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Biomedical subjects

N Berman

Publications and source records attributed to N Berman.

At least 73 records · Page 4Linked to original sources

Hypothalamic-pituitary-adrenocortical function in mixed and pure mania.

There is little information about hypothalamic-pituitary-adrenocortical (HPA) axis function in mania, particularly in mixed states. We therefore investigated HPA function and its relationship to clinical state in 19 hospitalized manic patients meeting Schedule for Affective Disorders and Schizophrenia - Research Diagnostic Criteria for acute manic episodes, compared patients with and without a mixed presentation, and examined correlations between HPA activity and behavior. Data were available from 13-16 patients. Behavioral and biochemical analyses were conducted during a 15-d placebo period. Patients with mania had elevated cerebrospinal fluid (CSF) and urinary free cortisol excretion compared with healthy subjects, and did not differ from depressed patients in any cortisol measures. Mixed manics had significantly higher morning plasma cortisol, postdexamethasone plasma cortisol and CSF cortisol than pure manics. Five of 7 mixed manics and 3 of 9 pure manics were dexamethasone suppression test (DST) nonsuppressors. Afternoon plasma cortisol and CSF cortisol correlated significantly with depressed mood; urinary free cortisol correlated with anxiety. None of the cortisol measures correlated with mania or agitation scores. These data suggest that increased cortisol secretion is a characteristic of the depressed state in mixed manics, although pure manics may also have increased DST nonsuppression.

Adult↗

Oscillations of lactate released from islets of Langerhans: evidence for oscillatory glycolysis in beta-cells.

Oscillations in the glycolytic process have been demonstrated in a number of different biological systems. However, their presence has never been demonstrated in insulin-secreting beta-cells. We used lactate as a marker for glycolysis and measured lactate and insulin concentrations in the effluent of isolated perifused rat islets of Langerhans. Sustained regular oscillations in lactate concentrations with an average period of 16-20 min were observed in islets that were perifused with medium containing 5.5 or 16.7 mM glucose. Sustained oscillations of insulin concentrations secreted by the islets were also observed in these experiments, and the average period of oscillation was 14.6 +/- 2.3 min at 16.7 mM glucose. Mean insulin concentrations at 5.5 mM glucose were too low to permit analysis of oscillations. Spectral analysis confirmed the regularity of the lactate and insulin oscillations and showed peaks that were consistent with the average periods obtained using the Clifton program. Moreover, spectral analysis demonstrated marked similarity between the patterns of lactate and insulin oscillation during perifusion with 16.7 mM glucose. Cross-correlation analysis found these oscillations not to be consistently in phase. In conclusion, sustained oscillations in lactate released from islets of Langerhans suggest that the glycolytic process in beta-cells also oscillates. The similarity of the periods of lactate and insulin raises the possibility that oscillations in glycolysis may provide a mechanism for pulsatile insulin secretion.

Animals↗

A biodegradable testosterone microcapsule formulation provides uniform eugonadal levels of testosterone for 10-11 weeks in hypogonadal men.

Limitations of presently available testosterone esters (enanthate and cypionate) include the fluctuating serum testosterone levels and the need for relatively frequent injections (every 10-21 days). These limitations of testosterone esters have prompted the development of more physiological and longer acting systems for androgen delivery. This paper reports pharmacokinetic and pharmacodynamic data with a second generation long-acting testosterone microcapsule formulation in hypogonadal men. This was a single dose, open label, nonrandomized study. Ten hypogonadal men with primary (n = 6) or secondary (n = 4) hypogonadism, otherwise in good health, received 630 mg microencapsulated testosterone in dextran solution (IM) on day 1. Serum total and free testosterone; LH; FSH; dihydrotesterone; estradiol; sex hormone-binding globulin; total cholesterol; high, low, and very low density lipoprotein cholesterol; triglycerides; and apoprotein-AII and -B were measured on multiple occasions during the 2-week control period and the 16-week treatment period. In addition, on days 0, 1, 28, 56, and 84, subjects were hospitalized for detailed hormone analyses over the 24-h period. Serum total and free testosterone levels rose quickly into the midnormal range and stayed uniformly in the eugonadal range for about 70-77 days, after which serum testosterone levels declined gradually into the hypogonadal range. Testosterone release from the microcapsule formulation over the first 10 weeks approximated zero order kinetics. Serum dihydrotestosterone levels rose into the normal range, and testosterone to dihydrotestosterone ratios remained in the physiological range. Serum estradiol levels rose and stayed in the midnormal male range. Serum sex hormone-binding globulin levels decreased significantly during treatment. Serum LH and FSH levels also significantly decreased in the six hypergonadotropic men. Total cholesterol low and very low density lipoprotein cholesterol and triglyceride levels did not change, but plasma high density lipoprotein cholesterol levels decreased significantly during treatment. These data indicate that testosterone microcapsule formulation provides uniform eugonadal levels of testosterone for about 10 weeks. The long duration and zero order kinetics make it an attractive alternative to existing methods of androgen replacement.

Adolescent↗

"Train-of-four" fade during clinical nondepolarizing neuromuscular block.

UNLABELLED: Previous clinical studies on the train-of-four (TOF) fade have used different recording techniques, anesthesia agents and muscles for measurement, thus comparison of the results has become difficult. On 49 surgical patients divided into 6 groups, we compared: 1) The TOF fade ratios (T4/T1) produced by d-tubocurarine (dTc), pancuronium (P), atracurium (A), and vecuronium (V) and 2) the influence of previously given suxamethonium on TOF ratios (dTc and P). Neuromuscular block (NMB) was monitored simultaneously by electromyography (EMG) and by mechanomyography (MMG). Differences between the TOF fade ratios of different groups were determined and statistically analyzed by ANOVA of repeated measures, 1) at onset, as compared to spontaneous recovery with the same agent, 2) between NMB agents at (a) onset and (b) during recovery. RESULTS: TOF fade was significantly more pronounced during spontaneous recovery than during onset of NMB: a) with all NMB agents, b) with both EMG and MMG responses, with bolus dose administration of the agents, c) the degrees of TOF fade significantly differed between NMB agents during onset, d) the degrees of TOF fade (MMG) were more pronounced during onset when the agents were given in incremental doses following succinylcholine as compared to degrees of fade following single bolus doses in the absence of succinylcholine. During recovery, there was also difference in the TOF fade ratios among the agents: dTc and P produced more fade than A and V.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Oscillations of circulating plasma insulin concentrations in the rat.

In previous studies, we found that insulin is secreted in a pulsatile fashion in vitro in isolated rat pancreatic islets. This study evaluated whether similar plasma insulin fluctuations occur in the rat in vivo. Freely moving rats were implanted with a chronic jugular catheter and serial blood samples were obtained 48-72 hrs post surgery. Blood was sampled at 3 min intervals for 60 mins with volume replacement using a red cell preparation. Plasma insulin concentrations were observed to fluctuate around a mean of 10.6 +/- 1.1 uU/ml, with an amplitude of 4.7 +/- 0.5 uU/ml and a period of 13.3 +/- 1 mins (n = 6). This was similar to the cycling observed in isolated islets at similar glucose concentrations. Sampling during the dark phase of the light-dark cycle in the rat was associated with an increase in the mean plasma level, amplitude and period of insulin oscillations compared with values obtained during the light phase (n = 3). These data are the first in vivo demonstration of oscillatory circulating insulin concentrations in the rat and show that the pulsatility in this species is similar to that observed in other mammals including man. We conclude that the chronically catheterised rat is a useful model for the evaluation of oscillating insulin concentrations in vivo, and may provide interesting insights by comparison with in vitro data in the same species.

Animals↗

The effect of age of exposure on lead-induced testicular toxicity.

The present study was designed to assess the significance of age of exposure on the expression of lead toxicity on the male gonad. Male Wistar rats, age 42 days, 52 days and 70 days were treated with lead acetate in their water for 30 days prior to sacrifice. The lead treated groups in all cases had blood lead values significantly greater than control animals. Blood lead levels in control animal groups were less than 7 micrograms/dl. Serum testosterone and sperm concentration and production rate were significantly suppressed in those animals that were exposed to lead acetate starting at age 52 days and 70 days, but not 42 days. These data indicate that prepubertal rats may be less sensitive to the toxic effects of lead than are rats whose exposure begins after puberty has been initiated.

Age Factors↗

Sustained pulsatile insulin secretion from adenomatous human beta-cells. Synchronous cycling of insulin, C-peptide, and proinsulin.

The endocrine pancreas secretes insulin in a pulsatile fashion. This rhythm is generated at a site within the pancreas, although its precise location has not been determined. With an in vitro system, we tested the possibility that beta-cells might generate spontaneous pulsatile insulin secretion in the absence of any external influence. Human insulinoma tissue from five patients was perifused for 7-10 h with RPMI-1640 medium and constant concentrations of glucose (5.5 mM). Insulin, C-peptide, and proinsulin were measured in the effluent collected at 3.3-min intervals. All three peptides demonstrated pulsatility of secretion in a similar, synchronous fashion that was sustained throughout each study. The Clifton cycle detection program demonstrated cycling in all five tumors, with an average period for all tumors of 28, 29, and 26 min for insulin, C-peptide, and proinsulin, respectively. Spectral analysis confirmed the regularity and consistency of the hormonal secretory patterns. Mean hormone concentrations secreted by different tumors varied, but insulin and C-peptide were secreted in a nearly 1:1 ratio. This study demonstrates 1) that beta-cells are able to generate spontaneous pulsatile insulin secretory activity, which is independent of innervation or the presence of other islet cells, and 2) proinsulin secretion from the beta-cell also has an inherent pulsatility. The synchrony observed in the cycles of proinsulin and its peptide products confirms their common secretory pathway in the beta-cell. We conclude that the beta-cell may be the originator of insulin cycling.

Adenoma↗

Assigning priority to patients requiring coronary revascularization: consensus principles from a panel of cardiologists and cardiac surgeons.

In light of lengthy waiting lists for coronary surgery in Canada, a panel of 16 cardiologists and cardiac surgeons was convened to derive guiding principles for ranking how urgently diverse patients with angiographically proven coronary disease require revascularization. Factors likely to affect urgency were agreed upon by the panelists and incorporated into a case scenario questionnaire. Each panelist then rated 438 case scenarios with respect to maximum acceptable waiting time on a scale with seven time frames ranging from emergency surgery ('level 1') to delays of up to six months ('level 7'). The scenario rating process facilitated attainment of a panel consensus. The purpose of the principles is to assist in assigning priorities to patients according to both symptoms and risk of death or additional morbidity from ischemic events. The pattern or severity of the patient's anginal symptoms and the response of those symptoms to medical therapy emerged as the single most important determinant of the level of urgency. Anatomy and noninvasive tests of ischemic risk were the other key determinants of priority. All other factors were less important, and operated largely within a given level of urgency on the seven-point scale. The principles, including explicit ranking criteria divided according to angina class, are outlined in this final report. The panel specifically cautioned that adoption of such principles is not designed to countenance delays in treatment, but if necessary, should help form more rational queues for coronary revascularization.

Canada↗

Lithium distribution in mania: single-dose pharmacokinetics and sympathoadrenal function.

We examined lithium distribution after a single dose of 25 mEq in 14 drug-free manic patients. Lithium concentrations were measured in plasma, red blood cells, and urine. Maximum concentrations of lithium, times at which they were attained, and influx and efflux rate constants for extracellular fluid, red blood cell, and muscle-like compartments were estimated using a three-compartment pharmacokinetic model. Tissue lithium concentrations may continue to increase for hours after plasma lithium concentrations have peaked. Rate constants for absorption, excretion, and influx and efflux for the tissue compartments were similar to those previously reported for normal subjects. Rate constants for transport into and out of the tissue compartments correlated negatively with norepinephrine or epinephrine excretion and positively with the plasma/red cell Na+ gradient. Rate constants for efflux from red blood cell and muscle compartments correlated with measures of adrenocortical function and were higher in dexamethasone nonsuppressors than in suppressors. These data show that distribution of lithium may be related to sympathodrenal activity and Na+ distribution in manic patients.

Adrenal Cortex↗

Catecholamine metabolism and disposition in healthy and depressed subjects.

Depressed patients as a group have been found to excrete greater amounts of catecholamines (CAs) and metabolites than healthy control subjects, but these differences were not uniform for all metabolites. Patients may differ from controls in the metabolism and/or disposition of CAs. We analyzed the suggested metabolic-dispositional differences by determining 24-hour urine values for norepinephrine (NE), epinephrine (E), normetanephrine (NM), metanephrine (M), vanillylmandelic acid (VMA), and 3-methoxy-4-hydroxyphenylglycol (MHPG). For each subject, we calculated ratios of CAs or metabolites to an estimate of CA synthesis and determined ratios of CAs and metabolites to each other based on a precursor-product paradigm. The results indicate that as a group, patients have modestly but significantly greater CA synthesis rates than controls; patients excrete disproportionately more NE and E and disproportionately less MHPG relative to estimated CA synthesis, as well as other metabolites, than do controls; in contrast to NE, E, and MHPG, the increased NM, M, and VMA excretion rates by patients are proportional to each other as well as to the increase in CA synthesis; and the differences in NE, E, and metabolite excretion in the patients as a group are due principally to unipolar rather than bipolar depressives. The differences would be expected if patients, relative to controls, released more NE and E into the circulation. These data indicate the need to measure several CAs and metabolites when evaluating differences between groups since the significance of any given metabolite value needs to be examined in the context of total CA and metabolite production and excretion.

Adult↗

Lithium distribution in mania: plasma and red blood cell lithium, clinical state, and monoamine metabolites during lithium treatment.

We examined red blood cell (RBC) and plasma lithium concentrations and RBC/plasma lithium ratios in 14 manic patients during lithium treatment as part of the National Institute of Mental Health's Collaborative Program on the Psychobiology of Depression, Biological Studies. All of the lithium measures increased during treatment, especially RBC lithium. There were positive correlations between the RBC lithium concentration and the RBC/plasma lithium ratio and their maximal values in a single-dose pharmacokinetic experiment before treatment. After 5 and 16 days of treatment, patients with good subsequent outcome had higher RBC/plasma lithium ratios than did patients with poor outcome. Early in treatment, there was a negative correlation between lithium concentrations and severity of mania. During treatment, there was a negative correlation between RBC lithium and urinary MHPG excretion. There was a positive correlation between RBC or plasma lithium during the first few days of treatment and subsequent reduction in norepinephrine excretion during treatment. At 3 weeks, there were negative correlations between reductions in catecholamine measures and lithium concentrations. These data suggest that there are changes in the sensitivity of behavior and catecholamine function to lithium during treatment. RBC concentrations of lithium appear to be a potentially useful indicator of its behavioral and neurochemical effects.

Adult↗

Deafferentation and axotomy of neurons in cat striate cortex: time course of changes in binocularity following corpus callosum transection.

Single neurons were recorded in the callosal terminal and cell zones of area 17 in the cat to assess the time course of changes in the proportion of binocular neurons produced by corpus callosum transection. The callosal terminal zone contains all the degenerating terminals in area 17 after corpus callosum transection. The callosal cell zone contains all the cells in area 17 which contribute axons to the corpus callosum. The cell zone is larger than, and partially overlaps, the callosal terminal zone. After corpus callosum transection there was an initial change in ocular dominance of neurons in both callosal zones. This initial change was followed by a reduction in the proportion of binocular neurons in both zones. This reduction became maximal 2-4 weeks after transection. In the callosal terminal zone, binocularity did not recover even at the longest postoperative periods examined (31-42 weeks). In the part of the callosal cell zone outside of the callosal terminal zone, the proportion of binocular neurons began to recover after 5 weeks and was at normal levels at the longest survival periods studied. Corpus callosum transection deafferents and axotomizes cells in the callosal terminal zone and, since central neurons do not regenerate their long-ranging axons, the combined effects of deafferentation and axotomy in this zone are permanent. The callosal cell zone outside of the callosal terminal zone contains axotomized cells and no degenerating terminals following transection. The recovery of binocularity in this region may be attributed to the transient changes which axotomized cells undergo. The zone which contains no callosal cells or terminals is unaffected by transection of the corpus callosum.

Animals↗

Contralateral corticofugal projections to cat visual thalamus.

Contralateral corticofugal projections from visual cortical areas to thalamic nuclei were demonstrated in the cat using anterograde transport of tritiated proline. Thalamic nuclei receiving projections from contralateral visual cortex include both subdivisions of the lateral-posterior nucleus, the posterior nucleus of Rioch, and the posterior nuclear complex.

Animals↗

Role of corpus callosum in functional organization of cat striate cortex.

The short-term (3-51 days) and long-term (31-42 wk) effects of corpus callosum transection on the receptive-field properties of neurons were assessed at the single-cell, architectural, and topographical levels of organization in the cat striate cortex. Corpus callosum transection decreased the proportion of neurons that could be activated from both eyes. In short-term animals, the reduction in binocularity was restricted to the representation of a vertical strip of visual space extending from the vertical meridian to at least 12 degrees lateral. In the long-term animals, the reduction in binocularity was restricted to the representation of visual space 4 degrees lateral to the vertical meridian. Therefore, the reduction in the representation of 4-12 degrees was only temporary. In both groups, the reduction in binocularity was less in the representation of area centralis than at other retinal locations in the same vertical strip. The region of area 17 affected permanently by the transection receives fibers from the contralateral hemisphere in normal animals. The region affected temporarily by the transection contains callosal cells but does not contain callosal terminals. Binocularity was assessed separately for simple I, simple II, and complex receptive-field types. The reduction in binocularity in the 12 degrees strip in short-term animals and in the 4 degrees strip in long-term animals was accounted for mainly by a reduction in binocularity of simple I and complex cells. As in normal animals, complex cells in callosum-transected cats were always more binocular than the other cell types. An analysis of the effects of corpus callosum transection on different cortical layers showed that a greater proportion of cells in the supragranular layers II and III showed a reduction in binocularity than in the infragranular layers V and VI. The proportion of binocular neurons in layer IV was not significantly different from normal. The major decreases in binocularity occurred in layers II, III, and VI for simple I and simple II cells and in layers II, III, and V for complex cells. The binocularity of simple II cells in layer IV and complex cells in layer VI was not affected. The effects of the transection on the columnar organization of the cortex were assessed by making electrode tracks that passed in the radial or laminar dimensions of the cortex. Reconstructions of the radial tracks showed that cells within one radial column tended to be dominated by the same eye. In adjacent columns, cells tended to be dominated by different eyes.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Critical periods in development for susceptibility to the effects of stroboscopic rearing in the rabbit visual cortex.

Previous studies have shown that rearing rabbits in a stroboscopically illuminated environment results in a decrease in orientation and direction selectivity and an increase in responsivity to stroboscopic stimuli among neurons in area 17. In the present study, the critical period for susceptibility to these effects was studied by varying the time of onset of the deprivation. Groups of Dutch belted rabbits were reared normally and then placed in a stroboscopically illuminated environment at ages 1, 2 or 3 months, and response characteristics of visual cortical neurons were compared with those obtained from normal rabbits and from rabbits reared in a stroboscopic environment from birth. Results show that the different effects of strobe rearing have different critical periods. Increased responsivity to stroboscopic stimuli was seen only in rabbits deprived from birth. The effects of strobe rearing on both direction and orientation selectivity decreased with increasing age at the time of onset of the deprivation. However, only direction selectivity was modified by deprivation beginning at 3 months of age.

Age Factors↗

Iodine-125-labeled triiodothyronine in rat brain: evidence for localization in discrete neural systems.

Autoradiograms prepared from adult rat brains demonstrate that nerve cells and neuropil in different brain regions selectively concentrate and retain intravenously administered triiodothyronine, by mechanisms susceptible to saturation with excess triiodothyronine. A neuroregulatory role for thyroid hormones, strongly supported by the observations, may account for their marked effects on behavior and the activity of the autonomic nervous system.

Animals↗