Histology and cytochemistry of human skin. XXXVI. The nose and lips. The skin of the nose is characterized by often conspicuously dilated openings of the ducts of many subaceous follicles. Histological sections are dominated by gigantic sebaceous follicles, but there are also numerous vellus hairs with small sebaceous glands. All hair follicles on the surface of the nose and in the vestibule are completely invested with nerve end organs. In the vestibule, the glabrous upper surface has intraepidermal nerves and a few mucocutaneous end organs. the vermillion zone of the lip, which seperates the skin of the external lip and the mucosa of the inner lip, is keratinizing glabrous epithelium, often with numerous  sebaceous glands in the upperlip. The transitional area between the keratinizing epithelium of the vermillion and the nonkeratinizing epithelium of the labial mucosa is abundantly supplied with mucocutaneous end organs, with only a few in the labial mucosa. The mucoserous glands of the labial mucosa are richly innervated.


Tachyphylaxis to topically applied steroids. Acute tolerance to the vasoconstrictive effect of topically applied glucocorticoids in humans has recently been described. Similar acute tolerance to the antiproliferative properties of topically applied steroids in proliferating and normal hairless mouse epidermis is now shown to occur. Thus, at first, topically applied steroids cause profound inhibition of DNA synthesis and mitosis in the epidermis, but with continued treatment, DNA synthesis and mitosis recover and the tissue becomes insensitive to further stimulation. This suggests that there is an optimum approach to therapy with topically applied steroids that might reduce the incidence of side effects and improve therapeutic efficacy.


Lichen planus subtropicus.

Lichen planus subtropicus. Among all the clinical varieties of lichen planus that have been reported in literature, a unique and clinically distinct type is seen in the Middle East countries. The lesions are annular, usually develop on the exposed parts of the body, and worsen by exposure to the sun. I describe this condition based on observation of 20 cases and review the literature.


Noninflammatory destruction of actinic keratoses by fluorouracil. Sequential topical application of fluorouracil and 0.5% triamcinolone acetonide cream is as effective in the treatment of actinic keratoses as fluorouracil alone, but the combination obviates the unpleasent irritation caused by fluorouracil. Diluted (0.1%) triamcinolone acetonide cream preparations are ineffective in the suppression of the associated inflammation. There is no detectable difference in the number of new actinic keratoses between the combination therapy and fluorouracil alone. These findings demonstrate that the degree of success with fluorouracil therapy in actinic keratosis is not related to the degree of inflammation associated with the treatment and are consistent with a chemotherapeutic explanation of fluorouracil's effect on actinic keratosis.


Xanthelasmoidea. An unusual case of urticaria pigmentosa. Xanthelasmoidea is an old term that has been used to describe yellow papules of urticaria pigmentosa. I used it to describe the cutaneous lesions in a young child with 1- to 2-cm oval papules, each of which was studded with 10 to 20 yellow puncta. Biopsy disclosed the puncta to be small nests of mast cells separated by normal dermis.


Relapsing polychondritis treated with dapsone. Relapsing polychondritis is a rare and sometimes fatal disease of unknown cause and pathogenesis. Results of recent studies suggest that it is an immune disorder probably caused by the production of autoantibodies to possibly the mucopolysaccharides. Perpetuation of the cartilage inflammation may be maintained by a proteolytic process. Treatment primarily has been with orally given corticosteroids. Dapsone has been shown to possibly inhibit lysosomal enzyme activity. We present a patient who, to our knowledge, is the first with relapsing polychondritis to be treated successfully with dapsone. The rapid response of the patient's condition to treatment with dapsone suggests an alternative, if not preferred, method of controlling this disease.


Staphylococcal scalded skin syndrome in an adult and a child. Two patients had staphylococcal scalded skin syndrome (SSSS) with typical clinical and histopathologic findings. In both cases, the disease was reproduced by injections of staphylococci into mice. The adult patient, who had no other physical or laboratory abnormalities, showed intact humoral and cellular immunity; her uneventful clinical course was clearly different from the eight previously reported cases in adults. To our knowledge, the child represents the first case report of SSSS as a result of infection by a non-group 2 Staphylococcus.


Lichen planus pemphigoides. Immunofluorescence findings. A 56-year-old woman developed a vesicular and bullous eruption followed by an efflorescence of lichenoid papules. The clinical and histologic features of this case were consistent with a diagnosis of lichen planus pemphigoides. Direct and indirect immunofluorescence studies demonstrated both in vivo-bound and circulating IgG with specificity for the epidermal basement membrane zone. A common pathogenic immunologic mechanism may exist for both lichen planus and lichen planus pemphigoides, which we believe are clinical variants of a similar disease process.


Treatment of relapsing polychondritis with dapsone. Three patients with relapsing polychondritis were treated successfully with dapsone. Mounting evidence suggests an immune-related pathogenesis for relapsing polychondritis. Dapsone may be effective in certain immune-related diseases because of its inhibition of lysosomal enzymes.


Immediate hypersensitivity in hand dermatitis. Role of food-contact dermatitis. A patient had a chronic hand eczema, presumably as a manifestation of atopy. Treatment resistance appeared due to handling certain foods that produced burning and stinging in the chronically eczematous skin and not in otherwise normal skin. Selected tests for delayed hypersensitivity and for immediate hyper sensitivity on intact skin of the back produced negative results, but on chronically inflamed skin of the arm and back, application of the pertinent foods produced a wheal and flare response. On intact skin, scratch tests with the foods produced positive results. Intradermal tests with commercial antigens were negative. Avoidance of these foods, as contactants, led to resolution of the dermatitis. Reappraisal of the role of immediate-type hypersensitivity in chronic hand eczema is important.


Simultaneous systemic lupus erythematosus and dermatitis herpetiformis. In April 1973, a 28-year-old woman had an eruption that was subsequently found to be dermatitis herpetiformis. In March 1974, she developed polyarthralgia and mriteria for each diagnosis were present. The concurrence of these two diseases has not been previously recorded, but we present reasons for believing that the two disorders may have similarities in pathogenesis based on disturbances in immune mechanisms.


Epithelioma Cuniculatum.

Epithelioma Cuniculatum. A 57-year-old man had a tumor for five years on the plantar surface of his foot. It was treated successfully by surgical curettage. Clinical and pathological features of the tumor are identical and pathological features of the tumor are identical to descriptions of the rare tumor of the foot designated as epithelioma cuniculatum.


Pyoderma gangrenosum associated with active chronic hepatitis: report of two cases. In two patients, active chronic hepatitis was complicated by the development of pyoderma gangrenosum. The favorable response of the pyodermatous lesions to azathioprine therapy suggests that this drug may be of value in treating this disorder in patients for whom corticosteroid therapy produces no benefit or is contraindicated because of side effects. Azathioprine, too, is a potentially toxic drug and may need to be discontinued. Possible causal relationships between pyoderma gangrenosum and active chronic hepatitis are discussed.


Cutaneous extramedullary hematopoiesis.

Cutaneous extramedullary hematopoiesis. An asymptomatic skin nodule in a patient with myelofibrosis was shown to consist of extramedullary hematopoiesis. It was a soft bluish nodule that resembled a hemangioma. Microscopically, both erythroid and myeloid cells, but not megakaryocytes, were found. This case demonstrates the ability of the skin to recapitulate dermal hematopoiesis seen in a stage of human fetal development.


Acrodermatitis enteropathica. Successful zinc therapy. Acrodermatitis enteropathica (AE) is a familial syndrome with a high incidence of morbidity and mortality. The pathogenesis is unknown. Diiodohydroxyquin and related preparations have been the mainstay of treatment for the past 20 years. Recent evidence indicates that zinc therapy given orally may be the most effective treatment. We will describe the case of a 21-year-old woman who had had AE since she was 3 months old. Successful results were obtained with zinc therapy alone.


Acquired generalized anhidrosis.

Acquired generalized anhidrosis. A patient developed generalized anhidrosis, probably following sunstroke. Light microscopy showed an atrophic, deeply lobulated or elongated configuration of the eccrine sweat glands, most of them containing many vacuoles that possessed strong acid phosphatase activity. Electron microscopy revealed that the vacuoles were bound by a unit membrane and that the contents varied. Fusion of the vacuoles and accumulation of cellular debris in the lumen were also seen. It was concluded that the vacuoles showed areas of autolysis and were classified in the group of lysosomes. In addition, it is postulated that the anhidrosis resulted from a critical rise in body temperature with subsequent changes in the secretory cells.


Origin of intraventricular haemorrhage in the preterm infant. A technique has been developed for the injection and stereomicroscopic examination of blood vessels in the preterm newborn brain. Using this technique it can be seen that in the immature brain there is a rich capillary bed in the germinal layer region supplied mainly by Heubner's artery. Capillary channels drain directly into the terminal vein and its main branches. Study of 19 cases with spontaneous germinal layer haemorrhage (GLH) with or without intraventricular haemorrhage (IVH) failed to show rupture of the terminal vein or germinal layer infarction. In babies of up to 28 weeks' gestation GLH developed most frequently over the body of the caudate nucleus, whereas in babies of 29 weeks' gestation or more the haemorrhages were usually over the head of the caudate nucleus. Histological study of 10 cases of GLH failed to show rupture either of arteries or veins, though evidence of rupture at a capillary-vein junction was seen in one case and masses of fibrin adjacent to the vein wall in 2 others. Injection through the carotid artery caused prominent leaks of injection mass within the germinal layer capillary bed, often adjacent to the veins. Injection through the jugular veins in 2 cases failed to rupture the terminal vein but caused multiple vein ruptures at the junction of deep and cortical venous systems. Additional small ruptures in the germinal layer occurred in one of the cases only. It is suggested that the capillaries within the germinal layer may be ruptured by a rise in arterial pressure, particularly in conditions of hypercapnia and hypoxia.


Metaphyseal chondrodysplasia, neutropenia, and pancreatic insufficiency presenting with respiratory distress in the neonatal period. Two pairs of brothers suffered respiratory distress in the newborn period because their ribs were abnormally short. The diagnostic radiological features of metaphyseal chondrodysplasia appeared only in the second year. Pancreatic insufficiency and neutropenia were present. One died of overwhelming infection and his brother survived a life-threatening episode of gangrenous proctitis.


Arterial oxygen tension and response to oxygen breathing in differential diagnosis of congenital heart disease in infancy. Arterial oxygen tension was measured from radial artery samples in 276 infants referred for cardiological investigation. Values obtained during air breathing in infants with congenital heart disease showed considerable overlap between 'cyanotic' and 'acyanotic' groups, and are of limited diagnostic use. By contrast, values obtained while breathing oxygen in concentrations of over 80%, measured in 182 infants, allowed clear differentiation between these groups. All infants with acyanotic, but only 2 of 109 with cyanotic lesions, achieved an arterial oxygen tension of more than 150 mmHg. In the cyanotic group the response to oxygen breathing was significantly greater in common mixing situations and in the hypoplastic left heart syndrome than with either pulmonary outflow tract obstruction or transposition of the great arteries. Infants with transposition had a significantly lower mean arterial oxygen tension in air than infants with other forms of cyanotic congenital heart disease. Of 23 infants whose final diagnosis was primary lung disease but in whom cyanotic congenital heart disease had been suspected, 7 achieved arterial oxygen tensions of more than 150 mmHg during oxygen breathing, and on this basis cardiac catheterization was not performed. We therefore conclude that measurement of the arterial oxygen tension while breathing high concentrations of oxygen should be routinely performed in the initial assessment of sick infants with suspected congenital heart disease.


Growth hormone response in fetal alcohol syndrome. In the fetal alcohol syndrome (FAS) there is severe physical growth retardation both prenatally and postnatally. Secretion of growth hormone (GH) after insulin-induced hypoglycaemia and arginine infusion was analysed in 5 cases of FAS to find out whether changes in GH secretion might account for the abnormal growth pattern. Results showed a normal or slight hyper-response of GH up to 150 ng/ml, and normal somatomedin activity in those blood samples with high GH level. It was concluded that the growth retardation in FAS is not caused by GH or somatomedin deficiencies.


Multifocal osteolysis with nephropathy.

Multifocal osteolysis with nephropathy. A patient with progressive osteolysis of the carpal and tarsal bones with glomerulonephritis of unusual severity is described. There was a notable absence of osteodystrophy in this and other reported cases who had chronic renal failure.


'Juvenile' myasthenia gravis in early infancy. A previously well infant developed severe muscle weakness and hypotonia at 6 months of age. This was reversed by anticholinesterase medication. However, she had subsequent further weakness and died at 10 months after an acute respiratory arrest. The clinical pattern was that of the 'juvenile' form of myasthenia gravis rather than the 'congenital' forms which have previously been described in early infancy.


Female phenotype in a male child due to 17-alpha-hydroxylase deficiency. The discovery of testicles in a 3-year-old girl with XY karyotype led to a diagnosis of testicular feminization. Subsequently, however, hypokalaemia, hypertension, and severe prostration during a mild infection suggested adrenal involvement, and investigations showed a 17-alpha-hydroxylase deficiency. Diagnosis of testicular feminization should not be made without excluding a defect of testosterone synthesis.


Some aspects of the mode of action and metabolism of orthonil in plants. A study of the physiological behaviour of the synthetic compound Orthonil (alpha-chloro-beta-(3-chloro-o-tolyl)-propionitrile revealed a strong auxin activity in higher plants. Otherwise, Orthonil appeared not to be a herbicide-auxin. It is metabolized intensively in plant tissues. Among the identified metabolites, two compounds were detected which also exert a high auxin activity. It is concluded that at least a part of the apparent auxin activity of Orthonil may be due to alpha-(3-chloro-o-tolyl) acetic acid, one metabolite of Orthonil. Although Orthonil strongly stimulates elongation growth, this growth is not accompanied by a stimulated ethylene evolution as is the case with other auxins. A possible metabolic pathway of Orthonil is discussed.


Some patterns of herbicide and growth regulator intake, persistence, and distribution in sugarcane. Absorption of 14C-labeled herbicides from nutrient culture solution through the roots of sugarcane plants (Saccharum spp. hybrids) resulted in three major types of distribution. Labeled residues from atrazine, ametryne, and metribuzine moved easily through the xylem to the green leaves and were deposited mainly at the leaf margins and tip. Senescence and leaf abscission removed most of the deposit from the plant. Picloram translocated rapidly into the leaves, but appeared to recycle from older to younger leaves with only small portions remaining in the senescent leaves. Asulam and pentachlorophenol (PCP) were absorbed by the roots; residues did not pass into the xylem and remained fixed in the roots. Foliar additions of labeled herbicides and growth regulators generally showed only minor absorption and translocation within the leaf. Weathering processes and volatility during a 6- to 12-week period left variable amounts of residue, characteristic of individual compounds, absorbed at the treated sites.


Nondestructive neutron activation analysis of marine organisms collected from ocean dump sites of the middle eastern United States. The concentrations of eight metals were determined by a nondestructive neutron activation technique for eleven species of fish and shellfish. The marine organisms were collected from ocean dump sites off New York City, off New Haven, Connecticut, and off Delaware Bay. Antimony was not detected in most of the organisms examined in thid study; the detection limit was about 0.02 to 0.05 ppm. Antimony levels ranged from 0.01 to 0.129 ppm in fish that had detectable levels. Cobalt levels were low in all samples with most levels in the range of 0.1 to 0.3 ppm. Chromium concentrations at 0.3 to 1.0 ppm were only roughly quantitated by the procedure employed. Most marine organisms examined had chromium levels at or below these values. Nickel was not detected in any of the organisms examined; the detection limit was in the 3 to 6 ppm range. Rubidium concentrations were 0.6 to 1.5 ppm for most organisms; only rough quantitative measurement was possible at these levels. Selenium levels ranged from about 0.3 to 3.8 ppm in all samples. Silver concentrations were below 0.3 ppm in most organisms. Silver concentrations as high as 10 to 30 ppm, however, were found in the digestive gland of rock crab. Zinc levels in windowpane flounder liver were about 6 to 9 times greater than the 4 to 10 ppm levels found in muscle. Zinc concentrations in rock crab muscle, on the other hand, were only slightly higher than the 15 to 32 ppm concentration found in the digestive gland. Fish other than windowpane flounder had zinc levels that ranged from 4 to 9 ppm in the muscle and 14 to 42 ppm in the liver. Shellfish other than rock crab had zinc levels of 15 to 30 ppm in muscle and 17 to 40 ppm in the digestive gland.


Effects of leached mirex on experimental communities of estuarine animals. Experimental communities of various estuarine animals in outdoor tanks were exposed to a continuous flow of water containing mirex for 10 weeks. The mirex was leached from fire ant bait (0.3% active ingredient) by fresh water which was then mixed with salt water to yield exposure concentrations averaging 0.038 mug/L. The experiment simulated runoff from treated land into estuarine areas. Mortality of grass shrimp (Palaemonetes vulgaris), pin, shrimp (Penaeus duorarum), common mud crabs (Panopeus herbstii), and striped hermit crabs (Clibanarius vittatus) was significantly high in tanks containing the toxicant. Mortality of ribbed mussels (Modiolus demissus) and American oysters (Crassostrea virginica) was significantly lower in treated tanks, probably because numbers of both species of crabs, which ate the bivalves, were reduced. Sheepshead minnows (Cyprinodon variegatus) were least affected by mirex. Almost all deaths occurred after 10 or more days of exposure. All exposed animals accumulated mirex, with maximum concentrations ranging from 5,500X (pink shrimp) to 73,700X (soft tissues of oysters) above the concentration in the water. Sand substratum contained mirex up to 1,500X that in the water. The study demonstrated that mirex can be leached from bait by fresh water and concentrated by and affect survival of members in an experimental estuarine community.


Effect of a smelter complex on the regional distribution of cadmium, lead and zinc in litters and soil horizons. The distribution of cadmium, lead and zinc concentrations in litter and mineral soil horizons from the Kootenay region were studied to determine the effect of the 70-yr operation of the world's largest base-metals smelter complex at Trail, British Columbia. Metals were retained near the surface in litter and surface mineral horizons and concentrations in deepest horizons were lower and normal for uncontaminated soils. Metal concentrations in surface horizons were significantly related to distance from the smelter and site elevation in the mountainous region. Regression equation models to predict metal concentrations as functions of distance and/or elevation accounted for 69.8, 93.3 and 76.7% of variance in litter concentrations of Cd, Pb, and Zn, respectively, and 91.3, 50.6, and 64.0% of their variances in surface mineral horizons. In view of concomitant random distribution of metal concentrations in deepest horizons, these relationships and low Zn/Cd ratios in surface horizons nearest to the smelter indicated surface deposition of airborne smelter emissions was responsible for metal contamination of Trail area surface soils.


Mirex-induced hepatic changes in chickens, Japanese quail, and rats. Mirex was fed in the diet to chickens at 0 to 160 ppm for 12 and 16 weeks, to Japanese quail at 0 to 80 ppm for 12 weeks, and to rats at 0 to 100 ppm for 2 and 4 weeks. Mirex did not affect the concentration of protein or cytochrome P450 in hepatic microsomes of chickens or Japanese quail, nor did it affect hydroxylation of aniline or demethylation of aminopyrine. However, structural changes were apparent in livers of chickens fed mirex at 10 ppm and above and included regions of necrosis and nonspecific cellular aberrations and alterations of sinusoids and bile canaliculi. Mirex caused liver enlargement in rats and increased microsomal protein and cytochrome P450 but did not affect hydroxylation of aniline or demethylation of aminopyrine. Hepatic structural changes in rats that were associated with mirex included proliferation of smooth endoplasmic reticulum and degeneration of some bile canaliculi.


Absorption and metabolism of a selective insecticide, 2,2-dimethyl-2,3-dihydrobenzofuranyl-7 N-dimethoxyphosphinothioyl-N-methylcarbamate, in bean plants. The absorption and metabolism of 2,2-dimethyl-2,3-dihydrobenzofuranyl-7 N-dimethoxyphosphinothioyl-N-methylcarbamate (PSC), a selective, insecticidally active carbofuran derivative, was studied in red kidney bean plants. PSC was absorbed from hydroponic culture media and was translocated throughout the plants. PSC was metabolized to carbofuran, 3-hydroxycarbofuran, and 3-ketocarbofuran and these materials accounted for 25% of the recovered radioactivity. Each of these compounds are more toxic to mice than the parent compound. Additionally at least four other oxidized, hydroxylated and/or hydrolyzed metabolites were formed.


Importance of the indoor environment in air pollution exposure. A portable personal air pollution sampler was used to measure the exposure of twenty children to respirable particulates, sulfur dioxide, and nitrogen dioxide over a 24-hour period. Particulate exposures were significantly higher among children who lived with one or more smokers, and exceeded the primary air quality standard in nineteen of the twenty subjects. To a large extent, an individual's respirable particulate load appears to be determined by exposure to indoor rather than outdoor pollutants.


Carboxyhemoglobin trend in Chicago blood donors, 1970-1974. An 18% reduction in the carboxyhemoglobin (HbCO) saturation in nonsmoking Chicago blood donors occurred between 1970 and 1974, indicating that current donors are being exposed to a lower average carbon monoxide (CO) concentration than had been experienced by 1970 donors. In contrast to the situation in 1970, when it was discovered that 74% of the nonsmokers in Chicago were being exposed to CO in excess of the amount permitted by the federal air quality standards, in 1974 only 41% of the nonsmokers were being overexposed. The observed reduction in HbCO correlates well with both the ambient CO levels recorded at the air monitoring stations and the reduction in CO emission from automobiles. If the current trend continues, Chicago should reach compliance with air quality standards for CO by 1985. The measurement of HbCO in a representative urban population is an accurate index of actual CO exposure and supplements the air pollution data provided by air monitoring stations.


The surgical management of toxic dilatation of the colon: a report of 28 cases and review of the literature. Experience with 28 patients with toxic dilatation of the colon is reviewed. The operative mortality in this series was 32% (9/28). Eight of the 9 patients who died were found to have colonic perforations at operation; in contrast, the group of patients with no perforations had a mortality rate of only 6%. Colonic perforation and sepsis were the most significant factors contributing to mortality and morbidity in this series. A review of the literature showed an overall operative mortality rate of 19.5% for patients with toxic megacolon; the mortality rate was 41% for patients with perforations and 8.8% for patients without perforations. It appears that the keystone to successful management is the avoidance of colonic perforation and sepsis; protracted medical management of toxic megacolon seems to have been at least partly responsible for these complications. Sixteen of the 18 survivors following subtotal colectomy required removal of the rectum within 9 months because of continued symptoms and disease in the rectal stump.


Delayed gastric emptying following gastrectomy. The characteristics of 46 patients unable to take a solid diet within two weeks of gastric resection and had no other post-operative complications are reviewed. The incidence of delayed gastric emptying was found to be 2 1/2 times greater in patients with vagotomy and hemigastrectomy than in those with subtotal gastrectomy. In addition, postoperative delay was often prolonged in the hemigastrectomy and vagotomy group. Mechanical factors were responsible for delay in only 10% of these patients. Possible explanations for these delays are made and it is suggested that localized starch peritonitis may explain many cases of "functional efferent limb ileus." Measures to evaluate the source of delay are recommended and suggest conservative management for the majority of patients. Reoperation is reserved for those who require feeding or draining enterostomy tubes and those whose clinical course and evaluation suggest obstruction.


Long-term patency of vein grafts preserved in liquid nitrogen in dimethyl sulfoxide. Autogenous canine jugular veins were stored in 15% dimethyl sulfoxide (DMSO) in liquid nitrogen vapor for one to 28 days and then implanted in the carotid artery as autografts. The patency rate at one year was 62.5-87.5%. The patency rate of fresh jugular vein autografts placed in the carotid artery for one year was 75%. Similar autografts stored in liquid nitrogen vapor for one to 28 days without the cryopreservative DMSO exhibited a zero to 12.5% patency rate at one year. Scanning electron microscope studies revealed preservation of theendothelium in DMSO protected veins and a damaged or sloughed endothelium in veins frozen without DMSO cryopreservation.


Blood gas and carotid pressure: factors in stroke risk. The internal carotid back pressure and arterial blood gas measurements have been employed in 269 patients undergoing 332 carotid endarterectomies in an effort to identify individuals at high risk of stroke during surgery. Patients having an internal carotid back pressure less than 25 Torr were operated using an inlying shunt. There were 159 patients having a PaCO2 greater than 45 Torr, 95 individuals with a PaCO2 between 35 to 45 Torr and 78 cases with a PaCO2 less than 35 Torr. The mean internal carotid back pressure was 63 Torr in the hypocarbic group and 45 Torr in the hypercarbic patients which represents a highly significant inverse relationship between PaCO2 and carotid back pressure (P less than 0.0002). There were four neurological deficits following surgery in the hypercarbic group and one each in the normocarbic and hypocarbic groups. These findings suggest a lower stroke incidence in patients having hypocarbic or normocarbic general anesthesia than those receiving hypercarbic general anesthesia. The low overall stroke rate of 2% indicates the safety of selective shunting during carotid endarterectomy.


Acute pancreatic pseudocysts: incidence and implications. Of 92 patients with moderately severe acute pancreatitis initially studied within three weeks of onset by ultrasonic tomography, 52 developed an acute fluid collection in the lesser sac. Documentation of the ultrasound prediction of pseudocyst was  achieved by surgery or autopsy in 26 cases. Spontaneous resolution of the acute pseudocyst was demonstrated by serial ultrasonography and radiogrphy in another 10 patients. Exploration exposed 3 false positive predictions of pseudocyst. Eleven other patients with a cystic configuration either refused surgery or were lost to followup. Acute pseudocyst formation is a relatively common phenomenon in the early phases of moderately severe pancreatitis. While spontaneous resolution of acute pseudocysts is frequent, in approximately 50% of cases acute pseudocysts progress to chronic pseudocysts. A distinction between acute and chronic pseudocyst is necessary since specific surgical management depends upon the phase of pseudocyst development. Unless regional sepsis supervens, acute pseudocyts of less than three weeks' duration may be followed by serial ultrasonography in the hope of spontaneous resolution. When a pseudocyst has achieved chronic status, spontaneous resolution is rare. Persistent conservative management under these conditions invites the excessive mortality and morbidity of spontaneous rupture.


Aneurysm of the aorta treated by wiring: case report of a 38-year survival. A patient with a syphilitic aneurysm of the aorta treated by the insertion of wire is presented. The patient remained well for almost 40 years, but finally succumbed after rupture. The autopsy findings are discussed. To our knowledge, this represents the longest reported survival after treatment of an aortic aneurysm by wiring.


Clearance of mercury (HG-197, HG-203) vapor inhaled by human subjects. Five human subjects inhaled a mixture of stable and radioactive mercury vapor for periods of 14 to 24 minutes. The subjects retained an average of 74% of that inhaled. Evidence is submitted to show that the retention occurred almost entirely in the alveoli. For 3 days after exposure, the exhaled breath was passed at intervals through activated charcoal traps for sampling periods of 10 to 35 minutes. The data indicated that an average of 7% of the retained mercury was lost in the expired breath, with a half time of 18 hours. Examination of the subjects in a whole body counter yielded average half times for mercury clearance from different parts of the body as follows: lung, 1.7 days; head, 21 days; kidney region, 64 days; chest, 43 days; and whole body, 58 days.


Impact of air pollution by lead on the heme biosynthetic pathway in school-age children. Blood-lead level (Pb-B), erythrocyte delta-aminolevulinic acid dehydratase (ALAD) activity, free erythrocyte porphyrin (FEP) concentration, delta-aminolevulinic acid concentration in urine (ALAU), hematocrit value, and hemoglobin concentration were compared for groups of children 10-13 years old from areas differently polluted by lead (rural area and lead smelter area). The biological responses of the children were also compared with those observed in adults similarly exposed to lead (Pb-B: 10-40 mug/100 ml). Compared with the rural children, children living less than 1 km from the smelter exhibited a significant increase of Pb-B and FEP, a significant inhibition of ALAD, and a slight positive correlation of ALAU with Pb-B; however, they showed no biological signs of anemia. In children living approximately 1.5 km from the smelter, there was still a significant increase of Pb-B and a concomitant inhibition of ALAD, but no change in FEP concentration. Comparison of the dose-response curves between Pb-B and FEP in adult males, adult females, and children indicates that the sensitivity to lead is in the order of children larger than or equal to women greater than men. Based on the FEP response, it is proposed that 25 mug Pb/100 ml blood be regarded as the maximum biologically allowable concentration of lead in blood of school-age children.


Stimulation by cigarette smoke of glutathione peroxidase system enzyme activities in rat lung. This study was undertaken to evaluate the effect of in vivo cigarette smoke exposure on glutathione peroxidase--related enzyme systems of the rat lung. These enzymes, acting in concert, are thought to be responsible for disposing of toxic lipid peroxides in pulmonary tissue. Thirty-day-old rats were exposed to thirteen cigarettes per day for 21 days with a Walton reverse-smoking exposure apparatus. After 21 days of smoke exposure, the activities of glutathione peroxidase, glutathione reductase, and glucose-6-phosphate dehydrogenase were increased 34%, 24%, and 38%, respectively, over control values. This level of cigarette smoke exposure did not cause detectable histological lesions. We present the hypothesis that short-term, low-level cigarette smoke exposure is capable of initiating metabolic alterations in lung cells at exposures at which histological changes are not detectable by light microscopy.


Carcinoembryonic antigen (CEA) assays in obstructive colorectal cancer. Four of 40 patients with resectable colon or rectal cancer had tumors causing acute large bowel obstruction with colonic dilatation; all 4 patients had preoperative CEA titers above 10 ng/ml with a mean of 28 ng/ml. Thirty-six cancer patients without acute colon obstruction had a mean CEA titer of 4.5 ng/ml; only 6 of 36 patients had circulating CEA titers 10 ng/ml or greater. This suggested that pre-treatment CEA titers in patients with obstructing cancer are unusually high. Multiple CEA assays were performed on two of the 4 patients with colonic obstruction before and after bowel decompressive procedures and prior to their definitive treatment. Relief of obstruction alone produces marked reduction in circulating CEA; this suggested that not only the extent of disease but also the pathophysiological changes associated with obstruction influenced circulating CEA levels.


Biochemical effect of ozone exposure in rats exposed to cigarette smoke. Rats were exposed to three cigarettes per day for 35 days, under realistic conditions. Pulmonary glucose-6-phosphate dehydrogenase (G-6-PD) activity in the exposed animals increased 27% over control values (P less than .05). Subsequent exposure to acute, high-dose ozone (3 ppm for 4 hr) decreased the augmented G-6-PD activities to near normal levels, whereas ozone exposures in animals not exposed to cigarette smoke caused mild decreases in pulmonary G-6-PD activities. The importance of these findings with respect to the susceptibility of the smoker to oxidant exposures is unknown.


Note on the classification of the Leishmania sp. responsible for cutaneous leishmaniasis in the East Central Region of Brazil. The authors studied a species of Leishmania which is the causative agent of cutaneous leishmaniasis in Mato Grosso, Brazil. The parasite displays unusual characteristics which do not fit exactly into either the L. mexicana or L. brasiliensis complexes. The buoyant density DNA resembles that of the L. mexicana complex but the culture and hamster inoculation results resemble those of the L. brasiliensis complex. Further comparative studies are required to elucidate the relationship of the Mato Grosso Leishmania to the L. mexicana complex.


The epidemiology of 2056 remote site infections and 1966 surgical wound infections occurring in 1865 patients: a four year study of 40,923 operations at Rush-Presbyterian-St. Luke's Hospital, Chicago. Over a 4-year period 40,923 operations and 44,716 surgical admissions were monitored for both community and hospital onset infections. One thousand eight hundred sixty-five patients had 1966 surgical wound infections and 2056 remote infections including 1652 hospital onset and 404 community onset infections. One thousand one hudnred forty-four patients with multiple infections averaged 40 days in the hospital contrasted with 24 days for 721 patients with a single wound infection. The total excess cost of hospitalization for these patients was $951,150. A statistically significant reduction occurred for urinary tract infections, lower respiratory infections and clean and contaminated surgical wound infections. It is suggested that these are all inter-related and a significant reduction in surgical wound infections can be achieved through control of infections at remote sites, particularly those associated with medical devices. The coagulase positive staphylococcus is still the most important single bacterial species in the primary etiology of surgical wound infections. When the gastrointestinal tract is entered or "supra" infecting organisms appear, gram negative bacteria and mixed gram negative and gram positive infections are dominant. Reduction in remote site infections occurring in surgical patients is necessary to reduce the incidence of surgical wound infections, suggest preventive and control measures, and document the effectiveness of such measures.


Cadmium in kidney cortex, liver, and pancreas from Swedish autopsies. Estimation of biological half time in kidney cortex, considering calorie intake and smoking habits. Cadmium and zinc have been analyzed in tissues from 292 persons autopsied in Stockholm. In kidney cortex, liver, and pancreas the individual cadmium levels are distributed in a lognormal way. In kidney cortex there is a continuous accumulation of cadmium with age up to 50 years, followed by a decrease. Smokers show a higher cadmium accumulation. For nonsmokers, the biological half time of cadmium in kidney cortex is estimated at 30 years, with an average concentration at age 50 of 11 mug/g wet weight. When smokers are included, the average cadmium concentration at age 50 is 22 mug/g wet weight. Based on the more pronounced cadmium accumulation among smokers than nonsmokers, the respiratory absorption rate of cadmium from tobacco smoke is estimated to be approximately 50%.


Cutaneous leishmaniasis in the Libyan Arab Republic: distribution of the disease and identity of the parasite. The endemicity of cutaneous leishmaniasis in northwest Libya was confirmed. Although the strains isolated from man had variable biological properties they were all biochemically similar according to the tests used. The Libyan strains resemble those of zoonotic cutaneous leishmaniasis in parts of the Middle East, but can be differentiated from urban or highland strains. It is suggested that the recent discovery of the disease is due partly to the improvement in medical services, and partly to the development of new areas of land for agriculture and housing.


In vitro studies on the use of penicillamine with tartar emetic against Schistosoma mansoni worms. In vitro studies were carried out to test Sb125 tartar emetic (T.E.) in concentrations of 75, 100, 125, 150 and 200 mug/ml of rabbit serum and these concentrations together with penicillamine in ratios ranging from 1:1 to 1:6 for their effect on the motility and antimony uptake by Schistosoma mansoni worms. The motility was observed microscopically every half hour for six hours and the Sb125 content was measured by a scintillation counter at one hour intervals for five hours. Results indicate that the ratio in which penicillamine is used with T.E. is very important. The antimony uptake by the worm is reduced, and the onset of T.E. action is delayed when it is used with penicillamine in a ratio exceeding 1:2.


The influence of Seitz filtration on the activity of hydatid fluid antigen. Filtration of hydatid fluid through Seitz EK filter pads results in an initial retention of a part of sensitizing proteins on the filter disc. Filtration through membrane filters allows the passage of most of the proteins of the fluid and may be considered as a more satisfactory procedure for the preparation of antigen for Casoni skin tests. Membrane filtrates are likewise reactive in indirect haemagglutination tests.


Multiple infection with Toxocara canis. Influence of antihistamines and corticosteroids on the histopathological response. The histopathology of the tissues of mice infected with ten doses of 100 embryonated eggs of Toxocara canis and the influence of antihistamines and corticosteroids on these findings is described. The main lesions were confined to the liver and lungs. In infected but untreated control mice hepatic lesions consisted of periportal infiltrates, widespread foci of liver cell necrosis and polymorphonuclear and mononuclear accumulation and a few fibrotic granulomata. Treatment with antihistamines did not change these findings significantly, but corticosteroids decreased the amount of cellular infiltration and the size of the lesions. Pulmonary lesions consisted mostly of confluent infiltrates of polymorphonuclears, eosinophils and mononuclear cells with some macrophage proliferation. Neither drug seemed to affect the lung involvement.


Effects on murine trichinosis of niridazole, a suppressant of cellular but not humoral immunological responses. Two groups of mice infected with Trichinella spiralis were treated with niridazole (100 mg/kg), one on alternate days, the other daily. Both regimens failed to influence the numbers of adult worms in the intestines or larvae in the muscles compared with untreated control mice. Mice treated with niridazole daily, but not those treated on alternate days, showed a significant reduction in the inflammatory reaction to larvae in the muscles. Immediate footpad swelling in response to injection of soluble Trichinella larval antigen was not affected by niridazole treatment. Niridazole appears to have a highly selective action on immunological responses suppressing cell-mediated reactions but leaving humoral antibody formation relatively intact. Elimination of worms may require the presence of both cellular and humoral immune mechanisms, while inflammation around larvae in the muscles may be largely a cellular reaction.


The role of the house fly (Musca domestica) in the dissemination of hookworm. Eggs and larvae of Ancylostoma caninum were recovered from the crop, mid-gut and hind-gut of Musca domestica; only larvae were recovered from the vomitus and one dead infective larva was recovered from the faeces on one occasion. All eggs recovered from the gut hatched after incubation for 48 hours. Up to 319 eggs and 1485 larvae were recovered from the legs of experimentally contaminated flies. The viability of the eggs and the longevity of the larvae recovered from the gut and external surface of the flys varied but larvae survived longer in the gut than on the external surface.


Partial loss of cytoplasmic incompatibility with age in males of Culex fatigans. The cytoplasms of Paris and Delhi strains of Culex fatigans have been reported to be bi-directionally incompatible. However, in the present study it is shown that with increasing age males with Paris cytoplasm show an increasing degree of partial compatibility with Delhi females. A male history of previous mating seems a contributory effect in enhancing the degree of partial compatibility. The relevance of partial compatibility to genetic control of C. fatigans is discussed.


Studies on the host-flea relationship. III Nutritional efficacy of blood meal of rat fleas Xenopsylla cheopis (Rothschild) and Xenopsylla astia (Rothschild). Rat fleas, Xenopsylla cheopis (Rothschild) and X. astia (Rothschild) were fed artificially on whole blood, milk and blood fractions in an attempt to identify the factor(s) which trigger ovarian maturation. Blood from the white rat, house rat, white mouse, frog, chick and man fed artificially induced vitellogenesis in over 50% of fleas of all combinations except in X. cheopis fed on chick blood. Gut distension alone had no influence on initiation of vitellogenesis as judged by feeding milk. Washed white rat blood cells resuspended in saline initiated vitellogenesis, but plasma did not. Addition to plasma of ATP, glutathione and serotonin did not initiate yolk deposition. However, raising the protein concentration of the rat plasma had a decided influence on vitellogenesis. The protein concentration of the diet appeared to be a decisive factor in initiating yolk deposition in these fleas. A change from whole blood to plasma diet caused all the mature oocytes to resorb in both the species of fleas.


The society of thoracic surgeons.

The society of thoracic surgeons. The opportunity to discuss evolving socioeconomic issues affecting the medical profession as a whole was rejected in favor of personalizing The Society of Thoracic Surgeons for a membership that has grown to almost 1,500 persons. Drawing on historical insights gained through participation in the origin, growth, and development of The Society, I take readers behind the scenes and introduce to them the many people and vast resources that serve our membership. Particular attention is focused on the services of The Society's headquarters office, which is housed and managed by Smith, Bucklin and Associates, Inc, of Chicago, a multiple-association management firm that serves 60 national organizations; on our prestigious publisher, Little, Brown and Company of Boston; and on its link with our Editorial Office in Ann Arbor.


Open-heart experience in infants using normothermia and deep hypothermia. During the 9-year period from 1967 through 1975, 124 open-heart operations were performed on infants less than 1 year of age with 35 operative deaths (28%). Ninety-seven of these procedures used continuous cardiopulmonary bypass with normothermia or mild hypothermia, and 27 were done under deep hypothermia and circulatory arrest. Mortality and morbidity were similar regardless of the operative technique, although deep hypothermia facilitated the repair of complex lesions. The highest mortality occurred in infants less than 3 months of age. Respiratory insufficiency, usually requiring prolonged ventilatory support, occurred only among infants who had pulmonary overcirculation or congestion prior to operation. Adequacy of intraoperative repair and postoperative care were the major determinants of survival.


Effect of hypothermic anoxic cardioplegia on myocardial contractility. A study was undertaken to ascertain the protective effect of topical hypothermia on the anoxic heart. The presence or absence of myocardial damage was judged by myocardial contractility. The papillary muscle of an excised rabbit heart was detached from the mitral annulus and interposed between a fixed point and a force/displacement transducer. The maximal net developed tension (TNmax) of the papillary muscle with normothermic coronary perfusion was used as an index of myocardial contractility. With each temperature drop of 10 degrees C, the anoxia time that resulted in the same recovery level of TNmax was prolonged by a factor of 2.8. A nomogram was constructed correlating percent of myocardial recovery seen with different degrees of myocardial hypothermia during various anoxic periods. Optimum protection was noted at a myocardial temperature of 18 degrees C.


Effects of morphine and halothane anesthesia on coronary blood flow. This study was undertaken to determine the relative effects of morphine and halothane anesthesia on coronary blood flow. Right heart bypass was instituted in 20 dogs by draining the vena cava blood into a cardiotomy reservoir and returning it to the main pulmonary artery. Coronary sinus drainage was measured by a right ventricular cannula. Group I (10 dogs) was sequentially given 0.5, 1, 1.5, 2.0, and 2.5% halothane. Group II (10 dogs) was given 1, 2, 3, 4, and 5 mg per kilogram of morphine intravenously. Arterial pressure, coronary sinus blood flow, cardiac output, arterial pH, PCO2, and PO2 were determined and repeated at each dose level of anesthesia and compared to the control values. Morphine significantly increased coronary flow at 3, 4, and 5 mg/kg without pressure adjustment and at 2 mg/kg after pressure adjustment. Coronary flow with halothane was unchanged from control values except for a decrease at 2.5%. Coronary flow was significantly greater with 3, 4, and 5 mg/kg of morphine than with 1.0 and 1.5% halothane.


Resuscitation of the moribund patient using portable cardiopulmonary bypass. The advancements in extracorporeal cardiopulmonary support through oxygenation and pumping units have permitted the explosive development of heart surgery. A battery-powered portable cardiopulmonary bypass machine has been used in 39 patients whose conditions precluded transport to the operating room. Nineteen patients with massive pulmonary emboli, 10 with extensive cardiopulmonary trauma, who had sustained massive drug overdose, and 2 with cardiogenic shock from acute myocardial infarction were successfully placed on cardiopulmonary bypass at the bedside within 15 minutes of cardiac arrest using femoral artery and femoral vein cannulation. Six patients who had cardiac arrest and suspected massive pulmonary emboli were found to have no mechanical cause for their arrest. Thirteen of the patients with massive pulmonary emboli were saved. Eight of the 10 patients who required portable cardiopulmonary bypass for massive traumatic thoracic injuries had control of hemorrhage and repair, allowing bypass to be discontinued. Two of these 8 patients had sustained transection of the proximal left anterior descending coronary artery. Sixteen patients survived for more than 30 days, and there are 15 long-term survivors.


Clinical and hemodynamic performance of a totally flexible prosthetic ring for atrioventricular valve reconstruction. A new, totally flexible ring for atrioventricular annuloplasty is described. The technique for its insertion closely follows the principles of Carpentier's selective annulus reconstruction [4]. Ninety-nine such rings have been inserted (47 in the mitral and 52 in the triscuspid position); 45 valves were simultaneously replaced. There were 6 (4 hospital and 2 late) deaths. The thromboembolic incidence was 4.8%. No instances of dehiscence or late ring deterioration have been detected. Thirty-four patients have been recatheterized, 19 of them with mitral rings. The mitral gradients and angiographic findings show the correct functioning of the implanted ring. It is concluded that use of this flexible ring, which adapts to the continuous changes of the normal mitral annulus, produces a more physiological type of valve operation.


The surgical treatment of Wolff-Parkinson-White Syndrome: evolution of improved methods for identification and interruption of the Kent Bundle. Fifty patients have been operated upon for the tachyarrhythmias associated with Kent bundles. The indications for operation were supraventricular tachycardia (SVT) in 23 and life-threatening tachyarrhythmia in 27. Among the unusual variants noted were multiple Kent bundles that conducted only retrograde in 3. Forty-nine patients underwent attempted interruption of the bundle of Kent followed by His bundle division in 6. One had elective division of the bundle of His. The surgical problems occurred in 13 patients with posterior septal Kent bundles. A new approach is outlined for this group. Division of the Kent bundle was successful in 31 patients, but 2 deaths occurred from cardiomyopathy. Seven patients had successful control of SVT by His bundle interruption. One patient with postoperative retrograde conduction has the SVT controlled with drugs. Eight have postoperative delta waves, but their SVT is controlled with drugs. There were 3 failures.


Acute penetrating tracheal trauma.

Acute penetrating tracheal trauma. During the past ten years, 20 patients with acute penetrating tracheal injury (15 cervical and 5 thoracic) have been treated at Grady Memorial Hospital. Ten of the 20 patients had other major associated injuries: 6 had esophageal wounds, 5 had arterial injuries, and 2 had additional wounds. In the first 5 patients treatment of the tracheal injuries consisted of tracheostomy alone. Later on, the tracheal wounds were managed according to type, site, size, and the type of other organ injury. Repair of the tracheal wound and tracheostomy were done in 3 patients, repair of the tracheal wound and temporary tracheal intubation in 4 patients, tracheocutaneous stoma in 1 patient, temporary tracheal intubation alone in 4 patients, and observation alone in 3 patients. Seventeen patients recovered from their injuries and 3 died from sepsis, respiratory insufficiency, or cerebrovascular accident. All 3 deceased patients had other major injuries. This experience suggests that the treatment of penetrating tracheal injury should depend upon the type, size, and site of the wound and the type of coexistent injury to other organs, and that primary repair of the tracheal wound can be carried out in the majority of the patients.


Surgical treatment of acute aortic regurgitation in infective endocarditis. During a six-year period 15 consecutive patients with isolated aortic regurgitation due to infective endocarditis were encountered. None had prior significant aortic valve disease. Elective valve replacement was performed in 13 patients; emergency operation was needed in only 1 patient because of intractable pulmonary edema. One patient died suddenly from acute heart block while undergoing medical treatment. Preoperative cardiac catheterization studies in 10 of the 14 patients revealed gross elevations of left ventricular end-diastolic pressure, pulmonary hypertension, depressed cardiac output, and 3 to 4+ aortic regurgitation. There was 1 early and 1 late postoperative death, both due to systemic embolism, yielding an overall surgical mortality of 14%. After a mean follow-up of 18 months, 10 of the 11 patients are in New York Heart Association Functional Class I. Most patients with acute aortic regurgitation secondary to infective endocarditis have clinically observable congestive heart failure and will eventually require valve replacement. If congestive heart failure can be stabilized by a medical regimen, a course of antibiotic therapy can be administered and elective valve replacement can be performed. The time taken for preoperative antibiotic treatment is not associated with irreversible myocardial damage sufficient to influence the results of operation.


Spectrum of pulmonary sequestration.

Spectrum of pulmonary sequestration. Bronchopulmonary sequestration was diagnosed in 17 patients ranging in age from newborn to 64 years. The sequestration was intralobar in 14 patients and extralobar in 3. The spectrum of symptoms could be divided into three patterns: no symptoms (6 patients), respiratory problems (8 patients), and cardiovascular problems (3 patients). Cardiovascular problems usually manifest themselves in the first few weeks or months of life and often have a respiratory component. In older patients the sequestration is first manifested by recurrent pulmonary infections or, if it remains uninfected, an asymptomatic density on chest roentgenogram. The definitive diagnostic study is arteriography. Operative treatment for the intralobar variety consists of segmental resection or, if the inflammatory process is more extensive, lobectomy. An extralobar sequestration may simply be excised.


Intrathoracic presentation of amebic liver abscess. Amebic infection is endemic in tropical and subtropical countries and still remains a common cause of chronic morbidity in these areas. This is a report of 10 patients with different intrathoracic presentations of amebic liver abscess who were treated surgically after conservative measures had failed. Five of these patients had empyema when first seen, 3 had lung abscess, and 1 had intrathoracic shadow that proved on exploration to be an amebic liver abscess. All of these 9 patients had abscesses  on the right side secondary to amebic liver abscess of the right lobe of the liver. The tenth patient had amebic pericarditis secondary to amebic abscess of the left lobe of the liver. Failure of conservative treatment in these patients is attributed to the thick nature of the amebic pus and the severe reaction of the pleura and pericardium to the amebic infection. To avoid the serious complication of pleuropulmonary amebiasis, early operation is advised for large liver abscesses that are unlikely to be controlled by conservative treatment. Transpleural drainage of such abscesses gives direct approach to their sites, which are commonly located in the superior part of the right lobe of the liver. Such drainage has proved to be safe provided that the patient is receiving antiamebic drug treatment.


Bypass of superior vena cava with spiral vein graft. The superior vena cava was successfully bypassed in a patient with superior vena cava syndrome due to granulomatous mediastinitis. A spiral vein graft constructed from autogenous vein was utilized. Complete relief of symptoms and graft patency documented by venography six months after the operation confirm the usefulness of this procedure in patients with superior vena cava obstruction.


A new instrument for measurements in cardiovascular surgery. An instrument for performing measurements in cardiac and vascular operations is described. This device is a modification of a vascular clamp that provides an accurate and simple method for making intracardiac measurements. The instrument is constructed to provide easy readout of even extremely small measurements.


A further look at tricuspid annuloplasty. Is it necessary to replace the tricuspid valve or insert a tricuspid ring for pure tricuspid insufficiency, or is repair satisfactory? In 96 of 113 patients with pure tricuspid insufficiency the tricuspid valve was repaired by converting the incompetent three-leaflet valve into a two-leaflet one. To avoid liver damage in these critically ill patients, the inferior caval tie was omitted during the open-heart procedure. There have been 5 deaths in the last 51 consecutive operations. Three patients developed recurrent tricuspid insufficiency secondary to failure of the mitral repair or replacement. It is concluded that tricuspid repair for pure tricuspid insufficiency is a simple and excellent method for treating severe, pure tricuspid insufficiency.


Experience with internal mammary artery grafts in 298 patients. The internal mammary artery (IMA) was used as a graft in 298 patients undergoing coronary bypass procedures. Two patients died during the operative period and 2 others died one year later. Most of the survivors are free of angina. Of the IMAs restudied 9 to 24 months postoperatively, 95% were patent. This group included nearly all the patients having angina after operation. There are some situations in which the IMA may have inadequate flow in comparison to the vein graft. These results suggest the IMA is an excellent graft in most coronary bypass procedures.


Evolving indications for preoperative intraaortic balloon pump assistance. Over a two-year period about 1,000 operations were performed with cardiopulmonary bypass. Intraaortic balloon pump assistance (IABP) was employed on 150 occasions, and a review of these has permitted clarification of the indications for its use. Sixty patients had IABP for carcinogenic shock either after infarction or cardiotomy, and 37 (62%) survived. Preoperative IABP in 90 high-risk patients resulted in survival for 79 (88%). The indications for prophylactic IABP included: (1) relief of severe pain, which occurred in 42 patients with acute coronary insufficiency, (2) improvement in the coronary perfusion pressure, which was accomplished in 20 patients with significant left main coronary artery occlusion or its equivalent, and (3) protection of left ventricular function, which war carried out in 28 patients with an LV ejection fraction of less than 0.40. The significance of the preoperative endocardial viability ratio (EVR) in relation to prophylactic IABP was also assessed: an EVR below 0.70 appears to be an indication for preoperative IABP.


A servocontrolled atrial-aortic assist device: experimental findings and clinical experience. A servocontrol system was developed to regulate a single roller pump left atrial-aortic (La-A) assist device. Responsiveness of the servomechanism to blood volume changes, myocardial damage, and mitral regurgitation was evaluated in 5 sheep and 6 dogs. Myocardial damage was induced by occlusion of coronary arteries. and the hemodynamic effects of La-A assistance were evaluated. While La-A assistance reduced left atrial pressures to low levels, the left ventricular end-diastolic pressure remained elevated in the severely damaged heart. LaA-assistance was used in 3 patients. Two were weaned from cardiopulmonary bypass after failure of intraaortic balloon counterpulsation, and 1 is a long-term survivor. The third was supported for 48 hours after attempt repair of complex congenital heart disease. The servocontrol device added to the safety of prolonged La-A assistance. This mode of assistance should be considered when intraaortic balloon counterpulsation has failed.


Surface-induced profound hypothermia in infant cardiac operations: a new system. A new system of surface-induced profound hypothermia for infant cardiac operations has been developed in order to overcome problems inherent in the current techniques using crushed ice, water baths, and similar methods. The hypothermic chamber consists of two parts: a lower part, containing a refrigeration unit and a blower fan capable of lowering the air temperature in the chamber to -6 degrees C, and an upper part made of Plexiglas that has a completely detachable end to allow easy access to cannulas, the anesthesia hose, and the infant. A temperature panel recorder to monitor the infant's esophageal and rectal temperatures and the ambient chamber temperature is incorporated into the unit. Following evaluation in the animal laboratory, the hypothermic chamber has been successfully used in 10 infants without any complications attributable to the technique. This method provides a rapid and uniform drop of the body temperature and even skin cooling, eliminates the possibility of contact skin lesions, saves medical and paramedical personnel time in preparation of the infant and equipment, and allows observation of the child during the cooling phase. This hypothermic chamber has facilitated infant hypothermic operations.


Myocardial injury associated with potassium arrest. The relative efficacy of potassium-induced ischemic arrest using buffered, isosmotic potassium (25 mEq/liter) was compared with hypothermic arrest in an experimental protocol employing an intact canine heart preparation. Myocardial function (LVSW, dp/dt max), serum creatine phosphokinase levels, myocardial perfusion, and light and electron microscopical examination of the heart were assessed in five groups of 5 dogs each. There was one control group (90 minutes of bypass, no anoxia) and four experimental groups, each subjected to 1 hour of ischemic arrest and 30 minutes of reperfusion, comparing normothermic ischemic arrest (NIA), hypothermic ischemic arrest (myocardial temperature less than 25 degrees C) (HIA), normothermic potassium arrest (NKA), and hypothermic potassium arrest (HKA). Myocardial function decreased significantly following NIA and NKA but remained essentially equal in the control, HIA and HKA groups. Serum creatine phosphokinase analysis documented a significant increase in each group of animals: 2,250 mU after NIA, 1,778 mU after NKA, 1,388 mU after HIA, 1,220 mU after HKA, and 838 mU after control bypass. Left ventricular myocardial perfusion was unmeasurably low after NIA, reduced to 111 m/100 gm of tissue/min after NKA, and increased to 165 to 188 ml/100 gm/min in the control, HIA and HKA groups. Electron microscopical studies showed a range of myocardial changes, from probably irreversible damage after NIA to similar but less diffuse changes after NKA, and to potentially reversible changes after HKA and HIA with the least alteration from control after HIA. The results indicate that potassium arrest alone is not as effective as hypothermia in preventing ischemic injury, and the combination of hypothermia with a single 150 cc administration of potassium (25 mEq/liter) does not appear to provide significant additional protection.


Results following physiological repair for tricuspid atresia. Fourteen patients underwent a physiological operation for tricuspid atresia. Seven patients survived up to 3 years after operation. Six patients underwent hemodynamic studies 2 to 34 months postoperatively (mean, 15 months). Average age at the time of operation was 14 years (range, 5 to 25 years). Postoperative studies showed 4 patients to be in sinus rhythm and 2 in junctional rhythm. Right atrial pressure was elevated an average of 17 mm Hg (range, 10 to 34 mm Hg). All patients showed good atrial transport function regardless of their rhythm. Two had a right atrium-left pulmonary artery gradient of 1.5 to 10 mm Hg across the conduit. Average arterial saturation was 92% (range, 87 to 97%), on improvement of 13% over preoperative values. Residual hypoexmia was due to pulmonary vein desaturation and to atrial right-to-left shunting early postoperatively and later, to atrial right-to-left shunting alone.


Permanent cardiac pacemakers in children: technical considerations. Placement of permanent cardiac pacemakers in children presents technical problems that are not encountered in the adult. Problems unique to pacemaker implantation in children are related to the patient's size, the relative bulkiness of pulse generators, the lack of subcutaneous tissue, and the child's growth and long life expectancy. Based on our experience with implantation of 27 permanent cardiac pacemakers in 13 children, we have found that the use of small pulse generators, placement of epicardial leads, insertion of properitoneal pulse generators, and use of recharabeable pacemakers are satisfactory methods in children.


Management of uremic pericarditis: a report of 11 patients with cardiac tamponade and a review of the literature. Uremic pericarditis remains a significant cause of morbidity and mortality in most hemodialysis programs. A review of the literature and out own experience show that uremic pericarditis should be vigorously treated when detected. Usually an increase in the dialysis program with regional heparinization is sufficient to control the pericarditis. When signs of pericardial effusion are manifested, patients often progress rapidly to cardiac tamponade. A surgical anterolateral pericardiectomy is the most satisfactory measure in controlling pericardial effusion and preventing fatal cardiac tamponade. Although these patients have severely impaired renal function, the operation can be performed safely with a low morbidity and mortality.


Method for replacement of the ascending aorta and aortic valve with reimplantation of the coronary arteries. A method for replacing the entire ascending aorta and aortic valve is described that employs direct anastomosis of the coronary ostia to the graft, facilitated by appropriately time periods of hypothermic ischemic cardiac arrest. The advantages of this technique are that proper placement of sutures around the coronary ostia is simplified and that hemostasis at the aortic annulus and coronary anastomosis can be evaluated before the aortic clamp is removed and suture lines become inaccessible.


Pulmonary artery sling.

Pulmonary artery sling. A case of pulmonary artery sling in a 1-year-old boy, treated by resection of the left pulmonary artery (LPA) at its origin from the right pulmonary artery (RPA) and reanastomosis of the LPA to the main pulmonary artery (MPA), is reported. In this patient the LPA-MPA anastomosis was demonstrated to be patent in a follow-up pulmonary angiogram six months after the operation. Pulmonary artery sling should be kept in mine when assessing respiratory distesss syndrome in children.


Glomerular filtration rate and effective renal plasma flow following treatment with phenobarbital. SPF-male rats were treated intraperitoneally with phenobarbital (30 mg/kg/day) or 0.9% sodium chloride for 4 days. Endogenous creatinine clearance in conscious rats and inulin clearance in nondiuretic rats under inactin anesthesia were measured 24 hr following the last injection. In an additional group of treated rats diuresis was induced by sodium chloride and mannitol and then inulin- and PAH clearance were measured simultaneously. Following 4 days treatment with phenobarbital, endogenous creatinine clearance and inulin clearance were not significantly different in control and phenobarbital-treated animals. In contrast significant changes were found in urine volume and PAH clearance in the phenobarbital-treated animals. These results do not reflect any change in glomerular filtration rate, but might be attributed to an increase in renal plasma flow or an activated tubular transport system following phenobarbital administration.


Suppression of ethanol intake following administration of dopamine-beta-hydroxylase inhibitors in rats. A comparison was made between the efficacy of action of dopamine-beta-hydroxylase and/or aldehyde dehydrogenase inhibition in suppressing voluntary ethanol consumption in rats. Calcium carbimide, which caused the largest increase in blood acetaldehyde levels following ethanol injections, was the least effective in reducing ethanol consumption, whereas FLA-63, which had a smaller effect on blood acetaldehyde levels, was the most potent suppressor of ethanol ingestion. Disulfiram, which inhibits both aldehyde dehydrogenase and dopamine-beta-hydroxylase had an intermediate effect in terms of raising blood acetaldehyde levels and in suppressing ethanol intake. It is suggested that the inhibition of dopamine-beta-hydroxylase may be at least partly responsible for the suppression of ethanol intake seen following disulfiram administration, and that disruption of catecholamine synthesis may prove to be a more effective method for suppressing ethanol consumption.


Hepatic function after acute of subchronic nicotine administration in untreated mice and mice treated with hepatotoxic chemicals. Male mice treated with nicotine hydrochloride either acutely (5 mg/kg i.p.) or subchronically (5 mg/kg i.p. daily for 3 weeks; 25 mg/liter in drinking water for 2-3 months) showed no evidence of hepatic dysfunction, as measured by serum glutamic-pyruvic transaminase or serum alkaline phosphatase activities. Neither acute nor subchronic administration modified the hepatotoxic response to a potent hepatotoxin (carbon tetrachloride), nor that of less potent hepatotoxins chloroform or 1, 1, 1-trichloroethane, nor was the cholestatic effect of alpha-naphthylisothiocyanate modified.


[The effect of mepyramine and 48/80 on the histamine content of pleural exudates in the rat]. The influence of pretreatment with the antihistaminic, mepyramine, or with the histamine liberator 48/80 was studied on the volume and the histamine content of pleural exudates induced in rats by intrapleural injection of turpentine, silver nitrate or carrageenan. The fluorometric determination of histamine was performed in the exudates collected at different times after injection of the irritant. In control animals the histamine levels were different from those previously found by the authors using biological assays. In rats pretreated with mepyramine or compound 48/80, the effects observed varied according to the nature of the irritant used to induce pleurisy.


The interaction of acetylcholine and d-tubocurarine on the end-plate free muscle membrane of rat diaphragm in low chloride solution. The interaction of acetylcholine (ACh) and d-tubocurarine (dTC) on the membrane potential of end-plate free parts of rat diaphragm muscle fibres was studied using a conventional microelectrode technique. ACh only caused membrane depolarizations when the external chloride concentration was diminished. Therefore, all experiments were performed in a 40 mM Cl- containing medium. A bell-shaped log-dose response curve was obtained with ACh. Maximal depolarization occurred at 3.10(-4) M. The pD2 value for ACh was calculated to be 4.2. The log-dose response curve was shifted to the right in the presence of dTC; besides, the maximum seemed to be depressed. The pA2 values for dTC appeared to be 4.9. It was concluded from these data that the cholinergic receptors outside the end-plate region have binding properties, which differ considerably from those of end-plate or postdenervational receptors.


[Sleeping time and awaking blood concentration of hexobarbital influenced by glucose and adrenaline in rats of both sexes]. Sleeping times in male and femal rats are prolonged after the simultaneous i.p. administration of adrenaline and hexobarbital sodium. The blood concentration of hexobarbital at awakening is unchanged in male rats, while in females this concentration is decreased. When adrenaline is given s.c., no change in sleeping times is observed in female and male rats, while the blood concentration of hexobarbital for the two sexes is decreased. Glucose, given p.o. or i.p., has no influence on sleeping times or on hexobarbital concentrations. The hexobarbital concentrations at awakening is higher in female than in male rats.


A new model of active avoidance conditioning adequate for pharmacological studies. A model of rapid learning (active avoidance conditioning), using rats, is described which induces retention depending on the number of trials to which the animals are submitted. For 3 trials (double stimulation) adequately spaced, the memory trace lasts for 48 hr, whilst 6 trails induce a trace for 10 days. One single application of the double stimulation does not give any apparent retention in normal rats for 24 hr. This experimental fact is used to study and screen the activity of substances on the learning process. Animals treated with piracetam, pemoline, methamphetamin, strychnine, pyritinol and meclofenoxate before this single trial, display evidence of retention 24 hr later. Other substances, with known clinical CNS activites, eg, tranquillizers, analgesics, etc... show no positive effect on the mnesic trace.


The importance of amino and ester functions for the curarizing activity of quaternary ammonium salts. The curarizing and the depolarizing activities of derivatives of suxamethonium and decamethonium have been studied. A receptor model for suxamethonium and for decamethonium is proposed.


Discriminative stimulus properties of a low dl-amphetamine dose. Using a two-lever food-reinforced operant procedure, rats (n = 10) were trained to discriminate 0.16 mg/kg dl-amphetamine from saline. Over the dose range 0.08 to 0.63 mg/kg, cue detection was found to be dose-dependent (ED50: 0.13 mg/kg). However, 5 mg/kg dl-amphetamine was not generalized with the standard treatment. Further generalization experiments indicated that hydroxyamphetamine (ED50: 0.16 mg/kg) produces a discriminative stimulus similar to that of 0.16 mg/kg dl-amphetamine. Apomorphine (0.16 mg/kg), chlordiazepoxide (10 mg/kg), desipramine (10 mg/kg), fentanyl (0.04 mg/kg), haloperidol (0.04 mg/kg) and isopropamide (0.04 mg/kg) were not generalized with dl-amphetamine. Haloperidol (0.04 to 0.16 mg/kg) blocked the perception of 0.16 mg/kg dl-amphetamine in a dose-related way (ED50: 0.092 mg/kg). It is concluded that the discriminative stimulus properties of low dl-amphetamine doses differ qualitatively from those of high doses. The discriminative stimulus produced by 0.16 mg/kg dl-amphetamine presumably originates peripherally, whereas that produced by high doses of the drug reportedly is of central origin.


Calcium-dependent toxic effects of digoxin in isolated myocardial preparations. On isolated guinea-pig papillary muscles as well as on electrically driven atria digoxin was infused into the bath fluid until cardiac arrest occurred. The concentration of digoxin which caused standstill is defined as the toxic one. The toxicity was determined under various Ca2+-concentrations. On the papillary muscle the increase of extracellular Ca2+ from 0.9 to 7.2 mM increased the toxicity of digoxin, i.e. significantly diminished its toxic concentrations. Likewise, on electrically driven atria an increase of Ca2+ from 0.45 to 7.2 mM increased the toxicity of digoxin. These results demonstrate that with regard to the toxicity Ca2+ and digoxin act synergistically.


Morphine effects on the cardiovascular system of awake, freely behaving rats. The effects of small, i.v. infusion of morphine on the heart rate was studied in unanesthetized rats. A dose-response study indicated that all values of morphine between 5 and 1000 mug/kg resulted in a transient bradycardia. In addition, morphine doses above 20 mug/kg induced cardiac irregularities including atrial fibrillation, atrioventricular block and temporary cardiac arrest. When morphine was delivered daily over a period of eight weeks, cardiac responding (first arrhythmias and then the bradycardia) became tolerant at a time when catatonia was still present. These results indicate that in an unanesthetized rat, profound cardiovascular effects are seen to very small, mug range, doses of morphine.


Blockade by SKF 525A of the rat sympathetic ganglia and the adrenal medulla. SKF 525A (1.5-9 mg/kg), depending on the dose used, reduced or abolished the hypertensive effect of McN-A-343, DMPP and nicotine, but did neither noticeably affect the hypertensive effect of tyramine, adrenaline and noradrenaline, nor the hypotensive effect of acetylcholine and orciprenaline. It is concluded that SKF 525A blocks the rat sympathetic ganglia and the adrenal medulla. This blockade is non-specific. It is suggested that the blockade results from the stabilizing effect of SKF 525A on postsynaptic membranes of the sympathetic ganglia and the adrenal medulla.


Metabolism and pharmacokinetics of orciprenaline in various animal species and man. The physiological disposition of tritiated orciprenaline, the 3,5-dihydroxy-isomer of isoprenaline, has been studied in rat, rabbit, cat and man. In the lungs, liver and kidneys of the rat higher 3H-concentrations were found than in the plasma after i.v. injection. A higher percentage of unchanged drug was located in the heart, lungs and skeletal muscle only. In the plasma of rabbit and cat as well as man the decline of 3H-activity was biphasic after i.v. administration with a half-life of 15 hr in the rabbit 6 hr in cat and man for the slower phase. The pharmacokinetic analysis of the post-infusion data in man resulted in an open two-compartment model with a high volume of distribution (ca. 700 liters). The total clearance (1400 ml/min) was rather high. The renal clearance contributed to 10 per cent only. The amount of drug absorbed after oral administration amounted to 44%, the reduced biovailability of 10 per cent indicated a fist-pass effect. The metabolism lead only to conjugates with glucuronic acid, most probably at one of the phenolic hydroxyl groups in rat, rabbit and man. The cat did not metabolize orciprenaline to an appreciable amount.


Pharmacokinetics of sulpiride after oral and intravenous administration in the rat and the dog. The plasma concentration of sulpiride was measured in the rat and in the dog after oral and i.v. administration of the drug. In the rat only traces (less than 1 mug/ml) of sulpiride were detected in plasma after an oral dose of 100 mg/kg. The peak concentrations in 3 dogs given 25, 50 or 100 mg/kg orally were 6.1, 15.6 and 23.9 mug/ml, respectively. The pharmacokinetic data after i.v. injection were compared to earlier observations with the related orthopramide compound, metoclopramide. The half-life of sulpiride in dog plasma (1.6 -- 3.4 hr) is longer than that of metoclopramide, but in the rat there is little difference between the two compounds. Both of the compounds have large total apparent volumes of distribution (1-2 1/kg) in the two species. The marked species difference in the systemic bioavailability of oral sulpiride should be taken into account when the orthopramide drugs are evaluated in pharmacological tests.


Probenecid-induced effects on bile flow and biliary excretion of 3H-ouabain. Probenecid-induced effects on bile flow and biliary excretion of exogenous compounds, e.g. 3H-ouabain were investigated on bile-fistula rats. Clearance measurements of 14C-mannitol under incresed doses of probenecid gave evidence that the drug acts at the canalicular site only. Biliary excretion of radioactivity after 14C-probenecid administration was found to be saturated at a dosage of 100 mg X kg-1. Probenecid exerts its choleretic effect by osmotic activity in a "bile acid-like" manner. This is confirmed by a close positive correlation between the excretion of radioactivity after treatment with 14C-probenecid and bile flow. The effects of probenecid on the biliary excretion of exogenous compounds, e.g. ouabain, imply beside choleresis also inhibitory effects on transport systems. As a result of both effects the biliary excretion of ouabain remains unchanged within a within a wide range of probenecid doses.


The influence of extracellular calcium on muscarinic receptors in vascular smooth muscle. The present study was designed to investigate the influence of extracellular calcium (Ca++) on the affinity of cholinergic agonists and antagonists for muscarinic receptors in isolated rabbit aortic strips. Dose-response curves which demonstrate the effect of acetylcholine on the force of contraction in the presence of various Ca++ concentrations were made. The affinity constant was calculated and the intrinsic activity was determined at each of the different Ca++ concentrations used. In addition, the relationship between extracellular Ca++ and the pA2 value for atropine was determined. No apparent relationship between the affinity of acetylcholine for the cholinergic receptors and Ca++ concentration in vascular muscle was demonstrated. However, the intrinsic activity was altered when the extracellular Ca++ was varied. In addition, atropine was effective to the same degree both in the presence and complete absence of Ca++. These results are discussed in relation to the dependency of acetylcholine on extracellular Ca++ to induce contractile responses after receptor occupancy in vascular muscle.


Anticholinergic activities of D(-)R- and L(+)S-mandeloylcholines. The nature of the antagonism of the D(-)R- and L(+)S-mandeloylcholines to acetylcholine (ACh) was investigated at the muscarinic receptors of the guinea-pig ileal longitudinal muscle. The nature of the inhibition of acetylcholinesterase (AChE) and serum cholinesterase (ChE) by the mandeloylcholines was also investigated. Both optical isomers of mandeloylcholine were reversible competitive antagonists of ACh at the muscarinic receptors. One molecule of mandeloylcholine combined with one receptor. The apparent affinities (1/KB, where KB = dissociation constant) of the mandeloylcholines were in the following order: homatropine greater than D(-)R-mandeloylcholine greater than DL(+/-)RS-mandeloylcholines = L(+)S-mandeloylcholine. Therefore, the mandeloylcholines were stereoselective for muscarinic receptors. The mandeloylcholines were (mixed) reversible inhibitors (competitive and noncompetitive) of ACh hydrolysis by AChE. There was no significant difference between the apparent K1 values of the mandeloylcholines in the inhibition of AChE. The mandeloylcholines were mixed reversible inhibitors (competitive and noncompetitive) of ChE. D(-)R-mandeloylcholine had a higher apparent K1 than its isomer.


Effects of morphine, chlorpromazine and chlordiazepoxide on shock-induced changes in basal skin conductance. Chlorpromazine (12.5 and 25 mg/70 kg, i.m.) and chlordiazepoxide (25 and 50 mg/70 kg, i.m.) were compared with morphine (15 and 30 mg/70 kg, i.m.) and placebo in their effects on electric shock-induced increases in basal skin conductance. Morphine and chlorpromazine attenuated the increase compared with placebo, while chlordiazepoxide did not. None of the treatments produced reliable effects on the phasic responses to the stimuli.


Tremorogenic effects of intracaudate d-amphetamine and their suppression by dopamine. Pronounced tremors were produced in unanesthetized cats following intracaudate (I.C.) injections of either d-amphetamine (15 mug), dl-methamphetamine (20 mug), l-amphetamine (48 mug) or 3-methoxytyramine (68-120 mug). Yet, a series of other chemically and pharmacologically related phenylethylamines, including dopamine (90 mug), were not tremorogenic even at substantially higher doses. The d-amphetamine tremors developed rapidly, failed to exhibit tachyphylaxis to repeated challenging doses (15 mug) and were not influenced by pretreatment with alpha-methyl-p-tyrosine. They also developed independently of local acetylcholine activity as evidenced by the inability of cholinergic antagonists (scopolamine and hemicholinium) to interfere with the tremors. Significant qualitative differences were found between the I.C. effects of d-amphetamine (15 mug) and dopamine (15-90 mug): d-amphetamine further increased the intensity of ongoing tremors induced by physostigmine (111 mug I.C.), whereas, dopamine readily inhibited the latter. When superimposed, I.C. dopamine was equally effective in suppressing d-amphetamine tremor activity. The results emphasize the selective tremorogenic actions of d-amphetamine and call attention to the contrasting stabilizing role of dopamine. This would suggest that two types of adrenergic receptor sites are operative in the caudate in neuroregulation of involuntary movements.


Potentiation of morphine-induced seizure by 6-hydroxydopamine. The influence of 6-hydroxydopamine on morphine-induced convulsions were investigated in rats. Morphine, in doses up to 100 mg/kg did not produce any convulsive pattern in vehicle-pretreated rats. The pretreatment of rats by 6-hydroxydopamine strongly potentiated the seizure producing activity of morphine and the dose-response curve of seizure severity shifted to the right. These results suggest that brain catecholamines are involved in the mechanism of morphine-induced convulsions.


Effect of chlorpromazine or sulpiride and alcohol on psychomotor skills related to driving. A double-blind cross-over trial was conducted with 20 healthy paid volunteers for the evaluation of the subacute effects of chlorpromazine (CPZ) and sulpiride, in oral doses used for anxious outpatients, on psychomotor skills related to driving. Psychomotor performance was measured on the 7th and 14th days of treatment at 30, 90 and 150 min after the intake of 0.5 g/kg of an alcoholic or placebo drink. After the neuroleptics alone, reaction and coordination skills, but not attention, were slightly impaired, CPZ differing significantly from the placebo on the 14th day. Both drugs interacted additively with alcohol. The combined administration of CPZ and alcohol led to inaccuracy, a slowing of reactions and impaired proprioception and coordination. The combination of sulpiride and alcohol increased the error rate in the choice reaction test and impaired coordination in the coordination test driven at a free speed. It is concluded that the psychomotor decrement that occurs after 2 weeks of treatment with small doses of CPZ may effect the ability to control a motor vehicle. The concurrent administration of alcohol during treatment with CPZ or sulpiride may cause some extra risk in traffic or occupational life.


The influence of reserpine on the responsiveness to norepinephrine and electrolyte contents of rabbit atria. This study was designed to investigate the relationships between reserpine-induced supersensitivity and electrolyte levels in isolated rabbit atria. Atria from reserpine-treated (1, 3 or 4 mg/kg 24 hr before) and untreated rabbits were placed in an isolated organ bath for determination of dose-response relationships for norepinephrine, or were used for electrolyte assay. Reserpine-treated atria had greater resting and maximum rates of beat than did untreated atria. However, the ED50 concentrations of norepinephrine producing a rate response were similar. Atria pretreated with 1 or 3 mg/kg reserpine were supersensitive to the inotropic effect of norepinephrine. 4 mg/kg reserpine did not induce inotropic supersensitivity. Atrial sodium contents were significantly increased by 3 mg/kg reserpine. Potassium contents were increased by 1 and 4 mg/kg reserpine. Calcium contents were significantly decreased by 4 mg/kg reserpine, while magnesium contents were increased by 1 and 4 mg/kg. Reserpine induced supersensitivity to the inotropic effects of norepinephrine but did not alter the sensitivity to the chronotropic effect of the drug. This supersensitivity may be linked to alterations in the tissue's homeostatic mechanisms for calcium.


Mechanism of the hypotensive effect of prazosin. Prazosin is a quinazoline that has a long lasting hypotensive effect. To investigate the mechanisms underlying its action experiments were performed in 75 dogs anesthetized with pentobarbitone sodium. Prazosin, after i.v. injection, lowered arterial pressure without altering heart rate and venous pressure, and decreased pressor responses to epinephrine, norepinephrine and splanchnic nerve stimulation. Orthocarboxybenzeno-seleninic acid, an alpha-adrenoceptor blocker, antagonized the hypotensive effect of prazosin. Neither administration of propranolol nor carotid sinus local anesthesia impaired prazosin hypotensive effects. Topical application of prazosin on both carotid sinuses had no effect on general arterial blood pressure; after intravenous administration it did not change the hypotension caused by electrical stimulation of the carotid sinuses. The depressor effects of papaverine and sodium nitrite on blood pressure were enhanced by prazosin. It is concluded that this drug exerts its hypotensive effect by blocking, alpha-adrenoceptors and by possibly relaxing vascular smooth muscle.


The infectious complications of sarcoidosis: a current perspective. The incidence of indections requiring hospitalization was determined in 122 patients with sarcoidosis. The group was remarkably free of infection except for three patients with Aspergillus mycetoma occurring in areas of long-standing parenchymal involvement with cystic degeneration. There was a single instance of complicating pulmonary tuberculosis, and the only extrathoracic infection was a single instance of disseminated herpes zoster. This study confirms that aspergillosis, not tuberculosis, is currently the most common infectious complication of sarcoidosis. Although previous case reports have suggested an increased incidence of invasive fungal infection in patients with sarcoidosis, there is little to support this concept. None of the patients in the present study group developed these fungal infections during a mean 7.2-year follow-up. The clinical presentation of many of the previously reported cases suggests that the entire course of the granulomatous illness was infectious in nature rather than sarcoidosis with complicating infection.


Acute renal failure in patients with acute pancreatitis. We describe five patients with acute pancreatitis in whom acute renal failure developed in the absence of hypotension. Pancreatitis was diagnosed clinically, with mean serum and urinary amylase levels of 766 +/- 197 (SE) and 2,378 +/- 572 units/100 ml, respectively. Acute renal failure developed within 24 hours after admission in all patients. It was manifested by oliguria, elevated levels of serum creatinine (mean, 6.9 +/- 1.1 mg/100 ml) and BUN (105 +/-28 mg/100 ml); a urinary sodium level of 72.0 +/- 6.6 mEq/liter; and isosmotic urine (355 +/- 31 mOsm/liter). The mean uric acid level was 18.6 +/- 1.6 mg/100 ml. Blood pressure was recorded frequently, and the lowest mean diastolic pressure was 96 +/- 6 mm Hg. The duration of the oliguric phase of acute renal failure was 8.2 +/- 1.7 days, and all patients recovered from both the acute pancreatitis and acute renal failure. In summary, acute pancreatitis, per se, can precipitate acute renal failure. It occurs early in the course of the pancreatitis, and extreme hyperuricemia is frequent finding that does not adversely affect the recovery of renal function.


Elevated IgM levels, edema, and fatigue syndrome. Two patients with nonpitting edema associated with extreme fatigue were found to have hyperimmunoglobulinemia M and eosinophilia. Additional laboratory abnormalities included an elevated ESR and the presence of rheumatoid factor. One patient had the symptom complex continually, and it was controlled with minimal amounts of prednisone. The other patient had intermittent symptoms, with eosinophilia in the asymptomatic state and decreased eosinophil counts while symptomatic. His symptomatic episodes were diminished in duration by methylprednisolone. We believe these cases, which have been evaluated for eight and four years, respectively, constitute a new syndrome that has substantial morbidity, but that is apparently benign and that can be controlled with corticosteroids.


[Behavior of various metabolites of carbohydrate metabolism in the liver of young pigs following inhibition of C-11 hydroxylase and adrenalectomy]. The effects of glucocorticoid depression by C-11 hydroxylase inhibition and total adrenalectomy upon certain metabolites of the plasma, liver, and muscles that are related to gluconeogenesis were studied on ten store pigs. Metopiron caused decline of glucose and pyruvate concentrations in plasma and drop of liver glycogen. Total adrenalectomy caused changes of the same kind but much stronger in the agonal phase, yet without rendering the animals hypoglycaemic. Muscular glycogen dropped to one third of the normal. The results are discussed with reference to earlier studies into store pig.


[Experimental hypocalcemia as a model for the study of etiopathogenetic factors of hypocalcemic hysteroparesis due to parturition in dairy cows]. Hypocalcaemia was experimentally induced to cattle of different age groups, and the resulting model showed that intraplasmic parathormone-induced calcium rise due to activation of calcium from the apatite crystals of the skeletal depot was a function of age and a sufficiently plausible explanation for age-dependent growing morbidity rates in the context of hypocalcaemic hysteroparalysis in concomitance with parturition. High vitamine D3 doses are recommended for systematic prophylaxis.


[Studies on endocrine and spermatogenic testicular function. 5. Relationship between dietary protein quality and blood plasma levels of free and bound testosterone in adult rats]. The blood plasma content of testosterone-linking globulins, free testosterone, and total testosterone in 80 adult Wistar rats which received different qualities of feed proteins was determined by means of balancing dialysis and ultracentrifugation, using 3H-testosterone. The first group received casein with four per cent methionine added, the second maize gluten complement with amino acid, and the third casein with methionine and gelatin in a 2:3 ratio, while the fourth group was fed pure maize gluten diet. (Biological valence declined in the given order.) Assays of 100 ml blood plasma of each animal in the first and second groups gave 0.9 mug of testosterone-linking globulins (0.18 mug in third and fourth groups), about 9.0 mug total testosterone (2.5 mug in third and fourth groups), and some 1.4 mug free testosterone (0.55 mug in third and fourth groups). Discussed in this paper is the possible mechanism of regulation by which feed protein quality leads to variation of free testosterone levels in the blood plasma.


[LD 50 and selenium concentration in the organs of rabbits following oral administration of sodium selenite and testing of the toxicity of Ursoselevit-Prämix]. LD50/24hr was established in the first of a series of experiments on 72 rabbits for orally applied sodium selenite. The dosage was 8.62 mg/kg live weight, the confidence interval being (1 - alpha = 0.95) +/- 0.13 mg/kg. The value was four times as high following intravenous application. Complete lethality was recorded from 15 mg Na2SeO3/kg live weight within 21 hours. Thirty-six animals were involved in the second experiment of the series. They had 50 or 100 per cent Ursoselevit-Prämix (30 ppm Se) in their rations. Body mass development of the test animals was superior to that recorded from the controls in the first 50 days, after which limit the former declined strongly in a few days. Their general condition worsened. Postmortem findings, following slaughter, included catarrhal enteritis, toxic liver dystrophy, scattered pulpous tumours in the spleen, and interstitial nephritis. In the third experiment (50 per cent Ursoselevit-Prämix with 60 ppm Se in the rations), the test animals developed better than the controls during the first two months, after which point they exhibited the same clinical symptoms as those observed in the second experiment, stopped to put on weight, and eventually turned cachectic. The pathomorphological findings were identical with those obtained from the second experiment. The selenium concentrations in the organs of the test animals all were much higher than those of the controls. Their amounts in excess to base values were up to eleven times in the blood, nine times in the liver, twelve times in the kidneys, and 13 times in the muscles.


[Single and complex effect of ammonia and hydrogen sulfide in the air on small laboratory animals (rats) under various environmental conditions. 1. Effect of ammonia]. The maximum per-animal-position concentration of ammonia was studied under defined environmental conditions and with reference to basic stress on thermoregulation. The normal value of 30 ppm NH3, laid down in TGL 29084, was experimentally confirmed.