Segregation of ACP1 and MNSs in families with structural rearrangements involving chromosome 2.

Data from seven families carrying rearrangements and variants of chromosome 2 have been analysed in relation to the assignment of ACP1 and MNSs. The data are consistent with the regional assignment of ACP1 to 2p23, but not with that of MNSs to band 2q14.


Correlated odour threshold bimodality of two out of three synthetic musks.

The odour threshold bimodality for exaltolide described by Whissell-Buechy & Amoore (1973) among American whites is confirmed for a population sample in London. A highly correlated bimodality presumed to be caused by the absence of inactivity of certain receptor sites is shown to exist for another structurally different musk substance, musk ambrette. The thresholds for musk ketone show no bimodality and their correlation with the thresholds for the two other musks is low.


Racial differences in pigmentation and natural selection.

The inheritance of skin colour in man is not well understood. A clearer understanding could be obtained by taking into account the biological basis and genetical control of pigmentation in other mammals, particularly the experimental species. In these, most of the loci governing pigmentation are pleiotropic, colour being only one of the traits affected by them. Their products are evidently concerned with other metabolic pathways as well. There is strong evidence for inter-specific homology of pigmentation loci in mammals, and the situation in man may not be radically different. It is therefore possible that racial differences in skin colour may have resulted from the action of natural selection on these other functions of pigmentation genes.


[Comparative immunoelectrophoretic analysis of culture and bloodstream forms of "trypanosoma" (Trypanozoon) brucei gambiense". Demonstration of stage and antigenic type specific antigens (author's transl)].

The comparative immunoelectrophoretic analysis of the antigenic structures of culture and bloodstream forms with cross absorption tests confirm the existence among Trypanosoma gambiense antigens of: --numerous antigenic components common to culture and bloodstream forms;--several antigenic components specific of either culture forms or bloodstream forms. Among the latter, two components are shown to be specific of the antigenic type and appear to support the immunochemical specificity of each variant.


Modulation of the immune response to transplantation antigens. IV. Enhanced growth of tumour allografts in mice immunised with papain-solubilised transplantation antigen.

C57/Bl mice have been immunised with papain solubilised CBA transplantation antigen and subsequently challenged with a CBA tumour. Variations in antigen dose, immunisation schedules and routes of injection were compared. Two procedures in particular led to enhanced growth of the tumour allograft: (a) a single injection of antigen seven days before graft, and (b) a two-pulse immunisation spaced over 42 days. Mice given the seven-day course showed impaired cell-mediated cytotoxicity and blocking antibody at the time of challenge which was succeeded by blocking antigen in the circulation after challenge. Mice immunised by the two-pulse course developed heightened cell-mediated cytoxicity, but showed a persisting level of blocking antibody in the serum. Thus, although both immunisation regimes enhanced tumour growth, they did so by different mechanisms.


Mineral nutrition of Streptomyces kanamyceticus for kanamycin formation.

Kanamycin production by Streptomyces kanamyceticus ATCC 12853 requires magnesium sulfate and potassium phosphate at concentrations of 0.4 and 1.0 g per liter, respectively. The optimal concentrations of Fe and Zn for production of kanamycin are 0.25 and 0.575 mug/ml, respectively, whereas Mo at 0.04 mug/ml allows maximal cellular growth and antibiotic synthesis. Mn and Ca are without any effect. Cu, Co, Ni, and V have inhibitory effect on growth of the organism as well as kanamycin formation.


Regulation of lymphocyte responses in vitro. VI. -Potentiation of the response to phytohemagglutinin by cytochalasin B.

Low concentrations of cytochalasin B (CB) potentiated the DNA-synthetic response of rat lymph node cells (LNC) to PHA. Maximal potentiation was observed at suboptimal concentrations of the mitogen, less at optimal and usually none at supraoptimal concentrations. Other metabolic responses (RNA and protein synthesis) as well as the actual number of morphologically transformed lymphocytes were also enhanced. The presence of serum in the culture was an absolute requirement for CB potentiation. A maximal effect was usually obtained when CB was present from the start of the culture. However, addition of CB as late as 46 h after PHA produced a lower but consistent potentiation. The responses to PHA of thymus cells and spleen cells were respectively more and less increased by the drug than that of LNC. These results suggest that CB acts by opposing a serum-dependent cell interaction.


Relationship of early readings of minimal inhibitory concentrations to the results of overnight tests.

Broth dilution minimal inhibitory concentration (MIC) readings were compared after different incubation periods and with different inoculum concentrations. The purpose was to determine the best conditions for obtaining early results as close as possible to overnight readings. Initially, 76 antibiotic-organism combinations were tested using the International Collaborative Study technique and inoculum and were read after 3, 8, and 18 h of incubation. Approximately 28% of tests showed fourfold or greater increases in MICs after 18 h of incubation compared with the 3-h readings. No overnight MICs were lower than early readings. MICs of single antibiotics against seven organisms were also read with an automatic particle counter to confirm the validity of the visual readings. Experiments were made to determine whether inoculum manipulation could reconcile the differences between 3- and 18-h MIC results. One hundred and eight organism-antibiotic combinations were tested comparing 3-h MIC readings using an inoculum of 10(7) organisms per ml with overnight readings using 10(5) per ml. In 71 cases, readings with both inocula were within the range tested and 57 (86%) were within +/-1 log(2) of each other and followed an approximately normal distribution. Improved comparability between early read and overnight MICs thus may be achieved by inoculum manipulation, and this may be a suitable approach in the future development of automated procedures.


Simplified method for antimicrobial susceptibility testing of anaerobic bacteria.

A simple, abbreviated broth dilution test (tube test) utilizing a commercially available medium and inexpensive disposable materials, and which could be performed entirely in room air, was developed and used to test the susceptibility of 100 strains of anaerobic bacteria to clindamycin, chloramphenicol, ampicillin, and tetracycline. Results are reported in categories of susceptibility: susceptible to concentrations surpassed in vivo with usual dosage, susceptible to concentrations surpassed in vivo with high dosage, and resistant to concentrations achievable in vivo. Results are compared to minimal inhibitory concentrations which were determined simultaneously by using a microdilution method in an anaerobic glove box. Twenty strains of Bacteroides fragilis, 10 strains of Fusobacterium, 20 strains of Clostridium, 10 strains of gram-positive non-sporeforming bacilli, and 30 strains of cocci grew to visible turbidity within 1 day of incubation. Of the 360 antibiotic-organism combinations tested, 98% were in a susceptibility category that corresponded (within one concentration) to the actual minimal inhibitory concentration as determined by the microdilution method. After 2 days of incubation, growth was more abundant, but results often indicated inappropriate degrees of resistance. Variation in inoculum size had little effect on results. Ten strains of B. melaninogenicus did not grow enough for susceptibility to be categorized accurately. The tube test could be used in any clinical microbiology laboratory for a limited number of susceptibility tests on anaerobic bacteria other than B. melaninogenicus without preparation of special media or purchase of special equipment.


Phagocytosis of autologous and heterologous erythrocytes by rat and guinea pig macrophages.

Rat and guinea pig peritoneal macrophages are compared in their ability to phagocytose guinea pig, rat and sheep red cells. The ability of the phagocytes to ingest autologous red cells does not seem to be drastically reduced compared to their ability to ingest alien cells.


Comparative in vitro activity and clinical pharmacology of ticarcillin and carbenicillin.

The in vitro activity and human pharmacology of ticarcillin, a semisynthetic penicillin more active than carbenicillin against Pseudomonas, were compared. There has been no increase in resistance to ticarcillin of Pseudomonas strains over the past 5 years, but resistance of indole-positive Proteus and Serratia strains has been documented. After intramuscular (i.m.) injection of 1 g of ticarcillin, mean peak levels occurred at 1 h (26.9 mug/ml) with a decline over 6 h (6.8 mug/ml). Serum half-life was 84 min. Dilution of ticarcillin lidocaine reduced pain on i.m. injection but did not alter serum levels. Blood levels after 1 g i.m. are adequate to treat infections produced by Escherichia coli, Proteus mirabilis, and some Enterobacter, but not Pseudomonas. After rapid intravenous infusion of 3 and 5 g, mean peak serum levels of ticarcillin were slightly lower for 1 h than those achieved with carbenicillin. Probenecid administered before infusion produced increases in blood levels, half-lives, and volume of distribution. The biological half-life of ticarcillin was 72 min compared to 66 min with carbenicillin. There was a larger volume of distribution for ticarcillin than carbenicillin (15 liters versus 14 liters). The ticarcillin half-life when administered with probenecid was 108 min. Urinary recovery of ticarcillin was 77% against 95% of carbenicillin. However, approximately 10% of ticarcillin is recovered as penicilloic acid so that 95% of an intravenously administered dose is recovered.


Regulation of lymphocyte responses in vitro. VII. - "Cell contact inhibition", a possible regulatory mechanism for lymphocyte activation.

Potentiation by cytochalasin B (CB) of (3H)thymidine incorporation in lymphoid cell suspensions stimulated by phytohemagglutinin (PHA) is counteracted by adherent cells. The drug has no effect on the production of the macrophage product lymphocyte activating factor (LAF) and does not interfere with its potentiating activity. CB appears to inhibit agglutination of lymphocytes. Other factors (absence of serum, macrophages, mechanical disturbance of the cultures) diminishing the size of aggregates increase the response of lymphocytes. Responses to less agglutinating mitogens are less or not enhanced by CB. Factors increasing agglutination or/and cell contacts (high cell density, wheat germ agglutinin) diminish lymphocyte activation and make it susceptible to CB potentiating effect. The results suggest that topoinhibition (cell contact inhibition) is an important mechanism regulating the lymphocyte response to mitogens in culture. Its effect could be modulated by macrophages and certain serum factors, and CB would potentiate these responses by reducing contact inhibition.


Viral keratitis-inhibitory effect of 9-beta-D-arabinofuranosylhypoxanthine 5'-monophosphate.

Topical application of 9-beta-d-arabinofuranosylhypoxanthine 5'-monophosphate (ara-HxMP) significantly inhibited the development of keratitis induced by types 1 and 2 herpes simplex virus and vaccinia virus in the eyes of rabbits. Parameters for evaluation of efficacy were infectivity (corneal opacity, lesion size, and type), Draize (erythema, conjunctival swelling, and discharge), and reduction in titer of recoverable virus from the eye. When the relative efficacy of the related compounds 9-beta-d-arabinofuranosyladenine (ara-A), ara-A 5'-monophosphate (ara-AMP), and ara-Hx was determined against type 1 herpes simplex virus in a parallel experiment, the more water-soluble compounds (ara-HxMP, ara-AMP) were the most effective. The relative efficacy of ara-A was also determined against type 2 herpes and vaccinia virus-induced keratitis. Mortality in rabbits due to central nervous system involvement caused by types 1 and 2 herpes simplex virus was inhibited. Ara-HxMP was not discernibly toxic to the eye at concentrations of at least 20%; efficacy was still discernible with a 0.1% solution.


Inhibition of protein synthesis in intact HeLa cells.

Polysome analysis has proved to be a sensitive probe for the mode of action of inhibitors of protein synthesis in intact HeLa cells. To classify the active compounds as inhibitors of initiation, elongation, or termination, their effects on the cellular polyribosome pattern were compared under three conditions. These conditions tested (i) their direct effect on the polyribosome profile; (ii) their effect on ribosome run-off produced by hypertonicity; and (iii) their effects on recovery from hypertonicity. Using this technique, diacetoxyscirpenol, 2-(4-methyl-2,6-dinitroanilino)-N-methylpropionamide, and three alkaloids, harringtonine, isoharringtonine, and homoharringtonine, were found to be inhibitors of initiation. Polysome analysis indicated that in HeLa cells 7.8 x 10(-7) M pactamycin, which inhibited protein synthesis 94%, interfered with elongation as well as initiation under these conditions. Emetine, anisomycin, cycloheximide, and trichodermin each gave polysome patterns consistent with inhibition of elongation. Fusidic acid and aurintricarboxylic acid inhibited incorporation of [(14)C]leucine into intact HeLa cells, but polysome analysis did not localize any specific inhibitory effects to the initiation, elongation, or termination steps of protein synthesis. The use of specific inhibitors of initiation of protein synthesis has indicated that most, if not all, mammalian messenger ribonucleic acids contain a single initiation site.


Fluid and penicillin G dynamics in polyethylene chambers implanted subcutaneously in rabbits.

Chemical and cellular characteristics of fluid within subcutaneously implanted polyethylene chambers in rabbits were studied over a 3-month period. The fluid attained a relatively stable protein and cellular composition which was consistent with a mononuclear exudate. After a single dose of intramuscular penicillin G, the antibacterial activity of chamber fluid was found to be dynamic and similar to the serum antibacterial activity. This animal model may be useful for in vivo studies of the interaction of microorganisms with antimicrobial agents.


Response of yeast and mycelial phases of Histoplasma capsulatum to amphotericin B and actinomycin D.

The dimorphic fungus Histoplasma capsulatum exists in two phases: a unicellular yeast form at 37 C and a mycelium at 25 C. We have found that these two phases have selective drug susceptibilities. The mycelial form of H. capsulatum was much more susceptible to the polyene antibiotic amphotericin B than the yeast form; in contrast, the yeast form was more susceptible to the antibiotic actinomycin D. The changes in susceptibility occurred early in the transition between the two phases and permitted the transitions to be blocked by sublethal concentrations of the appropriate drugs.


Efficacy of the inactivation of bacterial spores in white petrolatum and a hydrophilic ointment by gamma irradiation.

To evaluate the possibilities of using gamma irradiation for the sterilization of ointments, the effect of irradiation on spores of Bacillus pumilus and Bacillus sphaericus in dry material and in two different kinds of ointments was studied. The results indicate that for sterilization purposes irradiation was less effective in white petrolatum as compared to irradiation in the dry state. No such protective effect was found in a hydrophilic ointment. Accordingly, the sterilization dose needed for the sterilization of an ointment can be decided upon only after inactivation experiments with suitable test organisms in the actual preparation.


Toxigenic Aspergillus and Penicillium isolates from weevil-damaged chestnuts.

Aspergillus and Penicillium were among the most common genera of fungi isolated on malt-salt agar from weevil-damaged Chinese chestnut kernels (16.8 and 40.7% occurrence, respectively). Chloroform extracts of 21 of 50 Aspergillus isolates and 18 of 50 representative Penicillium isolates, grown for 4 weeks at 21.1 C on artificial medium, were toxic to day-old cockerels. Tweleve of the toxic Aspergillus isolates were identified as A. wentii, eight as A. flavus, and one as A. flavus var. columnaris. Nine of the toxic Penicillium isolates were identified as P. terrestre, three as P. steckii, two each as P. citrinum and P. funiculosum, and one each as P. herquei (Series) and P. roqueforti (Series). Acute diarrhea was associated with the toxicity of A. wentii and muscular tremors with the toxicity of P. terrestre, one isolate of P. steckii, and one of P. funiculosum.


Psychrophilic microorganisms from areas associated with the Viking spacecraft.

Microorganisms capable of growth at 7 C were enumerated and isolated from soil samples from the manufacture and assembly areas of the Viking spacecraft. Populations ranging from 4.2 X 10(3) to 7.7 X 10(6)/g of soil were isolated from the 15 soil samples examined. Temperature requirements were determined, and those growing at 3 C, but not at 32 C, were designated as obligate psychrophiles in this investigation. Populations of soil bacteria, including aerobic sporeformers, ranging from 1.5 X 10(2) to 9.8 X 10(5)/g were capable of growth at 3 C, but not at 32 C. Bacterial isolates were identified to major generic groups. No psychrophilic sporeformers were isolated from soil from the manufacture area, but psychrophilic sporeformers ranged from 0 to 6.1 X 10(3)/g from soil from the assembly area.


Methane production in shallow-water, tropical marine sediments.

The in situ production of methane was monitored in several types of tropical benthic communities. A bed of Thalassia testudinum located in Caesar Creek (Florida Keys) exhibited the highest methanogenic activity (initial rates = 1.81 to 1.86 mumol CH4/m2 per h) as compared with another seagrass (Syringodium sp., 0.15 to 0.33 mumol/m2 per h) and two coral reef environments (Hydro-Lab, 0.016 to 0.10 mumol/m2 per h; Curacao, 0.14 to 0.47 mumol/m2 per h). The results suggest that a wide variety of benthic metabolic processes (e.g., photosynthetic oxygen production) influences methane production rates.


Effect of microflora on the free amino acid distribution in various regions of the mouse gastrointestinal tract.

The distribution of free amino acids in the contents of various regions of the gastrointestinal tract (stomach, upper small intestine, lower small intestine, cecum, upper colon and lower colon) was studied in germfree and conventionalized mice. Particular emphasis was placed on the conversion of tryptophan to indole as a probe for studying intermicrobial interactions and microbe-host interactions in vivo. Great differences were observed in the free amino acid content of the various regions of the digestive tract in each type of mouse and also in any one region between germfree and conventionalized mice. As would be expected, there were fewer differences in amino acid distribution between the types of mice in both regions of the small intestine. This correlates with a much lower population of microorganisms in these regions. The changes in free amino acid content and distribution produced by microflora are great enough to serve as a good probe for studying the interactions of a limited number of species of microbes in gnotobiotic animals and assign possible specific functions to each species.


Heterotrophic activity of deep-sea sediment bacteria.

Sediment samples, containing mixed microbial populations that were decompressed during retrieval from 7,750 and 8,130 m in the Puerto Rican Trench, were recompressed and incubated at the approximate in situ temperature (3 C) and pressure (775 or 815 atm) in the presence of 14C-labeled amino acids. Heterotrophic activity (total uptake, CO2 respiration, and cellular assimilation) and cellular-associated "pool" concentrations were measured. Compared with atmospheric controls held at 3 C, the total uptake at elevated pressure at 3 C was reduced, on an average, 55 times, CO2 respiration was reduced 45 times, and cellular assimilation was reduced 69 times. Rate of total uptake at elevated pressure was found to range from 4.0 X 10(-11) mug/cell per h for leucine to 2.61 X 10(-10) mug/cell per h for an amino acid mixture. Also, the percentage of total uptake at elevated pressures, respired as CO2, increased at the expense of cellular assimilation (ca. 22% increase). Two cellular-associated amino acid pools were detected, a large, loosely bound, outer pool and a small, tightly bound internal pool. The loosely bound outer pool was removed by a change in the pH of the incubation medium. Even though heterotrophic uptake and the outer, cellular-associated pool were markedly reduced at an elevated pressure, the percentage of total uptake calculated for the unincorporated, tightly bound, intracellular pool was 2 to 19 times that obtained for cultures held at 1 atm. The results were interpreted as indicating that bacterial metabolism and biosynthesis in the deep sea are markedly reduced, with a greater proportion of metabolic activity devoted to cellular maintenance.


Scanning electron microscope study of bacteria associated with the rumen epithelium of sheep.

Examination of the rumen epithelium of sheep by scanning electron microscopy revealed bacteria associated with the epithelial surface. Comparison of epithelial surfaces from 10 sheep revealed areas that were consistently densely covered with bacteria and other areas where the cover was consistently light. The bacterial populations were frequently of mixed morphological types, but areas populated with a single type were also observed. This finding, together with the discovery of bacterial forms not previously described in rumen contents, suggests that a specific flora may exist on the rumen epithelial surface. The functional significance of such a population is discussed.


Specificity of Ustilago maydis killer proteins.

Bacteria and fungi were tested for sensitivity to Ustilago maydis killer strains  carrying virus-like particles. Various species taxonomically related to U. maydis were sensitive.


Staphylococcal enterotoxin C: solid-phase radioimmunoassay.

A solid-phase radioimmunoassay test employing 125I-labeled enterotoxin C and polystyrene tubes coated with specific antibody was used for the detection and quantitation of entertoxin C in condensed milk, cheddar cheese, custard, and ham salad. The assay was sensitive to 1 to 10 ng of toxin per g of food; nonspecific inhibitions were 16% or less.


Factors affecting the production of sterigmatocystin in semisynthetic media.

Production of sterigmatocystin by Aspergillus versicolor was stimulated by inorganic phosphate when used in conjunction with citric acid cycle compounds.


Inhibition of methanogenesis in marine sediments by acetylene and ethylene: validity of the acetylene reduction assay for anaerobic microcosms.

Methanogenesis was irreversibly inhibited in sediments by concentrations of acetylene employed in nitrogen fixation assays (1 to 20%, vol/vol). Ethylene, but not ethane, also stopped methane production, and the inhibition was reversed by gassing with hydrogen.


Bactericidal effect of hydrogen peroxide on spacecraft isolates.

Solutions of 3, 10, and 15% hydrogen peroxide were found to have pronounced bactericidal effects, as a function of time of exposure, on sporeformers and non-sporeformers isolated from spacecraft.


Diagnostic accuracy in malignant melanoma.

The diagnostic accuracy and index of suspicion concerning malignant melanoma were calculated based on review of 5,538 histologically examined lesions (of which 99 were melanomas) that were recorded in the Oncology Section of the Skin and Cancer Unit from 1955 to 1967. The diagnostic accuracy of the physicians in the Section was determined to be 64.4%. Thus, in almost one of every three melanomas an error in clinical diagnosis was made. This "batting average" is, however, better than those of previously published reports. The index of suspicion in relation to malignant melanoma in our series was 96%. Thus, the physicians in the Oncology Section demonstrated an appropriate awareness of this tumor. However, coupled with a diagnostic accuracy of 64%, a problem nevertheless exists in the diagnosis of this serious cutaneous cancer. Our study emphasizes the importance of having histologic verification prior to definitive radical surgery on patients with malignant melanoma.


Effects of topical fluorouracil on normal skin.

Daily application of 1% fluorouracil cream to normal white skin results in definite morphologic alterations of the epidermis. Although clinical changes were not present, electron microscopic examination of the tissue demonstrates changes especially pronounced in the epidermal keratinocytes. These changes consist of cytoplasmic vacuoles, alterations in the mitochondria, Golgi complex, and endoplasmic reticulum, as well as widened extracellular spaces.


Metronidazole therapy for cutaneous leishmaniasis.

A man acquired cutaneous leishmaniasis in Afghanistan. The disease involved two sites and remained active for seven months. Treatment with metronidazole was followed by resolution of the skin lesions in one month.


Small intestinal biopsy in cows milk protein allergy in infancy.

Intestinal biopsies were performed in 31 infants with cow's milk protein intolerance. Mucosal damage was constant, partial villous atrophy being the most usual finding. Though these changes are nonspecific, small intestinal biopsy can be a useful investigation in these patients. With a milk-free diet, recovery of normal mucosal appearence is reached between 3 and 13 months.


Effect of lactose-induced diarrhoea on absorption of nitrogen and fat.

The absorption of fat and the absorption and retention of nitrogen were studied in 20 children with kwashiorkor. 13 of the 20 had lactose malabsorption and severe diarrhoea on milk feeds. Fat absorption was not affected by lactose-induced diarrhoea, but nitrogen absorption was impaired. Despite this, nitrogen retention was unaffected and it is concluded that milk and milk products would continue to be used in programmes to eliminate malnutrition.


Poststreptococcal nephritis--a rare disease?.

Forty-three children presenting with acute nephritis were studied for evidence of preceeding steptococcal infection. They were compared with a group of control children of similar age. Two-thirds of those with nephritis gave a history of a preceeding respiratory infection (compared with one-third of the controls). A significant rise of antistreptolysin O tire occurred in only 16 children with nephritis and within this minority several did not show a fall of serum C3 level. It is probable that only one-third of the children with acute nephritis had poststreptoccoccal glomerulonephritis. Poststreptococcal glomerulo-nephritis is no longer the main cause of childhood acute nephritis in the Leeds area. There may be many different aetiological factors and this diversity calls for more rigorous investigations and a more guarded prognosis.


Hypertension, oedema, and suppressed renin aldosterone system due to unsupervised salt administration.

This paper describes an infant with gastroenteritis, who developed hypertension and oedema after administration of inaccurately prepared oral glucose salt solution. The renin aldosterone system was suppressed in this child and it was suggested that this may be a factor in the development of hypernatraemia when abnormal water losses occur in infants fed on hyperosmolar feeds. Unless salt can be given accurately in small amounts it may be safer to advise feeds of glucose only in infants with mild diarrhoea.


Thymic dysplasia, persistence of measles virus, and unexpected infant death.

A case of sudden infant death in an 18-month female infant is described which occurred 3 weeks after clinical recovery from a typical attack of measles. At post-mortem examination no obvious cause of death could be found apart from some terminal aspiration of vomit. Histologically, the thymus showed selective absence of Hassall's corpuscles with a normal number of cortical lymphocytes. There were many atypical lymphocytoid cells in the lymph nodes, spleen, and portal tracts, and measles virus was subsequently isolated from the lung and tonsil. There was a raised titre of complement fixing measles antibody (1/256).


Bond, J.V. (1975). Archives of Disease in Childhood, 50, 691. Clinical significance of catecholamine excretion levels in diagnosis and treatment of neuroblastoma. The pattern of urinary excretion of vanillylmandelic acid (VMA) was studied in 50 children with neuroblastoma. There were 10 disease-free survivors, and 4 children who survive for 3 or more years with residual nonmetastatic disease, 36 children died with widespread metastic disease. The urinary VMA level was raised at diagnosis in 8 of the 10 disease-free survivors but rapidly returned to normal after treatment. In 3 out of 4 children with residual tumour, VMA remains persistently raised. In 28 of the 36 children who died VMA was raised at diagnosis and remained so throughout the course of their disease. In the majority of the children with metastatic disease the finding of a raised VMA revealed the nature of the primary tumour. Measurement of urinary VMA is a simple diagnostic test which confirms the presence of neurblastoma and avoids the need for more complex investigations. The prompt return to normal levels in the disease-free survivors confirms the importance of serial VMA estimations in assessing response to treatment and ultimate prognosis. The other good prognostic features in the surviving patients were young age at diagnosis, primary tumour in the thorax, and histologically well-differentiated tumours which had not metastasized.


Perinatal cardiac arrest. Quality of the survivors.

Steiner, H., and Neligan, G. (1975). Archives of Disease in Childhood, 50, 696. Perinatal cardiac arrest: quality of the survivors. Twenty-two consecutive survivors of perinatal cardiac arrest have been followed to a mean age of 4 1/4 years, using methods of neurological and developmental assessment appropriate to their ages. 4 showed evidence of gross, diffuse brain-damage (2 of these died before the age of 3 years). These were the only 4 survivors of the first month of life who took more than 30 minutes to establish regular, active respiration after their heartbeat had been restored. The arrest in these cases had occurred during or within 15 minutes of delivery, and followed antepartum haemorrhage, breech delivery, or prolapsed cord. The remaining 18 were free of any evidence of brain damage. In the majority of these the arrest had occurred during shoulder dystocia or exchange transfusion, or was unexplained; the heartbeat had been restored within 5 minutes in most cases, and regular, active respiration had been established within 30 minutes thereafter in all cases.


West, R. J., Lloyd, J. K., and Turner, W. M. L. (1975). Archives of Disease in Childhood, 50, 703. Familial insulin-resistant diabetes, multiple somatic anomalies, and pineal hyperplasia. A syndrome comprising unusual facies, dry skin, acanthosis nigricans, thickened nails, hirsutism, dental precocity and dysplasia, abdominal protuberance, and phallic enlargement is described in 2 sibs. Both have developed diabetic ketoacidosis with insulin resistance. The elder child, a girl, had recurrent septic episodes and died at the age of 7-8 years. At necropsy the pineal gland was hyperplastic, weighing 900 mg. Investigation of the younger sib over a 4-year period has shown decreasing glucose tolerance, and he was frankly diabetic with ketoacidosis by the age of 6-8 years. Serum insulin concentrations have always been grossly raised. Though the mechanism for insulin resistance has not been definitely established, a functional abnormality of the hypothalamus or pituitary is postulated to explain the many endocrine features of the syndrome.


Rutter, N., Milner, A. D., and Hiller, E. J. (1975). Archives of Disease in Childhood, 50, 719. Effect of bronchodilators on respiratory resistance in infants and young children with bronchiolitis and wheezy bronchitis. Respiratory resistance was measured using a forced oscillation technique in 16 infants and young children with bronchiolitis and wheezy bronchitis. Measurements were made before and after administration of nebulized salbutamol or isoprenaline. No significant change in resistance was found.


Perlman, M., Williams, J., Hirsch, M., and Bar-Ziv, J. (1975). Archives of Disease in Childhood, 50, 727. Familial non-cystic fibrosis mucus inspissation of respiratory tract. Two sibs, whose parents are first cousins, have had chronic obstructive airways disease from birth with recurrent otitis media, sinusitis, and mastoiditis. The disease, associated with clinically abnormal mucus, differs from other familial obstructive airways diseases and probably constitutes a new entity.


Dale, G., Goldfinch, M. E., Sibert, J. R., and Webb, J. K. G. (1975). Archives of Disease in childhood, 50, 731. Plasma osmolality, sodium, and urea in healthy breast-fed and bottle-fed infants in Newcastle upon Tyne. Plasma osmolality, sodium, and urea were measured on samples from 50 healthy infants, aged between 18 and 125 days, attending child health clinics in Newcastle upon Tyne. 3 infants had osmolalities greater than 300 mOsm/kg, a lower incidence of hyperosmolality than that previously reported. There was a difference (P less than 0-001) between the plasma urea levels of breast-fed and bottle-fed infants, but not between the osmolalities of these groups. The mean plasma urea of bottle-fed babies was 53 mg/100 ml (SD 12-47), 50-1 mg/100 ml (SD 10-9) if additional solids were being given, and 18-4 mg/100 ml (SD 7-81) for breast-fed babies. There was little difference between the plasma sodium levels of each group. The mean plasma sodium for all groups combined was 135-2 mmol/1 (SD 2-3); no plasma sodium exceeded 140 mmol/1.


Further in vitro studies on the biochemistry of the inhibition of nucleic acid and protein synthesis induced by arsenic.

Human lymphocytes, stimulated by PHA, and exposed to increasing Na2HAsO4 concentrations, show an identical incorporation rate for 14C thymidine and 14C-TTP into the DNA. 14C uridine is incorporated 3--4 per cent less at an As concentration of 1.0 mug/ml medium, above this however approximately 15 per cent less into the RNA as compared to 14C-UTP. In free pyrimidine bases, the incorporation of labelled triphosphates into the DNA and RNA is significantly reduced above 1 mug and 10 mug Na2HAsO4. Corresponding to its approximately uniform distribution into DNA and RNA, the incorporation rate of 14C-ATP above 10 mug Na2HAsO4/ml culture medium lies between that of 14C-UTP and 14C-TTP. The incorporation of 14C alanine and 14C leucine into cellular protein is not reduced below 10 mug Na2HAsO4/ml. The incorporation rate is 41 per cent at a concentration of 100 mug Na2HAsO4/ml medium.  Compared to 14C-UTP, 14C-ATP and 14C-TTP it is increased by the factor of 1.8; 2.5 and 6.8 respectively. The inhibition of enzymes of the dark repair mechanisms and the synthesis of biopolymers together with their altered sequence and the involvement of long-lived messenger RNA serve as an explanation of the observed alterations of the lymphocyte metabolism, caused by arsenic.


[Desmosomal structures in the cytoplasm of normal and abnormal keratinocytes (author's transl)].

The occurrence of intracytoplasmic desmosomes in normal, hyperplastic, and hyperkeratotic epithelia, in carcinoma-in-situ and in invasive carcinoma of the human oral cavity is demonstrated by electron microscopy. The mechanism for formation of these structures by invagination, separation and by intracytoplasmic incorporation of plasma membrane-desmosome-complexes are described in various oral epithelia, and other possible mechanisms are discussed. Intracytoplasmic desmosomes may occur in normal and pathological keratinocytes of all layers of the oral epithelium. Their ultrastructure in the peripheral cytoplasm is similar to that of the regular desmosomes on the cell surface. However, as they migrate centripetally, they show signs of degeneration, suggesting dissolution by lysosomal enzyme systems. Various surface membrane alterations involved in the formation of intracytoplasmic desmosomes may lead to a reduction of plasma membrane material and of desmosome structures and to defective intercellular adhesion. The intracytoplasmic incorporation of desmosome structures is a ubiquitous phenomenon exhibited by epithelial keratinocytes under certain physiological or pathological conditions.


Photodermatoses induced by oral contraceptives.

The pathogenetic role of liver damage in photodermatoses induced by oral contraceptives was investigated. From among 121 cases with photodermatosis, it was in 4 cases of polymorphic light eruption-like dermatosis and in 2 cases of porphyria cutanea  tarda that a longterm use of antibaby pills preceded the development of skin disease. Physical and biochemical studies of the liver of the patients suggested that the hepatotoxicity of the estrogen component of oral contraceptives can play a role not only in the pathomechanism of porphyric cases, but also in that of cases occurring with the clinical picture of polymorphic light eruption.


In vitro evaluation of methotrexate and azathioprine for antipsoriatic activity.

The effects of methotrexate and azathioprine, two drugs used in antipsoriatic therapy, on oxygen consumption of surviving human skin and on enzymatic activities of human skin homogenates were investigated. In concentrations of 1 mM/1, both substances provoked a significant decrease in oxygen consumption of human skin; in this respect, there was practically no difference between methotrexate and azathioprine. In the enzyme assays, however, azathioprine was, by far, less effective than methotrexate. After an incubation of 120 min azathioprine (1mM/1) inhibited lactate and glucose-6-phosphate dehydrogenase activities by about 10 per cent only, whereas the corresponding values with methotrexate amounted to 80 and 70 per cent, respectively. Methotrexate revealed an immediate inhibitory effect on pure glucose-6-phosphate dehydrogenase whereas azathioprine produced no changes in this mode. Furthermore, only methotrexate inhibited "acid" phosphatase activity of human skin homogenates.--These data sustain the theory that the better clinical efficacy of methotrexate in patients with psoriasis might be due to the more pronounced inhibition of important enzymes such as the enzymes of the pentose phosphate shunt.


[Ultrastructure of nuclear bodies in connective tissue cells of psoriatic lesions (author's transl)].

Electron microscopic observations were made in 6 psoriatic lesions of the skin. All specimens showed an increased number of nuclear bodies containing glycogen and lipids in the nuclear plasma of connective tissue cells. The results indicate an activation of connective tissue cell metabolism. They are discussed in connection with previously described signs of the participation of mesenchymal tissue in the psoriatic skin reaction. The increased metabolism could be part of a "nonspecific mesenchymal tissue reaction".


[Mitogenic activity of melanoma extracts in leucocyte cultures (author's transl)].

From a mixed cell suspension of five primary melanomas an aqueous sterile extract was made and added to homologue leucocyte cultures of eight melanoma patients and seven controls. The extract had a blastogenic and mitogenic effect in all cultures. There was no significant difference between the responses of patients and controls. In experiments with an equally prepared extract of normal skin, added to homologue leucocyte cultures of nine persons, none but one had a positive reaction. This indicates, that the motigenic principle of the melanoma extract is not related to the histocompatibility antigen nor caused by chemical or bacterial contamination of the primary cell suspensions. It seems to be derived from the cytoplasmic fraction of melanoma cells. Other experiments to solve the problem were impossible because of lack of material. There are several reports in the literature which by using different methods indicate, that there might be an immunological reaction to melanoma associated principles in healthy persons, too.


[Lamelate corpuscles in lymph nodes and their significance for metastasizing melanoma (author's transl)].

For the first time the occurrence of corpuscles of Vater-Pacini lacated in the hili of lymph nodes in patients with melanoma is described. As these corpuscles are pressure sensitive they participate in the regulation of blood and lymph flow inside the lymph node. By these means they may influence secondary deposition of melanoma cells.


[Fluorescence histochemical and microfluorometrical investigations of pigmentary tumors of the skin (author's transl)].

Junction nevus, dermal nevus, melanosis circumscripta praecancerosa Dubreuilh, superficial spreading melanoma, and nodular melanoma were investigated and characterized by use of the formalin induced fluorescence method (FIF). In the vicinity of junctional nevus cell clusters and near tumor cells of the superficial spreading melanoma increased numbers of melanocytes are found. These show different types of dendritic branching. Spherical nevus cells however are completely devoid of dendritic processes. On the other hand, the atypical pigment cells in melanosis circumscripta praecancerosa Dubreuilh exhibit a shape similar to that of melanocytes, whereas the globular cells of superficial spreading melanoma have the appearance of nevus cells. The arrangement of nodular melanoma cells resembles that observed in dermal nevus. However the characteristic decrease in fluorescence intensity from epidermal junction to deeper dermis as observed in the dermal nevus was missed in nodular melanomas. Dendritic pigment cells displaying formalin induced fluorescence (FIF) could be demonstrated in all types of malignant melanomas investigated in the present study. The fluorophores of the pigment lesions are characterized microspectrofluorimetrically by (1) ill-defined emission maxima between 470 and 490 nm and (2) a clear-cut excitation maximum at 430 nm accompanied by a lower one at 320 nm. Hydrochloric acid vapor induces a hyposochromic shift of the 430 nm excitation maximum to 370-380 nm and a marked elevation of the 320 nm maximum. These results indicate fluorophores of DOPA and its derivatives; in this respect there are no marked differences between melanocytes, nevus cells and the cells of malignant melanoma.


Biochemical and physiological particularities on the skin surface of diabetics.

Biochemical and physiological examinations were carried out on the skin surface of the following groups: on 16 newly diagnosed diabetics; on 26 diabetics receiving treatment; and on 2 control groups of 16 and 26 healthy persons respectively of corresponding age and sex. The tests on the surface of the skin of the newly diagnosed diabetics when compared with the corresponding control group show the following significant results: 1. An increase in the percentage of free cholesterol in the lipids of the skin's surface possibly as a result of an increased cell turnover in the epidermis. 2. An increase in the free fatty acid concentration to the disadvantage of the triglycerides in the lipids of the skin's surface as an expression of an improved bacterial lipolysis. 3. A decrease in the reducing substances as confirmed by the phenol-sulfuric acid method in the so called water solubles. 4. An increase in the amino acids as confirmed by the ninhydrin method in the so called water solubles. All the above mentioned changes were more pronounced in the newly diagnosed diabetics than in those already receiving treatment; it can be seen that these changes can partly be normalised under diabetic therapy.


The measurement of corticosteroid induced dermal atrophy by a radiological method.

Dermal atrophy due to the application of Clobetasolpropionate has been detected and measured by an X-ray method after four weeks topical application to the forearm. This effect was found to have recovered when the subjects were re X-rayed eight weeks after they had stopped using the steroid preparation.


Exposure of apple thinners to parathion residues.

In studies of potential exposure of a volunteer working under controlled conditions during apple hand-thinning operations at 1, 24, 48, 72, 96, 168, and 240 hr after application of conventional 0.03% parathion spray, both dermal and respiratory exposure values were greater where water-wettable powder formulations were used than where emulsifiables were used. Residue levels of parathion on leaves from the two types of applications were about the same. Only trace amounts of paraoxon could be detected at one and seven days after application. Highest exposure values (14.2 mg/hr dermally and 0.15 mg/hr respiratorily) were obtained within 24 hr of application. Exposure was considerably less after residues were 72 hr old. Greatest exposure was on the forearms and hands. Urinary p-nitrophenol excretion indicated slightly more absorption following exposure in water-wettable powder experimental plots. Potential exposure values indicate that absorption could reach hazardous levels after one or two hr of work, even at the 96-hr residue period, if all the pesticide were absorbed. Considering that only a small fraction of the total amount would be absorbed, it is calculated that at 75-hr residue period poisoning should not occur. There was no significant change in blood cholinesterase activity of the volunteer worker. Variation in spray deposit within an orchard due to poor tank mixing did not appear to be great enough to be considered an important factor affecting exposure.


Metabolism of terbacil in orange seedlings.

Orange seedlings were cultured in aqueous solutions of 3-tert-butyl-5-chloro-6-methyluracil (terbacil and terbacil-2-14C). Radioactivity was distributed throughout the plant with the largest amount in the roots and the smallest amount in the leaves. Terbacil was metabolized to form 3-tert-butyl-5-chloro-6-hydroxymethyl uracil, which was conjugated to form a beta-glucoside as the conjugate was hydrolyzed by beta-glucosidase. Identification of the metabolite was made by infrared and mass spectrometry after isolation and purification by column and thin layer chromatography. An additional unidentified water-soluble material was accumulated in the plant. 5-chloro-uracil was not detected as a metabolite of terbacil.


Concentration of mercury in animal products and soils of North Dakota.

Total mercury (Hg) was determined in milk, eggs, beef, pork, human head hair, soil and water obtained from four geographical areas of North Dakota. The sampling areas were selected on the basis of differences in prevalent agricultural practices, climate and topography. Statewide average Hg concentrations in ppb were milk, 0.8; eggs, 12; beef muscle, 5; beef liver, 10; pork muscle, 11; pork liver, 15; head hair, 1708; soil, 30; rainwater and well water, less than one. There were no significant differences observed among areas in Hg content of any substance sampled except beef muscle. Beef muscle obtained from areas 2 and 4 contained significantly (P less than or equal to 0.05) higher levels of Hg than beef muscle from the other two areas. However, the magnitudes of differences were small (4 to 6 ppb). Considerable variation among individual beef and swine were noted but only six beef of 453 sampled and three swine of 156 sampled had tissue Hg exceeding 50 ppb. Appreciable variation was observed in Hg in eggs with respect to farms within an area, eggs from the same farm, and sampling times within a year. Few eggs sampled contained more than 50 ppb. Significantly (P less than or equal to 0.01) higher levels of Hg were found in head hair of women as compared with men and relatively large differences among individuals were observed. Average Hg in hair was generally low irrespective of sex of donor or area of the state as compared with data given in the literature. Soil Hg levels were consistently low in all areas of the state, and no relationship between cropping practices and soil Hg was detected.


Establishment of reentry intervals for organophosphate-treated cotton fields based on human data: III. 12 To 72 hours post-treatment exposure to monocrotophos, ethyl- and methyl parathion.

Five human volunteers entered methyl parathion, ethyl parathion, or monocrotophos treated cotton fields for five-hr exposure periods when the residues of the respective pesticides had aged 12 hr, 24 and 48 hr and 72 hr. Foliage residues of methyl parathion disappeared fastest, those of monocrotophos slowest. Personal exposure to pesticide was evaluated from contamination of skin, clothing, and ambient air, while actual absorption of chemical was assessed from pesticide concentration in blood, urinary metabolite excretion, and effects on blood cholinesterase activities. There was good correspondence between magnitudes of foliar residue, estimates of personal contamination, and measures of chemical absorption. Field exposures caused no symptoms or clinical signs of organophosphate poisoning and depressed averaged blood cholinesterase activities by no more than 14% of pre-exposure levels.


The distribution of tracer doses of cadmium in the normal rat.

The distribution and excretion of a single tracer dose of cadmium-109 given intravenously to rats were studied in a 60-day time course experiment. The organs that accumulated the most cadmium were the liver, kidneys, and pancreas. Initial high plasma levels decreased rapidly, and most of the cadmium that remained in the blood after 24 hr was found in the red cells. In most organs and tissues a level was reached within 24 hr at which the cadmium concentration remained relatively stable. Kidney was a marked exception because the amount of cadmium found in that organ increased progressively. Excretion of cadmium was found to be predominantly via the feces. Twenty-five to 28% of the dose was excreted by that route in 60 days, the most rapid phase occurring during the first three days. Less than 0.15% of the dose was excreted via the urine.


An investigation of the safety of cotton reentry after organophosphate application.

Twelve cotton insect scouts were monitored during an entire pesticide application season by weekly determinations of para-nitrophenol excretion and biweekly cholinesterase measurements. These data were compared to weekly reentry intervals and pesticide application rates to study the validity of a 48-hr minimum reentry interval for methyl parathion-treated cotton. Methyl parathion represented 54.2% of the total amount of pesticide used with toxaphene 35.3%, ethyl parathion 4.1%, and other 6.4%. A significant decrease in erythrocyte and plasma cholinesterase was observed during initial exposure but during peak exposure the cholinesterase levels had returned to normal. The maximum mean amount of methyl and ethyl parathion absorbed by calculation from PNP excretion was 0.95 mg/24hr (n = 12). Twelve percent of all reentries were within two days and during one week 48% occurred during the first two days after pesticide application.


Dislodgeable azinphosmethyl residues from air blast spraying of apple foliage in Ohio.

The distribution and decay rates of dislodgeable residues of azinphosmethyl applied by two types of air blast sprayers on apple foliage in Ohio were investigated. Leaf discs were taken from nine sites located on the periphery of Cortland apple trees at five dates after spraying. The sprayer delivering the higher airflow rate, but lower velocity, deposited the pesticide much more uniformly over the trees and applied more in the top of the tree. The other sprayer deposited the greatest proportion of pesticide on the site nearest the sprayer. The residue decreased at all sites and ranged from 42 to near 100% decrease at 14 days after spraying.


Influence of humidity and rain on uptake and metabolism of 14C-azinphos-methyl in bean plants.

In several experiments the influence of relative humidity and rain on uptake and metabolism of carbonyl-14C-azinphos-methyl was examined in bean plants under the following environmental conditions: Growth room with 35/80%, 65/85% and 95/95% (day/night) relative humidity and open field with and without rain. Increasing relative humidity had an enhancing effect on the rate of uptake and metabolism. A higher portion of water-soluble compounds was found in the bean tissue, although the azinphos-methyl itself is relatively non-polar. Low relative humidity and possible dry periods in summer will reduce the uptake and will leave the azinphos-methyl relatively persistent on the leaf surface. Rain or spray irrigation easily removed azinphos-methyl from the leaves. The rate of this removal seemed to depend on the intensity and time of rainfall after application. However, repeated wettings by rain may simultaneously stimulate uptake and metabolism of azinphos-methyl by the leaves.


Seasonal effects of leached mirex on selected estuarine animals.

Four 28-day seasonal experiments were conducted using selected estuarine animals in outdoor tanks that received continuous flow of mirex-laden water. Mirex (dodecachlorooctahydro-1,3,4-metheno-2H-cyclobuta [cd] pentalene) leached from fire ant bait (0.3% mirex) by fresh water and then mixed with salt water was toxic to blue crabs (Callinectes sapidus), pink shrimp (Penaeus duorarum), and grass shrimp (Palaemonetes pugio) but not to sheepshead minnows (Cyprinodon variegatus), at concentrations less than 0.53 mug/L in water. The amount of leaching was greatest in summer and least in spring. Greatest mortality occurred in summer at the highest water temperature and concentration of mirex; least mortality occurred in spring at the next to the lowest temperature and at the lowest concentration. Earliest deaths of blue crabs occurred after six days of exposure and shrimps after two days. Small juvenile crabs were more sensitive to leached mirex than were large juveniles. Mirex did not appear to affect growth or frequency of molting in crabs. All exposed animals concentrated mirex. Among animals that survived for 28 days, sheepshead minnows concentrated mirex 40,800X above the concentration in the water, blue crabs 2,300X, pink shrimp 10,000X, and grass shrimp 10,800X. Sand substrata contained mirex up to 770X that in the water. Most control and exposed animals in samples examined histologically had normal tissues, but alteration in gills of some exposed fish and natural pathogens in some exposed and control crabs and shrimp were observed. The experiments demonstrated that mirex can be leached from bait by fresh water, concentrated by estuarine organisms, and can be toxic to crabs and shrimps.


Some new evidence on human joint lubrication.

Theoretical consideration has been given to the use of pendulum machines which are used to examine the frictional properties of human joints by incorporating them as fulcra. As a result, a new type of pendulum machine has been built which incorporates the facility to apply sudden loads to the joint on starting the swinging motion, and also the ability to measure directly the frictional torque experienced by the joint. The results obtained from natural hip joints indicate the presence of squeeze film lubrication under conditions of sudden loading of a joint. In addition, a self-generated fluid film process was observed at low loads while at higher loads boundary lubrication appeared to be important. These results have been used to describe the lubrication regimens occurring in a normal activity such as walking. A single experiment carried out on a hip from a patient suffering from severe rheumatoid arthritis has also been reported and the frictional resistance was seen to be increased fifteenfold compared to a normal hip.


Quantitative study of stiffness in the knee joint.

Data from a knee arthrograph, which imparts a passive sinusoidal motion to the joint and measures the resistive torque and displacement, have been shown to be reproducible. Tests carried out on joints (from 49 males, 21 females) showed that the energy loss per cycle of the joint increased with age for both sexes but the peak to peak torque (elastic stiffness) did not vary with age. Muscle bulk had a large influence on the stiffness (both dissipative and elastic) of the knee as did the size of the joint itself. Women's knee joints exhibited lower values of dissipative energy loss and peak to peak torque than men's for all ages and sizes of joints.


The foot in chronic rheumatoid arthritis.

The feet of 200 consecutive admissions with classical or definite rheumatoid arthritis were studied. 104 were found to have pain or deformity. Clinical involvement of the joints was seen more often than radiological joint damage in the ankle, but the reverse was the case in the midtarsal joints. The metatarsophalangeal joints were involved most frequently both clinically and radiologically. Sixty per cent of the patients required modified shoes but only a third of these had received them. The need for more shoes is clear, and although this is a highly selected group of patients they were all under specialist care. The increased expenditure on special footwear would benefit the patient, firstly by improving ambulation, and secondly perhaps by reducing the number of operations necessary. Hallux valgus was very common and occurred with similar frequency to disease in the other metatarsophalangeal joints. Although not exclusive to rheumatoid arthritis, hallux valgus must have been caused for the most part by the rheumatoid arthritis and if so, then it is suggested that the provision of suitable shoes for patients may be less costly than subsequent surgical treatment.


Attempt to classify patients with arthritis of the hip suitable for prosthetic replacement, and their femoral heads.

Using clinical, radiological, and morbid anatomical data about patients with arthritis of the hip and their femoral heads resected during total hip replacement, an attempt has been made first, to classify patients and femoral heads by a cluster analysis technique, and secondly and more realistically, to use existing clinical and radiological classification as a basis for seeking discriminating features in the data from the femoral head. Both types of analysis failed to give results, and led to a conclusion that arthritis of the hip is a spectrum of disease. This may not pose problems to the clinician, but it does to the investigator studying the pathogenesis of osteoarthrosis. This problem is briefly discussed.


Aortic valve incompetence and replacement in rheumatoid arthritis.

Five cases of aortic incompetence and nodular seropositive rheumatoid arthritis are presented. Four cases underwent aortic valve replacement. Two of these had granulomatous involvement of the aortic cusps similar to subcutaneous rheumatoid nodules, and another showed a nonspecific fibrosis. One case had definite coincidental rheumatic aortic and mitral heart disease. Two patients had undergone pericardectomy previously for constrictive pericarditis. Good results were obtained in all four operated cases and cardiac surgery enabled continuation of rehabilitation for the rheumatoid arthritis, including major orthopaedic procedures. A review of 22 cases from the literature with rheumatoid granulomata within the aortic valve shows that they are associated with mitral valve granulomata in 63-6%. Congestive cardiac failure was found in 75%. Macroscopical evidence of aortic incompetence was seen in 36-8% and of aortic stenosis in 15-8%. Associated pericarditis occurred in 59-1%, which was severe or complicated in 13.6%. The associated arthritis was severe in 77-8% with subcutaneous nodules (71-5%), rheumatoid factor (83-6%), and episcleritis (66-6%). From these cases and a review of the literature the following points are emphasized. (1) Both the granulomatous and nonspecific aortic valvulitis of rheumatoid arthritis may result in significant haemodynamic abnormality. (2) The valve lesions found are often clinically and macroscopically indistinguishable from rheumatic valve lesions. (3) Granulomata, when present, are usually found in the valve cusp or ring and only occasionally in the aortic wall. (4) Associated joint disease, although usually severe, may be mild. (5) The valve lesion may be accompanied by a severe pericardial involvement--either tamponade or constriction. (6) Aortic valve replacement for aortic incompetence in rheumatoid arthritis is both feasible and worthwile, despite severe joint disease.


Cardiac valvular disease in chronic inflammatory disorders of connective tissue. Factors influencing survival after surgery.

Three cases of cardiac valvular disease complicating chronic inflammatory disorders of connective tissue are described. Each underwent surgical valve replacement. The outcome in the first case, a patient with aortitis complicating Reiter's syndrome and in good health otherwise, has been excellent. The other two patients, one with rheumatoid arthritis and vasculitis, the other with systemic lupus erythematosus and nephritis, died after operation as the result of their systemic disease. The importance of systemic features in assessing this type of patient is emphasized.


Urinary copper excretion in rheumatoid arthritis.

The pattern of urinary copper excretion in relation to urine osmolality (as shown by series of aliquots of urine) was studied in rheumatoid patients and in control groups. Rheumatoid patients showed an abnormal copper excretion pattern compared with nonrheumatoid subjects. This was not a direct function of the raised serum copper in rheumatoid disease. Measurements based on 24-hour series of aliquots of urine (as distinct from total pooled 24-hour collections) have been shown to be a useful and sensitive method for studying copper excretion patterns.


Protein sulphydryl depression during adjuvant arthritis.

The changes in plasma protein sulphydryl level were measured during the course of adjuvant-induced arthritis in rats. Major depressions in the plasma sulphydryl level occurred at the onset of adjuvant disease, and the extent of the depression was related to the severity of the disease. Plasma sulphydryl levels remain unchanged when the systemic arthritis is suppressed by inclusion of a competing antigen in the adjuvant. Changes in sulphydryl content of the plasma were shown not to be due to weight loss or decrease in plasma protein level.


Uric acid, joint morbidity, and streptococcal antibodies in Maori and European teenagers. Rotorua Lakes study 3.

Two hundred and ninety-four New Zealand secondary school students were examined by questionnaire, and physical and biochemical methods. The sample contained almost equal numbers of Maoris and Europeans. The findings related to joint conditions are presented. Past injury and rheumatic disease accounted for some of the reported morbidity, but no important sex or race differences in these factors emerged. There were, however, significant differences in serum uric acid levels with the Maori having higher levels than the Europeans. A significant correlation with body mass was present in both race and sex groups but a correlation with haemoglobin was present only in the European females. While hyperuricaemia was not associated with morbidity in this young sample, ethnic differences anticipated the higher prevalence of gout already observed in Maori men.


Failure to show mycoplasmas and cytopathogenic virus in rheumatoid arthritis.

Synovial needle biopsies, joint aspirates, and joint tissue obtained at open operation from 41 cases of rheumatoid arthritis were inoculated onto PPLO media, L-form medium, and cell cultures for the isolation of mycoplasmas, L-form bacteria, and viruses. Medium suitable for the isolation of 'T' strain mycoplasmas was not employed. No mycoplasmas, L-form bacteria, or cytopathogenic viruses were shown. Similar specimens from nine patients diagnosed as having Reiter's disease were examined in a like manner and yielded only one Mycoplasma hominis type 1 isolate from a knee joint biopsy. It is concluded that known strains of mycoplasma and bacterial L-forms do not play a direct role in early and established cases of rheumatoid arthritis. Some of the cell cultures used in this study contained mycoplasma contaminants. Bacterial contaminants were also encountered in occasional batches of L-form medium.


Clinical echinococcosis.

In 221 patients (0.48% of hospital admissions) with hydatid disease (122 female and 99 males), 81% had single and 19% multiple organs involved. Lungs, liver and spleen as single sites of echinococcosis together represented 83.24% of cases and the liver alone represented 95.24% of instances with multiple organ involvement. One hundred seventy-nine single and 74 multiple cysts (ratio of 2.42/1) represented a total of 363 cysts (1.64 cysts/patient). The incidence of intact cysts was 51.52% and 48.48% had ruptured. Ruptures numbered highest in the lungs (73.44%) and greater in multiple (79.66%) than in single cysts (68.12%). In the liver, 27.14% of single and 54.55% of multiple cysts (40.44% of all liver cysts) had ruptured. Cysts varied in size from 0.8 to 35 cm diameter. Single cysts averaged significantly higher (14.16 cm) and multiple ones lower (5.71 cm) as did intact (6.75 cm) versus reptured cysts (4.33 cm). Except for 10 silent and 15 symptomatic cysts treated medically, all the rest were treated surgically by removal of the endocyst or resection of both endo and exocysts including 205 first, 31 second and 5 third procedures (1.75% of all major operations). Complications occurred in 28.57%. Surgical mortality (3.57%) was markedly lower than with conservative treatment (60%) and significantly less than that of the whole group (14.48%).


Total esophageal reconstruction after extraction of the esophagus.

During the period between 1971 and 1974, 25 cases of carcinoma of the hypopharynx and cervical esophagus underwent esophageal extraction and total esophageal reconstruction without operative mortality. The operative methods used for this series were blunt dissection, or everting stripping of the thoracic esophagus without thoractomy followed by pharyngogastro or -colostomy as a one stage procedure via a posterior mediastinal route created by esophageal extraction. The operative technique of esophageal extraction without thoracotomy is described. It is obvious that mediastinal tunnel is the shortest route through which to put the chosen organ for esophageal substitution. This operation is to be recommended for lesion of the hypopharynx and cervical esophagus as well as some esophageal stricture because of its operative simplicity, ease, safety and rare postoperative complications.


Intragastric microbial colonization in common disease states of the stomach and duodenum.

Forty-nine patients undergoing elective or emergent gastric surgery have been included in this study. Gastric needle aspiration was performed at the time of surgery in each case, followed by qualitative aerobic and anaerobic bacteriologic analysis. In 18 patients undergoing elective operation for chronic nonobstructing duodenal ulcer a gastric microflora was present in only three patients and no postoperative wound infections were observed. In 29 of 31 patients, in the other groups of patients with bleeding or obstructing duodenal ulcer or in those with gastric ulcer or malignancy, intragastric micro-organisms were present. Six of the 7 postoperative wound infections which developed in these groups of patients were due  to one of the same bacteria isolated at the time of original needle aspiration. It appears that the endogenous intragastric microflora is a significant factor in the development of postoperative wound sepsis following gastric resection, in those groups of patients with a compromise of their normal gastric antibacterial inhibitory mechanisms.


Studies in burns: XIV, Heling in burn wounds treated with Ethyl Linoleate alone or in combination with selected topical antibacterial agents.

Studies of the efficacy, in terms of burned wound healing, of a mixture of Ethyl Linoleate (ethyl 9-12 (cis, cis) octadecadienoate) with alpha-1-histidine, alpha-tocopherol, and TBHQ (hELate) was undertaken in 12 swine. The species was selected so as to study an animal with skin anatomy similar to the human. Statistically significantly greater healing occurred in 730 C/7sec contact burns (20% BSA) treated with hELate than in untreated burns in pigs. Further, there was no contracture noted in the hELate treated lesions, while marked contracture occurred in the untreated burns. Additionally, we noted that there was a proportional increase in weight gain amongst swine studied as their burn lesions epithelialized. In order to evaluate the compatibility of hELate with selected, currently-used topical antibacterial agents, 154 rabbits with 20% 730 C/7 sec contact burns were studied. The lipid was applied (0.01 ml/cm2 burn) at 1 hour postburning; the topical agent was applied at 2 hours post-burn and every 24-hours. All animals were washed once daily. hELate was applied only once. We found no statistical difference in the number of subjects healed or in the mortality between animals treated with hELate alone and those treated with the agent plus Gentamycin cream, Neosporin cream, and silver sulfadiazine 1% in Unibase USP (compounded at Medical College of Georgia specifically and only for this study.) We suggest that Ethyl Linoleate agent (hELate) may be used safely in combination with selected antibacterial substances. Further, these selected combinations seem to be non-toxic and appear to allow the calorie-saving and healing effects of the lipid to proceed unimpeded.


Tumor thickness, level of invasion and node dissection in stage I cutaneous melanoma.

From a retrospective study of 97 and a prospective study of 41 Stage I cutaneous melanomas, it was found that tumor thickness is a better measure of prognosis than is the level of invasion of the tumor. The chance of developing recurrent disease appears to be directly proportional to tumor thickness. Prophylactic lymph node dissection doubled the rate of survival for patients with lesions greater than 1.50 mm thick but had no effect on those with thinner lesions. Thirty-nine per cent of the patients had lesions less than 0.76 mm thick and all survived free of disease for 5 or more years. Six per cent of the tumors that recurred or metastasized were in an intermediate range of 0.76-1.50 mm thick, and no discriminant could be found to separate these 9 lesions with a bad prognosis from the remaining 18 in this group.


Operative management of pancreatic pseudocysts in infants and children: a review of 75 cases.

This report combines the findings and treatment in 15 infants and children with pancreatic pseudocysts with 60 additional cases from a literature review. The mean age at diagnosis was 7.5 years with pseudocyst being more common in boys (44:31). Sixty per cent were due to trauma, while in 32% the cause was unknown. Abdominal pain (68%), a mass (64%), and vomiting (52%) were the most frequent findings. The serum amylase was elevated and the upper gastrointestinal contrast study consistent with a mass in 88% of cases. Operative treatment included external drainage in 25 children (33%), cystgastrostomy or cyst-jejunostomy in 34 (45%), excision in 10 (13%) and miscellaneous procedures in 6 (8%). Complications were relatively few and there were no deaths recorded. Recurrence rate for cyst-gastrostomy was 4.7%, cyst-jejunostomy 7.6%, external drainage 8% and cyst-duodenostomy 50%. External drainage operations had prolonged cutaneous drainage. These observations suggest the appropriate operation is determined by the location and duration of pseudocyst. Internal drainage is preferred and avoids complications seen following resection and external drainage. Cyst-gastrostomy is effective when the pseudocyst is retrogastric and adherent to the stomach wall. Cyst-jejunostomy is most useful in instances in which the pseudocyst in not adherent to the stomach wall. Low recurrence rates and a zero mortality rate makes operative treatment highly acceptable therapy. Low recurrence rates are expected in childhood cases, (particularly related to trauma) due to an absence of underlying pancreatic disease and ductal obstruction.


Surgical treatment of 297 soft tissue sarcomas of the lower extremity.

The results of surgical treatment of 297 soft tissue sarcomas arising in the lower extremity were critically examined. En bloc wide soft part resection (158 cases) yielded five and ten year survival rates of 63% and 50%. Amputation or major disarticulation (139 cases) gave corresponding survival rates of 45% and 29%. The most frequent cause of treatment failure was distant metastases, commonly in the lungs. The tissue type of sarcoma, histologic grade of malignancy, and tumor size appear to be important determinants of survival irrespective of the type of surgical treatment. Local recurrence of sarcoma occurred in 18% of the cases, more commonly after soft part resections than amputations. The proximity of a sarcoma to major vessels, bone or joint tends to compromise the margins of a wide soft part resection, thus increasing the risk of local recurrence. In appropriate cases, the scope of soft part resection can be extended by en bloc excision of the femoral vessels, with the hope of improving local control of sarcoma. Amputation should br resorted to if an adequate margin of resection cannot otherwise be obtained. This decision must be weighted against the high frequency of distant metastases in this disease. Postoperative adjuvant chemotherapy and immunotherapy offer prospects of prevention of this tragic outcome.


Distal antrectomy with vagectomy for duodenal ulcer: results in 611 cases.

Distal antrectomy (25% or less) resection of the distal stomach with bilateral vagectomy, Billroth II, antecolic, Polya or Hofmeister gastrojejunostomy, continues to be our operation of choice for chronic duodenal ulcer. This is based upon our experience in 611 operations and as a result of careful complete repeat in-patient followup studies conducted since our original operation which was devised and performed in July 1953. This procedure controls or eliminates the two major gastric acid stimulatory phases responsible in the pathogenesis and chronicity of a duodenal ulcer: neurogenic (cephalic phase) via the vagel gastric pathways, and the humoral (gastrin) phase via antral stimulation. Even though part of the antrum may remain in the gastric remnant in some patients, antral control is maintained because the antrum remains in the gastric acid stream, there is no stasis, and it is vagectomized. The ulcer diathesis is controlled with a minimal disturbance in gastric physiology, in function, and in gastric reservoir capacity; the procedure will almost eliminate all of the undesirable postoperative gastrointestinal sequelase associated with other operations for duodenal ulcer. It insures the least chance for marginal, gastric, or recurrent ulcer formation, and a low morbidity rate.


Principles in the management of arterial injuries associated with fracture/dislocations.

Ten out of 355 patients admitted with fracture and/or dislocations of long bones secondary to blunt trauma had associated vascular injuries. The clinical recognition of the associated vascular injury and its vertification of arteriography, Doppler study or surgical exploration resulted in early vascular repair and limb salvage. The controversial aspects of bone stabilization followed by vascular repair versus primary vascular repari, skeletal traction and delayed internal fixation together with fasciotomy-fibulectomy are discussed. Our results with the injuries seen justify the principle of bone stabilization followed by vascular repair, particularly since a team effort resulted in little time lost prior to circulatory restoration. The problems following vascular repair-namely anterior compartment snydrome, acute renal failure and cardiac arrest are present with their principles of management.


Joining gut ends of unequal diameter.

A simple, safe and precise method for joining ends of unequal diameter is presented. Very little septum is created by either anterior or posterior rows. The figure-eight seems to crush the septum almost flat on the posterior row and the Halsted's create an absolutely minimal septum anteriorly where they are correctly placed. The posterior row used two layers of submucosa and the anterior one, four layers, and no reliance is placed on the serosa-muscularis layer. This technique is thought to have distinct advantages relative to strength, safety, and minimal septum formation.


Influence of the postoperative state on the intracellular free amino acids in human muscle tissue.

Five patients were studied before and two to three days after major, uncomplicated abdominal operation. Muscle tissue was obtained by needle biopsy from m. quadriceps femoris after eight hours overnight fast. Plasma free amino acids were analyzed in simultaneously obtained samples. In the homogenized muscle samples the intracellular concentration of each amino acid (IC) was calculated by subtracting the free extracellular part from the total amount, assuming the plasma concentration to be equal to the concentration in the interstitial fluid. Their relationships have also been calculated (IC/EC gradient). The extra- and intracellular water distribution was estimated using a modified chloride method. In similarity to the findings in normal subjects the majority of the amino acids showed much higher concentration in intracellular water than in plasma. Preoperatively all amino acids examined in muscle biopsies were formed within normal limits. Postoperatively the total amount of free amino acids in plasma and muscle was decreased, and the amino acid profiles differed from those observed in normal subjects. In plasma, as compared with normal controls, the most significant changes were an increase in phenylalanine and tyrosine and a decrease in serine, proline, histidine and isoleucine. In muscle the greatest decrease occurred in the concentrations of glutamine, arginine and lysine followed by proline and glutamic acid. The increase in taurine, valine and phenylalanine were all highly significant and in serin, glycine, alanine and leucine significant, whereas tyrosine showed only a moderate rise. Compared with normal values there were marked increases in the gradient between intracellular and plasma concentrations which were highly significant for glycine and valine and significant for serine, alanine, isoleucine and leucine. The shift in the methionine gradient was somewhat less. We confirm that alterations in the muscle free amino acid pool are not reflected in the values found in plasma. Further work is required to explore the clinical significance of the observed variations in individual amino acids.


An uncontrolled comparison of treatments for achalasia.

A series of 78 patients with achalasia, seen during a 10-year period, was like those reported by others with regard to age at onset, nature of symptoms, and duration of symptoms. Analysis of the results of 5 different treatment modalities administered allows an uncontrolled comparison heretofore not available from an institution at which no one treatment was favored over all others. Those who were not treated or who received only anticholinergic medication did not become asymptomatic. Those treated by single or repeated bougienage were not improved for more than a few weeks and suffered a 6% incidence of esophageal perforation. Forty-six per cent of those treated by a single pneumatic dilatation were asymptomatic for 1 year or more. Although esophagocardiomyotomy provided symptomatic relief for 1 year or more in 85%, there was a 25% incidence of gastroesophageal reflux.


Renal artery and vein injury following blunt trauma.

Blunt injuries of the renal vascular pedicle occur infrequently. The experience with fourteen cases of blunt renal vascular trauma is presented. Most patients were injured in motor vehicle accidents. The diagnosis was made immediately after admission in 6 patients, delayed in 5, and at autopsy in 3. Most patients presented with gross or microscopic hematuria. The diagnosis of renal vascular injury was suggested by IVP in most instances. Surgical management was used in the 6 patients in whom the immediate diagnosis of renal pedicle injury was made; primary vascular repair was carried out in 4 patients and nephrectomy in two. Conservative management was used in 4 of the 5 patients with delayed diagnosis, and nephrectomy was required in the fifth. Three patients received no treatment as two were dead on arrival and one die during laparotomy. Seven patients died (50%). One of the 7 survivors has a functioning kidney following repair of a renal vein laceration. Three patients with devascularized kidneys have been followed long term and have not developed hypertension. An IVP should be mandatory following severe blunt trauma, especially when hematuria is present. Renal arteriography is indicated with distortion of calyces, extravasation or nonfunction seen on IVP and allows a definitive diagnosis of renal vessel injury to be made.


Staging laparotomy in the treatment of metastatic melanoma of the lower extremities.

Twenty-six consecutive patients with melanoma of the lower extremities metastatic to the superficial inguinal lymph nodes were subjected to laparotomy. No patient had preoperative evidence of tumor dissemination past the superficial inguinal nodes. However three patients (12%) had metastases to the liver or para-aortic lymph nodes documented at laparotomy and were not subjected to iliac and obturator lymph node dissection. One of these patients had concomitant local recurrence of melanoma at the ankle. The other two patients had superficial inguinal lymph nodes at least 5 cm in diameter, although two other such patients with similar 5 cm lymph nodes did not have positive intra-abdominal findings. The remaining 23 of the 26 patients underwent ipsilateral iliac and obturator lymph node dissection, which proved positive in 3/23 patients (13%). Of these 23 patients undergoing iliac and obturator node dissection, 18 had clinically positive (and microscopically positive) superficial inguinal nodes prior to their dissection, while the remaining 5 patients had clinically negative (but microscopically positive) superficial inguinal nodes. The three cases of positive dissected iliac and obturator nodes occurred among the 18 patients with clinically positive superficial inguinal nodes (17%). Among the 5 patients with clinically negative, microscopically positive superficial groin nodes, there was no detectable deep inguinal nodal spread (or hepatic or para-aortic involvement).


Adenocarcinoma of the pancreas: a statistical analysis of biliary bypass vs Whipple resection in good risk patients.

A series of 297 patients with adenocarcinoma of the head of the pancreas was reviewed. Forty-eight patients was identified with disease limited to the pancreas or adjacent tissues. Twenty-four patients underwent Whipple resection. A second group of 24 patients underwent elective biliary bypass. No patient had liver, omental or peritoneal metastases. All cases of ampullary carcinoma and islet cell tumors were excluded. Assessment of clinical and laboratory parameters revealed the two groups to be statistically comparable. There were no 5-year survivors in either groups. Mean duration of survival was not significantly different. Life table analysis showed no significant difference between the survival rates of the two groups. Frequency of clinic followup, rehospitalization and reexploration were used to assess palliation. Success of palliation was poor in both groups and no statistically significant differences were noted. Surgical mortality in the resected group was 8% and did not differ from the 4% surgical mortality in the bypass group. Surgical morbidity was significantly higher in the resected group. Implications of this data in the management of patients with resectable carcinoma of the pancreas are discussed.


Is modified radical mastectomy adequate for axillary lymph node dissection?

The effectiveness of axillary dissection by modified radical mastectomy was assessed by a comparison of the total axillary nodes removed by this operation to that by radical mastectomy. In a series of 121 consecutive radical mastectomies performed during the period of 1964 to 1969, we found that the number of axillary nodes removed ranged from 3 to 63 with a median of 22 and a mean of 23.4 per patient. In a subsequent series of 111 consecutive modified radical mastectomies performed between 1969 and 1973, the total axillary nodes removed ranged from 6 to 77 with a median of 24 and mean of 25.7 nodes in each mastectomy specimen. These results strongly suggest that axillary dissection in modified radical mastectomy is as complete as that in the Halsted radical mastectomy.


Wound infection in colonic surgery.

Three hundred forty-one consecutive cases of colonic surgery performed by the Proctology service of our hospital have been reviewed. There was a total of 7 wound infections, constituting an incidence of 2.1%. The infection rate in clean contaminated cases was 0.8% and in contaminated cases, 4.7%. The mortality rate was 2.3%. Parenteral antibiotics were used in less than 50% of the operations. Our impression is that attention to one modality of wound infection prevention with disregard for the others will produce little. However, close attention to all the modalities by which we can hope to reduce wound infection appears to produce strikingly beneficial results.


Preserved allografts of dilated saphenous vein for vascular access in hemodialysis: an initial experience.

Arteriovenous fistulas constructed from preserved (frozen) allograft veins provided vascular access for maintenance hemodialysis in 14 patients with inadequate vasculature for conventional autogenous fistulas. Electromagnetic flows ranged from 200 to 250 cc/min. Dialysis flow of 200 cc/min were accomplished consistently. The allografts were useable for dialysis much earlier than autogenous A-V fistulas. Arteriography demonstrated a wide vasculature channel very suitable for dialysis needles. Allografts seemed superior to bovine heterografts in both patency and susceptibility to infection. Scanning electron microscopy revealed smoother initimal surfaces if the donor received small amounts of heparin systemically while the veins were being removed. Allograft veins appear to be a useful alternative means of vascular access for hemodialysis.


Carotid endarterectomy: an analysis of 234 operative cases.

This paper offers a computer-assisted analysis of the author's experience with 234 carotid endarterectomy procedures in 188 patients. The patients' ages, sex, smoking habits, symptoms, carotid bruits, arteriographic findings and associated diseases are summarized. There were 28 operations in asymptomatic patients, 170 operations in patients with transient ischemic attacks (TIA), 35-operations in patients with a completed stroke and one operation in a patient with a stroke in evolution. After surgery, transient neurologic deficits were noted in both the asymptomatic group (two instances) and the group with TIA (5 instances); permanent neurologic deficits followed 4 operations in the TIA group (2.4% incidence). Two operative deaths occurred in the TIA group (1.2% mortality), and 10 deaths occured after operation for a completed stroke (28.6% mortality). Nine of the deaths in the completed stroke group followed operations performed less than 2 weeks after a stroke. A 100% followup was obtained, and the average period of followup was 48 months. Of the patients surviving operation, all in the asymptomatic group were judged functionally normal, 94% of the TIA group were either functionally normal or improved, 76% with a completed stroke were improved, and the patient with a stroke in evolution was unchanged. There were 69 late deaths with heart disease accounting for 58% of the deaths and stroke another 17%.


Infection in war wounds: experience during the 1973 October War in Israel.

The development of infections in 420 wounded soldiers, admitted to the Hadassah University Hospital in Jerusalem between October 7, 1973 and November 31, 1973, was studied. An attempt was made to relate the development of infection to the type of injury. The overall infection rate was 22%, but varied with the type of injury. Three "risk factors" were found to be associated with infection regardless of the number of injuries: 1)penetrating abdominal wounds involving the colon; 2) fractures involving the femur; 3) burns involving more than 25% of body surface. In patients with comparable injuries, the presence of infection was found to prolong the duration of hospitalization. Pseudomonas was the most common single pathogen. There were no cases of myonecrosis (gas gangrene). Of the 8 soliders who died, 5 died with or because of infection.


Operative management of renovascular hypertension.

From 1966 to 1975, 38 patients underwent 42 procedures for renovascular hypertension; 35 operations were aortorenal bypasses and 7 were nephrectomies. Forty-five per cent of the patients were cured, 43% were improved and 12% were unimproved. There were no operative deaths and only three late deaths. Two grafts occluded and 2 became stenotic, giving a graft complication rate of 12%. Curability was best correlated with a short history of hypertension and a pathologic diagnosis of fibromuscular hyperplasia, but not with patient age. Most patients selected for surgery had elevated renal venous renin ratios, and of these 95% were cured or improved. Of those with normal renin ratios, 85% were still cured or improved. Postoperative aortography and peripheral renin measurements offered valuable information in predicting the ultimate response to surgery. Preservation of renal function was a principal indication for surgery in 11 patients. In 8, azotemia was documented preoperatively. Hypertension was cured or improved in every case and 5 patients demonstrated a 10-50% reduction in BUN and creatinine following revascularization.


Mesenteric leaf repair of pelvic defects following exenterative operations.

Perineal enterocutaneous fistula and hernia are unique complications of radical pelvic exenterative operations. A technique for management of these complications is presented. A vascularized segment of small bowel mesentery is interposed as a peritoneum covered pelvic "lid" to separate the abdominal contents from the pelvic defect.


Effect of intravascular cellular aggregate dissolution in postoperative patients.

It was the purpose of this study to confirm whether the increase in packed cell (PC) viscosity that occurs in humans after elective surgery is accompanied by a decrease in total body O2 consumption as previously noted in animals, and further to define the effect of resolution of intravascular cellular aggregates (ICA) on these parameters. Thirty nine patients were studied. Total body O2 consumption was 76% of normal 6 hours postop, 81% of normal 24 hours postop and 87% of normal 48 hours postop. Twenty four hours after operation PC viscosity and increased markedly. Saline infusion had no significant effect on total body O2 consumption or PC viscosity, either pre- or postop, but WB viscosity decreased linearly in proportion in the drop in hematocrit. Resolution of ICA by dextran-40 infusion was associated with return of total body O2 consumption and PC viscosity to normal; a decrease in WB viscosity was disproportionately greater than would have been seen had the decrease been due solely to the drop in hematocrit. It is concluded that in humans surgical trauma causes an increase in PC viscosity and microcirculatory impairment as evidenced by a decrease in total body O2 consumption. Resolution of ICA by dextran-40 infusion reverses that detrimental changes.


Surgical technique for creation of an arteriovenous fistula using a looped bovine graft.

We have used bovine grafts in a looped configuration in the forearn in 150 patients for chronic hemodialysis and have evolved a simple technique for their successful implantation. The critical technical points include: 1) use of large-diameter long grafts (7.0-8.0 mm diameter; 34-40 cm in length); maintenance of the heterograft in a distended and pulsating state throughout the procedure to prevent distortion and twisting; 3) creation of a wide smooth-looped tunnel with Bakes dilators; and 4) anastomosis to the largest avialable antecubital vein. Thirteen cases of late graft occlusion (3-36) months) have been found to be produced by a localized obstructive lesion just distal to the venous anastomosis. These grafts were easily restored to a functional status by thrombectomy and patch graft angioplasty of the stenotic segment. The looped graft technique is not applicable to all patients requiring hemodialysis but it is especially helpful when distal vessels have been obliterated by previous procedures or when home-dialysis is planned. This surgical technique should be among the alternatives considered by surgeons concerned with problems of vascular access in patients with chronic renal failure.


Interstitial irradiation for unresectable carcinoma of the lung.

From 1963 to 1971, 105 patients with histologically proved cancer of the lung were explored at Memorial Hospital and underwent interstitial implantation using encapsulated sources of radon 222 (53 patients) or iodine 125 (52 patients). These lung cancers were considered unresectable because of extension of the disease into the mediastinum with fixation or invasion of the major vessels, trachea, and esophagus or chest wall involvement. No apical lesions, which have a better prognosis, are included in this review. Sixty-nine patients had epidermoid cancer, 24 had adenocarcinoma, and the remaining 12 had various other histological types. All patients were staged according to the criteria proposed by the American Joint Committee using the TNM definitions (standing for tumor, nodes, and metastasis). Local control was obtained in 8 of 10 patients (80% with clinical Stage I and II unresectable cancers of the lung and in 44 of the 95 (46%) with clinical Stage III lung cancer. The two-year survival was 50% for Stages I and II and 7% for Stage III. Five patients have survived for five years or more. The complications, disease-free interval, local recurrences, distant metastases, and survival are presented and indications for this type of therapy outlined.


Primary cancer of the lung. A 42-year experience.

Between April, 1932, and July, 1974, 3,808 patients with primary lung cancer were studied and 1,848 underwent resection. Among untreated patients, 95% were dead with a year. Unresected cancer of the lung is so lethal that efforts to streamline surgical management should not be neglected. In good-risk patients with isolated lesions the approach can be direct. If surgical excision is indicated, regardless of a positive or negative sputum cytology, bronchoscopic biopsy, or brush biopsy, such investigations become superfluous. Needle biopsy is also inconclusive and in addition is hazardous. Preoperative investigation should focus on cardiopulmonary reserve more than on ways to obtain tissue for verification. With the passage of time, the extent of resection has become more conservative. The value of palliative resection is now better appreciated in terms of quality of life, its prolongation, and, for some, a possibility for cure.


The clinical assessment of selected patients with bronchogenic carcinoma.

This paper describes the clinical management of patients with malignant cells in their sputum and a normal chest roentgenogram and those with asymptomatic peripheral pulmonary masses. The source of malignant cells in the sputum of patients with no roentgenographic abnormalities can be localized by tantalum bronchography and fiberoptic bronchoscopy. Peripheral pulmonary masses can be diagnosed preoperatively by needle biopsy or transbronchial fiberoptic bronchoscopy with little morbidity and no mortality. These procedures are not necessary, however, if there is firm clinical and roentgenographic evidence of malignancy. Bronchogenic carcinomas presenting as asymptomatic circumscribed peripheral pulmonary masses have a 25% incidence of occult mediastinal lymph node metastases. In view of this relatively high incidence of metastasis, we think mediastinoscopy should routinely be performed prior to thoracotomy is asymptomatic patients with a peripheral pulmonary mass and no roentgenographic evidence of mediastinal widening.


Mitral insufficiency secondary to coronary heart disease.

Twenty-four patients were operated on for mitral regurgitation secondary to coronary heart disease. Their common features consisted of a history of myocardial infarction, congestive heart failure, coronary occlusive disease, left ventricular dysfunction, low cardiac output, pulmonary hypertension, and increased left ventricular end-diastolic pressure. Fourteen patients were in intractable congestive heart failure at the time of operation. The operative procedures employed consisted of aneurysmectomy in 4 patients; mitral valve replacement (MVR) in 7;MVR and revascularization in 4; MVR and aneurysmectomy in 5;MVR, revascularization, and partial ventricular resection in 3; and MVR with closure of ventricular septal perforation in 1 patient. Six patients died, a hospital mortality of 25%, and only 42% had good results. The degree of associated coronary artery disease and the status of the left ventricular myocardium were the most important prognostic factors.