Influence of hydrostatic pressure on the effects of the heavy metal cations of manganese, copper, cobalt, and nickel on the growth of three deep-sea bacterial isolates.

Increases hydrostatic pressure varied the 72-h growth yield of three bacterial isolates from the deep sea in the presence of heavy metal cations of Mn, Cu, Co, and Ni, depending on the bacterial isolate, the metal cation and its concentration, and the level of hydrostatic pressure. Above atmospheric, hydrostatic pressure was found to have one of the following four effects on the response of culture growth to a heavy metal cation. (i) It could be without effect; (ii) it could enhance inhibition by a metal cation; (iii) it could increase the 72-h growth yield by a metal cation; or (iv) it could protect against a growth inhibitory effect noted at a lower pressure. Possible reasons for these varied responses are discussed.


Fermentation of cellulose and cellobiose by Clostridium thermocellum in the absence of Methanobacterium thermoautotrophicum.

The fermentation of cellulose and cellobiose by Clostridium thermocellum monocultures and C. thermocellum/Methanobacterium thermoautotrophicum cocultures was studied. All cultures were grown under anaerobic conditions in batch culture at 60 degrees C. When grown on cellulose, the coculture exhibited a shorter lag before initiation and growth and celluloysis than did the monoculture. Cellulase activity appeared earlier in the coculture than in the monoculture; however, after growth had ceased, cellulase activity was greater in the monoculture. Monocultures produced primarily ethanol, acetic acid, H2 and CO2. Cocultures produced more H2 and acetic acid and less ethanol than did the monoculture. In the coculture, conversion of H2 to methane was usually complete, and most of the methane produced was derived from CO2 reduction rather than from acetate conversion. Agents of fermentation stoppage were found to be low pH and high concentrations of ethanol in the monoculture and low pH in the coculture. Fermentation of cellobiose was more rapid than that of cellulose. In cellobiose medium, the methanogen caused only slight changes in the fermentation balance of the Clostridium, and free H2 was produced.


Fermentation of mucin and plant polysaccharides by strains of Bacteroides from the human colon.

Ten Bacteroides species found in the human colon were surveyed for their ability to ferment mucins and plant polysaccharides ("dietary fiber"). A number of strains fermented mucopolysaccharides (heparin, hyaluronate, and chondroitin sulfate) and ovomucoid. Only 3 of the 188 strains tested fermented beef submaxillary mucin, and none fermented porcine gastric mucin. Many of the Bacteroides strains tested were also able to ferment a variety of plant polysaccharides, including amylose, dextran, pectin, gum tragacanth, gum guar, larch arabinogalactan, alginate, and laminarin. Some plant polysaccharides such as gum arabic, gum karaya, gum ghatti and fucoidan, were not utilized by any of the strains tested. The ability to utilize mucins and plant polysaccharides varied considerably among the Bacteroides species tested.


Variations in the microbial log reduction curves of irradiated cod fillets, shrimp, and their respective homogenates.

When cod (Gadus morhua morhua) and headless white shrimp (Penaeus setiferus) were gamma irradiated with a series of low-ionizing radiation doses, a "shoulder(s)" was observed in the graph (log microbial counts versus dose) in the approximate range of 25 to 75 krads. When the microbiological survivors were differentiated into total counts, proteolytic and pseudomonad-type bacteria, it was observed that the pseudomonad-type bacteria were rapidly destroyed by 25 krads and that proteolytic bacteria were destroyed at a faster rate than the rest of the microorganisms. When cod fillets and shrimp were compared with their respective homogenates and irradiated at doses of 0, 10, 20, 30, 40, 50, 60, 80, 100, 150, 200, and 300 krads, the homogenates did not exhibit the characteristic shoulders. A further experiment was designed to test surface versus uniform dispersion of microorganisms on/in gelatin disks subjects to low doses of irradiation. Differences were found that may explain the observed differences between solid food materials such as fish fillets and shrimp and their homogenates.


Isolation and identification of xanthomegnin, viomellein, rubrosulphin, and viopurpurin as metabolites of penicillium viridicatum.

Four of the metabolites of Penicillium viridicatum 66-68-2 grown on rice cultures were isolated and identified as xanthomegnin, viomellein, rubrosulphin, and viopurpurin. Melting points, elemental analysis, and infrared, ultraviolet, and field desorption and electron impact mass spectra of the isolated compounds were consistent with values reported in the literature for these compounds. In addition, diacetate and triacetate derivatives were prepared, and the chemical and physical analyses of the derivatives were also consistent with literature data. Proton magnetic resonance spectroscopy and thin-layer chromatography were also used for the additional identification of selected compounds.


Microbiological profiles of the Viking spacecraft.

Planetary quarantine requirements associated with the launch of two Viking spacecraft necessitated microbiological assessment during assembly and testing at Cape Canaveral and the Kennedy Space Center. Samples were collected from selected surface of the Viking Lander Capsules (VLC), Orbiters, (VO), and Shrouds at predetermined intervals during assembly and testing. Approximately 7,000 samples were assayed. Levels of bacterial spores per square meter on the VLC-1 and VLC-2 were 1.6 x 10(2) and 9.7 x 10(1), respectively, prior to dry-heat sterilization. The ranges of aerobic mesophilic microorganisms detected on the VO-1 and VO-2 at various sampling events were 4.2 x 10(2) to 4.3 x 10(3) and 2.3 x 10(2) to 8.9 x 10(3)/m2, respectively. Approximately 1,300 colonies were picked from culture plates, identified, lypholipized, and stored for future reference. About 75% of all isolates were microorganisms considered indigenous to humans; the remaining isolates were associated with soil and dust in the environment. The percentage of microorganisms of human origin was consistent with results obtained with previous automated spacecraft but slightly lower than those observed for manned (Apollo) spacecraft.


Nitrogen-fixing Enterobacter agglomerans isolated from guts of wood-eating termites.

Two strains of facultatively anaerobic, N2-fixing bacteria were isolated from guts of Coptotermes formosanus and identified as Enterobacter agglomerans. The deoxyribonucleic acid base composition of isolates was 52.6 and 53.1 mol% guanine plus cytosine. Both isolates and a known strain of E. agglomerans carried out a mixed acid type of glucose fermentation. N2 fixation by E. agglomerans was inhibited by O2; consequently, N2 served as an N source only for cells growing anaerobically in media lacking a major source of combined N. However, peptone, NH4Cl, or KNO3 served as an N source under either aerobic or anaerobic conditions. It was estimated that 2 x 10(2) cells of E. agglomerans were present per termite gut. This value was 100-fold lower than expected, based on N2 fixation, low recoveries of E. agglomerans may be related to the marked decrease in N2 fixation rates observed when intact termites or their extracted guts were manipulated for the isolation of bacteria. It was concluded that the N2-fixing activity of E. agglomerans may be important to the N economy of C. formosanus.


In situ morphology of the gut microbiota of wood-eating termites [Reticulitermes flavipes (Kollar) and Coptotermes formosanus Shiraki].

Light microscopy and scanning and transmission electron microscopy were used to examine the in situ morphology of the gut microbiota of Reticulitermes flavipes and Caoptotermes formosanus. Laboratory-maintained termites were used and, for R. flavipes, specimens were also prepared immediately after collection from a natural infestation. The latter endeavor enabled a study of different castes and developmental stages of R. flavipes and revealed differences in the microbiota of field versus laboratory specimens. The termite paunch microbiota consisted of an abundance of morphologically diverse bacteria and protozoa. Thirteen bacterial morphotypes in the paunch were described in detail: seven were observed only in R. flavipes, three were observed only in C. formosanus, and three were common to both termite species. The paunch epithelium was densely colonized by bacteria, many of which possessed holdfast elements that secured them tightly to this tissue and to other bacterial cells. Besides bacteria, the protozoan Pyrsonympha vertens adhered to the paunch epithelium of R. flavipes by means of an attachment organelle. Cuplike indentations were present on the paunch epithelial surface and were sites of bacterial aggregation. Ultrastructural features of cups suggested their involvement in ion absorption. In addition to the paunch, the midgut was also colonized by bacteria that were situated between epithelial microvilli. Results suggest that bacteria are an integral part of the gut ecosystem.


Reduction of sulfur by spirillum 5175 and syntrophism with Chlorobium.

A small spirillum, designated 5175, was isolated from an anaerobic enrichment culture for Desulfuromonas in which the major medium constituents were acetate and elemental sulfur. The organisms grew only under anaerobic or microaerophilic conditions. Elemental sulfur was formed anaerobically in a malate-sulfide medium, and cell densities of 10(8) cells/ml were obtained. Hydrogen and formate were actively oxidized as substrates for growth under anaerobic conditions; S0, S032-, or S2O32-, but not SO42-, served as electron acceptors and were stoichiometrically reduced to sulfide. Malate or fumarate likewise served as electron acceptors and were reduced to succinate. Nutritional requirements were simple, no vitamins or amino acids being required. For growth in inorganic media when carbon dioxide was the only carbon source, the addition of acetate was required as a source of cell carbon. The organism is gram negative. Cells had a diameter of 0.5 mum and a wavelength of 5.0 mum. Cell suspensions exhibited an absorption spectrum indicative  of a cytochrome with peaks in the reduced form at 552, 523, and 416 nm. Well growing syntrophic cultures with Chlorobium were established with formate as the substrate.


Bacterial oxidation of polythionates: determination of tetrathionate with an ion-selective electrode.

A commercially available ion-selective electrode for nitrate was used to continuously monitor tetrathionate oxidation by Thiobacillus dentrificans. The  electrode was much more sensitive to tetrathionate than to nitrate. The same electrode could also be used for the determination of trithionate.


Leakage of cellular material from Thiobacillus ferrooxidans in the presence of organic acids.

Thiobacillus ferroodixans cells released varying amounts of iron, phosphate, sugar, ribonucleic acid, deoxyribonucleic acid, and substances that absorbed light at both 260 and 280 nm, when exposed to 10(-2) to 10(-1) M concentrations of these organic acids: propionic, butyric, valeric, hexanoic, and oxalacetic. These acids also retarded iron oxidation by the cells. Electron microscope observation of cells after exposure to the organic acids showed varying degrees of cell envelope disruption, suggesting that the mode of inhibition of autotrophic iron oxidation in the cell involves interference with the function of the cell envelope, possibly the cell membrane.


Plating medium for differentiation Salmonella arizonae from other salmonellae.

A differential plating medium developed for isolation of Salmonella arizonae produces a uniform reaction for both lactose-negative and -positive S. arizonae and differentiates S. arizonae from other salmonellae.


One hundred and nineteen patients with gastrointestinal fistulas.

One hundred and nineteen patients with gastrointestinal fistulas were treated in the Massachusetts General Hospital, Boston, in the period from January 1960 to January 1970. None of these patients was hyperalimented. The mortality in this seris amounted to 15%; 78.2% of the patients had their fistulas closed. These results are correlated with primary disease, etiology, fistula output, fistula location, type of treatment, malnutrition, electrolyte disturbances and sepsis. In the discussion it is concluded that treatment based on sound surgical principles acquired in the past decades, with the support of modern techniques of intensive patient care, should considerably diminish mortality and improve closure rate.


Lobular carcinoma of the breast.

Lobular carcinoma of the breast, both the in situ and the infiltrating type, is discussed on the basis of three observations. Mammography may be useful, although if often leads to the diagnosis of mastopathy. In cases of in situ lobular carcinoma, ablation of the breast constitutes an adequate therapy. The adequacy of subcutaneous removal of the mammary parenchyma is doubtful. In infiltrating lobular carcinoma, radical mastectomy by Halsted's or Patey's method is the treatment of choice. In view of the frequent bilaterality of the condition, an ample elective biopsy of the identical quadrant of the contralateral breast should be performed in every case.


Results of surgical treatment of rupture of the Achilles tendon with use of the plantaris tendon.

During the period from January 1968 to June 1974, 21 patients were subjected to surgical repair of a ruptured Achilles tendon in the Eindhoven Deaconess Hospital. In 19 of them, the plantaris tendon was used as autogenous suturing material. Followup examination revealed 'excellent' or 'good' results in 19 cases. In one case, the result was classified as 'bad' because of a fistula still present at the time of the follow-up, although functionally the patient was not handicapped. In view of the above, we regard the technique with use of the plantaris tendon for reconstruction of the ruptured Achilles tendon as reliable and worthy of recommendation.


First results obtained with an epicardial screw-in electrode.

A description is given of the introduction of an epicardial screw-in electrode (Medtronic, model 6917) by the infrasternal approach in 22 patients with severe cardiac conduction disorders. Special attention is given to the surgical technique, the electrode and the measurement of the threshold value. Comparison of the various techniques of pacemarker implantation leads to the conclusion that this method of treatment offers many advantages.


Treatment of intussusception in children operative treatment versus hydrostatic reduction.

Intestinal intussusception is a serious abdominal emergency in infancy and childhood, with a high mortality-rate if not diagnosed and treated early. Since the management of intussusception in children is still controversial, the pro's and con's for barium enema reduction and for surgical treatment are discussed. The results of our own series of 19 patients primarily treated by barium-enema reduction compare favourably with a previous series of 14 patients treated by primary surgery.


Zinc correction of defective chemotaxis in acrodermatitis enteropathica.

Three patients with acrodermatitis enteropathica (AE), a disorder of zinc metabolism, demonstrated a zinc-responsive defect in chemotaxis of neutrophils and monocytes. Monocyte chemotaxis was depressed during a controlled period of zinc deficiency and increased to normal values after administration of oral zinc sulfate supplements that was sufficient to restore normal plasma zinc levels. In the only patient in whom neutrophils were also studied, a similar defect in chemotaxis of neutrophils was corrected by administration of zinc sulfate supplements. Preincubation of defective cells in vitro with zinc sulfate increased chemotaxis in an almost linear dose-response relationship. These findings suggest an important role for zinc in neutrophil and monocyte chemotaxis and demonstrate a correctable immune defect in AE.


Transient acantholytic dermatosis: a reevaluation.

Transient acantholytic dermatosis is a self-limited, primary acantholytic disease that occurs predominantly in persons over 50 years old. The primary lesions, discrete papules and papulovesicles, are distributed mainly on the chest, back, and thighs and may be intensely pruritic. The disease lasts less than three months in the majority of patients, but occasionally may go on for two or three years. Four distinct histologic patterns are present in the biopsy specimens, namely, Darier-like in which there is focal acantholysis and dyskeratosis overlying suprabasilar clefts; pemphigus vulgaris-like, in which there are a few acantholytic cells above discrete suprabasal clefts having a mostly intact overlying epidermis; Hailey-Hailey-like, in which there are numerous acantholytic cells overlying suprabasilar clefts; and, finally, spongiotic, in which a few acantholytic cells are present within, or contiguous with, spongiotic foci. Some cases show a predominance of one pattern, but more frequently two or more of these patterns can be found in a single biopsy specimen.


Curettage-electrodesiccation treatment of basal cell carcinomas.

Cure rates after treatment of basal cell carcinomas with curettage-electrodesiccation were compared among three groups: group A, 597 lesions treated in the Skin and Cancer Unit in 1958 to 1962; group B, 91 lesions treated in the Skin and Cancer Unit in 1970; and group C, 210 lesions treated in private practice in 1962 to 1973. The following were the five-year cumulative recurrence rates: group A, 18.8%; group B, 9.6%; and group C, 5.7%. In all three groups, there were high recurrence rates for tumors treated on the nose, paranasal areas, and forehead. Few complications occurred after curettage-electrodesiccation with the exception of hypertrophic scars. The cosmetic results following curettage-electrodesication improved with time. Curettage-electrodesiccation, when performed by experienced physicians, is a very useful modality for the treatment of basal cell carcinomas, with cure rates of over 90%, satisfactory cosmetic results, and few significant complications.


Host-defense mechanisms in hidradenitis suppurativa.

Host-defense mechanisms were studied in seven patients with active hidradenitis suppurativa (HS). Granulocyte phagocytic function was measured by ingestion of Staphylococcus aureus labeled with radioactive carbon 14 and intracellular killing was determined by bactericidal pour plate method. Chemotaxis was measured by radioactive counting of sodium chromate Cr 51 granulocytes migrating in modified Boyden chambers. Granulocyte adherence was estimated in vitro by filtering blood samples through nylon fiber columns. Cell-mediated immunity was measured by intradermal delayed hypersensitivity responses to Candida, mumps. streptokinase/streptodornase, and purified protein derivative antigens. No abnormality was demonstrated in any granulocyte or cell-mediated immune function tests. Moreover, all patients had normal immunoglobulin levels and elevated total hemolytic complement. Therefore, we conclude that HS is a localized chronic infection of apocrine glands without a generalized defect in host defense.


Topical chemotherapy and immunotherapy of mycosis fungoides: intermediate-term results.

A group of 220 patients with mycosis fungoides (MF) and other lymphomatous diseases was treated with sustained topical applications of dilute aqueous solutions of mechlorethamine hydrochloride for intervals ranging in excess of seven years. Response to treatment, immunologic responsiveness, and subsequent course and survival were inversely related to magnitude of disease at time of starting treatment. Relapses were common and in most instances were related to failure to maintenance of topical therapy rather than to drug resistance. In selected patients topical therapy with an analog of mechlorethamine (nor-mechlorethamine) and with topical immunogenic agents provided additional improvement.


Thrombocythemia as a cause of erythermalgia.

Erythermalgia is a distinctive clinical entity characterized by local redness, warmth, and burning pain in the distal portions of the extremities. In this study, erythemalgia was observed in two patients with myeloproliferative disease. A new theory suggesting abnormally rapid platelet aggregation as a cause of erythermalgia was advanced. The following evidence is presented: (1) histologic evidence of thrombi occluding the arterioles and probably composed of platelet aggregates; (2) reversal of the clinical findings with platelet aggregating drugs, such as heparin sodium and acetylsalicyclic acid; (3) disappearance of the erythemalgia with the adequate control of the myeloproliferative disease.


Hidrotic ectodermal dysplasia with diffuse eccrine poromatosis.

Eccrine poromatosis (EP) of remarkable severity has been observed in a patient with hidrotic ectodermal dysplasia (HED), a member of the kindred originally described by Clouston. Neither the EP nor its association with HED has been previously reported.


Phenytoin-induced pseudolymphoma syndrome: an immunologic study.

In vitro and in vivo immunologic studies were performed on a 28-year-old woman with phenytoin sodium-induced pseudolymphoma syndrome. During the acute phase of the syndrome, the patient appeared immunologically depressed. Six months after resolution of lymphadenopathy, repeat studies demonstrated a return to immunologic competence. In vitro studies of the patient's lymphocytes when incubated with phenytoin failed to indicate a delayed hypersensitivity reaction to the drug; These findings suggest that the patient developed a clinical lymphatic proliferation at a time when she was immunologically depressed. This may result in an increased chance of a mutant malignant clone developing at a time when the immunosurveillance system is impaired and explains why a rare patient with this syndrome may develop a frank malignant lymphoma.


Unilateral nevoid telangiectasia: three new cases and the role of estrogen.

Over a period of one month three patients attending a women's outpatient clinic at a general hospital were observed to have unilateral telangiectatic lesions. To our knowledge, only 12 cases of unilateral nevoid telangiectasia have been previously reported; this report would bring to 15 the number of cases of this syndrome. The temportal aspect of the onset of the lesions among these patients strongly supports the role of estrogen in the appearance of unilateral nevoid telangiectasia.


Secondary syphilis presenting as a pruritic dermatosis.

Three patients had secondary syphilis with severely pruritic skin lesions. This presentation contradicts several modern medical texts in which the lesions of secondary syphilis are described as nonpruitic.


Giant melanosomes in multiple lentigines syndrome.

Biopsy specimens of normal skin and lentigines from an 82-year-old man with multiple lentigines syndrome were examined with light and electron microscopes. Giant melanosomes were found in dermal melanophages, melanocytes, and keratinocytes in all epidermal layers. Morphologic characteristics of these melanosomes are described, and other conditions in which they have been found are discussed.


Depressed immune function in epidermodysplasia verruciformis.

Epidermodysplasia verruciformis (EV) is a rare disease characterized by the early onset and unremitting progression of wart-like lesions and frequent association of cutaneous carcinomas. We report two siblings with EV. Immunologic study of both patients demonstrated normal immunoglobulin levels, normal numbers of T-lymphocytes and B-lymphocytes, but markedly depressed in vitro blastogenic reactivity to mitogens and antigens. Cutaneous anergy to a variety of common skin test antigens was noted. These observations may reflect an inherited abnormality in immune function, or the depressed immune function may result from the viral infection of EV.


Eruptive vellus hair cysts.

Two children had a hyperpigmented monomorphous papular eruption of several years' duration. Biopsy specimens demonstrated cysts in the middle dermis that contained multiple fragmented vellus hair shafts. The eruption in one child involuted spontaneously. The cause of these lesions is obscure. The term eruptive vellus hair cysts is proposed for this entity.


Laser treatment of extensive mixed cavernous and port-wine stains.

An extensive, disfiguring mixed nodular cavernous and port-wine stain of the face of an adult who had psoriasis and diabetes was treated with ruby and argon lasers for a period of seven years with substantial cosmetic improvement. There was no deep scarring, secondary granuloma telangiectatic reactions, or chronic radiation changes. Prolonged treatments were necessary because of the small size of the laser emission impact areas.


Clinical and biochemical assessment of a modified evaporated milk for infant feeding.

A clinical and biochemical evaluation has been made of a new milk formula, Modified Carnation milk (MCM), based on cows' milk but with the mineral content and concentration of caloric nutrients altered to make it correspond more closely to human milk. MCM produced higher plasma calcium and magnesium concentrations in 6-day-old infants than those produced by unmodified evaporated and dried milks, achieving concentrations closer to those of breast milk. Plasma free amino acid concentrations in MCM-fed infants are nearer breast-fed values than those in unmodified milk-fed infants where higher individual plasma amino acid concentrations persist during the first 3 months. MCM-fed infants had low plasma urea concentrations and lower urine osmolalities at 6 days, 3 weeks, 6 weeks, 3 months, and 6 months than infants fed on the evaporated and dried milks, and similar plasma urea and urine osmolalities to those of breast-fed infants. MCM is likely to be superior to unmodified evaporated and dried milks in preventing convulsions of the hypocalcaemic/hypomagnesaemic/hyperphosphataemic type, and seems less likely to cause hypertonic dehydration. MCM is easily prepared, readily accepted by babies, and appears to be nutritionally adequate for the feeding of term infants.


Neurological sequelae in children surviving mechanical ventilation in the neonatal period.

The incidence of mental defect, visual and hearing disability, major neurological handicap, and such minor neurological handicap as can be detected on examination at 2--9 years without formal intelligence testing, is presented among survivors of neonatal mechanical ventilation at Hammersmith Hospital between the years 1966--1973 inclusive. 77(21%) of 367 children survived, over three-quarters of them being born elsewhere. 3 died before the age of 6 months, 2 suddenly and unexpectedly at home, the third accidentally. 1 child was lost to follow up. 11 (15%) of the remaining 73 children had neurological sequelae as defined. In two-thirds this was moderate to severe. Spastic diplegia may no longer be the commonest form of cerebral palsy among those of low birthweight, particularly those surviving severe neonatal illness.


Timing of intraventricular haemorrhage.

The detection of the onset of intraventricular haemorrhage (IVH) during life is a necessary preliminary to understanding the cause of this condition. In 10 infants of very low birthweight treated with serial transfusions of adult blood the proportions of transfused cells circulating after each transfusion were compared with the proportion of transfused cells found in the intraventricular clot at necropsy. This allowed the timing of IVH to be restricted retrospectively to the period between consecutive blood transfusions. In addition, the proportional changes of transfused cells produced by infusion of a known red cell mass allow changes in the babies' original red cell mass to be followed during life. A fall in this value occurred in 8 infants dying with IVH and was taken to indicate haemorrhage. Comparison of the two methods in 9 infants suggested that, while in some cases intraventricular bleeding occurs rapidly, in others it takes place over a period of time. The interval between birth and the onset of haemorrhage was directly proportional to the gestational age of the infant.


Role of routine investigations in children presenting with their first febrile convulsion.

To assess the role of routine investigations in children presenting with their first febrile convulsion, the results of investigations carried out in 328 children over a 2-year period were reviewed. Lumber puncture was performed in 96% of cases and resulted in the detection of 4 cases of unsuspected meningitis, one of which was bacterial. 2 children had normal lumbar punctures on admission but developed meningococcal meningitis within 48 hours. Sugar, calcium, urea, and electrolyte estimations, and blood counts were commonly performed but were unhelpful. We suggest that lumbar puncture in those children presenting with their first febrile convulsion under the age of 18 months is the only useful routine investigation.


Aetiology of idiopathic growth hormone deficiency in England and Wales.

Information on height, sex, age, and condition of mothers' pregnancy and labour was obtained on all first- and second-degree relatives of 140 cases of idiopathic growth hormone deficiency (GHD). Less detailed information was available for 68 further cases, the two samples together constituting all cases from England and Wales treated under the Medical Research Council Clinical Trial of Human Growth Hormone up till 1974. Compared with the Perinatal Mortality survey of 1958, idiopathic GHD cases showed a significantly greater incidence of breech births (13-7%), of forceps deliveries especially in multiparae (5-6%), and of reported early vaginal bleeding (7-1%). The incidences of breech and forceps were both higher in cases with multiple pituitary hormone deficiency than in cases of 'isolated' GHD. The frequency of either breech or forceps was 43% in multiple and 20% in 'isolated' GHD. Heights of fathers and sibs of affected cases averaged the 50th centile; those of mothers the 35th centile. The ratio of boys to girls affected was 3-8. There were 4 families with more than one member affected; 4-5% of the brothers of probands were themselves affected, 2% of fathers and 1-5% of both sisters and mothers. In the world literature the sex ratio averages about 2-9 with little difference between series; the frequency of breech delivery averages 21% with large differences (2% to 50%) between series. A table of relative risks is given from which a screening procedure may be constructed; following 1% of selected births would give 10% of cases, and 20% of births 50% of cases. We propose a multifactorial aetiology for GHD which brings it into line with malformations such as anencephaly, cleft lip and palate, and pyloric stenosis. An underlying liability to the disease is postulated, continuously distributed in the population and depending on both polygenic and environmental factors among which sex and birth trauma are important. The disease becomes manifest when the liability value reaches a fixed threshold. On this assumption, heritability of idopathic GHD is approximately the same as that of coeliac disease, pyloric stenosis, and patent ductus.


Long-term management of abetalipoproteinaemia. Possible role for vitamin E.

Eight patients with abetalipoproteinaemia have been followed for 3-4 to 15-8 years. Management included dietary fat restriction and supplements of the fat-solublevitamins A, E, and K. In the 3 oldest patients serial studies of retinal and neurological function suggest that treatment with large doses of oral vitamin E may have delayed the development or progression of the neurological and retinal lesions.


Outcome in congenital stridor (laryngomalacia).

Twenty-one children who had been diagnosed as having laryngomalacia by direct laryngoscopy in infancy were reviewed 7 to 12 years later. The natural history of the disease is documented. A wide variation in the time of onset and duration of the stridor was found and there was a high incidence of feeding difficulties. A previously reported association with mental retardation or cerebral palsy is not confirmed. 4 out of the 21 children had early speech problems.


Assessment of total body fat in infancy from skinfold thickness measurements.

A formula is given, allowing a value for total body fat to be calculated from skinfold thickness measurements at two sites (subscapular and triceps), in conjunction with nine body dimensions. For newborn infants total body fat so calculated accorded satisfactorily with published data from cadaver analyses. The formula has been tentatively applied to infants up to the age of 40 weeks, and to preterm infants. The difference between the growth of male and female infants was analysed in a series of 27 normal infants; the greater growth of musculoskeletal tissue in the male contrasted with the relatively greater growth of fat tissue in the female.


Oral treatment of subacute bacterial endocarditis in children.

Fourteen episodes of subacute bacterial endocarditis in 11 children were successfully treated with antibiotics, which in 13 cases were given largely by mouth. It is suggested that oral treatment of bacterial endocarditis should be considered for children who are only moderately but not severely ill, and who have sensitive organisms.


Duodenal bacterial flora in early stages of transient monosaccharide intolerance in infants.

The aerobic and anaerobic bacterial flora of the duodenum were studied in 10 infants with transient monosaccharide intolerance. 5 infants had protracted diarrhoea after an episode of acute gastroenteritis and 5 had acute gastroenteritis. The duration of monosaccharide intolerance ranged from 1 to 20 days. Serial intubations were performed on 8 infants. In 5 of 8 cases the bacterial flora were of a normal type at the first intubation at 0--4 days after the onset of monosaccharide intolerance. In 4 of those 5 patients there was an increase in bacterial count a few days later and anaerobes appeared. These findings are not consistent with the suggestion that monosaccharide intolerance is caused by abnormal bacteria in the upper small bowel.


Neonatal hypocalcaemia after intrauterine exposure to anticonvulsant drugs.

Two cases are reported of prolonged hypocalcaemia with tetany in infants born at term, whose mothers had been treated with phenytoin and phenobarbitone in high doses. Both infants presented with jitteriness and tetany in the first and second weeks of life, and in both the hypocalcaemia was resistant to therapy over a longer period. An effect on the fetal vitamin D metabolism by phenytoin and phenobarbitone, resulting in defective bone mineralization and neonatal hypocalcaemia is suggested.


Pure oestrogen-secreting feminizing adrenocortical adenoma.

A 6-year-old boy presented with gynaecomastia. There was no clinical or biochemical evidence of excessive androgenic or glucorticoid activity, but urinary oestrogen levels were raised. An adrenocortical adenoma, demonstrated by x-ray, was surgically removed. Oestrogen levels fell immediately. 3 years later the boy shows complete regression of the gynaecomastia and no signs of recurrence.


Host preference and trypanosome infection rates of Glossina morsitans morsitans Westwood in the Republic of Zambia.

Examination of data on the host preference and trypanosome infection rates of Glossina morsitans morsitans Westwood in Central Zambia showed a marked preference for suids (62%); bovids (17%), 'other mammals' (14%), primates (4%), reptiles (3%) and birds (less than 1%) accounted for the remaining feeds. Trypanosome infection rates in G. m. morsitans were very low (0-3-66%), with higher rates in males; only vivax-type trypanosomes were encountered. The heterogeneity of monthly and seasonal infection rates was not significant; the highest rate was recorded in the hot dry season. There was a significant correlation between age and infection rates (P less than 0-01). A regression of monthly male infection rates and monthly mean temperature showed a significant correlation (P less than 0-05). Possible reasons for the low infection rates are discussed.


Cigarette smoke in enclosed public facilities.

A portable carbon monoxide detector (catalytic electrode) was used to record carbon monoxide concentrations in enclosed public facilities, including night clubs, bars, restaurants, stores, hospitals, and public transit vehicles. The highest concentrations of carbon monoxide were found in night clubs, where evening indoor readings averaged 13.4 ppm, which was 4.1 +/- 1.5 ppm higher than outdoor readings. In one poorly ventilated establishment, values ranged from 20 to 40 ppm, with substantial gradients around the room. Adequate ventilation and screening of restaurant employees for ischemic heart disease should prevent problems from cigarette-induced build-up of carbon monoxide. Unfortunately, much lower concentrations of other constituents of smoke cause symptoms and changes of pulmonary function in the nonsmoker. If carbon monoxide is used as an indicator of cigarette smoke accumulation, concentrations should not exceed ambient readings by more than 5 ppm.


Long term variations in trypanosome infection rates in highly infected tsetse flies on a cattle route in south-western Nigeria.

One thousand, nine hundred and ninety-seven male and 1988 female Glossina morsitans submorsitans were dissected at Ogbomosho, on a trade cattle route in south-western Nigeria, from June 1970 to August 1973. Of male flies, 1307 (65-45%) were infected by Trypanosoma vivax trypanosomes, 66 (3-31%) by the subgenus Nannomonas (congolense group) and three (0.15%) by the subgenus Trypanozoon (brucei group). Of flies, 1236 (62-17%) had T. vivax infections, 80 (4-02%) had infections of the subgenus Nannomonas and two (0.10%) had infections of the subgenus Trypanozoon, The great majority of T. vivax infections were mature, while a high proportion (10% in males and 22% in females) of infections of the subgenus Nannomonas were immature. No infection with the subgenus Trypanozoon was found after October 1971. Overall infection rates, for male and female flies respectively, rose from 77% and 80% in June 1970 to peak values of 91% ad 90% in April and June 1971 and thereafter declined to lowest values of 37% and 43% in 1973. The incidence of T. vivax infections was the major component of the rises and falls in overall infection rate. During the period of peak infection rates (April-June 1971), all female flies over about 40 days old were infected. It was assumed that all these had T. vivax infections; some also had subgenus Nannomonas infections and one also had an infection of the subgenus Trypanozoon. Of 72 specimens of G. tachinoides dissected at Ogbomosho from June 1970 to August 1972, 20 (27-8%) were infected by trypanosomes, 19 with T. vivax and one with immature subgenus Nannomonas. In this species, also, infection rate was related to the age of the fly. Of 43 specimens of G. m. submorsitans dissected at Ilorin, north of Ogbomosho on the same cattle route, in February 1975, seven (16-3%) had T. vivax infections. One of two specimens of G. tachinoides dissected here at the same time had an immature infection of the subgenus Nannomonas. In G. m. submorsitans, variations in age structure of the population did not account for the temporal fluctuations in infection rates. It appeared that since 1970 events further north, especially tsetse eradication and the natural decline of tsetse populations (due probably to drought) reduced the trypanosomiasis risk to cattle proceeding southwards. The declining infection rates at Ogbomosho, after 1971, reflected this.


Lung clearance of 4-micron particles coated with silver, carbon, or beryllium.

Lung clearance in rabbits during the first week after inhalation of 4-micron teflon particles tagged with chromium-51 and coated with silver, carbon, or beryllium was studied by external measurements of the radioactivity in the lungs. Ten rabbits were exposed to silver- and carbon-coated particles on two separate occasions within 3 weeks. Clearances of the two types of particles were quite similar. Clearance in eight other rabbits that had inhaled silver-coated particles was quite similar to clearance in eight rabbits that had inhaled beryllium-coated particles. The result is regarded as evidence that alveolar macrophages do not play an active role in removing intact particles from the lung the first week after inhalation.


The pattern of parasitic infection in human gut at the Specialist Hospital, Benin City, Nigeria.

In a survey of 6213 persons conducted between January 1973 to December 1974, at the Specialist Hospital, Benin City, the most common helminths were Necator americanus (16.8%), Ascaris lumbricoides (19l5%) and Trichuris trichiur (5-9%). Dicrocoelium hospes (0-06%) was also recorded and this may become an important liver parasite of man in Nigeria. Its snail vectors are believed to be species of Limicolaria and Achatina which are widely dispersed in Nigeria. Entamoeba coli and E. histolytica showed peaks during the "fly seasons", indicating that the housefly, as well as water, may be an important source of contamination. Trichomonas hominis showed peaks in the rainy seasons, and this suggests that in Benin City transmission is chiefly via contaminated domestic water-supply. The incidence of A. lumbricoides and N. americanus was high throughout the rainy and dry seasons, indicating poor disposal of human excreta and a continuous pattern of infection. The type of food and method of cooking prevented or reduced the incidence of Taenia solium, T. saginata, Diphyllobothrium latum and Fasciola gigantica.


Schistosoma haematobium in a Gambian community. I. The intensity and prevalence of infection.

The intensity and prevalence of Schistosoma haematobium infection has been measured in a community in the laterite plateau area of the McCarthy Island Division, The Gambia. The prevalence reaches 100% by the age of 10 years and counts of over 1000 ova in 10 ml of noon urine are common. During the second and third decade prevalence and intensity of infection decline and the mean egg output of a cohort falls by approximately 50% every three years. In subjects aged over 30 sex differences in exposure to infection and egg output suggest the possible effect of protective immunity.


Housing, hygiene, and health; a study in old residential areas in Copenhagen.

The effect of 109 social, medical, housing, and hygienic factors on morbidity of 2,096 individuals was studied in 881 apartments in Copenhagen. "Thriving" (satisfaction), followed by "housing standard" and "personal hygiene," turned out to be the most prominent predictor for health. "Thriving of parents" was also important for the health of children. Excluding "thriving" in the analyses, "housing standard" and "personal hygiene" or components of these group factors were the important predictors for the health of the population studied, except for children below 3 years of age. For the health of these, the number of rooms used for sleeping purposes was the best predictor. The only other parameter found to influence the morbidities investigated was the total yearly income of the family, which was found to be a secondary predictor for adult morbidity during the last month of the investigation (March 1973). The analyses applies were Pearson correlation, AID-program, factor and multiple regression analyses.


Comparison of the sensory irritation response in mice to chlorine and hydrogen chloride.

Groups of male Swiss-Webster mice were exposed to concentrations of chlorine varying from 0.7 to 38.4 ppm and to concentrations of hydrogen chloride varying from 40 to 943 ppm. The total exposure time to both gases was 10 minutes. Dose-response curves were plotted for both chlorine and hydrogen chloride, using the percentage decrease in respiratory rate during each exposure as the response reflecting sensory irritation of the upper respiratory tract. The results showed chlorine to be 33.0 times more irritating than hydrogen chloride, with 95% confidence limits of 18.6 and 57.1. Guidelines for obtaining a range of acceptable threshold limit values (TLV) based on sensory irritation of the upper respiratory tract are discussed. It was concluded that the current TLV of 1 ppm for chlorine is the upper acceptable limit, and that the established TLV of 5 ppm for hydrogen chloride lies at the lower limit of the predicted range. The mechanism of chlorine's and hydrogen chloride's sensory irritation may be explained by their reaction with various functional groups in the membranes of the trigeminal nerve endings lining the nasal mucosa.


Schistosoma haematobium in a Gambian community. II. Impaired cell-mediated immunity and other immunological abnormalities.

A decreased response rate in delayed hypersensitivity reactions was found in a population heavily infected with Schistosoma haematobium. Laboratory studies showed a depressed response of lymphocytes to PHA in infected subjects. Together these findings suggest the presence of a defect in cell-mediated immunity in some infected subjects. IgG and IgM levels were increased and the prevalence of rheumatoid factor was greater in the infected population. The possibility of non-specific changes in the control of the immune system in schistosome infections and the relation of the present findings to the increased prevalence of lymphoproliferative tumours in infected subjects are discussed.


Field trial of metrifonate in the treatment and prevention of schistosomiasis infection in man.

A field trial was set up to test the prophylactic properties of the organophosphorous drug metrifonate (Bilarcil Bayer AG). Subjects were rural African children living in an area of Rhodesia where Schistosoma haematobium and S. mansoni are highly endemic. The trial was conducted in three stages, a preliminary period of therapy followed by two six-month periods of prophylaxis. Parasitological and haematological tests were carried out monthly and major assessments (including clinical examinations) were carried out prior to the start of the trial and at the end of each of the three stages. Drug was given to the appropriate groups at a dose rate of 7-5 mg/kg once per fortnight for three doses during the therapy stage and four-weekly during the prophylaxis stage. Results with S. haematobium were very good. A 60% cure-rate was observed six weeks aection was obtained in those children continuing to receive the drug as a prophylactic, even during the season of highest transmission; intensities of infection in those who became infected were very low. Infection rates in the treated but unprotected group rose steadily from 40% at week 11 to 95% at week 70. There was a sigificant effect upon the intensity of S. mansoni infections only when pre- and post-trial data were  compared. Apart from the anticipated (and previously reported) depression of plasma cholinesterase values no side effects were recorded. Drug tolerance and acceptibility were very high. It is likely that the costs of a year's protection against S. Haematobium using metrifonate will be significantly lower than protection by molluscicidal techniques or single courses of treatment with established drugs.


Preliminary trials against Biomphalaria glabrata of a new molluscicide formulation: geletin granules containing Bayluscide wettable powder.

Tests were conducted with gelatin granules containing Bayluscide (niclosamide) w.p., 23-3% w/w a.i. Granules rendered a simulated field habitat (banana drain) lethal to Biomphalaria glabrata for 40 days when applied at a rate calculated to give 5 mg/1 in the water. At this dose, Bayluscide e.c. was effective for 8-12 days. Granules exposed to various combinations of natural or simulated tropical climatic factors for up to 56 days gave variable kills of snails, apparently unrelated to the factors tested. The rate at which the molluscicide was released from the granules was affected by climatic factors: high temperatures and low humidities slowed the rate, probably by hardening the granules; rainfall and high humidities accelerated the rate, probably by softening or disintegrating the granules. There was no apparent loss of molluscicidal activity in granules exposed for 56 days to various combinations of climatic factors. The results suggest that this formulation may be applied during droughts to temporary habitats when these are dry and accessible. The molluscicide would then be released at the unpredictable start of the next wet season and kill any snails which survive the drought by aestivation.


The susceptibility of Marisa cornuarietis, a predator of schistosome bearing snails, to N-tritylmorpholine.

Introduction of the ampullariid snail, Marisa cornuarietis (L.), into water treated with molluscicides, in order to secure the success of chemical control of schistosome host snails, is promising. Adult Marisa can be introduced only two days after treating water of pH less than or equal to 7-9 with N-tritylmorpholine (= FresconR Shell) at a concentration of 0-03 ppm. There is considerable variation in the susceptibility of different strains: the LT50 in a concentration of 0-03 ppm Frescon at 25 degrees C was about 27-3 hours for a Puerto Rican and 44-6 hours for a Floridan strain, both 52 weeks old. At sexual maturity, i.e. approximately 18 weeks at 25 degrees C, the LT50 for the Floridan strain was approximately 31-8 hours; experiments with a hybrid stock of the two strains had an LT50 of 30-0 hours. Younger snails were significantly more susceptible to the molluscicide, and eggs were approximately four times more resistant than adults; this agrees with findings by previous authors for other snail species. In the case of the accidental uncontrolled spread of Marisa to cultivated areas it is suggested that a concentration of 0-03 Frescon is applied for at least four days.


Tricuspid atresia: corrective operation without a bioprosthetic valve.

A case of successful correction of type IB tricuspid atresia is described in which the patient's own normal pulmonary valve was used in its natural location. Morphological features of tricuspid atresia suggest that use of the in situ pulmonary valve is possible in most patients with normally related great arteries. Elimination of the requirement for valved conduits and bioprosthetic valves may eventually permit corrective operation in the very young child.


Automated identification of cardiac conduction tissue in L-TGV and Ebstein's anomaly.

The specialized cardiac conduction tissue was identified quickly and easily at operation in 2 patients with corrected transposition (L-TGV) and 1 with Ebstein's anomaly. In each of the former cases the tissue was located along the upper rim of the VSD, beneath the pulmonary outflow tract; in neither patient was there a disturbance in cardiac rhythm as a result of operation. In the patient with Ebstein's anomaly the bundle of His descended onto the ventricular septum more directly than was anticipated. There was only a transitory disturbance in atrioventricular conduction following tricuspid valve replacement. Accurate identification of the cardiac conduction tissue is a prerequisite to the safe repair of certain forms of complex congenital heart disease.


Surgical treatment of right ventricular aneurysm: an uncommon procedure.

Most ventricular aneurysms result from transmural myocardial infarction and are located in the left ventricle. Right ventricular aneurysms are unusual, and their origin at times is obscure. A patient with two discrete right ventricular aneurysms is reported. The literature on operative excision of right ventricular aneurysms is reviewed, and the various etiological factors are discussed.


Traumatic hemopericardium and chronic constrictive pericarditis.

Chronic constrictive pericarditis following traumatic hemopericardium has been reported in recent years, but it has not been reproduced experimentally in dogs. The present study attempted to produce posttraumatic constrictive pericarditis in 34 experimental animals. Hemopericardium by means of trauma to the epicardium or pericardium was produced by a sharp instrument or by the injection of autologous blood inside the pericardial sac. All animals were killed at intervals between 3 and 31 months. The animals in which hemopericardium was induced by injecting blood into the pericardial cavity showed no changes. The hemopericardium was completely resolved without noticeable residual trace. Animals having hemopericardium as a result of trauma evidenced a well-developed constrictive pericarditis that was documented clinically, hemodynamically, and histologically. These experimental findings indicate that chronic constrictive pericarditis may well be due to traumatic hemopericardium rather than to specific infection.


Flow velocity of cardiac lymph and contractility of the heart: an experimental study.

The flow velocity of cardiac lymph in various abnormal conditions of the heart and in control situations was studied experimentally in dogs. The time needed for the cardiac lymph node to become stained after injection of contrast medium into the muscle layer of the left ventricular apex was measured as an indicator in determining flow velocity of cardiac lymph. Left ventricular contractility was studied simultaneously. The hypoxic dogs had a short staining time with a vigorous cardiac beat. (Short staining time means accelerated lymph flow through the heart). The hearts in which the coronary sinus was ligated revealed the shortest staining time with an insignificant contractile change. The exsanguinating dogs had a long staining time with reduced contractility. The dogs with ventricular fibrillation had the longest staining time. When the heart rate was fixed by pacing, the staining time reflected contractile change. The contractile force of the heart plays an important role in the flow velocity of cardiac lymph.


Topical cardiac hypothermia and phrenic nerve injury.

The relationship between ice-chip cardioplegia and impaired left diaphragmatic function was evaluated in dogs. Direct or indirect contact of the phrenic nerve with crushed ice for 30 or 60 minutes resulted in phrenic paralysis for 6 to 28 days, with responsiveness returning from 7 to 62 days later. Microscopical examination of injured nerves revealed injury to the myelin sheath and preservation of axons. Paralysis of the left diaphragm after topical cardiac hypothermia may be secondary to cold injury of the phrenic nerve, which is reversible.


Electroencephalographic and neurological correlates of deep hypothermia and circulatory arrest in infants.

At present there is much interest in the use of surface-induced deep hypothermia with circulatory arrest in infants undergoing an open-heart procedure for repair of congenital defects. This paper presents our experience with infants who have been monitored by preoperative, intraoperative, and postoperative electroencephalograms as well as by preoperative and postoperative neurological assessments. Our results indicate that young infants tolerate deep hypothermia with circulatory arrest quite well, and we therefore continue to advocate use of this procedure in operations for congenital cardiac disease.


Valvotomy in young patients with rheumatic mitral stenosis.

Twenty-nine patients younger than 18 years of age with mitral stenosis were operated upon in the Osaka University Hospital. Five patients who underwent operation in the early period of this study died postoperatively. Follow-up study was made in 20 of the surviving patients for a period of 6 to 20 years. Three died during the follow-up period. Twelve of the survivors were in NYHA Functional Class I, 4 were in Class II, and 1 was in Class III. Reactivation of rheumatic disease did not occur after mitral valvotomy.


Tetralogy of Fallot with a single pulmonary artery: operative repair.

Surgical repair was performed on 8 patients with tetralogy of Fallot and congenital or acquired absence of the left pulmonary artery. Prior palliative systemic-pulmonary artery shunts had been performed in the 5 patients with acquired absence of the pulmonary artery, and in none was repair of the damaged pulmonary artery possible. A valve-containing conduit (Hancock) was used in each patient to prevent pulmonary valvular regurgitation during the early postoperative period. All patients survived operation and have exhibited marked symptomatic and hemodynamic improvement. This contrasts with the poor results of corrective operation previously reported in patients in this diagnostic category. We believe that the present improved results are due in large part to the valved conduit, and we therefore recommend its use during repair in children or adults with tetralogy and a single pulmonary artery.


Posttraumatic empyema.

This is a report of the experience gained from treating 18 patients with posttraumatic empyema during a 36-month period. The objectives of treatment were twofold: complete reexpansion of the lung, and evacuation of infected foreign material from the pleural space. The techniques of achieving these objectives were tube thoracostomy initially, followed by early thoracotomy if necessary.


Needle suction of the aorta for left heart decompression during aortic cross-clamping.

Needle aspiration of the aorta is a simple, effective, and safe method of left heart decompression when the aorta is cross-clamped during coronary artery operations. This technique avoids cardiac incisions, and air embolism does not occur. We have used this technique in more than 300 patients without complications.


A method of enlarging the distal transverse arch in infants with hypoplasia and coarctation of the aorta.

Immediate operation in infants suffering from severe congestive heart failure and coarctation of the aorta associated with hypoplasia of the distal transverse aortic arch often poses a difficult technical problem. Frequently the anastomosis between the hypoplastic arch and the descending thoracic aorta fails to relieve the gradient across the hypoplastic segment appreciably. A technique of enlarging the lumen of the distal arch and thereby further lowering the gradient has been found effective and is presented.


A new wire-supported shunt for carotid endarterectomy.

An intraarterial shunt for cerebral protection during carotid endarterectomy is described. It combines the features of the U-shaped shunt of Hallin and the straight shunt of Sundt, and incorporates a side-arm that can be used for perfusion, irrigation, and intraarterial pressure. The shunt is a molded Silastic tube with wire coils at each end to prevent collapse, and its funicular collar and rim obviate sudden expulsion. Its use allows endarterectomy to be performed in a deliberate manner, permitting careful attention to prevention of an intimal flap and unhurried repair of the arteriotomy.


Correction of anomalous subdiaphragmatic inferior vena caval drainage of the right pulmonary veins (scimitar syndrome).

Correction of anomalous infradiaphragmatic inferior vena caval drainage of the right pulmonary veins can be repaired under conventional cardiopulmonary bypass by placing a circumferential tape below the diaphragm between the hepatic veins and the scimitar vein entrance. During repair, creation of an atrial septal defect in the distorted septal-left atrial junction of scimitar syndrome is facilitated by first incising the anteromedial aspect of the fossa ovalis to better delineate the optimal posterolateral margin. A case history illustrates the technique.


Horizontal interventricular septum in congenital heart disease: surgical considerations.

A patient with complex congenital heart disease associated with a horizontal interventricular septum is described. In addition the ventricles were inverted, both great vessels arose from the left-sided right ventricle in the dextrotransposed position, and he had a ventricular septal defect of the type usually seen in endocardial cushion defect. Correction was performed using a Rastelli type procedure with good hemodynamic results.


Counterpulsation catheter fracture: an unexpected hazard.

This paper presents a previously unrecognized hazard associated with intraaortic balloon pumping: fracture of the catheter due to chemical damage by acetone at the time of removal. Common hospital chemicals such as acetone, ether, and Vi-Drape spray may damage the catheter. Contact between these agents and polyurethane intraaortic balloon catheters should be avoided during dressing changes or repreparation of a sterile operative field. Isopropyl alcohol, Betadine, benzoin, and Cidex do not damage the catheter.


The performance of the Braunwald-Cutter aortic prosthetic valve.

Four hundred seventy-five patients underwent aortic valve replacement with the Braunwald-Cutter ball-valve prosthesis at two institutions. The early (30-day) hospital mortality was 4.7% for those with isolated aortic valve replacement and 6.9% for the entire group. For the former, 5-year actuarial survival of the hospital survivors was 72 +/- 5.7%; for the latter group it was 71 +/- 4.4%. Eleven patients (5 since the date of follow-up inquiry) have suffered poppet escape, 9 of whom died. The actuarial incidence of known poppet escape is 4 +/- 2.6% at 47 months; when the 5 patients suffering poppet escape since the date of follow-up inquiry are included, with certain assumptions, the incidence is 3.7 +/- 1.14%. The projected probability of poppet escape using all 11 patients is 12.2% at 5 years; the 70% confidence bands of projected probability of poppet escape separate from those of the risk of re-replacement at 61 months. This and other analyses indicate that in general, patients with the Braunwald-Cutter aortic prosthesis should have it replaced 4 1/2 to 5 years after its insertion.


The early risk of re-replacement of aortic valves.

One hundred two patients underwent re-replacement of the aortic valve, 95 having a first reoperation, 6 a second, and 1 a third. The early (30-day) mortality among the 81 patients undergoing an elective first reoperation was 3.7% (with 70% confidence limits of 1.63% and 7.32%). Fourteen patients undergoing their first reoperation did so urgently, and 6 (42.9%) died early postoperatively. Technical problems during reoperation were uncommon. Fifteen of the 102 patients underwent reoperation because of infection in or around the device; 2 (13.3%) died early postoperatively, and at least 3 more died within nine months of operation. These data, with their 70% confidence limits, are useful in arriving at a decision for or against reoperation in individual patients.


Thromboembolic phenomena in patients with prosthetic aortic valves who did not receive anticoagulants.

Seventy-two patients with Starr-Edwards aortic prostheses of the 2300 series were followed for 1 to 73 months (average, 22 months) without receiving anticoagulants. Nine patients had clinical evidence of an embolic episode (12.5%). One of these patients died, and 5 were left with a significant residual neurological deficit. Two other patients had hemiparesis but recovered fully. Only 1 episode could be considered minor. The reported lower incidence of thromboembolism in patients receiving this prosthesis with adequate anticoagulation has now led us to reverse our previous position and recommend anticoagulation for patients receiving Starr-Edwards aortic prostheses.


Triple-valve replacement: an analysis of eight years' experience.

The total experience with combined aortic, mitral, and tricuspid valve replacement in 38 patients during an eight-year period ending in December, 1974, is reviewed. The hospital mortality was 23.7% (9 patients) and was influenced by the preoperative New York Heart Association Functional Class: 18%(5 of 28 patients) in Class III and 40%(4 of 10) in Class IV. Intraoperative myocardial injury was the other important factor affecting hospital mortality. The majority of late deaths were related to cardiac causes. The five-year survival was 53% (20 patients) for the entire group and 62% (17 patients) for the Class III patients. At latest follow-up (mean, 44 months), 22 (76%) of the hospital survivors had improved by at least one functional class. It appears that surgical intervention before patients reach Class IV status should give better early and long-term results. Our current indications for tricuspid valve replacement as opposed to repair are presented.


Cardiac valve prostheses, anticoagulation, and pregnancy.

A series is presented of 7 women who underwent cardiac valve replacement and who ultimately became pregnant. The only infant death was that of a premature baby whose mother received oral anticoagulants until delivery. The remaining 6 babies were normal and survived. One mother died suddenly on the fourth postpartum day and was found to have a periprosthetic clot on postmortem examination. Although a certain risk exists for the fetus whose mother receives oral anticoagulants since they cross the placental barrier, this risk is far lower that that for the mother who does not receive anticoagulation. From a prospective point of view, it would appear preferable to use prostheses such as the porcine heterograft that do not necessitate the administration of anticoagulants.


Transcervical thymectomy with the aid of mediastinoscopy for myasthenia gravis: eight years' experience.

Fifty-eight patients with myasthenia gravis, including 12 children, underwent thymectomy. Eleven of them (19%) had total stable remission and 42 (72%) showed clinical improvement and were able to reduce their anticholinesterase medication. These two groups combined comprised 53 patients (91%). There was no operative or postoperative mortality. Histopathological examination of the resected thymuses revealed a tumor (benign thymoma) in 4 patients (7%), thymitis in 36(62%), and no pathological changes in 18(31%). Patients with few or no germinal centers tended to achieve remission more rapidly than those with numerous germinal centers.


Contemporary management of myasthenia gravis: the clinical role of thymectomy.

Thirty-six patients with myasthenia gravis have been evaluated and treated over the past five years. Eleven patients had ocular myasthenia gravis and responded well to anticholinesterase medications. Twenty-five patients had generalized myasthenia gravis, and 22 of them were initially treated with anticholinesterase medications; 18(82%) failed to improve or to maintain an initial improvement on medication, and 14 of these 18 patients underwent thymectomy. In addition, 3 patients underwent thymectomy as part of their initial treatment during the later part of this study. All thymectomies were performed through a median sternotomy. All 17 patients manifested sustained improvement as judged by a gain in strength and decrease in medications. Thymectomy is beneficial in the treatment of myasthenia gravis, and it is most efficacious when performed early in the course of the disease.


Prosthesis for correction of single ventricle.

A prosthetic right ventricular conduit that may be applicable in repair of the single ventricle anomaly is reported. The final conduit evolved from a series of animal experiments, which are described.


The hemodynamic effects of dopamine following cardiopulmonary bypass.

The hemodynamic effects of dopamine were studied in 19 patients following intracardiac operation or myocardial revascularization using extracorporeal circulation. The heart rate, mean blood pressure, central venous pressure, left atrial and pulmonary artery pressures, cardiac output, and urine output were recorded before and at the end of one-hour infusions of dopamine at 5, 10, and 15 mug/kg/min. Infusion of 5 mug/kg/min of dopamine resulted in the highest gain in cardiac output and stroke work without an increase in myocardial oxygen consumption, as evidenced by lack of significant rise in heart rate. In addition, this dosage was not accompanied by an increase in pulmonary or systemic vascular resistance, nor were other untoward effects observed after administration of 5 mug/kg/min of dopamine.


Repair of pectus excavatum in children under 3 years of age: a twelve-year experience.

From 1964 to 1975, 50 children under 36 months of age had operative repair of severely deforming pectus excavatum. No child died or suffered a serious complication from the operation. Most young children needing early repair of progressive pectus excavatum can be identified by 18 months of age. Forty-five patients in this series (90%) have had a totally satisfactory cosmetic and anatomical result on one- to twelve-year follow-up. Early repair of marked pectus excavatum in young children is safe and is efficacious in providing a suitable body contour.


Open-heart surgery in Jehovah's Witnesses: experience in a Canadian hospital.

Jehovah's Witnesses have religious belief precluding the use of blood. Few centers have attempted open-heart surgery bound by such strictures; as a result, availability of therapy for such patients has been limited. Many groups that have extensive experience with hemodilution for cardiopulmonary bypass have noted that these procedures can often be done with little or no use of blood. Our experience with 21 adult patients is presented in this paper.


Hemolysis due to chemical contamination of clinical perfusion apparatus.

A chemical contaminant found on the interior surface of the extracorporeal apparatus manufactured by the William Harvey Corporation was believed to have caused severe hematuria in 2 children. The biological activity of the contaminant was tested by mixing 50 ml of whole blood in contaminated cardiotomies; after 5 minutes of exposure lysis of one-sixth of the red blood cells was found. This hemolytic agent was concluded to be bisphenol A dissolved in an organic solvent, but the mechanism of contamination was never found.


Universal cardiac valve holder.

A valve holder has been designed to facilitate the insertion of porcine cardiac valves. This holder allows a return to the operative technique established with the earlier generation of mechanical cardiac valves.


Subannular mitral prosthesis in aortic position.

Björk-Shiley subannular mitral prostheses have been used in the aortic position in 36 patients with calcific aortic annulus. We believe that the flange in the sewing ring of these prostheses offers added protection against perivalvular leakage; over an 18-month period there have been no instances of periprosthetic leakage in these patients.


Congenital left aortic sinus-left ventricle fistula and review of aortocardiac fistulas.

A fistula from the left aortic sinus to the left ventricle is reported that was successfully repaired using cardiopulmonary bypass. In addition, 175 cases of fistula to the heart from the aortic sinuses published in the English literature from 1839 through 1972 were studied, with particular emphasis on the 126 patients who underwent operative repair. The major cause of the fistulas (76%) was found to be rupture of a congenital aortic sinus aneurysm, usually during the third or fourth decade of life. The remainder of these fistulas to the heart consisted of simply a tract in an otherwise normal sinus. Ventricular septal defect was the most common associated defect and, when present, was nearly always related to a fistula arising from the right aortic sinus. Repair was successful in 86% of the 126 operated patients. The principles of operative treatment of these fistulas are reviewed.


Some effects of pentazocine and cyclazocine on the isolated guinea-pig atria.

Experiments carried out on spontaneously beating and electrically driven guinea-pig atria, have shown that pentazocine and cyclazocine when used in equal concentrations induce a reduction in rate and contraction amplitude. An initial positive inotropic response always precedes with a negative deflection in electrically driven atria. Atropine and nalorphine do not antagonize the drug-induced reduction in rate and contractility. Practolol does not influence either the initial positive or the negative inotropic effects of pentazocine. An apparent tachyphylaxis to the pentazocine-induced positive inotropic response is observed even after the first exposure when the same concentration of pentazocine is tested on the same preparation. Increasing the Ca++ concentration in the medium antagonizes the negative inotropic and chronotropic effects of adenosine and acetylcholine. It is concluded that the negative inotropic effects of the tested drugs may be due to an interference with the Ca++ balance within the atrial cells and/or a direct nonspecific effect on the cell membrane.


Procaine-induced positive chronotropic and inotropic responses of the isolated, blood-perfused dog atrium.

In the isolated, blood-perfused canine atrium preparations, procaine given into the cannulated sinus node artery induced frequently significantly positive chronotropic and inotropic effects at a dose level of 30-1000 microng. Above a dose of 100 microng, initially brief negative chronotropic and inotropic effects were usually observed. Procaine-induced negative effects were not blocked by an adequate dose level of atropine. Procaine-induced positive effects were inhibited by treatment with propranolol but not modified by tetrodotoxin or desmethylimipramine. Procaine suppressed acetylcholine-induced negative chronotropic and inotropic effects. On the other hand, procaine did not block norepinephrine-induced positive inotropic and chronotropic effects. From these results, it is concluded that procaine may have sympathomimetic and atropine-like properties.


Cardiovascular pharmacology of bepridil (1[3 isobutoxy 2 (benzylphenyl) amino] propyl pyrrolidine hydrochloride) a new potential anti-anginal compound.

In dogs intravenous bepridil (2.5 mg/kg) increased coronary sinus blood flow and PVO2. Arterial pressure was briefly lowered, and heart rate was slowed in animals with intact or denervated hearts, or after propranolol administration. Ventricular inotropism was reduced at higher doses. Bepridil (5 mg/kg i.v.) showed a partial antagonist activity on isoprenaline cardiovascular effects (or cardiac sympathetic stimulation effects) i.e. tachycardia, increase in left dP/dt max. and diastolic hypotension. The antitachycardia activity was particularly pronounced. It was found to be non-competitive. It was also found to be non-specific since glucagon, theophylline- and papaverine-induced tachycardia were also reduced. The continuous infusion of high doses of bepridil did not cause any disturbance in atrio-ventricular or intraventricular conduction. In rats, after 50 mg/kg/day p.o., bepridil did not alter myocardial noradrenaline levels.


Further studies on the action of ultraviolet light on vascular smooth muscle: effect of partial irreversible receptor blockade.

Isolated rabbit thoracic aorta which is pharmacologically contracted will relax when exposed to ultraviolet light. The relaxation is reversible in that the tension is restored when the light source is removed. The purpose of this investigation was to study further the phenomenon of photorelaxation on vascular smooth muscle. Restoration kinetics were examined for two cases: 1) norepinephrine alone 2) norepinephrine plus phenoxylbenzamine. The photo-induced relaxation in the presence of the irreversible blocker phenoxybenzamine produced a more rapid restoration than the photo-induced relaxation in strips contracted with norepinephrine alone. Angiotensin, which is not blocked by phenoxybenzamine, produced no change in the restoration characteristics of a perturbation on the angiotensin-induced contractions. Strips treated with glycerin, a process which removes storage sites for Ca++, are responsive to exogenous administration of Ca++ but demonstrate no photorelaxation. These results lend supportive evidence to the hypothesis that ultraviolet radiation interferes with the drug-receptor complex.


Effects of probenecid on methotrexate exchange between the blood and the cerebrospinal fluid.

In rabbits anesthetized with urethane, only a small fraction of 3H-methotrexate administered by an i.v. infusion reached an artificial cerebrospinal fluid solution perfused through the cerebroventricular system. This movement was not altered significantly by probenecid administered either i.v. or in the perfusing artificial cerebrospinal fluid. When the 3H-methotrexate was perfused through the cerebroventricular system, one third of the amount normally lost during the perfusion was retained when probenecid was also added to the solution. Therefore, at least a portion of the apparent blood-brain barrier that exists for methotrexate is due to removal from the cerebrospinal fluid by a process that can be inhibited by probenecid.


The action of serotonin on basal gastric secretion in the conscious rat after intraventricular and intraperitoneal administration.

In unanesthetized rats with chronic gastric fistulas the effect of various doses of 5-HT and atropine given intraperitoneally (i.p.) or into the lateral cerebral ventricle (i.c.) on basal gastric secretion was investigated. 5-HT given i.e. reduced HCl secretion more strongly than by the i.p. route. Atropine reduced gastric secretion equally after i.p. or i.e. administration. 5-HT given i.p. or i.c. produced a weaker inhibitory effect on basal gastric acid secretion than atropine. The stronger antisecretory action of 5-HT after i.c. than after i.p. administration indicates that the amine directly depresses the vegetative brain centers responsible for the basal secretory activity of the gastric mucosa.


Regional acetylcholine content in mouse brain after morphine tablet implantation.

Implantation of a 75 mg morphine tablet in mice caused a significant decrease in the body weight and hypothermia. After 3 days, the concentration of acetylcholine decreased in all brain regions with the exception of the cerebellum. A significant decrease in acetylcholine content was observed in the midbrain, corpus striatum and the cerebral cortex 3 days after implantation. It is postulated that the decrease in Ach content is due to an increased release of acetylcholine as a result of development of tolerance to morphine.


Subacute imipramine: changes in single dose pharmacokinetics in rats.

Imipramine (10 mg/kg, p.o.) administered to male Wistar rats (133-178 g) twice daily for 3 weeks more than halved the control rate of body weight gain. A bile fistula was inserted after this period and 14C-imipramine (10 mg/kg, p.o.) was administered 14-18 hr after the final scheduled dose. Biliary excretion of radioactivity during the subsequent 50 min was decreased to 16% of control. Higher levels of gastrointestinal radioactivity (mainly in the stomach lumen) indicated a slower imipramine absorption rate in the subacute group. Liver metabolite ratios revealed that the treatment group had decreased rates of 2-hydroxylation and 10-hydroxylation, but not demethylation, of imipramine. After incubation of the 25-50 min bile sample with glusulase, bile-to-liver ratios of metabolites indicated a lower entry rate of imipramine, desmethylimipramine and 2-hydroxydesmethylimipramine, but not of 2-hydroxyimipramine or 10-hydroxyimipramine, into bile of the subacute imipramine group.


Tryptamine: bimodal actions on the EEG and behavior of rabbits.

EEG tracings from conscious restrained rabbits were analyzed by inspection and amplitude integration (electrogenesis). Intravenously, tryptamine in doses of 0.1 and 0.5 mg/kg increased electrogenesis, whereas 1 mg/kg initially decreased and subsequently increased electrogenesis. Higher doses (3, 6 and 12 mg/kg) always caused an immediate and dose-dependent decrease in electrogenesis. Neither atropine nor reserpine pretreatment prevented this decrease, whereas chlorpromazine and methysergide abolished it. Intravenous infusions of tryptamine at 1 mg/kg/min caused a nonsignificant increase in electrogenesis but 2 and 4 mg/kg/min infusions caused a sustained decrease. These results show that tryptamine has a biphasic effect on the cortical EEG: low doses enhance synchrony while high doses alert the EEG. Moreover, analysis of the behavioral, EEG and peripheral effects of tryptamine indicate that different sites of action account for the multiple responses observed. Chlorpromazine and methysergide selectively inhibit the exictatory responses.


Comparative diuretic activity of delta9-tetrahydrocannabinol, cannabidiol, cannabinol and hydrochlorothiazide in the rat.

Orally administered delta9-tetrahydrocannabinol (THC) produced a dose-dependent increase in urine output in hydrated rats similar in mg/kg potency and magnitude of effect to hydrochlorothiazide (HCT). Whereas HCT promoted marked excretion of Na+, K+ and Cl- and an increase in the urinary Na+/K+ at all diuretic doses (1.25-20.0 mg/kg), THC had only a slight effect on Na+ and K+ excretion but not Cl- even after the highest dose tested (20.0 mg/kg). Hypophysectomy and adrenalectomy abolished the diuretic effect of THC, thus suggesting both central and peripheral sites of action for the diuretic effect of THC. Tolerance to the effect on urine output by THC developed after 15 days of repeated dosing, while urine output and electrolyte excretion remained significantly elevated after 25 days of HCT administration.


Pentobarbital, diazepam and bemegride: their effects on open-field behavior in the gerbil (Meriones unguiculatus).

Open-field activity was measured in female mongolian gerbils treated with pentobarbital, P-barb. (15 and 20 mg/kg) or diazepam, DZP (2,4 and 8 mb/kg), either when given singly or in combination with the analeptic bemegride, BMG (20 and 40 mg/kg). The results indicated that the addition of BMG normalized certain behaviors of the gerbils treated with P-barb. and DZP. The median effective doses of BMG in inducing convulsion and death respectively were 12.0 mg/kg and 22.5 mg/kg. A mutual antagonism is apparent since no animal died after treatment with the drug combinations and seizure activity was also very much reduced.


An alternative model for non-competitive antagonism.

An antagonist acting on its own receptor leading to a gradual decrease in the affinity between an agonistic drug and its own but different receptor, is a metaffinoid antagonist. The presently published models for metaffinoid antagonism predict a parallel shift in the concentration-effect curves of the agonist by the metaffinoid antagonist, due to a gradual change in the affinity between the agonist and its receptor. An alternative model is proposed where the presence of an antagonist changes the affinity of only a fraction of the agonistic receptors, leading, in contrast to the presently published model to: a) non-parallel shifts in concentration-effect curves and b) metaffinoid antagonistic curves that look like the curves obtained in metactoid antagonism. Experimental support for the alternative model is found in the interaction between various beta-adrenergic agonists and serotonin in the guinea-pig tracheal chain and rat stomach fundus strip preparations.


The desensitizing interaction of hexafluorenium with the cholinergic receptor in the diaphragm of the rat.

1. The interaction of hexafluorenium with acetylcholine, carbachol and suxamethonium with regard to the depolarization of the end-plate of rat diaphragm was studied. The depolarization was measured with the moving meniscus technique of Fatt. The competitive antagonist d-tubocurarine was included in the studies. 2. Hexafluorenium inhibited acetylcholinesterase in the end-plate. 3. The receptors in the end-plate were desensitized by carbachol and suxamethonium. Hexafluorenium enhanced the desensitization by suxamethonium. d-Tubocurarine had no direct influence on desensitization 4. The desensitization of the receptors in rat diaphragm is compatible with a cyclic model of desensitization. 5. The desensitizing interaction of hexafluorenium with the receptors may explain the non-competitive antagonism with depolarizing drugs with regard to the depolarization of the end-plate and the synergism with these drugs with regard to the paralysis of the indirectly stimulated muscle reported earlier. 6. The affinities of carbachol, suxamethonium and d-tubocurarine to the sensitive receptors are 4.9, 5.2 and 6.8, respectively.


Interactions of narcotics and their antagonists with human serum esterase. VI: The behavior of 14-hydroxylated morphine derivatives.

Study of the interaction of 14-hydroxylated morphines and morphinans with human serum esterase revealed behavior similar to that of other morphine derivates as shown by similar acceleratory efficacies and affinity constants. However, 14-hydroxydihydro-6-morphinones showed anomalously low apparent affinities and anomalously high apparent efficacies, while at the same time seemingly interfering with the attachment of another drug to the enzyme. These anomalies are satisfactorily explained by assuming a second receptor site for which only the hydroxyketones have affinity and which interacts with the receptor site common to all opiates and opiate antagonists. Equations derived from this assumption allow to determine the parameters of the interactions of drugs with both receptor sites.


The effects of drugs and denervation on removal and accumulation of adrenaline in the perfused hind-limb of the dog.

Removal of adrenaline by the perfused hind-limb of the dog, as well as its accumulation in the femoral artery and saphenous vein, were studied. Saturation of accumulation occurred at the dose level of 1.5 microng/kg.min-1, whereas removal was not saturated at the dose of 4.5 microng/kg.min-1. Removal of adrenaline was significantly reduced by pretreatment with cortexone, cocaine, phenoxybenzamine and reserpine or by surgical denervation of the limb; enzymatic inhibition by iproniazid or U-0521 had no significant effect on removal. Denervation, reserpine and cortex-one blocked the accumulation of adrenaline, whereas U-0521 was the only drug to increase accumulation of adrenaline. The blood vessels perfused have shown a high capacity of removal of adrenaline from the circulating blood, and thus may play an important role in termination of action of both exogenous and adrenal adrenaline.


Interference by fenfluramine with the storage of 14C-5-hydroxytryptamine in rat platelets.

(+)Fenfluramine decreases the 14C-5HT stored in rat platelets both in in vitro and in in vivo systems, indicating a release of the amine. The effect of (+) fenfluramine in vitro increases by increasing the concentration of the drug, the time of incubation with platelets and the temperature. It is not accompanied by loss of lactate dehydrogenase thus excluding an unspecific damage to the platelet membrane induced by the drug. In addition it is not inhibited either by inhibitors of the uptake of 5HT (chlorimipramine, Lilly 110140) or by inhibitors of the platelet 'release reaction' (acetylsalicylic acid) or by an excess of cold 5HT in the incubation medium. The effect of (+) fenfluramine in vivo is dose-dependent and increases gradually up at least 18 hr after i.p. drug's administration. It is significantly inhibited in rats pretreated by either chlorimipramine or Lilly 110140, but not by acetylsalicyclic acid. In analogy with the effect of (+) fenfluramine on rat brain 5HT, it is suggested that this drug could enter platelets by utilizing the 5HT uptake mechanism, at least in vivo.


The effects of indomethacin on the tone and spontaneous activity of the human small intestine in vitro.

The effects of indomethacin on the tone and spontaneous activity of muscle strips from the human terminal ileum were studied. On the longitudinal muscle layer indomethacin caused a loss of tone and a decrease in spontaneous activity. If the drug was added at the beginning of the experiment then the characteristic increase in tone was not observed. On the circular muscle layer indomethacin either initiated or markedly increased spontaneous activity of the muscle strips. Evidence from the in vitro experiments suggests that prostaglandins may be involved in the maintenance of tone of longitudinal muscle and suppression of spontaneous activity in circular muscle from the human terminal ileum.


Some pharmacological studies on the cardiotonic effects of furanosteroidal glycosides.

Cardiotonic effects and cardiotoxicities of three furanosteroidal glycosides were compared with those of standard cardiac glycosides (digitoxin, gitoxin, etc.). Furanosteroidal glycosides showed positive inotropic effects in both isolated guinea-pig atria and rabbit hearts. The positive inotropic effect of 17beta-(3-furyl)-5beta,14beta-androstane-3beta,14,16beta-triol-3-bisdigitoxoside(FGBD) corresponded to that of digitoxin in isolated guinea-pig atria and frog hearts. Intravenous and oral administration of FGBD and 17beta-(3-furyl)-5beta,14beta-androstane-3beta,14,16beta-triol-3-tridigitoxoside(FGTD) in higher doses induced cardiac arrest after vomiting, bradycardia, ventricular rhythm, and ventricular fibrillation in pigeons and cats. Comparison of lethal doses between intravenous and oral administration of cardiac glycosides in pigeons and cats suggested that gastrointestinal absorption of FGBD and FGTD is inferior to that of digitoxin but superior to that of gitoxigenin bisdigitoxoside and gitoxin. Cardiotonic effects of furanosteroidal glycosides were confirmed in isolated guinea-pig, rabbit and frog hearts.


Interaction of quinidine and propranolol in experimental cardiac arrhythmias in the dog.

Quinidine, propranolol and their combination were studied in atrial fibrillation induced by the topical application of acetylcholine or aconitine, injury-stimulation-induced atrial flutter and ventricular ectopic tachycardia produced by coronary occlusion in the dog. The effect of combination of quinidine and propranolol was significantly greater than that of the individual drug in atrial arrhythmias but not in ventricular arrhythmias. The study provides experimental support for the combined clinical use of quinidine and propranolol in the treatment of atrial arrhythmias.


Effects of reticular stimulation, d-amphetamine and scopolamine on acetylcholine release from the hippocampus of brainstem transected cats.

The effects of i.v. and topical scopolamine and i.v. d-amphetamine were determined on spontaneous release of acetylcholine (ACh) from the dorsal hippocampus of the cat. Animals were prepared under halothane anesthesia with a brainstem transection and either intact or transected fornices. Subsequently, they were placed on room air. ACh was bioassayed using the leech muscle preparation. The amount of spontaneous ACh release varied markedly with each animal with a range of 10 to 21.5 ng/cm2/10 min. There was no mean difference in ACh release between midpontine pretrigeminal and midcollicular brainstem transections. Stimulation of the mesencephalic reticular formation with 300 H/e every sec for 9 sec produced a 28% increase in ACh release from the hippocampus in midpontine pretrigeminal brainstem transected preparations. After section of both fornices, spontaneous ACh release was not altered, although the increased release due to reticular formation stimulation was prevented. d-Amphetamine, in doses of 2.5 mg/kg given i.v., also produced an increase in ACh release from the hippocampus in midpontine pretrigeminal brainstem transected preparations. The d-amphetamine increase in ACh release from the hippocampus was also prevented when both fornices were cut. In contrast, scopolamine in doses of 0.75 mg/kg i.v. increased ACh release in midpontine pretrigeminal brainstem transected cats, either with intact or cut fornices. Topical application of scopolamine (1 microng/ml) to the hippocampus (with or without cut fornices) caused an increase in hippocampal ACh release. It is concluded that the spontaneous or evoked release of ACh from the cat hippocampus provides additional evidence for its role as a neurotransmitter.


Effects of alpha-methyl-p-tyrosine, adrenolytic compounds, pimozide and other neuroleptics, on the narcotic cue.

Using a two-lever food-reinforced operant procedure, rats (n=11) were trained to discriminate the narcotic analgesic fentanyl (0.04 mg/kg, s.c.) from saline. In rats so trained, alpha methyl-p-tyrosine (150 mg/kg, i.p.) was found not to affect the discriminability of fentanyl. Pretreatment (s.c.) with either adrenolytic compounds (10 mg/kg aceperone, 40 mg/kg dibenamine, 10 mg/kg phenoxybenzamine, 20 mg/kg propranolol) or sedative neuroleptics (0.63 mg/kg azaperone, 1.25 mg/kg chlorpromazine, 10 mg/kg pipamperone) likewise failed to attenuate the narcotic cue. Pimozide (0.63 mg/kg) and, to some extent, spiperone (0.04 mg/kg) reduced the percentage of responding on the selected lever, and pimozide antagonized drug lever selection in some animals. The results suggest that specific neuroleptics (e.g. pimozide) may affect the subjective effects induced by narcotics in humans.


Neurochemical properties of 3,3-dimethyl-1-[3-(methylamino) propyl]-1-phenylindan HCl (LU 3-049) and selected tricyclic antidepressants.

Lu 3-049 was compared to certain antidepressants on biogenic amine metabolism. Like desipramine, Lu 3-049 was found to possess potent and selective inhibitory effects on norepinephrine uptake. In rat brain and mouse heart, both agents were found to be considerably more potent than imipramine and chlorimipramine. Unlike the latter, Lu 3-049 and desipramine possessed weak inhibitory effects on serotonin uptake in brain or spleen. Brain norepinephrine levels were unaltered following single or repeated doses of either agent. Desipramine caused a marked increase in norepinephrine turnover; Lu 3-049 caused no change or a slight decrease in turnover. Lu 3-049 had neither inhibitory effects on monoamineoxidase activity in brain or liver nor affected norepinephrine release from brain slices. Presumptive of inhibition of amphetamine metabolism, and in decreasing order of potency, iprindole, desipramine and Lu 3-049 elevated brain levels of amphetamine. Thus, Lu 3-049 shares some but not all of the biochemical properties of tricyclic antidepressants.


Determination of lead III Q waves significance. Utility of deep inspiration.

The relative clinical significance of lead III Q waves and the effect of inspiration has received added impetus after the finding that Q waves have predictive value for coronary artery disease and asynergy. We studied the effect of deep inspiration on Q waves in leads III and aVF in 31 patients and correlated it with the findings at cardiac catheterization. We found that phasic respiration can alter Q-wave duration significantly in leads III and aVF, regardless of the presence or absence of significant associated coronary artery disease and asynergy, and is therefore of no clinical value in this regard.


Tonometry screening on the medical service.

Screening for glaucoma by Schiotz tonometry was carried out for two years on a general medical service. Of the 61% of patients who were over the age of 45 years, 5.5% had pressures equal to or greater than 21 mm Hg and were referred for ophthalmologic evaluation; 44% of those referred were diagnosed as having glaucoma or suspected glaucoma. The overall prevalence of glaucoma in patients on the general medical inpatient service was 3.3%. Because of the high prevalence of glaucoma in the population surveyed, the low incidence of side-effects of tonometry, the small amount of time required to perform tonometry, and the relatively high percentage of glaucoma patients found by routine tonometry used regularly, the present experience supports the view that Schiotz tonometry is a useful procedure for the internist to perform.


Metastatic pulmonary calcification in primary hyperparathyroidism.

Metastic pulmonary calcification (MPC) developed in a patient with primary hyperparathyroidism. Renal function was only minimally impaired (creatine clearance of 65 ml/min) the day prior to appearance of the lung infiltrate, but deteriorated (creatinine clearance of 14 ml/min) concomitantly with the appearance of MPC. Lung imaging with 99mTc bone-scanning agents helps differentiate MPC from other problems with similar clinical and roentgenographic findings, thus allowing prompt therapy.


RBC transfusions in paroxysmal nocturnal hemoglobinuria.

Frozen-thawed, deglycerolized RBCs can be substituted for saline-washed RBCs for transfusion of patients with paroxysmal nocturnal hemoglobinuria (PNH). The effect of transfusion is to decrease bone marrow production of RBCS, which results in a decreased percentage of complement-sensitive erythrocytes. In the presence of small numbers of complement-sensitive erythrocytes, major vascular surgery can be performed without hemolytic problems. This study suggests that the percentage of complement-sensitive RBCs, as well as the complement sensitivity of these cells, influence the severity of hemolysis in persons with PNH.


Surface fixation as a rapid test for diagnosis of toxoplasmosis.

Surface fixation is a rapid and simple method for the detection of antigen-antibody reactions. It has been used as an epidemiologic and diagnostic criterium for brucellosis, typhus and typhoid fever and recently found to be an encouraging test for amebiasis. Data concerning its application in toxoplasmosis has been considered a justified addition to the more complicated procedures used for the diagnosis of this infection, which has become a world-wide problem. It may thus be used as a screening test, as well as a simplified method of titration of postive sera.


[Chromosome analysis in professional subjects exposed to lead contamination].

Chromosomes were analyzed in cultured lymphocytes of 44 male workers from a lead oxide factory, and from a control group of 15 nonexposed individuals. Lead concentration in blood ranged from 30 to 75 mug/100 ml in exposed subjects and from 15 to 35 mug/10 ml in controls. Length of exposure to lead ranged from one month to 11 years eight months. In subjects occupationally exposed to lead, a significant increase in chromatid and chromosome aberrations was found. The frequency of such findings parallels exposure time to lead.