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Biomedical subjects

M P Jacobs

Publications and source records attributed to M P Jacobs.

At least 19 recordsLinked to original sources
PubMed1999

17alpha-ethyl-5beta-estrane-3alpha, 17beta-diol, a biological marker for the abuse of norethandrolone and ethylestrenol in slaughter cattle.

The metabolism of the illegal growth promoter ethylestrenol (EES) was evaluated in bovine liver cells and subcellular fractions of bovine liver preparations. Incubations with bovine microsomal preparations revealed that EES is extensively biotransformed into norethandrolone (NE), another illegal growth promoter. Furthermore, incubations of monolayer cultures of hepatocytes with NE indicated that NE itself is rapidly reduced to 17alpha-ethyl-5beta-estrane-3alpha, 17beta-diol (EED). In vivo tests confirmed that, after administration of either EES or NE, EED is excreted as a major metabolite. Therefore, it was concluded that, both in urine and faeces samples, EED can be used as a biological marker for the illegal use of EES and/or NE. Moreover, by monitoring EED in urine or faeces samples, the detection period after NE administration is significantly prolonged. These findings were further confirmed by three cases of norethandrolone abuse in a routine screening program for forbidden growth promoters.

Animal Husbandry↗
PubMed1992

The clinical utility of provocative radionuclide oesophageal transit in the evaluation of non-cardiac chest pain.

We combined edrophonium provocative testing with the technique of radionuclide oesophageal transit (RET) in 30 consecutive patients with non-cardiac chest pain (NCCP) and 12 controls. The oesophageal transit time of aqueous technetium-99m sulfur colloid was determined before and after intravenous infusion of 80 micrograms/kg edrophonium chloride (ED). Patient symptoms during provocative RET (P-RET) were recorded. Thirteen (43%) of the patients had abnormal study results, whereas all control subjects had normal results. Three groups considered abnormal were observed: (a) in two patients (6%), the pain was reproduced and transit pre- and post-ED administration was prolonged (greater than 15 s); (b) in six patients (20%), the pain was reproduced, but transit was normal pre- and post-ED; (c) in five patients (17%), transit pre- and post-ED was prolonged, but no pain was reproduced. In five patients (17%), ED prolonged the transit time greater than 15 s without pain, but the baseline transit was normal. Transit time was measurable in 23 patients. Mean pre-ED transit time was 10.2 +/- 7.4 s (mean +/- SD) and post-ED, 12.4 +/- 8.0 s (P = 0.3). We conclude that ED has no significant effect on transit time, and the pain induced by ED rarely correlates with an abnormal transit; P-RET provides additional information to baseline RET, increasing sensitivity, and may be a useful screening method in the evaluation of patients with NCCP.

Chest Pain↗
PubMed1991

Cortisol escape from suppression by dexamethasone during depression is strongly predicted by basal cortisol hypersecretion and increasing age combined.

We determined baseline 0800h plasma cortisol concentrations, 24-hr urinary free cortisol (UFC) excretion, the post-dexamethasone cortisol values at 0800h and 1600h, and the 0800h dexamethasone concentrations in 60 depressed patients categorized according to the DSM-III. Up to 59% of the variability in the 0800h post-dexamethasone cortisol values could be explained by the multiple regression on UFC, 0800h basal plasma cortisol, age (all positively related), and dexamethasone concentrations (negatively related). The 1600h post-dexamethasone cortisol data were best explained (i.e., 55% of the variance) by the multiple regression on basal plasma cortisol, UFC (positive) and dexamethasone (negative). After controlling for UFC, baseline plasma cortisol, and age no significant effects of the depressive state (diagnostic classification or severity of illness) on the post-dexamethasone cortisol values could be detected. It can be deduced that cortisol non-suppression during depression is related strongly to baseline cortisol hypersecretion and increasing age. These factors are additive and contribute independently towards cortisol escape from suppression by dexamethasone.

Adult↗
PubMed1991

"Superscan" appearance in distal renal tubular acidosis.

Distal renal tubular acidosis (RTA) is known to cause metabolic bone abnormalities. For the first time to our knowledge, a case of distal RTA is reported in association with a superscan on bone scintigraphy. Reported cases of metabolic bone diseases producing a superscan appearance were reviewed, and underlying mechanisms are discussed. We speculate that impaired hydrogen ion secretion in this patient with distal RTA subclinically increased bone turnover, contributing to the superscan appearance on bone scintigraphy.

Acidosis, Renal Tubular↗
PubMed1991

Felbamate for partial seizures: results of a controlled clinical trial.

Felbamate (2-phenyl-1,3-propanediol dicarbamate) has a favorable preclinical profile in animal models of epilepsy. We present the results of a double-blind, randomized, placebo-controlled clinical trial in patients with partial seizures. Criteria for entry included a requirement for four or more partial seizures per month despite concomitant therapeutic blood levels of phenytoin and carbamazepine. Fifty-six patients (mean age, 31.4 years; 32 men, 24 women) completed the trial. The mean seizure frequencies for the 8-week periods analyzed were felbamate = 34.9, placebo = 40.2. Felbamate was statistically superior to placebo in seizure reduction, percent seizure reduction, and truncated percent seizure reduction. The mean felbamate dosage was 2,300 mg/d. Plasma felbamate concentrations ranged from 18.4 to 51.9 mg/l, mean = 32.5 mg/l. Adverse experiences during felbamate therapy were minor and consisted primarily of nausea and CNS effects. This trial indicates that felbamate is safe and effective in the treatment of comedicated patients with severely refractory epilepsy.

Adult↗
PubMed1990

Prediction of the DST results in depressives by means of urinary-free cortisol excretion, dexamethasone levels, and age.

This study investigates the relationships between cortisol escape from suppression by dexamethasone during a depressive episode, and the baseline activity of the hypothalamic-pituitary-adrenal (HPA) axis, circulating dexamethasone levels, and age. To this end, we measured urinary-free cortisol (UFC) excretion in 24-hr urine samples and the 8 AM cortisol and dexamethasone levels after administration of 1 mg dexamethasone in 50 depressive patients. We found that up to 54% of the variance in the postdexamethasone cortisol values could be explained by the multiple regression on UFC, age, and dexamethasone levels. By utilizing these three parameters, the dexamethasone suppression test (DST) nonsuppressor/suppressor state was correctly identified in 92% of the subjects. It was shown that an important part of the variance in postdexamethasone cortisol is actually background variance, irrelevant to depression and produced by the cumulative effects of the three aforementioned parameters. Only a small part (less than 20%) of the variance in postdexamethasone cortisol is determined by the actual depressive state. It was concluded that (1) baseline hypersecretion of cortisol, (2) decrements in the bioavailability of the test substance, (3) increasing age, and (4) the depressive state per se--all of which are cumulative--contribute independently to cortisol escape from suppression by 1 mg dexamethasone.

Adult↗
PubMed1990

Effects of dexamethasone on the availability of L-tryptophan and on the insulin and FFA concentrations in unipolar depressed patients.

Several authors have shown that the availability of L-tryptophan (L-TRP) in the serum is lower in patients with major depression than in controls. It has recently been reported that the administration of a dose of dexamethasone sufficient to cause cortisol suppression also caused significant decrements in the availability of L-TRP. In order to elucidate the putative pathophysiological mechanisms underlying this decreased L-TRP disposition, the authors examined 37 depressed women categorized according to the DSM-III. L-TRP, the sum of five competing amino acids (CAA), the L-TRP/CAA ratio, and insulin and free fatty acid (FFA) levels were determined both before and after oral administration of 1 mg dexamethasone. The availability of L-TRP was significantly lower in depressed women with melancholia compared with simple major and minor depressives. The baseline disposal of L-TRP was related neither to insulin nor to FFA concentrations Dexamethasone administration significantly reduced the L-TRP and L-TRP/CAA values and increased FFA and insulin levels. Postdexamethasone L-TRP and FFA levels were significantly and positively correlated.

Adjustment Disorders↗
PubMed1990

An augmented escape of beta-endorphins to suppression by dexamethasone in severely depressed patients.

Baseline beta-endorphin and cortisol levels and their responses to 1 mg dexamethasone were measured in 11 healthy controls and in 35 depressed patients, categorized according to the DSM-III. Dexamethasone significantly suppressed beta-endorphin levels. Depressed patients with melancholia/psychotic features exhibited significantly increased post-dexamethasone beta-endorphin levels compared with healthy controls, minor and simple major depressives; the baseline beta-endorphin levels did not differ between those study samples. Post-dexamethasone beta-endorphin and cortisol values were found to be significantly and positively correlated. Accordingly, cortisol non-suppressors showed significantly higher post-dexamethasone beta-endorphin levels. Post-dexamethasone beta-endorphin may be the most sensitive and specific reflection of the disorder in negative feedback exerted by dexamethasone in depression.

Adult↗
PubMed1990

Suppressant effects of dexamethasone on the availability of plasma L-tryptophan and tyrosine in healthy controls and in depressed patients.

Formation in the brain of serotonin from L-tryptophan (L-TRP) and noradrenaline from tyrosine are pathways related to the pathophysiology of major depression and to the regulation of the hypothalamic-pituitary-adrenal (HPA) axis. In the past, decrements in L-TRP availability and disorders in the HPA axis have repeatedly been observed in major depressed patients; both factors were shown to be inversely correlated. In order to investigate the relationships between glucocorticosteroid activity and the availability of L-TRP and tyrosine, the authors measured L-TRP, tyrosine, valine, leucine, isoleucine and phenylalanine in baseline conditions and after treatment with 1 mg dexamethasone in 16 healthy controls and in 50 depressed patients. The ratios between L-TRP and tyrosine and the sums of the amino acids known to compete with them during transport across the blood-brain barrier were computed as an index of (respectively) the serotonin and noradrenaline synthesis in the brain. We found significantly decreased plasma L-TRP and tyrosine levels after treatment with dexamethasone compared with basal levels. Accordingly, the plasma ratios between L-TRP and tyrosine and the sum of the competing amino acids were significantly reduced by dexamethasone administration. It was hypothesized that through these actions of dexamethasone on peripheral amino acids, the central noradrenaline and serotonin control over the HPA-axis could be altered.

Adult↗
PubMed1989

Murine monoclonal anti-myelin basic protein (MBP) antibodies inhibit proliferation and cytotoxicity of MBP-specific human T cell clones.

Myelin basic protein (MBP)-specific T cell clones, isolated from two patients with multiple sclerosis, expressed the CD4+ phenotype and induced MBP-dependent cytolysis of autologous Epstein-Barr virus (EBV)-transformed B cells. The proliferation and cytolytic activity of the T cell clones were inhibited by four of a panel of five murine monoclonal anti-MBP antibodies in a dose-dependent manner. An isotype-matched antibody with an irrelevant specificity did not have such an effect. These MBP-specific monoclonal antibodies did not block phytohemagglutinin-induced T cell proliferation or allospecific cytotoxicity. These results suggest that some antibodies directed at the autoantigen MBP may play a regulatory role in T cell activation, rather than a pathogenic role, for which there is currently little supporting evidence.

Autoantibodies↗
PubMed1989

Cortisol, ACTH, prolactin and beta-endorphin responses to fenfluramine administration in major-depressed patients.

In the past, some researchers found increased cortisol and prolactin responses to the administration of fenfluramine in major-depressed patients. It was believed that the fenfluramine test could prove to constitute another challenge probe to reflect the central serotonergic function. The present study was conducted in order to investigate the pituitary/adrenal responses to fenfluramine in major- versus minor-depressed patients. To this end we administered 60 mg D,L-fenfluramine p.o. to 40 depressed patients categorized according to the DSM-III. The basal levels of cortisol, adrenocorticotrophic hormone (ACTH), beta-endorphins and prolactin and their levels 2 and 4 h after fenfluramine administration were measured. We found no significant effect for fenfluramine treatment on cortisol, ACTH or beta-endorphins. There was a significant (p = 0.02) effect for fenfluramine treatment on prolactin. The enhanced secretion of prolactin was only significant (p = 0.006) in major (296.X2, 296.X3, 296.X4) and not in minor (300.40, 309.00) depressives. It was concluded that our findings corroborate the thesis of a hypersensitive serotonergic neurotransmission during a major depressive episode.

Adrenocorticotropic Hormone↗
PubMed1987

Complement-mediated neutrophil activation in sepsis- and trauma-related adult respiratory distress syndrome. Clarification with radioaerosol lung scans.

Complement-mediated neutrophil activation (CMNA) has been proposed as an important pathogenic mechanism causing acute microvascular lung injury in the adult respiratory distress syndrome (ARDS). To clarify the relationship between CMNA and evolving lung injury, we studied 26 patients with multiple trauma and sepsis within 24 hours of risk establishment for ARDS. Pulmonary alveolar-capillary permeability (PACP) was quantified as the clearance rate of a particulate radioaerosol. Seventeen patients (65%) had increased PACP (six developed ARDS) while nine (35%) had normal PACP (none developed ARDS; clearance rates of 3.4%/min and 1.5%/min, respectively). These patients, regardless of evidence of early lung injury, had elevated plasma C3adesArg levels and neutrophil chemotactic desensitization to C5a/C5adesArg. Plasma C3adesArg levels correlated weakly, but significantly, with PACP. Thus, CMNA may be a necessary, but not a sufficient, pathogenic mechanism in the evolution of ARDS.

Adult↗
PubMed1987

Increased pulmonary alveolar-capillary permeability in patients at risk for adult respiratory distress syndrome.

Two methods for predicting adult respiratory distress syndrome (ARDS) were evaluated prospectively in a group of 81 multitrauma and sepsis patients considered at clinical high risk. A popular ARDS risk-scoring method, employing discriminant analysis equations (weighted risk criteria and oxygenation characteristics), yielded a predictive accuracy of 59% and a false-negative rate of 22%. Pulmonary alveolar-capillary permeability (PACP) was determined with a radioaerosol lung-scan technique in 23 of these 81 patients, representing a statistically similar subgroup. Lung scanning achieved a predictive accuracy of 71% (after excluding patients with unilateral pulmonary contusion) and gave no false-negatives. We propose a combination of clinical risk identification and functional determination of PACP to assess a patient's risk of developing ARDS.

Adult↗
PubMed1985

Radioaerosol lung clearance in patients with active pulmonary sarcoidosis.

Pulmonary radioaerosol clearance rate of 99mTc diethylenetriamine pentacetate (DTPA) in 14 patients with untreated sarcoidosis was compared with 67Ga lung scan and increased lymphocytes in the bronchoalveolar lavage (BAL) fluid. Nine healthy nonsmoking subjects had a mean DTPA clearance rate of 1.18%/min (range, 0.54 to 1.60%/min). Eight of 14 patients with sarcoidosis had clearance rates greater than 1.60%/min. Of those 8 patients with abnormal DTPA clearance, 4 had positive gallium scans, 4 had more than 17% lymphocytes in the BAL fluid, and 3 had both tests positive. To study the cause of abnormal DTPA clearance, 23 subjects (including 3 normal controls, all 14 patients with sarcoidosis, and 6 patients with localized disease on chest roentgenogram) underwent both DTPA clearance studies and BAL for quantitation of the amount of albumin in lung fluid. There was a positive correlation between the rate of DTPA clearance and the albumin concentration in lung fluid (r = 0.87, p less than 0.01).

Aerosols↗
PubMed1975

Thrombosis with low-estrogen oral contraceptives.

A retrospective study of the relationship of oral contraception to thrombosis was made in 104 idiopathic cases, 357 other thrombotic cases (exclusive of cerebrovascular thrombosis), and 1302 matched controls. The relative risk for idiopathic case users was 7.2 times that for non-users; for the whole series it was 1.9. The apparent low risk for non-idiopathic cases is considered to be due to selective prescription of this method of contraception. The risk for women using formulations containing 100 mug or more of estrogen was higher than that for users of lower doses. Among the controls, the risk of gallbladder surgery was twice as high for users as non-users. Several theoretical sources of bias were searched for and shown not to be present. Histories of oral contraceptive use were found to be accurate. A definite risk of thrombosis exists even with the low-estrogen dosage currently employed in oral contraceptive steroids.

Adolescent↗