Contact urticaria provoked by balsam of Peru. Six patients with chronic urticaria are described in whom immediate type hypersensitivity to balsam of Peru was proven by patch test.


Simple methods for demonstration of epoxy resins of bisphenol A type. Low molecular weight oligomers of epoxy resins of bisphenol A type are common sensitizers. For demonstrating the presence of sensitizing oligomers of these resins, two simple methods are described. The first one, a colour reaction, demonstrates the presence of the bisphenol A skeleton. If this test is positive, thin-layer chromatography is carried out to demonstrate the presence of low molecular weight oligomers of epoxy resins. Some practical applications are reported.


An investigation of the possible immunological relationship between allergen extracts from birch pollen, hazelnut, potato and apple. In a retrospective study on selected group of patients, the coincidence of birch pollen allergy and a clinically relevant positive prick test reaction to apples and potatoes was confirmed. Immunochemical comparison using the crossed line immunoelectrophoresis technique (CLIE) confirmed partial identity between birch pollen and hazelnut. By the same method no partial immunological identity between birch pollen and extracts and fresh peel from apples and potatoes was found. However, both apples and potatoes gave rise to non-immunological affinity precipitates. On this basis it is discussed, whether the active agents from apples and potatoes were extremely labile allergens, plant lectins, or low molecular weight substances with a direct or indirect histamine release effect.


Sensitization and testing of guinea pigs with cobalt chloride. The guinea pig maximization test was used to study the sensitizing potential of cobalt chloride; 1 % CoCl2 was used for injection and 5 % for topical application. The animals were challenged twice; in series I epicutaneous testing was performed 3 weeks after sensitization and intradermal testing after yet another week. In series II the reverse schedule was used, i. e. intradermal testing after 3 weeks and epicutaneous after 4 weeks. CoCl2 was found to be a grade V allergen. The differences between cobalt-exposed and control animals (which had been treated with Freund's adjuvant, petroatum, occlusion, etc.) were statistically significant (P less than 0.001). however, the administration of cobalt at the first challenge testing caused this difference to diminish.


Immediate and delayed allergic contact reactions to polyethylene glycol. The lower molecular weight liquid polyethylene glycols (PEG) varying from 200 to 700 are extensively used as solvent vehicles in topical medicaments. Four patients showed allergic reactions to these liquid polyethylene glycols in topical medications. Two had immediate urticarial reactions to PEG 400. Two other patients had delayed allergic eczematous reactions, one to PEG 200, and one to PEG 300. Cross reactions occurred between PEG 200, 300 and 400, but not between these liquid polyethylenes and the higher molecular weight solid polyethylenes from 1000 to 6000.


Day 7 (D7) patch test reading - valuable or not? Day 7 (D7) reading of 15,469 patch tests was carried out in 499 patients. In one fifth of them, positive reactions were observed at D7 having been judged negative at D2. The significance of the findings is discussed.


Factors influencing nickel dermatitis. I. The nickel concentrations in urine and blood plasma of a very hypersensitive female patient have been followed during two periods of 34 and 42 days each. A limited degree of correlation was found between the course  of the nickel concentration in plasma, the nickel concentration in urine and the clinical activity of the dermatitis. Evidently other factors also influence the activity of the dermatitis; among these menstruation and stress might be expected to play a role.


Factors influencing nickel dermatitis. II. The nickel concentrations in urine and other data of a very hypersensitive female patient have been followed during two periods exceeding 30 days each. Only a limited degree of correlation was found between the course of the nickel concentration in urine and the clinical activity of the dermatitis. In order to better evaluate the measure of the correlation and the influence of some other factors upon the activity of the dermatitis, a pathway analysis scheme has been constructed. Consideration of this scheme reveals the need for more extensive data regarding the nickel ion climate in the body.


Cosmetic regulatory activities in the United States: past, present and future. To protect consumers from unsafe or decptively labeled cosmetics, the Food and Drug Administration promulgates regulations, conducts factory inspections, investigates mardeted products, evaluates consumer complaints, maintains registries of voluntarily submitted formulation and adverse reaction information, and carries out analytical, microbiological and toxicological studies. There has been a significant shift in program priorities from surveillance activities to scientific research and the determination of systemic hazards to health. Major scientific efforts involve studies to determine the dermal toxicity of cosmetics, develop methods for predicting the efficacy of preservatives, and answer questions about the skin penetration and carcinogenicity of nitrosodiethanolamine. A further issue of concern is the carcinogenic hazard of hair dyes.


Bacteriologic culture results obtained before and after elective midtrimester urea abortion. Twenty patients undergoing elective midtrimester abortion by urea amnioinfusion had bacteriologic culture data obtained before and after the procedure. Despite the presence of pathogens in the vagina and cervix prior to the procedure, only 20% of patients exhibited endometrial growth following abortion. Factors that seem to favor such endometrial growth include increased injection-abortion intervals and the requirement for curettage to manage incomplete abortion.


No increase of the fibrinolytic activity of the human endometrium by progesterone-releasing IUD (progestasertR). An increase in menstrual blood loss is one of the most common side effects of plastic IUDs and, though less often, also of copper IUDs. This has been explained by the observation that IUD enhances the fibrinolytic activity of the endometrium. A progesterone-releasing IUD (ProgestasertR) does not increase menstrual bleeding. The fibrinolytic activity of the endometrium was studied in 17 women before and after insertion of a progesterone-releasing IUD. It did not enhance the histochemically determined fibrinolytic activity in the endometrium.


Pathogenesis and renal function in acute toxic nephropathies. Acute toxic nephropathy may be produced by a variety of poisons and drugs. Cellular poisons, such as mercuric bichloride, produce tubular necrosis. Many drugs induce an immunologically mediated response presenting as interstitial nephritis, glomerulonephritis or angiitis. Substances, which are not primarily nephrotoxic but induce dehydration, shock, hemolysis, rhabdomyolysis and/or electrolyte disturbances may also lead to secondary acute renal failure. Reduced renal blood flow, suppressed glomerular filtration, increased tubular pressure due to obstruction, and tubular leakage are responsible for the functional breakdown. In addition, specific tubular functions may be impaired. Complete or incomplete recovery is the rule.


Nephrotoxicity of gentamicin. Action on subcellular organelles and pharmacokinetics in the kidney. Our findings on the renal pharmacokinetics of gentamicin explain why: (1) gentamicin concentrations in the kidney reach levels high enough to provoke injuries to the organelles; (2) the morphological manifestations of toxicity involve primarily the convoluted proximal tubule (which constitutes the largest part of the cortex), since antibiotic concentrations in this area are especially high; (3) nephrotoxicity is related to duration of treatment; (4) urine may contain small quantities of gentamicin up to 3 weeks after the end of therapy (14, 22, 30); (5) nephrotoxicity continues after discontinuance of the treatment, and (6) the hepatocytes, whose lysosomes are very sensitive to the action of gentamicin, show no obvious signs of toxicity, since the antibiotic never attains a high enough concentration in this organ.


Nephropathies due to analgesics.

Nephropathies due to analgesics. Analgesic drugs causing kidney functional disturbances and histologically evident kidney derangements are reviewed. Today, not the pathological changes, which have dominated the scene of pathogenesis for analgesic nephropathies are in the foreground of investigative interest, but rather the biochemical interactions of analgesics or their metabolites in the renal cell and prospective epidemiologic studies. As the term 'phenacetin nephropathy' has been replaced by 'analgesic nephropathy', it seems likely that metabolic activation responsible for renal injury caused by analgesic mixtures will be of primary importance in furture investigations as well as the unravelling of immunogenic processes for a variety of analgesics and their metabolites.


Nephrotoxicity of chromium. Remarks on an experimental and epidemiological investigation. Observations conducted on a group of workers exposed to chromium (who showed a rapid urinary excretion of the metal and progressive increase of clearance with cumulative years of exposure), induced the authors to evaluate the nephrotoxic action of chromium in rats exposed to acute and chronic intoxication. The progressive Cr accumulation in the renal cortex during the course of testing explains the increase of the excreted fraction of filtered Cr, and therefore, the clearance, of the metal through the reduction of the tubular lumen-epithelium gradient. Paralleling the anatomical lesions (demonstrated only at the level of the proximal tubular cells), are the increasing modifications of the cellular lesion or altered reabsorption registered by several urinary indicators. Similar changes were found in subjects chronically exposed to the metal; their reversibility is linked to the possibility of repairing the epithelial damage by stopping exposure.


Aggravating factor in lupus nephritis; electron microscopic observation. 47 renal biopsies from 36 patients with SLE were examined in detail to compare with clinical courses and ultrastructural findings. Of 36 patients, 8 cases were free from renal involvement. The severity of electron dense deposits in glomeruli with lupus nephritis were generally well correlated with each clinical feature obtained. Moreover, mesangiocapillary cell proliferation was considered to be the main morphological promoting factor in poor prognosis of the lupus nephritis. Prominent circumferential subendothelial dense deposits were suggested to enhance to enhance the proliferation of mesangial cells, mostly with a mode of circumferential interposition. In each deposit with lapse of time and/or treatments, subepithelial deposits were gradually degraded to granular material but not lucent, though most subendothelial deposits rapidly disappeared without any remnant structure or with only a few flocculent materials. Mesangial deposits were mostly stabilized and rarely turned membranous.


Mesangial IgA glomerulonephritis. Clinicopathological study of 85 cases. A clinicopathological study was made on 85 cases of mesangial IgA glomerulonephritis and of 49 controls. Predominant incidence of male over female was noted in IgA glomerulonephritis. The disease developed insidiously in a considerable number, and occupied 68% of chance proteinuria and/or hematuria. Macrohematuria was often experienced, but in a statistical comparison with controls, no specific features were observed clinically except that hypertensive cases were rarely encountered in this disease, which may reflect the better prognosis. Serum IgA levels were not different significantly in two groups. Histological changes were those of various natures and intensities, and no specific type of lesions were observed. The negative staining of C1q and C3PA in glomeruli of IgA glomerulonephritis offered no possibility to elucidate either of the complement pathways as active.


The correlation of antibodies to nuclear ribonucleoprotein (RNP) and nuclear acidic protein (Sm) with nephritis in patients with systemic lupus erythematosus (SLE). The role of antibodies to Sm and RNP in renal diseases in SLE was investigated using counter immunoelectrophoresis (CIE). Antibody to RNP was found in about 50% of lupus patients irrespective of the degree of renal involvement as evaluated clinically, histologically and immunopathologically. Antibody to Sm was found more frequently in lupus patients with renal lesions than in those without renal disease. Antibody to RNP was demonstrated in 8 of 10 (80%) and antibody to Sm in 4 of 10 (40%) specimens obtained by elution of autopsied kidneys. These results suggest that antibodies to RNP and Sm are also of importance in the pathogenesis of lupus nephritis in addition to the already recognized role of antibody to ds-DNA.


Dominant IgM deposition in experimentally induced amyloid kidney of the mouse and its immunological implications. Prolonged hyperimmmunization of C3H mice with casein resulted in immune deposits in glomeruli which led to subsequent amyloid deposition. During the immunization, the animals were in state of extreme antigen excess without any detectable circulating antibodies. The immunofluorescent findings in the later period revealed predominant IgM deposition in glomeruli, which was quite consistent with the dominant presence of IgM antibody-forming cells in spleen in the apparently tolerant state.


Plasma renin activity in acute renal failure induced by norepinephrine infusion in unilaterally nephrectomized dogs. Plasma renin activity was determined by bioassay prior to, during and following a 2-hour infusion of norepinephrine into the renal artery in unilaterally nephrectomized dogs in order to examine the role of renin-angiotensin system in norepinephrine-induced ARF. ARF was induced in 5 of 8 dogs receiving 0.75 microgram/kg/min of norepinephrine, but not in the remaining 3 dogs and 2 dogs infused with 0.6 and 0.4 microgram/kg/min of norepinephrine. There proved no difference in plasma renin activity in renal venous blood between the dogs with and without ARF when followed up to 2 h after the discontinuation of the infusion. The same results were obtained when the plasma renin activity in the foreleg vein was followed at 24, 48 and 72 h after the infusion. The renin-angiotensin system does not seem to contribute to the reduction of renal function in norepinephrine-induced ARF in dogs.


Application of vasopressin radioimmunoassay to clinical study: role of vasopressin in hypo- and hypernatremia and some other disorders of water metabolism. Plasma and urinary arginine vasopressin (AVP) in normal subjects and in patients with various water metabolism disorders was measured using a sensitive, specific radioimmunoassay. The AVP plasma levels in normal subjects were 3.1 +/- 1.2 pg/ml. The parallel changes in plasma osmolality, plasma AVP concentration, and urinary osmolality were observed after water load. In patients with various kinds of hyponatremia and impaired water excretion, plasma AVP concentrations were within or over normal levels, suggesting that persistent secretion of AVP may play an important role in the pathogenesis of hyponatremia. Variable levels of plasma AVP were observed in patients with essential hypernatremia, which in turn suggested that osmoreceptors may be selectively damaged in some patients, and that ADH-secreting neurons are also involved in others. Our radioimmunoassay facility made it possible for us to measure plasma and urinary DDAVP in the treatment of diabetes insipidus.


Serum lipid and lipoprotein abnormalities in major clinical entities of renal disease. More than half of the patients with glomerulonephritis, nephrotic syndrome and renovascular hypertension showed obviously abnormal profiles of serum lipoproteins (Lps). The abnormal profiles returned to normal or near-normal when the disease was ameliorated or corrected surgically. A unique Lp profile (broad midband pattern, BMP) was observed in approximately 89% of uremic patients on hemodialysis therapy. The results of the current investigations indicated that the BMP could probably be formed by the accumulation of catabolic remnants of VLDL.


Identification of beta-aspartylglycine in uremic serum and its toxicity. An unidentified ninhydrin-positive substance of acidic nature was found in the serum of uremic patients. This substance was isolated from hemodialysate by the methods of ion-exchange chromatography, gel-filtration and paper electrophoresis, and identified as beta-aspartylglycine by amino acid analysis, N-terminal amino acid determination and comparison with authentic sample synthesized in this laboratory. The quantitative determination of beta-aspartylglycine in serum revealed that the serum concentrations of beta-aspartyl-glycine in uremic patients increased much higher than those in normal subjects. The toxicity of beta-aspartylglycine in mice with acute renal failure induced by uranyl acetate was investigated. The mice given more than 1,0 g/kg body weight of beta-aspartylglycine showed behavioral alterations: low response to the stimuli and low activity, and some mice died by the injection of 4.0 g/kg body weight of the peptide. These results suggested that beta-aspartyl-glycine might be a possible factor which influences the development of uremic toxaemia.


Studies on nitrogen and amino acid metabolism in hemodialysis patients using 15N-labelled compounds. The degree of 15N incorporation into serum albumin studied by 15N-urea administration in dialyzed patients on a 1.3 g/kg/day protein diet was shown to be almost the same as in non-dialyzed uremic patients on low protein diet, while there was no incorporation in a normal subject. 14.1 g of EAA and histidine was intravenously given in dialyzed patients on the high protein diet and improvements in the level of BUN and anemia were observed. The study with 15N-leucine in a patient proved that about 36% of EAA infused during dialysis was transferred into dialysate. AAD was prescribed by giving 15-20 g of EAA, histidine and tyrosine to patients at each dialysis. The AAD enabled us to give a large amount of EAA asymptomatically in a short time, improving anemia and decreasing the BUN level. 15N-glycine administration in a dialyzed patient proved that 15N incorporation into serum albumin was 3 times greater than his non-dialyzed uremic stage on a low protein diet, and that EAA serum concentrations and non-EAA which had not been added into dialysate were elevated.


Catheterization of the colic branch of the ileocolic vein in swine. A surgical procedure for repeated collection of blood from the colic branch of the ileocolic vein was established as an aid for nutritional studies on the colon in swine. With the animal in the dorsal position, a cannula was inserted from the ileal vein into the colic branch with a median incision at the lower part of the abdomen under a general anesthsia. Blood samples were collected intermittently every hour for 7 hours.


IgA nephropathy: clinicopathology and immunopathology. In a total of 283 biopsies, 100 (35%) were found to be IgA nephropathy. The incidence reached 40% among primary glomerulonephropathies. On the basis of histopathologic changes in glomeruli, these biopsies were classified into 3 groups. The criteria employed correlated well with clinical, laboratory and immunofluorescent findings. Immune complex pathogenesis was discussed in relation to our findings.


Vitamin D toxicity. Initial site and mode of action. Two groups of weanling pigs, injected with 45Ca, were fed diets containing optimal calcium and phosphorus, and vitamin D3 at 1320 IU/kg feed in the control group, and 825,000 IU/kg feed in the test group. The groups were further subdivided with 2 pigs in each subgroup, with survival times of 1, 2, 3, 4, 7, and 14 days. Pigs fed the high level of vitamin D3 lost weight and anorexia, weakness, rough hair coat and labored breathing were observed. Hypercalcemia began at 12 hours and progressed rapidly after 2 days. Radioisotope sutdies interpreted in the light of histopathologic findings indicated that bone was the primary source of increased plasma calcium. Calcium was released at a rapid rate into blood from prelabeled bone which was undergoing necrosis; it was also removed from blood and deposited into bone at a slower rate due to decreased apposition. Histopathologic examination of bones from test pigs showed regressive changes in the osteocytes, chondrocytes and osteoblasts which bean within 1 day of treatment and resulted in evidence osteopenia within 7 days. Arrested osteocytic osteolysis led to the appearance of cementing lines and to chondroid core retention. Further regressive changes in the osteocytes resulted in osteocytic death and osteonecrosis with subsequent osteoclasia and osteopenia. Retardation and arrest of cartilage maturation as well as osteoblastic deficiency contributed to the osteopenia. The osteopenia was further evidenced by decreased specific gravity and ash content per unit volume of humerus. The initial negative effect on the osteocytes, chondrocytes and osteoblasts is attributed to a direct toxic effect of excessive dietary vitamin D3 since hypoparathyroidism and hypercalcitoninism, which occur secondarily to hypercalcemia, could not account for the rapid appearance of this effect, nor are they known to induce osteocytic death. The release of bone calcium and the resulting hypercalcemia in vitamin D3 toxicosis is therefore due to a direct toxic effect of the vitamin, or its metabolites, on the osteocyte resulting in osteonecrosis. It is not due to increased resorption as has been reported previously from both in vivo and in vitro investigations. Degeneration, with subsequent inflammation, but without calcification, was observed in the kidneys and in the lungs. Epithelial cells, basement membranes, and smooth muscle were affected. This conclusively demonstrates that degeneration is the primary soft tissue lesion in vitamin D3 toxicosis, and that the subsequent calcification is therefore dystrophic. Degenerative changes occurred in the parathyroid glands within 1 day of treatment resulting in necrosis, inflammation and atrophy within 4 days. Relative fibrosis was seen as the parenchyma receded. The parathyroid gland changes were considered a direct effect of vitamin D3 toxicity since they occurred with only mild hypercalcemia and since necrosis of parathyroid cells has not been demonstrated with hypercalcemia either in vivo or in vitro.


Accumulation of mercury and selenium in tissues of kittens fed commercial cat food. Six kittens, three males and three females, were fed exclusively for one hundred days a commercially canned red meat tuna found to contain elevated concentrations of Mercury (Hg) and Selenium (Se). A similarly sized control group was fed for the same period a dry commercial cat food comparatively low in the concentration of these elements. At the end of the feeding trial, concentrations of Hg Se were markedly higher in blood, bone, brain, kidney, liver, muscle and spleen of the kittens fed the tuna diet as compared to the corresponding controls. No behavioral abnormalities or pathological lesions were detected in any of the kittens.


Clinical, pathologic and cytogenetic observations on two intersex dogs. Two "bitches" presented with histories of non-attainment of puberty were diagnosed as intersexes. Data on gross morphology, histology of the genitalia, and genetic sex using blood, skin and gonads were employed for the classification of the type of intersex in each case. Both cases were classified as true hermaphrodites.


Rabies and cerebrospinal nematodosis in woodchucks (Marmota monax) from New York. Abnormal behavior, suggestive of rabies, is not an unusual finding in woodchucks (Marmota monax). Necropsy records, rabies antibody tests, and necropsy examinations performed by the authors indicate that migration of ascarid larvae usually is responsible for the abnormal behavior, and that rabies is an infrequent finding. Baermannization of brain tissue is suggested for a differential diagnosis.


A mixed mesenchymal sarcoma in the soft palate of a dog: light and electron microscopic findings. Soft tissue tumors containing a mixture of neoplastic fibrous tissue, cartilage, and bone have previously been classified as extraskeletal osteosarcomas in the dog. These tumors are often poorly differentiated, contain multiple neoplastic cell types, and might be more appropriately called mixed mesenchymal sarcomas. The present neoplasm caused clinical signs of stridorous respiration and dysphagia in a four and one-half year old dog. Four neoplastic cell types were demonstrated by light and electron microscopy.


Are hair transplants successful?

Are hair transplants successful? Fifty-three patients who had undergone hair transplantation over a six year period were queried as to their satisfaction with this operative procedure. Approximately 90 percent of the patients were pleased with the results. The limitations of this procedure had been stressed in the initial interview and served to select a high proportion of pleased patients.


Extruding pilomatricoma. Report of a case. A young girl presented with an inflammatory papule, located on the right cheek, from which granular calcific material extruded. Histopathologic examination revealed the lesion to be a pilomatricoma. This type of clinical presentation, although apparently not unique, has not previously been reported. Furthermore, histochemical staining revealed that calcification may be seen early in the life history of a pilomatrixoma.


Porphyria cutanea tarda: response to vitamin E. A review and two case reports. Porphyria cutanea tarda is a disease characterized by a triad of cutaneous manifestations: "fragile" skin, usually involving the dorsal aspects of the hands, forearms, legs, or feet; mild hyperpigmentation; and hypertrichosis, especially of the face. The condition is due to a metabolic defect of liver function involving heme synthesis, resulting in the formation of abnormal amounts of uroporphyrin, and sometimes, coproporphyrin or both, which can be measured quantitatively in the urine. Present methods of treatment, including repeated phlebotomy, alkalinization, or chloroquine leave much to be desired. Based on recent experimental and clinical reports and on our personal experience with two patients, we suggest a more logical therapeutic approach in the form of large doses of vitamin E, which apparently corrects the metabolic defect causing the disease.


Horny syphilid.

Horny syphilid. A thirty-seven year old man presented with volar lesions resembling widespread clavi. Careful physical examination and serologic tests established a diagnosis of secondary syphilis. The unusual lesions best fit the rare clinical entity of horny syphilid. The case emphasizes the importance of maintaining a high index of suspicion of syphilis and the value of the serologic tests in evaluating cutaneous eruptions.


Milia en plaque.

Milia en plaque. Two patients with an unusual cutaneous lesion consisting of milia on an erythematous edematous base are presented; the clinical and histologic features are described. The name "milia en plaque" is proposed for this unusual condition.


Lichen nitidus of the palms.

Lichen nitidus of the palms. A case is presented of lichen nitidus that evolved into an acquired palmar keratoderma in a fifty year old woman; this is a rare manifestation of the disease. Lichen nitidus must be considered in the differential diagnosis of keratoderma palmaris.


Norwegian scabies. A new complication of immunosuppressive therapy. The second reported case of Norwegian scabies in an immunosuppressed patient is presented. This uncommon fulminant form of scabies is difficult to diagnose and may give rise to numerous secondary cases of routine scabies. Because of the current widespread use of immunosuppressive medication, it is believed that an increasing number of cases of Norwegian scabies will be seen and that an increased awareness on the part of clinicians will be necessary in order to diagnose such cases early in their course before numerous hospital personnel are infested.


Characterization of sister chromatid exchange induction by 8-methoxypsoralen plus near UV light. The combination of 8-methoxypsoralen and near UV light is highly effective in inducing sister chromatid exchanges (SCEs) in Chinese hamster ovary cells. Appreciable increases in SCEs can be effected by treatments compatible with cell survival, and effects of a single dose of alkylation persist over multiple generations. Both the frequency and location of SCEs induced at different times within the DNA synthesis period varies in a manner indicating that exchange induction is restricted to regions which replicated during or after DNA damage.


The localization of mouse globin genes: a test of the effectiveness of hybridization in situ. Hybridization of rabbit reticulocyte mRNA to banded mouse chromosomes in situ labeled several regions, including the globin loci. Whereas the labeling was sufficient to detect unknowns in the globin size class, the chromosome assignments would be doubtful without some means of removing trace contaminants from the probe or of recognizing chromosomal regions to which they hybridize. Mammalian gene mapping by means of hybridization in situ might be feasible with probes cloned in microbial host-vector systems or with kinetic analysis of the hybridization process at every labeled site.


Association of the frequency of acute cardiorespiratory complaints with ambient levels of carbon monoxide. Intial cardiorespiratory complaints in an emergency room were studied to determine their relationship to ambient levels of carbon monoxide recorded at a nearby permanent station. All 8,556 encounters with patients (daily mean, 93) were studied during Denver's peak season for carbon monoxide pollution (three-month winter period). The one-hour mean maximum level of carbon monoxide was above 17.8 ppm, averaging 27.2 +/- 4.3 ppm (vs 12.1 +/- 1.8 ppm on "low carbon monoxide days," P less than 0.0001); and when significantly higher frequencies of cardiorespiratory complaints occurred (7.9 +/- 0.7 percent vs 6.4 +/- 0.3 percent [+/- 1 SE]; P less than 0.04), the mean 24-hour level of carbon monoxide averaged 9.3 +/- 1.4 ppm (vs 5.9 +/- 0.8 ppm on "low carbon monoxide rays;" P less than 0.001). The frequency of cardiorespiratory complaints also was correlated with each measurement of the ambient level of carbon monoxide (one-hour mean maximum level, 24-hour mean level, and two-day moving averages of each) in six of eight comparisons. These observations strongly suggest that the frequency of thoracic complaints in an emergency room can be affected by the ambient level of carbon monoxide.


Use of irradiation in lymphomatoid granulomatosis. A middle-aged white man with lymphomatoid granulomatosis was studied over the ten-year course of his disease. Both a large subcutaneous mass in his thigh and life-threatening massive involvement of the right lung occurred on separate occasions, and each responded to therapy with irradiation after immunosuppression failed. Irradiation should be considered as one of the primary forms of treatment of lymphomatoid granulomatosis in those with localized lesions.


Anomalous left coronary artery from pulmonary artery. Unusual case complicated by coronary arterial disease and fistula from coronary artery to left ventricle. A 42-year-old woman with an anomalous left coronary artery originating from the pulmonary artery and a fistula from the left coronary artery to the left ventricle was treated by aortocoronary bypass grafting of an autologous saphenous vein. The presence of an abundant collateral circulation and of fistulous communications between the left coronary artery and the left ventricle, in our opinion, was the reason that this patient remained asymptomatic until the age of 40 years. We believe that this is the first report of the findings in an adult patient who had these two rare congenital anomalies complicated occlusive coronary arterial disease.


Agenesis of the left lung and total anomalous pulmonary venous connection. Hemodynamic studies before and after complete surgical correction. A female infant with unilateral pulmonary agenesis developed congestive heart failure dominated by symptoms of obstructive disease of the airways at 3 1/2 months of age. Cardiac catheterization revealed total anomalous pulmonary venous connection to the right atrium. Despite a massive left-to-right shunt with one pulmonary artery receiving the entire right ventricular output since birth, the patient's resting pulmonary vascular resistance was normal. Open heart surgery to repair the cardiac lesion was performed when the infant was four months of age. Subsequent studies revealed an excellent anatomic and functional repair, with normal pulmonary arterial pressures. One year following surgery, the child is asymptomatic and has normal growth and development.


Unsuspected cerebral perfusion. A complication of the use of a central venous pressure catheter. Cardiac resuscitation is accompained by rapidly performed life-saving procedures. Central venous pressure catheters may be inadvertently inserted into the internal jugular vein, and infusion of pharmacologic agents through such a catheter may lead to potentially serious complications. Rapid detection of these iatrogenic complications is required.


Retching and termination of ventricular tachycardia. Report of two cases. Two patients had ventricular tachycardia that reverted to sinus rhythm during retching. These cases are consistent with recent experimental and clinical observations that suggest the presence of significant vagal innervation of the ventricles and an important vagal effect on some ventricular arrhythmias.


Transient elevation of serum activity of MB isoenzyme of creatine phosphokinase in drivers involved in automobile accidents. Drivers involved in automobile accidents were screened for the presence of occult cardiac injury without regard for apparent severity of the accident or injury. An electrocardiogram was recorded, and serum levels of total creatine phosphokinase and the MB isoenzyme of creatine phosphokinase (myocardial form) were measured as soon as possible after the accident and subsequently during admission (or on the following day in patients treated and discharged from the emergency room). Electrocardiographic abnormalities were observed in 18 of 82 patients but correlated poorly with other evidence of the severity or location of injury. Of the 22 drivers admitted to the hospital (for any cause), nine demonstrated significant early elevations of the activity of the MB isoenzyme of creatine phosphokinase. We conclude that blunt cardiac trauma is a clinical subtlety; to be found, it must be sought. The ECG is of limited value. Measurement of the serum activity of the MB isoenzyme of creatine phosphokinase early after injury would appear to offer the best evidence of cardiac trauma.


Follow-up of patients with tuberculosis treated in a general hospital program. Treatment largely as outpatients by community physicians. As of December 1975, there had been 5 to 8 1/2 years of observation on 263 patients with bacteriologically proven tuberculosis who were initially admitted to a general hospital and were treated largely as outpatients by community physicians from July 1967 through December 1970. Ten patients died during hospitalization, and 253 were released to therapy as outpatients. Although smears or cultures of sputum remained positive at discharge in 136 (54 percent) of the 253 patients, no new infections were subsequently detected among their contacts. During initial therapy, 24 patients died of causes other than tuberculosis. Of the remaining 229 patients, the original 18-month treatment was successful in 197 (86 percent). The treatment failed initially in 11 patients, eight of whom represented relapses from previous therapy. During long-term follow-up of the 229 patients, there were only six relapses (3 percent) after the initial success. An overall rate of successful treatment of 92 percent (211/229) was achieved in the program, with 18 failures of treatment (8 percent); ie, 11 patients were lost to supervision, four died of tuberculosis, and in three, treatment was never successful.


Characterization of normal and abnormal pulmonary surface by reflected ultrasound. The use of reflected ultrasound in the diagnosis of pulmonary disease has been limited due to the strong reflection and high absorption of acoustic energy by alveoli containing air. Our study reports the ultrasonic characteristics of normal and diseased pulmonary surface. Two measurements, the coefficient of pulmonary reflection and the tissue frequency signature, were studied with specially calibrated instuments. The coefficient of pulmonary reflection in 23 normal subjects was - 19.6 +/- 0.1 dB at 5.5 MHz. In ten patients with documented pulmonary emboli, the coefficient of pulmonary reflection was -47.4 +/- 0.1 dB, significantly less than normal (P less than 0.1). The tissue frequency signature in 18 normal subjects was specular at higher and nonspecular at lower frequencies, with a typical dip at 5.2 MHz. In patients with chronic obstructive pulmonary disease, the tissue frequency signature was flat, and the typical dip was absent. In patients with pulmonary emboli, the characteristic shape of the tissue frequency signature was preserved, but there was a generalized loss of magnitude of the reflection. Thus, our preliminary data indicate that reflected ultrasound provides a noninvasive method for differentiating normal from diseased pulmonary surfaces.


A new oxygen cannula system using intermittent-demand nasal flow. A new cannula with a system of intermittent nasal flow was evaluated and compared with a standard constant-flow nasal cannula in 15 patients with chronic obstructive pulmonary disease. The intermittent-demand cannula released oxygen only when a negative pressure was detected in the nose (negative mode) or when a a positive pressure ceased to be detected in the nose (positive mode). At rates of flow varying from 0.63 to 5.60 L/min, the continuous-flow mode used 9 percent more oxygen than the negative mode and 31 percent more oxygen than the positive mode to achieve comparable improvement in arterial oxygen tension. The system using the intermittent-demand cannula was sensitive and reliable in over 150 hours of testing.


Abnormal pulmonic sound during acute massive pulmonary embolism. The findings in two patients with angiographically proven massive pulmonary embolism and with clinical and phonocardiographic evidence of abnormal respiratory movement of the pulmonic sound are reported. One patient with complete right bundle-branch block and another with normal conduction had a wide and fixed split second sound with a loud pulmonic component. Both patients had a moderate degree of pulmonary hypertension. Approximately two weeks after administration of heparin, the pulmonic sound moved normally during respiration in both patients. Thromboembolic pulmonary hypertension regressed in one patient and remained unchanged in the other. Changes in impedance through the large pulmonary arteries are are postulated to be responsible for the abnormal movement of the  pulmonic valve during both phases of respiration. Wide expiratory splitting of the second sound should be an important clue in the diag nosis of acute massive pulmonary embolism, and the reappearance of a normal inspiratory splitting could be used at the beside to assess indirectly the rate of resolution of the blood clots.


Hemodynamic monitoring in patients with hypotension after myocardial infarction. The role of the medical center in relation to the community hospital. Patients who develop hypotension after acute myocardial infarction are frequently transferred to medical centers for hemodynamic monitoring. To see if this practice is justified, we reviewed our experience with hemodynamic monitoring over a two-year period. Of 40 patients who underwent hemodynamic monitoring for hypotension, 28 were transferred from other institutions. Eleven (39 percent) of these 28 patients had a pulmonary capillary wedge pressure of 16 mm Hg or less. Ten (91 percent) of these 11 survived, compared with one survivor (8 percent) in the 13 transferred patients with a pulmonary capillary wedge pressure of 17 mm Hg or more (P less than 0.001). The pulmonary capillary wedge pressure did not correlate well with the presence of a third heart sound on physical examination or with chest x-ray films. All hypotensive patients with a low pulmonary capillary wedge pressure received fluids to expand the blood volume as their major form of therapy. Thus, hemodynamic monitoring in patients with hypotension clarifies their status regarding blood volume and identifies those who will benefit from expansion of this volume. Transfer of hypotensive patients for hemodynamic monitoring seems justified, as their status regarding volume of blood is frequently difficult to ascertain by noninvasive means.


Two-dimensional echocardiographic diagnosis of left atrial myxoma. Two patients with left atrial myxomas detected with one-dimensional echocardiographic studies were evaluated before and after surgery with real-time phased-array two-dimensional echocardiographic studies. This latter technique provided relatively quantitative information regarding the size, shape, and mobility of the tumor and its effect on cardiac function. In case 1, the two-dimensional echocardiogram showed a relatively immobile tumor measuring 3 x 4.5 cm in diameter in the left atrium only. At surgery a 2 x 4.5-cm myxoma that was attached to the left atrium by a broad-based short stalk was removed. In case 2, the left atrial mass appeared to be 3 x 4 cm in diameter, with much movement during the cardiac cycle. At surgery a 3 x 4-cm left atrial myxoma that was attached to the interatrial septum by a long stalk was removed. In both cases, masses in other cardiac chambers were excluded, the mitral valves were normal, and left ventricular function was normal, all of which were confirmed at surgery and  by postoperative echocardiograms. In one patient the information obtained by two-dimensional echocardiographic studies was believed to be sufficient to preempt the need for cardiac catheterization. These cases illutstrate that this new noninvasive technique may provide sufficient quantitative preoperative detail in patients with left atrial tumors to obivate the risk and expense of caridac catheterization.


Percentage of shortening of the echocardiographic left ventricular dimension. Its use in determining ejection fraction and stroke volume. The percentage of shortening of the echocardiographic left ventricular dimension (% delta D) was prospectively evaluated in 42 patients without detectable asynergy during diagnostic cardiac catheterization and was found to correlate well with angiographic ejection fraction (r = 0.90). Ejection fraction was calculated as the product of % delta D X 1.7 or as % delta (D2), both formulae having similar degrees of accuracy and a better correlation with the angiographic determination than conventional formulae. Ejection fractions (angiographic and echocardiographic) of 51 percent or greater were always associated with a % delta D of 30 percent or more. In five patients the echocardiographically derived ejection fractions were normal (greater than or equal to 51 percent), while the angiographic ejection fractions were reduced; four of these patients had valvular regurgitation. End-diastolic volumes were calculated from end-diastolic echocardiographic dimensions utilizing a linear regression equation derived from correlating the end-diastolic echocardiographic dimension with the end-diastolic volume in 27 patients without valvular regurgitation (end-diastolic echocardiographic dimension ranged from  3.7 to 8.2 cm). The value for stroke volume determined as the product of calculated end-diastolic volume times ejection fraction correlated with the angiographically determined stroke volume (r = 0.88; standard error of estimate, +/- 11 ml) better than the value for stroke volume derived from conventional echocardiographic formulae.


Ventricular reentry and automaticity in myocardial infarction. Effect of size of injury. The effects of the size of acute myocardial infarction on ventricular reentry and automaticity were studied in 36 mongrel dogs. Large transmural myocardial infarctions were produced by ligation of the left anterior descending coronary artery (major ligation; diameter of infarction above 4.0 cm), and small subendocardial or intramural infarctions were produced by ligating a small diagonal branch of the left anterior descending coronary artery (minor ligation; diameter of infarction less than 1.5 cm). Reentrant arrhythmias were induced by rapid ventricular stimulation, and ventricular automaticity was determined during vagal stimulation. Ventricular automaticity became enhanced only 30 to 45 minutes after both major and minor coronary arterial ligations; however, the animals with major ligations attained a higher level of increased automaticity. While automaticity became enhanced in both groups reentrant arrhythmias could never be produced artificially (or observed spontaneously) in the animals with myocardial infarctions. The dependence of the so-called reentrant arrhythmias on the size of the infarction is a major support for the theory of reentry as the basis for these arrhythmias.


Physiologic effects of the position of the body in experimental unilateral emphysema. The functional residual capacity (FRC), static compliance (Cst) of the respiratory system, minute ventilation, and arterial blood gas levels were studied in the prone, the suprine, and the right and left lateral decubitus positions in dogs with papain-induced emphysema of the right lung alone and were compared with control values. The FRC and Cst of the respiratory system were significantly increased in experimental animals in all four positions, as compared with controls. This was due entirely to increases in FRC and Cst for the right lung alone; for the unexposed left lung the FRC and Cst were significantly reduced, as compared to controls. The mean arterial oxygen tension (PaO2) was decreased in all positions, except the right lateral decubitus position, in which the mean PaO2 was not different from controls. This model demonstrates that in unilaterally distributed, experimentally induced emphysema, alterations alterations in the position of the body alone may significantly alter the FRC, Cst, and gas exchange either favorably or unfavorably, depending upon the position.


Clicks due to Swan-Ganz catheter.

Clicks due to Swan-Ganz catheter. Nonejection systolic and diastolic clicks appeared when a Swan-Ganz catheter was positioned in the proximal portion of the right pulmonary artery. The clicks disappeared on inflation of the catheter's balloon. Initial impressions included secondary prolapse of the mitral leaflets, an accentuated third heart sound, and the exposure of an occult opening snap. These high-frequency sounds are thought to be generated by the forward and backward movement of the catheter against either the proximal portion of the pulmonary artery or the right ventricular outflow tract or by a whipping action of the catheter itself.


Bilateral ductus arteriosus in d-transposition of the great arteries with right aortic arch. The rare anomaly of a right aortic arch, distal origin of the left subclavian artery, and posterior left ductus arteriosus (forming a vascular ring) plus a right ductus arteriosus is described in an infant with d-transposition of the great arteries with an intact septum. The presence of a right aortic arch and distal left subclavian artery with bilateral ductus arteriosus has not been described previously.


Corticosteroids in radiation-induced pericarditis. We describe a patient who developed acute pericarditis with effusion six weeks following irradiation of the chest for bilateral carcinoma of the breast. Oral therapy with corticosteroids was rapidly followed by a decrease of the cardiac shadow and by clinical improvement; the pericardial fluid did not reappear during a follow-up period of four years. It seems that acute pericarditis with effusion may appear in the early period after irradiation of the chest and can be treated with corticosteroids.


Hypersensitivity pneumonitis and extrinsic asthma. An unusual association. A farmer who had no prior history of pulmonary disease developed tightness in the chest of rapid onset, shortness of breath, fever, and pulmonary infiltration while farming. The symptoms of his disease worsened with repeated exposure to the dusty farm field but remitted after each of five hospitalizations. Provocative challenge with inhalation of a water-soluble extract of dust from the field reproduced both asthmatic and pneumonitic features of the disease, while administration of corticosteroids clinically controlled the entire process. The data suggest a common cause for asthma and pneumonitis in this patient.


Comparative antibiotic sensitivity testing of bacteria with a paper disc and a tablet method. A paper disc method (AB Biodisk, Sweden) and a tablet method (Neo-Sensitabs, A/S Rosco, Denmark) for antibiotic sensitivity testing of bacteria were compared. About three fourths of the bacterial strains could be classified in the same sensitivity groups when tested with the two methods. When discrepancies were noted, they were mostly of minor size.


Phenotypic variations in gentamicin-resistant isolates of Staphylococcus aureus. Eight clinical isolates of Staphylococcus aureus showing high level resistance to seven aminoglycosides are described. The resistance did not appear to be due to enzyme inactivation. Possible mechanisms of this resistance are discussed. Resistant strains showed phenotypic variations in the form of different colonial morphology and biochemical activity.


A pharmacological comparison of 3-methoxy-4,5-methylenedioxyamphetamine and LSD in the dog. 3-Methoxy-4,5-methylenedioxyamphetamine (MMDA), which has been reported to have hallucinogenic actions in man, was compared to LSD in single dose, antagonist interaction, cross-tolerance and appetite suppression studie in the dog. In single doses, MMDA partially resembled LSD: both facilitated the flexor reflex and produced tachypnea, hyperthermia, and analgesia; however, MMDA had greater activity than LSD in producing mydriasis. Only LSD consistently elicited the stepping reflex and produced tachycardia. In both the interaction studies and cross-tolerance studies in LSD-tolerant dogs the effects of MMDA were generally not like those of LSD, except for its spinal cord facilitatory effect. Cyproheptadine antagonized most of the effects of LSD but only the facilitatory effect of MMDA on the flexor reflex. On the other hand, phenoxybenzamine antagonized the mydriasis, analgesia, and hyperthermia caused by MMDA but not LSD. Cross-tolerance to MMDA developed only to its effects on the flexor and skin twitch reflexes. In intact dogs, the anorexigenic potency of MMDA was 16 times less than that of d-amphetamine. It is concluded that MMDA has primarily amphetamine-like activity with some LSD-like actions.


Precursors to heroin: a pilot study of young heroin addicts and their nonaddicted friends. To determine whether differences in life styles and patterns of drug use may help to account for willingness to try heroin and/or likelihood of becoming addicted, personal history interviews were conducted with 15 young heroin addict, 15 experimenters who used the drug but did not become addicts, and 15 nonusers who never tried heroin altough they wre exposed to it. The findings suggest that willingness to try heroin can be better understood within the context of a broader involvement in a deviant way of life. Unlike their nonuser peers, addict and experimenter subjects tended to have identified with deviant rather than conventional role models. Prior to first heroin use, most of them were heavily involved in multiple drug use and other illegal activities. Addicts and experimenters knew that one does not become addicted after trying heroin only once, and many believed they had enough "will power" to avoid a heroin habit.


Building a standardized alcoholism interview schedule. The clinical Alcoholism Interview Schedule (CAIS) is being developed as a standardized instrument for initial assessment of alcoholic patients and as a research tool. Fifty questions cover key areas of clinical concern, and accompanying guidelines describe the method of administration. An initial study of inter-rater reliability has been conducted with five raters independently rating taped interviews with each of ten patients. Agreement was assessed both by percentage agreement and by weighted Kappa. Detailed results, which are presented, in general show a fairly satisfactory level of reliability except for certain identified items which include the Jellinek classification of type of alcoholism.


Adolescent drug using groups in Chicago parks. In a northern Chicago neighborhood, observational and interview data were collected at parks, school lots, and beaches where adolescents congregate to buy, sell, and use nonopiate drugs. These sites were geographically distinct from areas where heroin is regularly distributed. Users at each area generally resided in the immediate neighborhood, were well known to one another, were predominantly male, displayed similar socioeconomic, religious and ethnic backgrounds, and had attended the same grade schools and high schools. These sites were relatively stable during the summer months, although visitors occasionally changed locations in response to police harassment. Attendance fluctuated with weather and time of day. Drug use was generally confined to the daily use of marihuana and weekend use of alcohol and sedative-hypnotics, but availability seemed to determine the type and frequency of drug use to a greater extent than drug perference. This study suggests the potential of a fieldwork model for prevention and intervention activities prior to the  onset of more intense and diversified drug use.


[Tetracycline ulcer of the oesophagus: clinical features and in-vitro studies (author's transl)]. During treatment with doxycycline capsules three patients (aged 24, 34, and 39 years, respectively) developed acute oesophageal ulcers with dysphagia as the cardinal symptoms. They became symptom-free and the ulcers healed promptly on symptomatic treatment. In-vitro experiments in rats indicated that doxycycline accumulates within the erythrocyte membrane and epithelial cells of the oesophagus. This accumulation is followed by cell destruction. It is assumed that doxycycline capsules remain within the oesophageal lumen and release doxycycline, causing epithelial destruction. This will occur more often after dry swallows of the capsules before going to bed.


[Haemodynamic effects of nefopam (author's transl)]. The haemodynamic effects of nefopam (0.3 mg/kg i.v.) were measured for 45 minutes in ten patients with coronary heart disease. The drug is a new and highly potent analgesic without any respiratory depressant effect. Arterial blood pressure and cardiac output rose moderately, while left ventricular enddiastolic pressure remained unchanged. Heart rate did not exceed 91/min. Max dp/dt, min dp/dt, Vpm and V40 rose by a maximum of 16% above control. Thus nefopam differs from other potent analgesics in having a slight inotropic effect.


[Juvenile gout with decreased activity of hypoxanthine-guanine-phosphoribosyl transferase and pheochromocytoma: partial persistence of tophi despite uric-acid reducing treatment for 12 years (author's transl)]. A now 45-year-old man with marked chronic tophous gout and recurrent nephrolithiasis has been followed for 12 years. First gouty symptoms appeared at age 18. Uric-acid reducing treatment freed the patient of symptoms, and bony and soft-tissue tophi in part regressed. The early onset and high urinary uric-acid excretion indicated increased uric-acid production. Decreased activity of the enzyme hypo-xanthine-guanine-phosphoribosyl transferase was demonstrated to be the cause of the hyperuricaemia, which led to an excessive purine synthesis. An almost complete loss of activity of this enzyme is the basis of the Lesch-Nyhan syndrome. In the described patient all of the neurological and behavioural disorders of the Lesch-Nyhan syndrome were absent. A pheochromocytoma was found to be the cause of malignant hypertension, which had been present for many years.


[Risk of infection with hepatitis B virus in laboratory staff (author's transl)]. Considerable differences were discovered when 61 student technicians and 86 qualified laboratory staff were investigated for presence of hepatitis B (surface) antigen and hepatitis B (surface) antibodies in the blood. HBs antigen was not found in the trainees whereas 4.7% of the qualified personnel were HBs antigen positive. Anti-HBs could be demonstrated in 6.6% of the trainees and in 36.1% of qualified technicians. These data demonstrate the considerable risk of medical personnel from hepatitis B virus particularly in laboratories. For prophylaxis of virus hepatitis B in laboratory personnel special hygienic measures, routine blood investigations for HBs antigen and anti-HBs, the planned placing of anti-HBs positive personnel and the value of passive immunisation with anti-HBs immunoglobulins are stressed.


[Propafenon and lidoflazine in chronic atrial fibrillation and flutter (author's transl)]. 60 patients with chronic atrial fibrillation and flutter were randomly allotted to two groups and treated alternately with two different therapy regimes. 30 patients (group I) received lidoflazine in increasing dosage up to 480 mg/24 h and in cases where there was no conversion to sinus rhythm propafenon in a maximal daily dosage of 1800 mg orally. The duration of treatment was limited to 4 days for each substance. 30 patients (group II) were treated in the reverse order, i.e. propafenon and in cases of ineffectiveness with lidoflazine. Atrial fibrillation could be overcome in 21 patients in group I and in 23 patients in group II. The combined success rate in both groups was 73%. The conversion rates for the individual substances were 41% for propafenon (17 out of 41 patients) and 59% for lidoflazine (27 out of 46 patients). The difference was not statistically significant. Successive use of both substances leads to an increased conversion rate. Dangers arising from therapy are a conduction inhibitory action and depression of sinus node function as far as propafenol is concerned and the risk of ventricular ectopy and tachyarrhythmia in lidoflazine.


[Early operation for acute cholecystitis (author's transl)]. 104 patients with acute cholecystitis were divided into four groups according to the kind of pre-operative treatment received: immediate; early; late; and interval operation. Total duration of hospital stay depended on the duration of pre-operative treatment. It was shortest (24.9 days) in those operated on within the first week, longest (71.1 days) in those operated on during the interval. Evidence of severe gallbladder wall changes (macroscopic and microscopic) was obtained in two thirds of patients, even after weeks of conservative treatment. Six patients (5.7%) died postoperatively, three of them after early operation. Overall mortality was only in part due to severe complications of the gallbladder disease.


[Ultrasound diagnosis of cholelithiasis: comparison with radiological studies (author's transl)]. Results of ultrasonic anc cholecystographic (oral or intravenous) gall-bladder studies were compared retrospectively. 302 radiological studies of the gall-bladder, 156 oral and 146 intravenous cholecystograms, had been performed on 223 patients tested by ultrasound within six months. The gall-bladder was visualised by ultrasound in 217 (97.3%), in the intravenous cholecystogram in 92 of 146 (63%) and the oral cholecystogram in 82 of 156 (53%). The diagnosis of cholelithiasis by ultrasound was made in 97 of 223 cases, confirmed in 96 by further studies or operation. There was only one false-positive result. 143 radiological studies in these 97 patients gave 87 negative cholecystograms, gall-stones being directly demonstrated radiologically in only 46. There was one false-positive intravenous cholecystogram. In a further 97 patients ultrasound studies failed to demonstrate any gall-bladder disease, but in three of them radiology demonstrated stone (2.9% false-negative results). Amond 49 normal intravenous cholecysto-cholangiograms 47 were confirmed; once the diagnosis was made by ultrasound and at surgery (2% false-negative results). Oral cholecystography was the least reliable study. In every fourth negative test ultrasound and intravenous contrast-medium injection demonstrated a normal gall-bladder (28% false-positive).


[False diagnosis of phlebothrombosis (author's transl)]. Clinical signs of deep vein thrombosis of the calf in diseases of the knee joint may lead to a false diagnosis. Two examples illustrate how bursae or herniated cysts at the back of the knee may resemble acute phlobothrombosis when they increase in size or rupture. Sonographic investigations are the method of choice for diagnosis and differentiation of cysts as well as for the follow-up.


[Special diagnostic procedures in atrial tumours of the heart (author's transl)]. A vascular myxoma which prolapsed into the mitral valve was found in the left atrium of a 47-year old man. Two-dimensional ultrasonic tomography yielded relevant non-invasive diagnostic information on the pattern of movement of the pedunculated tumour. Highly accurate determination of the tumour volume was achieved via angiocardiography and videometry. Coronography of the tumour vessels allowed identification of an unusual point of insertion of the myxoma. The risk of obstruction of the mitral orifice was documented haemodynamically by a steep gradient above the mitral valve when holding breath during the expiratory phase.


[Echovirus 30 epidemic (author's transl)]. Echovirus 30 was the cause of abacterial meningitis and pharyngitis in 22 cases in the Ludwigshafen on Rhine area in summer 1976 and in a further 26 cases in various regions of the German Federal Republic. In 11 children echotype-30-virus could be isolated from the CSF. In 47 children the diagnosis was established by a rise of neutralising antibodies. Positive virus isolation from the CSF was only possible during the first two days of the illness using rhabdomyosarcoma cell tissue cultures. These were particularly sensitive to the echovirus 30 subtype found.


[Cimetidine in the treatment of duodenal ulcer (author's transl)]. In a double-blind trial of patients with duodenal ulcer at three centres the healing rate after a four-week course of treatment (1 g cimetidine daily) was 79% (30 out of 38 patients), compared with 58% (23 out of 40 patients) on placebos. Cimetidine did not effect subjective symptoms or the need for antacids to relieve pain, except for a minor beneficial effect on diurnal ulcer symptoms during the second week of treatment. Results of long-term administration suggest that cimetidine at 400 mg daily prevent s relapses, but the possibility of an increased relapse rate after cimetidine withdrawal can not as yet be excluded.


[Noninvasive assessment of left ventricular dynamics (author's transl)]. ECG triggered scintiphotography has established itself as a reliable, reproducible, noninvasive method for the determination of ventricular volumes, left ventricular ejection fraction, and regional ventricular wall motion. It can be used with sufficient precision and accuracy in severely ill patients who are not suitable for invasive diagnostic procedures. The method is useful for follow-up investigations of known heart disease. In comparison with left ventricular cineangiocardiography a correlation coefficient of r=0.78 could be found for enddiastolic voluumes, of r=0.92 for endystolic volumes, and of r=0.91 for ejection fraction. The sensitivity of the method for recognition of disturbances of regional ventricular wall motion is 94%, the specificity 86%. In comparison with left ventricular cineangiocardiography the resulting accuracy is 90%.


[Treatment of metastasising soft-tissue sarcoma with a uniform combination chemotherapy of cyclosphosphamide, vincristin, adriamycin and DTIC ("CyVADIC") (author's transl)]. Combination chremotherapy with cyclophosphamide, vincristin, adriamycin and DTIC (CyVADIC") was used from 1974 to the middle of 1977 on 12 patients with various forms of metastisising soft-tissue sarcoma. An objective response was observed in seven of eleven patients. Full, although brief, remission occurred in two of six patients with fibrosarcoma and persists in one with an undifferentiated sarcoma. Partial remission was induced in one patients each with fibrosarcoma and alveolar-cell sarcoma. Mean survival time was 18 months. Those responding to treatment had a longer average survival time than those refractory to it. No statistically significant conclusions can be drawn because of the small number of patients, but these observations suggest that this combined treatment can favourable influence previously therapy-refractory forms of metastasising soft-tissue sarcoma.


[Lipid-lowering effect of bezafibrate in patients with diabetes mellitus and hyperlipidaemia (author's transl)]. 600 mg of bezafibrate daily were administered to 13 well controlled diabetics with hyperlipidaemia for 12 weeks. Placebo was given before and after the treatment period. Compared with pretreatment placebo, bezafibrate reduced triglycerides (between 37 and 47%) and cholesterol (between 12 and 19%) significantly. Blood glucose levels during treatment were significantly lower at 8 and 12 weeks compared with post-treatment placebo values. Urinary glucose excretion did not change. Hypoglycaemia was not observed. No change in antidiabetic medication was necessary. Bezafibrate was well tolerated. It lowered blood lipids effectively in diabetics with hyperlipidaemia. No additional precautions have to be taken to control carbohydrate metabolism during bezafibrate treatment.


[Danger of tuberculosis infection among medical personnel (author's transl)]. The prevalence of tuberculosis among juveniles and young adults is nowadays quite low. But these age groups are particularly endangered when working in the public health field. First-infection with tuberculosis and tuberculosis as an illness among medical personnel must be considered to be an occupational disease if tuberculosis infection had not been present previously and no infective source outside the medical professional setting can be demonstrated. Selective BCG immunisation should be required for their own protection among all persons working in the public health field.


[Controlled desferrioxamine treatment of congenital anaemia and transfusion siderosis (author's transl)]. A 19-year-old patient with congenital Blackfan-Diamond anaemia has been maintained on a regular red cell transfusion schedule since he was two months old. From the age of four he has received desferrioxamine injections at regular intervals with different dose levels. In spite of the treatment with the chelating agent secondary siderosis developed with typical endocrinological abnormalities and cardiac arrhythmias. Increasing the dose of desferrioxamine to 16 g/24 h resulted in an iron excretion of 184 mg/24 h. Such an intensification of treatment finally produced a negative iron balance and the cardiac arrhythmias disappeared. Desferrioxamine therapy should be done under controlled circumstances only, an iron balance is mandatory, and the dose should be adjusted to the results of the balance.


[Resistance testing and chemotherapy results of bronchial tumours (author's transl)]. In a pilot study of 40 patients with inoperable bronchiogenic carcinomas the results of clinical therapy were compared with those of in vitro tests by measuring the effects of cytostatic agents on the incorporation of precursors into DNA and RNA in tumour cells incubated in vitro for short periods. Tumour cells that showed little inhibition by the cytostatic agents in vitro (less than 30% inhibition at a concentration of 10(-2) mg/ml adriamycin) came from patients who responded poorly to cytostatic therapy. On the other hand, tumour cells that were strongly inhibited in vitro (greater than 30% inhibition) came from tumours which proved to be sensitive to the chemotherapy given to the patient. A strong correlation existed between the inhibition of uridine incorporation by the tumour cells in vitro by adriamycin and the responses of the tumour to clinical therapy even when combination-therapy was given without adriamycin. There was also a significant correlation between the inhibiting effect of adriamycin in vitro and the survival time of the tumour patients.


[The effect of progesterone uterine therapeutic system on dysmenorrhoea: prostaglandin F2alpha levels in menstrual blood (author's transl)]. The menstrual flow of five dysmenorrhoeic women was collected, four cycles with and two cycles without local intrauterine administration of progesterone (Progestasert). The menstrual flow of three eumenorrhoeic women served as control. Menstrual blood was collected by tampons stored in butyl-alcohol saturated with water. Prostaglandin F2alpha (PGF2alpha) was measured after purification and extraction by radioimmunoassay. The PGF2alpha production rate and concentration per ml of menstrual blood from dysmenorrhoeic women differed significantly from those of eumenorrhoeic women. In the treated cycles the PGF2alpha levels were significantly decreased (2 alpha less than or equal to 0,01), corresponding to eumenorrhoeic levels. These values were in accordance with the clinical results and indicate that uterine PG-synthesis is under progesterone control.


Thyroid function and polyamines. III. Changes in ornithine decarboxylase activity and polyamine contents in the rat thyroid during hyperplasia and involution. Changes in ornithine decarboxylase (ODC) activity and in polyamine contents of the rat thyroid were studied under various experimental conditions. Methylthiouracil (MTU) treatment produced several-fold increases in the thyroid ODC activity and in the content of putrescine, spermidine and spermine within a week. While serum thyrotropin (TSH) levels increased gradually up to 3 weeks, the content of both putrescine and spermidine tended to reach a plateau after 2 weeks of the goitrogen treatment; spermine content continued to increase progressively for 3 weeks. Discontinuance of MTU at 7 days resulted in a rapid decline in the elevated thyroid ODC activity, followed by a diminution of putrescine, spermidine and RNA contents. Thyroidal putrescine, spermidine and RNA responded more sensitively to both introduction and withdrawal of TSH stimulation than thyroidal spermine and DNA. Excess iodide, having no effect on the basal level of thyroid ODC, suppressed the MTU-induced increase in this enzyme activity without affecting circulating TSH, thyroxine (T4) and triiodothyronine (T3) levels. There was a significant negative correlation between the ODC activity and intrathyroidal concentration of iodine in MTU-pretreated rats. Theophylline increased the thyroid weight and ODC activity when  given to rats fed with a subeffective dose of MTU. Analyses of serum TSH, T4, T3 and of thyroidal iodine revealed that TSH-induced thyroid ODC activity was suppressed by increased circulating thyroid hormones and/or intrathyroidal iodine. Furthermore, it was suggested that thyroid hormones and excess iodide acted directly on the thyroid to alter polyamine biosynthesis, possibly by changing the responsiveness of the gland to TSH.


Adrenal steroidogenesis and hepatic corticosteroid metabolism in hypertensive rats. In vitro metabolism of progesterone and cholesterol by the adrenal glands and hepatic delta 4-reductase activity of SHR and ARH were investigated to clarify the possible hyperactivity of the pituitary-adrenal axis and abnormal steroid metabolism in SHR. The increased conversion rate of progesterone to 11 beta-hydroxyprogesterone, corticosterone and 18-hydroxy-deoxycorticosterone and the increased biosynthesis of pregnenolone from cholesterol were noted in ARH, which were similar to those seen with chronic ACTH administration. On the other hand, adrenal steroidogenesis in SHR showed no difference from that of control. Therefore the apparently normal adrenal steroidogenesis in SHR may suggest that the adrenal gland is not involved in the spontaneous hypertension of rats. The markedly decreased hepatic delta 4-reductase activity in ARH and SHR was observed in this investigation.


A radioimmunoassay of plasma 18-hydroxy-11-deoxycorticosterone. A radioimmunoassay for the measurement of plasma 18-hydroxy-11-deoxycorticosterone (18-OH-DOC) has been developed. The antiserum for 18-OH-DOC was produced in rabbits immunized with 18-OH-DOC-3-(0-carboxymethyl) oxime-bovine serum albumin. This antiserum was used at a final dilution of 1:40,000 and the main cross reactants were aldosterone at 29.4%, 18-hydroxy-corticosterone at 4.9% and 11-deoxycorticosterone at 3.6%. Silica gel column chromatography (7 X 30 mm, toluene saturated with propylene glycol: dichloromethane, 95:5) and Sephadex LH-20 column chromatography (7 X 60 mm, benzene: methanol, 85:15) were employed for the separation of these cross reactants. The sensitivity was 10pg and the method blank was consistently negligible. The intra- and inter-assay precision was 11.3% and 14.8%, respectively.


Effect of continuous light and darkness on the testicular histology of toad (Bufo melanostictus). Continuous darkness decreases spermatogenesis as well as Leydig cell function whereas continuous illumination suppresses spermatogenesis along with increased Leydig cell activity.


Effect of neurotensin on pituitary gonadotropin release in vivo. To investigate the effect of a newly purified hypothalamic tridecapeptide, neurotensin on LH and FSH release from the anterior pituitary gland in intact male rats, two different doses of neurotensin (0.2 nmole/animal: high dose, 0.02 nmole/animal: low dose) were injected intravenously into male mature Sprague-Dawley strain rats and blood was collected before and 30 min after the administration. Both doses of neurotensin increased serum LH and FSH levels but the alteration was slight and the values were not statistically significant and less potent to stimulate the anterior pituitary as compared to LH-RF. Neurotensin was suggested to be "kinin" rather than the releasing factor and its biological potency was discussed.


A radioimmunoassay of serum 16alpha-hydroxypregnenolone with specific antiserum. A radioimmunoassay for plasma 16alpha-hydroxypregnenolone has been developed using anti-16alpha-hydroxypregnenolone antiserum produced in rabbits immunized with 16 alpha-hydroxypregnenolone-3-succinate-bovine serum albumin. Radioimmunoassay data were processed and analysed for its validity using a four parameter logistic curve fitting routine with use of the IBM call system. The assay system was satisfactory for a routine use. The 16alpha-hydroxypregnenolone concentrations in the umbilical cord blood at term ranged from 223 to 324 ng/ml. Gas liquid chromatographic analysis revealed a similar result, and also the presence of this steroid in the adrenal gland of the human fetus at midtrimester was confirmed. It is speculated that this steroid is secreted from fetal adrenals.


Biosynthetic pathways for corticoids and androgen formation in human fetal adrenal tissue in vitro. Eleven incubations of minced human fetal adrenal tissue from two fetuses at midtrimester of pregnancy terminated for socio-economic reasons, were performed for different periods of time with labelled pregnenolone, progesterone, 17alpha-hydroxyprogesterone and deoxycorticosterone (DOC). The order of magnitudes of enzyme activity when progesterone was used as a substrate and incubated with midterm fetal adrenals was 17alpha-hydroxylase, 21-hydroxylase and 16alpha-hydroxylase. The activity of 3beta-hydroxysteroid dehydrogenase and delta5-4 isomerase was almost negligible as compared to other enzymic activities as mentioned above. Similar biosynthetic pathways for adrenal corticoids formation were observed in human fetal adrenals as reported in human adults and animals; once progesterone was converted into DOC, further 17alpha-hydroxylation did not take place.


Effect of ethanol on the peripheral metabolism of thyroxine. To determine the effect of ethanol on peripheral metabolism of T4, deiodinative clearance of T4 and serum concentration of T4, T3 and rT3 were measured in rats isotopically equilibrated with T4. Ethanol 8 g/Kg weight/day was given for 3 days to fasted rats and the results were compared with those normally fed or totally fasted animals. In fasted rats, deiodinative clearance of T4 and serum T4 and T3 concentration, and T3/T4 ratio, were decreased significantly, while serum rT3 concentration and serum rT3/T4 ratio was increased significantly when compared to those in normal rats. When ethanol was administered to fasted rats, deiodinative clearance of T4, serum T4 and T3 concentration and serum T3/T4 returned to normal level while serum rT3 concentration and rT3/T4 ratio remained at higher levels than in normally fed animals. These results could not be interpreted on the basis of shift of 5 monodeiodinase to 5' form or vise versa, and imply that the two deionative process may be independent each other.


Effect of alpha-D-mannose and equilibrated D-mannose of insulin release. The effects on insulin release of alpha-D-mannose and equilibrated D-mannose were studied in the isolated perfused rat pancreas. Although phosphomannose isomerase, in contrast to phosphoglucose isomerase, is stereospecific for beta-D-mannose-6-phosphate, the alpha anomer of D-mannose (2 mg/ml) was significantly more effective than equilibrated D-mannose in stimulating insulin release. The finding does not seem to accord with the view that the signal for hexose-induced insulin release arises from the glycolytic pathway, and suggests the existence of the stereospecific glucoreceptor(s) on the pancreatic B-cell membrane.


Inhibin-like effects of interstitial testis fluid: effects on serum FSH and androgen-binding protein in epididymis. Application of rat interstitial testis fluid (ITF) to orchidectomized rats diminishes significantly the rise of FSH in serum following castration. The effect is seen for 12-24 hours on day 3 and 50 after orchidectomy but not at 48 hours in rats treated 50 days after orchidectomy. LH levels are not significantly affected. These observations are assumed to be related to an inhibin-like activity in ITF. Therefore ITF (after extraction with ether) is given to intact animals and the testicular parameter of FSH, the androgen-binding protein (ABP), is measured by "steady-state" PAGE. Unexpectedly, ABP concentrations increase. At present, this effect cannot be explained. It is concluded that ITF contains only small amounts of inhibin and will be no good source for further studies.


Reversible inhibitory effect of the non-steroidal antiandrogen flutamide (SCH 13521) on spermatogenesis in mice. The effects of a prolonged subcutaneous administration of SCH 13521 dissolved in 0.3% hydroxypropyl cellulose (2-8 weeks in daily doses of 0.2 or 1.0 mg amounting to an estimated equivalent of experimental and curative doses used by others in laboratory animals and men) were studied in males of the mouse inbred strain C57BL/6. Following the treatment, the activity of spermatogenesis (expressed as the mean number of seminiferous tubules containing mature sperm and epididymal sperm count) was inhibited while the testis weight was not reduced, obviously due to an absolute increase of the interstitial tissue which was a marked histological feature of the testes, particularly following the higher doses of SCH 13521. Lower doses and shorter-lasting administration of the compound seem to inhibit the activity more effectively because after a prolonged administration reparatory processes tend to be triggered via a stimulatory effect on the synthesis of testosterone in Leydig cells. The solvent alone, hydroxypropyl cellulose, had some inhibitory effect on spermatogenesis. The lymphoid system remained both morphologically and functionally unaffected by SCH 13521 unlike the steroidal antiandrogen cyproterone actetate.


A basic experimental approach in perspective of pineal and melatonin involvement in photoperiod-induced alteration of spermatogenesis in toad (Bufo melanostictus). Blinding decreases spermatogenesis along with Leydig cell degeneration in toad. Pinealectomy decreases spermatogenesis with an increase in Leydig cell activity. Melatonin decreases spermatogenesis as well the Leyding cells. Possibly pineal and melatonin possess an inverse relationship with light and inhibit testis.


Decreased ratio of serum T3:rT3 in patients with hyperthyroidism. In 14 hyperthyroid patient serum T4:rT3 ratio was significantly lower (399 +/- 20) than in the control subjects (572 +/- 20; p less than 0.001). A similar pattern was found for serum T3:rT3 ratio. In the hyperthyroid group the ratio was significantly lower (10.5 +/- 0.5) than in the control group (12.5 +/- 0.6; p less than 0.05). The data suggest that in hyperthyroidism the organism might shift conversion of T4 from biologically active T3 to poorly calorigenic rT3. It seems possible that the proportionately increased generation of rT3 than that of T3 may be a defence mechanism of the body, as it was found in systemic illnesses and starvation.


CNS--endocrine pancreas system. III. Further studies on the vagal responsiveness to insulin deficiency. Distribution and activity of acetylcholinesterase (AChE) in the neurons of the central vagal nuclei at the level of the medulla oblongata were studied in intact and alloxan-diabetic adult male rats by Gomori's histochemical method. Peculiarities of intracellular distribution of the enzyme in the Nucl. dorsalis n. vagi (ND) and Nucl. ambiguus n. vagi (NA) of intact animals were demonstrated. Changes in the ratio of cholinergic neurons with moderate and strongly-positive AChE staining reactions were revealed in the ND of alloxan-diabetic rats. The dynamics of the changes attested to increased AChE activity of these neurons in response to insulin deficiency. The data obtained are additional evidence for the responsiveness of ND neurons to insulin deficiency, which was demonstrated earlier in alloxan-diabetic rats by karyometry (Akmayev and Rabkina, 1976 b). It is suggested that changes in the plasma glucose or insulin levels may be the stimulus that influences the activity of the ND cholinergic neurons. By means of this mechanism the central vagal nucleus at the medulla oblongata level may be implicated in the feedback control of insulin secretion.


The glucose tolerance, insulin response and pancreatic exocrine function in patients after acute pancreatitis. In 25 patients having a history of acute pancreatitis (AP) in anamnesis one year ago and in 12 control subjects the insulin response to oral glucose was investigated and in some cases the exocrine function of pancreas was evaluated. The disturbances in glucose tolerance occurred in about 30% of the patients and were associated with impairment of insulin response and deterioration of exocrine pancreatic function. The double cortisone and glucose load did not influence the glucose tolerance in the patients. In persons investigated during AP and one year later only slight improvement of insulin response was noted. The results support the significance of follow-up studies of carbohydrate tolerance and insulin response in patients after AP for the evaluation of the diabetic risk in such cases.


Zinc and copper content in rat epididymis and vas deferens. The zinc and copper content in the different epididymal segments and vas deferens of castrated rats were investigated with the help of atomic absorption spectrophotometer. The vas deferens showed maximum zinc content as compared to that of different parts of epididymis in all groups whether castrated unilaterally, bilaterally or in the intact control. Zinc content was reduced in the epididymis and vas deferens ipsilateral to the castrated side as compared to that of contralateral control and intake animals. Lowest zinc content was observed in the epididymis and vas deferens of bilaterally castrated animals from that of other groups. Absence of sperms was observed in all segments of epididymis and vas in bilaterally castrated animals and from the unilaterally castrated side. Copper content was unaltered in all epididymal segments and vas deferens. There appears to be a correlation between the absence of sperms in the male genital tract and the decrease in zinc content.


Evidence of hypocalcemic factor from corpuscles of Stannius of the teleost Heteropneustes fossilis (Bloch). The administration of acid extract of corpuscles of Stannius has no effect on the plasma calcium level, in the normal fish, whereas the same dose shows typical hypocalcemic response in hypercalcemic fish, H. fossilis. It is concluded that acid extract of corpuscles of Stannius is effective only in hypercalcemic condition.


Differences in cardio-respiratory responses to exhaustive exercise between athletes and non-athletes. To study the factors limiting the O2 supply in heavy exercise, O2 uptake at exhaustion was determined by progressive loading method with a bicycle ergometer in 33 well-trained male runners and 34 male sedentary adults. Pulmonary ventilation, oxygen removal, respiratory rate, tidal volume, pulmonary diffusing capacity, alveolar-capillary oxygen difference, cardiac output, arterial-venous oxygen difference, stroke volume and heart rate were measured. It was found that pulmonary diffusing capacity, cardiac output and stroke volume were correlated with the difference in O2 uptake at exhaustion between athletes and non-athletes.


Reactivity of normal airways to short-term exercise. Reactivity of airways to short-term exercise was tested once in 15 healthy subjects and repeated on eight of the group using Stead-Wells and Wedge spirometers and body plethysmograph. The pulmonary function tests were performed at rest and shortly after exercise, and the data were studied by means of a randomized block analysis of variance. It was demonstrated that overall post-exercise pulmonary functions were not statistically different from the pre-exercise baseline.


Total and alactic oxygen debts after supramaximal work. The total and alactic oxygen debts were measured in eight subjects following supramaximal treadmill running (14.5--16.1 km/h, 20% grade) to exhaustion, on two duplicate tests separated by 48 h. Mean total oxygen debts on the two trials were 5.28 +/- 0.42 1 and 4.57 +/- 0.46 1, (r = 0.34). Mean alactic oxygen debts were 2.81 +/- 0.21 1 and 2.74 +/- 0.121 (r = 0.89). Values for maximal total and alactic oxygen debts in this study were in close agreement to those found in the literature. The inability of the subjects to adequately reproduce an exhausting supramaximal effort was the major factor preventing reliable measurement of total oxygen debt. It is concluded that the method developed for the measurement of oxygen debt is both reliable and valid for the alactic portion of the debt.


Capillary supply of skeletal muscle fibers in untrained and endurance-trained women. Muscle fiber diameters and number of capillaries per fiber, per mm2 and around each fiber were determined in needle biopsies from the lateral part of the quadriceps muscles of 11 young women. Six subjects were untrained (UT) and five were endurance-trained athletes (ET). Average values for maximal oxygen uptake were 43.9 (UT) and 62.1 ml/kg X min (ET). Mean fiber diameter was somewhat smaller in the UT than in the ET group (39.1 and 42.7 micrometer), but the difference was not statistically significant. Fibers with the highest content of mitochondria were on the average 9 micrometer thicker than those with the lowest content. The capillary per fiber ratios were 1.11 +/- 0.07 (mean +/- S.E.) and 1.69 +/- 0.13 in the UT and ET groups, respectively. The number of capillaries around each fiber was 3.04 +/- 0.17 (UT) and 4.42 +/- 0.31 (ET). After correction for shrinkage the number of capillaries per mm2 was 301 (UT) and 404 (ET). The capillary per fiber ratio increased with increasing fiber diameter and with the content content of mitochondria.


Involvement of the cytoplasmic membrane in nitrogen fixation by Rhizobium leguminosarum bacteroids. 1. The nitrogen-fixing efficiency of freshly prepared suspensions of Rhizobium leguminosarum bacteroids from pea root nodules was considerably enhanced by addition of bovine serum albumin. Evidence was found that during preparation of bacteroids the cell membrane is exposed to the uncoupling effect of free fatty acids and to plant phospholipase D activity. Both effects could be counteracted by bovine serum albumin. 2. A technique was developed by which concentrations of free O2 and nitrogenase activity could be measured simultaneously under conditions of steady-state respiration. By means of this system it could be shown that in contrast to previous claims, high ATP/ADP ratios can be achieved in bacteroids even with a high concentration of O2 in the medium. 3. Nitrogen fixation was found to be controlled by the ATP/ADP ratio, the generation of reducing equivalents and the switch-off phenomenon. It was demonstrated that the generation of reducing equivalents for nitrogenase is regulated by the energized state and the integrity of the bacteroid cell membrane. The data indicate that the process of aerobic nitrogen fixation in R. leguminosarum bacteroids resembles that of Azotobacter vinelandii.


Snake venoms. The amino-acid sequence of trypsin inhibitor E of Dendroaspis polylepis polylepis (Black Mamba) venom. Trypsin inhibitor E from black mamba venom comprises 59 amino acid residues in a single polypeptide chain, cross-linked by three intrachain disulphide bridges. The complete primary structure of inhibitor E was elucidated. The sequence is homologous with trypsin inhibitors from different sources. Unique among this homologous series of proteinase inhibitors, inhibitor E has an affinity for transition metal ions, exemplified here by Cu2 and Co2+.


The nucleotide sequences of 5.8-S ribosomal RNA from Xenopus laevis and Xenopus borealis. 1. The nucleotide sequence of 5.8-S rRNA from Xenopus laevis is given; it differs by a C in equilibrium U transition at position 140 from the 5.8-S rRNA of Xenopus borealis. 2. The sequence contains two completely modified and two partially modified residues. 3. Three different 5' nucleotides are found: pU-C-G (0.4) pC-G (0.2) and pG (0.4). 4. The 3' terminus is C not U as in all other 5.8-S sequences so far determined. 5. The X. laevis sequence differs from the mammalian and turtle sequences by five and six residue changes respectively. 6. A ribonuclease-resistant hairpin loop is a principle feature of secondary structure models proposed for this molecule. 7. Sequence heterogeneity may occur at one position at a very low level (approximately 0.01) in X. laevis 5.8-S rRNA, while none was detected in X. borealis or HeLa cell 5.8-S rRNA.


A barley endonuclease specific for apurinic DNA. Isolation and partial characterization. An endonuclease specific for depurinated native DNA was isolated and partially purified from extracts of barley leaves. The procedure included streptomycin sulphate precipitation, ammonium sulphate fractionation, phosphocellulose, hydroxyapatite and Sephadex G-150 chromatography. Purity of the resulting enzyme was determined by gel electrophoresis and gel chromatography and specificity by testing the activity on intact and depurinated bacterial DNAs. At lower concentrations, the enzyme is specific for DNA containing apurinic sites. At higher concentrations, however, it degrades DNA in a non-specific manner. The nuclease has a pH optimum at 7.6, and a molecular weight of about 18000.


Synthesis of carp proinsulin in Xenopus oocytes. Total poly(A)-containing RNA from Brockmann boides of carp (Cyprinus carpio) directs the synthesis of authentic carp proinsulin in Xenopus oocytes. Neither preproinsulin nor further processing of the proinsulin to insulin can be detected in the oocytes.


Distribution of AMP-deaminase isozymes in rat tissues. 1. The distribution of AMP deaminase isozymes in rat tissues was analyzed by electrophoresis on cellulose acetate membrane, by chromatography on phosphocellulose column, and by the application of immunological technique employing specific antisera against three parental AMP deaminases (isozymes A, B and C). Skeletal muscle extracts and diaphragm extracts contain a single identical isozyme, isozyme A. The major isozyme species of liver, kidney and testes are also identical and they are isozyme B. Heart extracts contains isozyme C exclusively. Extracts of brain, lung and spleen contain five isozymes, presumably a complete set of five B-C hybrids. 2. Developmental patterns of AMP deaminase isozyme were studied. In early postnatal life, extracts of heart, liver, kidney and lung contain five isozymes similar to those observed in adult brain. During postnatal development, a shift to isozyme C occurs in heart, whereas a shift to isozyme B occurs in liver and kidney. Five isozymes in lung remain throughout development. In brain a shift of B to five isozymes is observed during development. Isozyme A is the predominant form in muscle throughout postnatal development. 3. AMP deaminase in the regenerating liver was analyzed, but the data indicated that there was no change of isozyme distribution during hepatic regeneration.


360-MHz 1H nuclear-magnetic-resonance spectroscopy of sialyl-oligosaccharides from patients with sialidosis (mucolipidosis I and II). 360-MHz proton nuclear magnetic resonance spectra were recorded of 10 sialyl-oligosaccharides isolated from urine of sialidosis patients. Their structures are related to the complex asparagine-linked glycan chains of glycoproteins. By correlation of these spectra and comparison with spectra of reference glycopeptides and sialyl-lactose isomers it was possible to assign all signals belonging to anomeric, mannose H-2, sialic acid H-3 and N-acetyl protons. The number of the consituting monosaccharide residues of the oligomers can be obtained by integration of the above-mentioned signals. The chemical shifts of the anomeric and mannose H-2 protons give information about the type of glycan structure (mono-, bi-, triantennary) and the presence of terminal sialic acid at each of the antennas. The chemical shifts of sialic acid H-3 protons are typical for sialic acid residues in 2 leads to 3 or 2 leads to 6 linkage to galactose.


Subcellular metabolite concentrations. Dependence of mitochondrial and cytosolic ATP systems on the metabolic state of perfused rat liver. Mitochondrial and cytosolic contents of adenine nucleotides and phosphate were measured in perfused rat livers employing a technique of fractionation of freeze-fixated tissue in non-aqueous solvents. From the subcellular contents the mitochondrial and cytosolic concentrations of ATP, ADP, AMP and phosphate and the phosphorylation potentials of the subcellular ATP systems were calculated. An attempt was made to elucidate the relationship between mitochondrial and cytosolic adenine nucleotide systems and the dependency on the metabolic state of the liver. The following results were obtained: 1. Under all metabolic conditions studied the mitochondrial ATP/ADP ratios were considerably lower than the cytosolic ratios (mitochondria: 0.1-0.7; cytosol: 2-11). 2. The ATP/ADP ratios calculated from overall tissue contents reflect mainly the cytosolic ratios. 3. An inverse relationship was found between mitochondrial and cytosolic ATP/ADP ratios, i.e. when the mitochondrial ratios tended to increase, the cytosolic ratios decreased and vice versa. 4. The phosphorylation potentials calculated from the subcellular concentrations were higher in the cytosol than in the mitochondria. The potential difference varied between 11 and 3 kj/mol in livers from fed and starved rats, respectively. 5. In the presence of mitochondrial inhibitors, i.e. amytal, dinitrophenol and carboxyatractyloside, the potential difference between the subcellular ATP systems decreased predominantly due to an increase in the mitochondrial ATP/ADP ratios. 6. A correlation between mitochondrial ATP/ADP ratios and the respiratory rates was not observed, but the subcellular ratios appeared to correlate with the rate of glycolysis. When the rate of lactate + pyruvate production was increased, the cytosolic ATP/ADP ratios were increased, too, whereas the mitochondrial ratios tended to decrease. 7. The adenine nucleotides in the cytosol appear to be in near equilibrium catalysed by the adenylate kinase. In the mitochondria, the AMP concentration is much lower than to be expected under equilibrium conditions. These results were discussed with respect to rate control of processes involved in ATP generation, i.e. oxidative phosphorylation, adenine nucleotide translocation and glycolysis.


Effect of high pressure, detergents and phospholipase on the break in the Arrhenius plot of Azotobacter nitrogenase. It is shown that lipids are responsible for the breaks in the Arrhenius plots of Azotobacter nitrogenase. The physical evidence is that temperature at which the break occurs increases with increasing pressure by 20 K/1000 atm. This is in agreement with the pressure dependence of the transition temperature of several synthetic phospholipids. We also find the same pressure dependence for the broad transitions observed in Escherichia coli phosphatidylethanolamine and in the membrane lipids from Azotobacter itself. Detergents and phospholipase remove the break. Reconstruction can be performed only with specific phospholipids.


Transcription of bacteriophage T4 DNA in vitro: selective initiation with dinucleotides. The transcription products of phage T4 DNA in vitro are separated on polyacrylamide gels. The influence of salt, polymerase, triphosphate concentration and glucosylation on the RNA synthesis are shown. Individual transcripts are initiated selectively with dinucleotides and a single triphosphate. This technique allows the prediction of the initiation sequences of several T4 transcripts.