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Biomedical subjects

J Steinberg

Publications and source records attributed to J Steinberg.

At least 19 recordsLinked to original sources

Amino acids and ammonia in the cerebral cortex, the corpus striatum and the brain stem of the mouse prior to the onset and after a seizure induced by hyperbaric oxygen.

The contents of amino acids (AA) and ammonia (NH3) were measured in corpus striatum, brain stem and cerebral cortex of two strains of mice exposed to hyperbaric oxygen (HBO). Mice of the HBO-sensitive strain (CD1) were exposed to 600 kPa O2 for 24 min versus 90 min for mice of the normal C57 strain, so that 50% of the mice in both strains developed a generalized convulsion. In the cortex of exposed but unconvulsed (EXUN) C57 mice, the contents of taurine, glutamine and NH3 increased while that of GABA decreased when compared to control mice. In the CD1 mice, NH3 content was increased while that of Asp decreased. After a convulsion, NH3 was increased in both strains, the AA contents returned to normal in C57 but Asp remained low in CD1 mice. Somewhat similar changes occurred in the striatum except that NH3 levels were less affected while GABA ones were significantly decreased in the CD1 mice exposed to HBO, whether convulsed or not. In the EXUN brain stem, Asp and Glu contents decreased. These decreases were greater in C57 on a percentage basis than in CD1 mice. GABA content was decreased in the C57 strain. After a convulsion, Asp and Glu levels remained low and NH3 accumulated in CD1 whereas in C57 only the Glu level was decreased. The cortical and striatal changes may indicate a lesser GABA supply in C57 strain and some Asp release in CD1 strain. In the brain stem of both strains, Asp and Glu release is possible in addition to GABA in C57 strain.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids

Management of recurrent priapism with epinephrine self-injection and gonadotropin-releasing hormone analogue.

A case of recurrent priapism in a young black man without sickle cell anemia is reported. Due to almost daily episodes of prolonged painful erections, the patient was instructed in intracorporeal injection using an epinephrine self-injection kit, which provided complete detumescence on 31 occasions. The patient refused surgical intervention and was treated with monthly intra-muscular gonadotropin-releasing hormone analogue. Priapism episodes completely abated by the second and final monthly gonadotropin-releasing hormone analogue injection without recurrence during 4 months of followup. Normal erectile function was maintained during and after gonadotropin-releasing hormone analogue therapy. Epinephrine self-injection and gonadotropin-releasing priapism.

Adult

[Radiologic visibility of breast fibroadenomas].

From a clinical point of view, all mammary fibroadenomas are similar. However some of them are not visible in mammograms, phenomenon probably related to glandular density. Aiming to elucidate whether the lack of visibility is caused by the glandular density or by tumor itself, a three stage study was performed. In 201 cases the mammographic visibility of fibroadenomas was determined and correlated with patient's age, the presence of fibrocystic disease and tumor histological type; after surgical excision, 18 fibroadenomas were sliced into 5 mm thick samples and X rayed to determine their visibility; finally 2 visible and 2 non visible tumors were calcinated at 550 degrees C and their ashes subjected to X-ray diffraction analysis. Twenty two percent of fibroadenomas were not visible on mammography, this percentage was higher for intracanalicular tumors, in younger women and in the presence of fibrocystic disease. Sixteen percent of excised and sliced tumors were not visible on X rays. Also, differences were found in X-ray diffraction studies between visible and invisible tumors, probably related to NaCl and KCl tumor content.

Adolescent

Effect of streptozotocin-induced diabetes on somatostatin receptors in the anterior pituitary, hypothalamus and cerebral cortex of the male rat.

In order to better understand the mechanisms underlying the reduction in GH secretion in diabetic rats, we have characterized and measured SRIH receptors in the hypothalamus and anterior pituitary gland 5 and 9 days after induction of diabetes in the rat. Experimental diabetes was induced by an intraperitoneal injection of streptozotocin (STZ) at a dose of 65 mg/kg. Basal plasma GH was significantly reduced in diabetic rats. Chronic insulin replacement therapy partly restored plasma GH and blood glucose levels in these animals. A significant reduction in SRIH receptor concentrations was demonstrated in the hypothalamus and anterior pituitary gland, 5- and 9- days after STZ injection. These changes were not significantly corrected by insulin replacement. Cerebral cortex SRIH receptor concentrations were unaffected by experimental diabetes. We conclude that hypothalamic and pituitary SRIH receptor levels are lowered in diabetic rats. These changes may contribute to aberrant GH secretion in diabetes and they indicate that pituitary sensitivity to exogenous somatostatin should be tested in diabetic patients.

Animals

Intramuscular versus oral antibiotic therapy for the prevention of meningitis and other bacterial sequelae in young, febrile children at risk for occult bacteremia.

Because studies of the treatment of children with occult bacteremia have yielded conflicting results, we compared ceftriaxone with amoxicillin for therapy. Inclusion criteria were age 3 to 36 months, temperature > or = 39 degrees C, an acute febrile illness with no focal findings or with otitis media (6/10 centers), and culture of blood. Subjects were randomly assigned to receive either ceftriaxone, 50 mg/kg intramuscularly, or amoxicillin, 20 mg/kg/dose orally for six doses. Of 6733 patients enrolled, 195 had bacteremia and 192 were evaluable: 164 Streptococcus pneumoniae, 9 Haemophilus influenzae type b, 7 Salmonella, 2 Neisseria meningitidis, and 10 other. After treatment, three patients receiving amoxicillin had the same organism isolated from their blood (two H. influenzae type b, one Salmonella) and two from the spinal fluid (two H. influenzae type b), compared with none given ceftriaxone. Probable or definite infections occurred in three children treated with ceftriaxone and six given amoxicillin (adjusted odds ratio 0.43, 95% confidence interval 0.08 to 1.82, p = 0.31). The five children with definite bacterial infections (three meningitis, one pneumonia, one sepsis) received amoxicillin (adjusted odds ratio 0.00, 95% confidence interval 0.00 to 0.52, p = 0.02). Fever persisted less often with ceftriaxone (adjusted odds ratio 0.52, 95% confidence interval 0.28 to 0.94, p = 0.04). Although the difference in total infections was not significant, ceftriaxone eradicated bacteremia, prevented significantly more definite focal bacterial complications, and was associated with less persistent fever.

Administration, Oral

Effect of one hyperbaric oxygen-induced convulsion on cortical polyamine content in two strains of mice.

In rat striatum, after one hyperbaric oxygen (HBO)-induced convulsion, polyamine changes are found that could promote N-methyl-D-aspartate (NMDA) activation. In the HBO-sensitive CD1 mouse, unlike in the common C57 strain, there is some support for NMDA activation after the HBO seizure. We measured PA cortical content before and after the first HBO-induced convulsion (about 608 kPa O2) in CD1 and C57 strains. Putrescine, spermidine and spermine were dansyl derived and analysed by HPLC. Exposure to HBO significantly increased putrescine content only in CD1 though a similar trend was observed in C57. No further increase was observed after convulsion whatever the strain. There were no significant changes in spermidine or spermine to support NMDA activation. Therefore, putrescine increase in CD1 cortex could reflect the free radical formation that is known to be greater in CD1 than in C57 mouse. Attempts to increase putrescine levels before HBO exposure hastened HBO-induced convulsion, less than spermidine or spermine. Because of physiological polyamine interconversion, additional experiments with indirect manipulation of putrescine levels and study of their time-course would precise these preliminary reports on putrescine and HBO.

Animals

Desipramine does not alter plasma GABA in patients with major depression.

Low plasma GABA is a biological marker for depression in a subset of patients tested. Plasma GABA has been shown to reflect brain GABA activity. This marker has many characteristics of a trait marker for depression, including stability with time, and lack of influence by coincident factors such as gender, season, time, activity or diet. We here report that plasma GABA remained stable after 4 weeks of treatment with desipramine in patients with major depression. Since the levels of plasma GABA did not change with time, nor with clinical improvement, plasma GABA is not a state marker of depression.

Adult

Prognostic factors in patients with metastatic colorectal cancer receiving 5-fluorouracil and folinic acid.

We have reported that 5-fluorouracil (5-FU) and folinic acid increased response rate and survival in patients with metastatic colorectal cancer. Now we have analysed prognostic factors for response, toxicity, survival and time to progression. The variables used for survival and response were treatment centre, treatment, age, sex, Eastern Cooperative Oncology Group (ECOG) performance status (PS), site of disease, previous radiotherapy, site of primary, disease-free interval, initial alkaline phosphatase (AP), albumin (A), lactate dehydrogenase (LDH) and aspartate aminotransferase (SGOT). The significant independent variables for survival were PS of 2 or more, initial albumin and SGOT, and treatment received, in order of importance. The relative risk of death when patients received 5-FU/folinic acid was 60% of that of patients receiving 5-FU alone. The variables predictive of response were treatment and PS. The variables used for analysis of toxicity were age, treatment centre, treatment, sex, tumour response, PS, number of courses, SGOT, AP and albumin. Treatment was found to be predictive of toxicity. Thus, baseline albumin and SGOT, and 5-FU/folinic acid treatment are significant determinants of survival, 5-FU/folinic acid and PS of 2 or more are major determinants of response and no clinical parameter could be identified as a predictor of toxicity.

Adult

Effect of diabetes on in vivo and in vitro hypothalamic somatostatin release.

In order to better understand the mechanisms underlying the reduction in growth hormone (GH) secretion in diabetic rats, we studied hypothalamic somatostatin secretion both in vivo (into hypophysial portal blood) and in vitro (from hypothalamic fragments) 5, 9 and 30 days after induction of diabetes. Experimental diabetes was induced by an intraperitoneal injection of streptozotocin (STZ) at a dose of 65 mg/kg. Basal plasma GH was significantly reduced in diabetic rats at all stages. Somatostatin levels in hypophysial portal blood was unaffected in 5-day STZ-diabetic rats and significantly increased 9 days after STZ administration. Chronic insulin replacement therapy in diabetic animals partly normalized somatostatin levels as well as plasma GH and glucose levels. A good correlation was observed between in vivo and in vitro experiments. Indeed, somatostatin release from hypothalamic fragments did not change 5 days after STZ-induced diabetes and significantly increased 9 and 30 days after STZ administration. The in vitro increase in hypothalamic somatostatin secretion was observed in 10 as well as in 33 mM glucose concentration in the incubation medium. In the same experiment, the in vitro hypothalamic corticotropin-releasing factor secretion was lowered 5 and 9 days after diabetes induction. We conclude that hypothalamic somatostatin release increases in diabetic rats. These changes may contribute to the reduction in GH secretion in these animals. However, since these changes occur after the onset of plasma GH decrease, a factor(s) other(s) than somatostatin may play a causal role in the reduction in GH secretion.

Animals

Cardiosynchronous limb compression: effects on noninvasive vascular tests and clinical course of the ischemic limb.

Some patients with chronic arterial obstruction of the limbs may still suffer the consequences of advanced tissue ischemia, including ulceration and rest pain, and face threatened limb loss in spite of available surgical, pharmacologic, and other treatments. Additional therapeutic modalities were thus sought to accomplish limb salvage. A literature review indicated that most reports on R-wave-triggered circumferential limb compression (cardiosynchronous limb compression [CSC]) demonstrate its ability to augment limb arterial blood flow and improve ischemic limbs. To determine the device's efficacy and safety, and possibly confirm earlier positive reports, a systematic study was undertaken, using older, as well as newer, more electronically reliable CSC devices. The present study was designed to determine the following: 1. objectively, by noninvasive vascular tests, changes in limb blood flow, if any, by CSC; 2. clinical effects of CSC, if any, on the ischemic limb; 3. duration of CSC-induced limb improvements, if any; 4. side effects or safety of CSC. The study demonstrated that CSC treatments: 1. caused increased limb blood flow as determined by increased ankle/arm indices and hallux photoplethysmograph waveform amplitudes during treatments; 2. led, in most cases, to improvement in or resolution of the presenting ischemic problem (eg, ulcer, cellulitis, rest pain); 3. induced limb improvements that persist for up to seven years 4. caused no adverse side effects.

Aged

Alcohol and breast cancer risk--putting the current controversy into perspective.

The potential association of alcohol intake with breast cancer risk is currently being debated in the literature and a clear consensus of opinion has not emerged. Clarification of the issues surrounding this controversy would be helpful in developing recommendations for the general public regarding alcohol use. A review of the available evidence regarding the association of alcohol with breast cancer is presented followed by an application of the Bradford Hill criteria for causal inference to this data to examine the existence and nature of the association of alcohol with breast cancer risk. Results of published studies demonstrated a weak association of alcohol with breast cancer risk that was consistent only for relatively high levels of intake (more than 1 or 2 drinks daily). Increasing daily intake was associated with increased risk, but the association was not linear. Criteria relating to temporality and analogy to other causal associations were satisfied while inconsistent evidence was available for those relating to epidemiologic and biologic sense. The criterion for specificity was not satisfied and no experimental evidence was available. It is concluded that insufficient evidence exists to support a causal association of alcohol consumption with breast cancer risk. Further research is recommended to resolve conflicting evidence and to provide additional evidence where needed. In the meantime, recommendations that women should reduce their consumption of alcohol beyond existing guidelines to modify breast cancer risk are probably premature.

Alcohol Drinking

Acute urinary retention secondary to Herpes simplex meningitis.

We report a case of acute urinary retention in a 24-year-old man with Herpes simplex meningitis without genital lesions. Since the differential diagnosis in young patients who present with acute urinary retention also includes multiple sclerosis, lumbosacral disk herniation, rheumatological disorders and drug intoxication, a thorough history and careful neurological examination are of paramount importance in distinguishing these syndromes. As part of a directed neurological evaluation prompt performance of lumbar puncture is indicated; a lymphocytic pleocytosis is suggestive of herpetic meningitis. Culture of Herpes simplex virus from the cerebrospinal fluid should be attempted. We recommend conservative management only, typically with intermittent catheterization, since bladder function usually normalizes within 10 to 14 days.

Acute Disease

Use of thermography in the differential diagnosis of phylloides tumour.

Thermography can be used as a method of diagnosing breast masses. We report our results of its use in the differential diagnosis of fibroadenoma from phylloides tumours (n = 47 and 20 respectively). Thermographic resolution (Th) and the difference in temperature between the tumour and a similar zone in the contralateral breast (delta 2) were compared. Thermograms were class Th1 (with a similar thermal pattern in both breasts without hypervascularization or hot points) and Th2 (with hypervascularization or a hot area with a thermal difference with the same area in the opposite breast (delta 2) of less than 2 degrees C) in most (95.7 per cent) of the patients with fibroadenoma and were class Th5 (having one or more pathological sign) in 85 per cent of the patients with phylloides tumours. Patients with phylloides tumours had a mean delta 2 of 2.99 degrees C whereas most of the patients with a fibroadenoma showed no difference in temperature. Their mean delta 2 was 0.2 degrees C (P less than 0.0005). We conclude that thermography helps in differential diagnosis between a fibroadenoma and a phylloides tumour.

Adenofibroma

Cognition and metacognition at extreme altitudes on Mount Everest.

The FACTRETRIEVAL2 test battery, which assesses both retrieval of general information from memory and metacognition about that retrieval, was administered to people before and after a recent expedition to Mount Everest and at extreme altitudes above 6,400 m (higher than any mountain in North America or Europe). The major findings were as follows: First, the same extreme altitudes already known to impair learning did not affect either accuracy or latency of retrieval, and this robustness of retrieval occurred for both recall and forced-choice recognition. Second, extreme altitude did affect metacognition: The climbers showed a decline in their feeling of knowing both while at extreme altitude and after returning to Kathmandu (i.e., both an effect and an aftereffect of extreme altitude). Third, extreme altitude had different effects than alcohol intoxication (previously assessed by Nelson. McSpadden, Fromme, & Marlatt, 1986). Alcohol intoxication affected retrieval without affecting metacognition, whereas extreme altitude affected metacognition without affecting retrieval; this different pattern for extreme altitude versus alcohol intoxication implies that (a) hypoxia does not always yield the same outcome as alcohol intoxication and (b) neither retrieval nor metacognition is strictly more sensitive than the other for detecting changes in independent variables.

Adult

A double-blind, placebo-controlled trial of thymostimulin in symptomatic HIV-infected patients.

The potential therapeutic efficacy of the thymic hormone preparation, thymostimulin (TP1), in HIV infection has been studied in a multi-institutional, randomized, double-blind, placebo-controlled trial. Fifty evaluable patients with advanced AIDS-related complex (ARC) were injected with TP1 or placebo twice weekly for 6 months after 2 weeks of daily injections. The primary endpoint, progression to AIDS, was reached in nine TP1- and 11 placebo-treated subjects after 1 year. CD4 cell numbers were not affected by administration of the study drug. No toxicity was associated with TP1 treatment. We conclude that TP1 is ineffective in altering the progress of HIV disease in patients with advanced ARC.

AIDS-Related Complex