Effect of age, cardiovascular disease, and vasomotor changes on transmission of arterial pressure waves through the lower extremities. Pressure waves were recorded by indwelling needles in the femoral and foot arteries. At the foot the systolic and pulse pressures were greater and the dicrotic wave more prominent. These changes during transmission increased during vasoconstriction and decreased during vasodilatation. The ratio of the distal to femoral pulse pressure (amplification) increasing from 1.13 +/- 0.05 during body heating to 1.47 +/- 0.06 during body cooling (P less than 0.01), and from 1.14 +/- 0.10 during infusion of trimethaphan to 1.42 +/- 0.02 during cooling (P less than 0.05). Amplification was also significantly greater following inhalation of amyl nitrite and during and after Valsalva maneuver. Greater pulse pressure at the foot paralleled greater amplitude of individual harmonics. Phase velocities decreased with increasing frequency and tended to level off at a value similar to the foot-to-foot pulse wave velocity. The findings are consistent with peripheral reflections of the waves which increase during vasoconstriction. In the absence of procedures that elicit vasoconstriction or vasodilatation, amplification averaged 1.35 +/- 0.03 in control subjects less than 35 years of age and 1.24 +/- 0.06 in older subjects (P less than 0.05). Amplification also did not differ significantly between control subjects and patients with hypertension or ischemic heart disease. In the absence of pronounced vasodilatation or encroachment on the lumen by atherosclerotic plaques, systolic and pulse pressures at the foot should be higher than in proximal pulses. These findings provide a firm basis for interpreting measurements of distal systolic pressures by using blood pressure cuffs when examining patients with occlusive arterial disease in the extremities.


Influences of the adrenergic nervous system on the repolarization phase of the electrocardiogram. The following conclusions can be drawn : (1) The nervous outflow to the heart may be varied from the baseline to opposite directions by different stressful stimuli. (2) ST-T alterations may be induced and abolished by adrenergic activation and inhibition respectively. (3) These effects are dissociated from or not necessarily associated with an exaggerated responsiveness of the cardiac beta receptors. (4) The adrenergic influences on the ST-T abnormalities of myocardial ischemia and hypertension are limited.


Noninvasive evaluation of peripheral arterial disease. Doppler ultrasound is the most simple, inexpensive, accurate and versatile of the available noninvasive screening techniques to assess peripheral vascular diseases. The four fundamental components of peripheral arterial evaluation with this technique are assessment of blood velocity signal, measurement of resting ankle pressure, determination of segmental leg blood pressures, and measurement of ankle pressure response to exercise or reactive hyperemia. Plethysmography permits graphic recording of pulse-wave morphology, determination of digit blood pressure, and pulsatile responses to compression maneuvers. These techniques are useful in objectively quantifying peripheral arterial occlusive disease, predicting the results of operative therapy, monitoring the success of arterial reconstruction during surgery, and following the physiologic status of the patient after surgery.


Risk factors for the development of allergic disease: analysis of 2,190 patient records. Records of 2,190 patients with demonstrable allergic disease, including 1,148 patients with asthma and 557 patients with allergic rhinitis, were analyzed for the impact of certain risk factors on age of onset of allergic disease and on sensitization to certain specific antigens. The risk factors examined included race, sex, maternal age, family structure, life style, feeding history, environmental factors and heredity of allergic disease. Age of onset was significantly earlier (P less than 0.001) in males, blacks, children of younger mothers, bottle-fed babies, children of rural origin, children of smoking parents and children with a bilateral family history of allergy.


Study of social, educational, environmental and cultural aspects of childhood asthma in clinic and private patients in the city of New York. A group of asthmatics treated in a clinic setting were compared to a group treated by private allergists. Statistical differences were found regarding family income, racial distribution, family structure, educational level, reading habits, management of acute asthma attacks, housing, living space, school absences and hospital admissions.


Routine laboratory determinations in pediatric allergic disease. Clinical and laboratory data were extracted from the medical records of 285 consecutive children after completion of their evaluations for suspected atopic disease. Blood eosinophilia, determined from a routine complete blood count, was present in more than 60% of patients tested. Nasal smear for eosinophils or a direct eosinophil count provided little additional evidence of atopic reactivity in simultaneously tested patients. Total serum IgE concentration was elevated in 75% to 81% of the children with asthma, nasal allergy and atopic dermatitis and an elevated serum IgE concentration or blood eosinophilia, or both, was noted in 85% of the patients studied. Selective IgA deficiency was documented in three children and hyperimmunoglobulinemia was found in 20 others. Serum complement activity was normal in 10 children with persistent urticaria, allergy, IgE, eosinophilia, immunoglobulins, complement.


Elevation of serum IgE in Japanese-American children. Serum IgE levels were determined in Japanese-American and White-American children--ages 6 to 14. The mean serum IgE level was significantly higher in the Japanese-American children (444 vs. 67; p less than .01). There was also a suggested incidence of personal allergic disease or familial allergy in a small sample of the Japanese-American children.


Enzyme determination and RAST inhibition assays for orchard grass (Dactylis glomerata): a comparison of commericial pollen extracts. Pollens release enzymes when they are dropped into water. Orchard Grass extracts were tested by two methods. The Api-Zym System determined 19 enzymes and colorimetric amounts of Leucine Aminopeptidases, Acid phosphatase and trypsin. These were compared with RAST inhibition assays. A good correlation was shown between the techniques. Thus the enzyme dosage may be useful for the standardization of pollen extracts.


In vitro immunological studies in atopic and contact dermatitis. Serum immunoglobulins, five lymphocyte markers and three mitogen assays were used in an investigation of 20 patients with atopic dermatitis. A slight impairment of the cell-mediated immunity was detected. Ten patients suffering from contact dermatitis had sub-normal lymphocyte reactivity.


Changes of serum complement and eosinophil count in antigen induced bronchospasm. By using house dust antigens, in addition to the relation between specific IgE antibody, precipitin antibody and bronchial provocation test (BPT), the changes of serum complement activities and eosinophil counts after BPT were studied. Decreased serum concentrations of C4 and Factor B were found in three of 15 skin-test positive asthmatic children, thus confirming the involvement of complement in the pathogenesis of immediate type BPT reaction. Eosinophil counts tended to increase after BPT but the increase did not correlate with the occurence of the immediate type BPT reaction.


[Rabies virus study by the plaque forming system. A simplified technique]. The author describes here a simplified and economical plaque forming system for rabies virus study. It is achieved in three steps (cells preparation and infection, apply of overlay, staining). It presents more advantages than previous techniques: time as well as culture media and handling spearing, easy and durable reading. Cells prepared with di-ethyl-amino-ethyl-dextran are added to equal quantities of diluted virus (for titration) or to virus-serum mixing (for seroneutralization) and overlaid after 4 hours with a carboxymethylcellulose medium. Reading is carried out after 6 days incubation and staining with amido black. Plaques obtained are to 2-3 mm in diameter, regularly reproductible, clear and easy to read. This technique enables titration and seroneutralization and even a rabies virus cloning.


[Application of polyacrylamide gel electrophoresis-SDS to the study of proteinuria (author's transl)]. The authors present a variant of the technique of sodium dodecylsulfate acrylamide gel electrophoresis (SDS-PAA) reported by Weber and Osborn, for the analysis of urinary proteins. SDS-PAA separates the proteins chiefly according to their molecular radius. SDS-PAA, as compared to acetate cellulose electrophoresis and immunoelectrophoresis, gives better resolution and may be recommended for the investigation of proteinuria.


[Estimation of aluminium in biological fluids by atomic absorption spectrophotometry in a graphite oven (author's transl)]. The possibilities of use of a graphite oven type HGA 74 (Perkin Elmer) for the estimation of aluminium in biological fluids by atomic absorption spectrophotometry are described, with a special study of the stages of drying, mineralisation, atomisation, flow of inert gas, requirement for correction of non-specific absorption, etc. Under fixed experimental conditions, the limit of sensitivity (absorption 1%) was 2.28.10.(-11) grams and the linearity was good up to 100 microgram/l. This method of analysis by direct treatment of the samples required only small volumes of the latter and reduces the risk of contamination.


[Estimation of aluminium and gallium in biological fluids (author's transl)]. The authors describe the conditions of treatment of samples and the conditions of measurement which permit estimation of aluminium and gallium in biological fluids by atomic absorption spectrometry.


[Estimation of clometacine in biological fluids by gas chromatography and electron capture (author's transl)]. The authors describe a method of estimation of clometacine in biological fluids based on extraction in the pure state of a pair of ions, purification by chromatography (in liquid phase, adsorption, then exchange, methylation by diazo-methane and gas chromatography associated with detection by electron capture.


Get the venous blood too.

Get the venous blood too. Although simultaneous gas analyses on arterial and central or mixed venous blood cost twice as much as on arterial blood alone, the benefits obtained, we believe, are increased by much more than twofold. The greatest benefits are those obtained from having more accurate and detailed information of pulmonary and hemodynamic function, particularly physiologic shunting in the lung and cardiac output.


Factors influencing morbidity and mortality after liver injury. The factors influencing morbidiy and mortality after liver injury were monitored prospectively in 637 patients. Death correlated with the number of associated injuries, severity of injury, presence of great vessel injury, active bleeding from liver at laparotomy, and severe shock on admission. Morbidity correlated most with presence of a colon injury, and the use of choledochostomy drainage. The first priority in treating liver injury is to stop bleeding. The simplest technique for this is multiple liver suture. Drainage is most safely achieved with soft rubber drains placed to the site of injury. Although several patients having no drainage may do well postoperatively, at least two patients in this series died because no drains were used. The use of choledochostomy drainage for decompression of the liver is associated with increased morbidity and mortality and is, therefore, contraindicated.


Hemodynamic analysis of septic shock in thermal injury: treatment with dopamine. Eleven burn patients were studied while in septic shock and during dopamine infusion. There was only one survivor. The shock state in septic burn patients is hyperdynamic with a marked increase in cardiac index but a significant loss of systemic vascular resistance. Dopamine infusion in low doses stimulated the heart by increasing the cardiac index but caused further vasodilation and exerted little beneficial effect on blood pressure. High doses of dopamine increased the systemic vascular resistance and the blood pressure to levels which more adequately perfused the kidney. Dopamine infusion in high doses will improve the septic patient's hemodynamic status. This may permit surgical treatment of the septic process to remove the cause of the shock state.


Survival of patients with bronchogenic carcinoma modified by BCG immunotherapy. Fifty-five patients with stage II and III bronchogenic carcinoma were randomized into one group of 21 treated conventionally, and another group of 34 additionally vaccinated with BCG. Vaccinated patients survived, on average, 11 weeks longer than controls. A lag of about six months existed before consistent differences became apparent.


Cholecystectomy during pregnancy.

Cholecystectomy during pregnancy. While cholecystitis has definitely been associated with pregnancy, performance of cholecystectomy during pregnancy seem to be a rare occurrence. To document this observation we reviewed the records of all cholecystectomies performed during a 10-year period on women between the ages of 16 and 45 in a university hospital and a busy community hospital. Six of the 749 cholecystectomies performed at the university hospital occurred during pregnancies of from four to 26 weeks' gestation. Four of the patients were operated on emergently after an average of one week of conservation management. In no instance did the operation induce premature labor or abortion. Operative cholangiography was performed in four of the patients without detriment to the fetus. This review indicates that the need to perform cholecystectomy during pregnancy is rare, but that it can be performed with minimal risk to the fetus regardless of gestation.


Accuracy of oral cholecystography in cholelithiasis. The accuracy of oral cholecystograms in the detection of cholelithiasis was assessed by comparing 100 patients who were examined both roentgenographically and by ultrasonography of the gallbladder. All normal oral cholecystograms had normal ultrasonography of the gallbladder. This study supports previous reviews indicating that the reliability of cholecystography in cholelithiasis is in the 98% range.


Noninvasive localization pheochromocytomas. Because of the propensity for extra-adrenal sites, preopertative localization of pheochromocytomas remains an important operative determinant. Although arteriography has been widely considered to be the procedure of choice for preoperative localization, in this series of 13 patients, falsely negative arteriograms were seen on two occasions while four patients experienced significant morbidity from attempts at angiographic localization. Emphasis is placed upon noninvasive techniques as the initial approach toward localization. The value of bolus infusion nephrotomography is re-emphasized and localization of a pheochromocytoma by ultrasound and computerized axial tomography is described.


Acute appendicitis in patients over sixty. In an investigation of 68 consecutive patients over the 60 operated on for acute appendicitis in 1969--1972 the symptoms and signs did not differ notably from those in younger patients. However, the disease was more advanced in the elderly patients with perforation of the appendix in 49%. Postoperative complications occurred in about one third of the series, but were never fatal. Use of broad-spectrum antibiotics (ampicillin) is recommended. The investigation showed that it is possible to reduce the mortality from acute appendicitis in elderly patients to a level comparable to that in younger ones.


Routine subclavian vein catheterization in thoracic surgical practice. A total of 101 routine subclavian vein catheterizations in patients with elective thoracic surgical procedures were performed at the Medical University of South Carolina Hospitals over a two-year period. This was done primarily to have ready access to large veins, particularly in the axial plane of the body and to free the patient's extremities from uncomfortable immobilization and the risk of superficial thrombophlebitis in the postoperative period. The procedure is very safe, and complications are rarely encountered if experienced personnel place and then care for the catheter.


Uncommon presentations of venous disease. Venous disease can manifest itself in unusual ways; three uncommon venous disease states are described, together with discussions of their treatment. The cases include an iliac compression syndrome, incipient venous gangrene of an upper limb associated with polycythemia and congestive cardiac failure, and venous edema of a lower limb as a sequel to previous radical pelvic surgery.


How I do it: Pedicle planning with surrogate skin. Preplanning a pedicle using foam polyethylene helps eliminate errors of size and location and allows less scarring, less wasted tissue, less anesthesia time, and better assurance of fit and survival of the pedicle. The foam sheet is inexpensive, easily cut, can be sterilized, and resembles skin in compressibility, tension, and torque resistance. This technique for pedicle planing with surrogate skin is demonstrated in a variety of large and small pedicles.


Legionnaires' disease: clinical features of 24 cases. Twenty-four cases of Legionnaires' disease were diagnosed at the Wadsworth Veterans Administration Hospital during a 5-month period. All cases occurred in persons exposed to the hospital environment during the usual incubation period of Legionnaires' disease. The clinical illness was quite characteristic. All patients complained of weakness, malaise, anorexia, and cough. Rigors, diarrhea, and pleuritic pain were frequent symptoms. All patients had a maximum temperature of greater than or equal to 39.4 degrees C. Thirteen of 22 patients had relative bradycardia. Chest roentgenograms documented pneumonia in all patients. Leukocytosis, hyponatremia, hypophosphatemia, and abnormal liver-function test results were typical. Diagnosis was made by serologic criteria in 20 patients, postmortem examination of tissue in two, and both serology and tissue examination in two. Four patients in whom the disease was not suspected died of Legionnaires' disease. One patient died of unrelated causes. Fifteen of 19 survivors received erythromycin therapy. The presentation of Legionnaires' disease was characteristic enough to allow early, specific therapy.


e Antigen in hepatitis B virus infected dialysis patients: assessment of its prognostic value. Many investigations consider the presence of e antigen (HBeAg) valuable in predicting which patients with acute hepatitis B are at risk of remaining infected and developing chronic liver disease. We tested this hypothesis in a retrospective study of serial samples from patients undergoing long-term hemodialysis. We found HBeAg in the early phase of all hepatitis B virus (HBV) infections. There was no significant difference between transiently and persistently hepatitis B surface antigen (HBsAg)-positive persons with regard to the frequency of HBeAg during the first 3 months of HBs antigenemia. Thus during the early period of viral activity, the presence of HBeAg is of no prognostic values in determining chronicity of HBV infection. We believe the disagreement on the prognostic value of HBeAg is a reflection of variations in time and frequency of sampling. The HBeAg remains, however, a useful indicator of potential infectivity of HBsAg(+)persons.


Achalasia secondary to carcinoma: manometric and clinical features. The clinical and diagnostic features of a secondary type of achalasia of the esophagus are described in seven patients with various types of malignancies. Patients with secondary achalasia presented with dysphagia of short duration and marked weight loss; mean age was 64 years. Esophageal manometry showed features identical to those of idiopathic primary achalasia: aperistalsis, poor lower esophageal sphincter relaxation, and elevated sphincter pressure. Endoscopy and barium swallow showed evidence of a tumor in only two cases. Various types of malignancies may produce a secondary form of achalasia that has diagnostic features identical to those of primary achalasia and is best identified by its clinical presentation.


Convoluted lymphocytic lymphoma in adults: a clinicopathologic entity. Twelve adults had a distinct clinicopathologic type of malignant lymphoma that closely resembles the mediastinal lymphomas of childhood. Nine patients presented with mediastinal masses, and seven had symptoms related to intrathoracic compression. Seven patients presented with or developed leukemia, and in four of these patients the central nervous system (CNS) became involved. Structurally, the tumor cells had a distinctive stippled chromatin pattern, in addition to the characteristic nuclear convolutions. Tumor cells from five patients were studied immunologically, and, in each case, the tumor cells formed rosettes with sheep erythrocytes. The response to combination chemotherapy was rapid and dramatic, but usually transient, with relapse in the CNS or previously involved sites. The above data strongly suggest that these cases represent a distinct clinicopathologic entity that should be treated similarly to childhood leukemia and lymphoma, with intensive multiple agent induction, CNS prophylaxis, possibly radiation therapy to initially involved sites, and prolonged maintenance.


Echocardiographic estimation of aortic-valve gradient in aortic stenosis. Fifty-five consecutive patients with aortic stenosis underwent echocardiography at the time of cardiac catheterization. Left ventricular systolic pressure was estimated from the echocardiogram assuming that peak systolic circumferential was stress was constant. Systolic blood pressure was substracted from the estimated left ventricular pressure to obtain the aortic-valve gradient. Of 44 patients with adequate echocardiograms and catheterization studies, 30 had their aortic gradient accurately estimated by the echocardiogram (r = 0.75). All 30 patients had normal left ventricular systolic function estimated echocardiographically. The echocardiogram underestimated the aortic gradient in all seven patients with poor left ventricular systolic function. An accurate echocardiographic estimate of aortic-valve gradient can be obtained in patients with normal left ventricular function. The technique can identify those patients with insignificant left ventricular outflow obstruction, thereby obviating the need for invasive studies.


Elevated urinary prostaglandins and the effects of aspirin on renal function in lupus erythematosus. We studied the urinary excretion of immunoreactive prostaglandin E-like material (iPGE) and renal function in seven women with systemic lupus erythematosus to evaluate the relation between urinary iPGE and the increase in serum creatinine in patients taking aspirin. The mean pretreatment excretion of urinary iPGE in patients with lupus erythematosus, 42.7 +/- 6.4 ng/h, was significantly higher than the value of 29.0 +/- 1.9 ng/h for normal subjects (P less than 0.02). With aspirin, the urinary iPGE decreased an average of 45% (P less than 0.001). Increases in serum creatinine and blood urea nitrogen confirmed our previous clinical observations. The concomitant mean fall in creatinine clearance of 18% (P less than 0.001) was accompanied by a 14% decrease in inulin clearance (P less than 0.005); p-aminohippurate clearance fell 29% (P less than 0.005). The decline in urinary iPGE preceded the fall in creatinine clearance but was significantly correlated with it (r = 0.78; P less than 0.001). The observed changes reversed rapidly when aspirin was stopped. These data show that, in these patients with high urinary iPGE excretion, aspirin causes significant changes in renal function that may be mediated by the inhibition of prostaglandin synthesis.


A behavioral treatment of alcoholic methadone patients. Alcoholism is a frequent complication of methadone treatment and is one of the few behaviors found to correlate with methadone treatment failure. To eliminate drinking among severely alcoholic patients, we tested the efficacy of incorporating methadone into a behavioral contingency to reinforce disulfiram ingestion. Methadone was dispensed to alcoholic narcotic addicts contingent upon their ingesting disulfiram, and as a control patients were urged to take disulfiram but received methadone regardless of whether they took disulfiram. The results indicated that the reinforced disulfiram treatment was highly successful in controlling alcoholism. In addition, nonstatistically significant trends suggested that the reinforced disulfiram treatment resulted in a superior adjustment, as reflected in arrest rate, unemployment, and illicit drug use. There appeared to be no significant physiologic or behavioral adverse effects.


Acromegaly and galactorrhea-amenorrhea with two pituitary adenomas secreting growth hormone or prolactin. A case report. A prolactinoma was removed from a nulliparous woman who had acromegaly, galactorrhea-amenorrhea, elevated serum growth hormone and prolactin, and hypogonadotropinism. Postoperatively galactorrhea decreased and cyclic vaginal bleeding ensued; serum prolactin concentration was normal but growth hormone remained elevated and the acromegalic complex was unchanged, even after subsequently administered bromocriptine. At a second transsphenoidal operation, an adenoma of somatotropes was removed; improvement in symptoms and signs and normalisation of pituitary function, including growth hormone, followed. The possible presence of distinctly separate pituitary adenomas should be considered in patients with galactorrhea associated with acromegaly.


Glucose-induced hyperkalemia with normal aldosterone levels. Studies in a patient with diabetes mellitus. A diabetic patient exhibited glucose-induced hyperkalemia despite normal plasma and urinary aldosterone levels. The patient received no diuretics, was not acidotic, and had a creatinine clearance of 39 ml/min. Insulin or pharmacologic doses of desoxycorticosterone acetate eliminated the glucose-induced hyperkalemia. Normal aldosterone levels may be insufficient to protect certain diabetic patients from glucose-induced hyperkalemia.


Interstitial pneumonia from mitomycin.

Interstitial pneumonia from mitomycin. Pulmonary disease has been associated with several chemotherapeutic agents but has not been reported in patients receiving the alkylating agent mitomycin (Mutamycin). We describe here the cases of three patients who developed interstitial pneumonia while receiving mitomycin therapy. Their clinical features including dyspnea, cough, and occasionally fever; reticular infiltrates were seen on chest roentgenogram. Histologically, diffuse alveolar septal edema, mononuclear-cell interstitial infiltrates, hypertrophy of alveolar lining cells, and alveolar septal collagen deposition were characteristic. Treatment with corticosteroids was associated with a rapid therapeutic response in all three patients.


Prevention of involutional bone loss by exercise. To ascertain whether exercise could prevent involutional bone loss, we studied 18 postmenopausal women, half of whom exercised for 1 h three times a week. Total and regional bone mass were measured before and after 1 year of exercise by the techniques of total-body neutron activation analysis (total body calcium) and photon absorptiometry (bone mineral content) of the distal radius. Total body potassium was measured by whole body counting. Bone mineral content and total body potassium did not change significantly in either group. Total body calcium increased in the exercise group from 781 +/- 95 g of 801 +/- 118 g (SD). In contrast, total body calcium decreased in each subject in the sedentary group. The daily calcium balance derived from the difference in total body calcium measurements was significantly different in the two groups of women (P less than 0.001). These data support the hypothesis that exercise can modify involutional bone loss.


Aprindine hepatitis.

Aprindine hepatitis. We have seen two patients whose hepatitis was due to the administration of aprindine, a new antiarrhythmic agent. In both patients evidence of hepatitis appeared within 3 weeks of initiating aprindine therapy and resolved rapidly when the drug was withdrawn. The reintroduction of aprindine in one patient was associated with the reappearance of hepatitis, which resolved despite continued administration of the drug.


Influenza vaccine: preliminary statement. Recommendation of the Public Health Service Advisory Committee on Immunization Practices. The primary influenza vaccine for 1978-79 will be an inactivated trivalent preparation of antigens representative of the three currently prevalent influenza viruses. A monovalent vaccine will also be produced if needed for optimum immunization of any population group. Annual vaccination is recommended for persons of all ages who have various chronic conditions. Physicians should evaluate pregnant women for influenza immunization according to the criteria applied to other persons.


[Circulating immuns complexes and infections endocarditis. 64 cases (author's transl)]. An immunological study, with examination for circulating immune complexes (CIC) by precipitation by polyethylene-glycol (PEG) and by fixation of labelled C1q, was carried out in 64 patients with infectious endocarditis (IE). One or more complementary studies during the course of the illness were possible in 23. CIC were found in 84 p. 100 of cases (66 p. 100 of acute IE and 89 p. 100 of subacute IE), during the active phase of the disease. High levels of PEG precipitate were correlated with typical cutaneous signs (including Osler's nodes), with the presence of cryoglobulins. With effective antibiotic treatment, the level of PEG precipitate (17 patients) returned to normal within one month, in parallel with a fall in rheumatoid factor and in cryoglobulins. By contrast, ineffective treatment was invariably reflected (6 patients) by a rise in levels of PEG precipitate. The estimation of CIC using the PEG technique during IE would already appear to be a value aid in cases of difficult diagnosis, and a research area worthy of further exploration within the context of IE.


Chevalier Jackson Lecture. Analysis of new optical systems in bronchoesophagology. A new image transmitting system (Hopkins rod lens) made it possible to redesign the entire armamentarium of rigid broncho- and esophago- laryngology. The introduction of an optical biopsy forceps made tissue sampling more accurate. The increased light transmission produces a brighter image and easier perception. The larger viewing angle facilitates orientation. The new miniature pediatric bronchoscope, with a telescope, changed the pinpoint vision to a panoramic view. The optical foreign body forceps is of great help in fast and precise manipulations. The indirect laryngoscope proved to be a great investigative tool with the capability to obtain, with ease, a movie filmstrip for detailed analysis in the outpatient clinic. The introduction of the flexible fiber bronchoscope brought new dimensions in tissue sampling of peripheral lesions, treatment of pulmonary complications in the intensive care units, and became an important aid in intubating patients with difficult anatomy. The possibility to obtain moive films and to study our visual findings, at leisure, is an important diagnostic and teaching aid.


Sputum cytologic diagnosis of upper respiratory tract cancer. Sputum cytologic testing has been applied in the screening of high-risk individuals for presymptomatic lung cancer. This same screening procedure sometimes identifies patients with upper respiratory tract cancers and thereby may permit earlier treatment. Patients enrolled in the Mayo Lung Project undergo sputum cytologic and chest roentgenographic screening at four-month intervals and are compared with matched controls who are not intensively screened. Experience to date indicates an incidence rate of approximately 1 per 1,000 per year of cancer in the upper respiratory and alimentary passages among males more than 45 years old who are heavy cigarette smokers. This compares with a rate of approximately 4 per 1,000 per year of lung cancer. Recognition of early cancer of the upper respiratory tract is an additional benefit of screening for lung cancer. Since cigarette smoking represents an etiologic agent common to both upper and lower respiratory tract cancers, tumors should be searched for in both sites in this high-risk population.


Mucociliary transport.

Mucociliary transport. Our laboratory has developed bronchofiberscopic and roentgenographic techniques to measure tracheal, bronchial and nasal mucus velocities in humans and animals. We found that inhalation of specific antigen is associated with depression of tracheal mucus velocity in dogs who may or may not display bronchospasm and the mediator for this phenomenon might be SRS-A. Corroboration of the depression of tracheal mucus transport after ragweed inhalation has been obtained in susceptible asthmatic patients; prior inhalation of cromolyn blocks this reaction. Depression of tracheal mucus transport may be the earliest adverse manifestation of cigarette smoking in young subjects. Slowing of mucus transport in the bronchi occurs after suctioning with suction catheters; a newly designed suction catheter tip, the Aero-Flo, displays less adverse effects on mucus velocity than standard end hold and side hole catheters. Nasal mucus velocity is enhanced by nasal decongestants, ingestion of hot fluids and exercise.


Epiglottitis. Twenty-year study with tracheotomy. One hundred and seventy patients with acute epiglottitis were admitted to the Childrens Hospital of Los Angeles between the years 1957 to 1977. No deaths occurred in any of these patients, all of whom were treated with tracheotomy to support and ensure the airway. The records of 147 of these patients were available for review. No serious complications occurred from tracheotomy in any of the patients in this study. Tracheotomy is a safe method for caring for the airway problem in epiglottitis in a setting such as is available at the Childrens Hospital of Los Angeles. The median range of total days with tracheotomy was five to six days, and the median range for total days of hospitalization was six to seven days. Complications were never severe and in the extreme, merely prolonged hospitalization by a few days. This highly lethal disease is curable with antibiotics and an artificial airway, and it is questionable whether conservative medical measures with observation should be acceptable. The establishment of an airway, whether by tracheotomy or endotracheal intubation, is mandatory in the treatment of this disease.


Effects of various drugs on canine tracheal mucociliary transport. A study of the effects of dehydration, atropine, terbutaline and N-acetylcysteine on canine tracheobronchial mucus is presented. Mucociliary clearance rates, mucus secretion volumes and mucus rheologic properties were studied. Clearance rates were studied by a radioisotope technique, mucus collected by a canine "tracheal pouch" method and rheologic studies performed on a microrheometer. Clearance rate was unaffected by dehydration and terbutaline, increased by N-acetylcysteine and decreased by atropine. Secretion volume was increased by terbutaline while dehydration and atropine were without effect. Rheologic factors were increased by dehydration and atropine while terbutaline was without an effect. The effects of N-acetylcysteine on secretion volume and rheologic properties could not be studied because of the  nature of the techniques employed.


Vascularized hyoid interposition for subglottic and upper tracheal stenosis. Chronic subglottic and upper tracheal stenosis can be treated successfully with lumenal augmentation using a vascularized hyoid-sternohyoid muscle interposition into the stenotic area. Successful decannulation was achieved in eight of nine patients. Follow-up periods varied from 6 months to 36 months. Concomitant laryngeal stenosis and vocal cord paralysis were treated successfully at the same time. The major complication was occasionally delayed but successful decannulation due to granulation tissue. Minimal wound and peritracheal stoma infections probably accounted for the granulation tissue.


Aortic arch anomalies in adult disorders of deglutition. Congenital vascular anomalies of the aortic arch are unusual etiologies of dysphagia in the adult. Swallowing abnormalities associated with compression of the esophagus primarily occur at birth or in the immediate neonatal period. However, as the result of arteriosclerotic vascular disease or aneurysm formation, anomalies which were asymptomatic postnatally may produce dysphagia in the adult. A retrospective analysis of 59 cases with aortic arch anomalies presenting initially in adulthood revealed characteristic clinical signs and symptoms. An aberrant right subclavian artery with left aortic arch was the most frequently encountered abnormality. The embryologic development of each vascular anomaly is described and the value of selective arteriography with contrast esophagography is stressed. Patients with minimal swallowing impairment are treated with dietary management alone. Surgical division of the anomalous artery is indicated only when severe dysphagia is associated with progressive life-threatening anorexia and weight loss.


Traumatically acquired conditioned dysphagia in children. A new diagnosis identifying a nonorganic basis of dysphagia is proposed in relation to behavioral conditioning processes and thereby labeled "conditioned dysphagia" (CD). Literature review of both animal and human studies documents that rapidly acquired and persistent avoidance responses are learned when autonomic functions are contiguous with traumatic physical events. Three case studies with primary diagnoses of TE fistula, congenital heart disease and pseudobulbar palsy demonstrated an association between CD and early childhood incidence of trauma involving the esophagus. Successful treatment was achieved by operant deconditioning therapy. Results of a pilot epidemiological study of 28 postpharyngeal flap surgery children and 47 controls showed significantly higher incidence of mild to moderate CD in the surgery group.


Unsuspected foreign bodies of the aerodigestive tract. The well-known tendency for children to place loose objects in their months not infrequently leads to the entrapment of foreign bodies in the aerodigestive tract. With prompt and adequate removal few complications occur. However, when the foreign body goes undetected or is neglected the patient may develop dysphagia, pneumonia, failure to thrive, lung or mediastinal abscesses, bronchopulmonary or bronchoesophageal fistulas, or erosion of major vessels. Fifteen cases of retained foreign bodies were identified in a chart review between 1971 and 1977 at the Children's Hospital of Philadelphia, calling attention to the problems of aerodigestive foreign bodies of prolonged duration. Early and late complications are discussed and early diagnosis and endoscopic removal emphasized.


Case for pneumatic dilatation in achalasia. A standardized method of performing pneumatic dilatation for the treatment of achalasia is described. Twenty-five patients were treated in this manner and 80% had excellent results. There was minimal morbidity and no mortality. Pneumatic dilatation is recommended as the primary procedure for achalasia as it is a simple and safe procedure which avoids unnecessary surgery. Local topical anesthesia, rather than general, is utilized and hospitalization time is two days, rather than the 14 days required following surgery. The Heller operation can be performed when pneumatic dilatation is unsuccessful.


Functional diseases of the esophagus: role of endoscopy. The use of endoscopic procedures in the evaluation of primary motor disorders, or functional diseases, of the esophagus is filled with both risks and benefits. Since both flexible and open-tube esophagoscopy carry a significant risk factor, it is necessary to have a clear concept of the indications and value of endoscopy in the management of functional diseases of the esophagus. A review of the literature reveals very little documentation on the value of endoscopy in diagnosing esophageal functional diseases other than Zenker's diverticulum and achalasia. Based on the current literature and the experience of the authors, observations and recommendations concerning the role of endoscopy in functional diseases of the esophagus are presented. These are: 1) In Phase I or upper esophageal sphincter dysfunctions, endoscopy contributes little to their understanding, is difficult to perform, and may be hazardous. In this group, esophagoscopy should be reserved for indications beyond the dysfunction itself. If endoscopy has to be performed, open-tube esophagoscopy should be performed by an experienced endoscopist. 2) In functional diseases of the esophageal body or Phase II dysfunction, endoscopy is frequently valuable. In spastic disorders, it helps to differentiate between primary spasm of neuromuscular origin and spasm secondary to esophagitis or an obstructive process. In scleroderma and pulsion diverticulum, endoscopy helps to identify such unsuspected complications as esophagitis, hiatal hernia, and carcinoma. 3) In Phase III or however esophageal sphincter dysfunctions, endoscopic examination is essential both to rule out organic lesions that stimulate functional disorders, and to determine the presence and extent of esophagitis.


Ultraviolet-fluorescence bronchoscopy in early detection of bronchogenic carcinoma. The still unsatisfactory prognosis of bronchogenic carcinoma prompted the search for possibilities of better early and detailed diagnosis. This led us to the idea of UV-fluorescence bronchoscopy. The patient inhales 5 ml of an aqueous 5% solution of fluorescein, together with a beta2 stimulator, 10-15 minutes before the bronchoscopy, by means of a pressure inhaler. While the normal mucous membrane cleanses itself by virtue of ciliary action (secretions containing fluorescein are expectorated or drawn off during the bronchoscopy), carcinoma, carcinomatous lymphangiosis, superficial tumor infiltrations and nonciliated metaplasias are stained. These places fluoresce in UV light, even when they cannot be observed with the naked eye or with an optical system. In this way, they are made visible for directed biospy. Malignant changes not discernible by means of the methods hitherto employed can thus be diagnosed and sites determined with greater accuracy for proposed resection.


Effect of topical anesthetics on ciliary activity of chicken embryo tracheal origin cultures. Study using total immersion and intratracheal injection. Because of conflicting reports concerning the effect of topical anesthetics on cilia, testing of four different agents was undertaken. The agents were hexylcaine 5% (Cyclaine), tetracaine 2% (Pontocaine), cocaine 5% and 10%, and lidocaine 4% (Xylocaine). Tracheas were removed from 19 to 20 day old chicken embryos. Ciliary activity was graded as to extent and vigor. Two methods of testing were used. In the first, dilutions of each agent were made, and tracheal rings were placed in the wells of microtiter plates and completely covered with the test drug. In the second method of testing, 0.8 ml of the test drug was injected in vivo into the exposed trachea of the embryo. In immersion testing, cilia stopping effect (CSE) in tracheal rings was noted in all drug dilutions tested within 1 to 20 minutes. When the drug was injected directly into the trachea, a complete CSE was noted the next day in the rings from the tetracine and hexylcaine injected tracheas. Three days following in vivo transtracheal injection of lidocaine and cocaine, ciliary activity in these and the control rings was similar. Although cilia did not tolerate total immersion in any of the agents tested, ciliary activity in tracheas injected with lidocaine and cocaine did not differ significantly from the control tracheal rings. Physicians who use topical anesthetics should be aware of this.


Biomechanical characteristics of the canine trachea. The trachea is a dynamic organ that responds to the demands of deglutition, respiration, and gravity. Following tracheal resection, reconstruction should allow the trachea to assume its dynamic functions. Experiments in dogs revealed that mercury-in-silastic strain gage apparatus can successfully be used to measure the biomechanical dynamics of the trachea and subglottis. The upper tracheal segments assume a larger stress load than the lower tracheal segments following tracheal resection.


Insufflation esophagoscopy.

Insufflation esophagoscopy. A new electroscope has been designed from the conventional Haslinger tubes. The new rigid scope combines the advantage of air insufflation in the flexible system with the therapeutic possibilities of the rigid tubes and is trustworthy in the following esophageal procedures; a) finding entrance of severe strictures; b) introducing nasogastric feeding tubes; c) extraction of foreign bodies; d) tumor coagulation/spur in hypopharyngeal diverticuli; e) washing and suction in cases with severe food retention; f)making tumor smears in patients with clotting disorders; g) taking substantial biopsies with an optical forceps, and h) objective photodocumentation of esophageal pathology.


Mediastinoscopy: the predictive survival value in staging carcinoma of the lung. One hundred and thirty-seven cases of Stage III lung cancer established by mediastinoscopy have been followed to determine their survival. The tissue was classified according to World Health Organization schema and the degree of dedifferentiation graded from well to poorly differentiated. Two percent of the presented cases are well-differentiated tumors; the remaining 98% are moderately well-differentiated (11%), or poorly differentiated or small cell tumors (87%). The degree of anaplasia suggests an increasingly aggressive metastatic behavior pattern. The average life span is approximately 5 1/2 months in all groups and subgroups which were studied. Recommendations are presented for the utilization of mediastinoscopy in Stage I and II cases. Further considerations are suggested for priority of diagnostic procedures in establishing the diagnosis of lung cancer.


[Comparative study of hematoporphyrin and psoralen effects on fibroblasts after black light irradiation (author's transl)]. The inhibitory effect of photosensitized substances such as psoralen and haematoporphyrin on fibroblast cultures of mice irradiated with black light has been studied by autoradiography and scintillation. Psoralen and haematoporphyrin used in constant concentrations produce significant changes in the captation of thymidin after 8 minutes' time of irradiation. The inhibitory effect of psoralen can be superposed to the one produced by haematoporphyrin and is increased when both substances intervene at the same time.


[Vertical striated sand-papered twenty-nail dystrophy (author's transl)]. Vertical striated sand-papered twenty-nail dystrophy, an entity observed in both children and adults, is suggestive of an expression of alopecia areata. When the vertical striated sand-papered effect is not uniformly distributed over the full surface of the nail plates the disorder may be caused by lichen planus.


Electrocochleographic study of sudden deafness. By performing electrochleography (AP, SP and CM) on 34 patients with sudden deafness, it was thought that the pathophysiology of this disease could be deduced. The various waveform patterns of AP and SP responses obtained in cases of sudden deafness were classified into the following types: 1) AP high response; 2) decreased AP high response; 3) AP low response; 4) dominant -SP; 5) -SP or +SP; and 6) AP, SP no response. The cases showing the type of dominant -SP and AP high response had satisfactory prognoses. In these cases the sensory epithelium and the cochlear nerve seemed to indicate a reversible condition being affected by the temporary functional block. Furthermore, it seemed to indicate that the neural regions related to the source of AP(N1) response were impaired in cases in which CM were recorded at normal response threshold in spite of the absence of AP(N1) response. In the unsatisfactory prognosis cases with decreased AP high response, AP low response and AP, SP no response in which only the extremely low or depressed CM responses could be recorded, it seemed that the sensory epithelium and the cochlear nerve were affected permanently, although the degree of impairment varied.


[Quantitative ultrastructural study of the epidermis basal layer in the vitiligo patches and in the marginal hyperchromic and normal skin (author's transl)]. To avoid any bias, the ultramicroscopic examination was performed by the morphologist without knowing whether the material examined was from the vitiligo patch or from the marginal hyperpigmented and normal skin. Only at the end of the investigation, he was informed about the code of the material. He had also been informed about the possibility of receiving skin biopsies from a patient without vitiligo, what in fact was done with the inclusion of one case of albinism. Six cases of vitiligo have been studied. The melanocytes usually have not been observed in the vitiligo patches, where a variable number of Langerhans cells were seen. In the melanocytes reached about 17 p. 100 of the cellular population; Langerhans cells were absents. In the marginal normal skin the average proportion of melanocytes was near 10 p. 100 of the cellular population and the Langerhans have been observed only in one case (1.8 p. 100 of the population). Regarding the keratinocytes of the marginal hyperpigmented and normal skin, respectively 75 p. 100 and 59 p. 100 contained melanin; in the vitiligo patches only in one case keratinocytes contained melanin (2.8 p. 100 of the keratinocytes population as an average).


[Urinary evaluation of 5-S-cysteinyldopa and seric evaluation of IgG4 subclass during follow-up of 27 primitive malignant melanomas (author's transl)]. 27 patients with SSM or NM level IV and V have been submitted to a monthly evaluation of their level of 5-S-cysteinyldopa in the urine and IgG4 subclass in their sera. For 5 patients who entered the stage II of their disease during the follow-up, 3 had elevation of the 5S and 5 had large variations of IgG4. On 21 patients in clinical remission, 10 had conjunctly an increase of 5S and variations of IgG4. The predictional value of these tests is discussed.


[Apocrine cystadenoma. About 3 observations with one balanic localization (author's transl)]. Description of three apocrine cystadenomas: two of the face and scalp and one of the glans (urethral meatus and left anterior surface of the navicular fossa) with no bibliographical precedent. From a clinico-histological standpoint the importance of objective data which make possible the clinical diagnosis is stressed allowing light microscope differentiation from eccrine hydrocystoma. The histogenesis is exposed and it appears convenient to name (eccrine or apocrine) cystadenoma the authentic cystic adenoma (among the organoid hamartoma of the cutaneous appendages, while reserving the term (eccrine or apocrine) hydrocystoma for glandular cysts. Due to the esthetic and occasionally functional repercussion, surgical excision is indicated.


[Stefansky's serodiagnosis and ulcerative and mutilating acropathy (author's transl)]. Systematic Stefansky's serodiagnostic test in the course of ulcero-mutilating acropathia reveals a frequent positivity (25/30 patients). Superinfection by atypical Mycobacterium of telluric extraction is considered. A delayed hypersensibility to several Mycobacterium antigens is proved to Mycobacterium kansasii, johnei, balnei. Perhaps, the same type of infection might exist in the course of chronic leg ulcers.


[Lamprene (Clofazimine) treatment of chronic lupus erythematoides (author's transl)]. Lamprene (Clofazimine) was administered over a period of three months, at a dose of 100 mg to 200 mg per day, to six patients with chronic lupus erythematosus. Remission was observed in these six cases, without any side-effect.


[Hypertrichosis in the malformative syndrome of Cornelia de Lange (author's transl)]. Some hypertrichoses are included in polymalformative syndroms. The authors, make a brief summary, about an observation of Typus Amstelodamensis.


[Keratosis follicularis spinulosa decalvans and amino-aciduria (author's transl)]. A new case of keratosis follicularis spinulosa decalvans (Siemens, 1925) in a 12 1/2 year old boy is related. This X-dominant inherited disturbance of follicular keratinization is associated with an amino-aciduria in the propositus and his mother, especially an increase of aspartic acid in urin and blood. The scarring infundibular plugs are constituted by nucleated keratin, which brightened up in polarized light and seems to be of internal trichilemmal origin.


Oestrogenic activity associated with ovarian cystadenomas after the menopause. In a group of 59 patients over the age of 55 years with ovarian serous and mucinous cystadenomas, a total of 29 (49%) showed moderate or strong oestrogenic activity as determined by maturation index in vaginal cytologic smears, in contrast to nine (13%) of 70 control patients with other gynecological disorders than ovarian tumours. The bacterial flora was dominated by Döderlein type bacilli in 24 of the 27 test patients with an elevated maturation index, also reflecting the abnormal oestogenic activity in these patients. When the serous and mucinous cystadenoma groups were compared, a striking difference was found: of the 30 patients with mucinous cystadenomas, 23 (77%) displayed moderate of strong oestrogenic activity, while this was the case with only six (21%) of the 29 patients with serous cystadenomas. These findings stress the importance of an abnormal oestrogenic activity, revealed by an elevated cytologic maturation index, as memento for the possibility of post-menopausal ovarian cystadenoma.


Treatment of premalignant lesions of the uterine cervix by means of moderate heat thermosurgery using the SEMM coagulator. 71 patients suffering from premalignant lesions of the uterine cervix and who were treated by the SEMM coagulator, is presented. The results are good, and at least equal to cryosurgery. The time of follow-up has been more than 2 years for 57 of the patients and more than 3 years for 39. Only in two cases has there been persistence or recurrence of suspicious cytology requiring new treatment, in one of them by conization and in the other by cryosurgery. One patient was hysterectomized for other reasons 2 years post-treatment, but no sign of persisting malignant or premalignant changes were found in the specimen. The method is judged to be a valuable alternative to conization and cryosurgery.


The development of "stagnant loop" syndrome following surgery for peptic ulcer disease. Although gastric resection may cause a variety of functional gastrointestinal disorders, malabsorption is rare. When such a disturbance occurs other complicating factors are mostly involved. Two patients who developed a severe malabsorption after partial gastric resection are presented. They both had the prerequisites for intestinal stasis--one had small bowel diverticula and the other a "blind loop" after previous surgery. Their malabsorption was cured by surgical correction of stasis.


The excretion of trace metals in human sweat. The concentrations of zinc, copper, iron, nickel, cadmium, lead, manganese, sodium and chloride in the sweat of six males and three females were determined after collections utilizing a total body washdown technique. From our results, sweat appears to be an important excretory pathway for zinc and copper. The mean concentrations of nickel and cadmium in sweat were higher than those reported for urine, that of lead was similar to urine. The loss of manganese in sweat is significant. Levels of zinc and iron were lower in sweat from females, possibly reflecting compensation for menstrual and other losses. Collections were made in six subjects simultaneously utilizing a total body washdown method and collections from one arm in an occlusive arm-bag. The arm-bag collection method gave higher and more variable results and is not recommended as an indicator of loss from the entire skin surface.


Plasma steroid dynamics in Cushing's syndrome. The dynamics of five plasma steroids were studied by CPB and RIA in twenty patients with Cushing's syndrome of differing etiologies: pituitary induced adrenal hyperplasia (10), recurrence after adrenal surgery or pituitary irradiation (4), adrenal carcinoma (4) and adrenal adenoma (2). Basal mean values of plasma steroids, showed increase of cortisol in hyperplasia and cancer groups, increase of 17-hydroxyprogesterone (17-OH-P) in recurrence and cancer groups and decrease of testosterone in male patients. In hyperplasia, the changes in 11-desoxycortisol and 17-OH-P (respectively by CPB assay and RIA after LH-20-Sephadex separation) were the reverse of those for cortisol 2 h and 24 h after metyrapone administration. Adrenalectomy determined in all but one patients, significant decrease of cortisol and in male patients, parallel gradual increase of testosterone.


Thyroglobulin complementary DNA as a means to investigate congenital goiters with impaired thyroglobulin synthesis. A congenital goiter with impaired thyroglobulin synthesis has been investigated for the presence of messenger RNA coding for thyroglobulin. Using complementary DNA to beef 33 S thyroglobulin mRNA as a probe, we have found that thyroglobulin related sequences are present in the goiter but at a concentration lower than in normal human thyroids. We conclude that the disease is not due to a complete deletion of thyroglobulin gene.


Hereditary disorders of albumin synthesis. Albumin, the major serum protein, is considered to be responsible for maintenance of normal serum colloid osmotic pressure, transport of certain hormones and maintaining an endogenous source of amino acids. The acute loss of albumin in the nephrotic syndrome leads to severe generalized peripheral edema and difficulties in maintenance of normal blood pressure as well as hypocalcemia. Yet, there are now 14 reported cases of congenital analbuminemia in which serum albumin is absent or greatly reduced without clinical evidence of edema, decreased hormone levels or abnormal amino acid requirements. These "experiments of nature" are reviewed in detail comparing clinical and laboratory findings in these patients with the postulated effects of a low serum albumin level.


The hypogammaglobulinemias.

The hypogammaglobulinemias. The immunoglobulin system initially evolved as a defense system to maintain genetic stability during evolution. Studies in the past two decades have resulted in the elucidation of immunoglobulin structure and the definition of their chemical composition. Disorders of immunoglobulin production have led to an enhanced understanding of the functional aspects of immunoglobulin chemistry. The recognition of these disorders has enhanced our knowledge of antibody specificity and led to the development of immunochemical techniques such as radioimmunoassay as well as the development of techniques of transplantation and immune reconstitution in man.


[Hypertrophy and hyperplasia of hyperactive thyroid cells: hormonal secretion is independent of apical phagocytosis (author's transl)]. Hyperactive thyroid are obtained by daily injections of TSH 15 I.U. I.M. in dogs for 8 days. The high secretion rate of butanol-extractible iodide (BE125I) in vitro by prelabelled slices is not related to apical phagocytosis (lack of apical pseudopods and intracellular colloid droplets, insensitivity to cytochalasin, vinblastine, vincristine and colchicine). The secretory process is insensitive to metabolic inhibitors, decreases exponentially with the temperature without step transition and could be related to micropinocytosis.


Renal handling of proteins and peptides. The kidney plays an important role in the metabolism of proteins and peptides. Current evidence indicates that only the proximal tubule possesses the mechanisms for absorption, transport and/or degradation of these substances. Large proteins and polypeptide molecules filtered by the glomerulus, are absorbed from proximal tubular fluid by luminal endocytosis into apical vacuoles which fuse with primary lysosomes where hydrolysis occurs followed by diffusion of metabolites out of the cells and into the blood. Recent evidence indicates that small peptides are handled by a different mechanism. It appears that small peptides are degraded at the luminal surface of the brush-border of proximal tubules, which contains many hydrolytic enzymes, by the process of membrane or contact digestion with reabsorption of the breakdown products. Proximal tubular mechanisms for handling of proteins and peptides are probably important biologically to conserve amino acids, inactive toxic substances and help regulate the circulating level of protein and peptide hormones.


[Sialic acid content of human thyroglobulins iodinated at different levels (author's transl)]. Sialic acid and iodine content were measured on 53 thyroglobulins from normal and pathological tissues. Sialic acid is significantly decreased in isolated cold nodules, and highly reduced in hot nodules and toxic adenomas. In these pathological situations, sialic acid defect could interfere with the iodination of the molecule.


Role of metallothioneins in copper transport in patients with Menkes syndrome. Fibroblasts from infants with Menkes kinky hair syndrome, which accumulate excessive quantities of copper, are thought to represent a disorder of copper storage or transport. Because of this abnormality, it was thought that they might provide a useful system for investigation of the presumed storage or transport protein metallothionein. Data are presented which are consistent with defective copper efflux from the mutant cells. Because of the more specific role of metallothionein in cadmium detoxification, studies of cadmium metabolism were undertaken which demonstrated abnormal cadmium retention and metallothionein induction in the mutant cells. The association, therefore, of a defect of cadmium metabolism and storage with an abnormality of copper efflux provides evidence implicating metallothionein in copper transport for fibroblasts.


[Amiodarone-induce "low T3-syndrome" (author's transl)]. Amiodarone induces in patients "low T3-syndrome" characterized by normal T4. T3 resin uptake and free T3, contrasting with low T3 and free T4 values, and enhanced concentration of r-T3.


An automated bichromatic measurement of serum immunoglobulins. A new, rapid, discrete sampling and automated bichromatic procedure for the measurement of various soluble antigen-antibody complexes of immunoglobulins is described. The incorporation of polymeric substances and salts into the reaction mixture has greatly increased the sensitivity, shortened the reaction time and decreased the cost of the tests. Statistical analyses of data from this method have shown them to correlate well with values obtained by a radial immunodiffusion procedure. The automated procedure is simple and specific, it can be run at a rate of 90 specimens an hour.


Unusual features of thyroid function in anterior pituitary failure. Endocrinological studies have been performed in 40 cases of adult hypopituitarism. In 5 cases, unusual features of thyroid function were observed, characterized by the coexistence of low levels of circulating thyroid hormones with a normal thyroid uptake and in 4 cases, a significant secretion of TSH.


[Pathogenesis of endemic goiter: evidence of a dietary factor different from iodine deficiency (author's transl)]. The role of cassava was investigated in particularly severe endemic goiter area (Ubangi). Dietary intake of cassava induces an increase of plasma thiocyanate concentration and an increase of urinary excretion of stable iodine. Generalized iodine deficiency induces very high thyroid uptakes; the other parameters of thyroid function are more or less affected according to the dietary intake of thiocyanate. When thiocyanate intake is high an adaptation is obtained only at the expense of a drop of plasma T4 level and very high increase of plasma TSH.


[Plasma oxytocin levels during lactation (author's transl)]. During suckling, endogenous plasma oxytocin levels were repeatedly determined by RIA. They showed rapid fluctuations varying from 10 to 129 muU/ml. This suggests spurt releases of ocytocin of an order of magnitude of 10 to 100 mU.


[Lipidogen effect of sorbitol with saturated fat in the diet of the male rat (author's transl)]. In the male rat, sorbitol, beef fat nor M.C.T. in the diet provoke hypertriglyceridemia but the association sorbitol-beef fat and sorbitol-M.C.T. significantly rise the triglyceridemia and the cholesterolemia. In the castrated male rat estrogens provoke a considerable rise of the triglyceridemia and the cholesterolemia with the diet enriched in M.C.T. but not modify the hypertriglyceridemia and the hypercholesterolemia provoked with the diet enriched with the association sorbitol-T.C.M.


Metabolism of testosterone by isolated semiferous tubules and interstitial tissue of rat testes. In prepubertal rat testes the main metabolisation of testosterone, which consists in 5alpha-reduction, is located predominantly in the Leydig-cells and is low in the seminiferous tubules. In adult rats, this metabolisation pattern has shifted to increased 7alpha-hydroxylation which is located mainly in the Leydig-cells, while 5alpha-reduction is performed in the seminiferous tubules. After prolonged treatment with HCG the 7alpha-hydroxylase activity in the Leydig-cells is strongly depressed while the metabolism of the seminiferous tubules is not influenced.


Influence of prolonged HCG administration on testicular steroids of hypophysectomized rats. Prolonged administration of HCG provokes both in normal and in hypophysectomized rats a shift of testosterone metabolism in incubated testes from predominating hydroxylation to reduction processes, indicating that this HCG effect can occur in the absence of the hypophysis.


Gastrin secretion in Addison's disease.

Gastrin secretion in Addison's disease. Out of a score of patients known as suffering from Addison's disease, tuberculosis was the cause in 7, and their serum fasting gastrin levels were normal, averaging 52 pg/ml. For the 14 remaining cases, with the auto-immune variety of the disease, there were high gastrin levels in 3; in 2 out the 11 others, with values within the normal range, there was total achlorhydria. Could it be that gastrin-secreting cells might occasionally be involved in auto-immune endocrine disorders?


[Serum thyroid hormones in hyperthyroid patients treated with carbimazole (author's transl)]. Serum thyroxine (T4), triiodothyronine (T3) and thyrotropin (T.S.H.) were measured in 32 hyperthyroid patients treated with carbimazole. A discrepancy between serum T4 AND T3 was present in 73 of 131 measurements: --normal T3 with increased T4 in 6 measurements; --increased T3 with normal T4 in 16 measurements: five times only there was a clinical hyperthyroidism; --normal T3 with decreased T4 in 49 measurements: three times only there was a clinical hypothyroidism. Serum T.S.H. level was increased in 13 of 19 measurements made in this group, state named "compensated hypothyroidism" according to Patel and Burger.


Variations in the lung size of children in Papua New Guinea: genetic and environmental factors. In Papua New Guinea, rural village children of both sexes living in the highlands (1500--2000 m) were found to have mean values of forced vital capacity 27 per cent greater than children at sea level. Urban children with an apparently lower level of habitual activity had a lung size similar to that of rural children living at the same altitude. In a number of healthy children of coastal parents reared in the highlands and of highland parents reared on the coast, the size of the lung was, in general, appropriate for the altitude rather than for the parentage. These findings suggest that the highland--coastal difference is probably environmental rather than genetic in origin.


Body size and form of children of predominantly black ancestry living in West and Central Africa, North and South America, and the West Indies. Stature, sitting height, hip width, arm and calf circumferences and body weight have been measured in black children of Richland County, South Carolina. Lower limb height and three indices of body shape were obtained from the measurements. Sample size exceeded 200 for each of five age-sex groups representing girls and boys aged 6 years, girls and boys aged 9 years, and boys aged 11 years. Comparisons are made with findings from previous research on children of predominantly black ancestry living in west and central Africa, the West Indies, and North, Central and South America. Black children of Richland County measured during 1974--77 are taller than black children studied since 1960 in Angola, Chad, Ghana, Liberia, Nigeria, Senegal, Uganda, Anguilla, Barbados, Cuba, Guyana, Jamaica, Nevis, St. Kitts, St. Vincent, and Surinam. Children of well-to-do black families in Accra and Ibadan are no taller or heavier than black children of Richland County taken without regard to socio-economic status. In hip width, averages for Richland County black children are larger than those for children of the Hutu and Yoruba tribes; in arm girth they are larger than children of the Hutu and Tutsi tribes. Age changes and group differences are reported for hip width relative to lower limb height, and lower limb height relative to sitting height. During childhood, the hip/lower limb index decreases, and the lower limb/sitting height index increases. Almost identical hip/lower limb indices characterize black populations in Africa, Cuba, and the United States.


Handedness, hand-clasping and arm-folding in Israeli males. Comparative analysis of handedness, hand-clasping and arm-folding frequencies in four groups of adult Israel Jewish males of East European origin (N=562), Central European origin (N=165), Middle Eastern origin (N=191), and North African origin (N=163), indicates a significant similarity between the groups. A high percentage of left-handed individuals was observed in all groups except the Middle Eastern one. Right-hand clasping and left arm-folding predominated in all but the Central European group in which left hand-clasping predominated. When a comparison is made between individuals born in Eastern Europe and those born in Israel to parents of East European origin, the frequency of left handedness was considerably higher among the latter. This may be attributed to an inhibitory effect of the educational system on the expression of sinistrality in the first sub-group. Relationships between handedness and hand-clasping and between hand-clasping and arm-folding was also observed.


Growth of schoolchildren with early, average and late ages of peak height velocity. A sample of Swedish urban schoolchildren (357 girls, 373 boys) born in 1954/55 followed from 10 to 18 years were grouped according to peak height velocity age (PHV age) into early, average and late maturers. Mean heights differed between the maturity groups at ages from 10.0 to 14.0 years for girls and 10.5 to 17.0 years for boys. Mean weights differed between the maturity groups at all ages up to 16.0 years for girls and up to 18.0 years for boys. The earlier the maturity process, the heavier for given height. The time differences between peak weight velocity (PWV) and PHV significantly differed between early, average and late maturers amounting to 0.9, 0.5 and 0.2 years respectively for girls and 0.6, 0.3 and -0.1 years respectively for boys. The time difference between menarche and PWV did not differ between the maturity groups and amounted to about 0.6 +/- 0.05 years (SD = 0.9). For boys a similar lack of difference between maturity groups was obtained concerning the time difference between secondary sex characteristics; stage 4 (SSC IV) and PWV. Mean height and weight for girls and boys differed between the maturity groups at PHV but not at PWV, menarche or SCC IV.


The hypothenar radial arch and parathenar loop in palmar dermal topology: sex, bimanual and regional variation in samples from the British Isles. Consideration is given to the regular recording of parathenar distal loops (Pa) and hypothenar radial arches (Ar) in palmar dermal topology. Frequencies are given for four British populations (the North Pennine Dales, the Mid Welsh Borderland, Pembrokeshire and Ireland) and regional variation noted together with sex and bimanual differences. Both Pa and Ar occur infrequently in normal populations, generally in less than 5% of individuals, Pa significantly less than Ar. Both attributes are similar in that they are significantly more common on right than left hands and in females than males. Three out of twelve comparisons between the North Pennine Dales, Welsh Borderland and Pembrokeshire data attained formal significance, in each case in the males. The former two regions were distinguished for both Pa and Ar; the latter two for Ar. This is more than expected by chance at the 5% level.


The esterase D polymorphism in patients with diabetes or carcinoma of the bladder and a matched sample of non-donor controls. Results are reported for the Esterase D polymorphism in a sample of the general population from the Durham area. Gene frequencies agree well with those previously reported from the north of England. No differences are revealed when the sample is subdivided on the basis of age. No significant differences are observed between this sample and two disease series from the same region, one with diabetes, the other with carcinoma of the bladder. This holds true when the disease groups are considered with regard to current age, age at diagnosis, and in the case of the diabetic, current treatment.


Variation in blood pressure in a New Guinea population. The contributions of age and anthropometric, biochemical and socio-economic variables to blood pressure variation in the population of Karkar Island, Papua New Guinea are examined. Blood pressure does not change with age in males; in females there is a decline from ages 21 to 40 and an increase (in systolic pressure) thereafter. Body weight and skinfold thicknesses decline with age in females; arm circumferences decline in both sexes. There were no age effects on serum cholesterol or serum sodium. Variation in ponderal index and subcutaneous fat contribute to variation in blood pressure. The correlations of blood pressure with physique are more important in males and the particular variables concerned suggest a nutritional basis. The socio-economic variables examined showed little variation and this was not associated with variation in blood pressure.


A multinational Andean genetic and health program: growth and development in an hypoxic environment. In 1972 a multidisciplinary study sought to assess the health status of the indigenous peoples of the Department of Arica in northern Chile, the Aymara, and to relate disease, morphological, physiological and biochemical variation, to the wide changes in altitude of the region. Presented here are the morphological changes which accompany age, altitude and ethnicity amoung 1047 children and adults, permanent residents of the coast, sierra and altiplano. At comparable ages, high-altitude residents were shorter, lighter and leaner but with more expansive and rounder chests than sea-level controls. None of these effects was systematically related to ethnicity (Spanish-Aymara surname), although when stature was held constant, children with greater Aymara ancestry had largest chest circumferences and longer bones. These results suggest that (1) altitude confers allometric growth changes (expensive growth of the chest and diminished growth of the structures less related to oxygen transport); and (2) size changes associated with altitude are acquired during development while shape changes may be under genetic control. Altitude appears to account for less of the variation in growth in this relatively homogeneous Chilean sample than has been reported for other Andean samples, suggesting other concomitants confounding the effects of hypoxia in Andean South America.


The effects of sex, birthweight, birth order and maternal age on infant mortality in a Nigerian community. Corrected registration returns in a rural area of Nigeria show that the average infant mortality rate during one five year period was 88.2 per 1000 per annum. The rate was 89.4 per 1000 for females, which did not differ significantly from that of 87.0 per 1000 for males. There were significant variations in the rates by maternal age and by birth order. Forty-two per cent of the infant deaths were of low birth-weight, the mortality rate among this group being approximately six times as high as for those with greater weights.


A study of phenotypic arrays derived from seven genetic systems in an Australian population sample. The phenotypic arrays for seven erythrocyte antigenic systems of a sample of the Melbourne population were found to be distributed according to Zipf's Law. A simple model of heterozygote selective advantage was unable to account for the excess of observed frequencies of arrays over those expected under the random-mating hypothesis. Persons with (ccDEe, MMss) were over-represented and those with (A1, MNSs P1--) were under-represented in the sample.


A critical analysis of the double and triple logistic growth curves. Recently a model of human growth from the age of one year to maturity, based on two logistic terms, has been proposed. The originators of the model claim that it provides biologically meaningful parameters, and allows total growth to be partitioned into a pre-pubertal and an adolescent component. More recently, they have suggested an improved model, with three logistic terms, which gives a better fit. While the double logistic model gives an adequate fit to the observed height curve, differentiating it leads to a height velocity curve which differs considerably from the observed velocity curve. The triple logistic model gives an excellent fit to both the attained height and height velocity curves. Both models, however, imply a considerable time interval during which both the pre-pubertal and adolescent components are simultaneously contributing to growth, a situation that is difficult to justify biologically. The double model should therefore be discarded, and the triple logistic model considered to be of descriptive, rather than of interpretative, value.


Transient environmental changes and age-limited genes as causes of variation in sib-sib and parent-offspring correlations. Correlations between 116 adult siblings in soft tissue measurements (weight, muscle, fat) diminished with increasing age difference between members of a sibling pair. This did not occur for bone measurements. The estimated heritabilities of the latter are less likely to vary among samples drawn from different environments than are estimated heritabilities of soft tissue.


Differential inhibition of the products of the human alkaline phosphatase loci. 1. Inhibition studies have been carried out on a series of ALPs derived from liver, bone, kidney, placenta and intestine, using L-phenylalanine, L-homoarginine, L-leucine, L-leucyl-glycyl-glycine and L-phenylalanyl-glycyl-glycine as inhibitors. 2. No differences between liver, bone and kidney ALPs with any of the inhibitors were observed. 3. L-phenylalanine and L-homoarginine give a major degree of discrimination between liver/bone/kidney ALP on the one hand, and placental and intestinal ALPs on the other. L-leucyl-glycyl-glycine and L-phenylalanyl-glycyl-glycine give a major degree of discrimination between placental ALP on the one hand, and intestinal ALP and liver/bone/kidney ALP on the other. L-leucine discriminates between the three classes, but to a lesser degree. Minor degrees of discrimination between placental and intestinal ALPs occur with L-phenylalanine and L-homoarginine and between intestinal and liver/bone/kidney ALPs with L-leucyl-glycyl-glycine and L-phenylalanyl-glycyl-glycine. By using an appropriate combination of inhibitors the ALPs can be separated into three clearly distinct categories: placental, intestinal and liver/bone/kidney. 4. The six common placental ALP phenotypes as defined by electrophoresis show identical inhibition profiles with the series of inhibitors. The same profile was found for several rare electrophoretic variants. However, two rare electrophoretic variants (P-187 and P-92) each encountered once in a sample of 225 plancentae, showed significantly deviant inhibitions with the various inhibitors and also differed from each other. From the electrophoretic patterns, both of these rare phenotypes appear to be heterozygotes. P-187 probably corresponds to the so-called D-variant previously described. P-92 represents a new type of placental ALP variant with an aberrant inhibition profile. In both cases the particular rare allele concerned evidently alters the primary structure of the enzyme so that it has an altered electrophoretic mobility and also an altered sensitivity to inhibition for each of the different inhibitors. 5. Treatment of the various ALPs with neuraminidase to remove sialic acid residues does not affect their inhibition characteristics or activities.


Characteristics of simple sibship variance tests for the detection of major loci and application to height, weight and spatial performance. Simple methods have been proposed as screening tests for major loci. These methods rely primarily upon the detection of differences in within sibship variances expected for segregating and non-segregating sibships when a major locus is present. In the present study, computer simulation was used to investigate power and robustness of the test statistics. Power of the analyses depends upon the specific major locus model, but, in general, their application is quite practical for small samples. The test statistics were shown to be sensitive to deviations from normality, but robust under the conditions of either a polygenic or environmental model. Application of the test procedures to sibship data from the Boulder Family Study led to significant results for a three-dimensional spatial rotation test, but results for height and weight were non-significant. The simplest interpretation of the results for the spatial performance test was in terms of a sex-linked major locus.


Search for heterozygosis in quantitative characters. A method is described of searching for heterozygotes in a quantitative character, based on the idea that heterozygotes have more variable children than homozygotes. The variability in a set of sibs is therefore partitioned into components from the mother and father, using a least squares technique; a large component indicates a probably heterozygous parent. The method is tried out on dermatoglyphic data.


A note on assortative mating, linkage and genotypic frequencies. It is shown that in the equilibrium position with respect to the assortative mating process given by Fisher's (1918) model, the population is in linkage disequilibrium, contrary to a result given by Vetta (1975).


The correlation between relatives with assortative mating. The equilibrium correlation between various close relatives is calculated for phenotypic assortative mating for a character determined by additive loci without dominance and an uncorrelated environment. It is supposed that the phenotypes of spouses have a bivariate normal distribution and environment and heredity are normally distributed. Heredity is Gaussian if either there are many alleles with approximately normally distributed effects at each of an arbitrary number of loci or the trait is controlled by many loci, each of which makes only a small contribution. It is also assumed that the regression of the phenotype or genotype of an individual on the phenotype or genotype of any one of his relatives is linear. The results show that with the above assumptions Fisher's formulae for the correlation between relatives hold with no restrictions on the linkage map.


Heritability of stature in a West African population. Heritability of stature in a West African population is calculated from longitudinal data collected over 26 years. Statistical and analytical difficulties encountered in the study include those due to variation in stature with age, sex, recording and measuring, variation in number of offspring, variation in number of spouses, and heterogeneity of within-sibship variances. The structure of the population allows a half-sib analysis which is particularly useful in interpretation of the intrafamilial correlations and regressions. The heritability estimate of 0.6 appears lower than that from studies in European populations. The environmental contribution to the stature variance is pronounced, but is not unexpected in the light of the rigours of the traditional way of life in West African surroundings.


Diabetes mellitus among first- and second-degree relatives of early onset diabetics. This study is based on a material consisting of all first-degree relatives and a group of second-degree relatives (all nieces and nephews) of 187 propositi affected by early onset (i.e. at or prior to 20 years of age) diabetes mellitus, diagnosed before 1946. The incidence of diabetes among the different groups of relatives is expressed as the risk of developing the disease at specified ages. It is concluded that the risk of siblings or children of early-onset diabetics developing the same disease is about ten times that of a normal population chosen for comparison, whereas the risk of siblings developing diabetes later in life does not differ from this normal population. On the basis of the data presented here, combined with reanalyses of previously published data from other authors, it is concluded that early onset and late onset diabetes cannot have an identical genetic background.


The origin of human triploids.

The origin of human triploids. A series of 26 triploid foetuses was ascertained in a survey of spontaneous abortuses and the origin of the additional haploid complement determined in 21 of them by the study of foetal and parental heteromorphisms. In 17 the additional haploid set was paternal in origin, in 3 it was maternal in origin and in one the parental origin could not be determined. The best fit for the data using a maximum-likelihood method was that 66.4% of the triploids were the result of dispermy, 23.6% the result of fertilization of a haploid ovum by a diploid sperm formed by failure of the first meiotic division in the male and 10% the result of a diploid egg formed by failure of the first maternal meiotic division. The possible sources of error inherent in the technique are reviewed and our results compared with previously published data.


On the probability of demonstrating differential fertility in genetic studies. Computer simulation has been used to investigate the probability of detecting genetic differences in fertility in small cohorts. It was found that in cohorts of size 200 which have the demographic characteristics of females born in the United States in 1921--5, the probability is approximately 0.50 of detecting, by analysis of variance, either a 20% reduction in the monthly probability of conception or a 15--20% increase in the rate of foetal loss in the first month after conception. Consideration is given to the relative sensitivities of various observable measures of fertility to variation in underlying fertility components.


An incorrect definition of fitness revisited. I have attempted to show that a certain mistaken definition of fitness, which surfaces occasionally, may turn out to have some merit. No claim is made that it is an improvement on, or should replace, the conventional definition of fitness; but it is different and has its own validity. Its generality is intriguing, its application is not limited either to selection or one locus models, and it may be easier to measure experimentally.


The generalized sib pair IBD distribution: its use in the detection of linkage. General expression for the distribution of identity by descent (IBD) scores at a marker locus have been derived given neither, one or both sibs affected with a disorder determined by a linked trait locus with arbitrary gene frequency and penetrance vector. It is shown that the distirbution of IBD scores depends only on the additive and dominance variances and the population prevalence of the disorder. A one-sided test is suggested as an appropriate means of statistically testing the hypothesis that the recombination fraction is significantly less than 1/2. This sib pair approach is designed primarily to detect the presence of a critical disease susceptibility locus but when the assumptions of the incompletely penetrant single locus model are correct the methodology proposed here results in consistent estimates of the recombination fraction. The affected sib pair methodology seems especially suited to traits determined by single loci with non-Mendelian transmission.


Ancestral inference. I. The problem and the method. A method for inferring the ancestral genotypes for the founders of a population is developed. This method uses the algorithms for the computation of probabilities on pedigrees of arbitrary complexity, developed by Cannings et al. (1978) and implemented by Thompson (1977b). When characteristics are simply determined by underlying genotypes the inference problem is simplified, and larger and more complex pedigrees may therefore be analysed. The problem of estimating the allele frequencies to be used in computing prior genotype probabilities for those founders on whom a likelihood function is not required is discussed. The same method allows us to compute extinction probabilities for any combination of original founder genes; these probabilities are interesting parameters of pedigree structure, which, since they relate to the actual genes present in a population, help to provide a clearer understanding of observed distributions of autosomal traits.


[Biological method of identifying antibiotic substances at an early screening stage]. A biological method was used in addition to the chemical methods of identification in the screening programme of new antibiotics. The method consists of evaluation of the effect of the crude antibiotic preparations on microbial forms resistant to various antibiotics. The efficiency of the biological method is shown. It provides more complete and rapid characterization of the properties of the new antibiotics and their rough identification at early screening stages.


[Separation of novobiocin, isnovobiocin and descarbamyl novobiocin by a thin-layer chromatographic method]. A thin-layer chromatographic method for separation of novobiocin, isonovobiocin and descarbamylnovobiocin using Silufol plates was developed. The method is simple and rapid. It provided clear separation of the components and using of diethyl ether, a simple individual separating solvent. The method allowed determination of novobiocin and the products of its isomerization in the fermentation broth, extracts and dry substances, as well as performance of operative control and regulation of the technological processes of fermentation and chemical purification of novobiocin.


[Directed isolation of Micromonospora generic cultures on a selective medium with gentamycin]. The results of using selective media with gentamicin for directed isolation of Micromonospora are presented. It was shown that the use of the selective media with gentamicin for isolation of actinomycetes from soils of usual humidity levels markedly increased the frequency of Micronomonospora detection. The use of the selective media with gentamicin for plating out silt substrates containing mainly Micromonospora had practically no effect on the increase in the number of the Micromonospora cultures grown. The number of antibiotic-producing Micromonospora isolated on the media with gentamicin was 3 times higher than that on the control media. The use of the selective media with gentamicin provided directed isolation of Micromonospora.


[Directed isolation of Micromonospora generic cultures from moist soils and silts]. The data on the study of various soils and substrates for isolation of Micromonospora from them are presented. It was shown that Micromonospora predominated in moist soils and especially in such substrates as silts where their content with respect to the all actinomycetous isolates amounted to 88.9 per cent. In the silts the content of Micromonospora amounted to 66.6--83 per cent, in the sopromely its content was 66 per cent, while in the ordinary non-moist soil its content was from 6 to 11 per cent. Predominance of Micromonospora in silts and moist soils makes its directed search possible.


[Data on the conditions for the prolonged storage of Micromonospora generic cultures]. Data on studying various conditions for prolonged storage of Micromonospora are presented. It was shown that Micromonospora were satisfactorily stored under conditions of all maintenance methods used. The optimal methods were the following: storage of Micromonospora on agarized media under a layer of vaseline oil, storage of Micromonospora in the form of a mature submerged culture on liquid media optimal for its growth and development. Stimulating effect of low temperature on the spore germination was shown.


[Standardization of the methods of determining microorganism sensitivity to antibiotics. The importance of the method of interpreting the results in determining microorganism sensitivity to antibiotics]. The significance of the methods of the data interpretation for determination of the microbial sensitivity to antibiotics is discussed. A necessity for using semi-quantitative or quantitative systems of calculation instead of qualitative interpretation of the inhibition growth zone diameters is presented. It is shown that the use of the standard nutrient medium for determination of the antibiotic sensitivity in the laboratory practice may be a base for applying the methods of interpretation of the diffusion test data.


[Sensitivity of the causative agent of tularemia to antibiotics]. Sensitivity of the tularemia causative agent of different geographical races to antibiotics such as streptomycin, tetracycline, gentamicin, rifampicin (20 strains), ampicillin, polymyxin M, erythromycin, oleandomycin (361 strains) and lincomycin (294 strains) was studied. High sensitivity of the tularemi a microbe to streptomycin, tetracycline, rifampicin (MIC of 10 gamma/ml), gentamicin (MIC of 1 gamma/ml) and resistance to 50 gamma of ampicillin and 1000 gamma/ml of polymyxin M were found. Combined use of 50 gamma of ampicillin and 100 gamma/ml of polymyxin M added to the nutrient medium for growth inhibition of the foreign flora on isolation of the tularemia causative agent from the infected material including stable laboratory animal carcases was recommended. Marked differences in sensitivity of the strains of different geographical races to the macrolides and lincomycin were observed. The strains of the non-Arctic and Central Asiatic races were of low resistance to the above drugs (the MIC of erythromycin, oleandomycin and lincomycin were 10--50, 50--400 and 25--100 gamma/ml respectively. Within the holarctic race 40 per cent were low resistant and 60 per cent were highly resistant to these drugs. The above drugs should not be used for treatment of tularemia cases.


[Drug resistance stability in staphylococci under different conditions. The mechanism of the recovery of streptomycin sensitivity of a staphylococcal population in patients 7 months after hospital discharge]. A method for analysis of antibiotic sensitivity restoration in staphylococcal populations in humans is described. The mechanism of streptomycin sensitivity restoration in staphylococcal populations on the nasal mucosa of 59 patients 7 months after discharging from surgical stationary was studied. Quantitative estimates for loss of superinfecting streptomycin-resistant staphylococci, initial streptomycin-resistant staphylococci and resistance determinants by the initial streptomycin-resistant staphylococci are presented.


[Argasid tick lysozyme action on HEp-2 cells]. The cytotoxic effect on Argasidae lysozyme was shown on a model of cell line HEp-2 in comparison to egg lysozyme. The lysozyme was obtained from homogenates of Ornithodoros papillipes of subfamily Ikodoidea. The lysozyme in concentrations of 300 and 500 gamma/ml had a cytotoxic effect, while in doses of 50 and 100 gamma/ml it has no such activity. The cells of line FL were not sensitive to the above concentrations of the lysozyme. In concentrations of 500 gamma/ml and higher the egg lysozyme had an analogous cytotoxic effect on the cells of line Hep-2. The comparative study of the cariogrammes of the cell monolayer treated with the Argasidae and egg lysozymes, as well as the study of the level of 3H-thimidine incorporation into the cell DNA showed the absence of the preparations effect of the mitotic activity of the cells and DNA synthesis by them.


[Biochemical shifts in the nuclear membranes of the kidneys of dogs after the prolonged intravenous administration of amphotericin B]. The protein composition of the nuclear membranes of the dog kidneys after intravenous infusion of amphotericin B in a dose of 3 mg/kg and sodium desoxycholate in a dose of 1.2 mg/kg for 8 days was studied. It was found that administration of amphotericin B and sodium desoxycholate was accompanied by pronounced changes in the membrane proteins. The changes were evident from a decreased content of histones in the nuclear membranes, elimination of the high molecular components, a decreased quantitative content of some fractions and appearance of low molecular bands. The effect of sodium desoxycholate on the nuclear membrane proteins was shown to be less pronounced than that of amphotericin B. The significance of the data is discussed in connection with high toxicity of polyenic antibiotics. The data provide elucidation of the causes of the nephrotoxic effect of the polyenic antibiotics.