[Gas gangrene after abdominal surgery].

[Gas gangrene after abdominal surgery]. This is a report on nine cases of gas-gangrene which developped after abdominal surgery. In five patients the diagnosis was made at the bedside, three of these patients survived. Cardinal symptoms were rapid deterioration of the general condition, severe pain around the incision, tachycardia, and the appearance of jaundice along with a fall of the hemoglobin.


[Splenic repercussions after Warren's distal spleno -renal shunt]. Volume and function of the spleen were checked in 14 patients 6 months to 7.5 years (average: 2.5 years) after Warren distal spleno-renal shunt. In addition to the shunt, the splenic artery was ligated proximally in 5 cases. Splenomegaly decreased in half of the patients. In 8 out of the 13 patients with preoperative hypersplenism, the latter improved or disappeared after operation. Increased splenomegaly or hypersplenism was never found postoperatively. Splenic effects of the distal spleno-renal shunt are related to the improvement of the venous stasis. Efficiency of the splenic artery ligation is so doubtful that we do not recommend such a procedure.


[Amebiasis as surgical emergency].

[Amebiasis as surgical emergency]. Report of 2 cases of systemic complications many years after inappercept infection with amoeba histolytica. Amoebiasis being a rare affection in Switzerland, diagnosis was missed and not revealed till operation. One case with multiple liver abscesses, healed after drainage and chemotherapy with metronidazol and dehydroemetine. In the other case with colonic perforation and multiple liver abscesses combined surgical and drug therapy failed, the patient died in hepatotoxic coma. Short cut of clinics and therapy in amoebiasis, pointing out that surgery is reserved for the complications as great liver abscess, colonic perforation or fistula between abdominal and pleural cavity.


[The precision of scintigraphic evaluation of liver metastases]. In a prospective study 491 liver scintigrams are examined. In 139 cases the precision can be tested by a comparison with the records of operations and/or sections. The evaluation amounts to a 21.6% quota of mistakes. The point is discussed whether in oncological surgery liver scintigraphy should not be abandoned in favour of an invasive procedure such as laparoscopy or laparotomy.


[Spontaneous rupture of the spleen during anticoagulant therapy]. Three cases of spontaneous rupture of the spleen in patients which were on long-term anticoagulant therapy are reported. In patients with the trias faulty coagulation, signs of hemorrhagic shock and of peritonitis in the upper abdominal part the possibility of a spontaneous rupture of the spleen must be considered. The diagnosis can then be confirmed by a positive peritoneal lavage. Once the diagnosis is made, the therapy is splenectomy.


[Respiratory complications in acute pancreatitis]. The analysis of 12 cases of severe hemorrhagic pancreatitis shows the importance of the detection of an early hypoxemia, which should be treated as soon as possible by a sufficient oxygenation. If the arterial p02 does not improve one should not delay the moment of endotracheal intubation with PEEP.


[Treatment of chronic recurrent necrotic pancreatitis]. 22 out of 180 patients with chronic relapsing pancreatitis showed an acute hemorrhagic-necrotizing exacerbation. in 11 out of these there was an indication for operative management of the chronic pancreatitis before onset of the acute exacerbation. The clinical picture is similar to that of the acute hemorrhagic-necrotizing pancreatitis. The surgical procedure consisted in digital removal of necrotic tissue and left-sided resection. 13 out of the 22 patients survived.


[Serum gastrins after duodeno-pancreatectomy]. 6 patients who have had a duodeno-pancreatectomy were starved and then given a test meal, to stimulate the serumgastrin which was measured by RIA. The fasting gastrin values were, by all the patients, in the lower range of the normal level (25-50 pg/ml). The stimulation with the meat-extract (25 g with 400 ml of water) did not lead to any significant raising of the fasting serum gastrin.


[Entero-mesenteric infarction: survival after subtotal enterectomy and partial colectomy]. A 55-year-old man, without any particular medical story, presents suddenly an increasing abdominal syndrome. The operation reveals an intestinal gangrene due to an acute mesenteric vascular insufficiency. The massive resection leaves 30 cm of the first jejunum anastomosed with the ascending colon. The patient has been attending follow-up clinic for the past eighteen months and, in spite of a "short bowel syndrome", feels well and works part time.


[Bronchoplastic methods in the resection treatment of malignant bronchial tumors]. 1548 patients who were hospitalized 1964--1975 for diagnosis and treatment of bronchogenic carcinoma, 779 underwent resection. 17 patients could be operated by lobectomy or bilobectomy and bronchial resection (sleeve resection). Postoperative complications were frequent (n = 8): 4 times bronchopleural fistula, 2 times empyema, once fatal pneumonia and once bronchial stenosis. The overalll mortality and the survival rates are comparable to those of patients with radical resections. Sleeve resection is therefore a suitable alternative to pneumonectomy in elderly patients with reduced pulmonary function, rarely indicated also by a favourable tumor size. Sleeve resection increases the resectability of malignant bronchogenic tumors by 2%. Methods to prevent or cure the postoperative complications consisted in the use of absorbable suture material and long lasting intrathoracic suction.


[3 cases of mucoepidermoid bronchial malignant tumors]. Mucoepidermoid tumors of the lung are extremely uncommon. Like the considerably more common mucoepidermoid tumors of the salivary glands, their histology is characterized by two components: a glandular mucoid element and an epidermoid element. The degree of malignancy is still a subject of discussion, but as with mucoepidermoid tumors of the salivary glands, mucoepidermoid carcinomas of the bronchus may be of either high or low-grade malignancy. The three cases reported here were of high-grade malignancy and metastasized irrespective of the degree of cellular differenciation. We have concluded that mucoepidermoid lung tumors should be considered as malignant lesions and the treatment has to consist in radical resection.


[Correlation between immuno-morphological parameters of regional lymph nodes and the mortality of patients with stage I and II bronchial squamos cell carcinoma]. Histological changes in tracheobronchial and bronchopulmonary lymph nodes of patients with operable (i.e. stages T 0/2, N 0/1, M0) bronchogenic squamous cell carcinoma were examined histometrically. Out of 29 patients 10 survived less than 12 months and 19 lived longer than two years after surgery. Quantitive methods were employed for measuring structural changes in lymph node sections at the histological and cellular level. The following parameters reflecting both cellular and humoral immune responses correlated with survival: relative numbers of large lymphoid cells and mitotic figures in the paracortical "thymus dependent") area; volume of the follicular (predominantly B-cell) cortex and volume of germinal centers. Pronounced accumulation of histiocytes or dust-loaded marcrophages in the paracortex and presence of "empty" lymph sinusoids (i.e. without sinushistiocytosis) correlated inversely with survival. Besides the theoretical importance and considerations of a documented immune response, such data could help in identifying high risk groups within the same stage of bronchogenic carcinoma of a given type.


[Septicemia in the intensive care of severely injured patients]. In surgical intensive care septicaemia, confirmed by bacteriological culture, was found in 46 out of 1143 severely injured patients. Source of this complication was infection of the respiratory tract in 43%, intraabdominal infection in 17%, and a septic wound in 15%. Mortality was 50%. Early diagnosis (fever, increase of leucocytes and toxic signs in differential blood count, thrombocythemia, decrease of anorganic phosphate), prophylaxis, and treatment are discussed.


[The technic of tracheotomy: experience with 250 tracheotomies]. The results of 250 tracheostomies, primarily or secondarily performed at the intensive care unit of the Surgical Department of the Basle University, are presented. The standardized technique of tracheotomy is described, details for the choice and management of large prestretched double-cuff tracheostomy tubes are given, a new method of low-pressure cuff-blocking is outlined. The follow-up studies --autopsy, clinical examination and tracheoscopy--demonstrate a very low complication rate, due to the technique of tracheostomy, the preferred tracheostomy tubes and the method of alternate low-pressure cuff-blocking.


[Subcutaneous Achilles tendon rupture. Experiences with 99 operations on fresh injuries]. Influenced by new publications about the conservative treatment of the rupture of the Achilles tendon we reviewed our own material. 99 operations were performed within the first week after the accident. There were 7 slight early complications, one rerupture after 3 months, healed after resuture, and 1 osteodystrophy. 94 patients answered our question forms, and the result of 92 operated ruptures could be examined personally within an average of 5 years after the accident. 2/3 of the patients had a measurable--although unimportant--muscular atrophy but only 1/5 of them felt a weakness. 7 patients had a reduced movement of the ankle joint. Only one patient was disabled by the scar. 85 patients have taken up again the same sport, only one had to give up. The result of the primary suture of fresh Achilles tendon ruptures is good if the operation is performed as soon as possible and by using a strictly atraumatic technique.


[An unusual case of neurinofibroma in the distal part of the duodenum]. A case of a neurinofibroma in the distal part of duodenum is reported by the author. It has caused a so-called blind resection of the stomach by Billroth II-type as the result of not clarified bleeding. But after restoration of the duodenal transit by the procedure reverting into Billroth I-operation there was the possibility of the accurate diagnosis of the origin of bleeding by means of gastroduodenoscopy and X-ray examination by duodenal hypotension and with it the definitive healing.


State health manpower poly: an appraisal. The health manpower policies of state governments are discussed on the basis of an appraisal of a set of recently completed health manpower studies. Examination suggests that both state health manpower policy processes and outcomes may be limited in fundamental ways. Resolution depends upon changes in the ways in which we perceive health manpower problems and in the institutional mechanisms used to deal with them.


Emergency medical services in small communities: volunteer ambulance corps. This paper examines volunteer ambulance corps that provide emergency medical care and transportation to their communities. The authors have compared volunteer corps to all ambulance services in Michigan and have focused on the relationship between organizational characteristics, such as membership and community characteristics as indicated by town size, and the support base for the volunteer corps. They conclude that governmental support for voluntary associations such as ambulance corps improves health care delivery in small communities.


The wellness process.

The wellness process. Wellness is viewed as a continually evolving and changing process related to the developmental stages of man and the individual's completion of certain developmental tasks. Wellness differs from good health; it is a measurable process in which individuals actively participate to become more healthy. The index proposed here for assessing or measuring wellness is based upon the individual's completion of the minimal wellness tasks appropriate to his developmental stage.


A cooperative pharmacy project: an autopsy on a community health intervention. An attempt to implement a cooperative pharmacy project within a public housing project for the elderly is described. It was designed to provide low-cost prescriptions and pharmaceutical counseling as well as a coordinated record system for the elderly residents and other members of the senior citizens association. The resistance of local pharmacists and others caused substantial alterations to be made, eliminating the more consumer-oriented elements and emphasizing the more professional and technical aspects. Because of insufficient participation by the pharmacists and the consumers, the project died. The reasons for this failure are explored.


Orungo virus: organ distribution with histopathology and development of experimentally infected Swiss albino mice. The organ distribution and pathogenecity of Orungo virus were studied in Swiss Albino mice following intracerebral and intraperitoneal inoculations. There was an age-related response in mice to Orungo virus ic infection. Virus multiplied to higher titres in the brain of newborn (2-day-old) mice than in the other organs. The histopathologic changes which were restricted to the brain included diffuse mononuclear cell infiltration, prominent perivascular and interstitial oedema in the cerebrum and cerebellum. In 10-day-old mice, low level infective virus was detected only in the brain, with resultant mild and focal mononuclear cell infiltration in the cerebral cortex. Recovery from Orungo virus ic infection in 10-day-old animals is accompanied by stunted growth. Orungo virus did not multiply in 21-day-old mice which were found to be histologically unremarkable. Following ip inoculation Orungo virus did not multiply, nor was there an histopathological change in inoculated newborn, 10-day or 21-day-old mice.


Effect of polycations on the early stages of reovirus infection. The polycation DEAE-dextran treatment of HeLa cells was found to interfere with the production of reovirus, appearance of viral cytopathology, and the induction of cytotoxicity by UV-irradiated reovirus. The data obtained showed that while the polycation pre-treatment of cells enhanced virus adsorption to cells, its addition early during virus adsorption or 2 h after infection markedly interfered with virus production. The interference was decreasingly effective when the polycation was added during the later stages of the infectious cycle. Isopycnic CsCl buoyant density ultracentrifugation analyses of infected cytoplasmic extracts revealed that there were more subviral particles formed in untreated infected cells than there were in polycation-treated cells. In vitro uncoating studies with infected cytoplasmic extracts indicated that the polycation did not interfere with the removal of the outer capsid structure of the complete virus, and uncoating occurred only in the presence of the polycation. Electron microscopical examination revealed significantly fewer virus particles present in polycation-treated infected cells. The accumulated data strongly indicate that interference by DEAE-dextran is an early event involving viral penetration. Corollary studies using other polycations, such as polybrene (hexadimethrine bromide and poly-l-lysine, revealed that while they also enhanced virus adsorption, they did not interfere with reovirus production, appearance of viral cytopathology, and the induction of cytotoxicity by UV-irradiated reovirus.


Studies on the bacterial spore coat. 6. Effects of alkali extraction on the spore of Bacillus thiaminolyticus. Thin sections of the spore of Bacillus thiaminolyticus Matsukawa and Misawa show a characteristic surface structure with five ridges, and a series of three distinct layers. The outer layer of the spore coat was peeled off by SDS sonic treatment, and then the middle layer was solubilized by alkali extraction of the SDS sonic-treated spore. The spores subjected to these treatments were still refractile, heat resistant, and contained dipicolinic acid, but lost their resistance to mechanical shock.


Differential stimulation and inhibition of growth of Rhizobium trifolii strain T1 and other Rhizobium species by various carbon sources. The physiological properties of Rhizobium trifolii strain T1 were studied in detail, since this strain has many useful characteristics and appears ideal for development as a reference strain for R. trifolii. Some tricarboxylic acid cycle intermediates and related compounds were found to stimulate growth in the presence of sucrose and arabinose, while others inhibited growth partially or completely. Other R. trifolii strains behaved likewise. Moreover, similar responses were also observed with other Rhizobium species, both fast-growing and slow-growing. On the basis of these growth responses, the various species of fast-growing and slow-growing rhizobia could be differentiated. Of the fast-growers tested, R. trifolii and R. leguminosarum are much more closely related to each other than either is to R. meliloti. Similarly, the slow-growing cowpea rhizobia are more closely related to R. japonicum than either group is to R. lupini. It is proposed that strain T1 should be developed as the reference strain for Rhizobium trifolii.


Interaction between impulses evoked by stimuli of different modalities in neurons of the parietal associative cortex. In acute experiments on cats anesthetized with chloralose and nembutal interaction between visual, auditory, and electrodermal stimuli in neurons of the parietal association cortex was studied. Two types of interaction were found; the first characterized by inhibition or by inhibition followed by facilitation of the response to the test stimulus, the second by facilitation or by facilitation followed by inhibition of spontaneous impulses. Interaction between stimuli of different modalities was shown to depend on the properties of the neuron. In polysensory neurons ability to interact was much higher than in bimodal or monomodal neurons.


Responses and properties of receptive fields of neurons in the visual projection zone of the pigeon hyperstriatum. Unit responses in the hyperstriatal region of the pigeon forebrain to the action of various visual stimuli were investigated. Particular attention was paid to the discovery of retinotopic projection in the Wulst region. It was shown that as the electrode was advanced in the caudal direction in the zone of visual projection of the hyperstriatum the receptive fields of the neurons recorded shifted in the opposite direction in the visual field. The receptive fields of neurons of the ventral and dorsal hyperstriatum lie higher in the visual field and are larger in diameter than those of neurons of the accessory hyperstriatum. Unit responses in the visual projection zone of the Wulst depend on the intensity of illumination, size, and speed and direction of movement of the test objects across the receptive field. The functional role of the retino--thalamo--telencephalic system in visual interpretation in birds is discussed and it is suggested that the Wulst region is comparable with the striatal and also with the frontal regions of the mammalian cortex.


Investigation of the functional role of the septum. A spectral-correlation analysis was made of the EEG recorded from the motor and visual cortex, hippocampus, and septum (in some series of experiments, the lateral geniculate body and mesencephalic reticular formation also) of rabbits in the presence or absence (background) of sensory stimulation. To investigate the functional role of the septum as a pacemaker the method of "rhythm binding" by electrical stimulation of the septum (lateral and medial nuclei) was used. By electrical stimulation of the medial nucleus of the septum at a frequency of 4-30 Hz rhythm binding was successfully obtained in all regions studied. Maximal rhythm binding was observed in cortical potentials. It is postulated that cortical rhythmic activity is generated as a result of physiological interaction between cortex and septum.


[Treatment of the gastric bezoar by endoscopy]. This paper deals with our experiences in a group of patients with gastric bezoars who were treated endoscopically. A group of 7 patients, 5 women and 2 men, from 41 to 62 years of age, with the diagnosis of bezoar was studied. In 6 cases both the clinical and roentgenographic diagnosis was bezoar; in one case the diagnosis was not established before endoscopy. Endoscopic studies were performed to confirm the diagnosis and for treatment. The bezoars were fragmented, under endoscopic observation, with the biopsy mechanism and, after removal of the endoscope, gastric lavage was done through a 12 mm. tube for removal of the bezoar fragments. Postendoscopically all patients were given metoclopramide and new films were take at one week. Confirmation of complete removal of the bezoars was also obtained by subsequent endoscopic control. No complications were observed in any of the patients. We propose that endoscopic removal of bezoars is the treatment of choice because it lowers morbility, mortality and eliminates the need for surgery as well as lowering hospitalization time.


[Acute emphysematous cholecystitis. Report of 3 cases]. Three cases of acute emphysematous cholecystitis are reported. Our experience has been that this disease, compared with the occurrence of common acute cholecystitis, is rare. The clinical picture is discussed and emphasis is made concerning the roentgenographic diagnosis and surgical findings, such as obstruction of the cistic duct, which is probable the cause of the histopathologic changes found in the gall bladder. The negative results from the culture of material obtained from the gall bladder was probably  due to antibiotic administration prior to surgery. A review of the recent literature and surgical treatment, after correction of metabolic and hydroelectrolito imbalances, is made.


[Mixed bezoar].

[Mixed bezoar]. The case of an adolescent psychopath who, following traumatic psychological experiences, ingested her own hair and cotton string over a 6 to 8 month period, is presented. This resulted in the formation of a mixed bezoar (hair and cotton string) with subsequent deterioration of her general condition. The diagnosis was made roetgenographically. Curative surgery was performed and psychotherapy was initiated. A review of the current literature is made and the frequency, clinical characteristics, treatment, management and recommended prophylactic considerations are discussed.


[Acute obstructive suppurative cholangitis]. Acute obstructive suppurative cholangitis is a potentially lethal complication of biliary tract obstruction, caused by passage of septic material into the circulation originating from pus under tension in the biliary ducts. Of the three cases presented herein, decompression occurred spontaneously in the second one, and was achieved surgically in the other two. The diagnosis is based in Charcot's triad of: Abdominal Pain, Fever and Jaundice, with or without history of biliary disease. Progression leads to septicemia, shock and death. Treatment is surgical and it should be carried out as soon as the diagnosis is made. Effective decompression of the biliary tract is obtained by cannalization of the choledoccus with a T-Tube. Delayed treatment increases mortality, thus the importance of early recognition.


[Familial polyposis of the colon. Analysis of 17 cases]. Seventeen cases of familiar polyposis of the colon seen in the National Institute of Nutrition are reviewed. In 12 of the cases (70%) there were family histories of colonic polyposis. Ten patients (50%) developed carcinoma and of these 7 were located in the rectosigmoide. Ten patients underwent total colectomy with abdominoperineal resection. Seven already had carcinoma at operation; 5 localized and with survival rates of more than 5 years without evidence of recurrence; the other 2 had distant metastasis at operation. Four patients underwent colectomy with ileoproctoanastomosis. In 2 of these cases subsequent abdominoperineal resection was necessary; another died of recurrent carcinoma and the fourth is alive and asymptomatic. Familiar colonic polyposis is an hereditary disease of the autosomic dominant type with a tendency to develope malignant changes at an early age. The treatment of choice is colectomy; however, controversy exists as to whether or not the rectum should be conserved. Based on our results, and those of other authors, we feel that the treatment of choice is total colectomy with abdominoperineal resection, because of the high probability of malignant recurrence.


The long-term prognosis in untreated cerebral aneurysms: I. The incidence of late hemorrhage in cerebral aneurysm: a 10-year evaluation of 364 patients. Three hundred sixty-four patients who suffered a subarachnoid hemorrhage from an aneurysm in either the posterior communicating or anterior communicating artery and who were not surgically treated have been followed for up to 21 years in order to determine the frequency of subsequent hemorrhage. For patients surviving six months: (1) rebleeding occurs on the average of 3.5% per year during the first decade; (2) the mortality associated with a late rebleed is 67%; (3) high blood pressure and female sex predispose to late rebleeding in posterior communicating artery aneurysms; (4) young patients take longer to rebleed than older patients but do so at the same rate; and (5) increase in aneurysm size as judged by routine arteriography six months after the initial hemorrhage did not correlate with rebleeding, although an increase in size had occurred in all patients who were studied angiographically at the time of their late rebleed.


Alpha-pattern coma: 24 cases with 9 survivors. Alpha-pattern coma denotes the association of a comatose state with an electroencephalogram consisting predominately of alpha-frequency activity. Over the past three years we have studied 24 such cases: 14 following cardiopulmonary arrest, 6 following respiratory arrest, and 3 following brainstem infarction. Of the 9 patients who survived, only 1 had a significant neurological deficit. It was found that: (1) alpha-pattern coma can result from a variety of neurological insults; (2) a significant proportion of patients survive, often with little or no deficit; (3) clinical evidence of intact brainstem function implies a favorable outcome; (4) the electroencephalogram was similar in survivors and nonsurvivors and did not differentiate diffuse cerebral dysfunction from focal brainstem disease; and (5) neuropathological studies demonstrated diffuse cortical as well as brainstem changes.


Polyradiculoneuropathy accompanying procainamide-induced lupus erythematosus: evidence for drug-induced enhanced sensitization to peripheral nerve myelin. Factors involved in the development of an insidious polyradiculoneuropathy in association with a procainamide-induced, lupuslike syndrome were explored. A 73-year-old man with this clinical syndrome had sural nerve changes consisting of loss of large myelinated fibers with evidence of remyelination and Schwann cell proliferation. The patient's lymphocytes showed marked incorporation of tritiated thymidine when cultured with either procainamide or extracts of human peripheral nerve myelin, and there was an enhanced response with the combination. We also found that procainamide-treated rats showed acceleration of lymphocyte sensitization to peripheral nerve myelin as judged by the early development of inhibition of macrophage migration and positive skin tests to extracts of peripheral nerve myelin. These studies suggest that procainamide can enhance lymphocyte sensitization to peripheral nerve myelin and may have predisposed this individual to development of a polyradiculoneuropathy.


Nonketotic hyperglycinemia: report of a case and review of the clinical, chemical, and pathological changes. A female infant with neonatal hypotonia and lethargy was found to have nonketotic hyperglycinemia. She died at the age of 5 days. Autopsy revealed slightly retarded myelination and severe spongy change in the well-myelinated areas of the brain. Analysis of this and the other 26 reported cases suggests that patients with nonketotic hyperglycinemia develop severe mental retardation, not seen in ketotic hyperglycinemia. Elevated glycine levels in the brain and cerebrospinal fluid appear to differentiate these two forms of hyperglycinemia better than the presence of ketosis or leukopenia, and high glycine levels apparently occur in the same areas as the spongy change. While both forms show defective glycine cleavage in the liver, defective glycine cleavage in the brain has been reported only in nonketotic hyperglycinemia.


Isolated myopathic involvement of the diaphragmatic musculature in a neonate. A myopathy restricted to the diaphragm was found in an infant who died at 3 months of age of respiratory failure due to immobility of the diaphragm. Grossly, the diaphragm was thin and translucent. On microscopical examination few muscle bundles were seen. Most muscle fibers were small, and numerous necrotic fibers with large sarcolemmal nuclei, focal cytoplasmic basophilia, and hyaline or homogeneous eosinophilic degeneration in the center of the fibers were seen.


The large apparent work capability of the blood-brain barrier: a study of the mitochondrial content of capillary endothelial cells in brain and other tissues of the rat. Volumes of mitochondria in capillary endothelial cells were determined stereologically from electron micrographs of rat cerebellum, cerebral cortex, spinal cord, cauda equina, choroid plexus, anterior pituitary, median eminence of the hypothalamus, renal proximal tubules, skin, cardiac and skeletal muscle, lung, and renal glomerulus. The capillaries of the first four of these tissue types exhibit blood-brain barrier (BBB) characteristics of permeability and capillary ultrastructure and were found to have mitochondrial contents amounting to 8 to 11% of the endothelial cytoplasmic volume. Tissues from non-BBB regions were determined to have mitochondrial volumes of 2 to 5% of their respective cytoplasmic volumes, with a variety of capillary ultrastructures. The apparent excess metabloic work capability of the BBB suggested by this greater number of mitochondria may be related to maintenance of ion differentials between blood plasma and brain extracellular fluid, to extrachoroidal cerebrospinal fluid formation, or to maintaining the unique structural characteristics of central nervous system capillaries.


Penicillin-induced epileptiform activity in the hippocampal in vitro prepatation. An in vitro preparation has been developed in which epileptogenesis in mammalian central nervous system tissue may be studied. Addition of sodium penicillin to the medium bathing slices of guinea pig hippocampus induced epileptiform activity similar to that seen in hippocampal penicillin foci in vivo. Epileptiform events were recorded as synchronous field potentials and correlated cellular bursts that occurred spontaneously and could be triggered by orthodromic stimulation. Intracellular recordings revealed that bursts were generated from large depolarization shifts in some neurons, while in others, burst discharges had little underlying baseline depolarization. This finding, and the presence of fast prepotentials in penicillin-treated preparations, suggested the involvement of dendritic activity in generation of epileptiform discharges.


Ethanol and spinal presynaptic inhibition in man. Ethanol, 0.65 gm per kilogram of body weight, was administered orally to 6 normal subjects. The mean blood ethanol levels ranged from 0.74 to 0.99 gm per liter over a subsequent 40-minute testing period. The proportion of the soleus motoneuron pool activated by the Achilles tendon reflex was reduced. Vibratory inhibition of the monosynaptic reflex was used as an estimate of spinal presynaptic inhibition. It was unaffected by ethanol.


An animal model for the production of intracranial pressure plateau waves. This communication describes a reproducible model for the generation of intracranial pressure plateau waves by obstructing the spinal cord central canal of cats with experimentally induced hydrocephalus.


Propranolol for the control of belligerent behavior following acute brain damage. The belligerence of 7 patients who had suffered an acute brain insult was effectively controlled by propranolol in doses of 60 to 320 mg per day. Of the 7 patients, 3 were treated in the acute stage after a stroke, a severe closed head injury, and a gunshot wound of the brain, respectively. A chronic postconcussion syndrome associated with chronic irritability was present in 2, and 2 were not chronically irritable but suffered from intermittent attacks of explosive rage in response to minor irritations. In all instances the belligerent behavior was controlled without inducing general sedation.


Therapeutic trials in muscular dystrophy: II. Ethylene and its derivatives. The plant growth stimulants ethylene dinitramine (EDNA) and ethylene have been reported to increase muscle regeneration. Such chemicals might therefore be of therepeutic benefit in the human muscular dystrophies. This report describes a series of experiments to reinvestigate the effects of EDNA, ethylene, and another plant-stimulating ethylene derivative, 2-chloroethylenephosphoric acid (Ethephon). EDNA and Ethephon administered two days after wounding both produced a significant increase of muscle protein synthesis seven days after the injury of normal muscle, though the increases were only 35 and 22%, respectively. The results suggested that early suppression of regeneration might explain the later increases. Ethylene administered in an identical way to that previously reported failed to increase muscle protein synthesis in murine muscular dystrophy or in wounded normal muscle. These studies suggest that treatment of human muscular dystrophies with ethylene derivatives is unlikely to prove of value.


Pedigree testing in Duchenne muscular dystrophy. Female relatives of 41 Duchenne muscular dystrophy proband cases were studied with a panel of carrier-detection tests. A total of 277 relatives were tested in order to determine which mothers had affected sons as a result of new mutation. In 39 of 41 pedigrees the data demonstrate that a mutation cannot be postulated; the 2 megative pedigrees were inadequately tested. Our data suggest that all mothers of affected sons should be considered genetic carriers (heterozygotes) until proved otherwise. Our findings also raise questions concerning what mechanisms skew the indirect statistical estimates of mutation that are in common use.


Quantitation of motion perception in the digits: a psychophysical study in normal human subjects. Threshold perception of motion of the digits was obtained in 14 normal subjects. The metacarpophalangeal joint of the index and the fifth finger of each hand and the metatarsophalangeal joint of the hallux of each foot were passively moved up and down with respect to a horizontal plane defined by the palmar or plantar surface. The motion was sinusoidal at frequencies of 0.5 and 5.0 Hz. A mpdified von Békésy paradigm similar to that used in audiometry was utilized to yield threshold levels of motion sensation. There was little difference in the thresholds obtained for the different joints. The difference between high- and low-frequency stimulation, however, was significant (p less than 0.001): the 0.5 Hz threshold was found to range from 0.8 to 1.0 degree, whereas the 5.0 Hz threshold varied from 0.4 to 0.6 degree. It is thought that motion sense is largely dependent on joint receptor contributions, but muscle and cutaneous receptors may also contribute to this proprioceptive sensation.


Familial paroxysmal dystonic choreoathetosis and its differentiation from related syndromes. Four generations of a family are described in which 7 of 8 affected members suffered from prolonged dystonic seizures; the eighth member's attacks were those of paroxysmal choreoathetosis. The attacks lasted up to 4 hours, were precipitated by alcohol, emotion, or fatigue, and responded poorly to phenytoin and barbiturates but were controlled by clonazepam. Autopsy on an affected child who died a "crib death" at the age of 2 years disclosed no major abnormality of the brain. This family appears to have the same condition as that described by Mount and Reback in 1940, Forssman in 1961, and Richards and Barnett in 1968, which the last authors termed paroxysmal dystonic choreoathetosis to distinguish it from the more common movement-induced (kinesigenic) form of the disorder. Analysis of reports of 100 cases of paroxysmal kinesigenic choreoathetosis shows that the attacks last less than 5 minutes, are precipitated by sudden movement or startle, and usually respond well to phenytoin or barbiturates. A clinical classification is presented in which the kinesigenic form is divided into a familial group (72% of cases) and a sporadic group (28% of cases) and contrasted with paroxysmal dystonic choreoathetosis. One family with an intermediate form, in which dystonic choreoathetosis was provoked by continued exertion and lasted for up to 30 minutes, is also reported.


The human thalamocortical sensory path in the internal capsule: evidence from a small capsular hemorrhage causing a pure sensory stroke. A patient is presented who suffered a strokelike event during life that resulted in a hemisensory dificit for some modalities. On pathological examination of the brain, the lesion responsible for the deficit was found to be a small slit hemorrhage located in the posterior limb of the internal capsule adjacent to and minimally involving the thalamus. Clinicopathological correlation suggests that the sensory thalamocortical radiations must lie farther posterior in the posterior limb of the internal capsule than the corticospinal motor fibers, and that they probably lie adjacent to the thalamus. The case emphasizes that small slit hemorrhages deep in the brain, although rare, must be considered in the differential diagnosis of sudden hemisensory deficits.


Inferior branch palsy of the oculomotor nerve. Three patients with inferior branch palsies of the oculomotor nerve are described. Two were under 10 years of age and the third was 30 years old at the onset. All 3 presented with painless diplopia. The onset was sudden in 2 patients and progressive in the third. The palsy cleared within a short time in the 2 patients with sudden onset, and a possible viral origin was considered. In the third patient, with progressive palsy, there was no change eight years later.


Tissue culture studies of demyelinating disease: a critical review. Tissue culture studies of human and experimental demyelinating diseases have demonstrated that sera from patients with multiple sclerosis reversibly demyelinate central nervous system cultures. Similar changes are evoked by sera from animals with experimental allergic encephalomyelitis induced by inoculation with whole central nervous system tissue but not by encephalitogenic myelin basic protein. Sera and buffy coat or lymph node cells from humans with idiopathic polyneuritis and animals with experimental allergic neuritis demyelinate cultures of peripheral nervous system tissue. While these studies have contributed to speculations about pathogenetic mechanisms of demyelinating diseases, including the role of both circulating antibodies and delayed hypersensitivity factors, a number of important questions remain unanswered. Among these are the identity of the antigens that evoke antimyelin antibodies and the precise relationship of serum or cellular antimyelin factors to the pathogenesis or clinical course of the demyelinating diseases. Further studies with this technique may provide more complete information about the role of immunological events in induction of disease.


Possible phenylethylmalondiamide (PEMA) intoxication. We have encountered a case of apparent intoxication with primidone (Mysoline) in a patient with severe renal impairment. Of interest were high serum levels of phenylethyl-malondiamide (PEMA), a metabolite of primidone.


Nerve-muscle interaction: changes in the cellular organization of a skeletal muscle upon denervation. The alterations in the organization of lumbrical muscle of the rat have been investigated following denervation, with emphasis on the structure of cytoplasmic constituents, sarcolemma in the synaptic and non-synaptic regions and acetylcholinesterase activity. The appearance of 15--18 nm intramenbranous particles in the non-synaptic sarcolemma is thought to be related to the known acetylcholine extrajunctional sensitivity which is manifested after denervation. The acetylcholinesterase activity is greatly reduced in the synaptic region in the denervated muscle. These changes are discussed in relation to the known physiological and biochemical data.


The ultrastructural cytology and chemical composition of fracture callus cartilage. The differentiation and calcification of fracture callus cartilage studied by light microscopy resembles that of the epiphyseal plate cartilage. In this study, a correlation between the ultrastructural cytology and the chemical composition of the various cartilage types found in fracture callus was attempted. Fibrocartilage cells were very active with profuse secretion of collagen into the matrix. Collagen fibres were observed in close proximity to the cell membrane. Cells from hypertrophic and calcifying cartilage showed progressive degeneration while their mitochondria contain dense osmiophilic granules. Mitochondria granules were occasionally seen in fibrocartilage cells. The intercellular matrix of hypertrophic and calcifying cartilage showed needle-shaped crystals quite often arranged as a cluster in a radiated pattern. Chemical analyses of the various types of cartilage found in fracture callus demonstrated the presence of a high molecular weight bound phosphate and an increase of sialic acid in the differentiated types of cartilage.


Definition of congenital malformations and detection of associations with maternal factors. Data collected from a cohort of 2913 pregnancies were analyzed to determine whether the varying definitions of congenital malformations influence the statistical result in the search for possible etiological factors. According to three different definitions of congenital malformations, three study groups were formed, i.e. structural malformations, all congenital defects, and all disorders or abnormalities with possible prenatal etiology. These consisted of 93, 197 and 334 cases, respectively. The control group consisted of 2579 cases. Positive associations were noted between the study groups and some factors concerning pregnancy, and the social history of the parents. The associations were strongest in the group of structural malformations and became weaker when this group was 'diluted' by other defects with questionable prenatal origin. Hence, when comparisons for evaluating the causality of significant associations in different materials are made, the definition of the concept of congenital malformations should be taken into consideration.


IgG deficiency in association with placental oedema. Deficiency of the immunoglobulin C (IgG) in the human newborn is rare in the absence of maternal hypogammaglobulinaemia. Low concentrations of IgG in cord blood were found in 3 conditions--the donor twin in the fetofetal transfusion syndrome, hydrops fetalis and congenital hepatic disease. These were all associated with placental oedema. It is suggested that the oedema may be responsible for a disturbance in maternofetal placental transfer.


Head circumference as an index of brain weight in the fetus and newborn. Postmortem brain weight and head circumference were measured in 485 fetuses and newborn infants. A cubic relationship was demonstrated between these two variables in normal infants. Statistically, a significantly larger brain weight for a given head circumference was found in small-for-gestational-age infants.


A comparative study of two developmental scales: the Bayley and the Griffiths. 50 high-risk infants consecutively selected from the population of a Neonatal Follow-up Clinic were tested using both the Bayley and the Griffiths Scales on the same day by the same psychologist without prior knowledge of the medical history. The mean age at testing was 13.1 mth with a range of 12--15 mth. Scores obtained from the Griffiths Scale were consistently higher than those obtained from either of the Bayley Scales (P less than 0.001). Intercorrelations between the Griffiths and the Bayley test were high at pH 0.01. These results suggest that, although the two tests may be used interchangeably, their numerical scores are not equivalent when administered at this age.


The narcotic-dependent mother: fetal and neonatal consequences. During the years 1971--1974, 230 infants born to drug-dependent women and 33 infants born to ex-addicts were studied. Heroin abuse declined while methadone usage increased during those years. Compared to heroin abuse, methadone maintenance treatment during pregnancy was associated with more consistent prenatal care, more normal fetal growth and reduced fetal mortality. Meconium staining of amniotic fluid was increased in the heroin and heroin-methadone groups; this was not associated, however, with an increase in meconium aspiration or a reduction in Apgar scores. Of special note was the equally severe intrauterine growth retardation of infants of former heroin addicts who were free of narcotic use during pregnancy. Neonatal withdrawal from methadone appeared to be more severe than from heroin, as judged by amount of medication required to control symptoms and duration of treatment. In all groups, central nervous system signs were the most common manifestations of withdrawal. Severity of withdrawal did not correlate with late pregnancy maternal methadone dosage. Neonatal seizures occurred in 1.5% of the heroin group and 10% of the methadone group. Discharge of an infant to a parent rather than to an alternate care-taker was more likely if the mother was enrolled in a methadone treatment program. Methadone maintenance programs appear to offer significant therapeutic benefits, balancing the untoward effects of the drug on the newborn infant.


Computerized transverse axial tomography in the newborn. 7 babies, aged 6 days--8 wk, who presented with abnormal neurological signs during the first days of life were investigated by computerized transverse axial tomography. 3 babies had suffered perinatal asphyxia. Only 1 baby required a general anaesthetic to facilitate the investigation. Structural intracranial lesions were seen in 6 babies and comprised hydranencephaly, cerebral agenesis with grossly dilated lateral ventricles, unilateral cerebral oedema, subarachnoid cyst of localized cerebral atrophy.


Neck extensor hypertonia: a clinical sign of insult to the central nervous system of the newborn. Abnormal hypertonia of the neck extensor muscles in newborns may be appreciated by observing spontaneous posture, evaluating resistance to repeated passive flexion of the head, and eliciting the head straightening reflexes. This sign correlates well with other signs of insult to the central nervous system. Of 1743 newborns over 37 wk gestational age, 17 appeared to have signs of cerebral insult according to the classical criteria of abnormal state of consciousness, tone, and reflexes. Of these 17, 12 (70%) had neck extensor hypertonia. 38 newborns appeared to have mild signs of cerebral insult with abnormalities of tone and excitability. Of these 38, 14 (37%) had neck extensor hypertonia. Only 12 (0.7%) of 1655 newborns with otherwise normal neurological examination had neck extensor hypertonia. Further studies are necessary to evaluate the prognostic value of neck extensor hypertonia in the neonatal period.


Glucose disappearance in infants of diabetic mothers. I. Relationship to maternal glucose tolerance and insulin production. Glucose disappearance and insulin response were determined in mother--infant pairs of normal, gestational diabetic and diabetic pregnancies following an intravenous glucose load. Mothers were studied in the third trimester of pregnancy and at least 6 wk postpartum. Significant differences were present in glucose disappearance and insulin response in both gestational diabetic and diabetic mothers during pregnancy compared with the control group. Infants were studied within 4 h of birth while fasting, and glucose and insulin levels followed through the first 3 days of life. Neonatal hypoglycemia did not occur and glucose disappearance (KT) was not different among the three groups. There was no correlation between maternal glucose tolerance or insulin production and that of their infants. The only distinguishing factor among the infants was higher insulin production in infants of diabetic mothers during the 60-min intravenous glucose tolerance test which persisted up to 4 h following the infusion. It is concluded that factors other than the degree of maternal glucose tolerance are responsible for the development of neonatal hypoglycemia in infants of diabetic mothers, most notably control of maternal diabetes, the amount of glucose infused immediately before delivery and neonatal glucose production.


Glucose disappearance in infants of diabetic mothers. II. Relationship to lowest neonatal blood glucose and amniotic fluid insulin. Neonatal glucose disappearance (KT) was measured in 26 infants of insulin-dependent diabetic mothers within the first 2 h of life. A significant correlation was found between the KT and the lowest blood glucose (LBG) in the first day of life (r = 0.64, P less than 0.001). None of 21 infants developed a LBG less than 20 mg/dl when the KT was less than 3.0%/min in contrast to 4 of 5 whose KT was greater than 3.0%/min (P less than 0.001). Amniotic fluid (AF) glucose and insulin were determined in 42 samples from 18 of these patients in the third trimester of pregnancy. There was a significant correlation between AF insulin values and the neonatal KT (R = 0.76, P less than 0.001). The correlation was higher when only amniotic fluid values obtained on the day of delivery were considered (n = 17, r = 0.90, P less than 0.001). 1 of 13 infants developed a LBG less than 20 mg/dl when the amniotic fluid insulin was less than 100 mu U/ml on the day of delivery in contrast to 3 of 4 whose AF insulin was greater than 100 mu U/ml (P less than 0.001). No correlation of AF glucose was found with infants' KT or LBG. These data suggest that both neonatal KT and AF insulin are of value for predicting neonatal hypoglycemia and detecting infants who will require treatment for its prevention.


Respiratory muscle EMG in newborns: a non-intrusive method. A non-intrusive method of recording the EMG of respiratory muscles with electronic suppression of the ECG artifact and averaging with a running window was employed in newborn infants at term to study respiratory patterns in different behavioural states. There are clear state-related differences in the diphragmatic and intercostal activity patterns. During most of the time in state 1 (quiet sleep) sustained tonic activity is found in the diaphragm as well as in intercostal muscles, but is  virtually absent during state 2 (active sleep). During state 1 intercostal activity slightly precedes diaphragmatic activity whereas in state 2 both muscles contract about synchronously and vary widely in their amplitude. During periodic breathing the inspiratory EMG activity is absent in the pauses, but tonic activity may be present during periodic breathing in state 1. Isolated respiratory pauses with silence in the respiratory muscles occur in state 1 after sighs and starties with deep inspirations. During state 2 many respiratory pauses accompany gross movements and simultaneous laryngeal muscle activity suggests upper airway occlusion. Respiratory pauses without movements cannot be due to general alpha-motoneuron inhibition, because chin muscle activity may be seen at the same time. Gross movements often act as a reset mechanism for increase or decrease in tonic activity and phasic respiratory activity. Some speculations on the neural mechanisms of respiratory control based on the preliminary findings from the EMG recordings are mentioned.


The functional growth and development of the lung during the first year of life. In this article much of the available data on lung volumes and mechanics in normal infants is assessed and summarized, and growth charts for the various parameters of lung function during the first year of life are presented. There is considerable evidence to show that lung development proceeds in a highly organized manner, and that strong linear relationships exist between lung volume and body size, between dynamic compliance and lung volume, and between airway conductance (the reciprocal of airway resistance) and lung volume. However, the latter relationship is affected both by the race and postconceptional age of the infant. Specific Airway conductance is higher during infancy than at any other time during life, and this gives the newborn infant certain advantages with which to counterbalance both the small size of his lungs and the fact that he is an obligatory nose breather.


Pregnancy after jejuno-ileal bypass.

Pregnancy after jejuno-ileal bypass. The clinical details of two patients who have conceived after jejuno-ileal bypass for gross refractory obesity are presented. One was a twin pregnancy which yielded a stillborn and a normal baby. The other yielded a normal baby. The management of pregnancy in patients with small bowel bypass is discussed.


The free diet: 150 cases personally followed-up after 10 to 18 years. One-hundred-and-fifty overweight patients, who were given advice about losing weight during a period of eight years in a suburban general practice of 2000 individuals in the British National Health Service, have been followed up for a minimum of 10 years. Treatment consisting of attempting to modify the individual's eating habits by means of a free diet low in carbohydrate and moderate in fat has resulted in some measure of success in about three-quarters of the individuals and almost one half (48 per cent) maintained significant weight loss at the end of the period. Frequent consultations and the judicious exhibition of anorectic drugs have both played a part in producing these results.


Attitudes of adolescents to their body build and the problem of juvenile obesity. Prevalence of obesity, attitude to body weight and dimensions, eating habits, opinions on good nutrition and on the causes and prevention of obesity were studied in two groups of Israeli children, each comprising about 500 boys and girls, 13--14 years old. Mean relative weight was close to median weight for height, although 9 per cent of both boys and girls weighed more than 120 per cent of median weight. Weight was closely related to triceps skinfold thickness. Twenty-six per cent of the boys and 15 per cent of the girls rated themselves as thin, 61 per cent of children of both sexes as medium, and 13 per cent of the boys and 25 per cent of the girls as obese. Self-perception of body build was more closely related to weight than to skinfold thickness. Two-thirds of the boys and over one-half of the girls were satisfied with their weight, but dissatisfaction with size and shape was often expressed. Boys wished to have larger muscles and chest circumference and many girls, even when not obese, wanted to be smaller in size and shape. Most of the obese children wanted to lose weight. Of 499 children examined, 16 boys (7 per cent of the sample) and 58 (21 per cent) girls reported for dietary therapy. While most of these children were obese, by either subjective or objective criteria, an appreciable number of nonobese children were also dieting. The children's own perception of their body build seemed to be a strong motivation to diet for weight control. Most of the dieters did not receive any dietary advice from professional people. Over two-thirds of both boys and girls believed that daily consumption of milk, bread, fruits, eggs, cheese, meat, and tomatoes is desirable. More overweight than thin and normal-weight children indicated that, to prevent obesity, all kinds of food are permissible, but only in limited amounts. Most children believed in the fattening value of cakes, sweets, fried and fatty foods, potatoes, bread and nuts. Overweight children, particularly girls, reported eating less bread, cake and cream, adding less sugar to beverages, and eating sweets and ice cream less frequently than thin and normal-weight children. Overweight teen-agers appear to be more conscious of their food intake than under- and normal-weight children.


The consequences of early overnutrition for fat cell size and number: the pig as an experimental model for human obesity. (1) The objectives of these studies were: (a) to determine the period during which fat cells were being formed in different fat depots in the pig; (b) to discover whether total fat cell number could be affected by overfeeding from weaning or later in life, and (c) to examine the domestic pig as a model for human obesity studies especially as to the influence of the energy intake at different stages in life on fat cell size and number. (2) Pigs were weaned at six weeks of age and allocated to one of four diets. Group H was fed to appetite on a high carbohydrate diet and became extremely obese. Group L was fed at half the energy intake of group H; these animals grew steadily but deposited little adipose tissue. Group L-H was fed as group L for 40 weeks and then as group H for the rest of the experiment, while group H-L was fed as group H for 40 weeks and then placed on a very restricted ("slimming") diet for the remainder of the experiment. (3) The volume of fat cells in group H was about four-fold greater than in group L at the end of the experiment. Cell volume increased rapidly when group L was fattened after 40 weeks and could be reduced significantly, albeit slowly, when group H was "slimmed". (4) There was a significant increase in the apparent number of fat cells in the depots of overfed pigs that did not diminish when the animals were "slimmed". However, in restricted pigs subsequently fattened, there was an apparent steady increase in fat cell number that eventually reached the same figure as in pigs overfed from weaning. (5) The standard methodology is inadequate to make broad generalizations about the influence of diet on cellularity. First, the development of fat cell size and number follows different time scales in different depots. It is essential to monitor several sites before attempting to estimate cell number. Secondly, since cells with diameters less than about 15 micrometer are not detected, "empty" cells, containing no fat, may be present from birth: subsequently they may be filled when energy intake is appropriate so that later they become visible, and are recorded as fat cells. In these cases there will be an "apparent" but not a real increase in cell number.


Serum cholesterol and triglycerides in relation to ponderal index and age in two contrasting populations. One hundred and seventy six mentally retarded adult patients had their serum cholesterol, triglycerides and ponderal index determined during a seven week period and compared with those of a normal group of business executives being routinely screened by the same laboratory. A comparison of cholesterol and triglyceride levels showed those of the former group to be significantly lower, as dealt with in a previous paper by Lawlor, O'Hara and Birtwistle (1974). The values in mentally subnormal males showed no correlations with ponderal index, whereas the normal males showed highly significant correlations throughout. Both the normal and subnormal females showed highly significant correlations of cholesterol with triglyceride levels, and of age with cholesterol concentration, but not of ponderal index with either cholesterol or triglyceride levels.


Transient insulin increase in reactive hypoglycemia in obese and non-obese subjects. (1). Insulin levels at the moment of glucose-induced reactive hypoglycemia have been compared with zero-hour insulin levels in 108 subjects in whom the blood glucose had decreased to 50 mg percent or less (50 to 31 mg) at the third, fourth, or fifth hour in the course of an oral glucose tolerance test (1.75 g/kg of body weight). (2). Of the 47 obese subjects, insulin levels at the time of the reactive hypoglycemia were inappropriately high, ie exceeded the fasting insulin level by 20 uU/ml or more in 38 percent and by 40 microunits/ml or higher in 26 percent of the tests. (3). In 61 non-obese subjects, employing the same criteria, inappropriately high insulinemia at the time of reactive hypoglycemia was recorded with about the same frequency. (4). In each instance of reactive hypoglycemia of 50 mg percent or less with concomitant insulin levels above the starting value to the degree stipulated, the so-termed inappropriate hyperinsulinemia was transient. In other words, judging by levels preceding and/or following the reactive hypoglycemia, insulin titers were decreasing and hence, the inappropriately high insulin level at the moment of hypoglycemia represented a lag phenomenon. (5). The above data suggest that insulin levels elevated above the starting value may play a role in reactive hypoglycemia. In subjects with insulin levels at the time of reactive hypoglycemia equal to or below the starting value, the low blood glucose level cannot be attributed to insulin. In such instances, delay or lag in hepatic glucose output and/or counter-regulatory responses probably play the dominant or sole role in the reactive hypoglycemia.


Epidemiological aspects and social importance of obesity. The situation in Italy compared with other developed countries. Epidemiological aspects of obesity have been the object of few studies in Italy, and the results of these are reviewed and compared with those obtained in other developed countries. The prevalence of obesity has been investigated in pre-school and school-age children, in young conscripts and in workers at the Riuniti Hospital in Parma, and the results show that the problem of obesity in Italy is a serious one. More than 2000 obese subjects, attending the First Medical Clinic of Parma University, have been studied to establish how far overweight is responsible for pathological and disabling complications. Obesity was implicated as a major contributing factor in diabeties, atherosclerosis, hypertension, arthritis and many other disabling diseases. The social aspects of the problems of obesity are discussed, together with possible preventive and curative measures.


Cardiovascular risk factors in gross obesity. In 500 obese patients (146 men, mean age 37 +/- 13 years, Broca index 147 +/- 24; 354 women, mean age 36 +/- 14 years, Broca index 151 +/- 28) cardiovascular risk factors (RF) were investigated. The most frequent RF was hypertension (71 per cent), followed by glucose intolerance (49 per cent), hypertriglyceridemia (31 per cent), hypercholesterolemia (22 per cent) and hyperuricemia (22 per cent). Only 12 per cent of the patients were without RF. These patients were younger and less obese than the patients with RF. The prevalence of RF increased with increasing age and overweight. Analysis revealed significant correlations between overweight and blood pressure, blood glucose, insulin and age. Significant correlations between age and hypertension, blood glucose cholesterol, triglycerides and overweight were detected. The correlation between overweight and the sum of all RF was higher (r = 0.35) than the one between age and the sum of all (r = 0.23). Obese patients had a high prevalence of RF. Increasing overweight and (to a lesser extent) age are both associated with increased prevalence of RF. On the basis of the prevalence of RF, patients with gross obesity (Broca index greater than around 150) were considered to be at a high risk in respect of coronary heart disease.


Some psychobiological aspects of adolescent growth and their relevance for the fat/thin syndrome (anorexia nervosa). Adolescent attitudes to body shape and weight are radically different between the sexes. Females, within a very short time of crossing their pubertal "threshold", usually wish to minimise their shape and often construe themselves as "fat" when it is evident that they are not in fact obese. The majority attempt to "diet" and often succeed, at least intermittently, in substantially reducing the amount of carbohydrate in their daily food intake. This "fatness" of females has important biological and social functions, being closely related to sexual reproductive tasks and being also an important aspect of their appearance and "attractiveness". In contrast, males rarely have such concern about their shape unless they are massively obese or have major gender identity problems. Fatness in both sexes is also associated with growth rate, being greater in those who reach puberty early. Such "puppy fat" together with the commonplace adolescent female's attitude to her own shape are, in the face of adolescent psychosocial stress, contributory factors to the development of anorexia nervosa (the thin/fat syndrome) in many such women who would otherwise tend to obesity. The relevance of body weight and fatness for the pubertal "threshold" process and the mobilisation of this as a central mechanism within the disorder is discussed.


Anticipated rate of weight loss during dieting. Two hundred and thirty-five females anxious to lose weight were asked to state their anticipated rate of weight loss each week or each month after the first few weeks of dieting. They were divided into four groups of 50 subjects, one group enrolling in a slimming club for the first time, one group already attending the same slimming organisation and two groups on first attendance at one of two hospital obesity clinics. The remaining group comprised 35 subjects re-enrolling in a slimming club. Only 27 per cent of those interviewed on their first attendance had a realistic concept of the anticipated rate of weight loss (AROWL) while 60 per cent of those re-enrolling and 90 per cent of those currently attending a slimming club were realistic in their expectations. The younger subjects were significantly more obese and the least realistic concepts of the AROWL were held by those subjects most in excess of their ideal weight. This study highlights the frequency with which unrealistic concepts of the AROWL are held and suggests the need to reinforce realistic concepts of weight loss in the obese.


Effects of submaximal physical exercise on adipose tissue metabolism in man. In order to follow early metabolic adaptations in adipose tissue, which may lead to a decrease in fat cell size and body fat obtained by physical training, two sets of experiments were performed. Obese subjects and a control group exercised on a bicycle at two-thirds of maximal working capacity for one hour. Twenty-four hours thereafter, either on ad libitum diet, or on an isocaloric diet supplemented with calories corresponding to the expanded calories during the work load, an adipose tissue biopsy was taken and fat cell metabolism studied. In obese subjects on and ad libitum or on an isocaloric diet the lipolytic process was increased after the exercise but no significant effects were found on the rates of glucose metabolism. Furthermore, a relationship between cell surface and metabolism was found before, but not after, the work in all groups. No changes were seen in lipoprotein lipase activity. Obese subjects on a controlled diet showed a somewhat higher insulin and catecholamine responsiveness of adipocytes than was the case in the obese subjects on an ad libitum diet. This may well be due to the differences in carbohydrate intake, a factor of importance for hormonal responsiveness of fat cells. The increased basal lipolysis after exercise may be caused by the release of lipolytic hormones, and may well be the first sign of an adaption of the organism to diminish the fat stores as seen in physically trained subjects.


Effects of gonadectomy on hypothalamic obesity in male and female rats. The effects of ventromedial hypothalamic (VMH) lesions on body weight, body composition, and food intake were examined in gonadally intact and gonadectomized adult rats of both sexes. The most striking finding was that, while gonadectomy only modestly augmented the weight gain following VMH lesions in females, castrated VMH males gained twice as much weight as gonadally intact VMH males. Furthermore, the weight gain of the castrated VMH males was comparable to that seen in VMH females. Thus, castration of males eliminates the sex difference in body weight gain that is ordinarily observed in gonadally intact animals following VMH lesions. The degree of weight gain in all VMH animals correlated highly with the amount of food eaten, and additional body weight of all VMH animals was accounted for by increased body fat.


Immunoreative insulin in obesity of adult women. The levels of immunoreactive insulin (IRI) in 58 obese women and 14 controls were studied. The investigation revealed: (1) higher IRI levels in obese patients compared to controls, with a tendency to normalization after weight reduction (2) a correlation between IRI values and the degree of obesity, the amount of fat and lean body mass. The closest relation was found between stimulated IRI values and the Broca index (3) the ratio glucose/insulin was lower in the obese women before and after a glucose load. After a decrease of body weight by 11 per cent this ratio did not change significantly (4) a negative correlation between the glucose/insulin ratio and body weight, overweight, body fat and lean body mass.


Lipodystrophic diabetes treated with fenfluramine. Congenital generalized lipodystrophy is considered to be a diencephalic syndrome with disturbance of hypothalamic transmitters. After puberty and arrest of growth the patients develop a serious untreatable diabetes mellitus. One of our patients, a girl 15 years of age, developed a lipodystrophic diabetes with fasting blood glucose levels above 300 mg/100 ml, increased serum insulin with insulin resistance, and hyperlipidaemia. Daily administration of fenfluramine gave a dramatic improvement. The voracious hunger and profuse perspiration were reduced, the patient's serum lipids became normal, her blood glucose fell, and her sensitivity to exogenous insulin increased. A normalization of the urinary excretion of the serotonin metabolite, 5-OH-indole acetic acid, was observed.


Differential effects of amphetamine and fenfluramine on appetite for palatable food in humans. Amphetamine (10 mg), but not fenfluramine (40 mg), suppressed appetite (ie salivation elicited by a palatable food) in ten subjects of normal weight one hour after ingestion. This result supports the hypothesis that the drugs operate through different neural mechanisms. Neither drug affected hunger and food appeal ratings.


Quality patient care through risk management. These four areas in risk management are most often the cause of failure to eliminate patient risks. If these four major areas were incorporated into the medical student's curriculum or into the continuing educational upgrading of the physician, he would be developing risk control habits as well as knowledge that would allow him to practice quality medicine. He would also be able to enjoy the practice of medicine with less concern for malpractice reprisal and peer review. The ability to minimize the risk of medical care to the patient is an important responsibility of every physician. It is essential for the provision of quality medical care and for preventing or reducing an adversary relationship between the patient-public and the physician.


Graphic analysis of forces acting upon a simplified model of the foot. Application of a graphical technique to analyse internal forces on a simplified model of the foot in various external loading patterns. The method is applied when the external load is acting purely upon the forefoot, the hindfoot and on both locations. The pes planus situation and the effect of the "rocker" and inlay sole are studied.


Clinical correlates of neoplastic involvement of the eight cranial nerve in man. This study of 25 cases of benign neoplastic involvement of the eighth nerve in man suggests: (1) Eighth nerve auditory dysfunction and minimal structural change in the internal auditory canal are the earliest reliable signs leading to tumor detection. (2) "Early" detection does not mean "small" tumor. (3) Schwannomas tend to grow more slowly in the elderly patient. (4) Compression and displacement of viable axons may be the primary pathophysiology of dysfunction.


[Quantitative and qualitative changes in the heart muscle of the left ventricle in male rats during development and maturation in the first 6 months of life]. In order to characterise the postnatal development and maturation of heart muscle cells the musculature of the left ventricle of male rats has been investigated electronmicroscopically at birth, at the 1st, 2nd, 3rd, 4th, 5th, 6th, 7th, 14th, and 21st day of life, as well as after the 1st, 2nd, 3rd, 4th, 5th, 6th month. On the basis of these investigations quantitative and qualitative data have been obtained. The development of the heart muscle cells is characterised by 2 processes. 1. Processes of synthesis and development - The ribosomes/polysomes which are to be found in great numbers are a characteristic of the synthesis of the myofilaments which plays an important role in the 1st phase of postnatal development. This synthesis of myofilaments takes place in the sarcoplasm by the formation of new individual myofilaments, in the interior and at the border of existing myofibrils, and at the level of the Z-lines. Mitochondria are developed in particular by the germination of small mitochondria the percentage of which amounts to about 16% at birth. The sarcoplasmic reticulum is developing in its longitudinal as well as transversal forms only during the 1st month. The disci intercalares, however, have been formed in the main already at birth. Cells are furthermore developing by mitotic processes during the first days. 2. Degradation processes - 2.1. The degradation is characterised by focal autophagocytotic processes in mitochondria concerning the cristae as well as the matrix and the outer membrane. During these processes autophagocytotic vacuoles are developing partly with myelin membranes. In addition, whole mitochondria are transformed into autophagocytotic vacuoles. Later on, mitochondria are also condensed and transformed into mitochondrial lipofuscin. 2.2. The autophagocytotic degradation of glycogen together with the sequestration and formation of vacuoles and myelin membranes are particularly striking. Lipofuscin, however, is to be observed in larger quantities only from the 4th month onwards. The investigations have shown that decisive phases of development can be determined: the day of birth, the 3rd, 4th, 5th, and 7th, and 14th day, as well as after the 1st, 3rd, and 6th month. This determination of the specific developmental phases of the heart muscle makes it possible to carry out investigations in a more economical and purposeful way.


[The external submucous plexus (Schabadasch) in the small intestine of the swine. I. Form, structure and connections of ganglia and nerve cells]. 1. There are described principles of organization of the plexus submucous externus (Schabadasch) in the small intestine of the pig. They can be summarized under the term of polarization of nerve cells. 2. The principle of polarization is realized for instance by the formation of type I and type II cell aggregates and by the specific course of the processes of both cell types. 3. These criteria of organization which are much clearer in the pig than in other animals, recommend the plexus Schabadasch of the pig as a suitable model for further investigations.


The role of mast cells in the development of adrenergic innervation in the rat iris. In the rat iris, during the development of the adrenergic ground plexus, intensely fluorescent mast cells, not observable after maturation of the same, could be revealed with the Falck technique. According to the electron microscopic investigations the mast cells are in close connection with the developing nerve fibres and Schwann cells in the early stage of postnatal life. On the basis of signs suggesting degranulation it is concluded that the mast cells can play a role in the regulation of the development of innervation by means of substances released from their granules.


[Morphological studies of the matrix in human hypothalamus]. The variations of matrix and ependyma in the hypothalamus was histologicaly investigated in 120 human brains of both sexes from the 13 week old fetuses up to the end of the first year of postnatal life. The plane of cuts were in the region of the anterior hypothalamic nucleus, of the ventromedial nucleus, and the arcuate nucleus. We have found that the exhaustion of the matrix begins in the 14 week old embryo in the anterior and medial hypothalamus. A subependymale zone is present in these areas in the 17 week old embryo and exists up to 23 week. The one-cell-layer ependyma appears in the anterior are of the ventromedial nucleus at first in the 24 week week old embryo. After this the ependyma appears from the 25 to the 28 week old embryo in the regions of the anterior hypothalamic nucleus and the other areas of the ventromedial nucleus. In the immediate surrounding of the arcuate nucleus we observed the first alterations in the 15 week old embryo. The exhaustion of matrix is a continuous process up to the 23rd week. The boundary of the third ventricle remained to be a multilayer and in all stages of development cells were found, which reach into the lumen. Only after birth the multilayer boundary was reduced. At the end of the first year of postnatal life the one-layer ependyma was developed at a few sites. We could not find any significant variations of matrix exhaustion in the different sexes.


Studies on the oogonial cycle in Puntius ticto (Ham.) III. Formation of degenerated follicles. In Puntius ticto, the atresia has been observed both in mature and empty follicles. In empty follicles, theca becomes highly vascularized and the granulosa layer hypotrophied. The later invades into the lumen of the empty follicle and finally disappears. In yolk laden follicles, both theca and granulosa show hypertrophy in their cells. The granulosa becomes multilayered and finally starts digesting yolk globules after liquefying it.


Comparative neurohistological observations on the intrinsic innervation of pancreatic artery (blood vessel) in the representative of bird and mammal. The present investigation was undertaken for the study of the comparative neurohistological observations of pancreatic-Artery (blood vessel) in Gallus domesticus (white leghorn) and Suncus murinus (Indian musk shrew) by cholinesterase technique. In Gallus, the innervation of arteries (blood vessel) was by a good number of non-myelinated nerevs, which formed the periarterial plexus in participation with the postganglionic fibres at one end and the fibres of the nerve cells of the other end. In Suncus, the periarterial and AChE-positive ganglia were arranged in chain-like fashion on the periphery of the artery. Periarterial plexus was formed by tortuous, myelinated nerves and the nerve fibres of the ganglia.


[Fecal fermentation in meteorism].

[Fecal fermentation in meteorism]. An old test to investigate fecal fermentation was modified with the purpose of changing it from qualitative to quantitative. The modified test consists in placing in stove, at 37 degrees C for 24 hours, 5 grams of feces, suspended in water. The fermentable alimentary residues, present in the feces, suffer the action of bacteria, also there present, yielding gas that is collected and measured. Using the test, fecal fermentation was determined in 3 groups of individuals: a) 40 patients with meteorism that had persisted or improved only slightly or fairly with treatment; b) 28 apparently healthy subjects; and c) 6 patients with meteorism that had disappeared or become minimal with treatment. In the group of 28 apparently healthy subject, the obtained results varied from 0.1 to 1.1 ml gas/24 h., with a mean +/- s.d. of 0.55 +/- 0.29 ml. gas/24 h. When a distribution curve was made with the results obtained in the group of 40 patients with meteorism, these results separated into 2 subgroups: one subgroup with 28 patients, in whom results varied from 1.0 to 13.3 ml. gas/24 h., with a mean of 4.8 gas/24 h. (only) in 1 of these 28 patients a normal result of 1.0 ml. gas/24 h. was obtained, while in the remaining 27 patients results of 1.5 or more ml. gas/24 h. were obtained); and the other subgroup with 12 patients, in whom results varied from 0.0 to 0.9 ml. gas/24 h., with a mean of 0.29 ml. gas/24 h. Finally, in the group of 6 patients with successfully treated meteorism, results were from 0.1 to 0.9 ml. gas/24 h., with a mean of 0.4 ml. gas/24 h. The above mentioned results strongly suggest the existence of a relationship between meteorism and exagerated fecal fermentation. The nature of this relationship has not yet been completely clarified. However, the test used to determine fecal fermentation already promises to be very helpful for a better understanding and management of meteorism.


[Simple method of measuring the physiological form the velocity of intestinal transit]. The velocity of intestinal transit was studied in 24 healthy volunteers using as a marker a small rubber bag which contained 7 to 10 microcuries of NaI 131. The bag was ingested and its passage along the digestive tract followed over the abdominal surface with the help of a collimated scintillation counter connected to an automatic counting system. The time elapsing since ingestion of the bag until its expulsion with feces was taken as the intestinal transit time. In a normal subject, transit of the bag was compared with the one of plastic radioopaque pellets whose passage along the intestine can be followed radiologically, and which at present are considered the best existent marker to measure velocity of intestinal transit. The bay and pellets progressed practically together along the digestive tract. The described method is thought to be very useful to measure in a phisiologic and simple way the velocity of intestinal transit.


[Gastric secretion in hypovolemic rats caused by acute hemorrhage]. Gastric secretion was studied in two groups of rats in which pyloric ligature with wire was previously peformed. One of the groups was acutely bled until hypovolemia. The following parameters were checked: gastric volume, acid and pepsin secretion, Pu/g of stomach, chloride, potassium, and sodium. A significant decrease in volume, acid and pepsin secretion, Pu/g of stomach and chloride and increase in potassium in the hypovolemic rats found. There was no significant change in sodium concentration. There was no significant difference in the pepsinogen concentration in gastric mucous between both groups of rats.


The diagnosis of liver hydatid disease in children by scintigraphy. The results of scintigraphy in 143 children with suspected hydatid disease are reported. In 65 cases, the presence of cysts as detected by scintigraphy was confirmed at surgery. In 78 cases, scintigraphy ruled out liver hydatid disease. In 52 cases with confirmed liver HC, only conventional colloid scintigraphy was carried out. A review of images is performed. In 13 patients, with a total number of 19 cysts, blood pool liver scintigraphy was done in order to investigate the degree of vascularization of the space-occupying lesion, disclosed earlier by colloid scan, and clarify its nature. A review of images is performed. The importance of the procedure is discussed reaching to the conclusion that it is advantageous to carry out colloid and blood pool liver scintigraphy prior to surgical treatment of liver hydatid disease.


Immunoglobulin in intestinal secretions. The objective of the present investigation is the study and interpretation of the role played by the immunoglobulins, especially IgA, during acute diarrhea in children. IgA, IGG and IgM values in serum and IgA in intestinal secretions were studied in a group of children (between 3 months and 5 years of age) during diarrhea, convalescence and in normals. The method of simple radial immunodiffusion according to Mancini was employed. IgA is the immunoglobulin which suffers the greastest alteration in acute diarrhea. The precipitation halos (the average values), were lower during the diarrhea than in convalescence and in normals.


Glycine-receptors in the vertebrate central nervous system. Evidence for the existence of glycine-receptors in the vertebrate central nervous system (CNS) has been reviewed and analyzed. Biochemical studies have supported iontophoretic findings that such receptors exist in several regions of the CNS. Subcellular studies on the displacement of 3H-strychnine binding by glycine and on the effects of strychnine on 3H-glycine binding have revealed that strychnine does not interact directly with glycine-receptors, lending support to studies performed in situ. Approaches toward glycine-receptors remain limited due to the inavailability of a specific glycine-antagonist.


On the mechanism of the cortical depression induced by afferent stimulation. The cortical depression induced by the stimulation of some afferent fibers affects strychnine spikes elicited in two different ways: by direct electrical stimulation, and through the evoked potentials induced at the somatosensory area by single shocks to the radial nerve. The effects on these two types of responses were found to be very similar, which was taken to indicate that the site of action of the mechanism involved is the same, that is, the non-synaptic membranes of the dendrites of pyramidal neurons. It is suggested that the depressant action is mediated through the serotonergic neurons, since the previous administration of 5,6-Dihydroxytryptamine (5,6-DHT) blocked the changes. The 5-Hydroxytryptamine (5-HT) liberated would act as a neurohumoral agent, since the synaptic mechanisms do not seem to be involved and the effects are manifested in a diffuse manner.


Brain death: I. Angiographic correlation with the radioisotopic bolus technique for evaluation of critical deficit of cerebral blood flow. An innocuous intravenous portable radioisotopic test using technetium 99m pertechnetate was employed to demonstrate the deficit of cerebral blood flow associated with brain death. The results are compared to those of bilateral carotid and vertebral angiography in 20 patients. Absence of a bolus tracing from the head in the presence of a control tracing of a bolus from the femoral artery in two successive studies one hour apart reliably correlated with the clinical and electroencephalographic findings signifying cerebral death in comatose, apneic patients. Angiography indicated absence of intracranial circulation in 10 patients. Stasis filling or retrograde emptying of arterial vessels (or both) occurred in 7 patients. There was no evidence of venous filling in any of these 17 patients; all of them had either an absent head bolus or an "intermediate tracing." Results indicate that either form of tracing represents a critical decrease of cerebral blood flow. Two other patients had evidence of severely impaired abnormal posterior fossa circulation without angiographic evidence of cerebral circulation; both of these patients had an absent head bolus. An additional patient had an unusually small head bolus, and angiography revealed extravasation of radiopaque material but no evidence of intracranial circulation. We conclude that the bolus technique is a helpful adjunct in diagnosing brain death.


Brain death: II. Neuropathological correlation with the radioisotopic bolus technique for evaluation of critical deficit of cerebral blood flow. Diffuse necrosis and autolysis were found in the brains from 6 comatose, respirator-supported patients in whom the bolus technique demonstrated no cerebral blood flow during a period exceeding 20 hours prior to cardiac death. When blood flow was insufficient to produce a bolus, there was no evidence of active tissue response to necrosis. In 6 similar patients, when cerebral blood flow was detected by the bolus technique, less extensive necrosis was observed postmortem and there was active tissue response.


A prospective study of nontraumatic coma: methods and results in 310 patients. Neurological signs and outcome are compared in the first 310 patients from a continuing prospective study of coma not caused by trauma or drugs. Sixteen percent of the patients achieved an independent existence within a month; severe disability or the vegetative state developed in 25% of patients comatose for six hours and in 79% of those still in coma after a week. The chance of regaining an independent existence was greater in patients who, by one day, obeyed commands or moved the limbs appropriately in response to noxious stimuli or who had attained any of the following: orienting eye movements, normal responses to oculocephalic or oculovestibular stimulation, or normal muscle tone. Conversely, the chance of regaining an independent existence fell in patients who, after one day, had either extensor responses of the limbs or failed to move them in response to noxious stimuli or who lacked eye opening, pupillary reactions, corneal responses, or any eye movement in response to oculovestibular or oculocephalic stimulation. Beyond these general guidelines, numbers of patients with particular signs are presently too small for confident prediction of outcome.


Pharmacological prophylaxis against the development of kindled amygdaloid seizures. The kindling of amygldaloid and cortical seizures in cats was used to study the prophylactic effects of phenobarbital, phenytoin, ethosuximide, acetazolamide, and dexamethason. Phenobarbital prevented the evolution of such seizures beyond stage 4 in all amygdaloid-kindling animals during 160 days of study. The prophylactic effect persisted on periodic challenge after the drug had been discontinued. Phenytoin, ethosuximide, acetazolamide, and dexamethasone appeared to have no prophylactic effect against the development of kindled amygdaloid seizures. With cortical kindling, both phenobarbital and phenytoin retarded the evolution of seizures without achieving true prophylaxis. The drugs appeared to act as suppressants. Prophylaxis was not an "all-or-none" phenomenon but rather a limitation of the stage of seizure evolution.


The relationship between Parkinson syndrome and vascular siderosis: an electron microprobe study. Vascular siderosis (VS) refers to the presence of mineralized small and medium-sized arteries in the globus pallidus, usually regarded as reflecting an aging process. The electron probe analysis of deposits in vascular siderosis in 10 patients dying of parkinsonism and in 8 other patients without parkinsonism is reported here. The microprobes identified a total of 11 elements in the VS in these 18 patients. Five elements--lead, aluminum, sulfur, manganese, and barium--were present only in VS associated with parkinsonism. Statistically, the association of lead was highly significant while that of aluminum and sulfur in 4. The significance of the presence of sulfur is difficult to assess since its compounds are normally present in large quantities in the brain. These findings raise the question whether lead and aluminum may be associated in some way with the pathogenesis of certain forms of Parkinson disease.


Biochemical correlates of illness and recovery in Reye's syndrome. Eight patients with Reye's syndrome were followed through the course of their disease with serial measurements of serum concentrations of ammonia, short-chain organic acids, and amino acids. Correlations were made between clinical status and biochemical alterations. Elevated short-chain fatty acids, hyperammonemia, and hyperaminoacidemia were found in all patients studied. Clinical improvement appeared to correlate most closely with clearance of short-chain fatty acids from the serum. These observations suggest that the clinical symptoms are at least in part related to organic acidemia and that treatment directed toward the rapid clearance of these compounds from the system is reasonable.


Chronic hydrocephalus associated with short stature and growth hormone deficiency. A 28-year-old man with chronic hydrocephalus due to aqueductal stenosis was found to have a subnormal response of growth hormone to arginine infusion. It is postulated that compression of the pituitary by the enlarged third ventricle produced a deficiency of growth hormone and short stature.


The therapeutic use of glucocorticoid hormones in the perinatal period: potential neurological hazards. The expanding perinatal use of glucocorticoids entails potentially hazardous effects of these hormones on nervous system development. Neonatal animal experimentation with pharmacological doses of glucocorticoids has revealed immediate effects on brain cell division, differentiation, myelination, and electrophysiological reactions. In addition, delayed (latent) effects include changes in control of circadian periodicity, altered biogenic amine levels, altered response to stress, and changes in ultimate behavior. Thus perinatal hormone therapy during critical periods of brain development is capable of exerting irreversible immediate effects on brain cell division and differentiation, resulting in latent or long-term physiological and behavioral effects.


Growth rates of epidermoid tumors.

Growth rates of epidermoid tumors. Consideration of the most likely method of growth of epidermoid tumors, either congenital or traumatic in origin, suggests that they grow linearly, at rates approximately those reported for normal human skin, rather than exponentially, as most tumors do. Such a linear rate of growth would be expected of tumors derived from a single layer of basal germinal cells spread out over a surface area.


Neurological complications of infantile osteopetrosis. Seven cases of infantile osteopetrosis are presented. Five of these were available for detailed clinical examination and 2 for retrospective review, including autopsy slides. Neurological deficits in these patients are reviewed. Involvement of the central nervous system parenchyma was suggested by observations of delayed development, ocular abnormalities, and reflex changes as well as radiographic and autopsy findings. Cerebral atrophy was present in several of our patients as well as some reported in the literature and may account for the ventricular enlargement found in many of these patients. Though hydrocephalus may be present, it is unclear that this is frequent or that it can occur without antecedent intracranial hemorrhage. The large head size is not accounted for by calvarial thickening or by hydrocephalus. Despite our patients' small stature, pituitary function appeared to be normal. Surgical decompression may stabilize cranial nerve function, particularly when the optic nerves are involved.


An electrooculographic study of internuclear ophthalmoplegia. The eye movements of 25 patients with internuclear ophthalmoplegia were recorded by electrooculography. The velocity of adducting saccades was markedly less than normal. The velocity of abducting saccades was within the normal range, but statistically there was a wider distribution. Recordings were made in 2 patients several months after the onset of internuclear ophthalmoplegia, at which time the adducting eye velocity was greater than the abducting eye velocity. A patient with a unilateral medial fasciculus lesion showed marked overshoot of the abducting eye on contralateral saccades and overshoot of both eyes toward the side of the lesion. Optokinetic and postcaloric nystagmus were recorded, and the slow phase showed increasing velocity exponential waveform for the abducting eye. The recordings also showed decreasing velocity exponential waveform for the abducting eye. Downbeat nystagmus was as common as upbeat nystagmus in our patients. The findings appear to confirm the theoretical analysis of the eye movement disorder in internuclear ophthalmoplegia provided by Pola and Robinson as modified by recent experimental work in primates.


Tonic pupils with acute ophthalmoplegic polyneuritis. Two patients with the symmetrical ophthalmoplegic variant of acute idiopathic polyneuritis (Fisher's syndrome) developed bilateral dilated pupils with cholinergic supersensitivity and light-near dissociation (tonic pupils), indicating involvement of the postganglionic parasympathetic neuron within the orbit. Supranuclear eye movement dysfunction also was present, indicated by relative levator sparing in both patients and by preservation of Bell's phenomenon in 1 patient despite paralysis of voluntary upward gaze. The lesions that produce the eye signs of ophthalmoplegic polyneuritis are not necessarily restricted to the cranial nerve trunks. The present cases support a relationship between the ophthalmoplegic variant of the Guillain-Barré syndrome and acute postinfectious encephalomyelitis (brainstem encephalitis) on the one hand, and idiopathic autonomic neuropathies such as the Holmes-Adie syndrome and pandysautonomia on the other.


The ocular motor defects in progressive supranuclear palsy. The results of quantitative infrared horizontal eye movement recordings in 8 patients with progressive supranuclear palsy are presented. Some of the patients had total paralysis of vertical movements, but none had completely lost the ability to perform horizontal eye movements. All patients had a defect in ocular fixation previously undescribed in this condition: the universal presence of square-wave jerks. Analysis of refixation saccades demonstrated hypometria, slow velocity/amplitude relationships, and profound prolongation of duration. The pursuit abnormality, characterized clinically by "cogwheel" eye movements, represented the inability to match eye velocity to target velocity. The ratio of peak eye velocity to peak target velocity (pursuit gain) was 0.2 to 0.5. Defects in the vestibuloocular reflex included inability to increase the gain of the reflex (ratio of peak eye velocity to head velocity) during viewing of a visible, stationary target and failure to suppress the reflex when viewing a target rotating with the head.