A method of estimating intracranial decompensation in man. A new method of estimating intracranial decompensation in man is described. An on-line computer system is connected to an intracranial pressure (ICP) monitoring system to compute regression plots of mean ICP vs standard deviation; standard deviation is used as a measure of ICP instability. Two zones with distinctly different slopes are a characteristic feature of these plots. It is thought that the changes of slope signify intracranial decompensation.


Intercavernous connections of the cavernous sinuses. The superior and inferior circular sinuses. Morphological features of the intercavernous connections of the cavernous sinuses are described and illustrated by photographs of vinylite casts. Surgeons should be aware of the course, potential size, and arrangement of the channels in the dura of the hypophyseal fossa. This is particularly important in exposure of pituitary gland by the transpheniodal route.


Anatomy of the cavernous sinus. A microsurgical study. Fifty cavernous sinuses from cadavers were studied in detail using magnification, with special attention to the relationships important in surgical approaches on the intracavernous structures, and to understanding arterial contributions to arteriovenous fistulas involving the cavernous sinus. Significant findings were: 1) The three main branches of the intracavernous portion of the carotid artery were the meningohypopyseal artery, present in 100% of the specimens, the artery of the inferior cavernous sinus (84%), and McConnell's capsular arteries (28%). In addition, the ophthalmic and dorsal meningeal arteries arose from the carotid artery within the cavernous sinus in 8% and 6%, respectively. The three main branches of the meningohypopyseal trunk were the tentorial artery, present in 100%, the dorsal meningeal (90%), and the inferior hypophyseal (80%). 2) The carotid artery was separated from the trigeminal nerve just proximal to the sinus by only dura in 84% of the specimens, and the artery was exposed in the floor of the middle fossa lateral to the trigeminal nerve in 38%. 3) The intracavernous portion of the carotid artery indented the lateral side of the pituitary gland in 28% of dissections but could be as far as 7 mm from it. 4) A triangular area, described by Parkinson, through which the intracavernous portion of the carotid artery could be exposed surgically was found in all specimens. 5) The sixth cranial nerve may split into as many as five rootlets as it passes lateral to the intracavernous portion of the carotid artery. 6) The three major venous spaces within the sinus were posterosuperior, anteroinferior, and medial to the intracavernous portion of the carotid artery.


Radiosotope evaluation of experimental hydrosyringomyelia. Kaolin-induced hydrosyringomyelia in dogs has been investigated by radioisotope ventriculography using both cerebrospinal fluid radioassay and scintigraphy. The hydromyelic central canal can be differentiated from the spinal subarachnoid space by scintigraphy, Serial studies show that hydromyelia arises rapidly to decompress the associated hydrocephalus in surviving animals. Syringomyelia, after a delayed onset, originates from the enlarged central canal. Radioisotope ventriculography may be a useful clinical aid in the diagnosis of hydrosyringomyelia.


Clinical radiosotope investigations in hydrosyringomyelia and myelodysplasia. Radioisotope ventriculography was applied clinically in myelodysplastic hydromyelia in three groups of patients: two patients with normal ventricles, two with obstructive hydrocephalus, and 16 with myelodysplasia. In the myelodysplastic group, radioassay in one patient demonstrated flow of radioistope down the hydromyelic cavity. Twenty scintigraphic studies on 16 myelodysplastic patients showed hydromyelia was present in all patients with spontaneously compensated hydrocephalus but in none of those with functional ventricular shunts. This relation between the hydromyelia and disordered ventricular hydrodynamics supports the Gardner hypothesis of myelodysplasia. Radioisotope ventriculography appears a safe and useful method of diagnosing hydrosyringomyelia and evaluating treatment by means of ventricular decompression.


Late results of cervical disc surgery.

Late results of cervical disc surgery. Late results of cervical disc surgery have been reported and statistically studied in 383 cases: 83% were lateral discs, 13% were central spondylosis discs, and 4% central soft discs. Central spondylosis occured at a higher spinal level, and caused cord compression with or without weakness of the hands, but no pain. A posterior approach was used in all lateral discs, and either an anterior or a posterior approach, with or without fusion, for central discs. Preoperative myelography was always done and is recommended postoperatively in central disc surgery to evaluate the results. Our results were good to excellent in 95% of lateral discs, in 64% of central spondylosis discs, and in an unexpected 91% of 11 cases of central soft discs. There were no recurrences and no serious complications, although 20% developed other cervical or lumbar disc herniations.


Posterior cervical fusion in chidren.

Posterior cervical fusion in chidren. Six cases of posterior cervical fusion with rib grafts in children are reported. Four of the children had sustained cervical spine injuries in accidents, and two had congenital absence of the odontoid. Three-level fusions (C1-3) were done in four children, and four-level fusions (C1-4) in two. One child died of unrelated causes 3 months after the operation. The other five children have been followed for 5 to 13 years. All are doing well and each has a remarkably supple, stable neck and no neurological deficit.


Sciatic entrapment neuropathy. Case report. A case of sciatic entrapment neuropathy is discussed. When evaluating patients with unilateral leg pain and paresthesias, one should consider the possibility of entrapment of peripheral nerve. Electrodiagnostic studies are helpful in establishing the diagnosis.


Hemorrhage in bilateral choroid plexus hemangiomas demonstrated by computed tomography. Case report. The authors present a case in which bilateral posttraumatic hemorrhages in choroid plexus hemangiomas were demonstrated by computed tomography and histopathological study.


Cerebrospinal fluid fistula from fractured acrylic cranioplasty plate. Case report. The authors report a patient who developed a cerebrospinal fluid fistula secondary to a fractured methyl methacrylate cranioplasty plate. There was no external evidence of trauma. X-ray films showed no evidence of the fracture. It is suggested that the impregnation of methyl methacrylate with a radiopaque material would result in visualization of such fractures.


Multifocal glioma of the brain. Case report. A case is presented in which two separate concurrent astrocytomas of the brain in the same patient were successfully operated on. The patient has been followed for 3 years and remains well. The authors believe that the diagnosis of multifocal tumors can be established on clinical grounds when the tumors are remote from each other, and when there has been no recurrence of neoplasm between the lesions after a long follow-up period. It is felt that a more optimistic approach to the treatment of multifocal tumors may yield good results.


Adaptive response of lysine and threonine degrading enzymes in adult rats. The mechanism of variation inlysine and threonine conservation was investigated by measuring the activity of the enzyme initiating the amino acid catabolism in adult rats adapted to different diets. Both liver threonine dehydratase and lysine-ketoglutarate reductase activities were increased by high protein intake. Supplementation with 2% L-lysine HCI to a 5% lactalbumin diet increased liver lysine-ketoglutarate reductase activity three-fold. Feeding a lysine-free diet or a 10% wheat gluten diet significantly decreased the activity below the level obtained by feeding a protein-free diet. In contrast, dietary threonine in either excess or deficiency did not change the liver threonine dehydratase activity. At the same level of lysine intake, an excess of dietary wheat gluten seemed to increase the liver lysine-ketoglutarate reductase activity much more than dietary lactalbumin. These data suggest that the activity of lysine-ketoglutarate reductase in rat liver might be influenced by dietary lysine as well as excesses of other amino acids in wheat gluten. The different response of these two catabolic enzymes to their substrate might explain the variation of lysine and threonine conservation during amino acid deficiency.


Plasma amino acids in reptiles after feeding protein or amino acids and after injecting amino acids. Turtles (Pseudemys scripta elegans) and alligators (Alligator mississipiensis) were fed fish, casein, or free amino acid mixtures, or were injected with free amino acid mixtures, quantities in each case being equivalent to about 42 mmoles of amino acids/kg body weight. The experiments were designed to determine whether protein synthesis normally precedes catabolism of the amino acids absorbed from digesting food. Both animals disposed of free or food-derived amino acids more rapidly than could be accounted for by catabolism alone, but the transient increases in turtle plasma concentrations consisted mostly of essential amino acids, whereas the alligator plasma showed little increase in essential amino acids and considerable rises in four nonessential amino acids, glutamine, glutamic acid, glycine and alanine. Despite some species variation, these two species with low metabolic rates apparently utilized protein synthesis to dispose of amino acid mixtures prior to the necessarily slow process of catabolism for energy.


Utilization of L-methionine sulfoxide, L-methionine sulfone and cysteic acid by the weanling rat. Three experiments were conducted to test the ability of weanling rats to utilize the oxidized forms of the sulfur amino acids methionine and cysteine for growth. In the first two experiments, diets were fed which contained graded levels of methionine, methionine sulfoxide and methionine sulfone. The third experiment included a comparison of two dietary levels of cysteine and cysteic acid. The 2 week weight gain and food consumption data indicated that methionine sulfoxide was utilized for growth with only 60% of the efficiency of that achieved by rats fed methionine. Methionine sulfone was not utilized for growth. Analysis of plasma sulfur amino acids showed that the rat has a limited capacity to utilize methionine sulfoxide by effecting its reduction to methionine. Cysteic acid did not support weight gain. This amino acid appeared to be rapidly catabolized to taurine. It was concluded that methionine sulfone and cysteic acid cannot be utilized by the weanling rat. Methionine sulfoxide cannot fully meet the dietary requirement of the rat methionine because of its limited capacity to reduce this amino acid.


Evidence for a lack of an effect of dietary fluoride level on reproduction in mice. The possible essentiality of fluoride for reproduction was studied in female mice fed a low-fluoride ( less than 0.5 ppm F) basal diet for three generations. Reproduction of mice fed this basal diet was the same as when mice were fed the basal diet supplemented with 2 or 100 ppm F. A previous study [Messer et. al. (1973) J. Nutr. 103, 1319-1326], utilizing the same diet did result in an impairment of reproduction and the development of an anemic condition. The results of the present study suggest that the apparent essentiality of fluoride previously observed was due to a pharmacological effect of fluoride in improving iron utilization in a diet marginally sufficient in iron. The data do not support the previous claims of an essential role of fluoride in reproduction.


Blood metabolites and glucose metabolism in the fed and fasted chicken. The effect of fasting on blood metabolites and glucose metabolism in the chicken was studied. Parameters of glucose metabolism were estimated in vivo using a single injection of [2-3H]-glucose or [6-3H]-glucose in combination with [U-14C]-glucose. Plasma glucose, blood lactate and blood acetoacetate levels were not significantly changed in chickens fasted for 72 hours. Pyruvate levels in chickens fasted for 24 hours were higher than those observed in blood from birds fasted 0 to 72 hours. Further, the lactate to pyruvate ratio was lower in chickens fasted for 24 to 72 hours than in fed chickens. Fasting chickens for 24 or 72 hours resulted in three- to fivefold increase in blood beta-hydroxybutyrate levels and a significant increase in beta-hydroxybutyrate to acetoacetate ratio. Plasma levels of alanine and serine were increased after a 24 hour fast but were not further changed when fasting was extended to 72 hours. Plasma aspartate and glutamate levels were not significantly changed in chickens fasted for 24 hours but were markedly decreased in chickens fasted for 72 hours. Plasma levels of glycine were significantly lower in chickens fasted 24 or 72 hours than in fed birds. Glucose replacement rates estimated with [2-3H]-glucose in chickens fasted 0,24 and 72 hours were 14.3, 9.1 and 9.4 mg glucose/minute/kg body weight, respectively. Fasting up to 72 hours did not influence the total body glucose mass in the chickens. The degree of glucose-carbon recycling in 24-hour fasted chickens estimated by using [2-3H]- and [U-14C]-glucose or [6-3H]- and [U-14C]-glucose averaged 42% to 52% and 27% to 30%, respectively. These observations indicate that rate of glucose utilization in the chicken is rapid and that substantial recycling of glucose carbon occurs in fasted chickens.


Thiamin deficiency and the pentose phosphate cycle in rats: intracerebral mechanisms. Previous studies have shown that transketolase activity is decreased in the brains of thiamin deficient rats. This study assesses the effect of decreased transketolase levels on the activity of the pentose phosphate cycle in murine thiamin deficient cortex and brainstem. Thiamin deficiency was produced in newborn and adult rats by either pyrithiamin administration or by feeding a low thiamin diet. Newborn rats were killed at 22 days of age, and adults were killed at the onset of moderate to severe nurological signs. Cortices and brainstems from thiamin deficient and control rats were analyzed for activity of the two regulatory enzymes of the pentose phosphate cycle, glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase. Flux through the pathway was measured by  the differentially labeled glucose technique in the brainstems of deficient and control adult rats. In both the brainstem and cortex of thiamin dificient rats, areas in which transketolase activity was decreased up to 65%, the activities of the two regulatory enzymes, glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase, were unaltered. Further, flux through the pentose phosphate cycle was not decreased as compared to pair-fed control rats. These data do not support the hypothesis that in thiamin dificient rats, a decrease in cerebral transketolase activity leads to a diminished pentose phosphate cycle activity.


Zinc deficiency in the weanling rat: effects on liver composition and polysomal profiles. Some effects of zinc deficiency and inanition on post weanling development of the liver and on polysomal profiles were investigated. Failure to provide the weanling rat with adequate zinc resulted in anorexia, cyclical feeding, and growth retardation. Liver growth was also impaired, but was consonant with body size. Zinc deiciency resulted in a severe impairment of DNA accretion and a lowered concentration of RNA; protein alent to that for pair-fed controls, suggesting that the lowered protein concentration was largely due to inanition. In response to zinc deficiency, there was a smaller percentage of the total RNA on the gradient incorporated into the heaviest polysomal fraction. The amount of RNase activity did not appear to account for this altered polysomal distribution.


Dietary lipid requirements of adult lobsters, Homarus americanus (M.E.). The effects of several dietary lipids on adult American lobster (Homarus americanus) were assessed over a 10 month feeding period. Cod liver oil (CLO) resulted in greater precent weight gains, feed conversion, percent edible meat and higher serum protein and hemocyte counts than either corn oil (CO) or hydrogenated coconut oil (HCO). These differences were probably due to an essential fatty acid (EFA) requirement by the lobster for linolenic series omega3 or other fatty acids present in CLO. The linoleic or omega6 fatty acids of CO appeared to have some sparing effect on several of the EFA deficiency symptoms. It was found that 5% CLO was optimal for mean percent weight gain, molt incidence, feed conversion and hemocyte counts of lobsters. Further increases in dietary CLO to 10% and 15% resulted in no significant improvement of any of the condition indices used. There was a decrease in serum protein and calcium when lobsters were fed a non-saponifiable sterol deficient diet. The addition of 1% cholesterol to the diet raised the serum protein, but resulted in even a greater decrease in the serum calcium level.


Trace mineral deficiencies in rats caused by feeding rapeseed flours during growth, gestation and lactation. The present study determined the effect of duration of feeding and dietary levels of rapeseed flours on growth, outcome of gestation and lactation and blood trace element content of rats. In the first two experiments, female rats were fed either casein or rapeseed flour diets during gestation and lactation, or prior to and during gestation. In the last two experiments, weanling male rats were fed for 4 weeks either casein or rapeseed flour diets with or without added zinc. Feeding rapeseed flours prior to and/or during gestation caused a reduction in weight gains and food consumption but did not affect the number or weight of the pups born. Plasma zinc levels were low in the mother rats at parturition and plasma zinc and iron levels were low in weanling rats after 4 weeks of feeding the rapeseed diets. Adding 300 ppm zinc to the diet prevented the decrease in food consumption, weight gains and plasma zinc levels in the weanling rats. It is concluded that the recommended levels of trace elements in the rat diet are inadequate for the purpose of bioassay and toxicological evaluation or rapeseed preparations. In order that the nutritional potenital of new protein sources be correctly evaluated, guidelines for adequacy of mineral in such diets should be determined.


Cholesterol synthesis in germfree and conventional rats. The synthesis of cholesterol from labeled acetate and mevalonate by the liver and intestinal tract was investigated in germfree and conventional rats. When a low cholesterol diet was fed, the rates of in vitro synthesis from acetate by the liver, ileum and cecum of germfree rats were 13%, 11% and 25% of those of conventional rats, respectively. Cholesterol feeding markedly inhibited hepatic cholesterol synthesis from acetate in both germfree and conventional rats. Such inhibitions were released by additional cholestyramine feeding. The rate of hepatic cholesterol synthesis was greater and the liver cholesterol level was less after cholestyramine feeding in germfree rats than in conventional rats, suggesting an importance of bile acids in the regulation of cholesterol metabolism in the germfree rat. There was an inverse proportionality between the logarithmic rate of hepatic cholesterol synthesis and the liver cholesterol level in the germfree rat. Data indicate that endogenous cholesterol synthesis in the germfree rat may not be responsible for the high cholesterol level in plasma or liver and that the liver cholesterol level may play a major role in the regulation of hepatic cholesterogenesis in the germfree rat by a mechanism similar to that in the conventional rat.


Effect of dilauryl succinate on reproduction of the cock and hen and preventive effect of vitamin E. Fertility of White Leghorn cocks fed a diet containing 12% of dilauryl succinate (LS) for 16 weeks was significantly lower than that of cocks fed the control diet. Little difference in fertility and hatchability of fertile eggs was observed between White Leghorn hens fed the control or LS diets, but the percentage of chicks at hatch, which showed signs of encephalomalacia with lesions on the cerebellum, and the percentage of the hens and offspring having fragile erythrocytes were much higher when LS was fed. Total tocopherol in the plasma of the cocks and hens fed LS and in the eggs laid by the hens fed LS was lower than that in birds fed the control diet, though that of the hens was within the range of plasma tocopherol of normal hens. Offspring of the cocks and hens fed LS died from encephalomalacia earlier than those fed the control diet. These observations with LS feeding were all prevented by oral administration of dl-alpha-tocopheryl acetate. The responses of the cocks and hens to LS were compared with those to linoleic acid in the literature. The direct effect of LS, or more likely of monolauryl succinate, independent of peroxides from unsaturated fatty acids was discussed.


Effects of dietary protein and lysine levels on plasma amino acids, nitrogen retention and egg production in laying hens. The effects of dietary protein and graded dietary lysine levels on plasma free amino acids (PFAA), nitrogen retention and egg production in laying hens were studied. There were no significant differences in the PFAA pattern and nitrogen retention between hens fed 15% and 12% dietary protein whereas the hen-day egg production was greater with hens fed the 15% protein diet. Supplementing the 12% protein diet with a nonessential amino acid mixture at the 2% level improved egg production to the level of hens fed the 15% protein diet. When hens were fed a diet containing varying amounts of lysine, plasma lysine remained at relatively low levels until dietary lysine was increased to a level where egg production and nitrogen retention were maximized but therefore increased rapidly. When dietary lysine was increased, plasma concentrations of essential amino acids except methionine and lysine, half cystine and tyrosine tended to decrease. The plasma taurine concentration decreased when dietary lysine increased from 0.35% to 0.55%. Thereafter, it was the same as at 0.55% lysine. The dietary lysine requirement of laying hens determined by plasma free lysine, nitrogen retention and egg production were 677, 664 and 687 mg/hen/day, respectively. The PFAA technique appeared to be useful in evaluating the dietary requirement of laying hens for lysine and perhaps other amino acids.


Utilization of energy for maintenance and for fat and lean gains by mice selected for rapid postweaning growth rate. The metabolizable energy intake (MEI) required for maintenance and the efficiency of utilization of metabolizable energy available for gain (MEA) were determined for a line of mice (rapid growth) selected for 41 generations for rapid postweaning weight gain and for a contemporarily mated line (control) that had been randomly selected. Feed intake of individually housed rapid growth and control males was restricted above maintenance or was ad libitum from 21 to 42 days of age. Regressions of change in body energy per unity metabolic body size on MEI per unit metablic body size showed that the maintenance requirement for each line of mice was 176 kcal per unit metabolic body size per day and that the rapid growth line was more efficient than the control line in utilizing MEA (50% vs. 23%) to promote an increase in body energy. Although the proportions of MEA used for fat (PF) and lean (PL) gains and the net efficiencies with which those proportions were utilized for fat (NF) and lean (NL) gains were unknown, the products of proportion and efficiency for fat gain (PF X NF or fat energy deposition coefficient) and for lean gain (PL X NL or lean energy deposition coefficient) were determined. The results demonstrate that 41 generations of selection for rapid postweaning weight gain did not change the lean energy deposition coefficient, but did alter the fat energy deposition coefficient. These data suggest that the two lines of mice use different proportions of MEA for fat gain and/or utilize MEA for fat gain at different efficiencies.


Prospective study of sickle cell anemia in infancy. Twelve infants with sickle cell anemia identified in the course of a cord blood screening program have been followed prospectively for up to three years of age. The development of hemolytic anemia paralleled the postnatal decline in fetal hemoglobin and was evident in all infants by 12 weeks of age. Vasoocclusive episodes occurred in more than half the infants and seven aplastic crises were documented in four patients. Febrile illnesses were common and one of the twelve infants developed pneumococcal sepsis. This study also demonstrated that functional asplenia is an acquired defect in sickle cell disease. The onset of functional asplenia was documented with splenic scans in six of the nine infants followed for more than one year after birth. There have been no deaths in this series.


Inflammatory myopathy, IgA deficiency, and intestinal malabsorption. Two IgA-deficient children with inflammatory myopathy and intestinal malabsorption were evaluated. The myopathy was characterized by weakness of facial and proximal limb muscles, increased serum concentrations of lactic dehydrogenase and creatine phosphokinase, and histologic evidence of inflammation and degeneration of muscle fibers. Features of the intestinal abnormality were blunted villi, interstitial inflammation, and reduction in IgA-containing plasma cells and IgA content of epithelial cells. The myopathy and malabsorption improved with corticosteroid treatment. Circulating antibodies to striated muscle could not be demonstrated in either patient, but one had antibodies to milk and chicken serum proteins. We speculate that IgA deficiency may predispose to the development of inflammatory myopathy.


Esophageal reflux--an unrecognized cause of recurrent obstructive bronchitis in children. Forty-three children with recurrent obstructive bronchitis but without prominent gastrointestinal symptoms were studied for esophageal reflux roentgenographically and by manometry. Roentgenographic evidence for reflux was shown in 26; these patients had a mean lower esophageal sphincter pressure of 6.3 mm Hg as compared to a mean LES pressure of 21.9 mm Hg in normal control infants. The remaining 17 patients had a mean LES pressure of 10.0 mm Hg, also significantly lower than that of control subjects. Fifteen of 20 patients with recurrent obstructive bronchitis noted alleviation of their pulmonary symptoms after medical treatment of their reflux. Sequential studies of another group with radiologically demonstrated reflux showed increases in sphincter pressures and disappearance of radiologically observed reflux in one third of the patients. It is suggested that esophageal reflux should be sought in patients with recurrent bronchitis: if found, antireflux therapy might be expected to improve the pulmonary symptomatology.


Shifting linear growth during infancy: illustration of genetic factors in growth from fetal life through infancy. A percentile linear growth chart, from the third to ninety-seven percentiles, was derived from longitudinal data on 90 normal full-term infants of middle class suburban families, and the individual growth curves of each infant was contrasted to the growth chart for the entire group. Individual shifting in growth rate was noted in two thirds of the infants. To better determine the timing and nature of these shifts in linear growth, a search was made for otherwise normal full-term infants who were at or below the tenth percentile for length at birth and who moved up to the fiftieth percentile or better by age 2 years and those who were at or above the ninetieth percentile at birth and moved down to the fiftieth percentile or less by 2 years of age. Those shifting upward had accelerated linear growth soon after birth; they achieved a new "channel" at a mean age of 11.5 months. Those shifting downward did not decelerate until after the first three to six months; they achieved a new channel by the mean age of 13 months. These findings plus the correlation coefficients relating parental size to the length of the infant at birth, one year, and two years of age are compatible with the following statements: Birth length relates predominantly to maternal size whereas by 2 years of age the length correlates best to mean parental height, reflecting the genetic growth factors of both parents. Those infants "catching-up" after birth usually do so in early infancy, whereas those "lagging-down" tend to do so in midinfancy.


A "community" of face-limb malformation syndromes. A boy with faciodigital malformations is reported who bears a striking resemblance to Charlie M, a patient described by Gorlin as representing a new syndrome, and to two other previously reported patients. One may interpret this as supporting the validity of the "Charlie M" syndrome as a nosologic entity. However, these patients share a number of features with several other face-limb malformation syndromes. We suggest that these syndromes form a "community," in which the overlapping phenotypes of the member syndromes reflect underlying developmental relationships.


The role of exchange transfusion in the management of low-birth-weight infants with and without severe respiratory distress syndrome. I. Initial observations. Exchange transfusions within the first 8 hours of life, as an adjunct to conventional therapy, were evaluated in two groups of infants: (1) infants with birth weights of less than 1,250 gm without severe respiratory distress and (2) infants of any birth weight with evidence of severe respiratory distress syndrome. A total of 63 infants were studied in Group 1. Infants who received an exchange transfusion had a survival rate of 86% as contrasted with a survival rate of 57% in the control group (p less than 0.01). A total of 82 infants were studied in Group 2. Infants who received an exchange transfusion had a 59% survival rate as compared with a 39% survival rate for the control group (p less than 0.04). The mechanism by which early exchange transfusion improves survival rate is unknown.


The effect of maternal partial exchange transfusion on the infants of patients with sickle cell anemia. The reproductive outcome of pregnancies complicated by severe sickle cell hemoglobinopathies is not usually satisfactory. In this study, prophylactic partial exchange transfusions have been used in 35 patients with sickle hemoglobinopathies. There was significant improvement in results, both maternal and neonatal, as compared to those in 29 pregnancies complicated by similar disease processes who did not receive this therapy. The former group was also compared to 61 normal pregnant patients and 31 patients with sickle cell trait, none of whom received blood as part of their therapy. The results were similar in the group receiving transfusions and in the group with sickle cell trait. There was a decrease in perinatal wastage, prematurity, and incidence of low-birth-weight infants in the transfusion group when compared to the patients with hemoglobinopathies who were treated conservatively.


Massive intracerebellar hemorrhage in low-birth-weight infants. The clinical and pathologic observations of massive intracerebellar hemorrhage (destruction of at least one-third of cerebellar tissue) are described in six low-birth-weight infants. In all infants, severe progressive apnea associated with a falling hematocrit were the prominent clinical features. Four infants were asphyxiated at birth. Some degree of cerebellar hemorrhage (macroscopic or microscopic) was observed in 21% of 157 newborn brains examined at autopsy. The cause of massive intracerebellar hemorrhage is unknown, but may result from deforming pressures on the skull secondary to perinatal trauma. A close follow-up of cerebellar function in low-birth-weight infants is important.


Intracranial hemorrhages in kittens: hypernatremia versus hypoxia. Although CNS hemorrhages have long been observed in infants with hyaline membrane disease, the etiology of these hemorrhages is still unknown. Two proposed etiologies are hypoxia with acidosis and iatrogenic hypernatremia secondary to sodium bicarbonate therapy. An experiment on kittens comparing these two hypotheses suggested that intracranial hemorrhages were related only to elevated serum sodium concentrations. The CNS hemorrhages were independent of experimentally induced hypoxemia and its consequent acidosis.


Serum thyrotropin, prolactin, and growth hormone levels during the early neonatal period in the human infant. Normal term newborn infants have been studied during the first four hours after birth. Cord blood and brachial venous blood samples were collected for measurement of serum prolactin (n = 15; 11 vaginal delivery; four cesarean section delivery), thyrotropin (n=8), growth hormone (n=7), tri-iodothyronine (n=7) and thyroxine (n=7). The mean cord serum TSH concentration was 12 +/- 2 muU/ml and peaked in all infants 30 minutes after birth (67 +/- 7 muU/ml). Blood PRL also increased in all of the 15 infants studied; the mean cord blood value of 165 +/- 15 ng/ml increased significantly to a mean of 214 +/- 22 ng/ml at 30 minutes and 204 +/- 17 ng/ml at 60 minutes. The peak blood PRL concentration was observed at 30 minutes in eight newborn infants, at 60 minutes in three, and at 120 minutes in four. Mean serum GH concentrations were statistically similar during the first four hours but there was a tendency for serum levels to fall somewhat during the first hour after birth. The mean cord serum T3 concentration (47 +/- 5 mug/ml) increased significantly to a peak value of 227 +/- 38 ng/dl at 120 minutes. The increase in T4 from a mean of 15.3 +/- 1.2 mug/dl to a mean of 17.9 +/- 2.6 mug/dl at four hours was less dramatic. These data are consistent with the possibility that the same mechanism responsible for the neonatal TSH surge may be responsible for a significant but lesser PRL surge during the early minutes after birth.


Drug ingestions associated with miosis in comatose children. The occurrence of pupillary constriction in children comatose as a result of the acute ingestion of common drugs has been studied in a large pediatric hospital by reviewing records of patients admitted between 1965 and 1974. Among 94 patients with an acute drug ingestion, the frequency of miosis in relation to the cause of coma was 88% for narcotics, 72% for phenothiazines, 35% for ethanol, and 31% for barbiturates. In contrast, miosis was noted in only 3% of 105 patients with coma from head injuries or infection of the central nervous system. Miosis was associated with all four drug ingestions among patients in deep coma and with narcotic and phenothiazine ingestions among patients in light coma. The frequency of miosis was found to increase with increasing depth of coma in patients with all four drug overdoses, particularly among patients with phenothiazine and barbiturate ingestions.


Diuretic effect of furosemide in acute glomerulonephritis. Twenty-five children with the diagnosis of acute glomerulonephritis were treated with oral or intravenous doses of furosemide. The intravenous administration of 1 mg/kg or greater resulted in an increase in urine volume in all patients. Oral doses of less than 2 mg/kg were not as effective, but there was wide variation in diuretic response to the drug. In 13 patients, plasma concentrations of furosemide were measured. The plasma half-life varied from 2.3 to 4.4 hours after intravenous administration of the drug. The plasma concentration of furosemide did not correlate with diuretic response.


Subtherapeutic dicloxacillin levels in a neonate: possible mechanisms. A neonate treated initially with oxacillin intravenously for two weeks and who was receiving phenobarbital for a seizure disorder subsequently failed to achieve therapeutic levels of orally administered dicloxacillin, even when the dosage was as high as 175 mg/kg/day. Intestinal absorption was documented by high serum peak levels. The low trough levels correlated with a high urinary excretion rate. The possibillity that renal tubular transport of dichloxacillin was stimulated by administration of penicillin derivatives (and/or phenobarbital) is suggested, and the need for careful monitoring of serum levels of antibiotics in neonates is emphasized.


Differences in the metabolic and hormonal response to exercise between racing cyclists and untrained individuals. 1. Six well-trained cyclists and six untrained subjects were studied during and immediately after four successive 7 min periods of exercise at 30, 45, 60 and 75% of their maximal work capacity. 2. Venous blood samples were taken at rest, at the end of each exercise period and 5 min following the end of exercise, for estimation of metabolites in blood and plasma insulin, growth hormone, cortisol and catecholamines. 3. The results showed significant differences in the mobilization and utilization of muscle fuels between the athletically fit cyclists and the untrained group. In the cyclists, glucose, glycerol and free fatty acid concentrations were higher, but lactate, pyruvate and alanine were lower than in the untrained subjects during exercise. 4. Plasma catecholamines rose in both groups during exercise but the rise was significantly less in the racing cyclists. Plasma insulin was depressed to a greater extent in the untrained subjects during exercise and plasma glucagon rose to a greater extent during strenuous exercise and remained elevated after the end of exercise in the untrained group. Plasma human growth hormone rose to a greater extent during exercise and remained elevated after the end of exercise in the untrained group. Plasma cortisol fell at low and moderate exercise rates in both groups, but to a smaller extent in the cyclists. Cortisol values rose at higher workloads and were significantly higher in the cyclists at the end of exercise. 5. It is concluded that there are significant differences in the metabolic and hormonal responses to exercise between athletically trained and untrained individuals, even when the physically fit subjects work at the same percentage of their maximal capacity as the unfit subjects.


Action potentials reconstructed in normal and myotonic muscle fibres. 1. Muscle fibres from goats with myotonia congenita show characteristic responses to stimulation with intracellular currents (Adrian & Bryant, 1974). To test whether the reduced surface chloride conductance can account for these myotonic discharges, we have calculated responses of a model 'muscle fibre' to intracellular current of long duration (greater than 100 msec), assuming that the current is applied at the end of the fibre, that the fibre is of finite length, that a regenerative action potential occurs in the transverse tubular system as well as the surface, and that the potassium current in the wall of the transverse tubular system raises the potassium in the tubular lumen. In the absence of information about the kinetic parameters of the ionic currents in mammalian muscle we have used numerical values from frog muscle (Adrian, Chandler & Hodgkin, 1970). 2. In calculations with a normal surface chloride conductance a long maintained current gives only one action potential. Reduction of the chloride conductance to a half produces repetitive firing during the current; reduction to a tenth produces repetitive firing during and a small number of action potentials after the end of the current. Elimination of the tubular potassium accumulation from the calculation reduces the number but does not eliminate action potentials arising after the end of the applied current. 3. With a tenth of the normal chloride conductance calculated responses show maintained firing following a constant current if the deactivating rate of the sodium channels (betam) is reduced by 25%. As before, eliminating potassium accumulation reduces the number of post-stimulus action potentials, but it does not eliminate them altogether. 4. We conclude that in the absence of a surface chloride conductance tubular potassium accumulation could certainly contribute to the instability of the membrane, but it is clear that potassium accumulation is not the only reason for the instability of myotonic muscle fibres. The kinetics of the sodium channels are important and we do not know that they are the same in normal and myotonic fibres. Nevertheless the presence of a surface chloride conductance does stabilize the response of a fibre to constant current or to repetitive stimulation, and its absence could be a sufficient condition for myotonic behaviour.


The regulation of respiratory evaporative heat loss in the rabbit. 1. Respiratory evaporative heat loss in the rabbit has a minimum value of 0-2-0-3 W/kg and a maximum value of about 1-1 W/kg in non-evaporatively limited environments. 2. Both skin temperature and hypothalamic temperature influence respiratory evaporative heat loss, and they do so in a multiplicative fashion. Thus, at low skin temperature the hypothalamic temperature threshold for the onset of panting is above normal hypothalamic temperature and hypothalamic thermosensitivity is high. On the other hand, at high skin temperatures, the hypothalamic temperature threshold for the onset of panting is well below normal hypothalamic temperature, but hypothalamic thermosensitivity is greatly reduced. 3. The influence of mean skin temperature (Tsk) and hypothalamic temperature on respiratory evaporative heat loss (Eres) in the rabbit can be described by the equation: Eres=1-1-0-08 (Tsk-39-7) (Thy-42-9) greater than or equal to 0-3 W/kg. 4. Thus, the ability of a lowered mean skin temperature to increase the thermosensitivity of the hypothalamus in response to local temperature changes applies to heat loss mechanisms as well as heat production mechanisms. It is suggested that the characteristics of this peripheral input into the C.N.S. are fulfilled by tonic cold fibre input originating from the peripheral cold receptors on the body surface.


The negative potential wave evoked in cuneate nucleus by stimulation of afferent pathways: its origins and susceptibility to inhibition. 1. The negative (N)-wave evoked at various depths in the cuneate nucleus by stimulation of afferents in the ipsilateral forepaw or dorsal column has been studied in the rat. 2. Micro-iontophoretic applications of gamma-aminobutyric acid (GABA) into the vicinity of the recording electrode markedly reduced the amplitude of the negative wave, but only when recordings were made near the base of the cuneate nucleus. Nearer the surface of the medulla, GABA was much less effective. 3. A similar depth distribution obtained for the depression of the negative wave by micro-iontophoretic Mg2+ and enhancement by Ca2+. 4. Depression of the negative wave by conditioning stimulation of the afferent pathway also showed a similar depth distribution. The conditioned depression of the negative wave was most marked during the first 30 ms after the conditioning stimulus and this early depression could be antagonized by iontophoretic (+)-bicuculline methochloride. A lesser degree of conditioned inhibition of the negative wave persisted up to 80-200 ms but this was resistant to (+)-bicuculline methochloride. Thus, conditioned depression of the negative wave appeared to be mediated only in part by a GABA-like transmitter. 5. It is concluded that the negative wave recorded near the base of the cuneate nucleus has some of the predicted properties of a post-synaptic potential. These properties are not seen when the negative wave is recorded more superficially, near the surface of the medulla.


The location of cardiac vagal preganglionic motoneurones in the medulla of the cat. 1. Electrophysiological techniques have been used to locate the origin of preganglionic vagal motoneurones supplying the heart of the cat. 2. The right cardiac vagal branches were identified anatomically and their ability to slow the heart was assessed by electrical stimulation. Control experiments revealed that contamination of cardiac branches by bronchomotor and oesophageal efferent fibres was likely to be small. 3. Fifty-seven neurones in the medulla were activated antidromically on stimulating the cardiac branches at up to 5 times the threshold for cardiac slowing. They had axons with conduction velocities between 3 and 15 m/sec, corresponding to B fibres. 4. None of these were located in the region of the dorsal motor nucleus of the vagus, in spite of repeated sampling there, but all were located in the region of the nucleus ambigus. Histological examination of marked neurones (forty-six of the fifty-seven neurones) revealed that they were associated with its principal column, rostral to the obex. 5. Sampling motoneurones of the dorsal motor nucleus revealed that most sent axons down the thoracic vagus below the cardiac branches. Only three of thirty-three could be activated antidromically by high intensity stimulation of the cardiac branches, but on the basis of their thresholds and conduction velocities, it is argued that they were unlikely to be cardio-inhibitory neurones. 6. It is concluded that preganglionic cardio-inhibitory neurones arise not in the dorsal motor nucleus, but in the principal column of the nucleus ambiguus.


Respiratory frequency response to progressive isocapnic hypoxia. 1. Ventilatory, tidal volume and frequency responses to progressive isocapnic hypoxia have been measured in twenty-nine healthy subjects by a rebreathing technique. 2. A strong correlation was found between ventilatory response to hypoxia (deltaVI/DELTASaO2) and frequency response to hypoxia (deltaf/deltaSaO2) (r=0-82, P less than 0-001). There was a lesser correlation between deltaV1/deltaSaO2 and tidal volume response (deltaVT/deltaSaO2) (r=0-50, P less than 0-01). These findings suggest that the wide range of ventilatory response to hypoxia among subjects is mainly determined by differences in frequency response and contrast with previous findings in studies of the response to progressive hypercapnia. 3. The breathing pattern during progressive hypoxia and hypercapnia was compared in ten subjects. Ventilation/tidal volume plots were constructed and patterns of response were further analysed in terms of inspiratory duration (TI), expiratory duration (TE) and mean inspiratory flow rate (VI). 4. Increments in ventilation during hypoxia were achieved with a greater respiratory frequency and a smaller tidal volume than during hypercapnia in eight of the ten subjects studied. In two subjects no difference in breathing pattern during hypoxia and hypercapnia was observed. 5. Changes in respiratory frequency during progressive hypoxia were achieved in all subjects by a progressive shortening of TI and TE. By contrast, TI remained constant during hypercapnia until VT had increased to 3-5 times the eupnoeic value; during hypercapnia the increase in frequency was achieved mainly by a progressive shortening of TE. 6. It is concluded that different mechanisms may be involved in altering respiratory frequency when ventilation is driven progressively by these different chemical stimuli.


A pharmacological study of Renshaw cell inhibition. 1. In cats anaesthetized with pentobarbitone a pharmacological investigation was made of the inhibition of Renshaw cells by dorsal root afferent volleys and ventral root antidromic volleys, and of the inhibition of motoneurones by Renshaw cells. 2. The effects of strychnine, bicuculline and tetanus toxin indicate that both glycine and GABA operate as inhibitory transmitters released on Renshaw cells by dorsal root volleys. 3. The 'mutual' inhibition of Renshaw cells, and the recurrent inhibition of motoneurones by Renshaw cells, are suppressed by strychnine: Renshaw cells are thus glycinergic inhibitory neurones, a proposal consistant with recent evidence for strychnine-sensitive inhibition of Ia interneurones by Renshaw cells. 4. The 'pause' which follows high frequency synaptic excitation of Renshaw cells is insensitive to strychnine, bicuculline and tetanus toxin, and is considered unlikely to be the consequence of synaptic inhibition.


Studies on renin release from isolated superfused glomeruli: effects of temperature, urea, ouabain and ethacrynic acid. 1. The effects of different energy substrates, of low temperature, of urea, and of ouabain and ethacrynic acid were studied on the rate of renin release from viable juxtaglomerular cells during superfusion of isolated rat glomeruli. 2. Neither lactate nor glutamate altered renin release rate from that observed using glucose as the sole energy substrate. Succinate 10 mM elevated release transiently but did not influence the release caused by reductions in osmolality through lowering sucrose concentration. 3. Peak renin release was more prolonged and returned more slowly to control following reductions in osmolality in phosphate-Ringer than in bicarbonate-Ringer. 4. At 37 degrees C, the peak of renin released induced by hypo-osmolality was smaller and delayed, and returned earlier to control than at 30 degrees C. Reduction in temperature from 30 to 4 degrees C resulted in a 32-fold increase in basal release rate. At 4 degrees C a 20 m-osmole/kg reduction in tonicity caused an additional 2-5-fold increase in release rate. 6. Increasing superfusate osmolality with urea did not affect basal renin release but 100 mM urea suppressed the releasing effect of a 15 mM reduction in NaCl concentration. 7. Ouabain (10(-4) M) caused a small (33 +/- 9%, P less than 0-025) transient increase in renin release. Ethacrynic acid (10(-3) M) provoked a progressive increase in release reaching 100 +/- 15% above control within 50 min. In the presence of both inhibitors the release provoked by hyposmolality was prolonged. 8. It is concluded that renin release in vitro is a function of actively regulated cell volume and it is proposed that a similar mechanism could underline both barorecptor and macula densa controls of renin secretion in vivo.


Direct and indirect activation of nerve cells by electrical pulses applied extracellularly. 1. The mode of activation of nerve cells by extracellular stimuli was investigated while recording from a selected cell with one electrode, and applying current pulses around this cell with another electrode. The analysis was done on motoneurones and on spinal border cells from lower lumbar segments in the cat. 2. Directly evoked action potentials were defined by their appearance in an all-or-none fashion with stable latencies of less than 0-5 ms. The lowest thresholds for their generation were 0-15-0-20 muA in the spinal border cells and 0-35-0-40 muA in the motoneurones. In the main series on motoneurones a correlation has been established between different positions of the extracellular stimulating electrode in relation to the cells and the thresholds for the direct excitation of these cells. The position of the electrode were defined on the basis of an analysis of the IS and SD components of the action potentials recorded extracellularly around the cell when evoked by current pulses applied through the intracellular electrode; both the amplitudes of these IS and SD components and their timing with the IS and SD spikes, which were simultaneously recorded with the intracellular electrode, were then taken into account. The lowest thresholds (less than 2 muA) for the direct activation of cells were found nearest the initial segment of the axon. Their values increased to about 5 mu A at near-soma positions and to greater than 10 muA at near-dendrites positions about 150 mum away. 3. Transsynaptically evoked action potentials which were clearly set up by the preceding e.p.s.p.s appeared with latencies greater than 0-7 ms. When single current pulses were used, the lowest thresholds for transsynaptic spike activation were usually greater than 5-10 muA but they considerably decreased with repetitive stimuli. These thresholds were higher than the thresholds for the direct activation of cells within the region of the initial segment, of the same order of magnitude near the soma, and lower when the stimulating electrode was nearer the dendrites than the soma and generally at all larger distances from the cells. 4. All the observations on direct excitation of cells by extracellular stimuli (generation of the IS spike before the SD spike, lowest thresholds near the region of the initial segment of the axon, similar rates of increase in these thresholds with distance as for fibres) lead to the conclusion that the effects of the extracellular stimuli are exerted primarily via spread of current to the initial segment of the axon and its depolarization. 5. Late extracellular negativities presumably related to dendritic activation were observed in a few cells. These negativities were synchronous with late components of the intracellulary recorded action potentials.


The clinical side of cytogenetics.

The clinical side of cytogenetics. In 1956 the correct number of chromosomes was established in man, and in 1959 the well-recognized syndromes of Down, Turner and Klinefelter were shown to be associated with chromosomal anomalies. During the following 10 years more than 100 chromosomal anomalies were discovered by what now appear to have been rather crude and undiscriminating techniques, as reflected in the repeated attempts to standardize the human karyotype, first at Denver in 1960, then in London in 1963 and in Chicago in 1966. At the Second Denver Conference in 1970 a dramatic change took place as a result of the introduction of a technique by which every individual chromosome could be distinguished; by the time the next Conference on Standardization in Human Cytogenetics was held, in Paris in 1971, additional techniques had been developed that could distinguish not only every chromosome but also different regions of each chromosome. We are now able to define normal variants reliably, identify extra chromosomes involved in abnormalities accurately, recognize small defects which were missed previously and map structural defects precisely by tracing exchange segments of chromosomes. Cytogenetics should be used by the clinician to establish a diagnosis as a guide to a rational plan of management, as a guide to prognosis and genetic counseling and for monitoring pregnancies in people at increased risk of having children with defects associated with chromosomal anomalies.


[UHT--behandeling van melk (author's transl)]. Pasteurisation of milk provides protection for the consumer against pathogens which may be present in the raw milk, and improves its keeping quality. Sterilisation provides indefinite keeping quality but has an undesirable effect on the flavour and nutritive value of the milk. Ultra high temperature (UHT) treatment produces a milk with prolonged shelf life at ambient temperatures yet has practically the same effect on colour, falvour and nutritive value as pasteurisation. UHT treatment of milk involves preheating to 80 degrees C and then quickly raising the temperature, either by indirect heating in a tubular heater or by direct steam injection, to 130 degrees-- to 150 degrees C at which temperature it is kept for 3 to 5 sec. Cooling follows immediately. Systems in operation in South Africa use steam injection for heating to sterilising temperatures. Evaporation cooling is obtained by subjecting milk to a partial vacuum. This removes any water added during heating by condensing steam and also removes steam-volatile off-flavours. UHT-treated milk is packed aseptically, usually into heat-sealed paperboard laminated cartons. Intact packages can be kept for up to three months. Absolute sterility cannot be obtained by UHT processing. The term "sterilising effect", introduced by Galesloot, means the log10 of the ratio of initial spore count to surviving spore count. A spoilage rate of not more than one litre package per 1000 is considered satisfactory. For laboratory control samples of the sterilized milk are incubated at temperatures favourable to germination of mesophilic and thermophilic spores respectively. After incubation the milk is examined for flavour and physical appearance, subjected to the standard plate count and tested for increase in acidity and decrease in stability towards the alcohol test. Milk for UHT treatment must possess protein stability in the alcohol test, be of good bacteriological quality, and a low spore count in particular.


Induced parturition in cattle. 1. Clinical studies. Parturition was induced in 17 Friesland heifers to decrease the possible occurrence of dystocia. The heifers were given 39 mg dexamethasone intra-muscularly on the 267th day of pregnancy and were observed for signs of impending parturition. The time of foetal membrane expulsion was noted. Parturition occurred on an average of 57 hours after corticosteroid administration. Three heifers required assistance during parturition. In one case a second injection of dexamethazone had to be given. The incidence of retained placenta was 68,8%. Rectal examination five to seven months after induction revealed that 76,5% of all animals were again pregnant. Of the four non-pregnant animals three had received assistance during parturition.


An outbreak of diphtheria in Boergoat kids. During an outbreak of diphtheria or ulcerative stomatitis in young Boergoat kids Fusobacterium necrophorum was consistently isolated under anaerobic cultural conditions from material taken from the edges of the ulcerative lesions from all of the cases examined. Corynebacterium pyogenes, Staphylococcus aureus, Actinobacillus lignieresi, Moraxella spp. and Lactobacillus spp. were also isolated anaerobically and/or aerobically. The typical symptoms and lesions were confirmed to the mouth, tongue and throat regions.


Bovine cerebral theileriosis: a report on five cases with splenic infarction. Five cases of bovine cerebral theileriosis are described. Macroscopically visible thrombosis of branches of the splenic vessels with associated infarction of the spleen are reported for the first time in this disease. The presence of Koch's bodies in thrombosed splenic vessels or vessels clogged with lymphocytes in the spleen is also a new finding. These changes were encountered in all five cases.


The prevalence of dourine in southern Africa. The geographical distribution of positive dourine cases found on serological testing at Onderstepoort during the period 1954 to 1975 is recorded, showing major foci of infection occurring in the northern Cape Province, northern Orange Free State, western and north-western Transvaal. Positive cases are also recorded from South West Africa, Botswana, Lesotho, Swaziland and Rhodesia.


Experiences in the diagnosis of brucellosis in dairy cows. The Milk Ring, Serum Agglutination, Biological, Mercaptoethanol and Rose Bengal Plate Tests were used in combination to diagnose brucellosis in cows in some herds supplying milk to Johannesburg. The work was done in conjunction with routine testing of bulk milk supplies for public health control. 4 769 cows in more than 76 herds were involved in the tests. Results confirm that no single test can demonstrate all infected cows in a herd and that repeated testing is necessary. In an infected herd in which Strain 19 adult vaccination has been used some negative and suspicious cows will have to be sacrificed in eradicating the disease.


Quantum chemical studies of methadone.

Quantum chemical studies of methadone. Quantum chemical calculations were performed on the flexible methadone molecule to test the hypothesis that it structurally mimics the fused ring structure of morphine. In these calculations using the semiempirical, PCILO method, protonated and nonprotonated conformations were considered representative of different types of intramolecular interaction at the morphine receptor. Calculated energies for these conformations were compared to those calculated for protonated and nonprotonated extended chain and crystal structure conformers. Lowest energy conformations showed intramolecular bonding but the resultant molecular geometries were not very morphine-like. A comparison of the structure of methadone to that of meperidine seemed equally as valid.


Structure-activity studies on sulfamate sweeteners. The structure-activity relationships governing sulfamate sweeteners are reviewed under the headings: size of the reduced ring, changes in the sulfamate function, substitution of hydrogen in the ring, and substitution of carbon in the ring and open-chain compounds. Fifteen compounds have been synthesized with a view to testing the limitations on structural changes which may be made within these categories without loss of sweetness. The presence of the grouping greater than CHN(R)SO3- is suggested as a necessary but not a sufficient condition for a compound to be sweet-tasting. Thus, the B center of the Shallenberger A-H,B theory of sweetness is best regarded as being -SO3- rather than -SO2- for sulfamates. Threshold levels and relative sweetness have been determined for seven sulfamates.


Synthesis and some pharmacological properties of oxytocin analogues having L-thiazolidine-4-carboxylic acid in position 7. [7-Thiazolidine-4-carboxylic acid)]oxytocin and [1-beta-mercaptopropionic acid,7-(thiazolidine-4-carboxylic acid)]oxytocin have been synthesized by a solid-phase method. Alpha-N-tert-Butoxycarbonyl- and S-ethylcarbamoyl-protecting groups were employed. The dipeptide Boc-Cys(Ec)-thiazolidine-4-carboxylic acid as well as individual residues was coupled to a H-Gly-dehydroalanine-resin with dicyclohexylcarbodiimide in the presence of 1-hydroxybenzotriazole. The appropriate protected polypeptide intermediates were cleaved from the resin by acidolysis, deprotected in NH3, and oxidized to the cyclic disulfide analogues with ICH2CH2I. Purification was effected by partition chromatography and gel filtration. Relative to oxytocin and [1-beta-mercaptopropionic acid]oxytocin, these analogues exhibit greatly enhanced oxytocic and avian vasodepressor potencies and unchanged rat pressor potencies.


Synthesis and antihypertensive activity of some thienylethanolamines. Synthesis of a series of thienylethanolamines having varying substituents on the thiophene ring and on the nitrogen atom is described using the general procedure reported earlier. In the determination of their pharmacological profile, some of the derivatives showed marked antihypertensive activity in the spontaneously hypertensive rat model. Tests are also reported which demonstrated that some of these derivatives antagonized alpha- and/or beta-adrenoreceptor activities. The ability of this class of compounds to inhibit catecholamine-induced release of free fatty acids by adipose tissue was demonstrated. Structure-activity relationships in different tests were also determined.


Tetramethoxydibenzoquinolizinium salts. Preparation and antileukemic activity of some positional and structural isomers of coralyne. Some positional and structural isomers of coralyne were prepared and evaluated in the P388 lymphocytic leukemia system for their inhibitory activity. The levels of antileukemic activity of coralyne, neocoralyne, isocoralyne, and stracoralyne were comparable, thus implying that two sets of the N-O-O triangular pharmacophore in a condensed isoquinoline molecule are preferable and the angle between these two sets has little influence on antileukemic activity. The importance of the environment around the C5-C6 region of the dibenzo[a,g]quinolizine ring to antileukemic activity was demonstrated by the activity differences between coralyne and allocoralyne.


Oxindole-3-spiropyrrolidines and -piperidines. Synthesis and local anesthetic activity. The synthesis and local anesthetic properties of five 1-dealkyloxindole-3-spiropyrrolidines and six 1-dealkyloxindole-3-spiropiperidines are described. The compounds studied include members of all five possible positional isomers of the two classes of spirooxindoles; all showed local anesthetic activity by the rat sciatic nerve block method. The coincidence of the least variability in the relative positions of basic nitrogen, amide carbonyl, and aromatic ring (compounds 1 and 6) with lowest normalized toxicity is noteworthy.


Synthesis of 5-substituted 2'-deoxyuridines. A series of thymidylate synthetase inhibitors was synthesized, some of which were potential irreversible inhibitors. 5-Formyl-2'-deoxyuridine (9) and its dithiolane derivative 11 were prepared by condensation of the bis(trimethylsilyl) derivative of 5-formyluracil dimethyl acetal and the protected chloro sugar followed by saponification of the protective groups. 5-Acetyl-2'-deoxyuridine (15) was prepared in the same way from 5-acetyluracil. Treatment of the diester of 5-allyl-2'-deoxyuridine (17 or 22) with m-chloroperbenzoic acid gave the corresponding epoxide. Dimethylamine removed the ester groups and opened the epoxide to give the amino alcohol 24. The diester of 5-chloromethyl-2'-deoxyuridine (27) treated with methanol or sodium azide gave 5-methoxymethyl- (29) and 5-azidomethyl- (31) 2'-deoxyuridines. Compound 27 also was converted to 5-iodoacetamidomethyl-2'-deoxyuridine by treatment with ammonia, chloroacetyl chloride, base saponification, and finally sodium iodide.


Quaternary pilocarpine derivatives as potential acetylcholine antagonists. 2. Alterations in the lactone and imidazole moieties. In order to investigate the chemical behavior of pilocarpine, as well as the factors which determine its pharmacological activity, systematic and specific structural changes involving the lactone and imidazole moieties have been performed. Series of model compounds with cyclic or open-chain structures and a variety of N-3 bonded chains obtained from previously prepared anticholinergic derivatives of pilocarpine have been synthesized. The changes included N-3 chains of different lengths with an acetylcholine-like structure, the introduction of nucleophilic groups such as ketoxime, hydroxamic, or both at the side chain, or following hydroxylaminolysis of the lactone, respectively. Specific structural alterations could be obtained by reacting with free hydroxylamine under carefully controlled conditions, and the existence of syn and anti isomers was disclosed in certain cases. The new groups in the pilocarpine derivatives influenced their degree of antagonism to acetylcholine. Several compounds displayed some antidotal activity.


6,11-Dihydro-11-oxodibenz [b,e] oxepinacetic acids with potent antiinflammatory activity. A series of 6,11-dihydro-11-oxodibenz[b,e]oxepinacetic acids was synthesized and the antiinflammatory activity determined. Studies on 29 compounds revealed certain structure-activity relationships. In the carrageenan edema test, eight compounds exhibited higher antiinflammatory activities than did indomethacin. Several compounds (2, 9, 14, 22, 25) also proved to have activities superior or comparable to indomethacin in suppressing chronic as well as acute inflammation and carrageenan-induced hyperesthesia. Gastric irritation and lethality rates were less frequently observed with these compounds.


Chemistry of nitrosoureas. Decomposition of Deuterated 1,3-bis(2-chloroethyl)-1-nitrosourea. BCNU-alpha-d4 [1,3-bis(2-chloro-1,1-dideuterioethyl)-1-nitrosourea] and BCNU-beta-d4 [1,3-bis(2-chloro-2,2-dideuterioethyl)-1-nitrosourea] were synthesized and decomposed in buffered (pH 7.4)water. The products were analyzed by GC-MS. The deuterium distribution in the products is inconsistent with vinylcarbonium ion or diazochloroethane intermediacy but is consistent with a 2-chloroethylcarbonium ion intermediate with some rearrangement to the 1-chloroethylcarbonium ion and the cyclic chloronium ion.


Tissue distribution of technetium-99m and carbon-14 labeled N-(2,6-dimethylphenylcarbamoylmethyl)iminodiacetic acid. The synthesis, radiochemical labeling, and tissue distribution characteristics of N-(2,6-dimethylphenylcarbamoylmethyl)iminodiacetic acid are described. The radiopharmaceutical prepared by labeling with 99mTc was rapidly eliminated through the hepato-biliary system of mice. Parent 14C compound was eliminated primarily through the kidney. The 99mTc ion appears to have a greater influence than the organic carrier molecule on the distribution of the radiopharmaceutical.


Adamantane and protoadamantanealkanamines as potential anti-Parkinson agents. The synthesis of 2-halo-1-adamantanemethanamines, 4-protoadamantanemethanamines, and 4-protoadamantaneamines is described. The anti-Parkinson activity of these amines in terms of reversal of reserpine-induced catalepsy in rats has been evaluated and compared with amantadine. 2-Bromo- and 2-chloro-1-adamantanemethanamines are shown to be twice as active as amantadine.


(Vinylaryloxy)acetic acids. A new class of diuretic agents. 4. Various ((2-substituted and 2,2-disubstituted vinyl)aryloxy)acetic acids. A variety of [(2-substituted and 2,2-disubstituted vinyl)aryloxy]acetic acids was synthesized in which the substituents were primarily electron-withdrawing groups. These compounds were tested in dogs for their saluretic and diuretic properties. Many of the compounds exhibited significant activity; however, they were generally less potent than those reported in the three earlier papers in this series.


Synthesis and antimineralocorticoid activities of some 7alpha-cyano and 7alpha-alkoxycarbonylamino steroidal spirolactones. The synthesis and antimineralocorticoid potencies of several steroidal spirolactones bearing novel nitrogenous substituents in the 7alpha position are reported. These substituents include the cyano, the isocyanato, and the alkoxycarbonylamino groupings. The nitrile 1b and the N-carbomethoxy compound 1h showed good antimineralocorticoid potency (MED less than or equal to 0.79 mg) on subcutaneous administration to adrenalectomized rats.


Interdisciplinary teamwork.

Interdisciplinary teamwork. A group of consultants of different disciplines working as a close-knit team is not a new idea in Britain, but including the patient or client in that team is a new concept when constructing an interdisciplinary team. Some of the lessons learned in working in interdisciplinary teams may have been tacitly understood in the past but in this paper Dr De Wachter expands and illustrates the philosophy behind interdisciplinary teamwork. He explains how communication grows into "another language" and how those of disparate disciplines become one in their thinking when solving a problem together. There is an ethic of teamwork, too, which is elucidated in this paper, especially in relation to the pitfalls of power and shared responsibility. A number of case histories illustrate the argument.


What is barbiturate dependence and who is at risk? The dependence on drugs today, particularly by young people, must concern many - doctors and nurses, social workers, lawyers and the police, and parents. The writers of the group of papers which follow, although inevitably overlapping in some respects, attempt to examine the questions raised from the particular point of view of each. When does taking a drug (generally a barbiturate) become a state of dependence is the question posed and answered by Dr Connell. He begins by setting out the series of offical definitions of addiction, habituation and dependence formulated by the World Health Organization and in Britain by the Interdepartmental Committee (the Brain Committee). With these definitions as a framework he examines barbiturate dependence and abuse in the setting of current medical practice.


Barbiturate abuse.

Barbiturate abuse. The barbiturates are the drugs most commonly abused, and in his paper Dr d'Orban gives the general reader a clear, sober account of the drugs so abused, the pattern of abuse and the prevalence of the abuse of barbiturates. Sadly, some addicts add barbiturates to their abuse of other drugs upon which they depend. Dr d'Orban concludes his survey by telling how those addicted to barbiturates obtain the drugs and the hazards to which they expose themselves.


The moral choice in prescribing barbiturates. Dr Wells, a general practitioner, looks at the problem of barbiturate dependence from the point of view of the prescribing doctor who has to choose for his patients - of all ages - the drug, usually a hypnotic, which is sought for insomnia or states of anxiety and stress. He argues that it is wise to prescribe non-barbiturates, but that even in elderly people it is possible and the right course of action is to wean these patients from their dependence on sleep-inducing drugs. Young people often acquire the drug habit by taking hypnotics from a bedside table or a bathroom cabinet in their own homes.


Some problems of confidentiality in medical computing. Patients have a right to consider that any information about themselves will be regarded as confidential, but inadvertently, and, very occasionally deliberately, that confidence may be broken. Therefore the principles on which the computer system at The London Hospital is based rest on maintaining confidentiality but at the same time using the facilities unique to the computer to the fullest extent for the benefit of patients. The system is described in outline, and a note is added of occasions when it would be desirable to suppress information on a patient and the reasons for so doing.


The teaching of medical ethics.

The teaching of medical ethics. The subject of medical ethics is intended to run like a thread throughout the whole undergraduate period at the Nottingham Medical School which was established in 1970, the first such foundation in Britain this century. Dr J S P Jones, who is the Clinical Subdean, and Dr D H H Metcalfe,of the Department of Community Health, describe the plan of the course leading to qualifying, and how the thread of medical ethics has been woven into that fabric. The final objective of the course is to train men and women to become technologically capable and at the same time alive to the human needs of their patients. The authors define the two crucial characteristics of the fully trained professional as a person - self regulating and self policing - who advises and does not command those who come to him as patients.


Volunteers at risk.

Volunteers at risk. An experiment is described in which three male volunteers, who fully understood the nature of the project, were given doses of heroin which could have led to addiction if the subjects had proved to be physiologically or psychologically vulnerable to developing a state of addiction. The experiment was discussed most carefully by the Ethics Committee of the unit where it was conducted, and the subjects were themselves the investigators. The objective was to learn about the initial stages of the adaptation to heroin, of which nothing was known as heroin addicts usually come to the doctor when the habit is firmly established. A physician, who has studied the subject of drug addiction in a special clinic, is the first commentator, the second a lawyer and the third an associate professor of social ethics. These three experts are not discussing the results or the methodology of the experiment but whether the decision of the Ethics Committe was the right one.


Theory of lipid monolayer and bilayer phase transitions: effect of headgroup interactions. Headgroup and soft core interactions are added to a lipid monolayer-bilayer model and the surface pressure-area phase diagrams are calculated. The results show that quite small headgroup interactions can have biologically significant effects on the transition temperature and the phase diagram. In particular, the difference in transition temperatures of lecithins and phosphatidyl ethanolamines is easy to reproduce in the model. The phosphatidic acid systems seem to require weak transient hydrogen bonding which is also conjectured to play a role in most of the lipid systems. By a simple surface free energy argument it is shown that monolayers under a surface pressure of 50 dynes/cm should behave as bilayers, in agreement with experiment. Although the headgroup interactions are biologically very significant, in fundamental studies of the main phase transition in lipids they are secondary in importance to the hydrocarbon chain interactions (including the excluded volume interaction, the rotational isomerism, and the attractive van der Waals interaction).


Simulation studies on the evolution of amino acid sequences. A model of molecular evolution in which the parameter (intrinsic rate of amino acid substitution) fluctuates from time to time was investigated by simulating the process. It was found that the usual method of estimation such as Poisson fitting underestimates this variation of the parameter when remote comparisons are made. At the same time, four distance measures (minimun base difference, Poisson fitting, random nucleotide substitutions and negative binomial fitting) were tested for their accuracy. When the substitution rate is not uniform among the amino acid sites, the negative bionomial fitting gives most satisfactory results, however, one needs to know the parameter beforehand in order to use this method. It was pointed out that the fluctuation of the evolutionary rate is expected if the nearly neutral but very slightly deleterious mutations play an important role on molecular evolution.


Amino acid sequence and immunological properties of chalchalaca egg white lysozyme. The amino acid sequence of lysozyme c from chachalaca egg white was determined. Like other bird lysozymes c, that of the chachalaca has 129 amino acid residues. It differs from other avian lysozymes c by 2 to 31 amino acid substitutions as well as by being devoid of phenylalanine. It contains substitutions at 9 positions which are invariant in the other 7 bird lysozymes of known sequence. Although the chachalaca is classified zoologically in the order Galliformes, which includes chickens and other pheasant-like birds, its lysozyme differs more from those of pheasant-like birds than do the lysozymes c of ducks. Phylogenetic analysis of the sequence comparisons confirms that the lineage leading to chachalaca lysozyme c separated from that leading to other galliform lysozymes c before the duck lysozyme c lineage did. This indicates a contrast between protein evolution and evolution at the organismal level. Immunological comparison of chachalaca lysozyme c with other lysozymes of known sequence provides further support for the proposal that immunological cross-reactivity is strongly dependent on degree of sequence resemblance among bird lysozymes.


Bone densitometry with L125 in the study of uraemic osteropathy: semeiological signifiance and limitations. Bone densitometry using I125 is a very easy method of investigation; it may be used repeatedly and simultaneously at different bone levels without distress to patients. The problems involved were those of the value, semeiological significance and possible limitations of this method in the investigation of uraemic osteopathy. These problems were solved successfully in tests carried out on 87 patients of both sexes suffering from various degrees of chronic nephropathy and on chronic haemodialysis patients. The method is reliable: reproducibility tests in normal and uraemic subjects were satisfactory; the indexes remain constant, usually in normal subjects. The parameters are "Bone Mineral Content" and "Bone Index". Trabecular bone is more sensitive than cortical bone, although comparisons between the two types of bone produce interesting data. There are difference dependent on sex. The method which is more sensitive than others enables: 1) Normal and nephropathic subjects, to be distinguished from one another. The latter generally show a lower mineral content and bone index (clinical picture of osteomalacia, osteoporosis, hyperparathyroidism) seldom a higher or a normal one. 2) The same bone sites to be examined over a given period. 3) Treatment of patients to be monitored.


Defective calcium absorption in the proximal small intestine in chronic renal failure: effect of dihydrotachysterol. Intestinal absorption of calcium was evaluated in 6 uraemic patients and in 7 control subjects by a two isotope technique exploring absorption in the four hours following ingestion of the dose. In the first two hours, calcium absorption in the patients was markedly lower than normal and was corrected by 6-10 day administration of dihydrotachysterol, 0.66 mg per day. The administration of 0.33 mg per day proved less effective. The data indicate the existence of impaired intestinal calcium absorption in chronic renal failure and reversal of the defect after DHT administration. The method of investigation appears to be a valid procedure for the study of calcium malabsorption of CRF and in the evaluation of the effect of vitamin D metabolities and analogs.


Studies on urolithiasis in Israel.

Studies on urolithiasis in Israel. The composition of 1,000 kidney stones in our area of Israel was analyzed. The predominant stones were a combination of calcium oxalate and calcium phosphate, and uric acid. We used chemical analysis to determine the relative incidence of urinary calculi in 500 patients of various ages and ethnic groups. The incidence of calcium oxalate and calcium phosphate calculi (44 per cent) in Jews born in Israel was lower than in other ethnic groups (54 to 64 per cent). The incidence of uric acid stones in Jews born in Israel, Lebanon, Iran, Iraq and Syria, and the Ashkenazim (16 to 29 per cent) was 2 to 3 times higher than in other groups. In more than 60 per cent of the patients urolithiasis developed after they were 20 years old. The age at onset was significantly younger in Jews born in Israel (25.7 per cent) and North Africa (13.8 per cent), and in Arabs (18 per cent).


Percutaneous nephrostomy.

Percutaneous nephrostomy. A safe and effective method for long-term relief of renal obstruction is presented. This method has been successful in buying time for patients in stiuations in which other approaches are hazardous or more complex. Its use can be modified for short-term therapeutic drainage of the upper urinary tract.


The protean manifestations of renal vein thrombosis in the adult. We reviewed 8 cases of renal vein thrombosis, 4 of which were detected at autopsy, 1 by laparotomy and the remaining 3 by venography. In 4 cases malignancy also was found and in 2 membranous glomerulonephritis was noted. In 1 patient the thrombosis occurred in a solitary kidney, while it was bilateral in 3. The 4 patients in whom the diagnosis was made during life were treated with anticoagulants alone and 3 are alive with stable renal function 3, 4 and 7 1/2 years after diagnosis.


Renal carcinoma discovered incidentally by arteriography during evaluation for hypertension. Since June 1, 1971 patients undergoing evaluation for hypertension have been evaluated with rapid sequence excretary urography, abdominal aortography and selective renal arteriography. Renal venous assays have been done in selected patients. Through July 31, 1974, 812 arteriographic studies in new hypertensive patients have been done. In 6 of these patients renal tumors were discovered by arteriography only and were not suggested by symptoms, urinalysis nor diagnosed on hypertensive excretory urography. This high incidence surprised us and we hope others will review their arteriographic series of hypertensive patients.


The role of ultrasonics in the evaluation of renal masses. Analysis of our experience with echography in the evaluation of renal masses reveals an error rate of 31 per cent. Presently, this technique may be useful in directing the evaluation of a renal mass to either arteriography, if a tumor is suspected, or needle aspiration and renal cystogram, if a cyst is suspected. However, echography should not replace more definitive studies.


Fibrous polyps of the ureter.

Fibrous polyps of the ureter. Two cases of fibrous polyps of the ureter are reported. In 1 case there was coexistent transitional cell carcinoma, Certain changes suggesting a benign lesion are described. Fibrous polyps are best treated by local excision.


The ureteral stump after nephroureterectomy. Herein we review 70 cases of transitional cell carcinoma of the upper urinary tract. When complete nephroureterectomy was not performed transitional cell carcinoma developed in 30 per cent of the remaining ureteral stumps. Single incision nephroureterectomy did not include the intramural ureter in 50 per cent of the cases in which it was performed. When nephroureterectomy is selected as treatment for carcinoma of the renal pelvis or ureter a cuff of bladder, which includes the ureteral orifice, should be removed. A second incision may be required for adequate exposure.


Diagnosis of retroperitoneal fluid collections by ultrasonography: a series of surgically proved cases. Herein are presented 18 patients with a variety of retroperitoneal fluid collections. Etiologic factors and culture results are discussed. Ultrasound was the single most valuable diagnostic study. Because of its accuracy and non-invasiveness it should be used early in the diagnostic study of a patient with a suspected retroperitoneal fluid collection.


Surgical repair of post-hysterectomy vesicovaginal fistulas. Herein we describe in detail the preoperative evaluation, surgical technique and postoperative care used in repairing 13 post-hysterectomy vesicovaginal fistulas by the transabdominal transvesical approach. We were successful in all 13 cases, although 1 required 2 operations. Excellent results can be obtained in these patients if a complete urological diagnostic study is done, a careful technique is used during the operation and specialized postoperative care is given. The transabdominal transvesical approach to this problem is safer and gives better results than the transvaginal operation.


Vesicocolonic fistulas in diverticulitis. Diverticulitis is a disease affecting patients in the fifth to sixth decades. The charts of 12 patients with cesicocolonic fistulas secondary to diverticulitis were reviewed. Their presentation was primarily urological with pneumaturia present in 10 of 12 patients and fecaluria present in 5 of 12. The process of fistulization occurs in stages. If the incipient stage can be identified early fistulization can be prevented and the morbidity and mortality rates will be reduced significantly. In older patients with bladder irritation (with or without positive urine cultures) a high degree of suspicion for diverticular disease will ensure an accurate diagnosis earlier. Patients with penumaturia or fecaluria present less of a diagnostic challenge. Cystoscopy is a reliable procedure and we recommend its use in discovering a vesicocolonic fistula. Surgical therapy should be individualized for each patient and good results were obtained with primary resection as well as staged repair.


Bladder trauma in the multiple injured patient. There was a 20 per cent mortality rate of 193 patients with bladder injury and in 94 percent of all patients there were associated injuries that caused the deaths. Blunt external trauma was responsible for 95 per cent of the injuries. Cystography revealed a falsely negative result in 3 patients with extraperitoneal rupture. Management of the 29 intraperitoneal, 36 extraperitoneal and 2 intraperitoneal and extraperitoneal ruptures comprised vesical repair and drainage in 60 patients, urethral catheter alone in 1 patient and no treatment in 6 in whom the rupture was found at autopsy. The advantages and disadvantages of urethral catheter drainage are discussed. Early diagnosis and treatment of bladder rupture are important if the significant mortality is to be reduced.


Squamous carcinoma of the bladder: treatment by radical cystectomy. Analysis of records of microscopic slides from 33 patients with pure squamous carcinoma of the bladder who underwent radical cystectomy and lymphadenectomy disclosed a 5-year survival rate of 48 per cent. This survival rate correlated closely with pathologic stage and histologic grade of tumor and was significantly better than for each corresponding stage of transitional cell carcinoma of the bladder. The favorable survival rate and reasonably low operative mortality rate support aggressive therapy of this uncommon lesion.


Smooth muscle tumors of the testicular adnexa. One of 3 patients with peiomyosarcomas of the epididymis and spermatic cord treated by inguinal orchietomy was cured, 1 died 18 months after diagnosis and 1 was living but had a pulmonary metastasis 4 years after excision of the primary tumor. All 3 patients with leiomyoma of the testicular adnexa were cured. The literature concerning smooth muscle tumors of the adnexa is reviewed.


Modern eligibility criteria for vasectomy in the United States. As more people seek to terminate, not just to limit their fertility, physicians should acknowledge the difference between temporary and permanent fertility decisions and make permanent methods more easily available. Recognizing that fertility decisions are personal, social and medical physicians and clinics should adopt eligibility criteria that allow the responsibility for fertility control to reside primarily in the individual. Rather than forcing patients to rely on temporary methods with high failure rates, physicians should attempt to assure the patient's future satisfaction as much as possible by using criteria related to satisfying decision-making in determining who is eligible for vasectomy. We believe that elective vasectomy for contraceptive reasons should be readily available to mature, competent, fully informed men when they have all the children they want.


Control of massive prostatic bleeding with angiographic techniques. In the 4 cases reported herein angiographic techniques with selective bilateral hypogastric embolization were used to control severe prostatic hemorrhage. The technique is offered as an alternative, non-operative procedure in the management of bleeding when other modes of therapy contain significantly higher potentials for morbidity and mortality.


A spectrum of malignant epithelial tumors of the prostate gland. Conceptually, the prostatic territory encompasses neoplams whose origins are intraprostatic, paraprostatic or extraprostatic. Our objectives in this review are to 1) present a classification of the spectrum of malignant epithelial growth encountered in the prostatic territory, 2) show examples of these neoplasms and remark upon their histogenesis, enzyme production and endocrine sensitivity, and 3) suggest re-evaluation of some of our current routine therapeutic procedures.


Urologic complications of inflammatory bowel disease. Urologic complications occurred in 54 of 233 patients with inflammatory bowel disease followed during a 15-year period. Urinary calculi, enterovesical fistulas and ureteral obstruction were the most common problems. Urinary tract complications may arise many years after primary bowel disease has been diagnosed. Symptoms frequently may be absent or obscured by those of the gastrointestinal disorder. We recommend that urologic evaluation be included periodically in the long-term management of patients with inflammatory bowel disease.


Genitourinary tuberculosis: a study of short course regimens. The problem in the treatment of genitourinary tuberculosis was to find a new regimen of chemotherapy that was shorter in time but equally effective as the traditional 2-year method, using streptomycin, isoniazid and para-aminoslicylate. A short course of treatment using rifampin, isoniazid and ethambutol was then devised, the method depending on the severity of the disease using the Semb classification. This short course of chemotherapy was combined with an early operation in advanced or extensive disease in the urinary tract. The regimen is as satisfactory as the traditional method and a followup of 2 years is all that is necessary.


Prostatic needle biopsy: comparison of needles. To clarify the advantages of the 2 most commonly used biopsy needles results of 100 routine needle biopsies of the prostate are evaluated. The series includes patients selected for study concerning the medical treatment of benign prostatic hyperplasia.


Urologic manifestations of hyperparathyroidism in childhood. Among renal stone-forming children 6 per cent suffer from primary hyperparathyroidism. Urologic complications were noted in 7 of 9 children (78 per cent) with surgically proved hyperparathyroidism seen in a 24-year period. These included nephrolithiasis and nephrocalcinosis (6), defective urinary concentration or acidification (5) and mild impairment of renal function (3). All children responded favorably to parathyroidectomy, which should be performed before treatment of stone disease is undertaken. The nature of urologic manifestations of hyperparathyroidism and their management are discussed.


Renal changes after an uncomplicated antireflux operation. Persistent defects were noted after successful ureteral reimplantations in 91 per cent of patients with preoperative pyelographic changes. The renal ratio between the kidney with reflux and its contralateral normal mate also was found to be static despite the eradication of infection. It is hypothesized that a degree of renal dysgenesis is not uncommon in association with reflux and may be the major factor in explaining these findings.


Renal growth and urinary infection following antireflux surgery in infants and children. The 223 children who underwent antireflux surgery for primary reflux were evaluated. Preoperative phylonephritic scarring was more commonly present with greater degrees of reflux. Antireflux surgery was successful in all cases. Postoperative infection occurred in 21 per cent with almost all episodes being clinical cystitis. Postoperatively, a statistically significant increase in renal growth was noted, which was thought to be related to the extent of preoperative nephron loss.


Sibling uropathology.

Sibling uropathology. Of 197 sibships that were evaluated 47.6 per cent, excluding the probands, had undiagnosed uropathology. When the proband had reflux 26.5 per cent of the asymptomatic siblings also had reflux, When the proband had a uropathology other than reflux 13.2 per cent of the siblings had reflux and 46 per cent had other abnormalities.


The natural history of reflux and long-term effects of reflux on the kidney. Spontaneous cessation of vesicoureteral reflux occurred in 42 per cent of 102 patients. It ceased in 65 per cent of the patients with unilateral reflux, in 50 per cent of those with bilateral reflux in normal caliber ureters and in 9 per cent of those with bilateral dilated ureters. Renal parenchymal changes were seen most frequently in patients with urinary infection after diagnosis. The likelihood of such infections lessened if reflux ceased. Proportionately more male than female subjects were free of infection. Renal damage may follow even 1 episode of infection. Lesions appeared with equal frequency during the entire followup period, whereas urinary infection was more common in the 5-year period after diagnosis. Renal damage was more likely to occur in kidneys that were already abnormal. Reflux should be controlled surgically if urinary infections occur after diagnosis and during long-term chemotherapy and careful observation. In the absence of infection indications for operation are infrequent. Non-surgical management may apply to normal caliber ureters and in infancy, while antireflux operation may be considered at diagnosis in dilated ureters, bilateral reflux or in the presence of renal lesions.


Unusual complications of transvesical ureteral reimplantation. Four of 8 cases that represent unusual and infrequent complications of the transvesicle Politano-Leadbetter ureteral reimplantation technique are reported. Approximately 90 per cent of ureteral reimplantations for vesicoureteral reflux may be done satisfactorily as a transvesical procedure but combining it with an extravesical approach of the ureter when necessary or indicated will serve to correct any conceivable congenital, acquired or iatrogenic lesion of the lower ureteral segment. The extravesical approach should be used if there is any difficulty in performing the procedure transvesically or if the patient has undergone previous attempts at antireflux operation. Obstructive complications may occur in either the early or late postoperative period. When discovered, surgical correction is usually indicated. We strongly advocate strict adherence to the surgical technique involved and meticulous postoperative followup of these patients.


Normal size of the urethral meatus in boys. Statistically valid sizes have been obtained for the normal male urethral meatus in children from 6 weeks through 12 years old. It is hoped that these values will allow the diagnosis of meatal stenosis to be made on an objective rather than a clinical basis and that such evaluation will allow for a more rational approach to the therapy of meatal stenosis in boys.


Urogenital rhabdomyosarcoma in childhood. Recent advances in chemotherapy and radiotherapy have improved the prognosis of urogenital rhabdomyosarcoma. Preliminary reports suggest that a mutilative operation may no longer be essential to cure this disease.


Echinococcal disease of the kidney.

Echinococcal disease of the kidney. A case of hydatid disease of the kidney is presented. The parasitology, diagnostic evaluation and surgical treatment for the entity are discussed.


Renal liposarcoma: case report.

Renal liposarcoma: case report. A case of renal liposarcoma is described. The clinical presentation, angiographic findings and treatment are discussed.


Carcinosarcoma of the bladder: case report and review of the literature. A 36-year-old man with carcinosarcoma of the bladder is described. The literature is reviewed and the clinicopathology is discussed. These tumors tend to be bulky, rapidly growing, invasive and recur locally. Metastases are generally hematogenous and may rarely involve regional nodes. Deaths are commonly owing to local invasion and sepsis. Preoperative overstaging may occur and pelvic arteriography and exploration are recommended in questionable cases. Because of the difficulty in locally extirpating these tumors radical cystectomy and urinary diversion are recommended.


Giant urethral calculus: a case report.

Giant urethral calculus: a case report. A case of a large urethral calculus in a woman with the unusual symptom of dyspareunia is presented. The patient had to manipulate a prolapse-like bulging of the anterior vaginal wall to ease micturition. The radiological appearance is interesting.