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Biomedical subjects

E Lane

Publications and source records attributed to E Lane.

At least 19 recordsLinked to original sources

Effects of adinazolam and diazepam, alone and in combination with ethanol, on psychomotor and cognitive performance and on autonomic nervous system reactivity in healthy volunteers.

Effects on psychomotor and cognitive performance of adinazolam (15 or 30 mg), alone and in combination with ethanol (0.8 g/kg), were studied in healthy male volunteers and compared to effects of 10 mg diazepam. Adinazolam 30 mg produced relatively long-lasting impairments on tests of tracking, attention, verbal and nonverbal information processing, and memory. Adinazolam 15 mg resulted in descreased visual information processing. Adinazolam decreased supine mean arterial pressure, but only the 15 mg resulted in a tendency for decreased plasma norepinephrine concentrations. After standing for 5 min, 30 mg adinazolam was associated with increased heart rate. Although ethanol consumption produced additive decrements on a continuous performance task, there was little evidence to support a synergistic effect. Adinazolam 30 mg was accompanied by increased self-reports of side effects, especially drowsiness.

Adult

Effects of single doses of alprazolam and diazepam, alone and in combination with ethanol, on psychomotor and cognitive performance and on autonomic nervous system reactivity in healthy volunteers.

Effects of alprazolam, alone and in combination with ethanol, on psychomotor and cognitive performance were studied in healthy male volunteers and compared to effects of diazepam. Alprazolam 2 mg produced relatively long-lasting impairments on tests of tracking, verbal and nonverbal information processing, and memory, and decreased blood pressure without a change in heart rate or plasma norepinephrine levels. Although ethanol consumption was demonstrated to produce additive decrements in performance on certain tasks, there was little evidence to support a synergistic effect. Alprazolam 2 mg was accompanied by increased self-reports of side effects, especially drowsiness. Low dose alprazolam, diazepam, and ethanol produced significantly fewer side effects than 2 mg alprazolam, but significantly more than placebo.

Adult

Abnormal neuroendocrine responsivity to acute i.v. clomipramine challenge in depressed patients.

The neuroendocrine responsivity to an acute serotonergic challenge with low-dose i.v. clomipramine was studied in seven drug-free depressed patients and seven age-matched healthy control subjects. The depressed patients had higher baseline prolactin concentrations than the healthy subjects, and their prolactin response to clomipramine, assessed as either the percent of baseline or the log-transformed concentration, was significantly different (delayed and blunted peak response) compared to healthy controls. The growth hormone response was exaggerated in the depressed patients, and there were also trends toward blunting in their cortisol and adrenocorticotropic hormone responses. These results are consistent with previous findings of altered neuroendocrine responses to a variety of putative serotonin agonists in depressed patients.

Adrenocorticotropic Hormone

Rapid diagnosis of typhoid fever through identification of Salmonella typhi within 18 hours of specimen acquisition by culture of the mononuclear cell-platelet fraction of blood.

Detection of Salmonella typhi in blood by culture of the mononuclear cell-platelet layer was compared with other methods currently used for the diagnosis of typhoid fever. Colonies of S. typhi were present in all mononuclear cell-platelet layer-positive cultures within 18 h of plating and were identified within an additional 10 min by a coagglutination technique. In contrast, identification of all positive cultures by conventional blood culture required 3 days.

Agglutination Tests

The use of a coagglutination test to presumptively identify Salmonella typhi in bone marrow-oxgall medium cultures from typhoid fever patients.

A study was conducted to test a coagglutination procedure for detection of Salmonella typhi in bone marrow cultures from suspected typhoid patients admitted to Friendship Hospital, Jakarta, Indonesia. The results of the coagglutination tests were compared to the results from standard cultural isolation and identification. Bone marrow aspirates (356) were cultured in oxgall medium and aliquots subcultured daily for 7 days while simultaneously testing for the presence of Salmonella group D and Vi antigens using coagglutination (COAG). S. typhi was isolated from 220 (62%) of the cultures and the D- and Vi-COAG tests were positive for those same cultures. The COAG test was also negative for 6 cultures containing S. paratyphi A. The COAG results were available within 10 minutes after 18 to 24 hours incubation of the primary cultures whereas the isolation and confirmed identification took 2 to 3 days longer. The COAG test is valuable as an aid to rapidly identify S. typhi in bone marrow-oxgall cultures.

Agglutination Tests

Use of a DNA probe to detect Salmonella typhi in the blood of patients with typhoid fever.

A DNA probe was used to detect Salmonella typhi from blood samples from 14 of 33 patients with culture-confirmed typhoid fever, using the equivalent of 2.5 ml of blood. In contrast, S. typhi was detected in 17 of the same 33 patients by culture of 8 ml of blood. The probe hybridized to blood samples of 4 of 47 patients from whom S. typhi was not isolated.

Autoradiography

The effects of intravenous clomipramine on neurohormones in normal subjects.

The neuroendocrine effects of iv administration of clomipramine (CMI), a serotonin reuptake inhibitor, were studied in normal subjects. Under double blind, placebo-controlled conditions, single 10- and 20-mg doses of CMI were administered. Ten milligrams of CMI led to significant increases in plasma PRL and cortisol concentrations; plasma ACTH increased slightly but not significantly. In contrast, plasma GH, melatonin, and norepinephrine concentrations did not increase. Plasma PRL, ACTH, and cortisol levels increased significantly after 20 mg CMI; again, there were no significant changes in plasma GH, melatonin, or norepinephrine concentrations. All subjects tolerated the 10-mg dose well, but the 20-mg dose caused nausea in three of six subjects. Desmethylclomipramine, a metabolite that inhibits reuptake of norepinephrine, was not detectable in plasma after either CMI dose. These results support the hypothesis that serotonin is involved in the regulation of PRL, cortisol, and ACTH in humans.

Adrenocorticotropic Hormone

Growth inhibition of transformed mouse fibroblasts by adenine nucleotides occurs via generation of extracellular adenosine.

The growth of transformed mouse fibroblasts (3T6 cells) in medium containing 5% fetal bovine serum was inhibited after treatment with concentrations greater than 50 microM ATP, ADP, or AMP. Adenosine, the common catabolite of the nucleotides, had no effect on cell growth at concentrations below 1 mM. However, the following results indicate that the toxicity of ATP, ADP, and AMP is mediated by serum- and cell-associated hydrolysis of the nucleotides to adenosine. 1) ADP and AMP, but not ATP, were toxic to 3T6 cells grown in serum-free medium or medium in which phosphohydrolase activity of serum was inactivated. Under these conditions, the cells exhibited cell-associated ADPase and 5'-nucleotidase activity, but little ecto-ATPase activity. 2) Inhibition of adenosine transport in 3T6 cells by dipyridamole or S-(p-nitrobenzyl)-6-thioinosine prevented the toxicity of ATP in serum-containing medium and of ADP and AMP in serum-free medium. 3) A 16-24-h exposure to 125 microM AMP or ATP was needed to inhibit cell growth under conditions where serum- and cell-associated hydrolysis of the nucleotides generated adenosine in the medium continuously over the same time period. In contrast, 125 microM adenosine was completely degraded to inosine and hypoxanthine within 8-10 h. Furthermore, multiple doses of adenosine added to the cells at regular intervals over a 16-h period were significantly more toxic than an equivalent amount of adenosine added in one dose. Treatment of 3T6 cells with AMP elevated intracellular ATP and ADP levels and reduced intracellular UTP levels, effects which were inhibited by extracellular uridine. Uridine also prevented growth inhibition by ATP, ADP, and AMP. These and other results indicate that serum- and cell-associated hydrolysis of adenine nucleotides to adenosine suppresses growth by adenosine-dependent pyrimidine starvation.

5'-Nucleotidase

Normal cerebral asymmetry in bipolar patients.

Reversal of normal cerebral asymmetry has been reported to be more frequent in children with higher cortical dysfunction and in schizophrenics, in whom it has clinical significance as well. As there are few studies of bipolar patients, we attempted to determine if significant reversal would be found in a clearly diagnosed sample of bipolar patients. As technical differences may account for varying results, we used two previously reported methods and a modified technique. Correlations of computed tomography (CT) findings with neuropsychological variables (Halstead Reitan Battery and WAIS subtests) were also studied. Bipolars and controls did not differ on any CT measure, nor were there meaningful correlations between asymmetry and neuropsychological variables. If if is confirmed that schizophrenics have increased reversed cerebral asymmetry but bipolars do not, it may point to an important difference, as all other CT abnormalities initially described in schizophrenics are now also noted in bipolar patients.

Adult

Treatment of childhood hyperactivity with desipramine: plasma drug concentration, cardiovascular effects, plasma and urinary catecholamine levels, and clinical response.

Twenty-nine boys with attention deficit disorder/hyperactivity were randomly assigned to receive desipramine (DMI; n = 17) or placebo (n = 12) for 14 days in a noncrossover, double-blind study. There was immediate behavioral improvement with DMI at day 3 that was sustained for 2 weeks; behavioral improvement did not correlate with plasma concentrations of DMI, hydroxy-DMI, or their sum at either days 3 or 14. There were no untoward side effects; there was a drug-induced increase in pulse and diastolic blood pressure. During drug therapy, the urinary excretion of norepinephrine, vanillymandelic acid, and 3-methoxy-4-hydroxyphenylglycol (MHPG) was decreased at both days 3 and 14. The plasma MHPG level was decreased at days 3 and 14 and (standing) plasma NE levels increased at day 14. The decreases in both urinary and plasma MHPG levels showed significant correlations with behavioral improvement during the second week. These data corroborate previous findings on sympathomimetic effects of tricyclic antidepressants in children and support a noradrenergic mechanism in the mediation of drug effects on attention deficit disorder/hyperactivity.

Administration, Oral

Biological activities of synthetic human parathyroid hormone (PTH) 1-84 relative to natural bovine 1-84 PTH in two different in vivo bioassay systems.

Synthetic 1-84 human PTH (hPTH) peptides (with either asparagine) or aspartic acid at position 76) were compared with natural bovine PTH (bPTH) in three in vivo bioassays. Surprisingly, in the chick hypercalcemia bioassay, the human 1-84 peptides were approximately 3 times more potent on a molar basis than bPTH. In contrast, in an in vivo mouse kidney cAMP accumulation bioassay, these human peptides were 3-6 times less potent than bPTH. This low potency of synthetic hPTH relative to bPTH in the renal cAMP assay is in accordance with published relative potency estimates for natural extracted hPTH in in vitro rat renal membrane adenylate cyclase assays. The human and bovine 1-84 peptides were weakly active in an in vivo mouse calvaria cAMP accumulation system, producing a shallow dose-response curve which was not suitable for any quantitative estimates of potency. In contrast, both human and bovine 1-34 fragments were highly active in stimulating accumulation of cAMP in calvaria thus emphasizing the qualitative differences between 1-84 PTH and the 1-34 fragment of both species of PTH. Despite the homology between human and bovine 1-84 PTH, they have markedly different quantitative biological effects on hypercalcemia in chicks and in vivo renal cAMP accumulation in mice. Any estimate of the biological potency of human 1-84 PTH, relative to bovine 1-84 PTH, will need to be defined in terms of the nature and species of the biological test system.

Animals

Major complications of radiotherapy in cancer of the oral cavity and oropharynx. A 10 year retrospective study.

In an attempt to determine the late effects and associated morbidity of radiotherapy on normal tissue, patients with squamous carcinoma of the oral cavity and oropharynx were retrospectively reviewed. Between 1964 and 1975, 569 patients with cancer of the floor of the mouth, oral tongue, tonsil, and retromolar trigone region of the anterior faucial pillar had their primary lesions treated by radiotherapy alone for cure. One hundred twenty-eight of the patients were evaluable for this study. Bone and soft tissue morbidity were graded according to the late radiation scoring scheme of the radiation therapy oncology group of the European Organization on Research and Treatment of Cancer, tallying only grade 4 changes. Patients were further classified according to site of tumor, age, sex, tumor stage, histologic grade, and dental status--none of which had a positive correlation with complications. Of 31 evaluable patients with cancer of the floor of the mouth (median follow-up 136 months), 71 percent (22 of 31 patients) had at least one complication involving bone (osteonecrosis, pathologic fracture) or mucus membrane (ulcer). Sixty-one percent (25 of 41 patients) with primary cancer of the oral tongue had grade 4 sequelae (median follow-up 112 months). In 26 patients with cancer of the tonsil, 13 (50 percent) had grade 4 sequelae (median follow-up 113 months). This included 11 patients with clinical and radiographic evidence of osteonecrosis, 6 of whom required mandibulectomy. Patients with cancer of the retromolar trigone region of the anterior faucial pillar fared the best (median follow-up 122 months). Late sequelae were noted in 40 percent (12 of 30 patients). The morbidity attendant to cure by radiotherapy included at least one significant complication of bone or soft tissue in 40 to 70 percent of the patients, depending on the location of the primary tumor. There was also a positive correlation with dose of radiation received.

Adolescent

Coal workers' pneumoconiosis.

Pathologic features and pathogenesis of coal workers' pneumoconiosis are reviewed. Roentenographic aspects of CWP have been examined; it is concluded that there is little or no correlation with physiologic abnormalities, and no abnormality is pathognomonic of this condition. It is suggested that coal workers who are physiologically disabled by any condition, usually heart disease or chronic obstructive pulmonary disease or both, be retired via an industry-government compensation plan. Chest roentgenograms should serve only to identify and retire those miners who have progressive massive fibrosis, and to identify those who have simple CWP; thus they may be moved to jobs in areas of the mine where dust concentrations are lower.

Chronic Disease

Cocaine self-injection behaviour under schedules of delayed reinforcement in monkeys.

Rates of lever pressing, maintained either by response-dependent intravenous injections of cocaine (250 mug/kg per injection) or by food-pellet presentation, were compared and found to vary systematically as a function of the delay (5-100 s) imposed between the response(s) and the occurrence of reinforcement. The control of responding by two schedules of delayed reinforcement was studied. The first scedule permitted responses to occur during the delay period without any programmed consequence; the second schedule required a response, and then the elapse of x seconds without any additional response(s). At imposed delays of 50 and 100 s, response rates were reduced significantly when the second schedule was in effect by comparison with the first. The effect was observed when responding was maintained either by intravenous cocaine injections or by food-pellet presentation. Across all comparable conditions, response rates were higher when maintained by scheduled cocaine injections than by food pellets. Rate enhancement, generally induced by drugs of the psychomotor stimulant type, could account for the observed difference.

Animals

Normalization of brain serotonin by L-tryptophan in levodopa-treated rats.

To test possible biochemical mechanisms by which L-tryptophan may reverse mental side effects of levodopa therapy in parkinsonism we administered levodopa, 250 mg per kilogram intraperitoneally, alone and with L-tryptophan, 500 mg per kilogram intraperitoneally, to rats pretreated with the peripheral dopa decarboxylase inhibitor, carbidopa (25 mg per kilogram). Rats were decapitated 0.5, 1, and 2 hours following amino acid injection and brain levels of amino acids, amines, and acid metabolites were determined. As expected, levodopa alone reduced tryptophan and serotonin and increased dopa and dopamine at the 1 and 2 hour intervals. Concurrent administration of L-tryptophan did not significantly alter the increased dopa and dopamine but did restore serotonin levels to within normal range at all time points. If similar events occur in parkinsonian patients, normalization of brain serotonin and not competitive reduction of brain dopa and dopamine may be the basis for the improvement in mental status.

Animals