the skull in the frontal fossa. This operation provides a more thorough en bloc excision than by conventional methods with reasonable safety since both the neurosurgeon and the head and neck surgeon are guided by each other during the mobilization of the specimen, and adequate repair of dural defects can be accomplished. Reconstruction of the bony defect in the skull base is performed with a pedicled periosteal flap from the scalp and a skin graft.


[The comparison of binaural balance-tests (author's transl)]. 14 normal-hearing persons were examined in 7 different versions of the balance-test. Thereby a severe dependence to the methods was found out, caused by psychological factors. By randomization of the side and the intensity (computer-controlled test-procedure) no case showed a significant recruitment. In 23 persons with inner-ear disturbance there was not only the randomized test performed, but also the methods of Jerger (keeping the intensity constant on the worse ear) and Hood (constant on the better ear). By using the randomized test all patients showed a significant recruitment, calculated as the deviation of the angle in relation to the diagonal of the diagram. In 7 cases the method of Jerger and in 20 of all the 23 persons the method of Hood brought a compensation of loudness.


Effect of dimethyl sulphoxide on the expression of nitrogen fixation in bacteria. Storage in dimethyl sulphoxide (DMSO) of Escherichia coli K12 hybrids carrying nif+ genes from Klebsiella pneumoniae can result in selection of a defective nitrogen-fixing phenotype. Similar results are obtained with E. coli K12 hybrids containing the nitrogen-fixing capacity from Rhizobium trifolii. DMSO appears to affect particular inner membrane proteins associated with energy metabolism in E. coli K12 and four chromosomal regions (chlD, chlG, his and unc) are associated with resistance to DMSO.


Studies on immune responses to larval cestodes in mice. Increased susceptibility of certain mouse strains and hypothymic mice to Taenia taeniaeformis and analysis of passive transfer of resistance with serum. Various inbred strains of mice vary markedly in their susceptibility to the larvae of the cestode, Taenia taeniaeformis. Males are generally more susceptible than females and the most susceptible common inbred mouse strains are those which are deficient in C5 and/or C4 components of complement. However, no genetic evidence is yet available to implicate loci controlling complement levels in susceptibility/resistance, and multiple genetic factors appear to be operative. Hypothymic, nu/nu ("nude") mice of the relatively resistant mouse strain, BALB/c, are highly susceptible in that cystic larvae in the liver develop in large numbers and more rapidly than in intact BALB/c.nu/+litter-mates. Cyclophosphamide pretreatment also increases the susceptibility of relatively resistant strains of mice in terms of both the number and size of liver cysts. Hypothymic and intact mice can be protected, absolutely, by an injection of serum from infected intact mice, provided the serum is given to recipient mice close to the time of oral egg administration. The protective activity of immune serum is absorbed totally by staphylococcal protein A-Sepharose columns and can be abolished by treatment of recipients with cobra venom factor. Cyst fluid from established larvae facilitates the activity of subhaemolytic amounts of guinea pig complement in a standard direct PFC assay. The data suggest that complement-fixing antibodies are responsible for inhibition of establishing larvae in mice and that one method of protection for established cystic larvae involves the alteration of host complement activity within the cyst.


The use of hormones in reproductive management of the mare. A brief review is presented of the use in equine veterinary medicine of anterior pituitary hormones, posterior pituitary hormones, placental hormones, steroid hormones and prostaglandins. These hormones are used frequently in clinical application without a scientific basis for their expected activity.


Biological differences between African Theileria mutans (Theiler 1906) and two benign species of Theileria of cattle in Australia and Britain. Serological and morphological comparisons between the theilerias found in Australian and British cattle and of these with African Theileria mutans (Theiler 1906) showed that the Australian and British parasites were similar to each other but different from T. mutans. Further investigations are required to determine taxonomic affinities between the Australian and British theilerias and T. sergenti, a similar parasite found in eastern Asia.


DNA in non Hodgkin-lymphoma--a cytophotometric study. Cytophotometric DNA determinations on 26 cases of non-Hodgkin's lymphoma yielded the following findings: 1. Follicular centrocytic/centroblastic lymphomas (M. Brill-Symmers) and diffuse centrocytic lymphomas (lymphocytic lymphosarcoma) have a diploid DNA stem line. Diploid DNA values are observed in benign tumors, so that the assignment of these lymphomas to the group of "low grade malignancies" appears justified. 2. Lymphoblastic sarcomas show an aneuploid DNA stem line, as do 96% of all malignant tumors. 3. Lymphoid cells, plasma cells, and immunoblasts seen in immunocytomas are aneuploid. Thus these lymphomas must belong to the group of "high-grade malignant lymphomas" as regards their DNA distribution. 4. Immunoblastic sarcomas have aneuploid DNA stem lines (1 case tetraploid), in which both the lymphoid cells and the plasma cells from those immunoblastic sarcomas arising from immunocytomas show atypical DNTA distribution patterns. 5. In two cases of angioimmunoblastic lymphadenopathy, the lymphoid cells, plasma cells, and immunoblasts are aneuploid. They are thus regarded as "high grade malignancy" lymphomas. The results are discussed with respect to clinical course and prognosis. Measurements on a larger series of cases and correlation to clinical data are needed to support these results. Ultrafast DNA measurements made by flow-through cytophotometry can perhaps be helpful in the future for making the decision between a "low" or "high" grade malignant lymphoma.


[A contribution to series sectioning of larynx (author's transl)]. A histological method for large series sectioning of larynx is described. The decalcification consists of 5% HNO3, absolute alcohol and 0,5 chromic trioxide. The larynx is imbedded in paraplast. Sections of 6--10 micron in thickness can be cut from blocs 8 X 6 X 5 cm and stained by general histological methods. The complete procedure took only six to seven weeks.


[The influence of medication with calcium and vitamin D2 on incorporation and micro-hardness of cancellous bone grafts and cortical grafts (author's transl)]. An investigation on the superiority of autogenous cancellous bone grafts compared to cortical grafts in guinea pigs by means of the micro-hardness test of Vickers revealed an improvement of hardness of the transplants as well as of the frame structure, i.e. an amelioration of physical bone properties due to medication with a calcium-vitamin D2 combination (Frubiase Calcium forte).


[Problems in serum-level determination during valproic acid therapy]. An investigation was carried out to determine whether or not a reliable and reproducible steady state serum level of the anticonvulsant drug valproic acid could be found, such that single values of a serum level determination could be used in therapeutic control. 1. A reliable and comparable serum concentration of valproic acid could not be found in 11 patients during a long-term investigation over a period of 8 weeks. Likewise this could not be found in the 24-h serum concentration profile in 8 of the above mentioned patients, who were receiving both mono and combined therapy. 2. The half-life values for valproic acid in these 8 patients lay between 8--12.5 h. 3. The maximum concentration of valproic acid lies in unforeseeable time spans after drug administration. 4. The morning fasting values are comparable only to a limited extent. In future daily profiles it must be decided whether, and if so to what extent, valproic acid serum concentration determinations can be of value to the individual treatment of epileptics.


T-lymphocyte subpopulation in untreated SLE. Variations with disease activity. An active subpopulation of T lymphocytes characterized by their ability to form early rosettes with sheep erythrocytes (active E-RBL) was studied in the blood of 50 patients with untreated systemic lupus erythematosus (SLE) and in 50 normal controls. The findings were related to the absolute number of circulating lymphocytes and total E-receptor-bearing lymphocytes (total E-RBL). Lupus patients with active disease had markedly decreased absolute lymphocyte counts, but the decrease of both the total and the active E-RBL surpassed what would be expected from the lymphopenia. Patients with inactive disease had moderately decreased absolute lymphocyte counts with a marked and disproportionate decrease in total E-RBL and a moderate decrease in active E-RBL, which seemed to reflect only the absolute lymphopenia. Patients with active disease had significantly lower active E-RBL than those with inactive disease. The changes of these and other lymphocyte subpopulations in relation to disease activity in SLE may reflect the influence of factors leading to T-cell depletion and immaturity. Circulating thymic products may be one of those factors.


Controlled double-blind trial on the clinical effects of the chenodeoxycholic acid-fentonium bromide combination in the symptomatic treatment of biliary spastic-dyskinetic conditions. A double-blind controlled trial was carried out to compare the effects of chenodeoxycholic acid combined with fentonium bromide (respectively, 125 and 20 mg for each capsule) vs. biliary acid alone in the treatment of biliary dyskinetic conditions with or without gallstones. Observations, concerning altogether 30 patients, showed a significantly higher and quicker efficacy of the combination (3--4 capsules daily during 14 days), in comparison to chenodeoxycholic acid alone, on the group of "painful" symptoms; on the contrary, no significant difference was noticed with regard to efficacy on "dyspeptic" symptoms. These results show the significant contribution of fentonium bromide and give experimental evidence of the usefulness and therapeutical advantages of the preparation under study.


Aspirin and delayed type hypersensitivity. The effects of aspirin on delayed hypersensitivity were assessed in 40 healthy subjects who were randomly assigned to two equal groups. In a double-blind format, the individuals in one group were placed on 4 gm aspirin daily for 5 days, and individuals in the other group were given placebo. Lymphocyte proliferation was measured before and 72 hours after the initiation of drug, by using three mitogens and four antigens. The percentages of T and B lymphocytes were likewise measured before and during therapy. The subjects were skin tested with the same four antigens 72 hours after the initiation of drug, and the skin tests were read 48 hours later. No significant differences between the two groups were detected when skin tests, lymphocyte proliferation, and percentage of T lymphocytes were compared.


[Double-blind comparison of vincamine and placebo in patients with presbyacusis (author's transl)]. 14-15-Dihydro-14beta-hydroxy-[3alpha,16alpha]-eburnamenine-14-carbonic acid methylester (vincamine, Vincapront) and placebo were compared in a double-blind trial, using daily doses of 60 mg p.o. in 30 out-patients suffering from peripheral and mainly centrally induced labyrinthine deafness (presbyacusis). The treatment lasted for 6 weeks. The diagnosis was established by otological examinations, the SISI test and pure-tone and speech audiometry. Other causes of disease were excluded. 6 patients suffered from an accompanying disease needing treatment (glycosides, antihypertensives). 1 patient had an intercurrent rhinopharyngitis. Any other drug was discontinued at the beginning of treatment. The result was checked by pure-tone and speech audiometry (monosyllabic word test) before and after treatment. The pure-tone audiometric test did not reveal any change in both groups while speech audiometry (monosyllabic word test) showed significant improvements in the vincamine group (p less than 0.004). Only random alterations occurred in the control group. Vincamine was well tolerated by all patients. The tolerance of placebo was rated to be moderate by two patients.


1-Methyl-2-nitroimidazol-5-yl derivatives. IVth Communication. The chemico-physical data and antimicrobial activities are described of a new series of 2-nitroimidazole derivatives prepared by condensing 1-methyl-2-nitroimidazole-5-carboxaldehyde with N-substituted hydroxylamines, N-aminopiperazines and N-aminopiperidines.


[Effects of intravenous administration of memantine in parkinsonian patients (author's transl)]. After a preliminary study in 6 parkinsonian patients concerning the effectiveness and tolerance of 1,3-dimethyl-5-aminoadamantane hydrochloride (memantine) an investigation to assess its short-term effects was performed. In an unselected group of 12 parkinsonian patients 40 mg of memantine diluted in 500 ml of laevulose were applied i.v. within 2 h. The patients were examined under standardized conditions before, immediately after and 2, 4 and 24 h, respectively, using a program of physchological tests. The results give evidence for a favourable influence on rigor and tremor in Parkinson's syndrome as well as on motor drive. In comparative studies memantine showed a better tolerance than adamantylaminosulfate. The short-time effects of the drug could be differentiated from placebo and learning effects.


Simultaneous gelatin embedding of multiple areas of the arterial tree. An embedding method for simultaneously cutting frozen sections of multiple segments of the arterial tree is presented. The segments are stacked in a standardized form and embedded in gelatin. Preparation of the blocks, cutting on a freezing microtome and storage of remnants are discussed. Alignment of the segments was easily achieved and the blocks were sectioned without difficulty. This technique saves space and effort and facilitates screening and rapid reading of slides.


Controlled trial of the effect of cycloalliin on the fibrinolytic activity of venous blood. Cycloalliin is a natural constituent of onion, sulphur-containing but odourless. It was synthesised for this randomised double-blind study; its effect on fibribolytic activity and platelet aggregability was tested in venous blood from 18 male volunteers. It increased the former to a highly significant degree but had no effect on the latter. It was well tolerated and harmless in the single oral dosage used.


[Immunofluorescence aspects of chronic hepatitis in children]. Liver biopsies from patients (mostly children) affected by chronic hepatitis (persistent or active, HBsAg positive or negative forms), part of them treated by immunosuppressive therapy, have been studied by means of immunofluorescence techniques. A cytoplasmic localization of HBsAg and a nuclear localization of HBcAg have been demonstrated. Moreover, a nuclear localization of immunocomplexes was demonstrated, as well as the presence of immunoglobulins. Persistent forms showed a lesser fluorescence than active forms, and so did the treated patients, if compared with recent, not yet treated subjects.


Once daily treatment of mild to moderate hypertension with xipamid: a controlled study. A double-blind, placebo controlled, crossover trial of 20 and 40 mg of xipamid once daily in the treatment of mild to moderate hypertension is reported and some of the difficulties and pitfalls of multicentre trials of this type are described. 2 Both doses were significantly more effective in reducing the blood pressure than the placebo and neither was superior to the other. Both produced some potassium loss. Xipamid acted for at least 22 h and was effective in up to 83% of the patients. 3 Further trials are suggested to investigate the activity of a lower dose than 20 mg.


A comparative trial of clonidine, propranolol and placebo in the treatment of moderate hypertension. 1 A double-blind cross over trial between clonidine, propranolol and a placebo in patients with moderate hypertension has been performed. 2 Thirty-two patients completed the study which consisted of three treatment periods in random order of 3 months each. Patients had their blood pressure recorded by an unbiased observer using a random-zero machine. 3 Both clonidine and propranolol produced a significant reduction in blood pressure (P less than 0.01), which was apparent by the second week of therapy. Propranolol gave a greater reduction in pulse rate than clonidine (P less than 0.01) but clonidine also reduced the pulse rate significantly (P less than 0.05). There was no evidence of postural hypotension on either drug. Side-effects were more common with clonidine but these tended to wear off after several weeks of therapy. 4 Clonidine and propranolol were equipotent in reducing blood pressure, but clonidine has more initial side-effects than propranolol.


Improved pepsin inhibitor derived from activation peptide 1-16 of porcine pepsinogen. The peptide Leu-Val-Lys-Val-Pro-Leu-Val-Arg-Lys-Lys-Ser-Leu-Arg-Gln-Asn-Leu, a known pepsin inhibitor, is derived from the first 16 amino acids of porcine pepsinogen. It was prepared from the activation mixture and was modified by guanidination of its three lysine residues to form homoarginine residues. The modified peptide is a better pepsin inhibitor than the native peptide; for 50% inhibition of the milk clotting action of pepsin at pH 5.3, the molar ratio of peptide to pepsin required is 9 for the native inhibitor and only 2 for the guanidinated inhibitor. The dissociation constants (k1) of the inhibitor-pepsin complexes are 7 X 10(-8) and 1.4 X 10(-8) M for the native and guanidinated peptides, respectively. The guanidinated peptide is more resistant to digestion by pepsin at pH 3.5. The native and modified peptides partially protect pepsin from inactivation at pH 7. Stepwise removal of the amino-terminal Leu-Val-Har residues from the guanidinated inhibitor by Edman degradation decreases the pepsin-inhibiting activity only slightly at the first step, but markedly at the second and third steps. Thus, all of the amino-terminal sequence except the leucine residue is necessary for full activity.


Magnesium ion requirements for yeast enolase activity. It has generally been concluded that two divalent cations are required for enolase activity, even though the enzyme is a homodimer that specifically binds four metal ions in the presence of substrate. This paper reports a reinvestigation of the stoichiometry of enolase activation. Specific ion electrode measurements of Mg2+ binding in the presence and absence of substrate are compared with stopped-flow measurements of the velocity of 2-phosphoglycerate dehydration. It is concluded that the enzyme is inactive when only two metal-binding sites are filled and that four sites must be populated with Mg2+ for full activity. An ordered binding mechanism is proposed that quantitatively predicts the activation of enolase by the four Mg2+ ions from their measured dissociation constants and the Michaelis constant for the dehydration reaction. To explain the loss of enzymatic activity at still higher metal concentrations, the binding of additional, inhibitory Mg2+ ions is postulated.


Evidence for a single essential thiol in the yeast hexokinase molecule. In yeast hexokinase B, two thiols per monomer appeared to be essential when enzymic inactivation was produced by the concurrent alkylation of both of them, by several reagents including the affinity reagent N-bromoacetyl-2-D-galactosamine. However, it is shown that only one of these thiols is actually essential. Three of the four thiols present can be blocked by alkylation in the presence of a substrate in appropriate conditions, without loss of enzymic activity. Subsequently, in the absence of substrate, the affinity reagent reacts at the one remaining thiol, with complete inactivation. The same behavior can be obtained by reaction with iodoacetamide or by the formation of the -SCN group. The affinity reagent inactivates hexokinase B faster than does the isomeric glycosidic compound (glycosides being nonsubstrates), although the latter has twice the reactivity of the former toward glutathione. The reactions with alkylating agents, with or without substrate present, are used to classify the four thiols in the monomer. The temperature dependence of the alkylation of the essential thiol provides evidence for a transition in the molecule at about 31 degrees C. The inactive monomer containing the -SCN group can regenerate, by thiolysis, active enzyme with the thiol free. It can also perform an intramolecular cleavage of the chain. The latter reaction was used to locate the essential cysteine residue in the chain, at 80% of the length from the N terminus.


Nonenzymatic reduction of prostaglandin H by lipoic acid. Lipoic acid has recently been found to stimulate prostaglandin biosynthesis by sheep vesicular gland microsomes (Marnett, L. J., and Wilcox, C. L. (1977). Biochim. Biophys. Acta 487, 222). The increase in oxygenated products is predominantly in the formation of prostaglandin F and its structure has been verified by gas chromatography-mass spectrometry. Endoperoxide trapping experiments employing reduced glutathione show that the conversion of prostaglandin H to prostaglandin F is slow in lipoate containing incubation mixtures. Therefore, the net effect of the addition of lipoic acid to vesicular gland microsomes is the stimulation of prostaglandin endoperoxide biosynthesis. Further experiments reveal that the reduction of prostaglandin H to prostaglandin F by lipoate is nonenzymatic and occurs after the termination of biosynthesis in the work-up mixture. The reduction takes place preferentially in the organic phase of a Folch extract (chloroform-methanol-2% formic acid 8:4:3). Authentic prostaglandin H2 is reduced by lipoic acid to prostaglandin F 2alpha in high yield under these conditions.


Mobile carrier ionophores for Fe(II).

Mobile carrier ionophores for Fe(II). A23187 and certain other carboxylate ionophores are capable of transferring Fe(II) but not Fe(III) across phospholipid bilayers (liposomes) and red cell membranes. A23187 is able to transfer Fe(II) from ferritin loaded liposomes when allied with a suitable redox couple and sink. The affinity of A23187 for Fe(II) is approximately five orders of magnitude greater than for Ca2+, as judged by two phase extraction techniques.


Phospholipid exchange between bilayer membranes. The mode of interaction of aqueous dispersions of phospholipid vesicles is investigated. The vesicles (average diameter 950 A) are prepared from total lipid extracts of Escherichia coli composed of phosphatidylethanolamine, phosphatidylglycerol and cardiolipin. One type of vesicle contains trans-delta 9-octadecenoate, the other type trans-delta 9-hexadecenoate as predominant acyl chain component. The vesicles show order in equilibrium disorder transitions at transition temperatures, Tt = 42 degrees C and Tt = 29 degrees C, respectively. A mixture of these vesicles is incubated at 45 degrees C and lipid transfer is studied as a function of time using the phase transition as an indicator. The system reveals the following properties: Lipids are transferred between the two vesicle types giving rise to a vesicle population where both lipid components are homogeneously mixed. Lipid transfer is asymmetric, i.e. trans-delta 9-hexadecenoate-containing lipid molecules appear more rapidly in the trans-delta 9-octadecenoate-containing vesicles than vice versa. At a given molar ratio of the two types of vesicles the rate of lipid transfer is independent of the total vesicle concentration. It is concluded that lipid exchange through the water phase by way of single molecules or micelles is the mode of communication of these negatively charged lipid vesicles.


Kinetics of phospholipid exchange between bilayer membranes. In an accompanying publication by Duckwitz-Peterlein, Eilenberger and Overath ((1977) Biochim. Biophys. Acta 469,311--325) it is shown that the exchange of lipid molecules between negatively charged vesicles consisting of total phospholipid extracts from Escherichia coli occurs by the transfer of single lipid monomers or small micelles through the water. Here a kinetic interpretation is presented in terms of a rate constant, k--, for the escape of lipid molecules from the vesicle bilayer into the water. The evaluated rate constants are kP- = (0.86 +/- 0.05) - 10(-5) S-1 and ke- = (1.09 +/- 0.13) - 10(-6) s-1 for phospholipid molecules with trans-delta 9-hexadecenoate and trans-delta 9-octadecenoate, respectively, as the predominant acyl chain component. The rate constants are discussed in terms of the acyl chain and polar head group composition of the lipids.


[The influence of chloramphenicol on synthesis of ribosomes and beta and beta' subunits of RNA polymerase]. The effect of low chloramphenicol concentrations on the biosynthesis of RNA, ribosomal proteins and RNA polymerase in E. coli CP 78 cells was studied. When protein synthesis was decreased by 50--70%, 14C-uracil incorporation in DNA increased twice, the rRNA synthesis being stimulated preferentially. In the presence of antibiotic the RNA/DNA ratio increased from 5,7 to 13,3. The differential rate of r-protein synthesis increased simultaneously with the stimulation of rRNA synthesis, so that alphar rises from 0,083 (without antibiotic) to 0,122 and 0,161 at 5 and 10 microgram/ml of chloramphenicol, respectively. The inhibition of protein synthesis by chloramphenicol is accompanied also by the increase of differential rate of synthesis of beta and beta' subunits of RNA polymerase. In the presence of 5 and 10 microgram/ml of chloramphenicol, alphap increased from 0,90% to 1,44 and 1,57%, respectively. It is assumed that the genes for beta and beta' subunits of RNA polymerase as the ribosomal genes are negatively controlled by guanosine tetraphosphate which intracellular concentration decreased in the presence of chloramphenicol. The known data on the influence of streptolydigin and rifampicin on the RNA polymerase biosynthesis are discussed in view of proposed hypothesis.


[In vivo and in vitro studies of phage T4 lysozyme mRNA translation]. Translation of phage T4 lysozyme mRNA is studied in vivo and in vitro. Polyribosomes, carrying growing lysozyme polypeptides, are found to be homogenous enough and to contain 6 ribosomes. Complete molecules of phage lysozyme, which possess an enzymatic activity and are similar to the native enzyme in its electrophoretic mobility in polyacrylamide gel, have been synthetized in vitro on RNA isolated from phage-infected cells. The efficiency of RNA translation in cell-free system is discussed on the model of synthesis of functionally active individual protein.


[Kinematics of fibroblast spreading. II. Individual locomotor activity]. An analysis of area changes of normal mouse fibroblasts during their spreading is made with time intervals of 5-50 s. A mean increase of the area takes place simultaneously with area fluctuations of various rhythms, which result from accidental undulations of the lamella edge. The fluctuations are also the same during intermediate temporary stopping of cell spreading. The central cell region--endoplasm--is stretched passively by centrifugal lamella forces and is an active antagonist of forces in squeeze processes. A description is made of the lamella edge undulations like the phase states change of protraction and retraction, and it is shown by two-dimensional phase diagrams that edge-activity has a zone organisation. These zones can migrate upon the cell perimeter as a wave in stohastic excitable medium.


A stimulator of stem cell proliferation in regenerating bone marrow. A factor, capable of stimulating resting haemopoietic stem cells into DNA-synthesis has been extracted from regenerating bone marrow. It has a molecular weight in the range of 30.000-50.000 daltons and is not detectable in normal bone marrow. Used in combination with a stem cell proliferation inhibitor, previously described, it will restimulate proliferation in stem cells initially stopped by the inhibitor. Conversely, stimulation produced by this factor can be reversed by the addition of inhibitor. It is concluded that stem cell proliferation is controlled by an appropriate balance of endogenously produced stimulatory and inhibitory factors.


[Interaction between a fluorescent probe and the surface structures of Escherichia coli]. The interaction of ANS with Escherichia coli cells, isolated cell walls, total cell envelopes and inner membranes was investigated in the presence and absence of Ca2+ ions. The addition of Ca2+ to intact cells at room temperature did not result in enhancement of fluorescence intensity. On the contrary the addition of Ca2+ to intact cells at 2 degrees C resulted in a progressive increase of fluorescence intensity with the maximum reached approximately by the 20th minute. The addition of Ca2+ to different membrane preparations showed a two-fold increase. Addition of Ca2+ to spheroplast membrane preparations did not result in any increase of the number of binding sites for ANS. There was a four-fold increase in quantum yields. All membrane preparations in titrations with Ca2+ showed saturation kinetics. The obtained results are discussed in terms of structural alterations in E. coli membranes and in relation with biological effects.


Midcycle doubling of uptake rates of adenine and serine in Saccharomyces cerevisiae. Rates of uptake of serine and of adenine were measured as a function of cell size, and therefore age, in asynchronous, exponential phase cultures of diploid Saccharomyces cerevisiae strain Y55. In both cases, uptake rates were constant during the initial third of the cell cycle and doubled during the S period in the middle part of the cycle to a constant value during the final third. Cell size and age at mid-step doubling were indistinguishable for serine and adenine uptake, and occurred during the period of DNA synthesis. The results extend an earlier hypothesis of constancy of cell growth rates (mass accumulation rates) and rates of uptake of all or almost all compounds into cells in exponential phase growth to one of piecewise constancy, with an abrupt doubling of growth and uptake rates during DNA synthesis.


Mechanisms of intercellular adhesion.

Mechanisms of intercellular adhesion. Investigations into cellular adhesion, both of a biochemical and biophysical nature, have not yet produced an established theory or widely accepted hypothesis to explain the mechanics of this fundamental biological process although much information concerning the structure and function of the mammalian cell surface has been gained. At the present time there is increasing evidence to suggest that cellular adhesion is mediated by specific cell surface macromolecules which are capable of forming protein-carbohydrate complexes possibly resembling those found between plant lectins and their carbohydrate substrates.


Evolutionary significance of the system utilizing D-amino acid enantiomers. The evolutionary significance of the system utilizing D-amino acid enantiomers in living organisms is discussed, based on an experiment in which the mutant from Escherichia coli K--12 4627 grown on D-tryptophan was used. The mutant shows the ability of D-tryptophan is degraded to indol which can be utilized for the synthesis of L-tryptophan in the presence of serine.


Chemical procedures for enzyme immobilization on porous cellulose beads. In a previous article, the method of preparation and the physical properties of porous (75 to 80% porosity) cellulose beads were described (Biotechnol. Bioeng., 18, 1057 (1976). The present article reports that the chemical procedures employed for immobilizing enzymes on ordinary cellulose can be applied to the porous cellulose beads. The results showed more enzyme loading on the beads than ordinary cellulose. The choice of the procedures might also affect the mechanical strength of the cellulose beads.


[Effect of erythrocyte breakdown products on mast cells and erythropoietin formation]. Experiments were conducted on CBA mice and albino rats. A study was made of the effect of erythrocyte destruction products (EDP) on the content of hemopoietic colony-forming units (CFU), differentiation of stem cells and the erythropoietin production. It was shown that 3 or 4 EDP injections to normal mice or to lethally irradiated (1000 rad) mice after the transplantation of bone marrow cells caused no changes in the CFU level of stem cells differentiation. In case of a daily (for 3 days) administration of EDP to mice before the irradiation (1000 rad) and bone marrow transplantation there was observed an increase of the colonies count in the recipients' spleen on account of the erythroid colonies. EDP injection caused no changes in the erythropoietic activity of the blood serum. A possible role of erythrocyte destruction products in the mechanism of erythropoiesis autoregulation is discussed.


[Kinetics of the basic sections of the hemopoietic system in radiation chimeras]. During first 3 days after mice irradiation and syngeneic bone marrow transplantation in them the number of CFUs (about 0,5% of the injected cells) was stable, although the proliferation induction began 24 hours after transplantation. As it was shown by the method of "thymidine self-distruction". Twenty four hours later all the CFUs entered the mitotic cycle. On the contrary, the commited cells (granulopoesis precursors) compartment (CFUc) enters the logarithmic growth phase since the first day. The exponential growth of the CFUs number was observed from the 4th day simultaneously with the increasing of the proliferation rate of CFUc and the beginning of the recovery of the bone marrow cells total number. In late radiation chimeras (1 month after radiation and reconstitution) the total number of CFUs was 50--70% of the initial. The other hemopoetic parameters were in the normal limits.


[Behavior of the F-like plasmids in bacterial cells with a varying capacity genetic recombination]. F-like plasmids (FBl, FBl drd, F-lac+) were transferred to the recipient strains E. coli, K-12 with different recombination ability. Then the sensitivity of these strains to ultra-violet irradiation and also the stability of the mentioned plasmids under conditions of bacteria treatment with elimination agents was determined. The presence of any F-like plasmids under study failed to influence the ultra-violet sensitivity of the bacterial cells. On the other hand, the research results of spontaneous and inducec elimination of these plasmids indicated considerable differences in relation to the elimination agents. It is supposed that the stability of individual F-like plasmids in the cells largely depended on the genetic differences in rec A gene in the bacterial cells containing them.


[Ultrastructural analysis of the effect of alloxan on the cellular elements of the pancreas in reptiles]. Intraperitoneal injection of alloxan to Testudo horsfieldi and Caspian tortoises in a dose of 300 mg/kg caused destructive and metabolic changes in the cell elements of both the endocrine and the exocrine part of the pancreas. Focal destruction occurred in the granular cytoplasmic reticulum of the acinar cells, and mitochondria--in the mucoid and centroacinar cells. Hydropic degeneration developed in B-cells. All the cell elements and nerve fibers displayed glycogen deposition, the most pronounced in the centroacinar and mucoid cells.


Discrete clusters of hematopoietic cells in the marrow cavity of man after bone marrow transplantation. Discrete aggregates of hematopoietic cells were observed in the bone marrows of patients with aplastic anemia or acute leukemia 14 days after marrow transplantation. The great majority of such colonies were of a single cell type, and less than 3% contained two or more cell types. Erythroid, myeloid, and undifferentiated hematopoietic colonies were approximately equal in frequency.


Immunofluorescent method for positive identification of null-cell type acute lymphocytic leukemias: use of heterologous antiserum. Acute lymphoblastic leukemia (ALL) patients could be subclassified into two groups depending on whether or not their leukemia cells expressed a B-lymphocyte antigen. The antigen was detected by an indirect immunofluorescence test using rabbit antisera. In the positive group, consisting of 26 of 32 patients, the leukemia cells were of the "null"-cell type, i.e., they did not appear to express currently recognized T- and -b-cell markers. Absroption studies indicated that the positive null-cell group expressed a common antigen which was not expressed on the negative group. Of the 6 negative cases,, 5 expressed complement receptors and 3 expressed T-cell markers. The negative group was also characterized by high white cell counts and the pressence of a mediastinal mass.


[Electrophoretic mobility of lymphocytes in chronic lymphatic leukemia (author's transl)]. Lymphocytes and other blood cells can be separated by means of free flow cell electrophoresis. Immunofluorescence of the separated lymphocytes of four healthy volunteers with antiimmunoglobulins IgD and IgM produced different distribution profiles for each immunoglobulin class, the IgD positive cells migrating faster than the IgM positive ones. Amongst five patients with chronic lymphocytic leukemia four with IgD positive lymphocytes (greater than 80%) showed an identical electrophoretic distribution. The IgM positive lymphocytes (greater than 80%) of the fifth patient migrated much more slowly. The weighted mean of each distribution profile of either the IgD or IgM positive lymphocytes in CLL is similar to that of normal subjects.


Tumors and amyloidosis in mice painted with crude oil found on bathing beaches. Oil lumps collected on the beaches of Israel in 1970, 1971 and 1973 were extracted with pure acetone and the extracts were used to paint the skin of mice twice weekly for 12 months. The oil lumps originated from crude oil spilled from tankers. The less recently collected oils induced papillomata and lymphomata in some animals. They were also more active than the recent oil in the induction of generalized amyloidosis. Mice painted for 12 months with acetone alone developed amyloidosis to a similar extent as those painted with the oldest oil. In previously reported experiments, however, acetone was much less active than the oil in producing amyloidosis after 5 months of painting. The possibility that acetone and oil might act both synergistically or to be antagonistic at different phases of amyloidogenesis is discussed.


Foundations of medical librarianship.

Foundations of medical librarianship. The development of medical librarianship during the last forty years is examined as reflected in the changes of its resources, technology, education, and knowledge base. A shift from historical to scientific inquiry constitutes the direction of medical librarianship. Its nexus is the gathering of information and the transfer of knowledge. The social and human resources for this ongoing change and the basis for a quest for excellence is seen in the pool of talent represented by hospital librarians and the aspirations of the women's movement for equality.


[Effect of hydrocortisone injections on bronchial obstruction in asthma (author's transl)]. In 14 asthmatic subjects with bronchial obstruction reversible by beta-sympathomimetic drug inhalation (salbutamol), the effect of intravenous injections of placebo and of 2, 4 and 8 mg/kg of hemisuccinate hydrocortisone (HSHC) has been measured by determining the forced expiratory volume in one second (FEV1) every two hours for eight hours. In four patients, FEV1 was not significantly altered by HSHC injection. It was improved in the ten other patients. The latency period lasted at least four hours and the peak action was observed between the sixth and the eighth hour. These two factors were related to the HSHC dose. The improvement obtained with 8 mg/kg HSHC was similar to that of salbutamol. The effect of the latter was potentiated by 8 mg/kg HSHC. These results suggest that HSHC should not be used when a fast reaction is wanted, on the one hand, and that the efficacy of the product must be controlled by objective measurements, on the other hand since not every subject is responsive.


[Gamma function extrapolation of dilution curves for pulmonary blood volume determination in chronic bronchitis (author's transl)]. The risk of incorporating inapparent recirculation under the extrapolated downslope of dye dilution curves is greater with exponential than gamma function extrapolation since the latter makes use of ascending and early descending limbs of the curve. Extrapolation of a true gamma function is not affected by the level at which extrapolation begins. With curves obtained in eight normal subjects, cardiac output (phi) was comparable by exponential and gamma extrapolation if the latter began between 75 and 55% of the peak concentration (Cmax.). phi was underestimated or overestimated according to whether extrapolation began higher or lower than the above limits. Therefore, experimental curves were not true gamma functions. However, the level at which extrapolation began had little effect on pulmonary mean transit time and pulmonary blood volume (PBV) calculated by use of the double injection-single sampling method. Similar effects on phi of the level at which extrapolation by a gamma function begins were found with 24 chronic bronchitics. PBV calculated with a gamma function extrapolated from 0.75 X Cmax. downwards and with an exponential function averaged approximately 340 ml and did not differ from one another. The data suggest that the low values of PBV in chronic bronchitis are not an artifact due to the method of extrapolation.


Is your dosage really necessary? Antibiotic dosage in urinary infection. Dense cultures of bacteria were exposed to changing concentrations of beta-lactam antibiotics in an in-vitro model of the urinary bladder. The results suggest that uncomplicated urinary infection may respond to lower doses than are usually given without compromising the success of subsequent treatment in those cases in which such minimal treatment fails.


[Technical and experimental study of two electronic spirometers (author's transl)]. Two electronic spirometers which use standard pneumotachographs were evaluated for their static and dynamic response, and clinically compared in 20 subjects to a reference flow channel. In the Pneumoscreen the data are digitalized and stored, permitting to play back the flow-volume curves at low or high speed. The instrument provides a direct read-out of forced vital capacity and of five indexes of forced expiration. It was found perfectly adequate with respect to linearity and frequency response. However, due to some systematic error in digital processing, maximum flow at low lung volumes appeared substantially over-estimated. Besides forced vital capacity and a number of indexes of forced expiration, the Medistor type M 010 may be used to measure ventilation, tidal volume, frequency and maximum breathing capacity. The data are processed by an analog computer. The transducer was found poorly linear with inadequate frequency response. However, no systematic bias in the measurements was found, except for peak flow and maximum breathing capacity.


[The effects of the pause at the end of inspiration on gas exchange and hemodynamics during artificial ventilation]. We have studied the effects of an inspiratory pause (PI) during artificial ventilation in 13 patients in acute respiratory insufficiency. The effects on gas exchange, haemodynamics and distribution of ventilation were observed. During the period of study the total volume, the inspiration/expiration ratio and the inspired oxygen concentration were all maintained constant. With the inspiratory pause arterial oxygenation has not changed significantly, whereas it did change favourably with PEEP. The physiological dead space (VD/VT) was reduced in proportion to the duration of the inspiratory pause. These results suggest that the inspiratory pause triggers regional modification of the ventilation/perfusion ratio, favouring a reduction of the VD/VT ratio. However, this improvement of the VD/VT ratio does not seem to influence the oxygenation or the total distribution of ventilation in this type of patient.


Prevention of obstruction of nasopharyngeal CPAP tubes by adequate humidification of inspired gases. Nasopharyngeal CPAP is a simple and useful technique for increasing FRC and stimulating respiration in small premature infants. However, as it is essentially a non-rebreathing technique, the gases used should be warmed and saturated to the level normally found in the pharynx with no artificial airway present (31 degrees to 33 degrees C, 90 per cent plus relative humidity). If this is not done, crusting, mucous plugging, atelectasis, hypoxia, and infection will occur rapidly. Excess humidity should also be avoided.


Purine metabolism in Saccharomyces cerevisiae. The synthesis, interconversion, and catabolism of purine bases, ribonucleosides, and ribonucleotides in wild-type Saccharomyces cerevisiae were studied by measuring the conversion of radioactive adenine, hypoxanthine, guanine, and glycine into acid-soluble purine bases, ribonucleosides, and ribonucleotides, and into nucleic acid adenine and guanine. The pathway(s) by which adenine is converted to inosinate is (are) uncertain. Guanine is extensively deaminated to xanthine. In addition, some guanine is converted to inosinate and adenine nucleotides. Inosinate formed either from hypoxanthine or de novo is readily converted to adenine and guanine nucleotides.


Intestinal emphysema (Pneumatosis cystoides intestinalis) in a gnotobiotic pig. A gnotobiotic pig monocontaminated with an enteropathogenic Escherichia coli was subsequently hyperimmunized to produce a monotypic antiserum. At necropsy, multiple, air filled cysts were found in the wall of the large intestine. The etiology of this condition is still conjectural. However, select strains of E. coli may cause or contribute to intestinal emphysema in swine.


Nonsteroidal anti-inflammatory drugs: a review. New applications in hypersensitivity reactions of cattle and horses. Nonsteroidal anti-inflammatory drugs inhibit the biosynthesis of kinins and prostaglandins and stabilize leukocyte lysosomal membranes. Nonsteroidal anti-inflammatory drugs also weakly block the biosynthesis of histamine and serotonin, and pharmacologically antagonize kinins, prostaglandins and slow-reacting substance of anaphylaxis. Nonsteroidal anti-inflammatory drugs effectively control both cardiovascular and respiratory manifestations of hypersensitivity in cattle and horses. This, coupled with the contrasting lack of effectiveness of "antiamine" drugs, suggests that bio-amines such as histamine and serotonin (5-hydroxytryptamine) may be less important than kinins, postaglandins and slow-reacting substance in the mediation of the hypersensitivity/inflammatory reaction, at least in cardiopulmonary systems of these species. Nonsteroidal anti-inflammatory drugs justify more prominence in the clinical control of acute respiratory disease in domestic herbivores.


Effect of heat stable and heat labile Escherichia coli enterotoxins, cholera toxin and theophylline on unidirectional sodium and chloride fluxes in the proximal and distal jejunum of weanling swine. Acute, isolated loops of proximal and distal jejunum of weanling swine were exposed to either heat stable porcine Escherichia coli enterotoxin, heat labile porcine Escherichia coli enterotoxin, cholera toxin or theophylline. Unidirectional sodium fluxes in response to heat stable in the proximal jejunum were dependent on the length of time that the intestinal mucosae was exposed to the enterotoxin. Net water, sodium and chloride and unidirectional sodium and chloride flux measurements in the proximal jejunum in response to each agent uniformly indicated that net secretion of fluid and electrolytes was the result of increased unidirectional sodium secretion or blood-to-lumen flux and decreased unidirectional chloride absorption or lumen-to-blood flux. In addition heat stable cholera toxin and theophylline but not heat labile decreased unidirectional chloride secretion a small but significant amount in the proximal jejunum. Sodium and chloride flux measurements in the distal jejunum demonstrated that all four secretory agents could stimulate net secretion of water, sodium and chloride in that region. The response to these secretory agents as measured by sodium and chloride unidirectional flux rates was not similar to changes observed in the proximal jejunum. In the distal small intestine, whereas heat labile cholera toxin and theophylline induced similar qualitative changes in unidirectional sodium and chloride fluxes, that induced by heat stable differed.


The metabolism of phenylacetic acid by Aspergillus fumigatus ATCC 28282: identification of 2,6-dihydroxyphenylacetic acid. Aspergillus fumigatus ATCC 28282 converted phenylacetic acid into a new dihydroxylated compound (2,6-dihydroxyphenylacetic acid) which was identified as 2,6-dimethoxyphenylacetic acid methyl ester. Two other new metabolites have been isolated also and identified as orthohydroxyphenylacetic acid and meta-hydroxyphenylacetic acid.


Phage typing of Escherichia coli isolated from chickens. Ten different bacteriophages were isolated from untreated city sewage water. These phages were stable at 57 degrees C for 40 min. A modified agar layer technique was used to obtain high titre phages. Ninety-four of a stock of 101 cultures of Escherichia coli, which were isolated from inflamed portions of intestines of chickens, were lysed by one or more of these phages. The E. coli of a known serological grouping were phage typed.


Flow-microfluorometric analysis of Escherichia coli, Rhizobium meliloti, and Rhizobium japonicum at different stages of the growth cycle. The applicability of flow-microfluorometry (FMF) to the study of bacterial samples was investigated on cultures of Rhizobium meliloti, Rhizobium japonicum, and Escherichia coli using fluorescent and light-scattering signals. This technique which analyzes individual bacterial cells in a population was used to monitor the relative change in nucleic acid content and cell size during the growth cycle of the three microorganisms which were known to have different growth rates. Early log-phase E. coli cells contained at least eightfold more nucleic acid and were significantly larger than the stationary-phase cells. Cultures of early log-phase R. meliloti cells contained three to four-fold more nucleic acid and were slightly larger than cells in the stationary phase. Rhizobium japonicum had very little change in either parameter. In general, the amount of change in both cell size and nucleic acid content upon initiation of log-phase growth was related to the overall growt rate of the organisms, with E. coli experiencing the greatest change and R. japonicum the least. Results obtained by FMF analysis, therefore, were consistent with observations reported by earlier workers. Cultures of R. meliloti also were used to demonstrate that the intensity of the fluorescent signals was sensitive to digestion by DNase and RNase and to prolonged storage and fixation. The potential use of FMF in the study of microorganisms is discussed.


Inhibition of Clostridium botulinum types A and B hemagglutinins by sugars. Chromatographically isolated hemagglutinins of Clostridium botulinum types A and B are serologically related but not identical. Of the sugars (5, 6, 12, 18 carbons, some derivatives, L  and D forms) tested, only D-galactose and some of tis derivatives were inhibitors of these hemagglutinins. O-Nitrophenyl-beta-D-galactopyranoside and isopropyl-beta-D-thiogalactoside were the most potent inhibitors. The two hemagglutinins were bound tightly by p-aminophenyl-beta-D-thiogalactopyranoside coupled to CH-Sepharose 4B. The ligands to which these hemagglutinins bind were determined as the sugars which inhibited the hemagglutinating activity.


Antimicrobial resistance and resistance plasmids in Salmonella from Ontario, Canada. Collections of 589 human and 204 animal strains of Salmonella isolated in Ontario during the summer of1974 were examined for susceptibility to 12 antimicrobial agents. Many isolates were found to be resistant to both chloramphenicol (12.4% of the human and 38.2% of the animal sample) and ampicillin. The chloramphenicol resistance almost always occurred in strains which were also resistant to ampicillin and was usually due to a self-transmissible plasmid with a resistance pattern of CmKmSmTc (chloramphenicol, kanamycin, streptomycin, and tetracycline) or CmTc. Ampicillin resistance in these strains was mediated by a variety of plasmids with patterns ApSu (ampicillin and sulfa drugs) and ApSmSu, many of which were nonself-transmissible. Ampicillin resistance in chloramphenicol-sensitive strains was transferable from 21% of the strains, and it was associated with resistance patterns which were different from the self-transferable ampicillin  patterns from the chloramphenicol-resistance strains.


Autopsy of an Egyptian mummy (Nakht--ROM I). Autopsy of a 3200-year-old Egyptian mummy by an international multidisciplinary team yielded much information about diseases of the ancient past. Major contributions were made by the disciplines of anatomy, dentistry, genetics, hematology, histology, microbiology, nuclear medicine, occupational medicine, orthopedic surgery, otolaryngology, pathology, pediatrics, plastic surgery, radiology and virology. Scientists from Toronto, Detroit, Philadelphia and Cardiff participated in the investigation. The following were the main findings of medical interest: skeleton, infection or malnutrition as suggested by Harris's lines in distal femoral metaphyses; muscle (intercostal), cyst of Trichinella spiralis; lungs, deposits of anthracotic pigment and granite particles; spleen, enlargement with evidence of possible rupture; liver, early cirrhosis and calcified ova of Schistosoma sp.; kidney, calcified ova of Schistosoma sp.; and large and small intestines, calcified ova of Schistosoma and Taenia spp. This autopsy demonstrated the value of well coordinated efforts by specialists in various medical disciplines. Such efforts are essential when such a rare scientific endeavour is to yield a maximum of useful and reliable information.


Type A and type B botulism in the North: first reported cases due to toxin other than type E in Alaskan Inuit. Botulism outbreaks shown to be due to type A and type B toxin occurred in Alaska, a region previously known for only type E botulism. The outbreak due to type A toxin involved three people, two of whom died. The outbreak due to type B toxin involved nine people, none of whom died. Both outbreaks were in Inuit villages, and native foods were incriminated. The occurrence of these outbreaks strongly suggests that Clostridium botulinum, types A and B are indigenous to Alaska. The outbreaks underscore the need for initial treatment of patients with antitoxin that is trivalent (ABE), even in Arctic regions.


Common injuries of the athlete's hand.

Common injuries of the athlete's hand. Hand injuries are among the most frequent accidents seen in sports medicine. All too commonly they are considered trivial since the athlete may continue to participate actively and neglect his injury. The consequent delay in diagnosis and proper treatment may result in long-standing or even permanent disability. This paper describes the more commonly encountered hand injuries, their diagnosis and their optimal treatment. Included are soft-tissue injuries, ligamentous injuries, fractures and tendon avulsions. The basic principles applicable to skeletal and soft-tissue trauma of the hand, which physicians at all levels of sports medicine may encounter, are stressed.


Primary malignant lymphoma cutis.

Primary malignant lymphoma cutis. Between 1934 and 1975, 16 patients with primary malignant lymphoma cutis were seen at the Ottawa clinic of the Ontario Cancer Foundation. The lesions were purplish, firm, dermal or hypodermal (or both) nodules, tumours and plaques. In all 16 the histopathologic diagnosis was diffuse non-Hodgkin's lymphoma; 12 were considered to have prognostically bad lymphomas. However, the prognosis of primary malignant lymphoma cutis is significantly more favourable than is implied by the stage IV designation that such localized extranodal involvement would have required under the Rye clinical staging classification.


The value of maintenance therapy following treatment of central nervous system leukemia. The efficacy of intrathecal (IT) maintenance chemotherapy following central nervous system (CNS) leukemia was demonstrated in a retrospective study of 77 such episodes. The median durations of CNS and bone marrow (BM) remissions were significantly longer for the 41 maintained episodes (10+ and 9.5 months, respectively) compared with the 36 unmaintained episodes (4 and 2 months, respectively). Patients were comparable in each of these two groups. For those patients receiving maintenance therapy, there appeared to be an advantage in using four or more doses of IT medications for treatment of CNS leukemia, regardless of the number of doses necessary to clear the cerebrospinal fluid (CSF).


Results with methyl-CCNU and DTIC in metastatic melanoma. This report is the result of an Eastern Cooperative Oncology Group (ECOG) study. Four hundred and 15 patients with inoperable metastatic malignant melanoma, excluding those with cutaneous metastases only, were randomized to one of three drug treatments: DTIC alone, methyl-CCNU alone, or the combination DTIC plus methyl-CCNU. Responses were seen in 14% of DTIC patients (19/127), 15% of methyl-CCNU patients (18/119) and 14% of DTIC plus methyl-CCNU patients (18/122). Duration of response was the same (14 weeks) for all three treatment groups. There was no difference among the treatments in achieving complete responses. Survival was improved significantly for responders (50 weeks) compared with nonresponders (15 weeks) regardless of treatment regimen. Toxicities were generally tolerable. DTIC caused significantly more gastrointestinal toxicity than methyl-CCNU. Methyl-CCNU caused significantly more bone marrow toxicity than DTIC. There were three drug-related deaths. All occurred in patients on combination DTIC plus methyl-CCNU. Important pretreatment characteristics that favor response are ambulatory status, female, less than 50 years old, no prior chemotherapy and no liver or brain metastases. Patients with favorable characteristics combinations had a 30% response rate, while those with unfavorable characteristic combinations had only a 9% response rate.


Tibial adamantinoma: its histogenesis from ultrastructural studies. Only three previous reports on the ultrastructural appearance of tibial adamantinoma have been found among some 120 cases of this tumor reported in the literature. The tumor in our case is less differentiated than the cases previously reported. We believe it is of epithelial character and the possibilities of its histogenesis have been narrowed down to either mesothelial, synovial or squamous origins among the many theories proposed. Ameloblastic origin, however, cannot be ruled out.