["Pearl necklace" arteries in vascular nephropathy with acute renal insufficiency (author's transl)]. The authors study "pearl necklace" arteries (PNA) in vascular nephropathies with acute renal insufficiency. Seventeen patients underwent aortography complemented by selective angiography of the renal, superior mesenteric and coeliac arteries to seek renal and extra-renal lesions. PNA were discovered remarkably often (mesenteric branches and renal arteries above all). Three types of PNA are described. PNA do not occur in acute angitis (3 cases, 2 PAN). They almost invariably occur in ATN (7 cases) and may be seen in ASMN (7 cases), which eliminates any diagnostic value in the distinction of these two types of acute anuric vascular nephropathy. The functional nature of PNA is open to discussion, but it appears that in the long term histological changes and functional modifications in the involved areas may occur. The role of hypertension and vaso-active substances in the aetiology of PNA is discussed.


[Azygography in the study of malignant tumours of the oesophagus (author's transl)]. Up to the present time, no simple method has existed for gauging the true size of an oesophageal tumour. The intimate relations between the azygos vein and the oesophagus in the thorax between D3 and D8 justifies this new study: azygography. On the basis of 40 examinations, 13 of which were followed by surgery in patients suffering from carcinoma of the oesophagus, as was indicated by classical anatomical data, azygography made possible the evaluation of tumour extension in the mediastinum and the involvement of adjacent structures, such as the right pulmonary artery. Azygography thus aided in the precision of surgical indications and in the delineation of the volume to be irradiated. The examination is carried out by selective opacification after catheterisation via the femoral vein. Radiological findings distinguish involvement by deviation, compression, invasion, obstruction and collateral circulation. In certain cases a part of the tumour itself is opacifield by vessels with an anarchic pattern. Comparison of the results of radiological study with surgical findings shows that the examination makes it possible to predict, between the level of the third and eighth thoracic vertebrae, difficulties in or impossibility of dissection of the tumour as well as, in the case of involvement of the arch, the necessity for total oesophagectomy with additional cervical approach. The accuracy of the information obtained is certainly less valuable as far as the lower third is concerned. Non-traumatic, simple and rapid, azygography would appear to be the examination of choice in defining the exent of a tumour of the middle third of the oesophagus, as a complement to clinical findings and barium swallow, being particularly valuable in determining the volume to be irradiated or on a pre-operative assessment.


[Diagnosis at arteriography of parathyroid adenomas. 45 cases (author's transl)]. The authors report the results of parathyroid arteriography in 45 patients in whom diagnosis was certain, with surgical confirmation of the radiological findings in 44. In this group arteriography led to the exact localisation of the parathyroid adenoma in 21 out of 34 cases. The angiographic signs of parathyroid adenomas are not constant and a negative arteriogram under no circumstances eliminates the possibility of an adenoma being present. In addition, the angiographic signs do not all possess the same significance, some being merely suggestive without definitely indicating the presence of an adenoma. By contrast, when there were highly suggestive or definite signs at arteriography, an adenoma was found surgically at the expected site in 21 of 22 cases. Finally, the authors stress the importance of comparison of the results of arteriography and thyroid scan in order to eliminate thyroid adenomas, as well as the necessity of a photographic substraction involving the different phases of the arteriogram, since this may reveal adenomas invisible on standard arteriography films.


[Angiographic study of coronary artery disease patients receiving circulatory assistance by intra-aortic diastolic counter-pulsion (author's transl)]. In patients receiving circulatory assistance by intra-aortic counter-pulsion for myocardial infarction, angiography may be carried out by the retrograde femoral route. It should include left ventriculography makes it possible to assess the number of segments which contract and to draw a correlation between the kinetics of a segment and its vascularisation. Vascular studies should be carried out at the time of maximum effect of the pump, i.e. from the 18th hour onwards. Indications for angiography are as follows: isolated or mechanical cardiogenic shock, early recurrence of infarction, refractory left ventricular failure and persistent arrhythmias. In cardiogenic shock and refractory left ventricular failure, the coronary lesions are diffuse. All our patients died. By contrast, in the group with early recurrence of infarction or persistent arrhythmias surgical treatment is often possible.


[A rare tumour of the orbit in a child (author's transl)]. The authors present an observation on a rare tumour of the orbit in an 8-years-old boy, revealed by a right unilateral exophtalmia with visual disturbances. This tumour poses the problem of the differential diagnosis of a localized osteolysis; in spite of the arsenal of investigations, the final diagnosis was laid down only upon intervention and histological examination: it was a case of a malignant haemangioendothelioma. The interest of the observation lies in:--the rarity of this type of tumour; --the complete nature of the observation, describing the course of events and the difficulties of diagnosis as well as the fatal evolution despite the surgical and radiochemotherapy treatments.


Phagocytosis of spermatozoa by the epithelial cells of the ductuli efferentes after epididymal obstruction in the rat. The effects of ligation of an isolated loop of the ductus epididymidis in the region of the caput were compared with those of the exfoliative lesion of the epididymis that follows administration of alpha-chlorhydrin to rats. Electron micrographs of the ductuli efferentes in both cases revealed early phagocytosis of apparently normal spermatozoa by the epithelial cells, followed at later intervals by invasion of macrophages and intraluminal phagocytosis. It is concluded that epithelial spermiophagy is a consequence of obstruction, whether mechanically or chemically induced.


Altered sexual development in male rats after oestrogen administration during the neonatal period. Male rats given 250 mug oestradiol benzoate by subcutaneous injection on Day 4 of postnatal life showed a marked delay in the onset of the pubertal increase in the weight of the testes and seminal vesicles and in spermatogenesis but not a complete failure of sexual development. The increase in plasma testosterone concentration at puberty was also delayed in oestrogen-treated males but the eventual increase in seminal vesicle weight was closely related in time to the delayed increase in plasma testosterone concentration. Both plasma LH and FSH concentrations were reduced for about 10 days after oestrogen administration as compared to control values. After 22 days of age, plasma LH concentration did not differ significantly from the control values. The plasma FSH concentration of the oestrogen-treated males showed a delayed rise to values equal to or higher than those of controls of the same age. The delayed rise in plasma FSH concentration in the oestrogen treated males preceded the delayed rise in plasma testosterone in these animals. The decrease in plasma FSH concentration from the high prepubertal values to the lower values in adults occurred at different ages in the control and in oestrogen-treated rats but in both groups the decrease occurred as plasma testosterone levels were increasing and the first wave of spermatogenesis was reaching completion. The increase in plasma FSH concentration after castration was reduced in oestrogen-treated males during the period throughout which FSH levels in the intact animals were subnormal but the levels in oestrogen-treated males castrated after the delayed rise in FSH had occurred did not differ from control values. It is suggested that the delayed sexual maturation of male rats treated with high doses of oestrogen in the neonatal period is related principally to abnormalities in the secretion of FSH.


Cyproterone acetate diminishes sexual activity in male rabbits. Cyproterone acetate (CA) was injected daily in eleven rabbits for 3 weeks at a dose of 20 mg/day, and for a further week at a dose of 40 mg/day. After 3 weeks of treatment, the ejaculation frequency was reduced but other measures of sexual behaviour were not significantly changed. There was no reduction in the fructose concentration of the semen, but the volume of the ejaculates decreased. The vesicular glands from the experimental animals showed histological changes typical of those occurring after castration. It was concluded that CA reduced the activity of at least one of the accessory sex glands as well as sexual behaviour. This lends support to the current hypothesis that the endocrine regulation of rabbit sexual behaviour differs from that of the rat.


Egg transfer in the cow: factors affecting pregnancy and twinning rates following bilateral transfers. A total of 112 heifers was used in an egg transfer study to examine some of the factors affecting egg survival and twinning rates following bilateral transfers. Seventy-two recipient heifers were involved and pregnancy rates of 82.0 percent, 66.7 percent and 61.5 percent were recorded for recipients in oestrus on the same day as (Day 0), 1 day before (Day + 1) and 1 day after (Day minus 1) the donor respectively. Short-term (10-day) intravaginal progesterone, or intramuscular prostaglandin treatments for synchronization of oestrus in recipient animals did not depress pregnancy rate following egg transfer. One egg was transferred to each uterine horn and twinning rates of 55.6 percent, 44.4 percent and 20.0 percent were recorded for transfers on Days 0, + 1 and minus 1, respectively. Of the recipients becoming pregnant following transfers on Day 0, 74.1 percent had twins. Embryo survival was higher (69.2 percent) in the uterine horn adjacent to the ovary containing the CL than in the opposite horn (30.8 percent). The storage period in vitro in TC199 (37 plus or minus 1 degrees C) aftected subsequent egg survival rates following transfer, with fewer eggs surviving the longer storage periods. The pH of the medium used for egg collection and storage did not affect the pregnancy rate between pH values of 7.0 to 8.6. Day of transfer (Days 3 to 7) did not seem to affect the pregnancy rate. The high pregnancy and twinning rates already reported following closely synchronized transfers were confirmed.


Salting out: experience in 9,000 cases.

Salting out: experience in 9,000 cases. A complete method of saline abortion has been presented.  This method has been well thought out, is physiologically sound, and has been proven safe and reliable.  Although we have reduced the potential for complications to a minimum, those specific to the salting-out procedure as well as those inherent in any mid-trimester labor and delivery cannot be completely eliminated.  Therefore, there can be no shortcuts.  Salting out must be performed only in a hospital where well trained specialists are available to handle any complications that may occur.


Intrauterine growth retardation: obstetrical aspects. We have just begun our study of fetal growth retardation. Prenatal influences upon fetal growth are poorly understood and little studied. One may list multiple etiologies, catalogue numerous physiologic processes, and still not know in any given child what went wrong. The questions far exceed our preliminary answers. How does maternal undernutrition significantly effect the fetal "parasite?" Is the syndrome of intrauterine growth retardation a manifestation of a host versus graft phenomenon, with "runting" in the offspring? Are deficits in cell number and size unalterable? Can these deficits be overcome with good postnatal care? How can we better detect the fetus who is undergoing deprivation in utero? What altered biochemical processes exist? Can we reverse such abnormal influences in utero and prevent their consequences to the fetus? Certainly there are numerous additional areas for investigation and thought.


Intrauterine growth retardation: a neonatologist's approach. Early recognition of intrauterine growth retardation, and recognition of these compromised infants at birth, is essential, to correct, if possible, any adverse intrauterine influence; then, to provide proper nursery care, screening for abnormalities, and proper post-natal nutrition.  Improved management of both the in-utero and the ex-utero environment may offer these neonates a more favorable prognosis for their physical, neurological, and intellectual development.


The intracellular distribution of cathepsins and other acid hydrolases in mouse peritoneal macrophages. Acid hydrolases, among them cathepsins A, B, C, and D, and their intracellular distribution have been studied in mouse peritoneal macrophages, a model commonly used for the study of mononuclear phagocyte functions in host-parasite relationships and in the immune response. Thioglycollate stimulated peritoneal macrophages showed high specific activities of acid hydrolases in compatison to liver and spleen. Fractionation of these macrophages by differential and isopycnic sucrose density centrifugation showed heterogeneous enyzme distribution patterns which were different for the various hydrolases studied. Thus, these enzymes appeared to be associated with particles of varying weight and density and in the different particles the ratios of the various acid hydrolase activities were quite dissimilar. With the majority of hydrolases a portion of the enzyme activity was found in fragile heavy particles of densities higher than 1.25 that sedimented together with the nuclei. Cultured macrophages derived from the non-irrated peritoneum exhibited a less heterogenous distribution pattern for acid phosphatase than did the thioglycollate stimulated cells. The heterogeneity of acid hydrolase distributions in the thioglycollate induced macrophages was attributed to their physiologic state of stimulated endocytosis causing a continuous formation of primary and secondary lysomes. Under certain conditions macrophages might contain lysosome-like particles with cathepsin ratios unfavorable for complete proteolysis. The existence of such particles is suggested as a possible explanation for the persistence of immunogenic protein within these cells.


The dendritic cells of the guinea pig popliteal lymph node: identification and classification of cells observed by scanning electron microscopy. Scanning electrom microscopy of guinea pig popliteal lymph nodes revealed that 3 types of cells adhered to glass and possessed extensive cytoplasmic processes. Two of these types were considered to represent extremes of a macrophage population on the basis of possession of surface receptors for cytophilic Abs, complement and immunoglobulin, as well as their distribution, quantity and morphology. The third cell type was characterized by possession of large numbers of filamentous dendritic processes. On the basis of morphology, quantity, distribution and the absence of receptors, this cell was considered to represent a cell type clearly distinct from the other cells observed in the normal lymph node.


Differences in surface morphology of alveolar macrophages attached to glass and to millipore filters: a scanning electron microscope study. The topography of alveolar macrophages (AM) attached to glass or to Millipore filters was scanning electron microscopy. The cells were obtained from normal and from BCG-vaccinated rabbits. Macrophages that adhered to glass tended to spread while essentially all of the cells that adhered to the Millipore filters remained rounded. The surface morphology of AM attached to Millipore filters closely resembles the morphology of these cells when viewed in situ on the alveolar wall. The use of Millipore filters to study the effect of microbial or host products on cell surface alterations of AM is discussed.


Isolated marrow reticuloendothelial activation and erythropoietic response following an acute blood loss. The radioassay technique with the 113mIndium-iron chondroitin sulfate colloid, developed in our laboratory, revealed that an isolated marrow reticuloendothelial activation takes place after bleeding 15 to 30 ml of blood per kg body weight from a rabbit. It parallels the erythropoietic response very well. The present stimulation method might deserve testing for studies where marrow reticuloendothelial function is important such as in cancer-bearing patients, the effects of anticancer chemotherapy and gross antigenization.


Repair of UV damaged DNA in systemic lupus erythematosus. The NZB/NZW hybrid mouse is an animal model of human systemic lupus erythematosus (SLE). Two breeding schemes were devised using NZB, NZW, B/W, and CBA mice, which permit definitive decisions regarding genetic and/or viral origin of the disease. It is proposed that at least two factors must be involved: (1) a genetic abnormality producing hyper-responsiveness to nucleic acid antigens, and (2) a DNA repair defect which results in liberation of DNA and RNA when cells are lethally injured. Evidence is presented for a DNA repair deficit in human SLE lymphocytes following in vitro irradiation with ultraviolet (UV) light. Lymphocytes from adult New Zealand and control mice were found to lack normal amounts of endonuclease necessary for repairing UV damage.


Persistence of DNA in the circulation of immunized rabbits. The clearance of deoxyribonucleic acid (DNA) from the circulation was studied in non-immunized New Zealand rabbits and in rabbits immunized with heat-denatured, single-strand DNA (ss-DNA). Animals were injected intravenously with 1-3 mug/kg of 125-I-calf thymus ss-DNA. Initial clearance rates were -0.154 +/- 0.005 per cent (dose/ml/min) in non-immunized rabbits as compared to rates of -0.064 to -0.123 per cent (dose/ml/min) in rabbits immunized with ss-DNA. In immunized rabbits, clearance rates were inversely correlated with relative amounts of antibody, and increased amounts of circulating radiolabel were precipitable with 50 per cent saturated ammonium sulfate, suggesting binding to rabbit immunoglobulin. Thus, the presence of antibody to ss-DNA may delay the usually rapid clearance of ss-DNA from the blood. This observation is similar to that made for a variety of small molecular weight materials, such as insulin, digoxin, and morphine, and is in contrast to that for multivalent protein antigens, such as serum albumin and thyroglobulin. Persistence of DNA in the circulation may be important in the pathogenesis of DNA-anti-DNA-induced immune complex disease.


Specificity of SLE serum antibody for single-stranded and double-stranded DNA configuration. The solid phase immunoassay for the measurement of serum antibody to double and single-stranded DNA is described. The technique allows a more accurate definition of the antibody specificity of SLE sera as defined by inhibition techniques. The clinical usefulness of immunologic assays in the management of patients with SLE is described, including measurement of urine light chain protein concentration. A core discussion is provided to illustrate how such a panel of tests is used in management.


Porphyria-inducing activity of a series of pyridine and dihydropyridine compounds. Investigation in a cell culture system. A series of analogs of 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-trimethylpyridine (DDC)was prepared and tested for porphyria-inducing activity in chick embryo liver cells. One of the analogs tested, viz.3,5-di-tert-butoxycarbonyl-1,4-dihydro-2,6-dimethylpyridine, was found to be highly active despite the absence of a 4-alkyl substituent. It was concluded that tert-butoxycarbonyl groups are resistant to enzymic hydrolysis and that compounds containing such groups are resistant to inactivation by chick embryo liver cells. Several analogs of DDC were found with considerably higher activity. These should be useful in inducing high levels of beta-aminolevulinic acid synthetase prior to undertaking the isolation of the enzyme.


Stereospecific synthesis of the 6beta-hydroxy metabolites of naltrexone and naloxone. The narcotic antagonists naltrexone (1a) and naloxone (2a) were stereospecifically reduced to the corresponding 6beta-hydroxy epimers 1b and 2b, respectively, with formamidinesulfinic acid in an aqueous alkaline medium. The reaction products were obtained with no detectable quantity of the 6alpha epimers 1c and 2c. The products 1b and 2b were formed in yields of 88.5 and 40%, respectively, and characterized by spectral methods. Compared to 1a and 2a, the stereospecific reduction products 1b and 2b and their 6alpha epimers 1c and 2c are all significantly less potent as narcotic antagonists in mice. Only 1c and 2c also possess antinociceptive activity.


Analgesic activity of  the epimeric tropane analogs of meperidine. A physical and pharmacological study. Condensation of cis-N-benzyl-2,5-bis(chloromethyl)pyrrolidine (6) and phenylacetonitrile afforded a mixture of epimers 7 and 8. Compound 8 was readily converted to the meperidine analog 1 prepared earlier by Bell and Archer. Compound 7 was converted to a new tropane analog of meperidine, compound 3. The ED50 of 1 and 3 in the D'Amour-Smith "tail flick" test for narcotic type analgesia, which differs by a factor of only 3 or 4 potency, supports the accumulated data that suggest that the analgesic activity of the meperidine type is not very sensitive to the conformation of the phenyl group in 4-phenylpiperidines. A proton and 13C magnetic resonance spectral comparison of 1 and 3, as well as a reevaluation of the conformational requirements of 17-19, leads to the conclusion that the differences in conformation of 1,3,17, and 18 are due to the varying degrees of flattening of piperidine ring. The 1H NMR and 13C NMR data are not consistent with the boat conformation suggested earlier for compound 17.


Carbon-13 magnetic resonance spectroscopy of drugs. Sulfonamides. The natural abundance 13C magnetic resonance spectra of a series of sulfonamide drugs(sulfanilamide, sulfaguanidine,sulfathiazole, sulfasuxidine, sulfadiazine, sulfamerazine, sulfamethiazine, and sulfapyridine) have been determined at 25.15 MHz employing the pulse Fourier transform technique. The chemical shefts have been assigned with the aid of off-resonance and selective proton decoupling techniques, as well as by long-range carbon-13 proton coupling patterns.


Antiinflammatory beta-arylamidoacrylic acids. A series of 34 beta-arylamidoacrylic acids was prepared and examined for antiinflammatory activity. These compounds are vinylogous carbamic acids, and several displayed activity equal to phenylbutazone in the rat pleural effusion model. Highest activity was associated with structures bearing halogen and cyano substituents. Amides were inactive.


Synthesis and thin-layer chromatographic ultraviolet, and mass spectral properties of the anticoagulant phenprocoumon and its monohydroxylated derivatives. Phenprocoumon and all of its aromatic monohydroxylated derivatives have been synthesized and analyzed by TLC, uv, and chemical ionization mass spectroscopy. By utilization of various combinations of these analytical techniques all of the titled compounds can be uniquely identified.


Biotransformation of phenprocoumon in the rat. The metabolic fate of phenprocoumon [3-(alpha-ethylbenzyl)-4-hydroxycoumarin] in the rat is described. The major metabolites, 4',-6-,7-, and 8-hyproxyphenprocoumon, have been identified yb mass spectrometry, TLC, and uv and compared with authentic smaples. Metabolites are mainly excreted via the feces. The results are compared with those previously reported for warfarin.


Preparation of [18-F]haloperidol.

Preparation of [18-F]haloperidol. A procedure is described that permits the preparation of [18F]haloperidol in 140 min at specific activities ranging from 4-5 muCi mg-1. A key step in the synthetic route involves the incorporation of 18F into the molecule through a Schiemann-type reaction, which involves the pyrolysis of the diazonium tetrafluoroborate salt of 4-[4-(p-chlorophenyl)-4-hydroxypiperidino]-4'-aminobutyrophenone.


Partition coefficients and the structure-activity relationship of the anesthetic gases. Partition coefficients of 32 gaseous anesthetics in the octanol-water system have been determined. It is shown that relative anesthetic potency depends on hydrophobicity of the anesthetic (as defined by log P) and on a polar factor. The presence of a polar hydrogen in the anesthetic greatly increases potency. A quantitative structure-activity relationship is formulated based on these two factors.


Liquid-lipquid partition coefficients by high-pressure liquid chromatography. Lipid-water partition values can be rapidly and reliably measured by high-pressure liquid chromatography (HPLC) on bonded octadecylsialne supports. This method has been developed and applied to a family of hypotensive triaminopyrimidine 3-oxides. The measured column retention values for this class of compounds correlate well with the values calculated by the Hansch method. We believe that this technique is an important addition to the methodology of Hansch analysis.


Synthesis and pharmacological properties of 4-piperazino-5-methylthiopyrimidines. Selection of new antiemetic agents. We have synthetized a series of 22 new 4-piperazinopyrimidines bearing a methylthio substituent in the 5 position of the pyrimidine ring. These compounds have been obtained by separation of the isomers formed during nucleophilic attack of the corresponding 2,4,6-trichloropyrimidine by amines. Pharmacological screening has shown that this chemical series displays a very interesting profile, which includes antiemetic, tranquilizing, analgesic, antiserotonin, and musculotropic-spasmolytic properties. We have particularly selected for clinical investigations two compounds with powerful antiemetic activity: 2-methylamino-4-(N-methylpiperazino)-5-methylthio-6-chloropyrimidine and 2-isopropylamino-4-(H-methylpiperazino)-5-methylthio-6-chloropyrimidine.


Nucleosides of 2-azapurines. 7 H-Imidazo[4,5-d]-1,2,3-triazines. 2. A number of nucleosides of 2-azaadenine (4-amino-7H-imidazo[4,5-d]-1,2,3-triazine) were prepared by a previously described route, and some of these were deaminated by means of adenosine deaminase. Alternatively, nucleosides of 2-azahypoxanthine (7H-imidazo[4,5-d]-1,2,3-triazin-4(3h)-one) were prepared from hypoxanthine nucleosides by a 2-azahypoxanthine (7H imidazo[4,5]-1,2,3-triazin-4(3H)-one) were prepared from hypoxanthine nucleosides by a ring-opening and reclosure sequence. The cytotoxicity of these compounds to human epidermoid carcinoma No. 2 cells in culture and to certain resistant sublines thereof was determined. 2-Azaadenine nucleosides chan be metabolized to nucleotides, the cytotoxic agents, by two pathways, but the activity of the 2-azahypoxanthine nucleosides appears to result only from cleavage back to 2-azahypoxanthine.


Decomposition of N-(2-chloroethyl)-N-nitrosoureas in aqueous media. A reinvestigation of the aqueous decomposition of N-(2-chloroethyl)-N-nitrosoureas has shown that their mode of decomposition is dependent upon whether or not the solution is buffered at or near physiological pH. In distilled water, the 2-chloroethyl compounds decompose with the loss of 1 mol, or slightly less, of chloride ion per mole in nitrosourea and the formation of acetaldehyde and 3-4% of 2-chloroethanol. In buffer, the yield of 2-chloroethanol increases to 0.3-0.6 mol per mole of nitrosourea, the yield of chloride ion decreases to 0.5 mol per mole of nitrosourea, and the yield of acetaldehyde decreases to 0.1-0.4 mol per mole of nitrosourea. Evidence for the formation of the vinyl cation, a possible precursor of acetaldehyde, in these reactions is presented. In contrast to the results obtained with the N-(2-chloroethyl)-N-nitrosoureas, the decomposition of N,N'-bis(2-fluoroethy)-N-nitrosourea in distilled water gave almost 1 mol of 2-fluoroethanol per mole of nitrosourea and only 0.04 mol of acetaldehyde per mole of nitrosourea.


2-Aryloxymethyl-2,3,5,6-tetrahydro-1,4-oxazines, a new class of antidepressants. Some 2-aryloxymethyl-2,3,5,6-tetrahydro-1,4-oxazines have been shown to possess marked antidepressant activity. The 1,4-oxazines were synthesized by lithium aluminum hydride reduction of the readily available 6-aryloxymethyl-2,3,5,6-tetrahydro-1,4-oxazin-3-ones. High antidepressant activity was associated with ortho substitution of the 2-phenoxymethyl group and with 1,4-oxazines devoid of 4-substituents.


3,4-Dihydro-1H-1,4-oxazino[4,3-a]indoles as potential antidepressants. A series of 3,4-dihydro-1H-1,4-oxazino[4,3-a]indoles bearing basic side chains has been synthesized by a novel chemical process. These compounds have been screened for potential antidepressant activity. One of these derivatives, 3,4-dihydro-1,10-dimethyl-1-(3-methylaminopropyl)-1H-1,4-oxazino[4,3-a]indole (AY-23,673), was particularly potent in the prevention of reserpine ptosis test in mice, with an ED50 of 0.5 mg/kg ip.


Oxidation of furans. 3. Estrogenic properties of lactones and anhydrides derived from the oxidation of 17alpha-[3-furyl]estradiol derivatives. The oxidation of 17alpha-[3-furyl]estradiol derivatives and the estrogenic properties of the resulting isomeric 17,21-and 17,23-dihydroxy-19,24-dinor-17alpha-chola-1,3,5(10)20(22)-tetraenoic acid(20leads to 23) gamma-lactones as well as those of the related 17-hydroxy-19-nor-17alpha-pregna-1,3,5(10)-triene-20,21-dicarboxylic acid anhydrides and gamma-lactones are described. Of these, only lactones 3c,e,h and 5b retained the same degree and profile of estrogenic activity as the starting 17alpha-[3-furyl]estradiols.


Quinuclidine chemistry. 4. Diuretic properties of cis-3-amino-2-benzhydrylquinuclidine. A number of 3-amino-2-benzhydrylquinuclidines were tested for diuretic activity in both rats and dogs. The Schiff base formed from 2-benzhydryl-3-quinuclidinone and benzylamine was reduced with NaBH4 to a mixture of isomers, the cis isomer being preponderants. cis-2-Benzhydryl-3-benzylaminoquinuclidine was isolated by chromatography and debenzylat:d to cis-3-amino-2-benzhydrylquinuclidine, the most active compound in this series. The corresponding trans isomer was considerably less active. It was made by reacting the mesylate of cis-2-benzhydr-l-3-quinuclidinol with Nan3 to form trans-3-azido-2-benzhydrylquinuclidine which was reduced with LiAlH4. In dose-response studies (sodium excretion as a function of dose) in rats the maximal or ceiling effect of cis-3-amino-2-benzhydrylquinuclidine was considerably greater than that of hydroflumethiazide but less than that of furosemide. An unusual biphasic dose-response was seen in dogs with cis-3-amino-2-bezhydrylquinuclidine, centering around 10 mg/kg.


Butyrophenones as hypotensive agents. Derivatives of 4-aryl-4-(hydroxymethyl)cyclohexylamine. The preparation of butyrophenone derivatives of 4-aryl-4-(hydroxymethyl)cyclohex-1-ylamines starting from the corresponding 4-cyano-4-phenylcyclohexan-1-ones is described. Substitution was varied with both rings; both isomers of 4-phenyl-4-(hydroxymethyl)cyclohex-1-ylamine were characterized. Those derivatives which carried p-fluoro substitution on the butyrophenone exhibited hypotensive activity in the rat with diminished CNS activity compared to compounds lacking the hydroxymethyl group. The effect of substitution on the 4-aryl ring is discussed.


Potential inhibitors of polyamine biosynthesis. 2. alpha-Alkyl- and benzyl-(+/-)-ornithine. Alpha-Methyl-(+/-)-ornithine hydrochloride was not a substrate for ornithine decarboxylase from rat prostate glands. It produced equal inhibition of ornithine decarboxylase obtained from rat prostate glands, spleens of mice inoculated with L1210 leukemic cells, and regenerating rat liver indicating its lack of selectivity for any of these tissues. In these three tissues the inhibition was competitive with L-ornithine. A number of alpha-alkyl- and alpha-aralkyl-substituted analogs of (+/-)-ornithine were synthesized and evaluated in vitro as inhibitors of the enzyme L-ornithine decarboxylase obtained from prostate glands of rats. These compounds were obtained by the reaction of alkyl iodide or benzyl bromide with the anion obtained by treatment of 3-(benzalimino)piperidin-2-one with sodium hydride. The following alpha-substituted analogs of (+/-)-ornithine were obtained: ethyl, n-propyl, n-butyl, n-hexyl, n-octyl, and benzyl. The synthesized compounds were found to be much less active than alpha-methyl-(+/-)-ornithine as competitive inhibitors of ornithine decarboxylase in vitro. The most active compound in the series was alpha-n-octyl-(+/-)-ornithine which was 60-fold less active than alpha-methyl-(+/-)-ornithine and the least active analog was alpha-n-butyl-(+/-)-ornithine which was 270-fold less active than the alpha-methyl-(+/-)-ornithine.


Physiochemical-activity relations in practice. 1. A rational and self-consistent data bank. A data bank of substituent constants of 26 ortho and 34 meta and para benzenoid substituents is presented for use in physicochemical-activity relations (PAR) studies. The distributive parameters pri and pri-, a bulk parameter based on molar refraction, and positionally weighted electronic parameters F and R are listed for the three substituent positions. There are no gaps in the table caused by missing values and the interparameter correlation are low.


Physicochemical-activity relationship in practice. 2. Rational selection of benzenoid substituents. A rational method is presented for the selection of substituents to be introduced into a benzenoid ring system of a biologically active compound in order to a defined physicochemical parameter space. The method, which may be readily programmed for use on a computer, relies on maintaining a minimum distance between compounds in the multidimensional physicochemical parameter space. The series of compounds produced will then have a well-spread set of minimally correlated physicochemical parameter values and could thus be used for the reliable correlation of the variation in the biological activities of the members of the series with changes in these physicochemical parameters. Some examples of the use of the present method under various conditions are given, and it is compared with alternatives in the literature.


Effect of 9-hydroxylation on benzomorphan antagonist activity. In a benzomorphan bearing an antagonist side chain, introduction on the methano bridge of a hydroxyl oriented away from nitrogen has little effect on antagonist activity whereas a hydroxyl oriented toward nitrogen enhances this activity. Hydroxylation tends to decrease analgesic activity.


Quantitative structure-activity relationships in the delta6-6-substituted progesterone series. A reappraisal. A quantitative structure-activity analysis concerning the progestational activity of a series of delta6-6-substituted progesterone is presented which differs from that published recently by other authors. In the current study all compounds in the data set for which parameters are available are included and activity is shown to relate to primarily lipophilic but also steric effects.


4-Amino-5-arylpyrimidines as antiinflammatory agents. 4-Amino-5-arylpyrimidines were synthesized by a variety of methods and have demonstrated antiinflammatory activity in the carrageenan-induced edema in the rat but displayed little activity against adjuvant-induced arthritis in rats or against uv-induced erythema in guinea pigs.


Synthesis of alpha-1-noracetylmethadol. A facile N-demethylation of alpha-1-acetylmethadol. A facile N-demethylation of the narcotic analgesic, alpha-1-acetylmethadol, was accomplished by allowing it to react with mercuric acetate under reflux in dilute acetic acid. The product, alpha-1-noracetylmethadol, was isolated as the hydrochloride in 50% yield. Methadone, when allowed to react with mercuric acetate under the same conditions, did not undergo N-demethylation and was recovered unchanged.


Synthesis of quinazoline analogs of isofolic acid. Four quinazoline analogs of isofolic acid were synthesized including 5-methyl-5,8-deazaisofolic acid (8a), 5,8-deazaisofolic acid (8c), as well as their 4-NH2 counterparts 8b and 8d. None of these showed significant activity against L1210 leukemia in mice at dose levels where amethopterin provided significant prolongation in survival.


Synthesis and biologic evaluation of major metabolites of N-(2-chloroethyl)-N'-cyclohexyl-N-nitrosourea. N-(2-chloroethyl)-N'-(cis-4-hydroxycylohexyl)-N-nitrosourea, a major metabolite of N-(2-chloroethyl)-N'-cyclohexyl-N-nitrosourea (CCNU), and its trans isomer were prepared from the corresponding 4-aminocyclohexanols. A convenient and stereospecific precursor was found in 2-oxa-3-azabicyclo[2.2.2]oct-5-ene hydrochloride, hydrogenation giving pure cis-4-aminocyclohexanol hydrochloride. The metabolites were, at nontoxic levels, at least as active as CCNU in tests against murine leukemia L1210 implanted both intraperitoneally and intracerebrally and, on a weight basis, were more active and more toxic. These observations and previously reported metabolic studies suggest that the anticancer activity of CCNU is due primarily to its metabolites.


Quantum chemical studies of morphine-like opiate narcotics.  Effect of N-substituent variations. Quantum chemical calculations including extensive conformational variations are performed on three morphine-like analgesics with varying N-substituents using the PCILO and INDO methods.  The three compounds, morphine, nalorphine, and N-phenethylmorphine, have been shown experimentally to exemplify opiate narcotic agonism, antagonism, and increased agonism, respectively.  In this study, these properties are correlated with the electronic and conformational results.  The electronic properties of the fused ring skeleton including specifically the cationic region around the nitrogen are relatively unaffected by varying N-substituents.  The properties studied include net charges, bond polarities, and the nature and energy of the highest filled and lowest empty molecular orbitals.  The conformational behavior appears to be the main cause of differing receptor binding and interaction with the active site and is discussed in these terms.


Conformation of histamine derivatives. 5. Molecular orbital calculation of the H1-receptor "essential" conformation of histamine. Conformational energies of histamine and 4-methylhistamine monocations are calculated using the EHT molecular orbital procedure; the results are expressed as potential energy surfaces in which bond rotations (theta1 for ring-Cbeta, theta2 for Cbeta-Calpha) are measured along the axes, and energy variation is indicated by contours. Using the classical Boltzmann partition function and Simpson's rule for normalization, corresponding probability surfaces are generated which take account of the potential surface entropy. Comparing the two surfaces provides regions which are within a given probability contour of histamine but outside this contour for 4-methylhistamine. Thus, at the 99% probability level, three conformational regions defined by the bond rotation angles are indicated as possible "H1-essential" conformations of histamine: viz. trans (theta1=290-330 degrees, theta2=150-210 degrees) and gauche (theta1=260-280 degrees, theta2=30-90 degrees and theta1=290-320 degrees, theta2=270-320 degrees). This procedure provides a quantitative basis for comparison with other histamine derivatives and may have a general value for studying relationships between conformation and biological activity of closely related small molecules.


N-Hydroxylation of 1-(2,5-demethoxy-4-methylphenyl)-2-aminopropane by rabbit liver microsomes. Metabolic N-hydroxylation of the potent psychotomimetic amine 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (5) by rabbit liver microsomal preparations has been investigated. Synthetic hydroxylamine 8 was obtained by sequential reduction of the corresponding nitropropene 10 with sodium borohydride followed by zinc reduction of the resulting nitropropane 11. Compound 8 in water (pH 7.4) was rapidly air oxidized to oxime 12; this oxidation was completely blocked by rabbit liver microsomes. Microsomal incubations of amine 5 or its bis(methoxy-d3)hexadeuterio analog 5-d6 resulted in the formation of 8 and 8-d6, respectively, identified as their bis(trifluoroacetyl) derivatives by GLC-MS. Quantitative estimations of metabolite formation employing selected ion monitoring with the aid of an accelerating voltage alternator were accomplished by stable isotope dilution analyses with 5-d6 as substrate and 8-d0 as internal standard. Similar analyses starting with "pseudoracemates" (R)-5-d0:(S)-5-d6 or (R)-5-d6:(S)-5-d0 as substrates established metabolite 8 to be enriched with its R enantiomer.


Triarylpyridylethanols and triarylpyridylethylenes.  Chemistry and antifertility effects. Triarylpyridylethanols were prepared by condensing the corresponding diaryl ketones and diarylmethanes. The ethylenes were obtained by the acid-catalyzed elimination of H2O from the ethanols. In the absence of electron-donating substituents, acid treatment of the carbinols resulted in predominant cleavage to starting ketone. The compounds were tested for their antifertility effects in pregnant hamsters. The most active compound was carbinol 3, which, at 30 mg/kg, prevented all of the treated animals from maintaining their pregnancies.


Synthesis and antiinflammatory activity of some-2-substituted alpha-methyl-5-benzimidazoleacetic acids. The synthesis of alpha-methyl-5-benzimidazoleacetic acid (17), its 2-amino, 2-phenyl, 2-(4-chlorophenyl), and 2-(4-chlorophenyl)-1-methyl derivatives (18,4,3, and 5, respectively), and alpha-methyl-2-oxo-2,3-dihydro-5-benzimidazoleacetic acid (19) is described.  None of the compounds were effective in reducing carrageenan-induced edema in rat paws.


Analgesics. 3. Selected 1-substituted and 1,3-disubstituted 5-propionoxy-5-(1-phenylethyl)barbituric acids. Several 1,3-disubstituted and 1-substituted derivatives of 5-propionoxy-5-(1-phenylethyl)barbituric acid were synthesized and evaluated for analgesic activity.  Three of these compounds, 1,3-bis(methoxymethyl)-5-propionoxy-5-(1-phenylethyl)barbituric acid (2), 1,3-dimethyl-5-propionoxy-5-(1-phenylethyl)barbituric acid (7), and 1-methyl-5-propionoxy-5-(1-phenylethyl)barbituric acid (10), exhibited better oral activity than codeine sulfate.


Hydrogenated benzo[f]quinolines and benz[e]indoles as analgetics. 1. A series of octahydrobenzo[f]quinolines(IIIa) and hexahydro-1H-benz[e]indoles(IIIb), rigid structures related to 3-phenylpiperidine and pyrrolidine analgetics, has been synthesized.  Structure-activity relationships were investigated by varying the structural parameters including a change in the stereochemistry of the ring junction.  Several of the resulting compounds had analgetic activity on the order of meperidine.


Analgesic properties of the tetrahydrocannabinols, their metabolites, and analogs. The tetrahydrocannabinols from marihuana were found to have moderate analgesic activity in mice by the hot-plate test (sc administration).  Of the several metabolites of these two compounds tested, only the 11-hydroxy derivatives were more potent than the parent compounds.  Analogs 1 and 2 (9-demethyl relatives which cannot be metabolized to 11-hydroxy compounds), both of which produce a pharmacological profile generally similar to that of delta8- and delta9-THC, were analgesically inert.  This suggests that metabolism to 11-hydroxy congeners may be necessary for the mediation of analgesic activity in the mouse hot-plate test but not for other pharmacologic effects produced by these substances which we have examined.


4-hydroxy-3-nitro-2-quinolones and related compounds as inhibitors of allergic reactions. The synthesis and biological activity of a number of 4-hydroxy-3-nitro-2-quinolones are discussed and compared with their related hydroaromatic analogs.  Antiallergic activity has been assessed by their ability to inhibit the homocytotropic antibody-antigen induced passive cutaneous anaphylaxis reaction in the rat.


Antiallergic activity of omega-nitroacetophenones. Selected omega-nitroacetophenones, formed by the alcoholic cleavage of 2-nitroindandiones, have been shown to inhibit the homocytotropic antibody-antigen induced passive cutaneous analhylaxis reaction in the rat.  The enzymatic cyclization of these derivatives to the parent nitroindandione has been demonstrated both in vivo and in vitro and this process is suggested as a possible prerequisite to biological activity.


Synthesis of an active hydroxylated glutethimide metabolite and some related analogs with sedative-hypnotic and anticonvulsant properties. Two synthetic pathways are described for the preparation of 4-hydroxy-2-ethyl-2-phenylglutarimide (2), an active hydroxylated metabolite of glutethimide (1).  Fourteen other glutethimide analogs were also synthesized and tested for biological activity.  Most of the analogs exhibited sedative-hypnotic properties and compound 2 possessed the greatest activity compared to the parent drug.  4-Amino-2-ethyl-2-phenylglutarimide and 4-hydroxy-2-ethyl-2-phenylglutaconimide (13) exhibited the greatest potential as anticonvulsant agents.  The structure-activity relationships of the series are discussed.


Quinoxaline studies. 23. Potential antimalarials. Substituted 5,8-dimethoxy-6-[N-(omega-dimethylaminoalkyl)amino]quinoxalines were prepared: the first series with identical 2,3-substituents H, CH3, C6H5, C6H4-4-Cl, and CH2C6H5; and the second with identical styryl groups CH=CHC6H5, CH=CHC6H4-4-Cl, CH=CHC6H3-3,4-Cl2, CH=CHC6H4-4-F, CH=CHC6H4-4-CF3, and CH=CHC6H4-4-NO2. None of the substances possessed antimalarial activity; several were toxic at highest dosage levels. 3-Hydrazinopyridazines substituted in position 6 with a primary amine, secondary amine, or an alkoxy group were synthesized and screened for antihypertensive activity.  In general, the 6-dialklamino derivatives are the most active; the (2-hydroxypropyl)methylamino chain provides the best combination of high antihypertensive activity and toxicity.


Ellipticine derivatives.

Ellipticine derivatives. Several acyloxy and alkyl derivatives of ellipticine have been prepared.  In addition, a modified synthesis leading to the hitherto unobtainable 8,9-dimethoxy- and 8,9-methylenedioxyellipticines is described.  Some of the derivatives described herein exhibit antitumor activity.  However, none of the compounds showed activity superior to that of the naturally occurring pyridocarbazoles, ellipticine and 9-methoxyellipticine.


Bradykinin analogs containing beta-homoamino acids. Two new analogs of bradykinin, [8-beta-homophenylalanine]- and [7-beta-homoproline]bradykinin, have been synthesized by the solid-phase technique.  In the anesthetized rat, [7-beta-HPro]bradykinin was equipotent with bradykinin and 30-100 times more potent than [8-beta-HPhe]bradykinin in vasodepressor activity.  Both analogs were resistant to degradation in vitro by dipeptidylcarboxypeptidase from rabbit lung.  Only the 7-beta-HPro analog seemed to be resistant to this type of degradation in vivo, since its hypotensive effect in the anesthetized rat was not potentiated by SQ 20881 (BPP9a), an inhibitor of dipeptidylcarboxypeptidase.


Potential central nervous system antineoplastic agents. Amides of 6-cyano-6-norlysergic acid. A group of amides of 6-cyano-6-norlysergic acid was prepared from their corresponding lysergamides.  None of these N-cyano derivatives showed anticancer activity against lymphoid leukemia L1210 in mice.  This is in contrast to the reported in vitro anticancer activity (P-815 mastocytoma) of 6-cyano-6-norlysergic acid diethylamide.


Studies in antifertility agents. 11. Secosteroids. 5. Synthesis of 9,11-secoestradiol. 9,11-Secoestradiol (9) and 11-hydroxy-9,11-secoestradiol (12) have been synthesized starting from 17-acetoxyestradiol 3-methyl ether (1) and found to possess significant antifertility activity in rats.  3-Methoxy-9,11-seco-9-oxo-17beta-acetoxyestra-1,3,5(10)-trien-11-oic acid (2), prepared by CrO3 oxidation of 1, on hydrogenolysis gave methyl 17beta-hydroxy-3-methoxy-9,11-secoestra-1,3,5(10)-triene-11-carboxylate (3).  The 17-O-THP derivative of 3 was treated with LiAlH4 to give 17beta-(O-tetrahydropyranyl)-3-methoxy-11-hydroxy-9,11-secoestra-1,3,5(10)-triene (5).  The 11-O-mesylate of 5 on LiAlH4 reduction followed by mild acid treatment and demethylation under alkaline conditions gave 9. LiAlH4 reduction of 3 gave 9,11-seco-11-hydroxyestradiol 3-methyl ether (11) which on demethylation gave 9,11-seco-11-hydroxyestradiol (12).


Programmatic computer simulation model for medical school planning. A comprehensive programmatic computer simulation planning model for a school of medicine was generated by integrating several separate simulation models with on-site cost study information. An elementary validation of the model was achieved. The model generated program costs in terms of both faculty hours and dollars. Results indicated that the size of the medical class could be increased from 75 to 100 students within the present resource limitations by transferring faculty time to education from other programs. The maximum class size was limited by the availability of clinical material. The basic science departments could handle this class size easily without significant reduction in other programs, but the clinical departments could not do so unless inpatient levels increased significantly.


Resident participation in residency programs. Residents need to participate more fully in decisions involving their educational process and their learning/work setting. In the Department of Family Medicine at the University of Miami School of Medicine, residents are involved in designing their curriculum, monitoring their work/learning settings, selecting their peers, and evaluating their peers and faculty. This style of residency program has significant implications not only for patient care but also for future physicians, medical departments, and medical associations.


Objectives of pharmacological education. Pharmacological education is presented as a continuous undertaking of preclinical students, clerks, and physicians and surgeons in training and practice (1). Carrying out this activity requires five operations: (a) selecting criteria of effective and safe drug use in patients; (b) defining attitudes, knowledge, and skills of clinicians who practice effective pharmacotherapy; (c) developing these attitudes, knowledge, and skills in prescribers: (d) evaluating the proficiency of prescribers at certification and in actual practice; and (e) identifying causes of prescribing deficiencies in order to amend inappropriate methods of instruction.


The Quebec health care system: its implication for medical education. Since November 1, 1970, doctors in Quebec have been operating under a government-controlled compulsory and universal "fee-for-service" insurance plan. After a review of some characteristics of the new system, the author describes the impact of this social legislation on physicians' lives, control of health delivery costs, and various policy issues. He examines the implications of these changes for medical education. A qualitatively different kind of physician must be able to deal comfortably and effectively with a reality which includes: (a) the concept of "global medicine" and its social implications, (b) greater external control of costs and increased public concern with quality, (c) a new concept of the role of the hospital and its integration within the system, and (d) the concept of team care. Possible changes associated with the new system include a reevaluation of the criteria for a good clerkship, an acquisition of a new perspective on community health ecology, and a need to become an efficient team-worker.


The two-course system in gross anatomy.

The two-course system in gross anatomy. In response to the continuing pressures facing anatomy and other basic sciences in medical education, the Department of Anatomy at the University of Colorado School of Medicine has instituted a parallel two-course system of teaching gross anatomy. Students in both the longer and shorter of the two courses appear to be prepared adequately by their experiences in the courses they elected. Statistically significant differences (students in the longer course scoring higher) were, however, observed on both departmental examinations and certain national examinations administered subsequent to the completion of the courses. Student responses to both courses were extremely favorable. Since the differences between the two groups were generally small and advantages were noted in presenting two courses simultaneously, it is concluded that the concurrent presentation of two differently organized basic science courses (within a single subject area) offers an effective response to the instructional needs of our medical school and medical students.


Predicting academic success for military paramedical personnel. The utilization of selected cognitive, demographic, and personal histroy measures as predictors of academic success for Naval Hospital Corps School personnel undergoing paramedical training was investigated using a smaple of 1,448 students. A composite criterion score reflecting grade-point average as well as administrative discharge was related to a number of preservice cognitive and noncognitive predictors. Multiple regression techniques were used to weight specific variables and to predict performance in a crossvalidation sample. Findings indicated that demographic and personal histroy measures contributed uniquely to prediction of academic success.


Consumer perceptions of health care services: implications for academic medicine. The factor analytic development of various measures of consumer perceptions regarding characteristics of doctors and health care services is described. Index scores meeting factor analytic and reliability criteria were used to study the importance of consumer perceptions in relation to behavioral outcomes. Numerous dimensions of consumer perceptions were identified and described, including beliefs about doctor conduct in terms of quality of care and humaneness of health care delivery as well as satisfaction with such enabling components as the continuity of care, availability and convenience of services, and various access mechanisms (cost, payment mechanisms, and ease of emergency care facilities). Measures of these perceptions were shown to be related to differences in several estimates of health services utilization. The use of the index scores which have met empirical criteria is in contrast to the common practice of using individual questionnaire items as the unit of analysis in health care research. Findings are discussed in relation to program planning and evaluation in medical education, and suggestions for future research are noted.


Clinical teaching reexamined.

Clinical teaching reexamined. In an effort to determine the most effective clinical teaching behaviors of clinical teachers or preceptors in individual or small group settings, investigators at the University of North Carolina and the University of Alabama developed an instrument to survey all clinical medical students at the two institutions. This process resulted in a compilation of the specific behaviors found to be most helpful to the responding students in facilitating their clinical learning. All items were then factor analyzed, resulting in six more general teaching dimensions or factors being identified. There were active student participation, preceptor attitude toward teaching, emphasis on applied problem-solving, a student-centered instructional strategy, humanistic orientation, and emphasis on content and research. The more specific behaviors which loaded on each factor were also examined.


Teaching of formal courses by medical librarians. Medical education should include formal course work on the use of the medical library. The formal teaching effort of medical librarians at the University of Tennessee Center for the Health Sciences is described. Three courses on the use of the library are offered to graduate students in basic medical sciences, dentistry, and pharmacy and to undergraduate students in medical records administration. A review of the literature covering teaching by medical librarians and the results of a questionnaire survey also are reported. A 95 percent response to a questionnaire sent to 105 health-science-related school libraries was received. Of the 100 libraries responding, only 18 offered formal course work. An additional 19 reported plans for offering formal courses on the use of the library.


A profile of clinical nutrition knowledge among physicians and medical students. The clinical nutritional knowledge of medical students and practicing physicians was assessed. Overall, nutrition knowledge was modest. However, there were substantial variations in knowledge among closely related topics. Knowledge often was highest among nutrition topics which have received the most publicity in the popular press. The nutrition knowledge profile suggests that medical students and physicians learn about nutrition haphazardly and are highly dependent for their knowledge on nonprofessional literature.


Molting in stomatopod crustaceans. I. Stages of the molt cycle, setagenesis, and morphology. The description of stages of the molt cycle in mantis shrimp (emphasizing Gonodactylus but compared in a number of Gonodactylidae, Squillidae, and Lysiosquillidae) includes data on texture, hardness, and color of the exoskeleton; behavior; and the micromorphology of the integument and developing setae. After stage A1, when the exoskeleton feels soft and soapy, and A2, when the abdomen attains parchment consistency, the exoskeleton continues to harden until stage C1, when the telson carinae can no longer be depressed with a fingernail. The propodus (C2) and the merus (C3) of the raptorial appendage are the last elements to become rigid. The meral spot achieves indistinct coloration at B1 and distinct but pale coloration at B2; body color continues to intesify until C4. Changes in behavior are particularly marked before and after the molt. After the molt defensive and avoidance behaviors characterize A1 and A2. Threatening increases from low to intense levels in A2 and B1. Striking and offensive behavior increase from weak to normal intensities from B2 to C4. One or two days before  the molt, animals lower activity and dominance and feeding levels, exhibit reclusive behavior, and sometimes seal the cavity entrance. The morphology of setagenesis is particularly valuable for determining the stage of the molt after the exoskeleton hardns. The raatio of setae containing cellular contents sthroughout the lumen to those condensed into strands separates stages A2 throught C3...


Relationship of the sarcoplasmic reticulum to fibril and triadic junction development in skeletal muscle fibers of fetal monkeys and humans. Examinations of stages of fibril development in muscle fibers of seven Rhesus monkey and six human fetuses reveal SR tubules encircling the Z lines at all stages of fibril development. The encircling SR tubules are continuous with the SR network of tubules which is found surrounding fibrils at all stages of development observed. The SR tubules encircling the Z lines show connections (electron-opaque strands) with the Z lines. The developing triadic junction shows a progressive increase in complexity of structures within the junction. First, membranes of T and SR become apposed with no visible structure between them- Second, tenuous connections are found traversing the space between apposed membranes. Third, well developed bridges are seen traversing the space. And finally, an intermediate density midway between the apposed membranes and parallel to them is found in favorable sections. Junctions between T tubule membranes were also observed and the structures in these junctions are somewhat similar to those found in junctions between T and SR membranes. The change in orientation of triads from predominantly longitudinal to predominantly transverse is complete in the 18-week monkey fetus and incomplete in the latest stage (28-week) of fetal development observed in humans.


Muscle activity in rat locomotion: movement analysis and electromyography of the flexors and extensors of the elbow. Footfall patterns and time sequence of activity are described for white rats conditioned to run freely in an activity wheel (which they drive). Motion is described in terms of soft contact, hard contact, soft contact, and flip phases. Duration of stride decreases and length of stride increases from walk to trot to canter to gallop. Myographic analysis shows that the brachialis has a major tonic function after it fires strongly during the flip phase and during much of the hard contact phase. Animals running at canter or gallop show major asymmetries between forelimb muscles on the first paw and on the lead paw sides.


Cytological events leading to the cleavage of golden hamster zygotes. Fertilized golden hamster eggs were examined between 6 and 20 hours post-ovulation to determine the events leading to the two-cell stage. Following their migration the pronuclei remain in the central region of the zygote for approximately ten hours. The morphologically, indistinguishable male and female pronuclei remain relatively unchanged during this period, i.e., they do not interdigitate or fuse with one another as described for the zygotes of other organisms. Following this period and at the time of pronuclear breakdown elongate vesicles appear along the nucleoplasmic surface of the pronuclear envelopes. Later the pronuclear envelopes fragment into elongate cisternae; these and the vesicles formed along the inner lamina of the pronuclear envelopes remain closely associated and constitute quadrilaminar structures. The chromosomes which condense prior to and during pronuclear envelope breakdown, migrate to the equatorial plate of the forming cleavage spindle. After cytokinesis the chromosomes in the blastomere nuclei disperse. Increase in the nuclear envelope to accommodate this dispersion may involve the addition of membrane from the quandrilaminar structures.


Aspects of germinal cyst and sperm development in Poecilia latipinna (Teleostei: Poeciliidae). The structure of the testis of Poecilia latipinna is described with particular reference to Sertoli cell-germ cell relationships during development and maturation of the germinal cyst. The cyst develops when primary spermatocytes become surrounded by a single layer of Sertoli cells at the testis periphery. As spermatogenesis and then spermiogenesis proceed, the cyst moves centrally in the testis toward the ducts comprising the vasa efferentia. In addition to being a structural part of the germinal cyst, the Sertoli cells phagocytize residual bodies cast off by developing spermatids and form an association with mature bodies cast off by developing spermatids and form an association with mature sperm, which resembles that observed in mammals, before the sperm are released into the vasa efferentia as a spermatozeugmata. The results of this investigation are discussed in view of what is known concerning testis structure in other teleosts and similarities between cell functions in teleosts and mammals. It is concluded that teleost Sertoli cells, teleost lobule boundary cells and mammalian Sertoli cells are homologous.


Morphology and function of Malpighian tubules and associated structures in the cockroach, Periplaneta americana. This paper describes the different regions of the Malpighian tubules and the associated structures (ampulla, midgut, ileum) in the cockroach, Periplaneta americana. There are about 150 tubules in each insect. Each tubule consists of at least three parts. The short distal region is thinner than the other parts and is highly contractile. The middle region comprises most of the tubule length and is composed of primary and stellate cells. Primary cells contain numerous refractile mineral concretions, while stellate cells have smaller nuclei, fewer organelles, simpler brush border, and numerous multivesicular bodies. Symbiont protozoa are sometimes present within the lumen of the middle region near where it opens into the proximal region of the tubule. The latter is a short region that drains the tubular fluid into one of the six ampullae. These are contractile diverticula of the intestine located at the midgut-hindgut junction. The ampulla is highly contractile, and consists of a layer of epithelial cells surrounding a cavity that opens into the gut via a narrow slit lined by cells of unusual morphology. The proximal region of the tubule and the ampulla resemble the midgut in that they have similar micromal origin and reabsorptive function for the proximal region of the tubule and for the ampulla. A number of inclusions found within the tubule cells are described, including peroxisomes and modified mitochondria. Current theories of fluid transport are evaluated with regard to physiological and morphological characteristics of Malpighian tubules. The possible role of long narrow channels such as those between microvilli and within basal folds is considered, as is the mechanism by which these structures are formed and maintained. Also discussed is the role of peroxisomes and symbionts in the excretory process.


Regeneration of digits and forelimbs in the Kenyan reed frog Hyperolius viridiflavus ferniquei. Newly metamorphosed individuals of the Kenyan reed frog, Hyperolius viridiflavus ferniquei, are able completely to regenerate amputated digits, including the morphologically complex digital pad. The sequence of morphological events is very similar to that seen in the typical epimorphic regeneration of amphibian extremities. Amputated forearms typically produce hypomorphic spike regenerates. Despite the lack of underlying hand and digital structures, an apical "digital" pad commonly differentiates.


Functional anatomy of the heart of the harbor porpoise, Phocaena phocaena. Thirty-six harbor porpoises, Phocaena phocaena, were caught off the coast of Southern New Brunswick and Nova Scotia as part of a study of the biology and ecology of these animals. The formalin-preserved heart was examined first in situ, then measured and studied in detail. If the weight of the thick layer of blubber is discounted, the heart is heavy relative to the total body weight as may be expected in an animal capable of fast swimming, great agility and frequent emergence from the water to breathe. The shape of the heart, the relative size of atria and atrial appendages, the morphology of the ventricular septum, the thickness of the walls of the sinus and conus of the right ventricle and the anatomy of the pulmonary veins were found to be constant for this animal and unlike that of non-cetaceans. It is suggested that the absence of respiratory movements during diving may lead to these modifications of cardiac structure in an animal that is particularly well adapted to a totally aquatic existence.


The motor units of cat medial gastrocnemius: electrical and mechanical properties as a function of muscle length. The effects of changing muscle length on the mechanical properties of 89 motor units from adult cat medial gastrocnemius have been studied in eight experiments. Few differences were found between the effects of length on tetanic tension, twitch tension, twitch-tetanus ratio, twitch contraction time, twitch half relaxation time, rate of force development and electrical activity for fast contracting (twitch contraction time less than or equal to 45 msec) and slowly contracting (greater than 45 msec) units. Those differences that did appear did not persist when these two groups were matched by tetanic tension. It is concluded that the biophysical mechanisms responsible for the changes in mechanical and electrical properties with length must be similar for fast and slow twitch units and not related to potential differences in their muscle fiber type. The effects of changing muscle length on the mechanical properties of the eight whole muscles suggest that changes in force output with length are of minor importance during normal movements as the muscle is found to be electrically active over a relatively narrow range of lengths close to the optimum length for tetanus of the whole muscle. The very shortest muscle lengths at which there is only minimal force development are not used in natural movements, while the declining limb of the length tension curve is at muscle lengths beyond the maximum in situ length.


Arteriography in the assessment of renal trauma. The impact of arteriographic diagnosis on preservation of renal function and parenchyma. The efficacy of arteriographic triage of patients who sustained renal trauma into two groups, one optimally handled by early surgical intervention and one in whom conservative management guarantees maximal preservation of renal parenchyma, is discussed, based on a study of 190 patients. A substantial increase in the number of patients managed conservatively (73%) is attributable to use of arteriographic selection criteria. A very low rate of complications (2%) appears to substantiate the validity of the criteria on which the selection was based. Similarly, arteriographic criteria made possible substitution of hemi- or partial nephrectomy in almost 42% of patients who would otherwise have been treated by nephrectomy. A very low rate of complications resultant from this procedure justifies its use in these cases. The very low mortality rate (1.6%) of the present series suggests a bonus contribution of arteriography toward the management of associated intra-abdominal injuries. The safety of angiography and the now general availability of angiographic facilities and skilled personnel on a round-the-clock basis, and the policy-determining information derived from these studies, recommend widespread deployment of this method for the assessment of renal injury.


A half-century of experience in the management of colon injuries: changing concepts. A total of 773 patients who sustained colon injuries during the period 1927-1974 at Charity Hospital of Louisiana in New Orleans was reviewed. For purposes of comparison the patients were grouped into three 15-year periods. The first period (1927-1942) represented patients treated in the pre-antibiotic era exclusively with exteriorization. The second period (1943-1958) included patients in whom a program of selective surgical treatment of colon injuries was instituted, and included the advent of antibiotics and improved resuscitation. The final period (1959-1974) represented the increased use of primary repair of colon injuries. In comparing the three consecutive periods there was a marked increase (106%) in the frequency of colon injuries, primarily due to gunshot wounds in young males. The average age of our patients during this last 15-year period was 27 years. The transverse colon was the most frequent site of the injury (37%) followed by the left colon (31%) and the right colon (20%). From 60 to 75% of the patients also had associated intra-abdominal or other injuries. The mortality from colon injuries has declined steadily from 67.5% in the initial period to a low of 9.2% during the past 15 years. This drop in mortality occurred despite the fact that a larger number of patients sustained associated injuries. When comparing the three methods of therapy, primary repair, repair with proximal colostomy, and exteriorization was used less frequently during the past 15 years. It was the exclusive form of therapy in all patients treated before 1942. With the advent of selective management and antibiotics we have seen a transition from exteriorization to primary repair without colostomy. During the past 15 years primary repair was used in 44% of the patients; repair with a proximal decompressive procedure was utilized in 22%; exteriorization was carried out in 33% of the patients. The selective use of primary repair has been associated with lower mortality, fewer complications, and a shorter hospital stay, despite the increasing incidence of multiple associated injuries in this latter group of patients. Based on these studies, a plea is made for the selective use of primary repair of colon injuries of patients in good general condition when the local injury to the colon appears to warrant such an approach=


Evaluation of three methods for managing penetrating colon injuries. Although primary intraperitoneal repair of selected penetrating colon injuries is a feasible method of treatment, injudicious use of this method, especially in wounds of the right colon, led to increased morbidity, in the group of 90 patients studied. Colostomy may be avoided in selected patients by using primary repair with exteriorization of the injured segment. The technique described is a reliable compromise which protects the patient from the danger of intraperitoneal suture line disruption and possibly avoids the inconvenience and morbidity of formal colostomy. Since exteriorized primary repair has been a safe, effective method of managing gunshot wounds of the colon in selected patients, we advocate its increased use.


Failure of tube thoracostomy for post-traumatic empyema: an indication for early decortication. Post-traumatic empyema has occurred in seven patients despite chest tube drainage and antibiotics. Early pleural decortication resulted in complete recovery of all patients with early discharge from the hospital in most instances. The surgical procedure is technically simple to perform if carried out before the organization of the pleural exudate. Criteria are offered for early decortication of the lung for post-traumatic empyema. They are: 1) Residual air-fluid levels despite chest tube drainage. 2) A clinically deteriorating course with evidence of infection or sepsis arising from the pleura. 3) Pleural restriction with inadequate expansion of the lung resulting in compromised ventilatory function. 4) Failure of chest tubes to allow for resolution of pleural contamination within 14 days of injury. If such indications are employed, excellent results can be anticipated from early decortication of post-traumatic empyema.


Cervical-thoracic transverse process fracture: further observations on the seatbelt syndrome. Fracture of the transverse process C7 and T1 may represent another seatbelt injury particularly related to the use of a system including a shoulder harness beltmfour cases are discussed and the proposed mechanism and potential implications of this injury are outlined.


Brachial plexus root avulsion: role of myelography--review of diagnostic procedures. Myelographic evidence of traumatic meningocele in brachial plexus injuries has been considered to be pathognomonic of root avulsion. Two such cases with myelographic evidence of root avulsion with excellent recovery at those levels are presented. Various diagnostic procedures in brachial plexus injuries are critically reviewed. The sequence in which these tests are of diagnostic value are: 1) clinical evaluation, motor and sensory, from the time of admission; 2) electroneuromyography at 2-3 weeks following injury; 3) axon reflex response at 2-3 weeks; 4) myelography; 5) very rarely, surgical exploration.


Bone cyst following gunshot wound: case report. A case of a large bone cyst developing in the distal femur of a 17-year-old boy requiring curettage and grafting 20 months following a low-velocity gunshot wound is reported. The etiology of such cysts remains obscure, and removal of bullets from weight-bearing bones is recommended when feasible, or followup roentgenograms of weight-bearing bones with retained missiles. The literature on civilian gunshot injuries is reviewed and implications from the present case are discussed.


Cerebral thromboembolism secondary to subclavian artery trauma: report of a case. A case of traumatic thrombosis of the left subclavian and left vertebral arteries is reported which presented with signs of basilar artery insufficiency and right homonymous hemianopsia 3 weeks after the injury. The diagnosis, which was clinically unsuspected, was made by angiography. Surgical removal of the thrombus was successful.


The use of the fiberoptic bronchoscope to facilitate endotracheal intubation following head and neck trauma. The fiberoptic bronchoscope is an invaluable aid in the difficult endotracheal intubation. Its successful use with three patient groups is described: those with soft-tissue contractures of the mouth or neck; those with severe fractures of facial bones and/or mandible; those with unstable fractures or fracture-dislocations of the cervical spine. Fiberoptic bronchoscopy is felt to be the technique of choice when intubation is difficult, especially when there are contractures or deformities of the larynx, manidible, or cervical spine.


Fiberoptic bronchoscopy in acute inhalation injury. Fiberoptic bronchoscopy proved to be a simple, safe, and accurate method of diagnosing acute inhalation injury. Both the anatomic level and the severity of large airway injury were easily identified. The identification of a supraglottic and infraglottic component to inhalation injury was not only helpful in determining the appropriate therapy but also in predicting ultimate pulmonary complications. When bronchoscopy was used in conjunction with the 133Xenon scintiphotoscan, both large and small airway injuries could be identified. The only clinical situation where bronchoscopy failed to identify an inhalation injury was in the immediate postburn period if the patient wasin hypovolemic shock. In this particular clinical circumstance the characteristic mucosal alterations may be absent; yet if bronchoscopy is performed after hypovolemic shock has been corrected, mucosal changes characteristic of inhalation injury will be seen.


Ventilatory patterns following burn injury and effect of sulfamylon. Seven burn patients treated with silver nitrate dressings were studied during the first 10 days after injury. Minute ventilation, oxygen consumption, and ventilatory equivalent were measured. Minute ventilation was increased two- to threefold, as was oxygen consumption. Ventilatory equivalent was only slightly increased. THree patients were initially treated with silver nitrate, and then, when clinically stable, were switched to Sulfamylon. They showed a 50% rise in ventilation, tidal volume, ventilatory equivalent, and a slight increase in respiratory rate and VD/VT. In addition, their PO2 increased and base excess fell. Five normal subjects were then given Diamox, and their minute ventilation, O2 consumption, and ventilatory equivalent were measured at rest, with a standard exercise, and with an added dead space. Diamox produced only a 25% increase in minute ventilation and ventilatory equivalent. The results suggest that, although some of the increased ventilation of Sulfamylon is due to carbonic anhydrase inhibition, another factor, such as pain casued by the topical agent, also plays a role.


Blood availability for the trauma patient-autotransfusion. Recovery of intrathoracic and intraperitoneal blood and reinfusion by autotransfusion has been demonstrated to be safe and practical in selected trauma patients. Autotransfusion is ideally applicable to the trauma patient in whom replacement of six or fewer units of blood is required. In addition, autotransfusion provides readily available blood for patients with unusual blood types and for those in whom multiple transfusions may rapidly deplete available stores. The properties of an ideal autotransfusion device include rapid assembly, relatively low cost, ease of operation, in-line filtration, minimized air blood interface, simplified anticoagulation, and safety from air embolism and coagulopathies.


Medial peritalar dislocation-associated foot injuries and mechanism of injury. 1) Two cases of medial peritalar dislocation with accompanying foot injuries considerably altering prognosis are presented. 2) Although most cases of this uncommon injury respond well to treatment, a careful investigation for accompanying injuries should be performed. 3) The mechanism of injury is discussed.


Alterations in hypothalamic function following thermal injury. Nine burn patients with a mean burn size of 39% (range, 23-65%) and five normal individuals studied in an environmental chamber selected optimal comfort temperature by regulating a bedside temperature control unit. The normal individuals selected 27.8 degrees C plus or minus 0.6 (SE) as the comfort temperature and their mean skin temperature was 33.4 plus or minus 0.6 and core temperature 36.9 plus or minus 0.1 while in this environment. In contrast, the burn patients maintained a higher ambient comfort temperature (mean 30.4 plus or minus 0.7, p less than 0.05 when compared to controls) associated with an elevated core (38.4 plus or minus 0.3, p less than 0.01) and surface temperature (35.2 plus or minus 0.4, p less than 0.05). Human growth hormone response to insulin hypoglycemia and arginine infusion was measured in nine additional burn patients (mean burn size, 52%; range, 23-90%) and five normals. Fasting HGH was significantly elevated (1.7 plus or minus 0.2 ng/ml, n = 18, versus control of 0.9 plus or minus 0.1, n = 10, p less than 0.001), despite fasting hyperglycemia in the burn patients (123 plus or minus 5 mg/100 glycemia in the burn patients (123 plus or minus 5 mg/100 ml versus 91 plus or minus 2, p less than 0.001). HGH response to insulin hypoglycemia was diminished in the burn patients with peak HGH value in patients averaging 12.6 ng/ml compared to 27.8 in the recovered patients and 32.6 in the controls (p less than 0.01). Patients receiving an arginine infusion also demonstrated diminished HGH response following injury. The HGH response to known stimuli returned toward normal with time and recovery in the surviving patients. Alterations in comfort temperature, fasting blood glucose, and glucose-HGH interaction occur following thermal trauma. These changes taken together suggest that metabolic responses to injury may be the consequence of homeostatic readjustment within the hypothalamus.


Massive right upper quadrant intra-abdominal injury requiring pancreaticoduodenectomy and partial hepatectomy. Three cases of massive right upper quadrant abdominal injury involving liver, pancreas, and duodenum are presented. The treatment of  choice for such extensive devitalizing injuries is pancreaticoduodenectomy combined with appropriate liver resection. There was no martality in this series and followup for at least 2 years shows no evidence of chronic morbidity with regard to pancreatic function. Principles of management of severe, combined injuries of organs in the upper quadrant of the abdomen are based upon rapid control of hemorrhage, repair of major vessels, pancreaticoduodenectomy when neither the head of the pancreas nor adjacent duodenum can be preserved ent-to-end inverting pancreaticojejunostomy, choledochojejunostomy and careful evaluation of the kidney and ureter.


Corneal changes associated with hypertrophic scars of the eyelids. Acquired astigmatism secondary to scar contracture of the eyelids was diagnosed in a burned patient, with decrease in visual acuity to 20/400. This was associated with a persistent mosaic pattern of the cornea when stained with fluorescein. Visual acuity returned to normal and the mosaic pattern disappeared after treatment of the scars. This unusual problem should be looked for in patients with scarred eyelids to decrease morbidity and prevent possible permanent corneal changes.


Unusual fracture-dislocation of the great toe: case report. An unusual fracture-dislocation of the great toe is presented and discussed. A review of the literature is included and a possible mechanism discussed. The lack of information in the literature relative to this injury led us to report this case.


Bilateral dorsal dislocations of the metatarsophalangeal joints of the great toes with a loose body in one of the metatarsophalangeal joints. An unusual bilateral closed dorsal dislocation of the metatarsophalangeal joints of both great toes is described, and surgical treatment and outcome reported. The importance of postreduction X-rays is emphasized.


Hemorrhage following pelvic fracture controlled by embolization: case report. This case report demonstrates the value of arterial management with embolization of hemorrhage following pelvic fracture. Surgical ligation and arterial embolization are briefly discussed as treatment modalities.


An evaluation of prednisolone as a routine adjunct to the treatment of T. rhodesiense. The purpose of this exercise was to evaluate the efficacy of a cortico-steroid in protecting the patient suffering from Rhodesian sleeping sickness from the complications of melarsoprol treatment. It is quite clearly shown that prednisolone was not effective in offering protection against the most serious treatment problem, encephalopathy. The apparent total success of the steroid in protecting the first group from the less severe treatment complications and in minimising early death need to be interpreted with some scepticism due to the smallness of the series. Nevertheless, it does help to substantiate the observations of others that in the case of the moribund patient, the immediate use of steroids might be life saving. On the basis of these findings the routine use of prednisolone as an adjunct to the treatment of T. rhodesiense was discontinued. The use of a cortico-steroid has been continued, however, as treatment for reactive encephalopathy, arsenical dermatitis and arsenical enteritis and with patients who are moribund on admission.


Epidemiology of sea-snake bites.

Epidemiology of sea-snake bites. Epidemiological features as reflected by 101 patients with unequivocal sea-snake bite received in north-west Malaya are reviewed. Enhydrina schistosa caused over half the bites, including seven of the eight fatal bites. It is the most dangerous sea-snake to man. Over 90 per cent of the victims were male and 80 of the 101 patients were fishermen bitten at their job. Most victims were bitten on the lower limb through treading on the snake, and this resulted in more cases of serious poisoning than upper limb bites (caused through handling nets, sorting fish and so on). Only 14 cathers were bitten (through treading on the sea-snake; no bathers were bitten while swimming). In patients coming to hospital more than six hours after the bite, there was a four-fold increase in serious poisoning compared with patients coming within six hours of the bite. Thus, as time elapses after the bite, the victim is less likely to seek medical help unless poisoning is severe. Despite the lethal toxicity of sea-snake venom, in patients seen during 1957-61 before sea-snake antivenom became available, the mortality was only 10 per cent. Trivial or no poisoning followed in 80 per cent of the bites. On the other hand, of 11 patients (20 per cent) with serious poisoning, over half (six patients) died despite supportive hospital treatment. These epidemiological features observed in Malaya probably apply to most fishing folk along Asian coastlines where sea-snakes abound. If this is so, sea-snake bite must be a common hazard feared by millions of fishing folk, and a common cause of illness and death. But it is unlikely that the extent of this problem will be revealed to orthodox medicine for many decades because most fishing villages are far from medical centres; and even if hospitals or medical centres are available, fishing folk are usually reluctant to attend them. Only one species of sea-snake, Pelamis platurus, extends to the east coasts of Africa and west coasts of the tropical Americas, but for various reasons this species does not appear to constitute much of a hazard to fishing folk in these areas. Although bathers are occasionally bitten along Asian coasts, when they inadvertently tread on a sea-snake, the risk of sea-snake bite in this area is extremely low. The prevention of sea-snake bite and poisoning is considered. Highly effective antivenom is now available for treating victims with serious poisoning; death should not occur provided adequate medical treatment is given within a few hours of the bite. The main problem is provision of adequate medical care at rural medical centres and overcoming the reluctance fishing folk often have in attending these centres.


Absorption of vitamin A in children with ascariasis. Absorption of labelled vitamin A was studied in normal children and in children with round-worm infestation. Absorption of the vitamin was significantly low in children with ascariasis. In two subjects, in whom the studies were repeated, absorption of vitamin A was significantly increased after antihelminthic treatment. These results suggest that ascariasis may aggravate vitamin A deficiency by interfering with the absorption of the vitamin.


Six cases of hyperosmolar non-ketotic diabetic decompensation in a hospital practice in West Africa. During 1972, of 18 patients admitted to St. Luke's Hospital Anua, Uyo, in S.E. Nigeria, with diabetic metabolic decompensation, six were suffering from hyperglycaemic hyperosmolar non-ketotic coma or pre-coma. The clinical features and treatment of these patients are described. All survived. It is suggested that even when biochemical monitoring is unavailable, the overall mortality could be improved by clinical awareness of this commonly unrecognised condition, combined with replacement therapy using half strength normal saline and modest quantities of insulin and potassium.


[Prevention of thrombo-embolic complications in urology using sub-cutaneous calcium heparinate (author's transl)]. Thrombo-embolic complications remain one of major preoccupations of surgery. As well as their treatment, prevention is of even greater importance. Following a discussion of the physiopathology of coagulation in the patient undergoing surgery, the authors study those factors peculiar to urology. Despite the risk of haemorrhage involved in such surgery, 158 patients underwent operation after having received anticoagulants in the form of sub-cutaneous calcium heparinate even before the procedure. The decrease in the number of thrombo-embolic complications appeared to confirm the effectiveness of this therapeutic measure.


[New concept on the T.U.R. prostate syndrome (author's transl)]. The T.U.R.P. syndrome is always secondary either to the perforation of the prostatic capsula or to the opening of a veinous sinus. If the T.U.R.P. syndrome occurs, it can be or early, or late. Generally attributed to hemolysis with hemoglobinemia, we denie it. In fact the T.U.R.P. syndrome is to be attributed to hypervolemia and hyponatremia. The proper treatment requires the use of hypertonic sodium solution. The use of sterile water as irrigant for the T.U.R. is absoluetly convenient and not dangerous, unless one perforates the capsule or open a veinous sinus.


[Radiological diagnosis of acute kidney abscess in adults. Early diagnosis apropos of 7 cases]. The authors report, in 7 cases, their experience of the early diagnosis of renal abscess. They emphasize the importance of recognising this disease by comparison of the findings of intra-venous urography and the clinical signs. They were thus able to avoid arteriography and surgical operation in 6 cases. The diagnosis depends on the finding of a mass in the right kidney (5 cases out of 7) on intravenous urography, usually in the upper pole (4 cases out of 7). This space-occupying lesion may be accompanied by a certain number of signs which are inconstant and not specific, e.g. disappearance of the normal calyx pattern which disappears under compression and is probably related to inflammation. In fact, this association of a tumour and fever, due to deep pus formation and urinary infection, suggests the diagnosis and leads to the prescription of antibiotics. The disapperance of the clinical and radiological négative signs within 10 days confirms the diagnosis. The persistence of the space-occupying lesion requires arteriography which will make the difference between chronic abscess and carcinoma.


[Vascular access for intermittent haemodialysis. Use of a Sparks obturator. Preliminary technical report (author's transl)]. It appears possible to envisage, and especially in patients where the vascular and in particular, venous system is defective, the insertion of a Sparks obturator as soon as the indication for haemodialysis is considered and before is indispensable. In the case of urgent haemodialysis, in most instances the nephrologist himself inserts a Scribner shunt in order to be able to dialyse his patient as rapidly as possible. There is no contraindication to the insertion, either at the same time or during the next few days, of an obturator which may be anastomosed to the vessels much later. All arterio-venous fistulae, all systems which may alter, should, in our opinion, be equipped in this way, so that as soon as maturation of the obturator has occurred immediate availability of an excellent means of access exists.


[Pseudo-tumoral suprarénal-renal dysgenesis (author's transl)]. Intimate fusion of the renal and suprarenal parenchyma, associated with cystic lesions in the zone of tissue juxtaposition, constitutes a form of suprarenal-renal dysgenesis for which the name "dystopia" has been suggested. The distinction must be made from suprarenal-renal adhesions in which a connective tissue barrier between the two parenchymas persists. In this present case, the malformation gave rise to a pseudo-tumoral syndrome of rapid appearance in association with a haemorrhage. Removal of the kidney cannot be avoided in view of the absence of any plane of cleavage with the suprarenal when the suprarenal tumour is removed.


[Urinary and vascular complications of a gastrointestinal tumour. Clinical picture and therapeutic problems (author's transl)]. In a 25-year-old woman presenting with a right ureteric stenosis, the authors had the surprise to find at operation an extensive tumour of the small intestine. The tumour compressed the ureter and involved the common iliac, artery, requiring a complex surgical procedure with major vessel repair.


[Some technical considerations on partial nephrectomy (author's transl)]. After some considerations on the problems of operation technique which are raised up by partial nephrectomy, the authors review its' indications. After presentation of the clinical experience based on ten cases of partial nephrectomy, carried out during the years 1972-1974, of which 7 were for lithiasis, 2 for renal tuberculosis and one for a solitary renal cyst, the authors advise primary ligature of the segmental vascular pedicle, whenever possible and use of the perinephretic fat to cover over the sectioned surface, as it has strong hemostatic action, good tolerance and that owing to this, nephropexy is carried out.


Structure and composition of the adenovirus type 2 core. The structure and composition of the core of adenovirus type 2 were analyzed by electron microscopy and biochemical techniques after differential degradation of the virion by heat, by pyridine, or by sarcosyl treatment. In negatively stained preparations purified sarcosyl cores reveal spherical subunits of 21.6-nm diameter in the electron microscope. It is suggested that these subunits are organized as an icosahedron which has its axes of symmetry coincident with those of the viral capsid. The subunits are connected by the viral DNA molecule. The sarcosyl cores contain the viral DNA and predominantly the arginine/alanine-rich core polypeptide VII. When sarcosyl cores are spread on a protein film, tightly coiled particles are observed which gradually unfold giving rise to a rosette-like pattern due to the uncoiling DNA molecule. Completely unfolded DNA molecules are circular. Pyridine cores consist of the viral DNA and polypeptides V and VII. In negatively stained preparations of pyridine cores the subunit arrangement  apparent in the sarcosyl cores is masked by an additional shell which is probably formed by polypeptide V. In freeze-cleaved preparations of the adenovirion two fracture planes can be recognized. One fracture plane probably passes between the outer capsid of the virion and polypeptide V exposing a subviral particle which corresponds to the pyridine core. The second fracture plane observed could be located between polypeptide V and the polypeptide VII-DNA complex, thus uncovering a subviral structure which corresponds to the sarcosyl core. In the sarcosyl core polypeptide VII is tightly bound to the viral DNA which is susceptible to digestion with DNase. The restriction endonuclease EcoRI cleaves the viral DNA in the sarcosyl cores into the six specific fragments. These fragments can be resolved on polyacrylamide-agarose gels provided the sarcosyl cores are treated with pronase after incubation with the restriction endonuclease. When pronase digestion is omitted, a complex of the terminal EcoRI fragments adenovirus DNA and protein can be isolated. From this complex the terminal DNA fragments can be liberated after pronase treatment. The complex described is presumably responsible for the circularization of the viral DNA inside the virion. The nature of the protein(s) involved in circle formation has not yet been elucidated.


Association of endonuclease activity with serotypes belonging to the three subgroups of human adenoviruses. Endonuclease activity has been detected in association with highly purified virions, pentons, and/or dodecons of adenovirus types 2, 3, 5, 9, 12, 15, and 16. Only single-strand scissions in substrate DNA were detected. The nuclease activity was detected by a highly sensitive ethidium bromide fluorimetric assay procedure.


Horseshoe kidneys: a 40-year experience. The results presented show that horseshoe kidney is a non-fatal anomaly of renal development that can be managed successfully by standard urologic procedures. Most clinical problems are caused by hydronephrosis and renal calculi. Careful attention to the anatomy, vasculature and drainage from renal pelves at the time of operation will assure good postoperative results. The Foley Y-V pyeloplasty is a highly effective procedure for relief of ureteropelvic junction obstruction in horseshoe kidneys. As with other genitourinary anomalies the presence of a horseshoe kidney should prompt a thorough urologic evaluation.