New antiarrhythmic agents: amiodarone, aprindine, disopyramide, ethmozin, mexiletine, tocainide, verapamil. The present status, clinical experience, side effects, clinical pharmacology and electrophysiologic actions of seven new antiarrhythmic agents are reviewed. The drugs selected for comment are amiodarone, aprindine, disopyramide, ethmozin, mexiletine, tocainide and verapamil. Each drug has been shown to have clinical efficacy in suppressing cardiac arrhythmias.


Electrical management of arrhythmias with emphasis on the tachycardias. Information from stimulation studies in human beings with tachycardia has resulted in the application of cardiac pacing in the treatment of such patients. Short-term pacing is especially useful in patients with atrial flutter. Long-term pacing with use of chronically implanted units can be applied to patients with different types of supraventricular and ventricular tachycardia. In these patients careful electrophysiologic studies are required before the pacing device is implanted. New developments enabling automatic and more individually designed modes of pacing are urgently needed.


Surgical treatment of arrhythmias: current status and future directions. A variety of surgical interventions have evolved for the treatment of intractable or life-threatening arrhythmias unresponsive to conventional pharmacologic or pacemaker therapy. Supraventricular arrhythmias associated with rapid ventricular responses can be indirectly treated with ablation of the atrioventricular conduction system and insertion of a pacemaker. Ventricular tachyarrhythmias have previously been treated with sympathectomy, resection of tissue or revascularization. More recent approaches include the simple ventriculotomy, encircling endocardial ventriculotomy, cryosurgical ablation and insertion of the automatic implantable defibrillator. Refinement of methods to localize more precisely the origin of ventricular arrhythmias may allow design of more direct surgical procedures. The surgical treatment of arrhythmias related to the preexcitation syndromes remains the model of electrophysiologic surgery. It is now feasible to divide accessory pathways with a high degree of success and at low risk in selected patients.


Pharmacokinetics of antiarrhythmic drugs. A knowledge of the determinants of the plasma concentrations of antiarrhythmic drugs is important because variation in plasma levels is often greater than the desired therapeutic range. The basic principles of pharmacokinetics are outlined and their application to the design of dosage regimens described. These principles are illustrated in a review of the pharmacokinetics of lidocaine and its congeners, procainamide and its active metabolite (N-acetylprocainamide), quindine, disopyramide, phenytoin and propranolol, with particular emphasis of the factors that contribute to altered disposition.


The psychophysics of taste.

The psychophysics of taste. Modern psychophysical studies of sensory systems have produced new insight into sensory function and new techniques that have application to the clinical evaluation of taste. Most previous taste evaluation has been done with threshold measures that are subject to a variety of problems and that also fail to provide an accurate picture of suprathreshold sensitivity. The scaling of suprathreshold intensity reflects a patient's taste world more accurately than thresholds.


Salt taste and disease.

Salt taste and disease. Sodium appetite reflects the importance of sodium homeostasis and the relative scarcity of sodium for many terrestrial animals. Man, for various reasons, also seems to have a specific preference for salt which he consumes in excess of need, and this has been characterized as an important contributor to hypertension. Gustatory sensibility is necessary for the development of sodium appetite. Thus, research on the possible role salt taste sensitivity plays in controlling NaCl consumption in the sodium deficient rat was reviewed as a potential model for the study of salt taste and hypertension in man. Taste acuity experiments began first by examining salt taste thresholds. These studies found that thresholds were not altered by sodium deficiency in rat and the results in hypertensive humans were inconclusive. Threshold determinations may not reveal true sensitivity differences because they varied significantly across experiments and because they are restricted to a small portion of the intensity domain. When research was directed to suprathreshold stimuli, concentrations a rat or man might normally experience, the evidence suggested that hypertensive humans, like sodium-deficient rats, were less sensitive to the taste of salt. This reduced sensitivity may account, in part, for the fact that these two groups consume more salt.


Lipids of human milk and infant formulas: a review. The amount of human milk ingested by the nursing infant is about 600 ml per day. The average lipid content of the mature ranges from 3.2 to 3.5% and the amount does not appear to be influenced by diet. About 98% of the lipid is triacylglycerol in which most of the secondary ester is palmitic acid, a unique structure possibly responsible for the relatively high absorbability of the fat. Small quantities of other lipids are present. Amounts of cholesterol reported, range from 200 to 564 mg per 100 g of lipid. While 167 fatty acids have been positively and tentatively identified as being present in human milk lipids, the major fatty acids are palmitic, stearic, oleic, and linoleic. The composition can be changed by diet, which linoleic acid contents of from 1.0 to 45.0% having been found. The "average" linoleic acid is about 10% and this amount is apparently adequate for the essential fatty acid requirements of the infant. The quantity of vitamin E also appears to be satisfactory. The hypothesis that a cholesterol challenge to the breast fed infant would enable the adult to more efficiently metabolize the sterol does not seem to be supported by available evidence, primarily, because the cholesterol content of human milks varies so markedly; 26 to 52 mg per 8 ounces. The compositions of most infant formulas currently in use in the United States are presented for comparison and convenience and a few possible problems associated with their consumption are discussed. We have suggested several areas where, in our opinion, additional research would provide useful information.


Detection of intracellular immunoglobulin in nodular lymphomas. In lymph node tissue sections, six of 11 human cases of nodular lymphoma showed immunoglobulin within malignant nodules, and seven of nine cases of benign follicular hyperplasia showed immunoglobulin within follicles. In addition, distributions of lymphocyte cell membrane markers for T cells and B cells were determined in ten of 11 cases of nodular lymphoma. Lymphocyte suspensions in five cases contained monoclonal immunoglobulins and in three cases neoplastic cells showed a lack of surface membrane immunoglobulins. In two cases, the distribution of lymphocyte surface markers could not be distinguished from cells of benign lymph nodes. Combined data from intracytoplasmic immunoglobulin studies and lymphocyte surface marker assays indicated that eight of ten cases are of B cell lineage. Thus, the detection of intracellular immunoglobulin is not helpful in differentiating benign follicular hyperplasia from nodular lymphoma, but is complementary to lymphocyte surface marker assays in the determination of the origin of neoplastic cells in lymphoreticular malignancies.


Depressed delayed cutaneous hypersensitivity in alcoholic hepatitis. Delayed cutaneous hypersensitivity was studied in 10 patients with severe alcoholic hepatitis, 9 patients with either inactive alcoholic cirrhosis or alcoholic fatty liver, and 10 agematched controls. The mean response of the alcoholic hepatitis group was significantly less compared to controls for SK-SD (P less than 0.001), mumps (P less than 0.001), trichophyton (P less than 0.025), and Candida albicans (P less than 0.025). Upon clinical recovery, the response of the 6 surviving patients with alcoholic hepatitis was similar to controls for 4 of the 5 antigens tested, and the improvements in response to SK-SD and Candida albicans were significant (P less than 0.02 and P less than 0.05). The mean percentage and absolute numbers of thymus-derived lymphocytes were significantly less in the alcoholic hepatitis group compared with controls. Both the alcoholic hepatitis patients and patients with less advanced alcoholic liver disease had a diminished response to concanavalin A and phytohemagglutinin. This study demonstrates a reversible depression of delayed cutaneous hypersensitivity in alcoholic hepatitis. Several mechanisms may help account for this finding. We recommend that skin tests in patients with alcoholic hepatitis be interpreted with this phenomenon in mind.


Gallstone dissolution by chenodeoxycholic acid and phenobarbital. Gallstone dissolution and biliary lipids were determined and compared in patients receiving either chenodeoxycholic acid (CDC), or CDC and phenobarbital (PB) for 11/2 to 2 years. Among patients with radiolucent gallstones, dissolution occurred in 53% of those receiving CDC alone and in only 25% of those receiving both CDC and PB. No dissolution occurred in 13 other patients with calcified gallstones. Patients with dissolution had a significantly greater molar percentage of CDC and a significantly lower saturation index in bile than those without dissolution. Diarrhea and transiently abnormal liver function tests were the most frequently observed side-effects but only diarrhea necessitated a reduction of the CDC dose. Gallstones recurred following dissolution in one of six patients followed for six months after discontinuation of CDC. In conclusion, PB did not enhance CDC-induced desaturation of bile or gallstone dissolution.


Treatment of gastric ulcer. The randomized clinical trials from 1964 to 1974 and their impact. Twenty-nine randomized clinical trials (RCTs) from the decade 1964-74 evaluating treatments of gastric ulcer have been analyzed. None of them ful-filled all criteria for an ideal RCT. The most frequent shortcomings were: short treatment or follow-up periods, incomplete description of the patients included, small patient samples, suboptimal experimental design, lack of double-blind testing, high number of drop-outs, less precise or less relevant types of evaluation of the treatment effect, uncontrolled ancillary treatment, or lack of statistical evaluation of the results. The most frequently tested drug was carbenoxolone, which has been shown to be clearly effective. Judged by the effect on the recommendations in standard medical textbooks the impact of the best RCTs have been small. This situation emphasizes the need for more well-planned and performed RCTs on treatments of gastric ulcer.


Guillain-Barré syndrome: epidemiology of an outbreak. In early January, 1976, an outbreak of gastroenteritis caused by contamination of the water supply system occurred in Salt, Jordan. This outbreak was followed by the appearance of peripheral neuropathy in 19 cases diagnosed as Guillain-Barré Syndrome. Clinically, gastroenteritis was suggestive of Shigellosis and one of nine patients with Guillain-Barré Syndrome, grew Shigella boydii. Epidemiology of the 19 cases with peripheral neuropathy is detailed. Seventeen patients had definite gastroenteritis symptoms prior to their neuropathy. The median incubation period was seven days.


A comparison of a WI-38 vaccine and duck embryo vaccine for preexposure rabies prophylaxis. Two types of rabies vaccine, WI-38 vaccine (WRV) and Duck Embryo Vaccine (DEV) were compared in rabies preexposure prophylaxis. Once group of veterinary students received four doses of DEV, a second group received four doses of WRV, and a third group received two doses of WRV. Adverse reactions were found to be similar for all three gorups. The antibody responses, however, differed markedly: the mean neutralizing titer after four doses of DEV was 1:75, after four doses of WRV was 1:1517, but was only 1:164 after two doses of WRV. All students who received three or four doses of WRV developed high titers of rabies antibody, making this vaccine very desirable for preexposure prophylaxis.


Tuberculosis: review of treatment failure, relapse and drug resistance. Factors affecting the success and failure of tuberculosis (TB) treatment programs are reviewed. Topics covered include incidences of primary and secondary resistance; methods and probability of bacteriologic transfer of resistance; factors affecting delivery of successful treatment of TB; and retreatment concepts, history and regimens for TB relapse and treatment failures. Isoniazid, rifampin and ethambutol hydrochloride produce a high percentage of cure in initial and retreatment TB therapy. Attention to patient compliance should be emphasized to assure effective treatment.


The syndromology of anorectal malformation (atresia, stenosis, ectopia). The syndromes, associations, and developmental field defects that include anorectal dysgenesis (atresia, stenosis, ectopia) as a principal or facultative sign are discussed. Most of these disorders are identifiable by their genetic or teratogenic etiology, their distinctive phenotype, or both. Their precise diagnosis is crucial for estimation of recurrence risk and other aspects of reproductive counseling, and it is essential for classificatory progress. The "VACTERL association" should not be used to label a patient with anorectal malformation and other anomalies except by exclusion; this rule is particularly relevant when the patient lacks tracheoesophageal malformation. The degree (or variety) of anorectal malformation that occurs in a given pattern of multiple congenital anomalies may be inconstant. Furthermore, anorectal malformation may be a solitary expression of a familial syndrome.


Cytologic detection and clinical significance of Actinomyces israelii in women using intrauterine contraceptive devices. Pancervicovaginal (Papanicolaou) smears exhibiting pseudomycilial-like clumps of organisms obtained from 35 women employing IUD's were studied by direct immunofluorescent technique for identification of A. israelii and A. naeslundi. In every case the specific fluorescence was achieved with species-specific antiserum against A. israelii. The clinical profile of these 35 women was retrospectively analyzed.


Injection of corticosteroids into mother to prevent neonatal respiratory distress syndrome. In this study, 500 mg. of hydrocortisone were injected intravenously into 126 women every 12 hours for four doses in a double-blind, randomized fashion. These 126 subjects were at risk for delivery of a premature infant because of premature labor of fetomaternal disease necessitating intervention. There were 67 patients in the treatment group and 59 in the placebo group. All patients had immature lecithin/sphingomyelin ratios and/or were at less than 34 weeks' gestation. From these data, it appeared that there was a significant decrease in respiratory distress syndrome when the treatment group was compared to the placebo group. The neonatal survival rates also were improved significantly by steroid treatment. There was no demonstrable adverse steroid effect in mothers of fetuses in the long-term or short-term follow-up period, although a significant number of patients were lost to follow-up and the methodology of infant evaluation was imprecise. It would appear from these data that the injection of steroids is beneficial in mothers at risk of being delivered of premature infants. However, many questions remain to be answered before this method can be relied upon as therapy for women with premature labor.


Cervical bacterial flora in patients with gynecologic malignancies. Radiation and gynecologic oncologists agree that pelvic irradiation in the presence of pelvic inflammatory disease, parametritis, or pyometra can be catastrophic. A temperature elevation in a patient having intrauterine radiation is very perplexing. This study was designed to investigate one of the three reported etiologies for this condition. Some investigators have suggested an exacerbation of a quiescent infection as a possible etiology because of the necrotic condition of many cancerous cervices. Aerobic, anaerobic, and fungus cultures were performed on 32 patients prior to intrauterine administration of cesium. The organisms cultured were similar to those identified as the normal cervical flora. The frequency of the organisms seemed independent of the amount of irradiation. The number of organisms cultured did not vary with the use or nonuse of cleansing vaginal suppositories. This study indicated no increase in bacterial growth in these cancerous necrotic cervices; also it did not indicate the growth of any unusual pathologic bacteria.


Enhanced fluid transport across gallbladder mucosa in experimental cholelithiasis. Fluid transport of the gallbladder has been studied in two models of experimental cholelithiasis: dihydrocholesterol-induced gallstones in the rabbit and lincomycin-induced gallstones in the guinea pig. Using the noneverted explained gallbladder of the rabbit and the guinea pig, the transport of luminal to serosal fluid has been quantitated before, during, and after stone formation. The everted gallbladder preparation of the rabbit has also been used to measure fluid transport before and during gallstone formation. In both models, an increased fluid transport was observed in the phase of gallstone induction and a return to normal after stones were formed. This abnormality preceded the appearance of conventional histological features of cholecystitis. There was also a coincidental increase in glycoprotein production from and cell proliferation of the gallbladder epithelium. This enhancement of fluid transfer may play a contributing role in the genesis of gallstones.


Imipramine response in deluded depressive patients. The authors examined how delusions and other psychotic features influenced treatment outcome with imipramine in patients with primary depression. Global improvement scores indicated that delusions or other evidence of psychosis do not contraindicate imipramine treatment. This finding does not support a recent report suggesting that deluded depressive patients should not be treated with imipramine. Possible explanations of the discrepancy between these two studies are discussed.


Reflections on military psychiatry.

Reflections on military psychiatry. The need for psychiatrists in the military was recognized for the first time during World War I, which involved millions of men in unusually protracted warfare. The policy of treating psychiatric casualties close to the from and returning soldiers to their military units as quickly as possible proved of great significance in the U.S. war effort. During World War II, the Korean conflict, and the war in Viet Nam, military psychiatry made great contributions and learned many lessions, both at home and abroad. The lessions learned by military psychiatry have important applications for the rest of medicine, especially in the fields of stress, crisis therapy, and community psychiatry.


History and the psychiatrist.

History and the psychiatrist. Historical consciousness is a valuable tool in psychiatry. History can be useful to psychiatrists by expanding their awareness and revealing general errors in the content of psychiatric knowledge, detecting drastic distortions that appear in the ways knowledge is applied to patients, helping to avoid mistakes in public policies that involve psychiatry and result from erroneous impressions of social history, and alerting us to possible future trends. Although history does not give answers--rather , a complex context within which to seek them--it still has value for the psychiatrist.


Drug therapy and psychobiological research advances in the psychoses in the past decade. There have been major advances in the treatment of psychoses in the past decade, particularly in the area of maintenance therapy with lithium, tricyclics, and neuroleptics. Such efforts have been enhanced by methods of relating plasma drug levels to clinical efficacy. Research in genetic factors, the mode of action of pharmacological agents, and hormonal influences on psychopathology has added to our theoretical understanding of the psychoses, and we can hope for further advances from sophisticated new methodological tools. Promising areas of investigation include the search for genetic markers, studies of postsynaptic neuronal receptors, and examination of the effects of polypeptides, including endogenous opioid compounds.


Tuberculous joint disease in transplant patients. Three patients with tuberculosis, all manifesting monarticular joint involvement, among 845 renal allograft recipients at the University of Minnesota are reported on. Clinical symptoms, methods of diagnosis, and optimal antibiotic regimes are discussed. The physician must suspect tuberculous joint disease when confronted with monarticular swelling and pain in the transplant recipient.


The other Pasteur. Changing views on the postoperative chest. The life and works of William Pasteur (1855-1943) are described and his thesis that pulmonary collapse is the harbinger of the development of postoperative lung pathology is discussed.


Epidemiological studies of the occupational hazards of anaesthesia--a review. The epidemiological literature on the ocupational hazards of anaesthesia which includes some sort of control data has been studied. It provides reasonably convincing evidence of a moderate increase in the risk of spontaneous abortion among exposed females, although it is possible that even this result is attributable to reporting bias. There is no convincing evidence of any other hazard. It has been pointed out by many authors that, even if spontaneous abortion is commoner among those working in anaesthesia, there is no particular reason to believe that this has anything to do with exposure to trace quantities of anaesthetic gases. The special emotional and physical rigours of the task, for example, might easily be responsible.


Etomidate and methohexitone. A comparative clinical study in out-patient anaesthesia. Etomidate compares favourably with methohexitone as an intravenous induction agent in out-patient anaesthesia excluding the incidence of involuntary muscle movement. The use of propylene glycol as a solvent for etomidate does not alter the previously claimed advantageous features of this agent.


Metoclopramide and the gastro-oesophageal sphincter. A study in pregnant women with heartburn. In a double-blind study the gastro-oesophageal sphincter pressure profile was measured in a group of twenty women in the last trimester of pregnancy, all of whom suffered from heartburn. The mean gastric and the maximum sphincter pressures were calculated from the pressure profile, and the difference between these two was defined as the barrier pressure. After resting sphincter measurement ten of the women were given 10 mg metocolopramide intravenously, and the other ten had a placebo intravenous injection; 15 min later the sphincter pressures were measured again. Metoclopramide significantly increased the mean maximum sphincter and barrier pressures compared to the baseline pressure, and there was no significant difference between the pre- and post-injection pressures in the placebo group. However, the raised mean maximum sphincter and barrier pressures following metoclopramide were made up of four patients having very high pressures and six patients on whom metoclopramine appeared to have little effect. The clinical usefulness of metoclopramide in women in labour is discussed.


Continuous positive pressure ventilation in children with bronchopneumonia. The application of a small end-expiratory pressure of 5 cmH2O to the assisted ventilation of nineteen children (mean age 19 months) with bronchopneumonia was compared with intermittent positive pressure ventilation. Within 1 h of introducing continuous positive pressure ventilation the alveolar-to-arterial oxygen gradient was reduced in most patients, with an increase in functional residual capacity and a decrease in total pulmonary blood shunt. Physiological dead space was also reduced, a feature not observed in other studies, and the significance of this finding is discussed. The use of continuous positive pressure ventilation in broncho-pulmonary infection was shown to be effective even at small pressures, and can be recommended especially for patients requiring long-term ventilation.


The safe use of sodium nitroprusside.

The safe use of sodium nitroprusside. The factors necessary for the safe clinical use of sodium nitroprusside are considered in the light of the author's clinical experience. The reasons for abnormal responses to the exhibition of this hypotensive agent are considered and the precautions necessary and the need to avoid overdosage are emphasised.


[Clinical trial of bupivacaine-CO2 (author's transl)]. One hundred and forty-one patients for general and urological surgery were anaesthetized by epidural anesthesia (PDA) using bupivacaine-CO2 0.5% solutions. A frequency peak for the initial dose between 21-23 ml was noted. The response time and latency period were found to be 2.99 +/- 1.40 min and 11.02 +/- 3.66 min (smallest time unit 0.5 min). The effective duration was 5.02 +/- 0.93 h. The sensory spread reached on average to T 6.06 +/- 1.41 segments for the patients with typical injection locations at L2/3-L4/5. A mean dose of 6.25 +/- 0.18 mg per spinal segment was used. Side effects were not seen apart from occasional hypotension. The failures were not related to the anesthetic drug. The degree of muscle relaxation was for the majority of cases evaluated at 2 +, which was sufficient for the abdominal operations. The results are compared with the data obtained using bupivacaine-HC1; the advantages of bupivacaine-CO2 are described.


[Ketamine--a suitable agent for emergency situations (author's transl)]. Various surgical procedures have been performed using ketamine alone (Group I) or ketamine-relaxant-air anaesthesia (Group II). In all patients we observed a significant rise in systolic and diastolic blood pressure and pulse rate. The intraoperative values showed a tendency to return to normal. Ten minutes after injection 2 mg/kg body-weight i.v., ketamine caused a significant reduction in arterial PO2 and oxygen saturation as well as a significant rise in arterial PCO2, though these changes were of no clinical importance. In both groups the intraoperative values were normal as compared to the preoperative level. In all cases base excess reflecting the metabolic side of blood gas analysis was within normal range. Based on our findings we recommend the use of ketamine as a sole anesthetic agent for IPPB ventilated as well as spontaneously breathing patients in disaster situations.


The effect of positive end expiratory pressure on rebreathing and gas dilution in the Ayre's T-piece system--a laboratory study. The effect of positive end expiratory pressure on the function of the Ayre's T-Piece System was studied using a simple lung model. Positive end expiratory pressure did not effect end tial CO2 during "controlled breathing" but caused an increase during "spontaneous breathing" when fresh gas flow was less than 3 times the minute volume. Gas dilution did not occur under any of the test conditions.


The effect of speed of injection on the potency of anaesthetic induction agents. The effect of speed of injection on the hypnotic actions of thiopentone, methohexitone, propanidid and Alfathesin was studied in elective surgical patients. The sequential up-and-down technique was used to determine ED50 values. A significant reduction in ED50 was observed for doses injected over five seconds when compared with doses injected over fifteen seconds for thiopentone (64%, P=.001) and methohexitone (83%, P=.05). In the case of Alfathesin, relatively wide confidence limits were observed at all injection speeds and reduction in ED50 at fifteen seconds (63%, P=.001) was noted when compared with the ED50 at five seconds. No significant differences were noted with any of the drugs studied, for variations in infusion time between fifteen, thirty and sixty seconds. It was concluded that only at very rapid infusion rates does the speed of injection influence the potency of the commonly used induction agents.


The bird respirator modified for PEEP, CPAP and IMV. A Bird Mk. 8 respirator has been modified to permit the use of PEEP, CPAP and IMV. Gas supply is from an oxygen blender to allow easy adjustment of the inhaled oxygen concentration. A special fitting was made to mount a flow meter which supplies the IMV reservoir. PEEP is generated by the Mk. 8 negative pressure generator mounted in opposition to exhalation and its magnitude can be adjusted by the negative pressure control of the respirator. This modified machine is simple, reliable and relatively inexpensive.


The elimination of pollution by a non inhalational technique. A method is described whereby major surgery can be accomplished without inhalational anaesthtic agents, thus completely eliminating operating room pollution. The method is based on the balanced use of three intravenous agents--morphine, alcuronium and gamma-hydroxybutyrate (GHB). In the dose chosen for GHB, reliable unconsciousness can be produced for surgery of any length, and using physostigmine as an antidote, patients can be wakened within ten minutes. The advantages are convenience, simplicity of equipment, low cost, absence of pollution and good patient acceptance. The disadvantages are a certain incidence of hypertension and in this series, a small failure rate with the antidote.


Comparative study of cloprednol versus placebo in asthma. This double-blind parallel trial evaluated the efficacy of cloprednol, a new synthetic glucocorticoid, in 40 patients with asthma. Patients kept daily records of wheezing, chest tightness, shortness of breath and cough. Analysis of these records showed cloprednol to be statistically significantly better than placebo for the relief of these symptoms (p values ranged from less than 0.01 to less than 0.0001). Weekly physician evaluations of asthma severity, symptoms since last visit and number of asthma attacks also showed a significant drug effect in favor of cloprednol. These subjective findings were confirmed by objective pulmonary function tests (FEV1.0, FVC and PEFR). There was a statistically significant difference favoring cloprednol for all the pulmonary function measurements. Previous studies have suggested that at equipotent anti-inflammatory doses cloprednol is less suppressive of hypothalamic-pituitary-adrenal axis function. Although plasma cortisol levels were not measured in this trial, none of the patients manifested clinically important side effects which required termination of their participation in the study.


The management of urticaria.

The management of urticaria. Urticaria is not by any means the most serious clinical problem with which the physician must deal but it is certainly the most tedious and capricious. Its management therefore calls for patience on the part of both the patient and the physician and for a plan of management that is thorough and detailed. In this paper the authors present a plan which has proved capable of fulfilling these criteria.


Effects of racemic epinephrine (Micronefrine) administered by intermittent positive pressure ventilation (IPPV) in airway obstruction: a double-blind study. Racemic epinephrine in doses of 4.5 and 9 mg were administered by IPPV with a Bird Mark 8 in a double-blind, crossover study on consecutive days to 12 normal subjects and to 12 patients with airways obstruction. Normal subjects did not react with any clinically significant change in pulse rate or blood pressure. PEFR in the patients increased by an average of 35% from 5 to 60 minutes after 4.5 mg and by 44-42% after 9 mg. The increase after the larger dose was significantly larger five minutes after inhalation. There was no clinically significant change in pulse rate or blood pressure but a slightly greater frequency of mild side effects among the normal subjects and after the larger dose.


Clinical use of non-invasive method for determining oxygen saturation: ear oximetry. Oxygen saturation can be estimated by measuring the absorption properties of the arterialized blood perfusing the ear. Simultaneous determination of oxygen saturation by blood gas and ear oximetry showed no statistical difference. This non-invasive method allows rapid and accurate monitoring of the oxygenation status of patients with respiratory insufficiency.


[Stewart-Treves syndrome. Apropos of a case with ultrastructural study]. An optical and ultrastructural study was performed on biopsy and autopsy specimens of Stewart Treves syndrome cutaneous tumours and their metatases. Various histological aspects are described: territories presenting typical vascular differentiation, spindle cell "Kaposi type" territories and undifferentiated territories. The ultrastructural study confirmed the angiomatous differentiation of these tumors and revealed a certain number of arguments in favor of blood rather than lymphatic capillary differentiation of the newly formed vessels. Upon completion of this study, it appeared possible to confirm that the Stewart Treves syndrome corresponds to an anatomo-clinical entity whose histological features are very close to those of primitive cutaneous angiosarcomas.


Immunofluorescence studies of canine distemper encephalitis on paraffin-embedded tissue. A paraffin-embedding technique for fluorescent antibody studies of canine distemper encephalitis was developed. Specific fluorescence was demonstrated in all brain tissue from dogs with canine distemper, and when compared with tissue on cryostat sections, the paraffin-embedded tissue showed superior preservation of tissue architecture. The preservation of viral antigen was good, and the appearance of fluorescence in gray- and white-matter lesions was described. In gray matter, extensive fluorescence was found mainly in neurons; fluorescence in white matter was less extensive and was mainly associated with astrocytes.


Detection of Moraxella bovis antibodies in the SIgA, IgG, and IgM classes of immunoglobulin in bovine lacrimal secretions by an indirect fluorescent antibody test. The relationship between clinical infectious bovine keratoconjunctivitis (IBK) and Moraxella bovis antibodies was evaluated in a herd of calves during one summer. The detection and the distribution of antibody response in lacrimal secretions of beef calves to natural exposure of M bovis were determined by an indirect fluorescent antibody test. Three classes of immunoglobulins--secretory IgA, IgM, and IgG--were monitored in lacrimal secretions over a 5-month period when IBK was enzootic in the herd. The 3 classes of antibody to M bovis were detected in all but 2 calves at the start of the monitoring, and the highest and most persistent M bovis antibody titers were in the IgG immunoglobulin class, and less so in IgM and secretory IgA classes. The specific antibodies present in the lacrimal secretions did not prevent the development of clinical IBK in the calves.


Bacteriology of expectorated sputum with quantitative culture and wash technique compared to transtracheal aspirates. Techniques to improve the reliability of expectorated sputum culture were evaluated in 46 patients using a wash technique, quantitative culture, and a combination of washing and quantification. The wash procedure consisted of a jet of tap water over the specimen contained in a tea strainer. The true lower respiratory tract flora was determined by percutaneous transtracheal aspirates, which served as the basis for evaluating the methods of processing expectorated specimens. Either washing alone or quantification alone decreased the number of specimens with organisms that were not present in companion transtracheal aspirates; however, results that were sufficiently improved to be clearly advantageous for clinical interpretation were achieved only when washing and quantification were combined. Washed sputum specimens yielded oropharyngeal "contaminants" in concentrations exceeding 10(6) bacteria per ml in 12 of 46 specimens (26 per cent). Using this technique, only one specimen contained a misleading potential pathogen, and only one specimen failed to yield a potential pathogen that was recovered with the transtracheal aspirate. The wash procedure decreased the mean concentrations of contaminants approximately 100-fold for all specimens and 1,000-fold for purulent specimens.


Comparison of homogeneous enzyme immunoassay and high-pressure liquid chromatography for the determination of theophylline concentration in serum. A comparison of the new homogeneous enzyme-multiplied immunoassay technique (EMIT, Syva) with a high-pressure liquid chromatographic technique for the determination of theophylline concentration is presented. The accuracy, precision, and specificity of the methods were compared. In addition, 100 samples from 61 pediatric patients receiving theophylline were assayed by both methods. The accuracy, precision, and specificity of the enzyme immunoassay support the use of this method for the quantification of theophylline concentration in clinical specimens. A significant correlation (R = 0.981, P less than 0.001) was found between results generated by enzyme immunoassay and high-pressure liquid chromatography for patient samples. The regression line relating these results had an intercept of 0.22 microgram per ml, a slope of 1.05, and a standard error of the estimate of 1.36 microgram per ml.


Influenza immunization in systemic lupus eruthematosus. A double-blind trial. Forty patients with systemic lupus erythematosus randomly received inactivated bivalent (A/NJ and A/Victoria) influenza vaccine or saline in a double-blind study. During 20 weeks of follow-up, no deterioration in major organ function or increase in disease flares was observed in the immunized group as compared with the group that received saline. Preimmunization antibody titers to A/Victoria were lower in the 40 patients with lupus erythematosus than in age-matched control subjects. Response to immunization, as measured by serum antibody titers, was also lower in the patients with lupus erythematosus, indicating that immune responses must be evaluated on an individual patient basis. Nevertheless, influenza vaccination can be safely carried out in patients with systemic lupus erythematosus.


Prehospital brady-asystolic cardiac arrest. Of 133 persons with spontaneous cardiac arrest attended by paramedics within 10 minutes, 100 (75%) had ventricular fibrillation as the initial rhythm and 33 (25%) had extreme bradycardia or asystole. The latter group of arrhythmias was characterized by sinus arrest or severe sinus bradycardia (90%) and complete A-V block (10%). Junctional escape rhythm was also absent or markedly retarded. Despite cardiopulmonary resuscitation and the administration of epinephrine, atropine, isoproterenol, and sodium bicarbonate, recovery of the sinus and junctional tissues was infrequent. Ventricular fibrillation developed in 11 cases (33%). One patient lived 12 days, but all others were dead on arrival or died in the emergency room. Among the 13 coronary causes of death proved at autopsy, 10 (77%) were due to a fresh thrombus and seven (54%) to an occluded proximal right coronary artery, suggesting a causal relation to this type of arrest.


Vancomycin revisited.

Vancomycin revisited. Vancomycin, virtually discarded after development of antistaphylococcal penicillins, has recently been receiving renewed attention. There are several clinical situations in which it appears to offer advantages over other available antimicrobial agents: infections due to methicillin-resistant staphylococci; bacterial endocarditis in patients allergic to penicillin; staphylococcal enterocolitis; staphylococcal infection in patients undergoing hemodialysis; infections caused by penicillin-resistant diphtheroids; and prophylaxis of bacterial endocarditis in patients with prosthetic valves or penicillin allergy. Its penetration into the cerebrospinal fluid suggests that vancomycin may be useful in treating certain infections of the central nervous system. Although its ototoxic and nephrotoxic potential cannot be ignored, these problems can be minimized by keeping the serum concentration at the proper level.


Articular damage in arthritis and its control. Erosion of joint surfaces in arthritic conditions is always associated with the degradation of the two principal matrix macromolecules of cartilage, proteoglycan and collagen. The major enzymes thought to be involved in articular catabolism have not been isolated, purified, and their properties studied, but precise spatial and temporal activities are still imperfectly understood. We are beginning to understand some aspects of cellular function in the control of catabolic enzyme function. Recent studies on molecular, cellular, and tissue mechanisms in this process are discussed here. Of particular interest is a possible natural control mechanism involving a recently discovered inhibitor of collagenase. A newly developed pharmacologic method of inflammation control utilizes the properties of liposomes in the closed environment of the joint cavity. Very low doses of modified steroids encapsulated within liposomes are capable of substantially reducing inflammation in experimentally arthritic animals and may be applicable to man.


Urticaria associated with acute viral hepatitis type B: studies of pathogenesis. To determine whether skin deposition of circulating immune complexes contributes to prodromal urticaria of acute hepatitis B, we studied two patients with hepatitis B who presented with urticaria and fever. During the urticarial prodrome but not thereafter, we found activation of both classic and alternative complement pathways. Hepatitis B surface antigen (HBsAg)-antibody complexes were identified (by electron microscopy) in cryoprecipitates from both patients and IgG (by immunodiffusion) in cryoprecipitates of one patient during urticaria. Light and electron microscopy of involved urticarial skin revealed necrotizing venulitis in both patients. Immunofluorescence microscopy showed fibrin within involved cutaneous vessel walls in one patient and C3, IgM, and HBsAg, which were not detected in simultaneously obtained uninvolved skin, in both patients. Our findings suggest that deposition of circulating immune complexes containing HBsAg is important in the pathogenesis of urticaria associated with acute hepatitis B virus infection.


Severe candidal infections: clinical perspective, immune defense mechanisms, and current concepts of therapy. Disseminated candidiasis has become an important infection, particularly in immunocompromised and postoperative patients. Although serologic tests may, in some settings, facilitate a premortem diagnosis, the disease is usually diagnosed by comprehensive clinical evaluation. Detection of the relatively newly recognized peripheral manifestations of candidemia may be vital to early diagnosis: endophthalmitis, osteomyelitis, arthritis, myocarditis, meningitis, and macronodular skin lesions. Studies in patients with chronic mucocutaneous candidiasis and in-vitro manipulations have begun to elucidate normal immune defense mechanisms against Candida, including serum factors, phagocytosis, intracellular killing mechanisms, and lymphocyte function (particularly T cell). The primary drugs for the treatment of disseminated candidiasis are still amphotericin B or amphotericin B plus 5-fluorocytosine; the mainstay of therapy for chronic mucocutaneous candidiasis is amphotericin B. Other antifungals and immune system-stimulating modalities (transfer factor, thymosin, thymus epithelial cell transplantation, and levamisol) may be useful for chronic mucocutaneous candidiasis in some settings and deserve further evaluation.


Morphological mutants of Escherichia coli: nature of the permeability barrier in mon and envC cells. Morphological mon mutants and a chain-forming envC mutant of Escherichia coli K12 are hypersensitive to detergents and to various other antibacterial agents. Electron microscopy shows that the cytoplasmic membrane of growing mon and envC cells is dissolved by detergents, and that the cytoplasm dissociates into two parts of unequal density. The mutant envC is sensitive to actinomycin D and to rifampicin, is lysed by lysozyme in the absence of EDTA, and releases alkaline phosphatase in the absence of osomotic shock, indicating a gross perturbation of its outer membrane.


[Deafness due to renal failure. Clinicopathological study (author's transl)]. In this series of 54 cases of chronic renal failure, the largest number of curves showed a curve of a presbyacousia type (3/4 of the total). This hypoacousia may be related to the length of time for which the renal pathology has existed and, parat from group 0 (patients treated without haemodialysis nor grafting), may be correlated with the curve of the speed of nervous conduction. This latter correlation is particularly close in patients with a strictly isolated renal disease. The aetiology of this deafness would appear to be related to the premature aging provoked by chronic renal failure. The method of surface preparation applied to 5 petrous temporal bones from 3 patients was felt to be of particular value in the study of this pathology. Whilst one case of unilateral sudden deafness of vascular aetiology is reported, no vascular changes were seen in the other petrous temporal bones. Case 7-11 was particularly demonstrative since bilateral deafness with a rapidly progressive descending occurred in the presence of changes in the pre-ganglionic cochlear fibres charaterised by demyelinisation. This was associated with a cell loss of approximately 25% in the spiral ganglion and less marked demyelinisation of the fibres of the vestibular nerve.


A double-blind comparison of levodopa, Madopa, and Sinemet in Parkinson disease. A sixteen-week study examined the effect of Madopa and Sinemet on patients with Parkinson disease disease suffering nausea or vomiting as side-effects of levodopa therapy and compared the efficacy of the three preparations in controlling the symptoms of Parkinson disease. Following a control period on levodopa, 20 patients underwent four consecutive four-week regimens as follows: (1) double-blind, in which a randomized half received levodopa and half received Madopa; (2) single-blind, in which all received Madopa; (3) double-blind, in which a re-randomized half received Madopa and half Sinemet; and (4) single-blind, in which all received Sinemet. Levodopa administration via Sinemet and Madopa was held to a fixed 20% of prior levodopa dosage. Almost all patients showed great reduction in nausea and vomiting with both Madopa and Sinemet. Seventy percent of the patients showed improvement in disability compared to their levodopa baseline levels. Group means showed no difference between the improvement seen on Madopa and that seen on Sinemet. However, examination of individual responses showed that the majority of patients fared distinctly better on either Sinemet or Madopa.


Virus envelopes and plasma membranes.

Virus envelopes and plasma membranes. In this review I have tried to describe the progress that has been made in studies of viral envelopes in the last few years. In every particular of structure, biogenesis, and assembly, increased knowledge has increased the apparent similarity between viral envelopes and plasma membranes. Thus, the viral envelopes provide unique experimental opportunities for investigating membranes. We can expect that progress in our understanding of membrane structure will continue through the study of viral envelopes over the next few years--most notably through study of the lateral organization of viral envelopes, and of the synthesis, processing, and mode of action of envelope proteins.


Neural circuits for generating rhythmic movements. Inasmuch as the identified neural circuits discussed in this review pertain only to the nervous systems of two invertebrate species, one may ask whether or not these findings are generally applicable to central nervous oscillators that generate rhythmic movements in animals of other species and phyla, particularly in the vertebrates. This question is not easy to answer at this time, because detailed cellular network analyses thus far have been possible only in a very few neurophysiologically favorable preparations, such as those presented by the cardiac and stomatogastric ganglia of the lobster and the segmental ganglion of the leech. Nevertheless it is significant that the mechanisms according to which these invertebrate circuits are now thought to generate their oscillations--endogenous rhythmic polarization, reciprocal inhibition, and recurrent cyclic inhibition--were all first proposed to account for generation of rhythmic movements in vertebrate animals (7-9, 51, 71, 79). Moreover, the pattern of motor neuron activity in rhythmic movements of vertebrates is not necessarily more complex than the corresponding pattern in analogous movements of invertebrates. Therefore, the very much greater number of neurons in the central nervous system of vertebrates does not necessarily imply a greater complexity of the central oscillators that generate their rhythmic movements; it may only place greater obstacles in the way of identifying the underlying neuronal circuitry. In any case, it is worthy of note that the current list of fundamentally different and theoretically plausible types of neuronal oscillators is not only quite short but also of long standing. Thus, on these grounds, it seems reasonable to expect that the identified circuits discussed here will prove to be of general applicability to the generation of rhythmic movements in the whole animal kingdom.


Interactions of liposomes with mammalian cells. In this review we have attempted to highlight each of the major areas of interest in liposome-cell interactions: the purely physical chemical, the cell biological, and the medical. Liposomes can be generated in a number of ways and are classified as small unilamellar, large unilamellar, and multilamellar vesicles. Although liposomes are easy to prepare, it is important to consider the effects of impurities, and also the possible changes in liposome properties with time (particularly at or below the phase transition temperature). Intelligent application of liposomes to cell biological and clinical problems requires an understanding of their mechanisms of interaction with cells. The mechanisms thus far delineated, largely by studies in vitro, are fusion, endocytosis, lipid transfer, and stable adsorption. In practice, demonstrating the occurrence of a given mechanism in an actual system is difficult because these are not mutually exclusive. Cell type, conditions of incubation, and liposome properties (charge, fluidity, size) are important in determining mechanism and appear to organize the literature effectively. However, this may be an oversimplification resulting from the sketchiness of current information. Liposomes have been used in cell biology to alter the phospholipid and cholesterol composition of cells, to bypass the membrane permeability barrier to normally impermeant solutes, and to promote cell-cell fusion. Perhaps the most fruitful of these applications has been the alteration of cholesterol, which can result in changes in cell permeability and morphology. On the other hand, delivery into cells of liposome-entrapped, water-soluble materials has not yet proved an effective tool in cell biology; delivery, and consequent physiological changes, have been demonstrated, but generally to answer questions about liposome-cell interactions, not to answer questions about the cells. Much of the current interest in liposomes derives from their potential applications in vivo. Liposomes are envisioned as pharmacological capsules for delivery of therapeutic agents in treatment of such conditions as diabetes, enzyme deficiencies, heavy metal poisoning, and neoplasms. Although much of the literature to date has been concerned with the end applications, it seems clear that a more systematic approach to the pharmacokinetics of liposomes will be necessary. In particular, such aspects as their leakage rates and their ability to cross cell and anatomical barriers require further study. Targeting of liposomes to particular cells or tissues will be essential for many applications. Finally, it must be remembered that all of these in vivo applications of liposomes are future tense; as with other technologies, passage from demonstration of the phenomenon to practical application is likely to be arduous.


Pharmacokinetics of aminoglycosides in subjects with normal and impaired renal function. Since aminoglycosides are antibiotics almost exclusively eliminated by the kidneys, their pharmacokinetic study in normal subjects and in uraemic patients is essential to establish dosage schedules adapted to various degrees of renal impairment. Many studies have been recently reported, particularly with regard to the newly developed desoxystreptamine aminoglycoside antibiotics. The present paper is a compilation of our own results and a review of the literature concerning Streptomycin, Kanamycin and its semi-synthetic derivation, Amikacin or BB-K8, Gentamicin, Tobramycin, Lividomycin, Sisomicin and its semi-synthetic derivation, Netilmicin.


The pharmacokinetics of nitrofurantoin and its related bioavailability. Nitrofurantoin is a urinary tract antibacterial agent whose clinical effectiveness depends on the high urinary drug levels encountered during therapeutic drug dosage. Under these conditions, only low blood drug concentrations are usually found. On the basis of urinary nitrofurantoin excretion determined after oral and intravenous drug administration, orally administered nitrofurantoin in a suitable dosage form is well absorbed. In vitro testing does not accurately reflect nitrofurantoin bioavailability, which is affected by formulation differences, drug particle size, and dosage form. Nitrofurantoin is readily absorbed and quickly distributed into most body fluids. It is rapidly excreted in large amounts in bile and urine. With the exception of the active drug secretion in the kidney tubule and biliary drug transport, nitrofurantoin transfer across body membranes occurs by diffusion. Nitrofurantoin has a short elimination half-life in whole blood or plasma. In conjunction with its rapid excretion by the primary routes, there is little evidence for any prolonged binding of nitrofurantoin to either plasma proteins or tissues. The first-order kinetics involved in nitrofurantoin absorption and elimination is most appropriately described by a one-compartment open model. Biliary and urinary excretion of unchanged nitrofurantoin and enzymatic degradation are the primary means of elimination.


New in vitro model to study the effect of antibiotic concentration and rate of elimination on antibacterial activity. A new apparatus is described which serves to investigate the in vitro antibacterial activity of antibiotics as a function of different concentration time curves. The apparatus can be adjusted to simulate the biexponential serum level curves observed in vivo after oral or intramuscular administration. Preliminary studies were carried out with a cephalosporin derivative, cefazolin, against Escherichia coli and Klebsiella sp. strains simulating initial concentrations of 5, 10, and 20 mug/ml that decreased exponentially with half-lives of 30, 60, and 120 min. Surviving cells were counted at 1-h intervals for 10 h. In all the situations tested there was an initial phase of rapid bactericidal activity followed by a phase of bacteriostatic activity, whose length depended on the drug elimination rate but was relatively independent of the initial concentrations. Bacterial regrowth occurred when the antibiotic concentration fell below the minimum inhibitory concentration of the drug against the strains tested. The antibacterial activity of cefazolin, cephacetrile, and cephradine against E. coli and Klebsiella strains was also investigated, in a medium containing 4% human albumin, simulating the serum level curves observed in humans after an intramuscular dose of 1 g. The results obtained suggest that, for cephalosporins, a longer half-life might be more useful than higher peak levels.


Human leukocyte interferon in the treatment of varicella in children with cancer: a preliminary controlled trial. Eighteen patients who developed varicella while being treated for malignancy received human leukocyte interferon in a randomized double-blind placebo-controlled trial. Complications of varicella occurred in six of nine placebo recipients, but in only two of nine interferon recipients. Interferon was tolerated without significant side effects.


Factors influencing susceptibility of Nocardia species to trimethoprim-sulfamethoxazole. Demonstration of synergism between trimethoprim and sulfamethoxazole against 10 Nocardia isolates was found to be critically dependent upon the isolate, the duration of incubation, and the trimethoprim-sulfamethoxazole ratio. Inoculum effect was not significant. The trimethoprim-sulfamethoxazole ratio in the commercial, fixed-dose combination was found to contain too little trimethoprim to be optimal for Nocardia.


Use of a heavy inoculum in the in vitro evaluation of the anti-staphylococcal activity of 19 cephalosporins. The in vitro activity of 19 cephalosporins against 105 clinical isolates of Staphylococcus aureus and S. epidermidis was determined by using a heavy inoculum, i.e., 10(8) to 10(9) organisms per ml, to maximally challenge the antibiotics. The anti-staphylococcal activities of cephaloridine and 87/312 were consistently decreased by the use of a heavy inoculum when compared with the activity obtained with two less-concentrated inocula. The activity of most of the other compounds was also decreased with the use of a heavy inoculum, but this was observed only with selected isolates. Cephapirin, cephalothin, and cefazaflur were the most active drugs against the methicillin-susceptible isolates. Cephaloridine, cefamandole, cefazaflur, and 87/312 had substantial activity against methicillin-resistant staphylococci even with heavy inocula. With the exception of cefaclor against S. aureus, the orally absorbed cephalosporins were generally one-half to one-sixteenth as active as the parenterally administered cephalosporins. The median minimal inhibitory concentrations of five of the 12 parenteral cephalosporins were lower with the methicillin-susceptible S. aureus than with the methicillin-susceptible S. epidermidis strains.


Comparative physiological effects of incorporated amino acid analogs in Escherichia coli. The relative toxicities of several incorporated analogs of phenylalanine, methionine, arginine, and proline were assessed by a variety of criteria in a derivative of Escherichia coli 15 requiring the antagonized amino acids. Toxicity of the analog-substituted cell protein was most consistently indicated by its insolubility at graded temperatures, its increased breakdown, the relative suppression of further cell growth, and lethality. The relative toxicity of poorly utilized analogs could be judged clearly only by the first two criteria. Toxicity generally increased as follows: selenomethionine < 2,5-dihydrophenylalanine and m-fluorophenylalanine < o-fluorophenylalanine and norleucine < ethionine < p-fluorophenylalanine < azetidine-2-carboxylate < canavanine. The overall perturbation of cell protein structure indicated by the toxicity of the methionine and phenylalanine analogs correlated with their alteration of charge and bulk and was greatly modified by minor positional modifications of fluorine. Among the more specific functional impairments, the activity and heat stability of beta-galactosidase were lowered in parallel by substitutions of phenylalanine and methionine analogs, but not in the usual order of toxicity. Flagella were transiently motile with p-fluorophenylalanine, moderately motile with m-fluorophenylalanine, and fully motile with all methionine analogs. Usually the analog incorporations were no more than bacteriostatic in E. coli strains, canavanine killing only the E. coli 15 substrain extensively in minimal media. Selenomethionine supported indefinite growth of procaryotes such as Bacillus subtilis and certain E. coli strains, but only upon supplementation, at least initially, with many nonessential metabolites.


Chloramphenicol resistance plasmids in Escherichia coli isolated from diseased piglets. The plasmids in 19 chloramphenicol-resistant Escherichia coli strains of three pig pathogenic antigen types were studied in conjugation and transduction experiments. The plasmids had identical resistance patterns: streptomycin, spectinomycin, sulfonamides, and chloramphenicol (Sm, Sp, Su, Cm) and belonged to IncFII. One plasmid carried ampicillin resistance in addition. Restriction enzyme analysis of the deoxyribonucleic acid from five of the plasmids originating from the same herd showed that their digestion patterns with EcoRI were indistinguishable. EcoRI cleaved the deoxyribonucleic acid of a sixth plasmid from the same herd and displayed nine of the ten bands of the other five plasmids plus an additional six. It appears that the five plasmids with identical restriction patterns have a common origin and may be copies of the same plasmid from which the sixth may have developed. Four strains carried two plasmids each. In two of these strains, a plasmid with a tetracycline marker (Tc), or possibly the tetracycline marker alone, recombined frequently with the Sm Sp Su Cm plasmid without destroying any known function of the latter. The possibility that Tc is carried on a translocation sequence is discussed.


Mode of action of quindoxin and substituted quinoxaline-di-N-oxides on Escherichia coli. The effect of quindoxin on the synthesis of deoxyribonucleic acid (DNA), ribonucleic acid, and protein in Escherichia coli KL 399 was examined under aerobic and anaerobic conditions. In the absence of oxygen the synthesis of DNA was completely inhibited by 10 ppm of quindoxin, whereas the syntheses of ribonucleic acid and protein were not affected. Quinoxalin-di-N-oxides (QdNO) induce degradation of DNA in both proliferating and non-proliferating cells. polA, recA, recB, recC, exrA, and uvrA mutants were more susceptible than the corresponding repair-proficient strains. All strains were more resistant in the presence of oxygen. Quindoxin was reduced to quinoxalin-N-oxide by intact E. coli cells or by a cell-free E. coli extract. Electron spin resonance measurements demonstrated the generation of free radicals during the reduction of quindoxin. Oxygen or deficiency of energy sources impaired the antibiotic activity and the reduction of QdNO. The QdNO reductase activity was demonstrated to be lower in QdNO-resistant mutants than in the susceptible parent strain. Based on these results it is concluded that an intermediate of reduction, probably a free radical, is responsible for the lethal effect of quindoxin. With three independent techniques no evidence has been found for binding of quindoxin to DNA.


Potentiation of antibiotic bactericidal activity by normal human serum. Combinations of certain antibiotics and normal human serum at concentrations at which there was no killing by the agents when used alone were found to be bactericidal for Escherichia coli K-12 cells. This effect was observed with tetracycline, streptomycin (SM), trimethoprim, and ampicillin, but not with chloramphenicol or nalidixic acid. Synergy between SM and human serum was also observed against four of nine smooth strains of E. coli. A plasmid-bearing strain of E. coli K-12 was also killed by combinations of tetracycline or SM plus serum, even though the plasmid conferred resistance to tetracycline and SM. Evidence is presented that the synergy between antibiotics and serum is due to a complement-mediated effect on the bacterial cells that makes the cells more susceptible to the bactericidal effects of the antibiotics.


Chronic urticaria-like lesions in systemic lupus erythematosus. A review of 12 cases. Twelve of 54 patients with systemic lupus erythematosus (SLE) had nonpuric, chronic urticaria-like lessions. Skin biopsy of the lesions was performed in 11 cases, and nine showed necrotizing vasculitis. The 54 patients, in general, had severe disease, and laboratory and clinical data suggested a postivite relationship between the urticaria-like lesions and disease severity. There was no consistent relationship between the course of the urticaria-like lesions and the serologic findings and clinical activity of the SLE. The frequency and importance of urticaria-like lesions in SLE deserve further study.


Stereotactic brain surgery: a method for rapid and precise positioning of a target in the Todd-Wells stereotactic instrument. We describe an improved method for positioning the head for stereotactic brain surgery of aneurysms. The method uses a mathematical calculation and requires some physical modifications in the Todd-Wells stereotactic apparatus. This procedure achieves (1) a reduction in the number of angiograms needed and (2) an increase in the speed and accuracy of positioning. The technique has been applied to operations on live dogs.


Bullous pemphigoid in children.

Bullous pemphigoid in children. Bullous pemphigoid in children appears to be the same disease as its adult counterpart based on a case in a 3-year-old boy. Generalized tense bullae over the skin and oral mucosa, characteristic direct and indirect immunofluorescence, elevated IgE levels, blood eosinophilla, and therapeutic response to corticosteroids parallel the disease in adults. The long-term prognosis, however, is still unknown. A review of bullous pemphigoid in children is presented.


alpha1-Antitrypsin deficiency associated with persistent cutaneous vasculitis. Occurrence in a child with liver disease. alpha1-Antitrypsin (alpha1-AT) deficiency is an autosomal recessive inherited disease. The serum concentration of the protease inhibitor (Pi) alpha1-AT is controlled by a set of codominant allelic genes, constituting the so-called Pi system. Abnormal conditions reported in connection with severe alpha1-AT deficiency of the PiZZ type have been, in the newborn, cholestasis and progressive juvenile cirrhosis, and in adults, panacinar pulmonary emphysema and liver disease. Skin changes have not been described previously in connection with this disease picture. The case is persistent cutaneous vasculitis in a 2-year-old child with alpha1-AT deficiency of the PiZZ  type, heterozygosity for the Duarte variant of galactose-1-phosphate uridyl transferase, and neonatal liver disease. A pathogenetic relationship may exist between the biochemical defects and both the skin and liver diseases.


A notable case of nephrosis.

A notable case of nephrosis. How a boy of 10 developed nephrosis more than 60 years ago, how he came to be seen by Sir Frederic Still with interesting later consequences, how his nephrosis cleared following measles, and how all this led to his becoming a distinguished paediatrician is told in a case history based on the diary kept by the boy's mother.


Pulmonary interstitial emphysema requiring lobectomy. Complications of assisted ventilation. An infant with hyaline membrane disease treated with intermittent positive pressure ventilation developed pulmonary interstitial emphysema localised to one lobe after collapse of the affected lobe. The development of tension and further symptoms necessitated lobectomy, after which the infant became totally asymptomatic. Microscopy of the resected lobe showed the unusual feature of giant cells lining the air-containing cysts. The presence of these multinucleate cells suggested the cysts may have represented greatly dilated lymphatic channels resulting from rupture of gases into the pulmonary lymphatics.


Infantile cortical hyperostosis with raised immunoglobulins. Two cases of infantile cortical hyperostosis are reported. Both had raised immunoglobulins. Particularly remarkable were the IgA and IgM levels, a finding infrequently reported.


Colon perforation after kidney transplantation. Between 1962 and 1977 approximately 2% of Denver kidney transplant patients developed colon perforation. The single commonest cause was diverticulitis of the left colon (6/13 cases). In spite of drastic reduction or discontinuation of immunosuppression, only 5/13 patients survived for more than 90 days after operation. Analysis of this experience suggests that the high mortality rate associated with this complication can be reduced by early operation which removes the perforation from the peritoneal cavity (either exteriorization or resection) without primary intestinal reanastomosis. We believe that candidates for kidney transplantation with a history of previously symptomatic diverticulosis coli should have elective colon resection prior to transplantation. Any kidney transplant patient with lower abdominal signs should be investigated and treated aggressively.


Incidence of anatomical variants in renal vasculature in the presence of normal renal function. This report defines the incidence of variations in the renal vascular pedicle in a group of patients with normal renal function as determined by standard laboratory criteria. The study group consisted of 166 patients undergoing renal arteriography as potential renal allograft donors. Ninety-seven patients were male and 69 were female. Ages ranged from 18-54 years, median age being 37 years. All patients underwent preliminary screening tests including blood chemistries, creatinine clearance, urinalysis, culture and excretory urography. If these studies were normal, renal arteriography was performed utilizing flush aortogram and, in 20% of cases, selective renal arteriography. The most common anomaly was the presence of multiple renal arteries supplying the same kidney, occurring in 32% of cases. Prehilar segmental branching was the second most common variation, occurring in 17% of patients. Other variations included fetal lobulation (4%), significant stenosis at origin of the renal artery (2%), fibromuscular dysplasia (2%), microaneurysms (0.5%), true aneurysms (1%) and dromedary hump (0.5%). Less than one-half of the patients demonstrated the simplest vascular pedicle, namely, single artery and vein bilaterally. The incidence of anatomical variations in the renal vascular pedicle is greater than attributed to normal subjects in previous reports. Anomalies determine the choice of kidney in renal allografting and may disqualify a potential donor, even in the face of ostensibly normal renal function. Routine arteriography should be considered a standard prerequisite in the evaluation of potential living related renal donors.


Metrifonate trial in the treatment of various presentations of Schistosoma haematobium and S. mansoni infections in the Sudan. The effect of metrifonate (Bilarcil Bayer) on Schistosoma haematobium and S. mansoni infections was studied in 174 patients near Khartoum. A high cure rate was obtained in S. haematobium infections, but anthelmintic efficacy was minimal in patients passing S. mansoni eggs in their stools. There was, however, a marked reduction of egg output in patients passing S. mansoni eggs in urine. This suggests that the site of infection in man, rather than the species of parasite, renders the parasite more susceptible to metrifonate. The significance of this and the possibility that these results further clarify the mode of action of metrifonate are discussed.


The chemotherapy of rodent malaria, XXXI. The effect of some metabolic inhibitors upon chloroquine-induced pigment clumping (CIPC) in Plasmodium berghei. The effect of metabolic inhibitors upon chloroquine-induced pigment clumping in intraerythrocytic Plasmodium berghei was studied in vitro. Oligomycin and venturicidin competitively inhibit the process with 'Ki' values of 0.18 and 0.41 mumol/l. DCCD, an agent thought to act upon a mitochondrial site close to that affected by oligomycin and venturicidin, causes pigment clumping in the absence of chloroquine ('Km' value 4.7 mumol/l). It is suggested that, after being concentrated in the cytoplasm by Fitch's high-affinity site, chloroquine interacts with a mitochondrial site, and this interaction initiates the pigment clumping process. Comparison of the effects of the ionophores 2,4,-dinitrophenol, monensin, and valinomycin indicates that a H gradient is involved at some stage in chloroquine-induced pigment clumping.


Changes in the hamster liver after experimental infection with Schistosoma intercalatum. An ultrastructural study. Syrian hamsters were exposed to cercariae of Schistosoma intercalatum. After 70 days, their livers were fixed by vascular perfusion and samples of liver tissue were studied by the electron microscope. Lesions consisted predominantly of mature egg granulomas, with some in earlier stages of development. The cells involved in both types of lesion are described together with their relation to the egg and the surrounding liver tissue. Only minor abnormalities were seen in the tissue distant from the eggs. These consisted mainly of (a) pigment accumulation, both in Küpffer and endothelial cells; (b) probably aspecific ultrastructural changes in the hepatocytes; (c) occasional slight fibrosis around portal veins. The Schistosoma pigment was compared with malaria pigment induced by infection of a hamster with Plasmodium berghei. The regular, crystalloid hemozoin particles in malaria infection were easily distinguishable from the coarser and irregular pigment deposits in schistosoma infection.


Experimental pulmonary edema: the effect of positive end-expiratory pressure on lung water. The effect of 10 cm of positive end-expiratory pressure (PEEP) on lung water was studied during pulmonary edema induced in dogs by inflating a Foley balloon placed in the left atrium. Colloid oncotic pressure (COP) was measured directly. Intrapleural pressure (IPP) was measured after surgical closure of the chest. Transmural left atrial (LA) pressure (LA minus IPP) minus COP was considered to be the net force driving water out of the capillaries. LA pressure was elevated so that transmural LA pressure minus COP averaged +7.5 mm Hg. Water accumulation was expressed as the ratio of wet to dry weight. The control ratio of wet to dry lung weight was 4.30 +/- 0.10 (+/- SE). After 2 hours of standardized pulmonary edema and ventilation without PEEP, wet-to-dry lung weight was 5.63 +/- 0.24. In animals ventilated with 10 cm of PEEP through 2 hours of pulmonary edema the ratio was 5.36 +/- 0.14. Animals ventilated with 10 cm of PEEP showed a significant increase in functional residual capacity and decreased intrapulmonary shunt. Ten centimeters of PEEP, however, had no statistically significant effect on water accumulation during experimental pulmonary edema.


Normal cardiac function with a hybrid heart. A left ventricular bypass procedure using a cardiac allograft was performed in a patient with a long history of rheumatic heart disease and two aortic valve replacements. Normal cardiac function was reestablished, and the only problem following transplantation was that of serious arrhythmias involving the recipient heart. Eighteen months after left ventricular bypass bacterial endocarditis which was resistant to medical treatment developed on the aortic prosthesis. The patient underwent operation, the prosthesis was removed, and the recipient left ventricle was partially resected and excluded from the circulation. Since then the patient has been asymptomatic and, at the time of writing three years after cardiac allograft, he is our longest survivor.


The relationship of antibody-coated bacteria to clinical syndromes as found in unselected populations with bacteriuria. In selected patients, detection of antibody-coated bacteria (ACB) in voided urine has correlated with upper urinary tract infection. From unselected patients, we studied 350 consecutive urine specimens submitted to the diagnostic laboratory with colony counts greater than or equal to 10(5)/ml. In 19% (55) among 288 specimens selected for final analysis ACB occurred. There were no substantial differences in the occurrence of ACB by age or sex of patients or by species of bacteria. The relationship of ACB to clinical syndromes was: asymptomatic bacteriuria, 15% (27/178); cystitis, 8% (6/75); acute hemorrhagic cystitis, 67% (4/6); prostatitis, 67% (2/3); and acute pyelonephritis, 62% (16/26). Among seven clinical findings, only structural abnormalities of the upper urinary tract correlated with the presence of ACB. Failure of fever and leukocytosis to correlate with ACB probably reflected the presence of other associated primary medical or surgical conditions.


The effect of renal function on the febrile response to bacteremia. The febrile responses of 73 bacteremic patients were retrospectively studied using peak temperatures and 24-hour areas under the fever curve on the day of the positive cultures. These responses were compared to their respective creatinine clearances calculated with the Nielsen-Hansen nomogram. Patients with clearances greater than or equal to 80 ml/min had a significantly greater febrile response than those with clearances less than or equal to 29 ml/min (P less than .025). Patients with clearances between these groups had responses that were in a mid position but not significantly different from either group. We conclude that patients with impaired renal function do manifest fever in response to infection, but that it is quantitatively less than those with normal renal function. Because of this blunted response, minimal elevations of temperature in such patients warrant a diligent search for the presence of infection.


Long-term dialysis and renal transplantation in lymphatic leukemia. With increasing experience and skill with renal transplantation and dialysis, many disorders that were previously thought to contraindicate these procedures are no longer regarded as contraindications. We have previously reported that transplantation can successfully be performed in patients who have had malignant diseases if they seem to be cured after approximately 12 months. Although incurable malignancies have usually been regarded as absolute contraindications, successful dialysis and transplantation have been achieved in a patient with chronic lymphatic leukemia.


Disseminated Nocardia caviae with positive blood cultures. Disseminated Nocardia caviae infection with multiple positive blood cultures occurred in a bone marrow transplant recipient. Positive blood cultures are unusual in disseminated Nocardia infections and N caviea is an unusual species of Nocardia to cause infections in man, although its virulence in laboratory animals is similar to N asteroides. Multiple positive blood cultures in this case suggest a continuous or recurrent bacteremia rather than a transient bacteremia as previously has been thought to occur in disseminated Nocardia infections. The marked immunosuppressed state of the patient and an indwelling venous line could also have accounted for the recurrent bacteremia.


[The importance and determination of follicle stimulating and luteinizing components in PMSG preparations]. Partial reference is made to some literature on the formation and properties of gonadotropine from the serum of pregnant mares (PMSG). Also an assessment is made of biological testing methods by which to determine gonadotrophic, follicle-stimulating, and luteinising activities in PMSG.


[The quantitative composition of the gastrointestinal flora in piglets during the first weeks of life. 1. The development of the gastrointestinal flora in naturally reared piglets]. Studies were conducted into the quantitative composition of the gastro-intestinal flora of 30 naturally raised piglets in four age groups. The gastro-intestinal tract was found to be "flooded" by Escherichia coli, Clostridium perfringens, micrococci, streptococci, proteus, and lactobacteria over the first hours after birth. Development of the intestinal flora was complete at the age of four days. The groups of germs recordable from naturally and artificially raised piglets were, basically, the same. Piglets, consequently, have no specific "lactoflora".


[Intravital diagnosis of saginata cysticercosis of cattle by means of the immunofluorescent antibody reaction]. Investigations in intravital diagnostics of fin infestation in cattle were performed in 3 month aged cattle experimentally infected by different doses of Taeniarhynchus-saginatus-eggs by means of immunofluorescent antibody technique using a standardized antigen. Regardless of the amount of the infection dose these occured already 2 weeks after infection positive antibody values of at least 1:40 reaching the maximum value of 1:640 4-6 weeks after infection (in cases of strong fin infestation) and 1:160, respectively (in cases of low fin infestation) and remaining positively up to the termination of experiments (23 and 18 weeks, respectively post infectionem). Negative reactions were not observed. With regard to the economy this method is superior to other immundiagnostical procedures hitherto used with success in detection of Cysticercus bovis.


[Localization of urinary tract infection in children by immunofluorescent study of bacteriuria and measurement of humoral antibodies]. In 62 children presenting with a urinary infection, the immuno-fluorescent (I.F.) study of immunoglobulins fixed on the cell wall of urinary bacteria was performed jointly with the titration of serum antibodies towards the same bacteria. This study revealed that: 1. There was a correlation between I.F. and serodiagnosis in 82% of the cases. 2. There was a correlation between the localization of the urinary tract infection, as assessed by the classical biochemical means, and the results of I.F. and antibody measurements. Positivity of either I.F. or serodiagnosis, or of both tests, is significantly related with upper urinary tract infection wheras the negativity of the two tests is observed, at the exception of children under 1 year of age, in lower urinary tract infection. 3. There was a correlation between the site of infection and the results of I.F. and antibody measurements. In upper urinary tract infections, either I.F. or serological tests, or both are positive, whereas in lower urinary tract infections both tests are negative, except in children under the age of 1 year.


[Butylcyanoacrylate--an adhesive for bonding strain gages to non-fixed biological materials (author's transl)]. Creep, hysteresis, stability, elongation capability and repeatbility of butylcyanoacrylate as a proper adhesive for bonding strain gages to non-fixed tissues have been tested with good results. Due to its excellent bonding performance butylcyanoacrylate provides the only means for bonding electrical resistance foil strain gages to biological materials for the time being. This opens new aspects for strain measurements with strain gages in the biomechanical field.


[The distal rupture of the biceps tendon. Aetiology, clinic and technique (author's transl)]. Compared to the proximal rupture of the Biceps tendon the distal rupture is extremely rare. The numerous published methods of repair show that a reliable method has not yet been found. Considering functional principles we developed a method which combines a safe fixation of the tendon and a good function. An autologous tendon is brought through a burrhole placed obliquely through the mid position of the tuberosity. The Biceps tendon is now placed between the ends of the autologous tendon and fixed with resorbable u-sutures (Sandwich-technic). Thereby the tension on the tendon is adapted as necessary. The achieved results is demonstrated on two cases.


[Morphometry of living and metal salt impregnated nerve fibers]. Quantitative comparison on diameter distribution of some structures in vital and fixed neuronal fibres treated with salts of heavy metals has been performed. Rabbit and frog myelin fibres of the ischiadic and vagal nerves impregnated after Bielschowsky--Gross, fixed in 12% neutral formalin and treated after Gomori for acid phosphotase with fixation in cooled acetone have been studied. The diameters of neuronal fibres, axial cylinders and cords have been measured through the microscope with an ocular micrometer. Quantitative comparison of survived and fixed fibres has demonstrated that in the preparations treated with silver and lead salts, as a rule, not the whole fibre is demonstrable, not its axial cylinder, but only a part of the axial cylinder, namely, its centrally situated filamentous cord. It is most probable that, in this case, the axial cord formation is connected with the effect of fixatives. However, axial cord formation is possible in vital, nonfixed fibres in the zone of intersections and swollen incisions. The working hypothesis explaining this phenomenon is represented.


Dysmyelination revisited.

Dysmyelination revisited. Dysmyelination describes an inborn error of metabolism affecting myelinogenesis that causes it to be abnormal, arrested, or delayed. Abiotrophy or myelin as defined by Gowers, due to metabolic failure of the myelin maintenance system, is yet another feature of dysmyelination. In addition to the leukodystrophies, genetically determined conditions such as infantile amaurotic idiocy, hematosidosis, Niemann-Pick's disease and several of the aminoacidopathies are examples of dysmyelinating diseases. In order to reconcile morphological and neurochemical data in these conditions, it is necessary to reexamine a number of pathogenetic hypotheses based on known enzymatic deficiencies, and the interpretation of fragmentary biochemical analyses. The obligatory role of the neuron and axon in myelin formation and maintenance is reviewed. The hypothesis is advanced that gangliosides and their degradative products constitue precursors for the synthesis of the characteristic myelin sphingolipids cerebrosides, sulfatides, and sphingomyelin. Alterations in axoplasmic flow and of ganglioside metabolism must be condidered as important factors in the pathogenesis of dysmyelination.


Pellucid marginal corneal degeneration.

Pellucid marginal corneal degeneration. Pellucid marginal degeneration of the cornea is a bilateral, clear, inferior, peripheral corneal-thinning disorder. Protrusion of the cornea occurs above a band of thinning, which is located 1 to 2 mm from the limbus and measures 1 to 2 mm in width. American ophthalmologists are generally not familiar with the condition because most of the literature concerning pellucid degeneration is European. Four cases are described. This condition is differentiated from other noninflammatory cornel-thinning disorders such as keratoconus, keratoglobus, keratotorus, and posterior keratoconus. It is also differentiated from peripheral corneal disorders associated with inflammation such as Terrien's peripheral corneal degeneration, Mooren's ulcers, and ulcers from connective tissue disease.


The deltoscapular flap.

The deltoscapular flap. The deltoscapular flap is described as an additional source of regional skin for head and neck reconstruction; this flap behaves in the manmer of an arterially based axial skin flap. On three occasions, I have used this back flap that is almost a mirror image of the deltopectoral flap.


Changes in the activity of the reticulo-endothelial system of rats during an infection with T. lewisi. Data presented show that during the course of a Trypanosoma lewisi infection in rats there was both an activation of the phagocytic cells of the liver and spleen and an increase in their numbers. There was a marked lymphoid hyperplasia in the white pulp of the spleen with an increase in the number and size of the lymphoid follicles. Degenerative changes occurred in the liver parenchymal cells during the infection, and at certain stages large numgers of mononuclear cells were observed in the vascular sinusoids and other vessels of the liver.


Studies in vitro on the reaction of peritoneal exudate cells from mice immune to infection with Nematospiroides dubius with the infective third stage larvae of this parasite. The results of the present study show that peritoneal exudate cells from mice immune to infection with Nematospiroides dubius are able in vitro to damage the third stage infective larvae as measured by a loss in infectivity. The ability of these cells to function in the absence of specific antibody seems to be related to the presence of trypsin labile factors on their surfaces. Lymphocytes from immune mice are also able to damage the larvae. The suggestion is made that 'activated' macrophages may play an important role in immunity to this infection.


Where is the immunology in cancer?

Where is the immunology in cancer? Whether the common human cancers possess tumour-specific antigens which produce an immune response in the host still remains the crucial question in tumour immunology. Recent reports and discussions at the Third International Congress of Immunology suggested that much of the previously published work was not valid. The reasons for this have been analysed by comparing the well-established experimental data with human cancer. It is suggested that much of the current confusion in tumour immunology stems from the poor models used to study human cancer and the inadequate assessment of in vitro assays which have measured the host response. The present methods require refinement, or new techniques need to be developed, before this question can be answered. The field has been well researched, and there do not appear to be any recent major advances in tumour immunology which can be applied in clinical practice.


Influence of a GABA transaminase inhibitor on central nervous system oxygen toxicity. A decrease in brain GABA concentration has been implied as the cause of convulsions induced by hyperbaric oxygen (HOP). We therefore examined the influence of sodium valproate, an anticonvulsant and GABA transaminase inhibitor on HOP-induced convulsions in rats. The mean latency of occurrence of the first electrical discharge in the ECoG and the appearance of the first clinical seizure in awake chronically implanted rats was unchanged by administration of sodium valproate prior to HOP exposure. We conclude that either the sodium valproate inhibition of GABA removal is insufficient to compensate for HOP inhibition of its production, or else that GABA concentration changes are not causally related to HOP-induced seizures.


Isolation and some properties of nontoxigenic derivatives of a strain of Clostridium tetani. Nontoxigenic derivatives of a toxigenic strain of Clostridium tetani were isolated gy treatment with acridine orange, N-methyl-N'-nitro-soguanidine, rifampicin or ultraviolet light. The frequency of appearance fo non-toxigenic derivatives on these treatments was 0.8 to 3.2 per cent. The nontoxigenic derivatives peoduced all the same extracellular antigenic and protein components as the toxigenic parent strain, except the toxin and materials cross-reacting with the toxin. The nontoxigenic strains, like the toxigenic parent strain, were lyzed by trratment with mitomycin C. Bacteriophage was detected in the lysates of all the nontoxigenic derivatives produced with mitomycin C, and this bacteriophage was morphologically indistinguishable from that obtained from the toxigenic parent strain. The genetic factor controlling tetanus toxin production is discussed.


The proton exchange of the pro-S hydrogen atom at C-1 in dihydroxyacetone phosphate and D-fructose 1,6-bisphosphate catalysed by class-I and class-II aldolases. The efficacy of class-I and class-II aldolases in catalysing the C-1 proton exchange in fructose 1,6-bisphosphate and dihydroxyacetone phosphate was investigated. The rate of this reaction was at least two orders of magnitude slower in class-II than in the class-I aldolases. It is suggested that this difference reflects the formation of different intermediates in the reactions catalysed by the two classes of aldolase.


Kinetic studies with the use of proton-magnetic-resonance spectroscopy of the specific alpha-deuteration of amino acids by Escherichia coli aspartate aminotransferase. Escherichia coli aspartate aminotransferase was exposed to aspartate or phenylalanine without oxo acid in buffered 2H2O. The alpha-hydrogen of the amino acids underwent first-order exchange with respect to both substrate and enzyme. P.m.r. spectroscopy gave consistent reaction-rate constants. The deuterium-exchange rate was only moderately increased by addition of oxo acids and was of the same order as the transamination rate. No beta-deuteration was observed. The C(alpha)-H-bond-breaking step is discussed as a part of the entire transamination mechanism.


The interaction of C-protein with heavy meromyosin and subfragment-2. C-protein has previously been shown to bind to the light-meromyosin region of the myosin tail. Examination of mixtures of C-protein with heavy meromyosin or subfragment-2 or subfragment-1 in the analytical ultracentrifuge shows that there is also a binding site for C-protein in the subfragment-2 region of the tail.


Clinical immunologic studies in systemic lupus erythematosus. This review of recent and new directions in clinical immunologic studies of systemic lupus erythematosus (SLE) is restricted to the areas of lymphocyte surface markers, antigen binding lymphocytes, immune complexes, and lymphocyte hyporesponsiveness in lupus patients. First, it is not clear whether the T-lymphopenia observed in SLE is related to viral destruction of T cells, anti-lymphocyte antibodies, or tissue sequestration. Second, the increase in DNA-binding B lymphocytes observed in active lupus patients may be related to minor alterations in the balance of immunoregulatory T cells or to a bypass of DNA-specific helper T cells. Third, it is speculated that the removal of immune complexes which play a role in lupus glomerulitis by various extracorporeal immune absorbents may be important in the future therapy of SLE. Fourth, the mechanisms of T-lymphocyte hypofunction are unexplained. It is postulated from studies done in other diseases that this hypoactivity may be mediated by the secretion of prostaglandin or other humoral agents from one leukocyte subpopulation suppressing another potentially responsive lymphocyte subpopulation. Also an investigation into the lymphocyte subpopulation reactive with virus-infected fibroblasts may be useful in delineating immunoregulatory lymphocytes important in the pathogenesis of SLE.


Natural history of murine lupus. Modulation by sex hormones. Pathologic and immunologic features of the spontaneous autoimmune disease of NZB and NZB/NZW F1 (B/W) mice resemble human SLE in three major respects: formation of antibodies to nucleic acids, deposition of immune complexes containing DNA in the kidney, and earlier onset of severe disease in females. Genetic, viral, and hormonal factors are involved in a pathogenetic mechanism that is manifest primarily as a disturbance in immunologic regulation. Recent studies on the sequential development of IgM and then IgG antibodies to DNA and RNA suggest that the thymus, spleen, and gonads exert important regulatory influences. We have found that sex hormones modulate the expression of autoimmunity in B/W mice, with androgens suppressing and estrogens accelerating disease. The hormones may act by restoring immunologic control.


[Arrest reaction in man: motor arrest response by electrical stimulation of the deep structure of the cerebrum (author's transl)]. In spite of many reports of arrest reaction in animals, there are very few reports in man. During a therapeutic stereotaxic operation we observed peculiar phenomena caused by electrical stimulation to the deep structure of the cerebrum. This phenomenon is quite similar to that reported by Van Buren, but there are a few differences between them. Arrest reaction was observed in 14 of 23 cases, 17 of 28 tracks. Stimuli which caused the arrest reaction were 60--100 Hz square waves of, 1 msec duration and 5--15 V. The electrical stimulation caused an interruption of counting and other motor actions, which could be resumed following release of stimuli. Psychic confusion or memory disturbances were not observed with the exception of a few cases. The arrest reaction that we observed is thought to be due to a direct effect on the head of the caudate nucleus, not due to secondary effects on the internal capsule and the motor fiber in the vicinity of the caudate nucleus. However, the possibility that the current spread to the motor fiber cannot be definitely ruled out.


A double-blind comparison of morphine and buprenorphine in the prevention of pain after operation. A double-blind, between-patient comparison has been made of the effects of morphine 10 mg i.v. and buprenorphine 0.3 mg i.v. on the prevention of pain after operation. The drugs were given by the anaesthetist at the end of the operation, and the onset and severity of pain were assessed by a trained nurse. Both drugs caused a significant delay in the appearance of severe pain when compared with the control group, but with buprenorphine the mean delay of 10.5 h was more than twice that of morphine. The only side-effect to occur more frequently after administration of the analgesics was drowsiness, the incidence being greater after buprenorphine than after morphine.


A history of nitrous oxide and oxygen anaesthesia IVD: Henry Hill Hickman in his time. Fresh evidence of Hickman in Ludlow is recorded: an advertisement for an apprentice and an annotation in the Shrewsbury Chronicle relate to his private museum. This and his household goods were auctioned in 1824. That he may have been inspired by Benjamin Collins Brodie is considered.


A longitudinal study of the mechanisms of action of debrisoquine and propranolol. 1 The mode of action of hypotensive drugs is not necessarily the same early and late in a course of treatment. 2 It was aimed to study this possible difference of effects for the drugs debrisoquine and propranolol, using a clinical trial design and measuring as many cardiovascular functions as possible by noninvasive methods in out-patients. 3 Several well known effects of these drugs were noted; in addition it was found that in some subjects there was a small but progressive salt retention during propranolol treatment, that the displacements  of the slopes in baroceptor function tests were different for the two drugs tested, and that venous distensibility was reduced at first with propranolol but soon increased again. 4 It is useful to combine longitudinal measures of body functions with a clinical trial when studying mechanisms of drug action.