Splenectomy for massive splenomegaly.

Splenectomy for massive splenomegaly. Removal of a massively enlarged spleen is a challenging surgical problem that is associated with higher death and complication rates than the removal of smaller spleens. Older age, serious and chronic primary diseases, and associated cardiopulmonary abnormalities contribute to the morbidity and mortality. Most patients with massive splenomegaly have been treated with corticosteroid and/or antineoplastic drugs, which impair wound healing, hemostatic function, and host resistance. Precise surgical technic is especially important in these cases because of the susceptibility to postoperative hemorrhage. Ligation of the splenic artery via the lesser peritoneal sac before mobilization of the spleen is associated with lower intraoperative transfusion requirements than when the spleen is mobilized before the splenic artery is ligated.


Survival after liver resection for secondary tumors. The results achieved by liver resection for metastatic cancer in more than 400 patients have been studied in a collected review. Certain conclusions seem justified: The liver is no longer the surgeon's "no-man's-land," and local excision of metastatic tumor can achieve clinical cure in some patients. The risk-benefit ratio for hepatic resection for secondaries seems to be shifting in favor of benefit for selected patients with primary colorectal tumors. At present liver resection for tumors metastatic from pancreas, breast, lung, stomach, kidney, reproductive organs, and skin (melanoma) cannot be recommended. Liver resection may play an important part in the multi-modal therapy of children with extensive malignant disease.


Parathyroid cysts.

Parathyroid cysts. Cystic neck masses may be accurately diagnosed by sonography, and some nonfunctioning parathyroid cysts can be cured by percutaneous aspiration. Primary hyperparathyroidism should be considered in all patients with cystic neck masses. Parathyroid cysts can often be recognized from the characteristics of the cyst fluid which is usually clear and colorless, contains elevated parathyroid hormone levels and normal or low thyroid hormone levels, and may contain parathyroid cells. Parathyroid cysts may be multiple; all four parathyroid glands should therefore be identified and appropriately removed or hyperparathyroidism may persist.


Metabolism, oxygen transport, and erythropoietin synthesis in the anemia of thermal injury. The relationship between metabolism, oxygen transport, and anemia was assessed in burn patients. A significant negative correlation was found between erythrocyte 2,3 DPG, the major modulator of oxygen transport, and erythropoietin synthesis. Simultaneous bioassay and radioimmunoassay for erythropoietin revealed elevated values in the anemic burn patients. Elevated 2,3 DPG values during convalescence from thermal injury may remove the "anemic hypoxia" stimulus to erythropoieitn production, resulting in persistence of the anemia.


The prevention of deep vein thrombosis and pulmonary embolism. The development of the 125I-fibrinogen technic in the diagnosis of postoperative deep vein thrombosis provides a valuable tool for the study of the condition itself and of the efficacy of prophylactic measures. These measures may be divided into two groups: the antistasis regimes and the antithrombotic regimes. Published reports based on the 125I-fibrinogen technic are critically reviewed. Although many regimes cause a significant diminution in the incidence of isotopically detected deep vein thrombosis, 90 per cent of which are confined to the calf, this does not necessarily imply a similar diminution in the incidence of major pulmonary emboli, most of which arise from thrombi in the proximal segment of the lower limb veins. The origin of these proximal thrombi, with particular reference to their relationship to calf thrombi, is discussed. The reported studies of the influence of antithrombotic regimes on the incidence of pulmonary embolism are reviewed. It is concluded that a reduction in the incidence of isotopically detected deep vein thrombosis is probably accompanied by a significant reduction in the incidence of major pulmonary embolism, but further studies are required.


Unusual problems of abdominal aortic aneurysms. Complications other than rupture occurred in 12 per cent of 254 patients operated on for an infrarenal abdominal aortic aneurysm. The unusual problems encountered included aortocaval fistula, inflammatory aneurysm, aortoenteric fistula, aortic thrombosis, peripheral embolization, and retropsoas rupture. The clinical manifestations and management of these lesions are discussed.


Prevention of complications from prolonged tracheal intubation. Eight commercially available soft cuff endotracheal tubes were studied to determine the relationship between inflation pressure distention of the cuff. Although the balloon cuff may be easily distensible in open air, when confined within the trachea small increments in the inflation volume may produce high pressures. This means that continuous external control of cuff pressure is required to prevent ischemia of the tracheal wall. Major tracheal complications in a busy ICU were examined before and after the introduction of a controlled pressure tube. Control of intratracheal cuff pressures decreased major tracheal complications tenfold and eliminated complications specifically related to the cuff.


Anaesthetic techniques for surgical correction of fractured neck of femur. A comparative study of spinal and general anaesthesia in the elderly. Fifty-five patients presenting with fractured neck of femur were randomly allocated to either a standard general anaesthetic or spinal block in the lateral position combined with light sedation. The comparability of the two groups was established. There was little difference in the intra-operative course of postoperative morbidity in the two groups. There was a statistically significant difference in post-operative mortality between two groups, the general anaesthetic group showing a much higher mortality than the spinal group.


Thiopentone and pancuronium crash induction. A comparison with thiopentone and suxamethonium. A method of 'crash induction' using pancuronium and thiopentone was studied in 100 patients at risk from vomiting or regurgitation. The technique was inferior to thiopentone/suxamethonium in terms of time to intubation, activity of vocal cords and responses to stimuli during induction. Six cases gave difficulty with intubation due to poor relaxation. Only two patients had a fall in systolic blood pressure of more than 20% following induction. No regurgitation occurred. The technique may be suitable for skilled anaesthetists in cases when suxamethonium is relatively contraindicated, when large doses of pancuronium can be used or when hypotension is likely to follow induction.


A case of locked twins managed under lumbar epidural analgesia. A case of locked twins is described in which delivery of the aftercoming head of the first infant, which presented by the breech, was prevented by the presence below it of the head of the second infant, which presented by the vertex. Disimpaction under lumbar epidural analgesia was achieved, the head of the second infant being pushed up out of the pelvis. Both infants survived. This is thought to be the first case to be described in which disimpaction was achieved rapidly under lumbar epidural analgesia, thereby minimising the period of hypoxia to which the first infant was subjected.


Blood microfiltration. A review.

Blood microfiltration. A review. The factors which contribute to the formation of microaggregates in stored blood for transfusion have been discussed and their significance assessed. The history of the development of blood microfiltration is described. The advantages and disadvantages of screen microfilters in comparison with depth filters are considered. Screen filters with a pore diameter of about 40 micron would appear to have definite advantages.


As others see us. The patient's view of the anaesthetist. One hundred hospital patients were given a questionnaire, designed to assess their beliefs about the anaesthetist in relationship to other workers in the United Kingdon national health service. The results of this survey, and the comments passed at a simultaneous interview, are discussed.


An appraisal of the anaesthetist-patient relationship. A questionnaire was used to obtain information from 100 patients about their knowledge of the anaesthetist and his work. The results are presented and discussed.


How much is Jack worth? A study of the work of anaesthetists' in the S.E. Thames Region. A study of anaesthetists' work in the S.E. Thames Region has indicated that about three-quarters of actual working time is spent giving anaesthetics, the rest of the time being spent on activities outside the operating theatre. In addition, however, equal amounts of time to that spent working is committed to being on call, so that the average total amount of time committed to the N.H.S. by the four grades of staff studied is 75.8 hours. While current maximum salary scales may (arguably) bear a resonable relationship to a 38.5 hour week, calculations of remuneration based on the data elicited from the study in respect of the amount of time actually committed and equivalent rates paid to junior staff or doctors in Europe suggest a considerable shortfall in consultant remuneration.


The cost of anaesthetic drugs and equipment. A review of the literature and an up-to-date estimate shows that despite inflation, the cost of anaesthesia has stayed fairly constant over the last 17 years. A questionnaire completed by a small number of junior anaesthetists showed only a fair, and at times widly inaccurate, knowledge of the cost of anaesthetic drug and equipment. An up-to-date price list of commonly used drugs and equipment is included, along with the cost of some common anaesthetic techniques.


Rational substitution therapy for steroid-treated patients. A rational approach to glucocorticoid substitution therapy in steroid-treated surgical patients is described. Betamethasone acetate/phosphate as a single injection, depot-preparation, has been used in 1461 steroid-treated cases of major and minor surgery. No complications or signs of adrenocortical insufficiency druing the pre- and post-operative period were noted.


Immunocytochemical and histochemical studies on intestinal epithelial cells producing both lysozyme and mucosubstance. The simultaneous demonstration of lysozyme using the unlabelled antibody enzyme method and mucosubstances by staining with the periodic acid-Schiff (PAS) and Alcian Blue pH 2.5 techniques has led to the identification of a new subpopulation of mucus-producing cells containing lysozyme in small intestinal specimens from normal rats and from patients with inflammatory bowel diseases. These cells, containing both mucosubstances and lysozyme, are located in the lateral walls of the crypts of Lieberkuhn, but can occasionally be found also in or near the tips of the villi. The specific staining for lysozyme was observed in the apical and/or basal cytoplasm of these mucus-producing cells and was readily detected in sections counterstained for mucosubstances with Alcian Blue. The localization of these mucus-producing cells was similar both in the normal rat and in the pathological human specimens. Absorption controls and controls where a non-immune serum was substituted for the specific antilysozyme serum confirmed the specificity of the lysozyme localization.


Growth, protein content and distribution of early pig embryos. Development of porcine conceptuses included transitions of five stages: blastocysts of spherical, ovoid, and tubular forms containing an embryonic disc and trophoblast, extremely elongated filamentous blastocysts, and stages of embryogenesis between days 9 and 18 after mating. Embryonic survival was reduced by 17% during this period. In this litter-bearing species, intense alteration in distribution patterns occurred at days 11 and 12, when blastocysts rapidly elongated to filamentous forms. Increased embryo mortality did not result from rapid changes in distribution patterns of conceptuses within the same uterine horn at this time. Filamentous blastocysts quickly reached lengths often exceeding 60 cm, and these conceptuses became regularly spaced with no overlap of tubular membranes from other embryos in that horn. The number of conceptuses within a uterine horn ranged from 1 to 13. Protein in individual conceptuses was used as an indicator of growth and denoted exponential increase, but at a lower rate for blastocysts of spherical, ovoid, and tubular forms as compared with that found in filamentous blastocysts and embryogenesis stage conceptuses. Growth on a conceptus, based upon its protein content, was independent of the developmental stage or potential loss of those neighbors nearest that conceptus.


Acetylcholinesterase activity of primary sensory neurons and dorsal root fibers in the cat. Dorsal roots and spinal ganglion cells of adult cats were studied for acetylcholinesterase (AChE) content. An inverse correlation exists between cell size and AChE activity; large neurons are AChE-negative whereas small ones are intensely AChE-positive. A few AChE-positive fibers were demonstrated in the dorsal roots. A possible correlation between AChE activity and substance P content of primary sensory neurons is discussed.


Lipids and cholesterol clefts in the lacunar cells of snake skin. The lacunar cell layer in rat snake epidermis contains many characteristic intracellular vacuoles. The lipid nature of these large round vacuoles was demonstrated by histochemical and ultrastructural investigations. Rhomboid-shaped clefts, similar to cholesterol ester clefts, were observed in proximity to the vacuoles.


Ultrastructural study of the nerve plexus accompanying the ovarian artery and vein in the rat. The ultrastructural characteristics of the nerve plexus that accompanies the ovarian vessels of the rat were studied. The nerve fibers were primarily unmyelinated with less than 5% myelinated. Two types of neuronal cell bodies were found along these nerves. They were located at variable distances along the nerve bundle. The first and more numerous was a larger cell type similar to the autonomic postganglionic neuron. The second and smaller cell type had granulated vesicles throughout the cytoplasm. Synapses of the axodendritic type and synapses between the neuronal cell bodies were found. Most of the synapses possessed agranular vesicles. The presence of neuronal cell bodies is an important characteristic to consider in evaluating denervation of the ovary by interruption of this nerve plexus.


Functional anatomy of lymph nodes. II. Peripheral lymph-borne mononuclear cells. In the rabbit a number of large mononuclear cells with ruffled surface membranes travel from the skin and superficial tissues of the leg, via the lymphatics, to the popliteal lymph node: they constitute 40-50% of the total cell population in the afferent lymph. About 10% of these cells are actively phagocytic when tested in vitro and about 3% are found to contain Langerhans granules. After isotopic labelling the majority of lymph-borne mononuclear cells can be detected within the regional node for at least 24 hours; most being located in the paracortex and a few in the interfollicular cortex. It is proposed that these cells, including those containing Langerhans granules, belong to the "mononuclear phagocyte system." Possible functions of these lymph-borne cells are discussed with particular reference to antigen transport.


Differentiation and migration of endoderm in the rat and mouse at implantation. The initial differentiation of endoderm at the time of onset of implantation, and the subsequent rapid differentiation of visceral and parietal endoderm were studied in the rat and mouse. Transmission electron microscopy illustrates the reorientation and loosening of embryonic cell mass cells during implantation, as well as cytological evidence that endoderm cells have differentiated. Using scanning electron microscopy, parietal endoderm consists of individual stellate cells with numerous peripheral branching filopodia. As these cells migrate abembryonically, the rest of the embryonic cell mass becomes recompacted. The visceral endoderm proliferates and forms a columnar epithelium which has the cytological characteristic of an absorptive epithelium and is able to ingest exogenous proteins. Thus, by 24 hours after implantation, the two endodermal derivatives have assumed widely diverse shapes and different types of associations and rates of replication, and are probably performing different functions.


Ultrastructural characterization of nuage in spermatocytes of the rat testis. At least six different types of nuage, as judged by morphological appearance, were found in spermatocytes of the adult rat testis. These were characterized by form, distribution, and association with other organelles. The appearance (with time) and the dissociation of some nuage types were recorded in conjunction with other events of the spermatogenic cycle. The data indicate that all types of nuage behave in a dynamic way. Especially interesting were the findings concerning the chromatoid body. This structure was first observed in mid-pachytene spermatocytes. By late diplotene and during the first meiotic division, it had lost its prominence such that its eventual fate could not be determined. Large dense (0.5 micrometer) bodies appeared de novo in the cytoplasm of newly formed secondary spermatocytes. They were seen scattered throughout the cell and in association with mitochondria. With time these bodies appeared to coalesce to form the large definitive chromatoid of a type similar to that known to be present throughout most of the remainder of spermiogenesis.


The blood-testis barrier and its formation relative to spermatocyte maturation in the adult rat: a lanthanum tracer study. An electron-opaque substance, lanthanum, was utilized to determine when germ cells of the rat first cross the blood-testis barrier in adult spermatogenesis. Intravascularly perfused lanthanum was shown to surround all spermatogonia. Intravascularly perfused lanthanum was shown to surround all spermatogonia, preleptotene spermatocytes and early leptotene spermatocytes of Stage IX in the adult rat testis. Lanthanum was excluded from the spaces around more mature cells by newly-formed tight junctions between adjoining Sertoli processes. These processes had previously intervened between the leptotene cells and the basal lamina. The results are in close agreement with those of a previous study (Russell, '77a) which indicated that leptotene cells are the first cells of adult spermatogenesis to enter the intermediate compartment and to reside beyond a permeability barrier.


Fertility, reproduction and postnatal survival in mice chronically exposed to halothane. Reproductive studies were performed in Swiss/ICR mice chronically exposed to subanesthetic and anesthetic concentrations of halothane. Male and female mice were treated five or seven days a week for nine weeks prior to mating; exposure of females was continued daily throughout pregnancy. Halothane exposures were 0.025, 0.1, 0.4, 1.2, and 4.0 MAC hours per day. No adverse effect on reproduction was observed at the lowest two exposure levels studied. Exposures to 0.4 MAC hour per day or more were associated with decreased maternal weight gain, fetal fetal length and weight, and early postnatal weight gain. Pregnancy rate, implantation rate, and number of live fetuses per litter were significantly decreased at 1.2 MAC hours per day. The percentage of resorption or fetuses dead in utero was not increased, and postnatal survival of offspring was unaltered. Subsequent matings between untreated females and males exposed to halothane, 1.2 MAC hours per day for 17 weeks, resulted in normal reproductive performance; this suggests that the adverse reproductive changes observed when both males and females were exposed represented a primary effect on females. The least exposure at which effects were seen is approximately 40 times greater than the level of human occupational exposure is unscavenged operating rooms.


Lidocaine, monoethylglycinexylidide, and isolated human uterine muscle. The effects of lidocaine and its primary metabolite monoethylglycinexylidide (MEGX) on isolated human muscle strips from non-gravid and gravid uteri were evaluated. No differences between the effects of lidocaine and those of MEGX on gravid and non-gravid muscle strips were observed. Lidocaine produced significant (P less than 0.01) dose-related depression of uterine contractility, although significant pharamacologic depression occurred only at lidocaine concentrations in excess of 25 microgram/ml. MEGX produced no consistent changes in any of the responses measured.


Anesthetic indices--further data.

Anesthetic indices--further data. Anesthetic indices for methoxyflurane, enflurane, and isoflurane in oxygen and halothane in nitrous oxide and oxygen (50:50), were determined in rats using measurements of heart and brain concentrations of the volatile agents at the endpoints of anesthesia, respiratory arrest and cardiac failure. The indices related respiratory arrest to anesthesia (respiratory index-A1r), cardiac failure to anesthesia (cardiac index-AIc) and respiratory arrest to cardiac failure (cardiorespiratory index-AIcr). Isoflurane had a significantly higher AIr (3.1) and AIc (5.7) than enflurane (AIr 1.8, AIc 3.3), methoxyflurane (AIr 2.2, AIc 3.7) and halothane in nitrous oxide and oxygen (AIr 2.4, AIc 3.7). These indices were also higher than those previously determined for halothane (AIr 2.3, AIc 3.0). Isoflurane had a higher AIcr (1.9) than halothane (1.6). Enflurane had a significantly lower AIr (1.8) than any of the other agents studied. These findings suggested a greater margin of safety for isoflurane, especially with respect to the heart, and a greater potential for respiratory depression for enflurane than for the other agents. Nitrous oxide decreased the amount of halothane necessary to produce anesthesia, but also that needed to produce respiratory arrest or cardiac failure. The addition of nitrous oxide, therefore, did not significantly enhance the overall safety of halothane anesthesia with respect to potential respiratory or cardiac depression.


A vagolytic action of neuromuscular blocking agents at the pacemaker of the isolated guinea pig atrium. To examine the basis of tachycardia seen clinically with some neuromuscular blocking agents, the potencies of d-tubocurarine, dimethyltubocurarine, gallamine, and pancuronium in antagonizing the effects of vagal stimulation on the guinea pig atrial pacemaker were determined and expressed as an ED50 for vagal blockade. These ED50 values were compared with the respective potency values of these agents at the motor endplate. This comparison showed that in clinical doses, gallamine and pancuronium may reach levels that produce vagal blockade. Comparison with atropine indicated that the vagolytic action of the neuromuscular blocking agents was not attributable to receptor occlusion, but reflected instead an action on the vagus nerve itself.


Cerebral effects of nitrous oxide in the dog. The cerebral effects of nitrous oxide, 60 per cent, were examined in 27 dogs. During administration of halothane, 0.2 per cent, nitrous oxide increased cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMR02) to a maximum of 203 and 121 per cent of control, respectively. Cerebrospinal fluid pressure paralleled the change in CBF. The electroencephalogram (EEG) showed low-voltage slow-wave activity. With halothane, 0.8 per cent, nitrous oxide increased CBF and CMR02 to maximum values of 164 and 108 per cent of control, respectively. After administration of thiamylal, 8 mg/kg, intravenously, nitrous oxide did not increase CBF or CMR02 for the first 30-min period, but thereafter, CMR02 increased to 11 per cent above control. Pretreatment with reserpine, 0.5 mg/kg, intramuscularly, for two days did not modify the cerebral circulator and metabolic responses to nitrous oxide. These results indicate that nitrous oxide causes cerebral metabolic stimulation accompanied by an increase in CBF and slowing of the EEG. Sympathoadrenal stimulation would appear not to be the mechanism for the increases in CBF and CMR02. The cerebral effects of nitrous oxide are modified by the background anesthesia.


Morphologic abnormalities in a case of malignant hyperthermia. An 8-year-old boy underwent general anesthesia and experienced an episode of malignant hyperthemia, characterized by elevated temperature, cardiac arrhythmias, markedly elevated serum enzymes (SGOT, LDH, and CPK), proteinuria, and hemoglobinuria. Sixty-six days after anesthesia a skeletal muscle biopsy was obtained for examination by electron and light microscopy, which showed skeletal muscle cells with abnormally numerous mitochondria, enlarged, and variable in shape. Some contained abnormal cristae. There were more lysosomes than normal, and lipofuscin was increased in quantity. Myelin-like bodies were also present. Previous reports of muscle abnormalities are reviewed and compared with the data in this case.


Coronary artery embolism and myocardial infarction. Although coronary artery embolism is a recognized entity, there is little morphologic information indicating it is a cause of myocardial infarction. We studied patients with coronary artery embolic infarcts, which comprised 13% of our autopsy-studied infarcts. Underlying diseases predisposing to coronary emboli included valvular heart disease (40%), myocardiopathy (29%), coronary atherosclerosis (16%), and chronic atrial fibrillation (24%). Mural thrombi were present in 18 (33%). Myocardial infaction, clinically diagnosed in 15 (27%) patients, caused death in 11 (20%). Most emboli involved the left coronary artery and lodged distally, causing infarcts that were usually transmural. Because of their distal location and recanalization, coronary emboli may be a cause of infarcts with angiographically normal coronaries. Thus, coronary emboli are not rare, may produce signs and symptoms indistinguishable from altherosclerotic coronary disease, and by lodging distally in coronary arteries that are usually previously normal, they most often cause small but transmural myocardial infarction.


Temporal arteritis: a 25-year epidemiologic, clinical, and pathologic study. Among the population of Olmsted County, Minnesota, 42 patients with temporal arteritis were identified during a 25-year period. The average annual incidence per 100 000 population aged 50 and older rose from 5.1 in 1950-1959 to 17.4 in 1970-1974. The prevalence of patients with a history of the diagnosis of temporal arteritis on 1 January 1975 was 133 per 100 000 population aged 50 and older. All patients received corticosteroid therapy for a range of 1 to 77 months (median, 7 months). Relapses in 10 of 11 patients were associated with corticosteroid reduction. The majority of patients recovered fully and were followed off corticosteroids for 10 months to 19 years (median, 5 years). Temporal arteritis had no significant effect on survival. Vertebral compression fractures and myopathy were the most serious complications of therapy. The presence of giant cells in biopsies was in part related to the number of sections examined, and their presence had no apparent influence on the clinical course.


Doxorubicin cardiomyopathy: evaluation by phonocardiography, endomyocardial biopsy, and cardiac catheterization. Right ventricular endomyocardial biopsy, right heart catheterization, and systolic time intervals were done in 33 adult patients receiving doxorubicin (AdriamycinTM). Doxorubicin administration was associated with a dose-related increase in the degree of myocyte damage, and 27 of 29 patients biopsied at doses greater than or equal to 240 mg/m2 had doxorubicin-associated degenerative changes identified on biopsy. The pre-ejection period to left ventriculr ejection time ratio (PEP/LVET) showed a threshold phenomenon and did not begin to increase until a total dose of 400 mg/m2 had been reached. Seven patients with catheterization-proven heart failure had a significantly greater amount of myocyte damage on biopsy than dose-matched control subjects (P less than 0.01). Preveious mediastinal radiation appeared to potentiate the doxorubicin-associated degenerative process. Mediastinal radiation and age greater than or equal to 70 years appeared to be risk factors for doxorubicin-associated heart failure. Dose limitation by combined clinical, noninvasive, invasive, and morphologic criteria offered an advantage over empirical dose limitation or dose limitation by PEP/LVET alone.


Hereditary nephritis: a re-examination of its clinical and genetic features. In order to re-evaluate current concepts of hereditary nephritis we studied the urinary findings, the course of the disease, and its genetic transmission in two large pedigrees. We identified 150 patients with hereditary nephritis. Our data show that microscopic hematuria is the most reliable urinary criterion for diagnosing hereditary nephritis in both male and female patients. The hematuria is frequently accompanied by erythrocyte casts indicating that the renal lesion is a glomerulitis. Men are more severely affected than women. They have striking urinary abnormalities, which are present in early childhood, and they progress to renal failure in adult life. Affected women have less obvious urinary abnormalities and rarely develop uremia. In these two families a sex-linked dominant mode of genetic transmission was present. The demonstration that hereditary nephritis is X-linked, at least in some families, helps to explain the difference in severity between men and women and the variable expression among affected women.


Neurogenic diabetes insipidus: management with dDAVP (1-desamino-8-D arginine vasopressin). We used dDAVP, the 1-desamino-8-D arginine analogue of arginine vasopressin with high antidiuretic and low vasopressor potency, to treat 29 patients with neurogenic diabetes insipidus for up to 22 months. Intranasal dDAVP, 2.5 to 15 microgram twice daily, provided excellent control in most patients. Individual responses were independent of age, weight, and severity of diabetes insipidus. Resistance to dDAVP may be a rare complication of prolonged therapy. Two patients with acute postoperative diabetes insipidus were effectively treated with 5 microgram of dDAVP every 14 to 18 h. Compared to previous therapy, side effects of dDAVP were minimal (headaches in two patients), and control of symptoms and urine volume was as good as with vasopressin tannate in oil or better than chlorpropamide and lysine vasopressin nasal spray. We conclude that intranasal dDAVP, because of efficacy, long duration of action, and infrequent side effects, is the preferred treatment of neurogenic diabetes insipidus in children and adults.


Autonomic epilepsy: clonidine blockade of paroxysmal catecholamine release and flushing. We studied a 59-year-old man with transient paroxysms of hypertension, tachycardia, and flushing in whom pheochromocytoma was excluded. Although catecholamine excretion was normal, plasma catecholamine levels rose from normal basal levels (282 +/- 14 pg/ml) to increased levels (585 +/- 67 pg/ml; x +/- SEM; n = 4) at the peak of spells. Other hormones or substrates expected to rise with nonspecific "stress" did not increase after paroxysms. Therapy with clonidine (0.2 to 0.4 mg/day) suppressed basal catecholamines to undetectable levels and markedly reduced peak levels during spells (80 pg/ml). An epileptic pathogenesis was suggested by stereotypic olfactory and epigastric prodromata before spells, and abolition of paroxysms with the anticonvulsant carbamazepine. This patient represents a rare case of autonomic epilepsy with the seizure focus in the temporal lobe.


Failure of chloroquine in human babesiosis (Babesia microti): case report and chemotherapeutic trials in hamsters. The failure of a 3-week course of chloroquine to eliminate an infection of Babesia microti acquired on Martha's Vineyard led to tests of selected drugs in hamsters infected with the strain from this patient. The results showed response to several antitrypanosomal drugs (pentamidine and 4,4'-diazoaminobenzamidine) but not to antimalarial drugs (chloroquine, sulfadiazine, and pyrimethamine).


Hypomagnesemia and impaired parathyroid hormone secretion in chronic renal disease. Severe hypocalcemia secondary to magnesium depletion has been described in numerous patients with gastrointestinal disorders. The development of profound hypomagnesemia in chronic renal disease is a rare finding. We studied three patients with advanced renal failure and magnesium depletion. Severe hypocalcemia also was present in these patients. Despite hyperplasia of the parathyroid glands, the levels of immunoreactive parathyroid hormone (PTH) in blood were inappropriately low for the degree of renal insufficiency. After the administration of magnesium there was a significant increase in the levels of circulating i-PTH in serum with a concomitant improvement in the hypocalcemia.


Phencyclidine-associated acute rhabdomyolysis. Phencyclidine (PCP) is a dissociative veterinary anesthetic and tranquilizer that at present is being abused as a psychedelic and hallucinogenic agent with increasing frequency. The cases of two young patients suffering from phencyclidine toxicity are reported. In each, central nervous system depression was accompanied by an acute dystonic motor reaction resulting in acute rhabdomyolysis and myoglobinuria. Skeletal muscle injury was felt to be the result of excessive involuntary isometrimc motor activity rather than a direct effect of phencyclidine on skeletal muscle. Patients suffering from phencyclidine intoxication should be screened for acute rhabdomyolysis. Phencyclidine intoxication should be included in the differential of nontraumatic rhabdomyolysis and should be considered among the potential causes of acute myoglobinuric renal failure.


Poliomyelitis prevention.

Poliomyelitis prevention. Recent data have indicated that 38% of 1- to 4-year-old children have not had primary vaccination against poliomyelitis. To ensure continuing freedom from poliomyelitis, all children should be immunized, beginning in infancy. The primary poliovirus vaccines in use today are the trivalent oral polio vaccine, which is the vaccine of choice for primary vaccination of children in the United States, and inactivated polio vaccine. Prospective vaccinees should be made aware of the reasons why recommendations are made for specific vaccines at particular ages and under certain circumstances.


Myocardial ischemia: detection and quantitation. Myocardial ischemia at rest occurs only late in the course of coronary artery disease, but transient ischemia can often be induced by increasing myocardial oxygen demand with exercise or atrial pacing. Myocardial ischemia causes a series of physiologic abnormalities that can be detected by assessment of myocardial perfusion, regional mechanical function, electrophysiology, and metabolism. Methods of assessment vary widely in sensitivity, specificity, cost, and ease of application. Although the appropriate choice of diagnostic test may be difficult, the morbidity and mortality that result from myocardial ischemia and infarction and the demonstrated potential of coronary artery bypass surgery to reverse myocardial ischemia before the development of permanent sequellae make the detection of ischemia an important clinical problem. Present methods for quantitating myocardial ischemia are imprecise and difficult to apply but have been used successfully to evaluate the efficacy of therapies designed to reduce the size of myocardial infarction.


Culture, illness, and care: clinical lessons from anthropologic and cross-cultural research. Major health care problems such as patient dissatisfaction, inequity of access to care, and spiraling costs no longer seem amenable to traditional biomedical solutions. Concepts derived from anthropologic and cross-cultural research may provide an alternative framework for identifying issues that require resolution. A limited set of such concepts is described as illustrated, including a fundamental distinction between disease and illness, and the notion of the cultural construction of clinical reality. These social science concepts can be developed into clinical strategies with direct application in practice and teaching. One such strategy is outlined as an example of a clinical social science capable of translating concepts from cultural anthropology into clinical language for practical application. The implementation of this approach in medical teaching and practice requires more support, both curricular and financial.


Malignant melanoma: an evolutionary theory to explain its behaviour. The behaviour of malignant melanoma is discussed in relation to the host/tumour relationships and the factors affecting them, and natural selection of tumour cells is suggested as a possible explanation of its variability. These considerations are taken into account in determining treatment, the results of which are briefly outlined.


Anatomical features of the origin and spread of tumours. All tumours have certain broad characteristics in common, though they vary widely in their origin, distribution, shape, and mode of spread. The part played by anatomical factors in determining these variations is discussed and the need for the surgeon to bear these factors in mind in diagnosis and treatment is emphasised.


Walker Prize Lecture, 1977. Choriocarcinoma: can we afford to cure cancer. The way the management of patients with trophoblastic tumours has depended on the acquisition of new knowledge and new drugs is demonstrated. Emphasis is put on the ability to detect early disease by biochemical markers and on the ability to define on a multifactorial basis the resistance potential of the tumours. This provides a basis for stratification of treatment and the use of prophylactic chemotherapy to prevent cerebral metastases in certain patients. Although chemotherapy is often intensive and prolonged, there has so far been little evidence of long-term effects and many women have had normal pregnancies subsequently, but the limitations of present data are discussed. The difficulties of matching available resources to society's needs in the cancer field make it necessary to consider whether such treatment is unjustifiably expensive. It is shown that for these tumours early diagnosis not only proves effective in therapeutic terms but provides substantial financial savings. It is suggested that screening programmes for cancer cannot be accepted or rejected on principle. In judging them on their individual merits it is appropriate to anticipate interaction between earlier diagnosis and more effective drug treatment.


Bilharzial portal fibrosis: an important cause of portal hypertension. Thirty consecutive cases of portal hypertension seen in a surgical unit in Lusaka, Zambia, are reported. Of these cases 70% were due to portal fibrosis caused by Schistosoma mansoni infestation. Portacaval shunting was undertaken in most cases. Patients with portal fibrosis responded more favourably to portal decompression than did patients with cirrhosis. It is probable that the condition is more common than is generally reconigzed in areas where S. mansoni infestation is endemic.


Partial trisomy 13 presumably due to recombination in an inversion heterozygote and by unequal crossing-over. Two unrelated infants with partial trisomy 13 for the distal of the long arm are described. In one, a familial pericentric inversion is present in three generations and crossing-over in the inversion loop is considered as cause of partial trisomy 13. The other showed a tandem duplication of the distal half of the long arm of chromosome 13 beyond 13q14. This is interpreted to have arisen by unequal crossing-over in mispaired synapsis. It is suggested that recombination rather than breaks is a distinctive although rare cause of human chromosomal imbalance.


The role of kin-structured migration in genetic microdifferentiation. Most current models of human population structure view migration solely as a deterministic force reducing the variance in gene frequencies among the local colonies of a subdivided population. By an empirical example and through simulation experiments, it is shown that migration structured along kinship lines (by analogy to the lineal or 'kinship' effect) does not always reduce the variances of gene frequencies arising through intergenerational random genetic drift. Thus populations experiencing high rates of migration may not be genetically homogenous.


Polymorphism of red cell enzymes in Alaskan ethnic groups. 1. Gene frequencies of esterase D, glyoxalase I and uridine monophosphate kinase in Alaskan populations were determined. 2. Improved methods for demonstrating phenotypes of glyoxalase I and uridine monophosphate kinase are presented. 3. Rare variants of adenylate kinase (AK1) and diaphorase (DIA) were found. One of the AK1 variants is new. 4. Gene frequencies were notably diverse within major ethnic groups. This variability was consistent with a population structure composed of small groups that were relatively isolated from one another.


Asymptotic behaviour of the mean of a continuous phenotypic diffusion process with overlapping generations. The equilibrium position is determined for the phenotypic distribution o f a continuous characteristic in a population which reproduces both randomly and assortatively, and wherein generations are overlapping. It is shown that the major assortative mating models so far proposed for continuous traits are not particularly satisfactory.


Assay conditions and the demonstration of nitroimidazole resistance in Tritrichomonas foetus. Tritrichomonas foetus KV(1), a nitroimidazole-susceptible strain, and KV(1)/M100, its nitroimidazole-resistant daughter strain, differed markedly in their in vivo susceptibility to metronidazole. In vitro susceptibility testing in multiwell plates and tubes with different trichomonad media containing no, or low concentrations of, ascorbate demonstrated that the resistant strain behaves like the susceptible one, if tested under anaerobic conditions (deep cultures in tubes or multiwell plates in anaerobic jars), but shows resistance if tested in the presence of air (multiwell plates exposed to air). In media containing high concentrations of ascorbate, no resistance was observed even in air. The results suggest that the two strains differ in the regulation of internal redox systems and underscore the role testing methods may play in the in vitro detection of nitroimidazole-resistant protozoan parasites.


Effect of metronidazole on the intestinal microflora of the american cockroach, Periplaneta americana l. The effect of feeding to cockroaches the antimicrobial agent metronidazole, which acts specifically against anaerobes, was assessed by light and scanning electron microscopy, bacteriological examination, and methane formation. Types of organisms and total numbers were greatly reduced from controls. The health of mature adults was unaffected, but stunting occurred in subadult animals maintained on the antibiotic from hatching. The intracellular bacteria of the fat body were not affected by the drug. The results are discussed with respect to a proposed microbe-host extracellular symbiosis.


Consequence of cerulenin-released beta-lactamase in clinical coliforms. Periplasmic beta-lactamase of certain clinical coliforms was released, without affecting cell viability, by perturbation of the outer membrane utilizing the fatty acid-mimicking antibiotic cerulenin. Release of such compartmentalized beta-lactamase, at high population density, seems to provide an extra margin of resistance to the organisms against cephaloridine.


Comparative in vitro activity of five cephalosporin antibiotics against salmonellae. The in vitro activities of five cephalosporin antibiotics against 121 strains of salmonellae were compared. Cefamandole and cefaclor were more potent than cefazolin, and these three drugs were more active than cephalothin and cephalexin.


PC-904, a new semisynthetic penicillin.

PC-904, a new semisynthetic penicillin. Sodium 6{d(-)-alpha(4-hydroxyl-1,5 naphthyridine-3-carboxamido)phenylacetamido} penicillanate (PC-904) is a new semisynthetic penicillin with broad-spectrum activity against gram-positive cocci and gram-negative bacilli. At a concentration of 1.56 mug/ml, it inhibited 100% of isolates of Proteus mirabilis, 89% of Pseudomonas aeruginosa, 67% of Escherichia coli, and 45% of Enterobacter spp. At a concentration of 12.5 mug/ml, it inhibited 75% of Klebsiella spp. and 67% of Serratia marcescens. PC-904 failed to inhibit the growth of gram-negative bacilli when large inocula were used. Some differences were noted when organisms were tested in different media or at different hydrogen ion concentrations. It is more active than mezlocillin, azlocillin, ticarcillin, carbenicillin, and amoxicillin against E. coli, Klebsiella spp., and P. aeruginosa.


Absence of strand breaks in deoxyribonucleic acid treated with metronidazole. The deoxyribonucleic acid (DNA)-degrading potential of metronidazole was evaluated in vitro by three techniques: determination of melting curve, measurement of viscosity, and centrifugation in neutral or alkaline sucrose gradients. Studies were performed on calf thymus DNA and on (3)H-labeled or unlabeled pneumococcal and T7 phage DNA after treatment with metronidazole alone or metronidazole reduced by sodium dithionite in the presence of DNA. This latter process is known to elicit covalent binding of metronidazole to DNA. Reduced or unreduced metronidazole had no effect on the melting properties, viscosity, or sedimentation velocity of the nucleic acids studied. Sodium dithionite alone, however, caused a 25% decrease in the intrinsic viscosity of pneumococcal DNA, and decreased the sedimentation velocity of pneumococcal and T7 phage DNA in both neutral and alkaline sucrose gradients. These data suggest that degradation of DNA is not important in the interaction of metronidazole with nucleic acids, an interaction assumed relevant to the cytotoxic, radiosensitizing, and mutagenic activities of this compound.


Simplified radioenzymatic assay for chloramphenicol. A simplified radioenzymatic assay for chloramphenicol was developed by eliminating the need for cumbersome extraction procedures. After the acetylation of chloramphenicol with [(14)C]acetyl coenzyme A in the presence of chloramphenicol acetyltransferase, the reaction mixture was added to a toluene-based scintillation fluid. Since (14)C-acetylated chloramphenicol is more soluble than [(14)C]acetyl coenzyme A in toluene, the radioactive product could be counted directly. The rapidity of this assay, as well as its accuracy, precision, and specificity, makes it particularly suitable for clinical use. In contrast to previous reports of enzymatic assays for chloramphenicol, we have found that results of the assay of standards prepared in serum were up to 25% higher than those of standards prepared in saline, cerebrospinal fluid, or urine.


Comparative nephrotoxicity of gentamicin and tobramycin in rats. A rat model was utilized to compare the nephrotoxic potential of gentamicin and tobramycin. Gentamicin, 40 mg/kg per day, predictably produced renal failure and morphological evidence of proximal tubular necrosis over 14 days of treatment. An identical dosage of tobramycin was associated with only minimal morphological changes and normal concentrations of serum creatinine and blood urea nitrogen. Similar results were obtained even after the tobramycin dosage was tripled to 120 mg/kg per day. A decrease in urine osmolality, mechanism unknown, was observed in all aminoglycoside-treated rats, but the lowest osmolalities were found in the gentamicin-treated rats. According to both histological criteria and renal function measurements, gentamicin was more nephrotoxic than tobramycin in this animal model.


Chemotherapeutic evaluation of 5-episisomicin (Sch 22591), a new semisynthetic aminoglycoside. 5-episisomicin (Sch 22591) is a novel semisynthetic aminoglycoside with a spectrum and potency similar to gentamicin in its activity against susceptible bacterial strains, but with increased potency against Pseudomonas, Providencia, and Proteus rettgeri. It is also more active than tobramycin and amikacin against these last-mentioned species.Against resistant strains, Sch 22591 is significantly more active than gentamicin or tobramycin. Against resistant gram-negative bacteria other than Pseudomonas, Sch 22591 has activity similar to that of amikacin, but Sch 22591 is more potent. Against Pseudomonas strains, it is active against most gentamicin- and tobramycin-resistant strains and is more active than the other three antibiotics. Some Pseudomonas strains are resistant to Sch 22591, but susceptible to amikacin. Against a selection of aminoglycoside-resistant staphylococci, Sch 22591 has very good activity against strains resistant to tobramycin, amikacin, and gentamicin. The superior in vitro potency of Sch 22591 against Pseudomonas has been confirmed in vivo in experimental infections in mice. Absorption in dogs is similar to that of other aminoglycoside antibiotics. The acute toxicity of Sch 22591 in mice is greater than that of gentamicin; its vestibular toxicity potential and nephrotoxicity potential in cats and rats appear to be similar to those of gentamicin.


Evaluation of the micro-media system for quantitative antimicrobial drug susceptibility testing: a collaborative study. Micro-Media Systems (MMS) has developed a procedure by which microdilution trays can be filled with dilutions of antimicrobial agents, frozen, and distributed to clinical laboratories. The trays are prepared in various distribution centers throughout the United States to supply clinical laboratories in the vicinity of each center. For use, trays are removed from the freezer, allowed to thaw, and then inoculated with inocula prepared as for any other susceptibility test, using a convenient disposable inoculator (ca. 5 mul per well). A collaborative study was planned to evaluate microdilution trays prepared in three Micro-Media Systems distribution centers. Microdilution minimal inhibitory concentrations (MICs) were compared to standard tube dilution tests (the international collaborative study group method). With gram-positive cocci, the two techniques gave essentially equivalent results. With gram-negative bacilli, the microdilution MICs were generally one doubling dilution lower than the standard tube dilution MICs. Similar results were seen with microdilution trays prepared with a Cooke Dynatech MIC 2000. Inter- and intralaboratory reproducibility with the macro- and microdilution techniques were quite satisfactory, i.e., at least 96% of the end points were within a range of +/-1 log(2) dilution intervals.


Frequency of resistance to kanamycin, tobramycin, netilmicin, and amikacin in gentamicin-resistant gram-negative bacteria. In vitro evaluation of 66 epidemiologically distinct, gentamicin-resistant, gram-negative isolates from four hospitals revealed that 92% were kanamycin resistant, 44% were netilmicin resistant, 41% were tobramycin resistant, and 6% were amikacin resistant. Combined resistance to gentamicin, tobramycin, and netilmicin occurred in 30% of the strains. Although the resistance percentage to amikacin was the lowest of the three newer agents, two strains were resistant to all of the aminoglycosides tested.


Treatment of experimental Staphylococcus aureus endocarditis: comparison of cephalothin, cefazolin, and methicillin. The effectiveness of cefazolin in Staphylococcus aureus endocarditis has been questioned because of in vitro inactivation by staphylococcal beta-lactamase. Cefazolin, although inactivated in vitro by S. aureus beta-lactamase, was as effective as cephalothin in the treatment of left-sided S. aureus endocarditis in rabbits. Cefazolin (20 mg/kg every 6 or 8 h), cephalothin (40 mg/kg every 6 h), and methicillin (40 mg/kg every 6 h), administered intramuscularly, were compared in the treatment of left-sided endocarditis caused in rabbits by a highly penicillin-resistant strain of S. aureus. The three antibiotics were all effective in reducing titers in vegetations. However, at the dose used, methicillin reduced the titers more rapidly than cephalothin or cefazolin. Cefazolin concentrations in serum were about double those achieved with cephalothin or methicillin. However, cefazolin was only half as active as methicillin and one-eighth as active as cephalothin in vitro in a serum assay. The half life in serum of cefazolin, cephalothin, and methicillin were each about 30 min. Serum bactericidal activities of the three antibiotics were very similar.


In vitro activity of antimicrobial agents on Legionnaires disease bacterium. Six isolates of Legionnaires disease bacteria were tested for their susceptibility to 22 antimicrobial agents. The most active agent was rifampin (minimal inhibitory concentration, </=0.01 mug/ml). On the basis of minimal inhibitory concentration breakpoints that have been used to categorize susceptibility for most of these drugs, the organisms were susceptible to rifampin, cefoxitin, erythromycin, the aminoglycosides, minocycline and doxycycline, chloramphenicol, ampicillin, penicillin G, carbenicillin, colistin, and sulfamethoxazole-trimethoprim (19:1 ratio); sensitive to intermediate in susceptibility to tetracycline, methicillin, cefamandole, cephalothin, and clindamycin; and resistant to vancomycin. More clinical data must be obtained before an optimal therapeutic regimen can be recommended.


Identification of an antibiotic-producing bacterium from the human intestinal tract and characterization of its antimicrobial product. An antibiotic-producing bacterium repeatedly isolated from human feces was characterized by standard bacteriological methods. The bacterium is a gram-positive bacillus possessing morphological and physiological features similar to those of Bacillus subtilis, except that it lacks temperature-resistant spore formation and has peritrichous flagella. The cell-free antibiotic produced by the organism in vitro was effective against some gram-negative and gram-positive bacteria and yeast in minimum inhibitory concentration and antibiotic disk assays. The 1,200-dalton antibiotic had an optimal activity against Proteus vulgaris within the pH range of 5.7 to 6.8. The activity was totally destroyed by digestion with pronase and trypsin but was resistant to pepsin, chymotrypsin, papain, and nuclease digestion. In addition, the antibiotic activity against P. vulgaris was stable between pH 3 to 9 and within the temperature range of 20 to 100 degrees C when tested in the fermentation medium. The activity was only partially retained by membrane filters which normally retain globular proteins of molecular weights between 500 to 10,000. Electrophoresis in phosphate buffer indicated that the activity against P. vulgaris had an isoelectric point of approximately 6.45. These properties are compatible with the antibiotic activity associated with a small peptide.


Pharmacokinetics of bacampicillin compared with those of ampicillin, pivampicillin, and amoxycillin. Bacampicillin, a new oral prodrug which in vivo is rapidly transformed to ampicillin, was compared with ampicillin, pivampicillin, and amoxycillin in a randomized cross-over study on 11 healthy volunteers. All drugs were given in oral doses equimolar to 400 mg of bacampicillin (800 mumol). The mean of the individual peak concentrations in serum was 8.3 mug/ml for bacampicillin, 7.1 mug/ml for pivampicillin, 7.7 mug/ml for amoxycillin, and 3.7 mug/ml for ampicillin. Furthermore, bacampicillin had a higher absorption rate than all the other drugs, although there were statistically significant differences only versus ampicillin. The peak serum levels of the individual subjects were more dispersed with ampicillin and amoxycillin, suggesting a more uniform absorption of bacampicillin and pivampicillin. The relative bioavailability of bacampicillin and pivampicillin was comparable, whereas ampicillin was only 2/3 that of the others.


Production of an antibiotic substance by Bacillus licheniformis within the digestive tract of gnotobiotic mice. In monoxenic mice, vegetative cells and spores of Bacillus licheniformis were enumerated and in vivo antibiotic production was measured at various levels of the digestive tract and in the feces. The apparent independence of vegetative cell and spore populations in the cecum and feces, as well as the marked fluctuations of these two populations in the stomach and small intestine, suggested that sporulation of B. licheniformis and production of antibiotic occur only in the upper levels of the digestive tract. Study of dixenic models wherein B. licheniformis was inoculated after Clostridium perfringens or Lactobacillus sp. or before Lactobacillus sp. revealed the simultaneous disappearance of B. licheniformis from the stomach and antibiotic from the feces. This strain persisted in the cecum, but only in the form of vegetative cells. These models demonstrate that the activity of the microflora in the upper segments can affect the equilibrium of the microflora throughout the digestive tract.


Long-term study of smoking by secondary schoolchildren. We report the methodology and some first year results of a 5-year longitudinal study of smoking. In 6330 Derbyshire secondary schoolchildren aged 11-16 years, 6% of boys and 2.5% of girls were smoking one or more cigarettes per week. Higher rates of regular smoking and of children who had tried smoking were found in secondary modern schools, followed by middle, comprehensive and grammar schools. The results clarify the relationship between children's smoking habits and those of the parents and siblings. Boys were more likely to smoke if their fathers smoked and girls were more likely to smoke if their mothers smoked. Irrespective of parental smoking, whether or not siblings smoked had a great influence on whether the child would smoke. Having more money to spend, working at a part-time job, spending more evenings out with a mixed-sex peer group, at a youth club, or out dancing, and playing truant from school were all associated with an increased risk of smoking.


Computerised axial tomography and acute neurological problems of childhood. The results of computerised axial tomography (CAT) in 80 children with neurological symptoms and/or signs of less than 3 months' duration are discussed in relation firstly to intracranial pathology and secondly to clinical presentation. 26 children had intracranial space-occupying lesions (tumour, abscess, haemorrhage, infarct). CAT was abnormal in 25 of these and diagnostic in 18. A further 20 children had meningitis or encephalitis, and CAT was abnormal in 12. In contrast with this high rate of scans showing pathology, CAT was abnormal in only 4 of the remaining 34 children who had less definite or no intracranial disease. Analysis of clinical presentation showed that 42 of 69 children presented with persisting neurological signs and of these, 25 had an intracranial space-occupying lesion and 29 had abnormal CAT. Only 5 of 27 children who had symptoms alone or signs lasting less than 24 hours had abnormal CAT, and no intracranial lesion requiring specific treatment was missed. CAT is useful for demonstrating the site, size, and nature of many lesions. The scan may not initially be abnormal in brain stem gliomas and in small subdural collections of fluid.


Fetal growth in different racial groups. Three racial groups of mothers and their newborn babies-- North European 75, Negro 75, and "Indian" Asian 37--were matched for parity, gestational age, sex, maternal age, maternal smoking habits, and social class. Multiple anthropometric measurements, including skinfold thickness, limb circumferences, and various linear measurements were made on the mothers and their infants to determine the effects of race and smoking on fetal size. Indian-Asian mothers, though shorter and lighter than Europeans and Negroes, had similar skinfold thickness and weight: height2 ratios and gained as much weight during pregnancy. Their infants, however, were lighter than the others, and had smaller head and limb circumferences, although their linear measurements were the same. Negro and European infants were almost identical in size. We found no effect on any of the fetal measurements which could be attributed to smoking.


Echovirus encephalitis and myositis in primary immunoglobulin deficiency. Two children are described with primary hypogammaglobulinaemia and encephalitis associated with echovirus infection. One also developed a condition resembling dermatomyositis which improved after he was given infusions of plasma containing antibody to the echovirus. Although both died of their encephalitis, the course of the brain disease in one of them may have been prolonged by treatment with specific antibody. These cases, together with another briefly mentioned case in an adult with congenital hypogammaglobulinaemia and echovirus infection, indicate that these patients are particularly susceptible to echoviruses.


Mycoplasma pneumoniae infections in children. Details are given of all serologically confirmed Mycoplasma pneumoniae infections in children referred to Bristol hospitals during an epidemic lasting 18 months. 44 children, many below school age, had lower respiratory infections. The majority had cough and malaise which had failed to respond to antibiotics given before referral. Chest x-rays showed no pathognomonic features: segmental or patchy consolidation was common; 3 cases of lobar consolidation. Cold agglutinins were raised in 9 out of 12 cases. In the majority of cases the total leucocyte count was normal and the absolute neutrophil count raised. Mean duration of symptoms was 4.2 weeks (range 1-16). Treatment with erythromycin or tetracycline appeared to have little effect in most cases. Seven nonrespiratory manifestations were seen in 6 children. These were meningitis (2 cases), Stevens-Johnson syndrome (4 cases, 1 case complicated by toxic epidermal necrolysis), and acute haemolytic anaemia (1 case).


Factors influencing jaundice in immigrant Greek infants. A study of 887 consecutively born immigrant Greek and 220 Anglo-Saxon Australian infants has shown that serum bilirubin concentrations are influenced by these factors: breast feeding, delivery with forceps, gestation, birthweight, sex of the infant, presence of hypoxia, presence of blood group incompatibility, a positive direct Coombs's test, maternal sepis, and administration to the mother of promethazine hydrochloride, reserpine, chloral hydrate, barbiturates, narcotic agents, diazepam, oxytocin, aspirin, and phenytoin sodium. Apart from the administration of promethazine hydrochloride, reserpine, chloral hydrate, and quinalbarbitone sodium, only two factors, breast feeding and delivery by forceps, occured with different frequencies in the immigrant Greek and the Australian infants. Among the Greek infants with jaundice, there were few where the cause of the jaundice was inapparent. The immigrant Greek and Australian newborn populations were therefore remarkably similar. Since differences of frequency and severity of jaundice do exist in infants born in Greece, this difference must be lost when the parents emigrate, and therefore an environmental factor must be incriminated as the causative agent for jaundice of unknown origin in Greece.


Simple method for measuring oxygen consumption in babies. A simple open-circuit method for measuring the rate of oxygen consumption in the neonatal nursery is described and preliminary results on 240 infants reported. The findings are consistent with previous studies using closed systems and artificial environments. The variation between one infant and another was great, which makes it difficult to predict for any one infant the thermal environment at which the rate of oxygen consumption will be minimal.


Thermoregulation in babies immediately after birth. The fall in body temperature that occurs in babies soon after birth is influenced by the baby's weight and its environmental conditions. The rate of oxygen consumption 1 1/2 hours after birth was unrelated to body temperature and only slightly raised, indicating a limited thermogenic capacity. A radiant heater effectively prevented cooling in babies kept with their mothers in the delivery room. Washing soon after birth caused a significant cooling. Healthy term babies were found to have a limited thermogenic response to a cool environment over the first 12 hour of life and efforts to limit heat losses should be concentrated on this period.


Motor nerve conduction velocities in Leigh's encephalomyelopathy. Slowed motor nerve conduction velocities were found in 3 of 4 cases of Leigh's subacute necrotising encephalopathy. 2 of the patients are sibs, one of whom is clinically normal apart from lactic acidosis and slowed motor nerver conduction velocities.


Psychological determinants of infantile pyloric stenosis. In order to investigate the possible contribution of maternal emotional stress to the aetiology of infantile pyloric stenosis, 100 mothers of affected infants, 100 "normal" controls who had not sought medical advice at any time concerning feeding problems, and 50 mothers of children with spina bifida were interviewed. All completed the Life Events Inventory, which gives a quantitative measurement of stressful life events during a given period. In addition, the subject mothers and "normal" controls completed form A of the Eysenck Personality Inventory, the Multiple Affect Adjective Check list, and Linear Analogue Scales for the subjective measurement of satisfaction with feeding and distress caused by feeding problems. A highly significant difference was found between the number of items given a heavy weighting on the Life Events Inventory experienced by the subjects and both control groups. This was particularly marked during the last trimester of pregnancy. Personality assessment was very similar in all groups, but maternal anxiety scores were higher in the subjects than in the controls. It is concluded that hypertrophic pyloric stenosis occurs unduly frequently in infants of normal mothers who have been subjected to particularly stressful events during pregnancy.


Diagnosis of meconium aspiration by spectrophotometric analysis of urine. The first urine passed by a newborn infant who has inhaled meconium or meconium-stained amniotic fluid often contains a dark-coloured water-soluble substance, recognisable spectrophotometrically by an absorption band at about 405 nm. Spectrophotometric analysis of the first urine can in this way be used to diagnose preceding meconium aspiration.


Establishing demand feeding in hospital. In the summer of 1975 demand feeding was introduced for all babies born at the John Radcliffe Hospital, where previously babies were fed according to a rigid schedule to fit in with ward routine--clock feeding. Over a 10-day period before demand feeding was introduced details were collected about infant feeds concerning 42 normal babies whose mothers had decided to breast feed. 2 weeks after the introduction of demand feeding similar details were collected about 43 normal breast-fed babies. At the time of the observations 65% of all babies born in this hospital were being breast fed. Comparing breast feeding patterns, there was a wider scatter of interfeed time intervals in the demand-fed group than in the clock-fed group, over the first 2 days after birth. By the end of the first week these differences were no longer present. The introduction of demand feeding presented no problems in ward management and is now the established routine in this maternity hospital.


Oxidative metabolism in cord-blood polymorphonuclear leucocytes. Polymorphonuclear leucocytes were isolated from cord-blood samples collected from healthy, term infants. Oxidative metabolism was assessed in these cells by hexose monophosphate shunt activity and chemiluminescence. Basal levels of oxidative metabolism were spontaneously increased in resting (nonphagocytic) cord-blood cells as compared to adult controls. As a response to phagocytosis, cord-blood cells initiated the expected increase in oxidative metabolism and reached normal peak values of activity. However, these cells were unable to maintain the high metabolic rate for as long a time as adult controls. This aberration of leucocyte function may indicate a deficiency of metabolic reserve and could be related to the increased susceptibility of newborns to bacterial infections.


Case of congenital nonobstructive, nonhaemolytic jaundice. Successful long-term phototherapy at home. Use of cholestyramine made it possible to shorten the daily duration of phototherapy in a case of congenital nonobstructive, nonhaemolytic jaundice. Treatment at home was therefore possible, allowing normal parental care. Development and neurological examinations were normal at the age of 27 months. Frequent determinations of reserve bilirubin binding capacity may be useful in controlling such management.


Serial lung function studies in cystic fibrosis in the first 5 years of life. Lung mechanics were studied in 8 infants with cystic fibrosis at 6 months of life and radiosotopic lung function was measured in 5 of them at 5 years of age. The children who were initially asymptomatic had normal lung mechanics in infancy but the 2 restudied later had abnormal radioisotopic lung function. The symptomatic children showed abnormalities in infancy and more marked changes later. It is concluded that the lungs in cystic fibrosis are probably normal initially and that damage occurs later even in the absence of symptoms.


Hyponatraemia in children with febrile convulsions. In a study of 23 children admitted to hospital with a febrile convulsion, mild hyponatraemia was found on 8 occasions. In 6 of these cases there was evidence of inappropriate secretion of antidiuretic hormone. The hyponatraemia is unlikely to be the cause of the convulsion, but probably predisposes the child to a subsequent convulsion during the same febrile illness.


Tumors of the thymus and thymic region: III. Clinicopathological studies on teratomas and tumors of Germ Cell type. In a series of 82 patients with tumors of the thymus and thymic region there were 11 with teratomas and germinal tumors. Four of these patients had benign cystic teratomas, 4 had malignant teratomas, 1 had an embryonal carcinoma, and 2 had seminomas. The benign teratomas were removed by simple extirpation without complications. The malignant teratomas were highly invasive, and despite extensive operations and postoperative radiotherapy, 3 of the 4 patients died within 9 months. One patient with predominantly seminomatous differentation of the teratoma was alive and well more than 3 years after the operation. The patient with an embryonal carcinoma died after 4 months. One of the 2 patients with seminoma remained alive 20 years after radical excision and postoperative radiotherapy. The other, who had a huge seminoma, died during operation. The prognosis in patients with seminomas or with predominantly seminomatous structures in teratomas seems to be good after combined radical excision and radiotherapy, although nonradical resection followed by raditherapy may be justified in high-risk patients.


Sustained-release implants of chemical carcinogens in the canine tracheobronchial tree. A proved carcinogen, benzo[a]pyrene (BP), was incorporated into liquid silicone rubber polymer which was then vulcanized into solid form. Discs of BP polymer containing 9.05 to 12.12% BP were sutured into the trachea and right main bronchi of 10 dogs which were observed for 3 to 8 months. The discs were either in contact with the endobronchial surface of the mucosa or placed into submucosal pockets. All discs that were implanted submucosally remain in place. Only 2 discs implanted by the fixation method were extruded. The pocket implants of BP polymer caused ulceration and erosion of the mucosa; these changes did not occur from discs of polymer without carcinogen. To date these implants have induced squamous metaplasia with atypical changes. A method for sustained-release implantation of carcinogens in the canine tracheobronchial tree has been developed.


Carotid endarterectomy: results in 100 patients. One hundred twenty-two carotid endarterectomies were done in 100 patients in various clinical states of occlusive disease (4 with asymptomatic bruit, 61 with transient ischemia attacks, 35 following stroke) with an overall operative mortality of 3.27%. The 4 deaths all occurred among patients who had existing deficits when operated on. Among 82 operations done for transient ischemia or asymptomatic bruit there were no deaths; 2 transient but no permanent deficits resulted. Surgical management is described. During long-term follow-up, 3 patients in the transient ischemia group acquired deficits (4.6%), but no strokes occurred among the patients with asymptomatic bruits. Six cerebral deaths are reported (both early and late); 5 of them occurred among poststroke patients and the sixth was related to an unoperated, diseased carotid artery.


Complete atrioventricular canal malformation: further clarification of the anatomy of the common leaflet and its relationship to the VSD in surgical correction. Thirty-four heart specimens showing complete atrioventricular (AV) canal malformation were studied. The size of defects underneath the anterior common leaflet was compared with the size of those beneath the posterior common leaflet. Wherever such defects were present, they were either of the same size or larger underneath the anterior leaflet. There was no correlation between the type of posterior common leaflet and the size of ventricular communication. The importance of the location of the ventricular defect in relation to surgical correction, especially in small infants, is discussed.


Fourteen years of implanted pacemakers in children. Twenty-six children who had permanent pacemakers implanted at 6 hours to 11 years of age have been followed for up to 163 months. There were 14 children with surgical heart block, 9 with congenital heart block, 2 with postcatheterization complete heart block, and 1 with bradytachydysrhythmia syndrome. Eighteen of the 26 patients (69%) are still being paced with their original electrodes, some for more than eight years. Sixty pulse generators lasted an average of 17 months (range, 1 to 55 months). Five of the 26 patients (19%) are dead. Three died of noncorrectable heart disease, but there were 2 sudden unexplained deaths at home, both apparently due to sudden arrhtthmias. Both of these patients had received fixed-rate pulse generators, and 1 had a known potential for competing rhythms. The current optimal choices of equipment and techniques, including the role of synchronized, demand, lithium-powered, and nuclear-powered pulse generators, are discussed.


Thoracic traction for median sternotomy dehiscence. Standard management of median sternotomy dehiscence sometimes fails to achieve lasting reduction and fixation of the sternal halves. An effective method of external thoracic traction that augments internal fixation of the sternal fracture is presented.


Reoperation for complictions after inflow correction of transposition of the great arteries: technical considerations. A right anterolateral thoracotomy through the fifth or sixth intercostal space is described as an easier approach for reoperations after the Mustard procedure for transportation of the great arteries. Advantages of this approach compared with repeated sternotomy include easier cannulation of the superior and inferior vena cava; less extensive dissection of adhesions, resulting in decreased postoperative bleeding; reduced risk of injury to the coronary asteries and the right phrenic nerve; and improved exposure of intracardiac pathways and the tricuspid valve.


A method for direct coronary sinus flow measurement and blood sampling in the dog. Various methods for sampling and measurement of coronary sinus flow in animals have been reported. All have disadvantages because of the need for fluoroscopy or for special tubing or equipment. A technique using readily available materials is described that provides direct measurement of coronary sinus blood flow and allows coronary sampling.


Successful intracardiac repair of the Taussig-Bing malformation in 2 children. Surgical repair of the Taussig-Bing deformity has been successful in 2 children weighting 7.7 and 11.1 kg, respectively. In the first case the right ventricular patch divered left ventricular blood to the pulmonary arter, thus creating a physiologically complete transposition which was then corrected by an interatrial Mustard baffle. In the second case a right ventricular tunnel diverted left ventricular blood to the aorta, and right ventricular blood was directed to the distal pulmonary artery by means of an external conduit bypassing a subpulmonic stenosis. These patients represent the seventh and eighth successful corrections of the Taussig-Bing anomaly. One case (Patient 2) is the youngest to undergo repair and the first to receive an external conduit for bypass of an associated subpulmonic stenosis.


Tumors of the thymus and thymic region: I. Clinicopathological studies on thymomas. A series of 43 patients with thymoma was reviewed. The patients were classified with respect to some factors of prognostic significance. The tumors were reclassified histologically, and a staging system with three defined stage-groups was applied to the series on the basis of operative findings and histological examination of surgical specimens. Surgical-pathological staging is of high prognostic and therapeutic importance in thymomas. Complete removal of the tumor was possible in the 25 patients with stage I or II disease and in 14 of the 18 patients with stage III tumors. Pleural metastases were observed in half of the patients with stage III disease. Even patients with extensive local spread or pleural metastases were subject to tumor resection. The treatment of choice is radical resection along in stage I; radical extirpation and, if indicated, postoperative radiotherapy in stage II; and radical resection whenever possible, even in cases of pleural spread, in stage III, with postoperative radiotherapy and chemotherapy. Myasthenia gravis is an indication rather than a contraindication to radical treatment of thymoma, although some patients may deterioratte. The importance of total thymectomy is stressed.


Tumors of the thymus and thymic region: II. Clinicopathological studies on Hodgkin's disease of the thymus. Among 82 patients with a tumor in the thymic region, 17 had a lesion that fulfilled the criteria for Hodgkin's disease of the thymus; the histopathological differentiation of this entity from thymomas is discussed. All patients received surgical treatment and postoperative radiotherapy. After a mean observation time of 10 years there was no local recurrence and no death due to the disease, though 3 deaths were cuased by the treatment. New clinical manifestations occurred in 3 of the 14 long-term survivors: they were treated successfully by operation or irradiation. A very aggressive surgical approach involving extirpation of all tumor tissue, extensive excision of the surrounding tissues and adjacent lymph nodes, and supplementary radiotherapy seems to be the treatment of choice.


Sleep apnea syndrome in a patient with Shy-Drager syndrome. A patient with autonomic insufficiency and extrapyramidal signs (Shy-Drager syndrome) and sleep apnea syndrome (SAS) underwent hemodynamic studies. In comparison to patients with SAS and intact autonomic reflexes, systemic hypertension was absent and marked sinus arrhythmia during sleep was blunted. Cyclical pulmonary hypertension associated with frequent apneic episodes during sleep persisted, reflecting a minor role of autonomic reflexes in the generation of this abnormality. Autopsy confirmed the Shy-Drager syndrome and multiple areas of degeneration were observed in areas of the CNS outside the medullary respiratory centers, suggesting their importance in the origin of the respiratory abnormalities in SAS.


Treatment of myocardial infarction in a community hospital coronary care unit. Experience with 1,246 patients. The hospital mortality in 1,246 consecutive acute myocardial infarction patients treated in a large community hospital coronary care unit was 14.4%. Of the total, 52.3% showed no evidence of heart failure, 25.8% had mild to moderate failure, 9.9% had pulmonary edema, and 12% developed cardiogenic shock; the mortality in these groups was 2.2%, 7.4%, 8.9%, and 87.2%, respectively. The mortalitiy in the 1,097 patints who did not have cardiogenic shock was 4.5%. Only one patient died as a result of primary ventricular fibrillation (0.08%). The mortality of complete heart block in the absence of cardiogenic shock (8.3%) was not significantly different from that of comparable patients who did not have complete heart block (4.3%). These results are lower than those generally reported.


Systemic factors contributory to retinal vein occlusion. This study was undertaken in 79 patients with retinal vein occlusion to assess the different systemic mechanisms contributing to the occlusion, namely, intrinsic vessel disease and abnormalities of the blood constituents and blood viscosity. In 55 patients older than 50 years of age, important associations were hypertension, abnormal results on glucose tolerance test, hyperlipidemia, chronic lung disease, and elevated serum IgA levels. In the 24 patients younger than 50 years of age, male incidence was high and important associations were head injuries, hyperlipidemia, and the use of estrogen-containing preparations. Hyperviscosity and cryofibrinogenemia were prominent in both groups. The pathogenesis of retinal venous occlusion is complex involving interaction between the vessel wall and blood constituents.


Lower esophageal sphincter pressure and serum gastrin levels after mapped antrectomy. We investigated the effect of mapped antrectomy with gastroduodenostomy on serum gastrin levels in fasting patients and resting lower esophageal sphincter (LES) pressure. Serum gastrin levels in fasting patients were lower in those who had an antrectomy without vagotomy (P less than .05) as compared to control subjects or patients with antrectomy and vagotomy. Resting LES pressure was similar in patients and controls and was not affected by the presence or absence of vagotomy. These findings suggest that (1) mapped antrectomy and gastroduodenostomy without vagotomy are followed by a decrease in serum gastrin and (2) resting LES pressure is not affected by mapped antrectomy and a decrease in serum gastrin level.


Rocky Mountain spotted fever and jaundice. Two consecutive cases acquired in Florida and a review of the literature on this complication. Rocky mountain spotted fever is increasing in Florida, a state that has had few cases in the past. The typical clinical illness has been well described, but jaundice has been rarely reported. In two patients with illnesses resembling leptospirosis, jaundice appeared on the sixth and ninth day of illness, and peak bilirubin levels were between 7 and 9 mg/100 ml. Liver biopsy specimen from one patient showed a nonspecific hepatitis. Hemolysis and renal dysfunction may have contributed to the production of jaundice in these patients. Fourteen instances of jaundice were reported in 43 autopsied cases as of 1941, but since that time only rare mention of jaundice has been made.


Abnormalities in the regulation of growth hormone in chronic renal failure. Carbohydrate intolerance is a common abnormality in patients with chronic renal failure. In this group of patients we investigated the interrelation among glucose, insulin, and growth hormone and confirmed the presence of carbohydrate intolerance and hyperinsulinemia. In addition we demonstrated alterations in growth hormone regulation, characterized by (1) the lack of suppression of growth hormone by orally induced hyperglycemia and paradoxical increase in serum levels of growth hormone after the administration of intravenous glucose or glucagon; (2) lack of release of growth hormone with induced hypoglycemia and an exaggerated response to levodopa administration. Furthermore, thyrotrophin-releasing hormone stimulated growth hormone release, a phenomenon not observed in the control population. Our studies show an impaired hypothalamic regulation of growth hormones secretion in patients with renal failure undergoing long-term hemodialysis.


Management of alcohol withdrawal syndromes. Withdrawal from alcohol (ethanol, ethyl alcohol) or other general sedatives leads to progressive hyperactivity that progresses from tremulousness, sleep disturbance, and hallucinosis, to the more serious rum fits and delirium tremens (DTs). Withdrawal can be prevented and, in most cases, arrested by prompt replacement of alcohol with paraldehyde, benzodiazepines or other general sedatives. Diazepam is appropriate replacement therapy for most patients. When delirium is manifest, the chance is greater than 15% that the patient will die, and this reaction cannot be aborted. The patient with DTs must be calmed with a general sedative that has a rapid onset of maximal effect to prevent overdosage. Diazepam, 5 mg intravenously every five minutes, permits evaluation of the maximal effect of each dose before the next dose is administered. Although some patients have advance sedative or alcohol withdrawal, great care must be taken to elicit the proper history of alcohol abuse so that sedative replacement therapy will prevent or abort early withdrawal, thus sparing the patient a mortality equivalent to that of acute myocardial infarction or Russian roulette.


Inflammatory bowel disease (ulcerative colitis). There is uncertainty as to the proper management of a patient with chronic ulcerative colitis who has had his disease for over ten years but has not been sufficiently symptomatic to warrant colectomy. Not all patients are at high risk to develop cancer. Wide extent and long duration of disease are correlated with increased risk. The ability to define a patient at risk beyond these single criteria are very limited. The definition and efficacy of the precancerous lesion observed in rectal biopsies is still a matter of dispute, and the routine use of proctocolectomy for patients with long-standing colitis is still not universally accepted. Careful follow-up is obviously indicated, but it is still uncertain whether roentgenography, colonoscopy, colonic biopsy, or a combination of these methods will ultimately prove the procedure of choice.


Carbamazepine-induced syndrome of inappropriate antidiuretic hormone secretion. Reversal by concomitant phenytoin therapy. The syndrome of inappropriate antidiuretic hormone secretion, with marked hyponatremia, was observed in an elderly women who was taking carbamazepine for trigeminal neuralgia. Subsequent studies revealed this effect to be directly related to the administration of the drug. Substantial water retention has not been previously described in patients taking normal volumes of fluid and taking standard doses of carbamazepine. Additionally, it was determined that the antidiuretic effect of carbamazepine could be blocked by phenytoin. The actions of both drugs on renal water excretion, and the interactions of the drugs were observed to be dose-related.


Feminizing adrenocortical carcinoma with Cushing's syndrome and pseudohyperparathyroidism. A patient with adrenocortical carcinoma had three major endocrine abnormalities attributable directly to the tumor: hypercortisolism (Cushing's syndrome), hyperestrogenism (feminization), and hypercalcemia (pseudohyperparathyroidism). There were higher levels of immunoreactive parathyroid hormone in venous effluent from the tumor or its abdominal metastases compared to that found in the veins draining the parathyroid glands. This, together with the presence of normal parathyroid glands on autopsy, established the diagnosis of pseudohyperparathyroidism as the cause of hypercalcemia in this patient.


Splenic sequestration with sickle cell-C disease. During an episode of pneumonia and multiple pulmonary thromboembolic events, an adult male patient with sickle cell-C hemoglobinopathy developed a severe anemia associated with rapidly increasing splenic size and diminished splenic uptake of technetium Tc 99m sulfur colloid, indicating diminished splenic function due to hypersequestration, a rare and noteworthy phenomenon in adult patients with sickle cell-C disease.


Iatrogenic arteriovenous fistula. An unusual complication of indwelling pericardial catheter and intrapericardial steroid instillation for the treatment of uremic pericarditis. The drainage and instillation of poorly absorbable corticosteroids has recently been suggested as an laternative to the present modes of therapy for uremic pericarditis. One patient who underwent such a therapeutic approach subsequently had a left internal mammary artery to right internal mammary vein arteriovenous fistula develop. To our knowledge, this is the first report of the development of arteriovenous fistula after either pericardiocentesis or intrapericardial instillation of steroids.


Carcinoma of the parathyroid.

Carcinoma of the parathyroid. We report on eight cases of parathyroid carcinoma seen at the Bowman Gray School of Medicine, Winston-Salem, NC, since 1969. Diagnosis of a parathyroid disorder was made on the basis of elevated serum calcium levels and associated disorders such as renal calculi, peptic ulcer disease, pancreatitis, and demineralization of bone. Six of the involved glands were on the left side. In seven patients, the disease was localized to the gland or adjacent structures; one patient had cervical lymph node invasion. Except for the last patient, in whom radical neck dissection and wide excision was done, local excision with adequate margins was the only procedure done. The patient with metastases died of his disease four years later. One patient died of myocardial infarction two years later, but had been normocalcemic in the interval between operation and death, and one patient is hypercalcemic and has had two local recurrences within a 3 1/2 year period. The other five patients are alive and well. The routine use of automated serum level determinations of all hospitalized patients has led to early detection of this malignancy, while it is still a stage I lesion in many instances. On the basis of this material, we conclude that radical neck dissection can no longer be advocated as a routine measure in the treatment of parathyroid carcinoma.


An assessment of routine liver scanning in patients with breast cancer. A retrospective review of the value of routine perioperative liver scanning for patients with breast cancer was performed. The liver was considered to be normal in 231 of 234 patients. The hepatoscan uncovered only one patient with unsuspected metastases. There were eight false-positive studies. Measurements of liver function, SGOT, SGPT, alkaline phosphatase, and bilirubin levels separated true positive from false-positive hepatoscans for all except one patient. Abnormal liver chemistry studies also identified liver metastases in an additional follow-up group of 192 patients. The low yield of detection of hepatic metastases during the initial work-up of breast cancer patients suggests that routine hepatoscanning be abandoned unless there is evidence of abnormal liver function.


Appendiceal abscess revisited.

Appendiceal abscess revisited. Appendiceal abscess developed in 2% of 2,621 patients with acute appendicitis seen between 1962 and 1976. While representing a commendable decline in frequency from earlier studies, in view of the demonstrated prolonged delay in seeking medical care, further decreases in incidence could be affected by increased patient education. Sixty-one of 68 patients underwent surgical drainage of the abscess, with a 28% complication rate. Interval appendectomy was performed in 42 cases, with a 19% complication rate. Two patients (3%) died. These rates do no differ appreciably from those reported during the preantibiotic era. Recurrent appendicitis developed in only one of 13 patients not undergoing interval appendectomy during a follow-up period averaging five years. Interval appendectomy should be withheld only in those poor-risk patients in whom the 10% to 20% incidence of recurrent appendicitis seems the smaller risk.


Abnormalities of phenylalanine and tyrosine kinetics. Significance in septic and nonseptic burned patients. The flow of phenylalanine, the essential amino acid precursor of thyroid hormone and catecholamines, was severely elevated in five septic burned patients (6.70 +/- 1.07 mg/kg) and six nonseptic burned patients (5.00 +/- 0.44 mg/kg) when compared with seven normal controls (2.10 +/- 0.33 mg/kg). Fasting serum concentrations of phenylalanine were elevated in the septic burned patients (2.33 +/- 0.37 mg/100 ml of serum) relative to the nonseptic patients (1.28 +/- 0.21 mg/100 ml) and the controls (1.01 +/- 0.15 mg/100 ml). The rate of appearance of the phenylalanine metabolite, tyrosine, after an oral phenylalanine dose was normal in all burn patients. Increased serum concentrations and increased flow of phenylalanine are an index of rapid protein catabolism, further augmented by sepsis in the thermally injured, and not a reflection of decreased hepatic conversion of phenylalanine to tyrosine.


Iatrogenic liver abscesses. A complication of hepatic artery ligation for tumor. The use of hepatic artery ligation, with or without placement of an indwelling infusion catheter for the instillation of chemotherapy, became widely employed in the late 1960s. This was a natural outgrowth of observations that it was reasonably well tolerated in man if certain precautions were followed and that tumors in the liver, whether primary or metastatic, received the major portion of their blood supply by that vessel. As tumor necrosis following ligation was the anticipated result, it followed that undrained collections of nonviable tumor might well be expected to develop in a certain number of patients and that such collections would form intrahepatic abscesses. It appears that development of the complication does not adversely affect the result of the procedure, and this must certainly only be true because of recognition and proper therapy directed to the complication.


Staged aortofemoropopliteal revascularization. Staged proximal and distal revascularization may be required in some patients with combined aortoiliac and femoropopliteal disease due to inadequacy of the profunda femoris artery or distal popliteal arterial disease. When these situations arise, one may expect that the procedures may be performed with very low morbidity (10% in this series) and mortality (0.0% in this series). Moreover, one may expect satisfactory results in most cases. In our series of 20 patients, 72.7% of extremities undergoing distal revascularization after previous proximal revascularization remain improved with over three years' follow-up.


Vaginitis emphysematosa. Importance of its radiologic recognition. Vaginitis emphysematosa (VE) is a benign, self-limited condition characterized by a myriad of gas-filled spaces in the subepithelial lining of the vaginal wall, which give it a distinct radiographic appearance. Failure to make the correct diagnosis may lead to an inappropriate course of treatment, including surgery. Although it is considered rare, we have encountered five cases of VE in the course of a year.


Choledochal cyst. Etiological considerations and surgical management in 22 cases. In a 14-year period from 1962 to 1976, there were 22 cases of choledochal cyst treated by two different approaches: choledochocystenterostomy to the duodenum in three and to the jejunum in a Roux-en-Y operation in four cases, and excision of the cyst with hepaticojejunostomy in 14 and with end-to-end anastomosis of the common bile duct in one case. There was one death in each group. In five cases, direct cholangiography, either operative or endoscopic, demonstrated a reflux of the contrast material from the biliary system to the pancreatic duct. In four cases, the amylase level of the cystic content was elevated, ranging from 182 to 50,820 Somogyi units. A reflux of the pancreatic juice into the biliary system was thought to be a possible cause of choledochal cyst. Excision of the cyst with hepaticojejunostomy in a Roux-en-Y operation seems to be the treatment of choice from the aspects of cholangitis, malignant change, and termination of the pancreatic reflux to the biliary system.


Benign polypoid adenoma of the ampulla of vater. Treatment by double sphincteroplasty. A patient with a symptomatic duodenal polyp was found at operation to have a 4 cm diameter adenomatous polyp of the ampulla of Vater, with both the common bile duct and pancreatic duct passing through the stalk and emptying from the polyp. The polyp was excised at the base of the stalk, and the two ducts reconstructed by a double spincteroplasty technique. The postoperative course and 2 1/2 year follow-up have been uneventful.


A burning issue. Phantom limb pain and psychological preparation of the patient for amputation. Fantasies concerning an amputated limb can contribute to the occurrence of persistent phantom limb pain. We report a case in which burning pain perceived as located in the amputated lower extremities was related to the patient's feelings about incineration of the removed limbs against her wishes. Hypnotherapy involving elucidation of the fantasy and suggestion was successfully employed in this case and may be a helpful approach in other such cases. Importantly, adequate preparation of the patient for amputation, including an awareness of concerns about the disposition of the limb, may help prevent pathological limb sensations.