Metabolism of quaternary carbon compounds: 2,2-dimethylheptane and tertbutylbenzene. Two Achromobacter strains capable of utilizing 2,2-dimethylheptane or tertbutylbenzene as the sole carbon and energy source were isolated from waste-water. Pivalic acid was found in the cultures of Achromobacter A1 containing 2,2-dimethylheptane. From cultures of Achromobacter A2 in the presence of tertbutylbenzene, a diol was isolated and identified as 2,3-dihydro-2,3-dihydroxytertbutylbenzene. Evidence for meta cleavage of the aromatic ring and for accumulation of pivalic acid in the cultures was also obtained. A metabolic pathway for tertbutylbenzene is suggested.


Metabolism of naphthalene by Cunninghamella elegans. Cunninghamella elegans grown on Sabouraud dextrose broth in the presence of naphthalene produced six metabolites. Each product was isolated and identified by conventional chemical techniques. The major metabolites were 1-naphthol (67.9%) and 4-hydroxy-1-tetralone (16.7%). Minor products isolated were 1,4-naphthoquinone (2.8%), 1,2-naphthoquinone (0.2%), 2-naphthol (6.3%), and trans-1,2-dihydroxy-1,2-dihydronaphthalene (5.3%). C. elegans oxidized both 1-naphthol and 1,4-naphthoquinone to 4-hydroxy-1-tetralone. The results suggest that C. elegans oxidizes naphthalene by a sequence of reactions similar to those reported for the mammalian metabolism of this hydrocarbon.


Requirement of heme for growth of Bacteroides fragilis. Heme or protoporphyrin IX was required for growth of Bacteroides fragilis in a defined medium. The amount of heme necessary for half-maximal growth was 2 to 10 ng/ml (3.8 to 15 pmol/ml) among the Bacteroides species and strains tested. The growth rate, metabolic products from glucose fermentation, and cell yields were affected by the concentration of heme in the medium and by the length of time the culture was incubated. When heme was growth limiting (4 ng/ml), growth rates decreased by 50%, cultures started producing lactic and fumaric acids, and the cell yields declined. The cell yield for B. fragilis (ATCC 25285) at 24 h in medium containing 6.5 microgram of heme per ml was 69 g (dry weight) of cells per mol of glucose compared to 16 g (dry weight) of cells per mol of glucose with 4 ng of heme per ml. B. fragilis was unable to grow in defined medium when a porphyrin precursor, delta-aminolevulenic acid or porphobilinogen, was added in place of heme.


Nitrate reduction to nitrite, a possible source of nitrite for growth of nitrite-oxidizing bacteria. Growth yields and other parameters characterizing the kinetics of growth of nitrite-oxidizing bacteria are presented. These parameters were measured during laboratory enrichments of soil samples with added nitrite. They were then used to reanalyze data for nitrite oxidizer growth in a previously reported field study (M. G. Volz, L. W. Belser, M. S. Ardakani, and A. D. McLaren, J. Environ. Qual. 4:179-182, 1975), where nitrate, but not nitrite or ammonium, was added. In that report, analysis of the field data indicated that in unsaturated soils, the reduction of nitrate to nitrite may be a significant source of nitrite for the growth of nitrite oxidizers. A yield of 1.23 x 10(4) cells per mug of N was determined to be most appropriate for application to the field. It was determined that if nitrite came only from mineralized organic nitrogen via ammonium oxidation, 35 to 90% of the organic nitrogen would have had to have been mineralized to produce the growth observed. However, it is estimated that only about 2% of the organic nitrogen could have been mineralized during the growth period. Thus, it appears that another source of nitrite is required, the most likely being the reduction of nitrate to nitrite coupled to the oxidation of organic matter.


Distribution of bacteria with nitrilotriacetate-degrading potential in an estuarine environment. Attempts to isolate estaurine bacteria capable of metabolizing nitrilotriacetate (NTA) as a sole carbon source from areas within Escambia Bay, Fla., were unsuccessful; however, bacteria from freshwater streams and from estaurine surface microlayers were easily adapted to degradation of NTA in freshwater medium. A Pseudomonas sp. strain (ATCC 29600), capable of growth on NTA as a sole carbon source, metabolized NTA at a reduced rate in a saline medium (15%), compared with a freshwater medium (0 to 15%). Microorganisms capable of degrading NTA exist in estuarine surface microlayers and in fresh subsurface waters just before entering the estuary; these data indicate an interference with NTA catabolism by some unknown factors of the estuarine environment rather than an absence of potential NTA-degrading bacteria.


Bile salt degradation by nonfermentative clostridia. Eight strains of nonfermentative clostridia were characterized on the basis of their intracellular nicotine adenine dinucleotide- and nicotinamide adenine dinucleotide phosphate-dependent hydroxysteroid dehydrogenase (HSDH) content, ability to deconjugate taurocholate, growth characteristics, and metabolic products, including utilization of lactate and pyruvate. Two cultures of Clostridium sporosphaeroides (representing one strain obtained from two different sources), one strain of Clostridium irregularis, four strains of an unnamed species (Clostridium group SPH-1), and one strain of an unnamed species (Clostridium group P) were studied. Both cultures of C. sporosphaeroides contained low amounts of 7alpha-HSDH; C. irregularis contained only a low amount of 3alpha-HSDH. All four strains of Clostridium SPH-1 contained both 12alpha- and 7alpha-HSDH in the ratio of approximately 10:1. The strain of Clostridium group P contained only 12alpha-HSDH and was devoid of any other bile salt oxidoreductases. The enzyme preparation from Clostridium group P was useful in spectrophotometric quantitative studies of 12alpha-OH groups. Correlation of bile salt degradative activities with other phenotypic tests for characterization of and differentiation among such organisms is discussed.


Urinary hydroxyproline as a measure in fracture healing. The determination of any pattern in urinary total OH-proline following bone fractures has been the purpose of this investigation. This was carried out in a group of 11 patients with major fractures, a group of 8 patients with minor fractures and a control group of 10 healthy laboratory technicians. Indeed, some patterns could be detected. In patients with major fractures a considerable elevation of urinary total OH-proline was found which was correlated to the size and number of fractures and the healing tendency of the fracture. Normal to only slightly elevated urinary total OH-proline values during the course of the healing process of major fractures could perhaps indicate delayed union, or even malunion. Since fracture healing is usually assessed by X-ray examination and clinical experience, this study could provide a more accurate measure of the healing process of fractures.


The management of secondary neoplastic deposits in long bones by prophylactic internal fixation. Pathological fracture through a secondary neoplastic deposit is a distressing event. Prevention of such a fracture is clearly of considerable benefit. To determine which secondary deposits are liable to fracture the notes and X-rays of 57 patients with 91 secondary deposits were examined. Fractures are unlikely (2.4%) to develop where the deposit involves less than 50% of the cortex as seen on radiological examination, but 2 out of 3 deposits with over 50% involvement will fracture. As the benefits of internal fixation in those that would otherwise fracture are so great, it is recommended that all deposits involving over 50% of the cortex of a long bone should be treated by prophylactic internal fixation. The results of 26 patients treated by prophylactic internal fixation are summarized. Apart from fracture-prevention, the benefits of such internal fixation were found to be: pain relief, simple operation, rapid postoperative recovery, facilitation of administration of radiotherapy and maintenance of the independance of the patient. The possible effects on local and general tumour spread are not considered to be a contraindication to operation.


Automatic stapling devices in gastrointestinal surgery. After a short historical review about the development of automatic stapling devices, information about clinical experiences with the 'Autosuture' instruments is given. On 50 transections with everted suture line and 43 anastomoses produced by means of the TA and GIA instruments, one complication was seen. These stapling devices are an important gain in gastrointestinal surgery.


Multistage scoring system for identifying infants at risk of unexpected death. Obstetric and perinatal records have been assembled on 250 infant deaths and an equal number of live controls including 55 deaths associated with congenital anomalies. The information was used to construct a scoring system to identify high-risk infants at birth. Parents of 115 of the cases and their controls were also interviewed and all hospital, general practitioner, and health service records abstracted. Cases and controls were compared item by item in respect of all information available up to the age of one month and a scoring system constructed for use at one month. The 'at birth' and combined scoring systems are presented. The chance of death by age attained is presented for various risk groups. In a small prospective test, the multistage scoring system was nearly 50% more effective than the birth score alone.


Natural history of childhood asthma. 20-year follow-up. Of 417 asthmatic children seen in hospital from 1941 to 1947, only 208 (50%) were still attending the hospital and were available for long-term follow-up, whereas a 91% follow-up was achieved from a personal follow-up of 267 asthmatic children seen in an East London group practice from 1948 to 1952 and followed for more than 20 years to December 1972. 125 patients (52%) were almost or completely symptom free; 51 (21%) had never had any symptom-free period for longer than 6 months; a further 63 (27%) had a remission of symptoms for 3 years before relapsing. 7 patients died, 3 due to their asthma. The final prognosis was influenced by the severity of the asthma at onset, by breast feeding, by the presence of associated atopic disease, and by a positive family history of atopic disease in first-degree relatives. It was uninfluenced by the age of onset of the asthma, by the sex of the patients, or by skin testing results. Short-term follow-up of such patients will fail to include those patients whose asthma remits and subsequently relapses.


Quality of survival after severe birth asphyxia. Thirty-one children who survived severe birth asphyxia defined by a 1-minute Apgar score of 0, or a 5-minute Apgar score of less than 4, have been seen at age 5 to 10 years for neurological and psychological assessment. Their progress has been compared with that of controls matched for sex, birthweight, gestational age, and social class. 29(93%) of the 31 asphyxiated group and all the controls had no serious neurological or mental handicap. 2 were severely disabled and mentally retarded. Detailed studies of psychological function showed no significant differences between the two groups. 2 apparently stillborn infants have made normal progress. It was not possible to identify any perinatal factor which predicted the occurrence of serious handicap with certainty. We considered that the quality of life enjoyed by the large majority of the survivors was such as to justify a positive approach to the resuscitation of very severely asphyxiated neonates.


Crohn's disease in childhood.

Crohn's disease in childhood. In 32 patients with Crohn's disease which started in childhood, abdominal pain, diarrhoea, and weight loss were the common presenting symptoms, but unexplained fever and failure to grow were also prominent. Stunted growth was the most frequent physical abnormality when first seen in hospital. The mean delay in diagnosis was almost 3 years and the principal contributing factor here was failure to consider the diagnosis and thus perform a barium follow-through examination. The cumulative relapse rate after medical therapy or surgical resection was disappointingly high, but because the median relapse time is much longer for surgically treated patients, surgery is recommended at an early stage, especially in those patients who are growth-retarded or whose education is suffering because of time lost from school.


Hepatic scintigraphy in management of infants and children with liver disease. Scintiscans of liver and spleen using technetium 99m sulphur colloid in 15 infants with extrahepatic biliary atresia and 11 infants with severe obstructive jaundice (7 with genetic deficiency of alpha 1-antitrypsin) showed similar hepatic size, pattern of isotope uptake, and splenic abnormality with no distinguishing features. In 37 older children with a variety of liver disorders, the scan was invaluable in showing filling defects in five instances. Selenomethionine was taken up not only by the two filling defects due to hepatoblastoma but also in a haemangioendothelioma. In the remaining patiens liver scanning confirmed hepatic abnormality and the necessity for more specific invasive diagnostic investigations.


Elimination of pethidine and bupivacaine in the newborn. Pethidine or an epidural injection of bupivacaine are common forms of obstetric analgesia in Britain. Bupivacaine has been thought to have little effect on the fetus, but neurobehavioural studies have cast doubt on this. We therefore investigated the elimination of these drugs by babies in similar population groups. Bupivacaine was largely eliminated in just over one day, while pethidine required between 2 and 6 days. This could account for the persisting depression in babies whose mothers had received pethidine.


Calcified pituitary concretions in the newborn. Anterior pituitary glands from 200 fetuses and infants ranging in age from 22 weeks' gestation to one year of life were examined histologically for the presence of concretions. Characteristically these are round, lamellated bodies, often strongly basophilic, containing phosphates and measuring between 10 micrometer and 70 micrometer in diameter. They decreased in incidence postnatally and were rarely seen 6 months after birth. It is suggested that these concretions are a degenerative change in cells subject to the vigorous secretory activity that is part of the normal physiology of the anterior lobe of the pituitary from mid-gestation.


Hereditary coproporphyria and epilepsy.

Hereditary coproporphyria and epilepsy. A 9-year-old boy with mental deterioration and epilepsy suffered an acute attack of hereditary coproporphyria associated with worsening of seizure control. Leucocyte coproporphyrinogen oxidase activity was undetectable in the patient during this attack, and was reduced in his mother, a latent case. The complex relationship between porphyria, epilepsy, and anticonvulsant drugs is discussed.


Psychiatric disturbance, urgency, and bacteriuria in children with day and night wetting. Forty children with day and night wetting were compared with 46 with night wetting only to see if day wetting was then associated with particular clinical features. Interviews with mothers, questionnaries completed by teachers, physical investigations, and measurement of functional bladder capacities were used. Day wetting combined with bed wetting occurred equally in boys and girls and was associated with daytime urgency and greater frequency of psychiatric disturbance. In boys, soiling was also associated. In girls, bacteriuria, which appeared to be caused by the day wetting, occurred in about 50%. Neither daytime frequency nor small functional bladder capacity were specifically related to day wetting.


Cystinotic rickets treated with vitamin D metabolites. A 22-month-old girl with cystinotic rickets was given 1 microgram 1,25-dihydroxycholecalciferol (1,25-DHCC) daily in addition to standard treatment. Her rickets healed and linear growth rate appeared to increase. It is suggested that the effect of 1,25-DHCC and its metabolically active analogues on cystinotic rickets should be further studied.


Short stature with pigmentation.

Short stature with pigmentation. Four hypomelic children of abnormally short stature had slight intellectual defect, melanotic skin, and some facial features in common. 3 were followed to the age of 23-26 years, and they remained small and pigmented.


Serum complement depression during viral lower respiratory tract illness in cystic fibrosis. Cystic fibrosis (CF) patients with viral lower respiratory tract illnesses (LRI) had depressed levels of the third and fourth components of complement, which returned to normal after recovery. There was no clinical evidence of immune complex disease. CF patients with LRI and no virus isolates, CF patients in stable status, and non-CF patients with LRI did not have complement depression. It is postulated that antigen-antibody complex activation of complement may occur in CF patients with viral LRI.


Urinary continence in open myelomeningocele. In a consecutive series of 200 neonates having undergone surgery for open myelomeningocele, 24 of the 106 survivors at 10 to 12 years of age proved to be continent of urine. These figures included 11 children who had considerable neurological involvement. 4 children did not acquire urinary control until after the age of 5 years. Therefore, we consider early urinary diversion in children with myelomeningocele, even in the presence of neurological deficit, to be indicated only for the prevention of progressive deterioration in renal function. Incontinence of urine itself is not an indication for urinary diversion in the first decade of life.


Diagnostic value of a psychological test in cases of suspected child abuse. The use of the Bene-Anthony Family Relations Test is described and illustrated by three examples of child abuse. This test should be considered in the investigation of definite or suspected cases of abuse and as part of the preparation of court evidence.


Anorectal myectomy in treatment of ultrashort segment Hirschsprung's disease. Report of 26 cases. A diagnosis of Hirschsprung's disease should be considered in children with constipation. An accurate neonatal history of bowel function and testing of anorectal pressure responses will aid the diagnosis. In the period 1971-75 inclusive, 140 children, aged 6 months to 14 years, were investigated by anorectal manometry. 26 showed a failed inhibition response to rectal dilatation, suggesting Hirschsprung's disease and were treated by anorectal myectomy. In 24 the disease was confirmed histologically. Two specimens were diagnostically unsuitable. 4 required repeat myectomies, and 3 anterior resection. At follow-up all had normal bowel movements without soiling.


Giant cell arteritis with gangrene in a child. After an episode of abacterial meningitis in a 5-year-old boy there developed splenomegaly, uveitis, and a granulomatous arteritis of the lower limbs requiring amputation of one leg. Immune complexes persist in the blood, but the precise antigenic stimulus remains conjectural.


Assessment of gestational age in twins.

Assessment of gestational age in twins. Pairs of twins born concordant for weight score equally on both neurological and external criteria. The assessed gestational age of discordant twins is significantly different; while scoring equally on neurological criteria, the lighter twin scores less on external criteria. It is suggested that this pattern of underscoring may also be present in growth retarded singletons. If external criteria are used in estimating the gestational age of growth retarded infants, the results should be interpreted with caution.


Poliomyelitis-like illness after acute asthma. Two children had pain in one arm, followed by weakness and wasting, after an acute exacerbation of bronchial asthma. Similar cases in which a poliomyelitis-like illness was associated with acute asthma have been reported, but the relationship between the two remains conjectural.


Anaerobic infection in a neonate. Early detection by gas liquid chromatography and response to metronidazole. A case of presumptive anaerobic infection in a neonate is described to illustrate the use of gas-liquid chromatography in the early detection of these potentially serious pathogens. Metronidazole is suggested as a possibly useful antimicrobial agent in these infections.


Thickness and distribution of human femoral head articular cartilage. Changes with age. The distribution of hyaline cartilage in the sagittal plane of the normal human femoral head was examined. 28 specimens from persons aged 10 to 68 years subject to post-mortem examination in a teaching hospital were anatomically orientated and x-rayed in a lateromedial projection. An optical technique was used to measure the cartilage thickness from the x-ray films thus produced. Measurements were made with a sensitivity of +/- 0-01 mm using a metrological projector. 11 defined sites on each femoral head were surveyed to give the distribution of cartilage thickness. The greatest thickness was identified anterior to the zenith. Between the ages of 20 and 45 years the thickness of this zone increased with age. The thickness of femoral head cartilage was not evidently related to femoral head diameter, femur length, or body weight.


Chronic synovitis with early cartilage destruction in sickle cell disease. Two patients with sickle cell disease presented with joint pain and early x-ray evidence of articular cartilage loss. Both later developed increasingly destructive arthritis with chronic synovitis identified in synovial biopsies. One patient developed demonstrable aseptic necrosis. Destructive arthropathy is much less common than the frequent transient effusions in sickle cell disease.


Serum uric acid in England and Scotland. Serum uric acid (SUA) was measured in 512 men and 254 women from two English regions and in 337 men from one Scottish region. Mean SUA levels were the same in the men (5-5 mg/100 ml) and similar in the women (3-9 and 4-1 mg/100 ml). The apparent rarity of gout in Scotsmen cannot be explained by regional differences in SUA levels or in the prevalence of hyperuricaemia (defined as SUA of 7-0 mg/100 ml or over) which was present in 6-6% of the English men and 8% of the Scots. SUA was positively correlated with weight and serum urea, and with age in women, but no variation was found with social class. Body weight was the most important predictor of SUA in both men and women and superior to measurements involving correction for height, such as ponderal index and calculated lean body mass.


Ulceration of the cornea in rheumatoid arthritis. Five patients with melting of the cornea in association with rheumatoid arthritis are described. The arthritis was often inactive and without systemic manifestations, in contrast to that seen in association with scleritis. In 3 there was evidence of reduced tear formation, but in none was tear production absent. In 3 patients the lesions healed during treatment with azathioprine or penicillamine.


Cellular immunity in systemic lupus erythematosus as evidenced in vitro by leucocyte migration inhibition tests. A leucocyte migration inhibition test was performed on 26 patients with systemic lupus erythematosus (SLE) and on 35 control subjects using three different antigens, fetal calf thymus DNA, baker's yeast RNA, and calf thymus extractable nuclear antigen (ENA). Leucocyte migration was inhibited by DNA in 17 out of 26 SLE patients (65-3%), and in only 2 of the 35 controls (5-7%). When RNA or ENA was added none of the patients or controls showed inhibition. In SLE patients migration inhibition by DNA was significantly correlated with the presence of proteinuria and/or granular casts in urinary sediment. When the migration inhibition test was positive, immunofluorescence verified active histology of the glomeruli obtained by a percutaneous renal biopsy.


Frequency and clinical significance of antibodies to ribonucleoprotein in SLE and other connective tissue disease subgroups. Antibodies to the ribonucleoprotein (RNP) component of extractable nuclear antigen were measured in patients with systemic lupus erythematosus (SLE) and other connective tissue subgroups by counterimmunoelectrophoresis. Antibodies to RNP were found in the sera of 32% of patients with a primary diagnosis of SLE, 29% of patients with features of SLE and erosive joint disease, none of 9 scleroderma patients, and in 75% of 8 patients with features of SLE and scleroderma. In the SLE patients overall there was an increased frequency of sclerodactyly and severe Raynaud's phenomenon in the patients with antibodies to RNP but no association of antibodies to RNP was found with the presence of erosive joint disease, Sjögren's syndrome, or the absence of renal disease in these patients.


Xeroradiography in assessment of the rheumatoid hand. Comparable conventional x-rays had xeroradiographs were obtained of the hands of 22 patients with rheumatoid arthritis. Each metacarpophalangeal and proximal interphalangeal joint was scored for juxta-articular osteoporosis, erosions, loss of joint space, soft tissue thickening, joint deformity, and osteophytes on a 0-3 scale. For 10 hands the films were reported again after 3 months, and each technique was reproducible. Comparison between the 2 radiographic techniques showed that overall they gave similar results, although osteoporosis was reported more frequently on conventional x-rays, and loss of joint space and synovial thickening on xeroradiographs.


Effect of penicillamine on complement in vitro and in vivo. In most normal human sera the addition of penicillamine to a final concentration of 0-2 mmol/l and subsequent dialysis caused a slight reduction in serum haemolytic complement (CH50). At 200 mmol/l, CH50 activity was no longer demonstrable. Even high concentrations of penicillamine were needed to inhibit the ability of immunoglobulin to fix complement to preformed or forming immune complexes. This indicated that the reduction of CH50 observed in serum was due to an effect on the complement factors. In vivo, a dose of 240 mg penicillamine caused a slight transient reduction in CH50 in rabbit serum, while 1000 mg penicillamine had no effect on serum CH50 in patients with rheumatoid arthritis. In arthritis patients there was, however, some evidence for removal of complement deposits in synovial tissue during penicillamine treatment. Since it is theoretically possible that concentrations high enough to cause reduction of complement activity can be achieved locally in synovial tissue, the effect on complement may be one of the mechanisms by which penicillamine exerts its effect in rheumatoid arthritis.


Significance of rubella virus infection in juvenile chronic polyarthritis. Fifty-three patients under the age of 5 years with definite juvenile chronic polyarthritis (JCP) were examined for serological evidence of rubella infection. The prevalence of rubella antibody was found to be low and did not differ significantly from that found in normal children of similar age. Patients with JCP and antibody to rubella virus had a clinical course indistinguishable from those with no detectable rubella antibody.


Transferrin iron uptake by human synovium. 55Fe-labelled transferrin was injected into the synovial fluid before synovectomy in 6 patients with rheumatoid arthritis. The results show that transferrin iron is taken up by synovial macrophages.


Bacteroides bacteremia.

Bacteroides bacteremia. When appropriate culture techniques are employed, Bacteroides bacteremia is found more frequently than might be expected and usually follows contamination from the gastrointestinal or genitourinary tracts. Survival is closely related to the extent of organ impiarment preceding the bacteremia. Proper therapy is based on early recognition of the source of bacteremia and adequate surgical drainage. Antibiotics do not appear to improve survival, particularly when used without drainage. Further studies are needed to identify patients with impaired host resistance who are particularly susceptible to these organisms.


Fat induced jejunal inhibition of gastric acid secretion in duodenal ulcer patients before and after truncal vagotomy. The effect of intrajejunal infusion of a fat solution on pentagastrin-stimulated (0.5 microgram/kg-hr) gastric acid secretion was studied in five duodenal ulcer patients before and three to five months after truncal vagotomy. Preoperatively mean acid output was reduced from 41 +/- 5.2 meq H+/hr to 15.4 +/- 1.3 meq H+/hr (p less than 0.005), and postoperatively from 17.4 +/- 2.6 meq H+/hr to 12.7 +/- 2.4 meq H+/HR (P less than 0.01), demonstrating that fat induced jejunal inhibition of gastric acid secretion partly or wholly is humorally mediated. Furthermore the study shows that fat induced jejunal inhibition of acid secretion in duodenal ulcer patients seem to be of the same magnitude as previously found in healthy subjects.


Left ventriculotomy for closure of muscular ventricular septal defects. Treatment of choice. Closure of muscular ventricular septal defects (VSDs) through the right atriotomy or right ventriculotomy may be difficult. These VSDs are often located behind the hypertrophied trabeculae carnae or papillary muscle. Residual or recurrent VSD may result from the difficult approach. Between March 1971 and December 1975, we have used the left ventriculotomy near the apex for closure of muscular VSDs in ten children. The patients' ages ranged from five months to eight years and three months. The diagnosis was established by cardiac catheterisation and left ventricular angiocardiogram in all patients. Six patients had multiple VSDs; in four patients VSD in the muscular septum was present (three apical, one midseptal). Operations were performed on cardiopulmonary bypass with moderate hypothermia and intermittent anoxic arrest. VSDs in the membranous septum were closed through the right atrium. Muscular VSDs were approached through a small vertical incision in the left ventricle near the apex. The postoperative course was uneventful in eight patients. Two patients, aged 16 months and eight years, died; histology showed grade IV pulmonary vascular disease in both. All survivors are well four months to five years after the operation, without clinical evidence of residual or recurrent VSD.


Follow-up studies of radical resection for pancreaticoduodenal cancer. In a study of 66 patients with pancreaticoduodenal cancer with pancreaticoduodenectomy, there were five (7.5%) hospital deaths. Five-year survival rates were 7.8% in 20 patients with carcinoma of the head of the pancreas, 16.7% in 31 patients with carcinoma of the bile duct, and 38.5% in 15 patients with carcinoma of the ampulla of Vater. Fecal fat loss measured was 10 g or less per day in nine of 12 patients. Of the 19 patients having glucose tolerance tests, 13 showed abnormalities including the two who were diabetic. Operative findings which were indicative of a poor prognosis included lymph node metastases, macroscopic invasion of the tumor into the pancreatic capsule in patients with carcinoma of the head of the pancreas, the size of the tumor in those with carcinoma of the common bile duct, and direct invasion of the lesion into the pancreas in patients with carcinoma of the ampulla of Vater.


Sclerosing cholangitis and primary biliary cirrhosis--a disease spectrum? Sclerosing diseases of the biliary system encompass a spectrum ranging from primary sclerosing cholangitis (usually of the extrahepatic biliary tree) to primary biliary cirrhosis of the intrahepatic bile canaliculi. In a study of 35 patients with primary intra- and extrahepatic biliary sclerosis, age of onset, sex distribution, symptomatology, associated diseases, radiographic abnormalities and chemical profile were considered. The difficulty of differentiating sclerosing cholangitis and biliary cirrhosis from other causes of obstructive jaundice preoperatively was stressed, in addition to points of differential clinical and laboratory findings. The etiology of these entities as well as the possibility that they represent variant clinical manifestations of the same disease process were also considered. Mechanical and pharmacological treatment alternatives that were attempted included drainage procedures, the easiest and most widely used of which was the T-tube. However, this could prove to be a source of infection and should therefore be removed early, inasmuch as cholangitis represents a major cause of morbidity. Steroids have been used with varying effectiveness; subjective improvement was generally attained, although objective improvement has been difficult to document. When choleuretics and cholestyramine were administered, we noted significant palliation. Antibiotics were reserved for treatment of cholangitis. Until the underlying etiology of this rare malignant sclerosing process is found, only symptomatic treatment can be offered.


Thin needle cholangiography: experience with 50 patients. Thin needle cholangiography (TNC) was performed in 50 patients with obstructive jaundice or jaundice of obscure origin. The purpose of this study was to assess the diagnostic accuracy and safety of this procedure. TNC was performed by the technique described by Redeker et al. using the Chiba needle (JAMA 231:386, 1975). Obstructed ducts were successfully demonstrated in 100% of cases (29/29). Non-obstructed ducts were opacified in 12/21 (57%). Overall success was 82% (41/50). Two septic complications occurred. It is concluded that 1) TNC is a highly reliable, easy to perform and safe procedure in the evaluation of the jaundiced patient; 2) Accurate demonstration of the biliary anatomy by TNC provided important information which often in (10/50 = 20%) led to a change in diagnosis, avoidance of unnecessary procedures, and shortening of hospitalization; 3) Failure to visualize patients with non-dilated biliary ducts occurred with advanced chronic liver disease or fatty liver.


Uneven ventilation of the lung following trauma. Ventilatory function of the lungs has been studied in 13 post-trauma patients using a two compartment analysis. The analysis is based upon a model of the lung which describes a nitrogen washout curve in terms of fast and slowly ventilated compartments. Data output from a digital computer provides values that compare the fractions of the alveolar ventilation and volume of the two compartments. All patients on initial investigation had large identifiable slow spaces. Subsequent evaluation at a time of clinical improvement showed that the ventilation of the slow space had increased significantly (P less than .003), whereas no change was evident in the volume fraction. The ventilation to volume ratio of the slow space, measured on these two separate occasions increased in twelve of the patients studied. An increase in this ratio correlated with improvement in the patient's clinical condition.


Metastatic carcinomas from occult primary tumors. A study of 254 patients. From 1950 to 1973, 254 patients with metastatic cancers from occult primary tumors, comprising 0.5% of all the referred cancer patients were seen. The average age was 59 years. Clinical presentation was commonly in the form of metastatic lesions in lung, cervical lymph node, bone or liver. Radiological and radioisotopic investigations proved helpful in determining the extent of disease rather than the origin of primary tumor. Adenocarcinoma was the commonest type, followed by undifferentiated and squamous cell carcinomas. The origin of the primary tumor was established in 77 (30%) patients, mostly at autopsy. It was in the lung in 40% of the cases, followed by stomach, pancreas, kidney, ovary and colon. Some correlation was found between clinical presentation and the origin of the primary tumor. Histologically different second cancers were detected in 28 (11%) patients. Overall median and five-year survival rates were nine months and nine per cent respectively. Longer survival was seen in patients with squamous cell carcinoma metastases, middle and upper neck lymph node lesions, and those who had "curative" surgery. In localized metastatic lesions, surgical extirpation should be done. Depending on the histological type of the metastatic lesions, chemotherapy and/or radiation therapy have definite roles in the management of these patients. Periodic follow-up examinations also prove valuable.


Prognostic factors in patients undergoing lymphadenectomy for malignant melanoma. Review of a 19 year experience in melanoma patients undergoinglymphadenectomy at the National Cancer Institute revealedthat the preoperative assessment of the status of theregional lymph nodes was accurate 91% of the time when thesurgeon felt the nodes were clinically positive, and accurate79% of the time when the nodes were judged clinically negative. The 10-year survival in patients with one to three histologicallypositive nodes or no positive nodes was 50-55%, compared to a25% 8-year survival in patients with four or more histologicallypositive nodes. Stepwise multivariate evaluation of prognosticfactors indicated that the most important factor for predictingprognosis is the number of nodes histologically involved. Nodepalpability was the second most important factor because of itshigh correlation with number of nodes histologically involved. Site of melanoma was the third most important factor, aspatients with extremity (upper or lower) melanoma had a bettersurvival (P = 0.002) than patients with axial melanoma (trunkor head and neck). Five years following lymphadenectomythere appeared to be substantial differences in survivalaccording to differences in the level of invasion of the primarylesion, however, these differences were not nearly aspronounced 10 years following node dissection.B The division of melanoma thicknesses into <1.50 mm and>1.50 mm provided some prognostic discrimination at fiveyears but again the differences were not pronounced 10 yearsfollowing node dissection. The thickness measurements wereeasier to determine than the level of invasion, and more reproduceableon resubmission to the same pathologist. Fourpatients with melanoma less than 0.76 mm had subsequentmetastases, but these may represent inadequate sampling of theprimary melanoma both in our series and in the four similarpatients previously reported with such thin metastasizingmelanomas.


Arterio-venous access utilizing modified bovine arterial grafts for hemodialysis. Forty-seven patients with chronic renal failure presenting with a loss of vascular access precluding hemodialysis were subjected to 105 surgical procedures to establish and to maintain an arteriovenous fistulae. 67 bovine heterografts were implanted over a 30 month period and observed for 6 or more months. Fifteen, or 32% of the patients, died during the study period. Eleven patients died with a functional fistula. Twenty fistulae continued to function at the end of 36 months constituting a 46.3% graft survival rate. Hemodialysis was continued in 11 of 12 patients via a P.T.F.E. Goretex graft or via a matured Brescia Fistula. The remaining patient experienced graft failure at the end of the study period. Graft thrombosis was observed in 31 of 67 grafts placed (46%). Successful thrombectomy was achieved in 52%. Fourteen grafts developed frank aneurysms with overt rupture in 8. All patients with aneurysms were negro. Six of 8 patients with aneurysm presented with severe hypertension. Thirteen aneurysms were resected without loss of life or limb. The use of bovine grafts in hypertensive negro patients is believed to be contraindicated.


Preservation of the ischemic leg by distal vascular bypass. Autogenous saphenous vein bypass grafts to tibial or personeal vessels have resulted in successful, long-term limb preservation in appropriately selected patients. This success appears to justify an aggressive approach to what has previously been considered end-stage" distal vascular occlusive disease. This report describes the clinical management and long-term follow-up of 41 patients with tibial artery reconstruction.


Multiple subcritical arterial stenoses: effect on poststenotic pressure and flow. Diminished poststenotic pressure and flow accompanied experimental application of multiple subcritical arterial stenoses in series. Effects of additional stenoses, causing equivalent constrictions, were cumulative in a nonlinear fashion. Seven-hundred-twenty measurements were performed using 10 cm ileofemoral canine arterial segments in vitro and in vivo with pulsatile and nonpulsatile blood flow. Pressures and flow volumes utilized for testing were within normal physiologic ranges. Data analysis included correlations of experimental observations with predictions generated from a theoretic hydraulic model. Kinetic energy losses with multiple subcritical stenoses were associated with decreased pressure and flow. Poststenotic pressure decreased as much as 51% in some experiments. Diminutions in flow paralleled pressure changes. Measured pressure changes were nonlinear and followed mathematic predictions of appreciable but lesser effects of added stenoses. Hemodynamic alterations of magnitudes documented in this study assume clinical importance. The assumption that a solitary critical stenosis must exist before significant hemodynamic changes occur is no longer tenable.


The nature of immunity against Babesia hylomysci and B. microti infections in mice. Mice which have recovered from Babesia microti infection lose their parasitaemia as soon as three weeks after recovery and become solidly immune. This sterile immunity is not affected by splenectomy and may last for the life of the mouse. Mice which have recovered from B. hylomysci infection continue to harbour parasites at a subpatent level and spontaneous relapses were common after recovery. Hence the type of immunity which developed against this parasite is premunition and may last for life. Such immunity was not absolute and considerable parasitaemias developed after challenge. Cross-protection occurred between the two species of parasite.


Study on trypanosomes of Sciuridae from Senegal: Trypanosoma (Megatrypanum) heliosciuri sp. n. and Trypanosoma (Herpetosoma) xeri Leger and Baury, 1922. This paper describes a new species of trypanosome, Trypanosoma (Megatrypanum) heliosciuri, from Heliosciurus gambianus gambianus, and gives a detailed description of T. (Herpetosoma) xeri Leger and Baury 1922, from Euxerus erythropus erythropus, all from Senegal, West Africa.


Cutaneous leishmaniasis in the Libyan Arab Republic: preliminary ecological findings. Preliminary results show cutaneous leishmaniasis in Libya to be, sometimes at least, a rural zoonotic infection. The parasites are transmitted, probably by Phlebotomus papatasi, between the rodents Psammomys obesus and Meriones libycus. The banks and 'islands' in the main channel of seasonal wadis provide the right combination of vegetation and permanence for the maintenance of an intense focus.


The resistance of intracellular Leishmania parasites to digestion by lysosomal enzymes. Infections of Leishmania mexicana in cultured normal mouse peritoneal macrophages show different morphological features depending on whether the parasites invade as promastigote or amastigote forms. Infections derived from promastigote invasion are characterized by parasitophorous vacuoles which develop slowly, and acquire only modest proportions. In contrast, the organisms in amastigote-derived infections lie within parasitophorous vacuoles which develop more rapidly, and attain a much greater size. From observation of promastigotes of different species of Leishmania, it appeared that survival subsequent to endocytosis by normal macrophages depends on the parasites' rapid transformation to the amastigote form. Activation of the macrophage population produced an enhanced parasiticidal effect only against incompletely transformed Leishmania promastigotes. Electron microscope investigations, involving enzyme histochemistry and lysosome labelling techniques, indicate that intracellular Leishmania avoid digestion by interfering with the activity of lysosomal enzymes that are freely delivered to the parasitophorous vacuole. It is proposed that this ability is acquired on transformation to the amastigote, and incidentally induces fluid distension of the parasitophorous vacuole through phenomena recently described by other workers.


The inheritance of a mutant yellow larva in the mosquito Aedes togoi. In the mosquito Aedes (Finlaya) togoi (Theobald), which usually breeds in seawater in tidal pools and is a natural or experimental vector of various species of filariae, the mode of inheritance of a new mutant yellow larva (y) was investigated; the y allele is recessive and inherited independently of sex and its linked alleles, and independently of ruby eye (ru) and pigmented pupae (p), both of which are not sex-linked; therefore y is presumed to be on the third linkage group in this species. The allele y is completely penetrant with little variation in its expressivity, but its phenotype could not be reliably distinguished from that of sex-linked allele straw-coloured larva (s).


Susceptibility to Brugia pahangi of geographical strains of Culex pipiens fatigans. Five strains of Culex pipiens fatigans from Kuala Lumpur, Tanga, Bobo Dioulasso, Ibadan and Maracay were tested for susceptibility to Brugia pahangi. The mosquitoes were membrane-fed on infected blood in which the parasite density ranged from 1-3 to 20-4 mff/mm(3). The susceptibility rates were low, and were not directly related to the parasitaemia. If the susceptible individuals represent homozygotes for the gene sb (the gene controlling susceptibility to B pahangi in C. pipiens), the gene frequencies in the five strains were 0-33, 0-23, 0-28, 0-12 and 0-31 respectively.


The fate of ingested Brugia pahangi microfilariae in susceptible and refractory strains of Culex pipiens and Aedes aegypti. The uptake and migration of microfilariae of Brugia pahangi in susceptible and refractory Culex pipiens and Aedes aegypti were compared after membrane-feeding the mosquitoes on infected blood and anti-coagulant. There was no difference between the strains within each species in the pattern of migration, but in C pipiens only 24% of the microfilariae reached the thorax whereas in A. aegypti 73-6% were successful. In both susceptible strains the filariae in the thorax developed normally to maturity, but in both refractory strains almost all filariae died within a few days.


Mode of inheritance of dieldrin resistance in Anopheles farauti No. 1 and A. farauti No. 2. The mode of inheritance of dieldrin resistance was studied in Anopheles farauti No. 1 and A. farauti No. 2. In both these species a susceptible strain was crossed with a resistant strain and F1 individuals backcrossed to the susceptible parental strain. After exposure to 0-4% dieldrin for one hour the survivors were again backcrossed to the susceptible. After successive backcrosses it was found that in both species dieldrin resistance was determinded by a single, semi-dominant gene which was not sex-linked.


Actuarial analysis of surgical results: rationale and method. The use of time-related methods of statistical analysis is essential for valid evaluation of the long-term results of a surgical procedure. Accurate comparison of two procedures or two prosthetic devices is possible only when the length of follow-up is properly accounted for. The purpose of this report is to make the technical aspects of the acturial, or life table, method easily accessible to the surgeon, with emphasis on the motivation for and the rationale behind it. This topic is illustrated in terms of heart valve prostheses, a field that is rapidly developing. Both the authors and readers of articles must be aware that controversies surrounding the relative merits of various prosthetic designs or operative procedures can be settled only if proper time-related methods of analysis are utilized.


Valve replacement in patients over 70 years. From July, 1972, to April, 1976, 54 consecutive patients over the age of 70 years underwent valve replacement at Tampa General Hospital. Twenty-one patients had isolated aortic valve replacement (Group 1), 14 had isolated mitral valve replacement (Group 2), and 19 had combined procedures that included at least 1 valve replacement (Group 3). There was 1 operative death (in Group 1), and another patient (Group 3) died three weeks post-operatively, resulting in an early mortality of 3.7%. Follow-up of the 52 hospital survivors from one to forty-one months reveals 2 additional deaths for a late mortality of 3.8%. Cardiac status improved noticeably in the surviving 50 patients. The data suggests that with current techniques, complex intracardiac procedures can be performed safely with acceptable operative mortality and a satisfactory prognostic outlook in elderly patients.


Successful course after supraarterial myotomy for myocardial bridging and milking effect of the left anterior descending artery. We report 3 patients having a grade II milking effect of the proximal left anterior descending artery (LAD) and suffering from angina. Preoperative myocardial ischemia was demonstrated by stress ECG in all 3 and by pacing and lactates studies in 2. Surgical decompression of the systolically constricted artery has resulted in disappearance of angina, milking, and ischemia. Severe milking of the LAD is a rare entity, probably congenital in origin, capable of producing myocardial ischemia and possibly causing sudden death. More studies regarding its etiology and pathophysiology are necessary. Biopsy of the myocardium surrounding the artery could be useful.


Intraoperative Doppler coronary artery finder. Time-consuming difficulty is occasionally encountered in finding coronary arteries or previously placed vascular grafts during coronary revascularization procedures. A catheter-tipped, continuous-wave Doppler ultrasonic probe with simple audio output has been shown to be capable of expediting the search for these vessels.


Hiatus hernia and the respiratory tract. Hoarseness, asthma, and bronchitis are common but sometimes obscure manifestations of gastroesophageal reflux, the etiology of when respiratory symptoms predominate. In 300 consecutive patients who underwent surgical correction for gastroesophageal reflux, 129 (43%) had major respiratory complaints. Group 1 patients (82, 64%) were those referred for respiratory problems alone. In Group 2 (patients referred because of peptic complaints), 47 had associated respiratory problems in various combinations, including an additional 10 patients who had bronchiectasis. Treatment with appropriate surgical resection, in addition to antireflux procedures, was carried out in these people. Noticeable relief of respiratory symptoms was obtained in 96 (74%) of the 129 patients; 30 were improved and 2 were unchanged. Recurrent hiatus hernia or esophagitis was documented in 21 (7%) of the 300 patients.


The clinical and physiological effect of whole-lung lavage in pulmonary alveolar proteinosis: a ten-year experience. We have utilized whole-lung lavage in the successful treatment of 18 patients with pulmonary alveolar proteinosis. Our ten-year experience includes serial evaluations of patients with disabling lung dysfunction who had a total of 49 whole-lung lavages under general anesthesia. Clinical and physiological responses were documented both before and after each lavage. There were no complications or deaths. All patients were radiographically, physiologically, and symptomatically improved within hours after the procedures. Five patients required from two to four repeat lavages one to three years later. The treatment of this disorder has included a wide variety of techniques. We attribute our results to the use of a lung lavage technique that includes: (1) unilateral whole-lung lavages at two to three day intervals; (2) isotonic saline as the lavage solution; (3) use of a mechanical chest percussor during lavage; and (4) measuring the total thoracic compliance of each side in the immediate postlavage period as a guide for extubation. We conclude that whole-lung lavage is a safe, highly effective, repetitively applicable treatment for pulmonary alveolar proteinosis.


False-positive cytological diagnosis of lung carcinoma in patients with pulmonary infarcts. Cytological examination of specimens obtained from the tracheobronchial tree has become an integral part of the evaluation of pulmonary lesions. Cytological criteria for the diagnosis of carcinoma exist and are well defined. Certain benign processes, however, may possess features strongly suggestive of carcinoma of the lung. We report 3 patients in whom a positive cytological diagnosis of carcinoma of the lung was made by an experienced cytopathologist. At operation each patient was found to have pulmonary infarct and no evidence of carcinoma. Review of this experience has disclosed cytological and clinical features that should alert the clinician to the possibility that the cytological diagnosis of lung cancer may be misleading in certain nonmalignant diseases.


Bronchobiliary and bronchopleural fistulas. In the course of treating approximately 2,000 patients with postoperative stricture of the bile duct, 16 bronchopleural and bronchobiliary fistulas were encountered. Three patients have been seen in the past year. This has prompted a review of our experience since it was previously recorded in 1955. Fistulous complications of obstructive biliary tract disease take three forms: (1) massive fulminating biliary empyema; (2) acute necrotizing bile bronchiolitis and pneumonia when pleural symphysis exists; and (3) a more indolent, chronic, recurring form of bronchobiliary communication. We have learned that transdiaphragmatic perforation occurs at a certain characteristic location in the diaphragm. An understanding of the pathological anatomy and pathogenesis has provided a specific and sequential mode of surgical treatment. When this has been adhered to strictly, cure has resulted.


Internal mammary artery cannulation.

Internal mammary artery cannulation. A technique of internal mammary  artery cannulation is described. This approach offers a safe method for arterial monitoring in infants undergoing thoracotomy for palliative cardiac procedures.


[3-dimension vectorcardiography. Preliminary study]. The authors study individuals in which the amplified electrical signal is fed into an analogic-digital converter in which the memory is stored in a mini-computer which at the same time feeds into two digital-analogic converters to obtain the reading. They conclude that the treatment of this curve in space is useful in the diagnosis of some heart diseases if some parameters such as acceleration and torsion are studied.


[Cardiac neurosis. Study of 100 cases with a healthy heart]. One-hundred records taken at chance from the archives of the Instituto Nacional de Cardiología de México, with the diagnosis of healthy heart, were studied. The following factors of these patients were analyzed: age, sex, civil status, socio-economic level, occupation, family antecedents, personal antecedents, smoking, alcoholism, presence of cardiac murmurs, arrhythmias, and electrocardiogram. In 80 of these patients there existed a clear neurotic alteration. The main symptoms which they suffered were: dyspnea, pain, palpitations, dizziness, and headaches. We found that the influence of the medical environment and living with cardiac patients in a neurotic individual were predisposing factors of a cardiac neurosis. In many cases the physician is responsable if he hesitates or does not advice properly. It can be concluded that it is necessary to establish a rehabilitation program for these patients since the illness is serious and invalidating and very frecuent, with repercussions at the familiar, social, and economic levels.


[The process of ventricular repolarization. I. Experimental study]. The sequence of ventricular repolarization process is studied in 25 dogs, using unipolar epicardial leads and some distant bipolar leads. It is concluded: 1. The sequence of ventricular repolarization process is from the base to the apex of the heart. 2. Its sense is independent from the activation process. 3. It is demonstrated the nature of the intrinsec deflection of the repolarization process. 4. The duration of the electrical systole is greater in the myocardial fibers of the right ventricle than in the fibers of the left ventricle. 5. The duration of the electrical systole is constant in the myocardial fibers of a blocked ventricle, but is delayed in the same proportion of the activation process. 6. The significance of the biphasic T wave is discussed, in the presence of bundle branch block. 7. Some bases are withdrown for the deductive interpretation of the T wave based upon the ventricular repolarization process.


[Value of the PLE and Q-PV in the diagnosis of atrioventricular disorders]. The values of the PLE and the Q-PV in the diagnosis of atrioventricular discordances are studied. In 9 patients precordiograms were registered in both ventricles and in 5 the intraventricular pressure curve was obtained by right or atrial retrograde catheterization. Statistical calculations were made in order to learn the similarities and limitations between the two different methods. In all of the cases the PLE of the anatomic left ventricle was less than in the right ventricle. The same was observed in the Q-PV intervals of both ventricles. The values of the p and r showed significantly high results.


The effects of ATP-receptor blocking agents on the response to the guinea-pig isolated bladder preparation to hyoscine-resistant nerve stimulation. The effects of very high concentrations of quinidine, imidazole and phentolamine were investigated on the responses of the guinea-pig isolated bladder to nerve stimulation in the presence of hyoscine in an attempt to determine whether or not ATP mediated the contractions. Quinidine reduced the response to nerve stimulation without affecting the histamine controls, though this was probably due to a local anaesthetic effect. Imidazole potentiated the response to histamine. Phentolamine and two experimental drugs (2-2' pyridylisatogen and 2-2' methoxyphenylisatogen) that are active against ATP-induced relaxations of the guinea-pig isolated taenia were nonspecific in their blockade of the contractions of the bladder to nerve stimulation.


[8-year experience in 40 patients with an axillary-femoral graft]. The 8 years (1967-1975) experience with axillary-femoral and femoro-femoral grafts in 40 patients is presented; 6 females and 34 males, between 50 and 90 years of age, with arteriosclerosis, all complicated by chronic illnesses. The results have been satisfactory, as the grafts are functioning from 2 months to 80 months (6 years, 8 months), most of them being more than 12 months old. Twenty eight of the 40 patients operated are alive. Four patients (10%) had infection of their grafts. In 6 (15%) the graft closed because of severe progresive distal obstruction. Three patients (7.5%) died in the first 32 post-operative days. In 9 (22.5%) the deaths were not related to surgery. The indications for placement of axillary-femoral and femoro-femoral grafts is established.


Biphasic response of the SA node of the dog heart in vivo to selective administration of ketamine. Effect of ketamine on the SA node of the dog heart was studied in vivo using a selective perfusion technique of the SA node artery. Injections of ketamine in doses from 100 microgram to 3 mg into the artery produced a depression of the SA nodal activity by a direct action. This depression was followed by the sudden appearance of a stimulatory phase. Bilateral vagotomy and sympathectomy or prior administration of a ganglion blocker failed to inhibit the occurrence of the ketamine-induced tachycardia, while it was completely abolished in the reserpinized dogs or by a prior injection of a beta-blocking agent into the SA node artery. This may indicate that an activation of the peripheral adrenergic mechanism plays an important role in the induction of the excitatory effect of ketamine injected in the SA node artery.


[Scimitar syndrome].

[Scimitar syndrome]. A case of the uncommon Scimitar syndrome is presented. The importance of cardiorespiratory functional studies is emphasized. This enables a better understanding of the pathophysiology in regard to the medical surgical theraphy.


Cardiovascular effects of 5-hydroxypropranolol (ORF 12592) in dogs. ORF 12592, the 5-hydroxy analog of propranolol, produced reductions in mean arterial pressure, heart rate, cardiac contractility and hind limb perfusion pressure in the anesthetized normotensive dog. Blood pressure and heart rate were also lowered in the carotid-sinus denervated dog. ORF 12592 blocked heart rate and blood pressure responses induced by isoproterenol. Similar results were observed with propranolol administration except for a transient decrease in blood pressure in the mormotensive dog. These results indicate that ORF 12592 possesses antihypertensive and beta-blocking properties in the anesthetized dog.


Effects of morphine and acetylsalicylic acid on kinin forming enzyme in rat paw. Coaxial perfusion was carried out in the rat paw; pinching the instep of the foot and electrical stimulation of the sciatic nerve caused an increase in the release of a bradykinin-like substance and kinin forming enzyme into the perfusate. Release of the latter was noted with pinching even independently of the release of the bradykinin-like substance. Acetylsalicylic acid (200 mg/kg i.p.) inhibited the release of kinin forming enzyme due to pinching or to sciatic nerve stimulation, while morphine (5 mg/kg i.m.) inhibited only the release of the enzyme due to sciatic nerve stimulation. Our results suggest that production of localized pain may be largely due to the activity of the released kinin forming enzyme and the bradykinin-like substance. In addition, the mechanism of inhibition by morphine on release of kinin forming enzyme appears to differ from that of acetylsalicylic acid.


Anti-inflammatory activity of EU-2972, 2-(3,4-dichlorphenylamino)quinolizinium bromide. EU-2972, a new and unique drug affecting the gastrointestinal tract, caused a dose-related inhibition of carrageenin-induced hindpaw edema in the rat. The acute anti-inflammatory effect of EU-2972 was absent in bilaterally adrenal-demedullated and in adrenalectomized rats. In the adjuvant-induced (Mycobacterium butyricum) polyarthritis rat study, daily peroral doses of EU-2972 for 14 days partially reduced primary and secondary lesions in therat hindfeet without improving the arthritis score or body weight loss. Phenylbutazone ameliorated all signs associated with polyarthritis in rats. These studies indicated that the acute anti-inflammatory effectiveness of EU-2972 was due to a release of adrenal catecholamines, and not to a direct effect or to a release of adrenal corticosteroids. A drug which releases adrenal catecholamines alone can be partially effective in reducing hindpaw lesion formation in rats with adjuvant arthritis. Nevertheless, the study shows that a drug which affects the gastrointestinal tract can be effective in an acute inflammatory condition.


Effect of phthalazinol (EG-626) on the mechanical activity and calcium influx of rabbit portal vein (1). Phthalazinol (EG-626), a newly synthesized cyclic AMP phosphodiesterase inhibitor, inhibited spontaneous phasic contractions (SPC) of isolated rabbit portal veins in a dose-dependent manner. Phthalazinol at a minimal concentration necessary to completely abolish the SPC did not alter 45Ca-uptake, 45Ca-influx, or the ED50S for methoxamine (me) and K+, but it did reduce the amplitude of the tonic contractions induced by ME and K+ by approximately 25%. On the other hand, verapamil, and La+3 abolished SPC, ME, and K+-induced contractions. Tetrodotoxin had no effect on SPC or on tonic contractions induced by ME and K+. Since extracellular Ca++ is known to be essential for SPC, ME, and K+-induced contractions in rabbit portal vein, the present results suggest that the abolishment of SPC and the partial inhibition of the ME and K+ responses by phthalazinol may be related to an action of this agent on intracellular Ca++ or Ca++-efflux.


Influence of MAO inhibitors on uptake and release of norepinephrine in rat brain in vitro. MAO inhibitors of diverse chemical structures were found to inhibit the uptake of 3H-NE into chopped rat cerebral cortex in vitro. The following molar (M) IC50 values to inhibit 3H-NE uptake were obtained: iproniazid, 7.9 X 10(-4)M; pargyline, 3.1 X 10(-4)M; pheniprazine, 6.3 X 10(-6)M; phenelzine, 3.9 X 10(-6)M; tranylcypromine, 2.5 X 10(-6)M; amphetamine, 2.5 X10(-7)M. In addition to decreasing deaminative catabolism, 5 X 10(-5)M amphetamine, tranylcypromine and pheniprazine plus 10(-3)M phenelzine produced a release of 3H-NE from tissue stores into incubation media. Similar concentrations of pargyline and iproniazid were ineffective to release 3H-NE from brain tissue.


Variations of histamine concentration in sleep and arousal hemodialysates (seasonal, thalamic and reticular influences). In hemodialysates of cerebral venous blood from rabbits kept asleep by electrical stimulation of the somnogenic intralaminar thalamus, a seasonal correlation was found between the histamine (H) concentration and the external daily temperature, with a minimum in winter and a maximum in summer. By contrast, in dialysates of rabbits aroused by electrical stimulation of the midtrain reticular formation, the H concentration reached in winter the same high level as in summer. During the winter, stimulation of the waking midbrain reticular system increased the H-level of the cerebral blood dialysate, whereas that of the somnogenic intralaminar thalamus did not enhance, sometimes even lowered, the H-concentration. This suggests that the mechanism of H release in blood might be associated with the midbrain activating reticular system and moderated by the intralaminar thalamus.


The effect of alcohol upon "muscle pull" of mice. Equipment is described for measuring the pull exerted by mice to escape tail restraint and enter a black box. Alcohol, at doses exceeding about 2.5 g/kg, intraperitoneally, significantly decreased "muscle pull", measured 5-60 min after administration. Fifty per cent depression of muscle pull was obtained with doses of about 3.04, 3.18 and 3.55 g/kg of alcohol, 15, 30 and 60 min after alcohol administration, respectively. Depression of muscle pull correlated with alcohol concentrations in the blood plasma. The data show that muscle pull was decreased in only a few animals with plasma alcohol concentrations of less than about 250 mg%, but was significantly depressed in animals with plasma alcohol concentrations of 350 mg% or more. Although differing from it in some respects, the method described is similar to the tilting-plane method which has been used in studies dealing with the effect of alcohol in rats and mice.


Delta9-THC as a discriminative cue in pigeons: effects of delta8-THC, CBD, and CBN. Pigeons, trained to discriminate the effects of i.m. injections of delta9-tetrahydrocannabinol (delta9-THC, 0.25 mg/kg) from the effects of the vehicle in a drug discrimination paradigm, were tested for generalization with the isomeric delta8-THC, cannabidiol (CBD) and cannabinol (CBN). When given in sufficient doses, delta8-THC and CBN were found to substitute for delta9-THC whereas CBD did not. CBD and CBN did not antagonize the stimulus effect of delta9-THC. The combination of CBN and delta9-THC rather appeared to accentuate the drug response.


Comparative activity of delta9-tetrahydrocannabinol, diphenylhydantoin, phenobarbital and chlordiazepoxide on electroshcok seizure threshold in mice. delta9-Tetrahydrocannabinol (THC) was compared with diphenylhydantoin (DPH), phenobarbital (PB) and chlordiazepoxide (CDP) using two electroshock procedures to determine anticonvulsant activity in mice, i.e., electroshock seizure threshold (EST) and the reduced EST caused by hyponatremia (injection of isotonic glucose). Using doses of each drug which were ineffective against MES, only CDP (10.0 mg/kg) was able to raise the EST by 20%. The lowered EST due to hyponatremia was reveresed by al four drugs. In these tests latency to convulsions and lethality associated with electroshock were more sensitive to THC.


Positive inotropic and antiarrhythmic actions of actodigin in dogs (1). The effects of actodigin were studied in dogs with decreased cardiac contractility or atrail flutter. When injected at 30 min invervals into dogs with barbiturate-induced heart failure, actodigin caused a marked positive inotropic action of short duration. Actodigin's pronounced but fleeting effect appears to be related to the novel attachment of its steroid nucleus alpha to the carboxyl function in the lactone. Cardiac glycosides with a conventional beta linkage of the lactone ring to the steroid nucleus (e.g., AY-22,248) had positive inotropic actions which were both slower in onset and cumulative when injected every 30 min. Apparently because of its short duration of action, actodigin was not as cardiotoxic as its isomer, AY-22,248. Lastly, a sustained atrail flutter was induced by intercaval crush and faradic atrial stimulation. Both actodigin and ouabain converted this arrhythmia to normal sinus rhythm.


Effects of lithium chloride, desmethylimipramine and cocaine on the cardiovascular actions of ouabain in dogs with or without carotid and aortic baro-receptor reflexes. The cardiovascular effects of ouabain as modified by LiCl, DMI and cocaine in anesthetized dogs with or without buffer nerves (carotid sinus and vagus nerves) were compared. Ouabain significantly increased the LV dp/dt in saline and cocaine but not in LiCl or DMI treated buffered animals. Significant ouabain-induced increase in MAP and decrease in HR were also observed in animals receiving DMI and cocaine. Neither the AD nor the LD of ouabain was modified by Licl or cocaine. DMI, while reducing the AD could not modify the LD of ouabain. In animals without the baro-reflex mechanism (debuffered), significant increase in both LVP and LV dp/dt were observed with ouabain following LiCl and DMI administration. Debuffering itself reduced the LD ouabain in saline treated animals. It was concluded that depending on the presence or absence of baro-reflex mechanism, lithium and DMI could either inhibit or facilitate the inotropic effect of ouabain. Cocaine did not interfere with the actions of ouabain. Ouabain-induced cardiotoxicites were not greatly modified by any of the drugs used.


Hepatic oxidative drug metabolism in rats with experimental renal failure. The activity of the drug-oxidizing system was investigated in liver homogenates of control and uraemic rats. Acute renal failure was achieved by ligation of the ureters or by intravenous injection of uranyl nitrate. In the uraemic state the concentration of cytochrome P450 and the activity of aniline hydroxylase were not significantly changed, but the activity of  aminopyrine N-demethylase was significantly decreased. In rats the hepatic oxidizing enzymes are not induced by the uraemic state, in contrast to what has been suggested in man.


Mechanism of inhibition of dopamine beta-hydroxylase evoked by FLA-63. An in vitro study. Bis-(4-methyl-1-homopiperazinylthiocarbonyl)-disulphide (FLA-63) inhibits in vitro purified bovine adrenal medullary dopamine beta-hydroxylase (BDH) concentration-dependently; 50% inhibition is produced by 2 x 10(-6)M FLA-63. Spectrophotometric experiments show that FLA-63 is reduced by ascorbate very likely to the corresponding dithiocarbamate-derivative, which acts as a Cu++-chelator. Cu++-ions are able to completely abolish the inhibition of the DBH caused by FLA-63 in concentrations up to 2.5 x 10(-6)M. It is concluded that FLA-63 inhibits the DBH mainly in its reduced form via the formation of a chelate-complex with copper ions derived from the DBH.


Comparative study of propranolol and dicyclohexylamine protection of alpha-receptor blockade. During the course of a study into protection against alpha-receptor blockade, it was observed that the dicyclohexylamine (DCHA) salt of 5-hydroxyindole acetic acid exhibited protection, whilst the free acid did not protect against alpha-receptor blockade. A study has been made into the protection of alpha-receptor blockade by DCHA and this compared with the beta-blocker propranolol, with which DCHA may share some structural similarity. It was also observed that at higher concentrations DCHA itself produced spiked contractions of the vas deferens. These properties of DCHA and their interrelationships with those of propranolol are discussed.


Effects of diltiazem on high-energy phosphate contents reduced by isoproterenol in rat myocardium. Effects of diltiazem on myocardial high-energy phosphate metabolism as well as on arterial blood pressure and heart rate were investigated in the rat treated with isoproterenol. Pretreatment with diltiazem prevented the reduction in both adenosine triphosphate and creatine phosphate induced by 2.5 mg/kg of isoproterenol. The ratio of creatine phosphate/inorganic phosphate in the rat receiving 100 mg/kg of diltiazem was higher than in the control. Heart rate was significantly decreased by the administration of 100 mg/kg of diltiazem not only in the non-pretreated rat but also in the rat given isoproterenol. This may partly account for the protective effect of diltiazem against the breakdown of high-energy phosphate in the isoproterenol-treated rat.


Influence of temperature and frequency on the positive inotropic action of phenylephrine in the isolated rabbit papillary muscle. On the isolated papillary muscle of the rabbit the maximal developed tension induced by phenylephrine bia alpha-adrenoceptors was not affected by changing the temperature, while the basal developed tension of the muscle was significantly increased or decreased by lowering the temperature from 37 degrees C to 32 degrees C or by raising it to 42 degrees C, respectively. When the temperature was lowered from 37 degrees C to 32 degrees C in the muscle stimulated at a frequency of 0.5 Hz, the dose-response curve for phenylephrine via alpha-adrenoceptors was shifted to the left (delta pD2-0.47), while that for phenylephrine via beta-adrenoceptors was also shifted to the left to a similar extent (delta pD2=0.43). When the temperature was raised from 37 degrees C to 42 degrees C, the dose-response curve for phenylephrine via alpha-adrenoceptors was markedly shifted to the right (delta pD2=1.58), whereas that via beta-adrenoceptors was not affected at all by this elevation of the temperature (delta pD2=0.04). The change of the stimulation frequency affected chiefly the intrinsic activity of phenylephrine but not the affinity of the drug for alpha-adrenoceptors expressed as the pD2-value.


Disopyramide phosphate: tissue uptake and relationship between drug concentrations in the plasma and myocardium of rats. Tissue uptake of total-14C and disopyramide (DP) was examined in rats following 5 to 100 mg/kg doses of [14C]-disopyramide phosphate [14C-DPP]. Disopyramide was the major 14C constituent in the plasma or tissues. The gastrointestinal absorption of [14C]-DPP was 86% as determined from the areas under the plasma total-14C concentration-time curves following 10 mg/kg oral or i.v. administration. Total-14C was widely distributed in tissues, and at 2 hr the highest uptake occurred in the fat, liver and spleen giving concentrations ranging from 7 to 15 times that in plasma. In the thymus, adrenals, lungs, salivary glands, testes and muscle the concentrations were about twice that in plasma, in the heart and eyes similar to that in plasma, and in the brain less than one-third that in plasma. The uptake and elimination characteristics of total-14C or DP in plasma and myocardium were similar. The two-hour plasma or myocardium DP concentrations were linearly related to the oral dose in the 5 to 50 mg/kg range. In three days about 30% (oral) and 39% (i.v.) of the 14C dose (10 mg/kg) was excreted in the urine, 64% (oral) and 54% (i.v.) in the feces, and less than 2.1% remained in the carcass. The composition of the urinary and fecal metabolites was similar after oral or i.v. administration of the drug.


Hypotensive and bradycardic activities of clonidine and related imidazolidines; structure-activity relationship. The hypotensive effect of clonidine and 27 of its structurally related imidazolidines, which differ in substitution in the aromatic moiety, was determined following intravenous application to pentobarbital-anaesthetized, normotensive rats. The decrease in cardiac frequency was measured at the moment of the maximal depressor effect. For all the compounds studied the same type of mechanism regarding their cardiovascular action is involved. Both the hypotensive and bradycardic effects were quantified by means of equipotent doses, calculated from dose-response characteristics constructed for each derivative. A wide range of bradycardic and hypotensive activities (greater than 4 logarithmic units) is covered by this selection of clonidine-like drugs. Moreover, a linear relationship is found between the hypotensive and bradycardic activities within the present series of compounds. The influence of structural modifications in the aromatic portion of the imidazolidines on hypotensive activity is described and discussed with respect to the structure-activity relationship (SAR) in centrally acting hypotensive imidazolidines.


Central hypotensive and antihypertensive activities of imidazolidines, structurally related to clonidine. A central nervous origin of the hypotensive effect of a number of clonidine-like drugs was demonstrated by means of infusions of low doses into the vertebral artery of chloralose-anaesthetized cats. Systemic injections of the same amounts were significantly less effective than after their application via the central route. In addition, pretreatment with the alpha-adrenoceptor blocking agent piperoxan effectively blocked the centrally induced hypotensive response. It is concluded that imidazolidines of the clonidine-type probably display the same mechanism of action as that manifested by clonidine itself. The centrally mediated depressor response was quantified by means of an ED25. The antihypertensive and bradycardic activities of clonidine and a number of its derivatives were quantified by means of ED20 values calculated from dose-response curves following intravenous administration to conscious, spontaneously hypertensive rats. Linear relationships were found between the hypotensive activity in the anaesthetized, normotensive rat, the central hypotensive potency in the anaesthetized cat and the antihypertensive efficacy in the conscious, spontaneously hypertensive rat. These findings indicate a similarity between central alpha-adrenoceptors in these different animal species.


Therapeutic fasting in morbid obesity.

Therapeutic fasting in morbid obesity. The weights of 207 morbidly obese patients were reduced via prolonged fasting. Half the patients fasted for close to two months, losing a mean of 28.2 kg; one fourth fasted for less than one month; and the other fourth fasted for more than two months, with a mean 41.4-kg loss. This latter group was heavier initially, and more than 50% attained near-normal weight. Patients with onset of obesity in childhood had the lowest tolerance for fasting and the lowest success rate in attaining normal weight. Over a 7.3-year follow-up period in 121 patients, the reduced weight was maintained for the first 12 to 18 months. Subsequently, regain proceeded equally in all groups irrespective of length of fast, extent of weight loss, or age at onset of obesity. Regain to original weight occurred in 50% within two to three years and only seven patients remained at their reduced weights. Regain to greater than original weight was more common in childhood-onset obesity.


Tests of fibrin metabolism in recurrent venous thromboembolism. Fibrinogen/fibrin degradation products (FDP/fdp) and soluble fibrin complexes (SFC) were measured serially in 60 patients heparinized for pulmonary embolism or deep venous thrombosis. Eight patients had recurrent thromboembolism. In patients without recurrence, FDP/fdp and SFC tended to normalize within three to five days. In patients with recurrence, results of both tests were significantly higher on admission, and FDP/fdp values were significantly higher throughout ten days of therapy, than in patients without recurrence. The SFC values were not different between the two groups during the first six days of treatment, but again became significantly higher on the seventh day in patients with recurrence. There were no differences in clotting times, heparin dosage, or any other clinical features between patients with and without recurrence. Measurement of FDP/fdp and SFC can help identify patients at risk of recurrent thromboembolism if performed serially during treatment.


Acute myocardial infarction in Newark, N.J. A study of racial incidence. The incidence of acute myocardial infarction (AMI) among urban blacks appears to be considerably less than that among whites. To evaluate this, all AMIs among Newark, NJ, residents in 1973 were evaluated, using the 1970 census for calculating age, race, and sex-specific rates. Death certificates of patients dead on arrival (DOA) from coronary heart disease (total 517) were also evaluated. Two hundred seventy-three AMIs were documented. Although crude rates per 100,000 population were higher for whites than for blacks, age-specific rates by decades from 20 to 80 revealed no differences. Coronary DOA rates were consistently higher among blacks than among whites, reaching approximately a 2:1 ratio in the older decades. The apparent rarity of AMI among Newark blacks is attributable to their relative youth compared to whites (77% under 40 vs 56%) and a higher out-of-hospital coronary death rate.


Age and the renin-aldosterone system.

Age and the renin-aldosterone system. Age effect on plasma renin activity (PRA) and PRA classification was studied in young and older normotensive volunteers. Ambulatory PRA was lower in the older age group than in the younger with both on an unrestricted diet and a low-sodium diet. Renal function, aldosterone excretion, and plasma renin substrate were comparable in both groups. Age had a substantial effect on PRA classification. When the young normotensives were controls, 32% (6/19) older normotensives had abnormally low PRA, or "low renin normotension." Similarly, 18% (2/11) of young patients with essential hypertension but 80% (12/15) of older hypertensives had low PRA. When the older volunteers were controls, however, the incidence of low renin hypertension (LRH) decreased to 53% in the older patients. The use of predominantly young controls for defining normal limits of PRA may result in an overestimate of the incidence of LRH and may contribute to the heterogeneity of LRH.


d-Transposition of the great vessels in the neonate. A clinical diagnosis. We reviewed the records of 66 neonatal patients with d-transposition of the great vessels (d-TGV) admitted to our institution. The initial history, physical examination by the cardiologist, chest rotengenogram, ECG, hemoglobin level, and hematocrit value were analyzed. Although all patients all patients were cyanotic and 65% were tachypneic, other signs of a major congenital cardiac anomaly were usually absent. The number of clinical signs (poor general status, cyanosis, respiratory distress, S2 increased and single, murmur, classical chest roentgenogram, abnormal ECG) present in each patient was three or less in 41%, only 13.5% had more than five signs.


Sulfonamide-induced hemolytic anemia and hemoglobin Hasharon. A patient with Hb Hasharon had severe hemolytic anemia after several days of daily ingestion of 2 gm of sulfisoxazole. After recovery, her erythrocytes were incubated with the drug, leading to preferential oxidation and precipitation of the abnormal hemoglobin. Since carboxyhemoglobin and cyanmethemoglobin Hasharon were as stable in the heat stability test as identically liganded Hb A, we conclude that the substitution of the hydrophilic aspartate residue by histidine on the surface of the molecule at alpha47 has led by a still unknown mechanism to an interaction of hemoglobin with the drug that labilized the heme-globin bond. Since Hb Hasharon has been found in several unrelated families, the risk of drug-induced hemolytic anemia in such carriers deserves emphasis.


Osteolytic lesions in secondary syphilis. A 37-year-old man was admitted with bone pain, night sweats, and skin lesions typical of secondary syphilis. His VDRL and FTA-ABS tests were reactive. Roentgenograms of the tibiae, fibulae, radii, and ulnae showed osteolytic lesions. A tibial biopsy examination showed bone necrosis, prominent vascularity, swollen endothelial cells, an intense plasma cell infiltrate, and numerous spirochetes. All manifestations responded to penicillin therapy. There have been few reports of osteolytic lesions in secondary syphilis. This is the first known case in which such involvement was unequivocally proven by histopathology with the demonstration of spirochetes.


Circulating anticoagulant in the procainamide-induced lupus syndrome. An elderly man with procainamide hydrochloride-induced lupus syndrome had a circulating anticoagulant against factor XI and a biologic false-positive (BFP) test result for syphilis. This was not associated with hemorrhagic problems. The activity of the circulating anticoagulant and the BFP disappeared within days following discontinuation of procainamide and the administration of corticosteroids.


Transient diabetes insipidus with elevated serum osmolarity associated with 'benign' febrile illness. A 38-year-old physician developed polyuria and hypodipsia four days after the onset of an upper respiratory tract infection. Subsequent investigation showed a concentration defect with dehydration that partially corrected with vasopressin injection (Pitressin) administration compatible with partial central diabetes insipidus (DI). Skull roentgenograms, EEG, and lumbar puncture were normal. The polyuria and hypodipsia slowly resolved without treatment. Normal urinary concentration ability was achieved by the 48th day, but a residual elevation in serum osmolarity persisted for one year. Review of the literature failed to show previous documentation of transient DI with elevated serum osmolarity from an acute, febrile illness. The mechanism is speculative, but may be related to a subclinical encephalitis. The true frequency of this syndrome and its relationship to the frequent observation of transient polydipsia and polyuria in "benign" febrile illness remains to be determined.


Tuberculous meningitis in an urban general hospital. We analyzed the clinical and laboratory findings of 19 patients with tuberculous meningitis seen between 1966 and 1974 at the Henry Ford Hospital. Eighteen patients were adults at the time of diagnosis. In eight patients, the history suggested that the infection with the tubercle bacillus had occurred in the remote past. Cerebrospinal fluid analysis was often typical for tuberculous meningitis; stains for Mycobacterium tuberculosis were usually negative. Of 16 patients who were treated, five died and five suffered permanent neurological sequelae. The addition to rifampin to isoniazid therapy did not improve either survival or permanent sequelae. We were not able to analyze the effect of steroids on the disease.


Fulminant pneumococcal infections in 'normal' asplenic hosts. Five asplenic persons with no other detectable underlying disease had over-whelming pneumococcemia. Four of the patients had undergoing splenectomy for trauma, and the fifth had asplenia as an isolated congenital abnormality. Including the cases presented here, there are now at least 26 reported instances of fatal or life-threatening pneumococcal infections in otherwise-normal asplenic patients. Thus, splenectomy per se is associated with an increased risk of over-whelming pneumococcemia. Although the magnitude of the risk is low, mortality associated with these infections is high. Analysis of the clinical data strongly suggests that undiagnosed febrile episodes in asplenic persons should be treated promptly with antibiotics while awaiting culture results. This strategy should be adopted regardless of the age of the patient or his general state of health. The observation that a limited number of pneumococcal serotypes, particularly type XII, appear to predominate in these cases suggests that pneumococcal vaccine might be highly efficacious in preventing overwhelming post-splenectomy pneumococcal infections in otherwise-normal hosts.


Criteria for the diagnosis of alcoholism. Manifestations of alcoholism in general hospital patients were studied retrospectively by review of medical records to determine their frequency of occurrence. Pathophysiological indications of alcoholism were far more commonly recorded than were behavioral or psychological changes, although most diagnostic clues were notable by their absence from a majority of the records. Optimizing the diagnostic efficacy of those features of alcoholism that did occur may require application of the methods of statistical decision making. Absence from the charts of behavioral criteria and of indications of tolerance reflects deficiencies in both patient interviewing and medical record keeping. The traditional structure of the medical history may require modification to ensure recording of these more specific manifestations. In addition, continued efforts are needed to improve the undergraduate and the direct-care education of physicians.


Host defenses during prolonged alcohol consumption in a controlled environment. To determine the pure effects of prolonged alcohol ingestion on host defenses, we studied six noncirrhotic alcoholic volunteers drinking in the Clinical Research Center. All had tests of granulocyte, humoral, and cell-mediated immune function before and at the end of eight to 28 days' intake of approximately 0.75 liter of 100-proof whiskey per day. Results of all tests were normal during the drinking period, except for the following: (1) granulocyte chemotaxis was depressed in three volunteers and improved on alcohol withdrawal; (2) antibody response to keyhole limpet hemocyanin (KLH) immunization was poor; and (3) delayed hypersensitivity could not be established to KLH. Although it is somewhat surprising that more abnormalities were not induced, the three defects noted may contribute to the alcoholic's poor resistance to infection.


Dopamine-related polyuria in patients with gram-negative infection. Two patients developed polyuria with natriuresis while receiving intravenous dopamine hydrochloride for the treatment of hypotension. Both patients had Gram-negative pneumonia and both had evidence of extracellular volume depletion that was considered to be a result of the dopamine-induced polyuria. Following restoration of extracellular volume and withdrawal of dopamine therapy, both patients became normotensive and required no vasopressors. The diuretic action of dopamine, which persisted despite the severe intravascular volume contraction and perpetuated the hypotensive state in these two patients, is not well understood. The Gram-negative infection could play an important role possibly by enhancing the effect of dopamine on the renal vasculature.


Is elevated plasma renin activity of prognostic importance in progressive systemic sclerosis? The pathologic lesions of the kidney in scleroderma in many respects resemble those of malignant hypertension, perhaps even in the absence of comparable blood pressure elevation. Because the malignant vascular changes have been related to hyperreninemia, we measured plasma renin activity in 23 patients with scleroderma with or without hypertension and/or renal failure. We found that high renin levels in most cases shortly preceded or coincided with a phase of sudden deterioration of the disease, characterized by a rapidly progressive renal failure. The outcome of this phase was invariably fatal, except for two patients in whom bilateral nephrectomy successfully arrested the rapid downhill course. These findings suggest that an unexplained increase in circulating renin levels in an otherwise stable patient with scleroderma may be taken as a possible marker of imminent deterioration requiring close monitoring and immediate therapeutic intervention.


Synergistic treatment of enterococcal endocarditis: in vitro and in vivo studies. Combinations of penicillin G sodium or ampicillin plus streptomycin sulfate do not produce synergism against all strains of enterococci. This lack of synergism was considered the cause of the failure in the treatment of enterococcal endocarditis. The effect of various combinations of antibiotics on 15 enterococcus strains, which had been isolated from patients with enterococcal endocarditis, was examined. The antibiotics included those that interfere with cell-wall synthesis and those that act on cell metabolism. The in vitro results have shown that while penicillin- or ampicillin-streptomycin combination was not synergistic in eight of 15 strains, penicillin- or ampicillin-gentamicin sulfate combination was synergistic in 100% of the cases. We report seven cases of enterococcal endocarditis that were successfully treated with penicillin- or ampicillin-gentamicin combination, thus confirming the effectiveness of this therapeutic regimen.


Hypertension in polycystic kidney disease without renal failure. Hypertension occurring in patients with adult polycystic kidney disease (PKD) without substantially decreased glomerular filtration rate (GFRs) has not been sufficiently evaluated. Seven patients with bilateral PKD and serum creatinine clearances greater than 70 ml/min were studied to examine the roles of sodium retention and the renin-angiotensin system in their hypertension. These individuals demonstrated evidence of volume expansion and sodium-dependent hypertension. However, the renin-angiotensin system was not consistently depressed as a consequence, and two of the seven had significantly increased plasma renin activity values. It seems that patients with PKD who had normal GFRs retain rather than waste sodium and may become hypertensive. The contribution of the renin-angiotensin system is variable and seems to be a function of such factors as symmetry of the cystic involvement and the degree of intravascular volume expansion.


Postmyocardial infarction complications requiring surgery. Papillary muscle rupture, ventricular septal defect, and ventricular aneurysm represent complications of myocardial infarction that require surgical intervention. Since operative mortality and morbidity are increased in proportion to the degree of myocardial and pulmonary disease, early diagnosis and surgical intervention is mandatory. Diagnostic procedures of choice include careful and serial ECG analysis and cardiac auscultation, especially in patients with postinfarction refractory angina or congestive heart failure; Swan-Ganz catheterization, echocardiography; and, in appropriate instances, ventricular and coronary angiography should also be performed preoperatively. With early identification of patients at risk of developing these complications, and careful preoperative hemodynamic studies, surgical repair should lead to improvement in myocardial function and more effective response to post-operative medications in patients previously resistant to such therapy.


Intermittent cholestatic jaundice and nonmetastatic prostatic carcinoma. Hepatomegaly and abnormal liver function can occur in nonmetastatic malignancies. A patient with metastatic prostatic adenocarcinoma that had spared the liver and extrahepatic biliary tree is described. He had puzzling episodes of jaundice for a period of 2 1/2 years. The results of appropriate investigations and an exploratory laparotomy performed dlring the patient's four antemortem hospitalizations were indicative of "recurrent intrahepatic cholestasis," the cause of which remained an enigma even after exploratory laparotomy. At autopsy, no evidence of hepatic metastases or extrahepatic biliary obstruction was found. Alcohol, hepatotoxic drugs, toxins, viral and chronic active hepatitis, hemolysis, and extrahepatic biliary obstruction were eliminated as causes of the jaundice. We believe that the intermittent intrahepatic cholestasis is one of the nonmetastatic manifestations (nonmetastatic hepatopathy of malignancy) of the prostatic adenocarcinoma.


Phonocardiographic study of sounds produced by a circulatory assist device: report of a patient with a ruptured ventricular system. A patient had a ruptured ventricular septum due to an acute anterior myocardial infarction. An aortic balloon pump was inserted and a subsequent phonocardiographic study was made showing inflation and deflation sounds and the diastolic pulse wave generated. This study defines the extra sounds and pulses generated by such a device so that they may be better understood for clinical interpretation.


Gardner-Diamond's syndrome in a man.

Gardner-Diamond's syndrome in a man. Gardner-Diamond's syndrome, or autoerythrocyte sensitization, is a disorder of spontaneous, painful ecchymoses whose pathogenesis is unresolved. The role of psychopathologic factors in this entity has been emphasized in previous reports. The patient in this study had a classical history and characteristic clinical features and is, to my knowledge, the first man described with this disorder.


Venous hum of the Cruveilhier-Baumgarten syndrome: response to the Valsalva maneuver. The response of the venous hum of the Cruveilhier-Baumgarten syndrome (CBS) to respiration, the cardiac cycle, and changes in posture is not predictable. The Valsalva maneuver may result in an increase in intensity of the hum rather than a decrease. The Cruveilhier-Baumgarten venous hum (CBH) is virtually diagnostic of portal vein hypertension. It may be mistaken for obscure cardiac murmurs. The Cruveilhier-Baumgarten venous hum, unlike the cervical venous hum (CVH), is never present in normal people.


Infantile polycystic kidney disease in the adult. We evaluated an adult with polycystic kidney disease that had been present since birth. Our evidence indicates that this patient is a unique example of survival into adult life of the recessively inherited, infantile form of polycystic kidney disease.