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Biomedical subjects

J Birnbaum

Publications and source records attributed to J Birnbaum.

At least 73 records · Page 4Linked to original sources
PubMed1989

Immunoheterogeneity of parathyroid hormone in parathyroid cysts: diagnostic implications.

Parathyroid cysts are uncommon lesions of the neck leading to hypercalcemia in a significant percentage of cases. The distinction between parathyroid and thyroid cysts is difficult to make on a clinical basis alone and relies on the demonstration of elevated PTH levels in cyst fluid. We describe a case of a parathyroid cyst in which intact PTH (1-84) levels were misleadingly low while midmolecule 44-68 PTH was markedly elevated. To explain this discrepancy, we studied cyst fluid from this and two other patients using Sephadex G-75 gel chromatography. Fractions were analyzed using an immunoradiometric assay for intact hPTH (1-84) and a RIA specific for the midmolecular 44-68 region of hPTH. Immunoreactivity corresponding to hPTH (1-84) was absent in the first case but present in the remaining two. Immunoreactive peaks corresponding to PTH fragments were demonstrable in all three cyst samples. Patients with elevated hPTH (1-84) in cyst fluid were hypercalcemic; in contrast, the patient with a low cyst level of hPTH (1-84) was normocalcemic despite having markedly elevated levels of midmolecule PTH (44-68) in both serum and cyst fluid. Parathyroid cysts may thus produce fragments rather than intact PTH; reliance on an intact hPTH assay could lead to misdiagnosis. The measurement of PTH by a midmolecular assay may be preferable to the measurement of intact PTH in the evaluation of fluid from cystic neck masses.

Aged↗
PubMed1989

Partial adrenalectomy for pheochromocytoma with maintenance of adrenocortical function.

A 30-yr-old woman with malignant hypertension was found to have biochemical evidence of pheochromocytoma. Bilateral adrenal tumors were demonstrated on computerized tomographic scanning and confirmed at the time of surgery. Complete removal of one adrenal gland with partial removal of the other adrenal gland resulted in normalization of her blood pressure and biochemical parameters (norepinephrine and epinephrine) with preservation of adrenocortical function.

Adrenal Cortex↗
PubMed1988

Lithium stimulates the release of human parathyroid hormone in vitro.

The effect of lithium on PTH release from human parathyroid tissue was studied using a perifusion system and an immunoradiometric assay for intact human PTH. Tissue was obtained from three patients undergoing surgery for thyroid disease, three patients with secondary hyperparathyroidism due to chronic renal insufficiency, and four patients with primary hyperparathyroidism due to a parathyroid adenoma. Addition of lithium in concentrations equivalent to the therapeutic serum levels normally attained in man (1.3 mmol/L) resulted in a significant (P less than 0.05) increase in PTH release under normocalcemic (1.15 mmol/L) conditions from normal and hyperplastic tissues. The magnitude of the lithium-induced response of PTH release ranged from a 1.4- to 5.3-fold increase above basal levels (perifusion with 1.15 mmol/L calcium alone) and was comparable to the response during a low calcium (0.42 mmol/L) perifusion. Although the response to lithium was delayed compared to that of hypocalcemia, PTH returned to basal levels immediately after removal of either stimulator. In contrast, parathyroid adenomas did not respond to either lithium or hypocalcemia in a characteristic manner, but, rather, functioned in an autonomous fashion with repeated pulsatile bursts of PTH release that were not suppressible even under hypercalcemic (1.70 mmol/L) conditions. These in vitro studies suggest that lithium therapy may elevate serum PTH levels in some patients and could, thus, be responsible for hypercalcemia in them.

Adenoma↗
PubMed1988

[The role of alpha-amylase in baker's asthma].

We report a case of asthma in a baker provoked by an additive which is generally used in bread making, namely alpha-amylase, an extract of Aspergillus oryzae. Skin tests to alpha-amylase were positive in a concentration of 0.1 micrograms/ml. Specific IgE was detected to this enzyme. A provocation test to alpha-amylase was positive with a fall of the FEV1 of 42%. Provocation tests to flour gave a negative immediate and delayed reaction. Progress was made towards the disappearance of symptoms after several months of avoiding the allergen. This observation has enabled us to show the specificity of the allergy to alpha-amylase, a glycolytic enzyme, coming in the group of occupational diseases n. 63 (asthma due to lyophilised enzymes) whereas baker's asthma is at n. 66.

Adult↗
PubMed1987

Lack of effect of sucralfate on prednisone bioavailability.

The relative bioavailability of single oral doses of prednisone with and without sucralfate administration was determined in 12 healthy male volunteers. Each subject participated in a randomized three-way cross-over study consisting of the following three phases: treatment A, prednisone given alone; treatment B, 2 days pretreatment with sucralfate with a concomitant dose of sucralfate administered with prednisone; and treatment C, 2 days pretreatment with sucralfate with a sucralfate dose administered 2 h after the oral prednisone dose. Plasma prednisolone concentrations (active moiety of prednisone) were determined by a specific and sensitive high-performance liquid chromatographic assay and unbound prednisolone concentrations were determined by equilibrium dialysis. Bioavailability was assessed by comparing the areas under the plasma prednisolone concentration-time curves as well as peak concentrations, time to peak concentration, elimination rate constant, and half-life. No significant differences were noted in any of the treatment phases for any of the parameters except for the time of peak concentration which was slightly delayed from 1.0 +/- 0.6 to 1.7 +/- 0.9 h when sucralfate was concomitantly administered with the prednisone. Thus, the data from this study indicate that sucralfate does not have a clinically significant effect on the bioavailability of orally administered prednisone. The use of these two drugs in combination does not result in an interaction requiring dosage regimen alteration.

Adult↗
PubMed1985

A potent nonpeptide cholecystokinin antagonist selective for peripheral tissues isolated from Aspergillus alliaceus.

A new, competitive, nonpeptide cholecystokinin (CCK) antagonist, asperlicin, was isolated from the fungus Aspergillus alliaceus. The compound has 300 to 400 times the affinity for pancreatic, ileal, and gallbladder CCK receptors than proglumide, a standard agent of this class. Moreover, asperlicin is highly selective for peripheral CCK receptors relative to brain CCK and gastrin receptors. Since asperlicin also exhibits long-lasting CCK antagonist activity in vivo, it should provide a valuable tool for investigating the physiological and pharmacological actions of CCK.

Animals↗
PubMed1985

Carbapenems, a new class of beta-lactam antibiotics. Discovery and development of imipenem/cilastatin.

The discovery of Streptomyces cattleya and its antibiotic product, thienamycin, has ushered in a new era of beta-lactam agents, the carbapenems. Numerous carbapenems were subsequently discovered; however, none had the potency, broad-spectrum activity, and lack of cross-resistance exhibited by thienamycin. Chemical instability encountered with thienamycin was overcome by the N-formimidoyl derivative, imipenem. Imipenem is distinguished from other beta-lactams by its outstanding activity against gram-positive organisms as well as against Enterobacteriaceae, Pseudomonas aeruginosa, and Bacteroides. However, development was hindered by extensive renal metabolism of imipenem, resulting in low urinary concentrations of antibiotic. A renal dipeptidase, dehydropeptidase-I, was responsible for hydrolyzing imipenem and other carbapenems. To counter its action, a specific inhibitor, cilastatin, was developed. Coadministered with imipenem in a one-to-one ratio, cilastatin provides prolonged, reversible blockade of imipenem metabolism, dramatically improving urinary recoveries to therapeutically significant levels. Cilastatin also contributes to the safety of imipenem, since its coadministration prevents proximal tubular necrosis which has been observed in sensitive animals receiving imipenem alone in high doses. Thus, the combination imipenem and cilastatin overcame the pharmaceutical and metabolic challenges presented by thienamycin, and allowed for the evaluation in humans of the outstanding antimicrobial activity of this new class of beta-lactam antibiotics.

Animals↗
PubMed1983

Glucose and lipid metabolism during acebutolol and propranolol therapy of angina in nondiabetic patients.

The metabolic effects of acebutolol, a cardioselective beta-adrenergic blocker, and of propranolol, a nonselective beta blocker, were evaluated. Our subjects were 20 men with chronic stable angina; none had diabetes. An initial 4-wk, single-blind control phase was followed by two drug treatment periods, each a 3-wk double-blind titration phase (using increasing doses of acebutolol or propranolol), followed by a 5-wk double-blind maintenance phase. Metabolic studies were performed at the end of the control and maintenance phases. Propranolol induced elevation in basal serum glucose concentrations and both propranolol and acebutolol decreased glucose tolerance at 2.5 and 3 hr. There was no noticeable effect on insulin secretion by either drug. Neither propranolol nor acebutolol induced hyperlipidemia. There was a small decrease in total serum cholesterol after propranolol. Both drugs decreased low-density lipoprotein cholesterol. No effects were noted on the levels of serum triglycerides, high-density lipoprotein cholesterol, or free fatty acids.

Acebutolol↗
PubMed1983

Thienamycin: development of imipenen-cilastatin.

Thienamycin, a natural product produced by Streptomyces cattleya is the first representative of a unique class of beta-lactam antibiotics, the carbapenems. Despite its outstanding potency and antibacterial spectrum, thienamycin was itself unsuited for further development because of its chemical instability in concentrated solution and in the solid state. Synthesis of the amidine derivative, N-formimidoyl thienamycin (imipenem, MK0787) resulted in a crystalline product with much improved stability and with antibacterial properties significantly superior to thienamycin. Imipenem has an unusually broad antimicrobial spectrum. A high order of bactericidal activity is found against Pseudomonas aeruginosa, Serratia, Bacteroides fragilis, enterococci and numerous other species intrinsically resistant to other antibiotics. Imipenem is refractory to hydrolysis by all important classes of bacterial beta-lactamases and thus exhibits no cross-resistance with penicillins or cephalosporins. Imipenem is distinguished from the new generation of extended-spectrum cephems by its unusually high potency against Gram-positive as well as Gram-negative organisms. Offsetting these excellent antimicrobial properties was an unusual susceptibility exhibited by imipenem to renal metabolism in animal species and in man. Very low urinary recoveries resulted without, however, any significant reduction in the serum half-life of imipenem. A brush-border dipeptidase, dehydropeptidase-I, was shown to be responsible for renal metabolism. Metabolism has been countered with the development of cilastatin (MK0791), a substituted amino-propenoate inhibitor of dehydropeptidase which is specific, potent and well matched in its pharmacokinetic properties for co-administration with imipenem. With the imipenem/cilastatin combination, uniformly high urinary concentrations and recovery are obtained regardless of the varying but often extensive metabolism suffered by imipenem in human populations. An additional benefit conferred by cilastatin results from its ability to exclude imipenem competitively from entry into and subsequent metabolism within the proximal tubular epithelium of the kidney. The tubular necrosis induced by imipenem alone when it is administered at very high doses to susceptible mammalian species is thereby eliminated. Thus the imipenem/cilastatin combination affords reliability and enhanced safety in the application of the antibiotic's unusual antibacterial potential in the treatment of difficult infections regardless of the site of disease.

Animals↗
PubMed1983

Long-term renal function in kidney donors. Sustained compensatory hyperfiltration with no adverse effects.

Twenty patients who underwent uninephrectomy for kidney donation between 1964 and 1968 participated in a long-term study of the function of the solitary kidney. Mean follow up after uninephrectomy was 15.8 +/- .3 years. One patient with a strong family history of essential hypertension developed de novo mild hypertension. The current creatinine clearance of the donors was 80 +/- 4 ml/min. The 1-week, 3-6 months and 14-18 years postuninephrectomy percentages of predonation creatinine clearance were 72 +/- 3%, 76 +/- 3% and 78 +/- 2%, respectively. The 24-hr urine protein excretion in kidney donors was significantly higher than in controls (141 +/- 20 mg vs. 74 +/- 3 mg, respectively, P less than .0005). Except for one donor who may have developed glomerulonephritis, the donors had normal urinary albumin excretion. The cause of the slightly elevated nonalbumin proteinuria is not known. However, this long-term study of kidney donors shows no adverse effects on the blood pressure and renal function after many years of compensatory hyperfiltration.

Adult↗
PubMed1982

Clinical studies with terfenadine in seasonal allergic rhinitis in France.

The results of a multicentre investigation carried out on 312 pollinic patients are presented. Efficacy of alpha-[4-(1,1-dimethylethyl)phenyl]-4-(hydroxydiphenylmethyl)-1- piperidinebutanol (terfenadine, RMI 9918, Triludan, Teldane, resp.) has been estimated from a global appreciation and the evolution of 11 symptoms, and tolerance on the frequency of diurnal sleepiness. The results showed a very good efficacy of terfenadine and the absence of a depressant effect.

Adolescent↗
PubMed1981

Epithienamycins. II. Isolation and structure assignment.

At least six distinct beta-lactam antibiotics of the epithienamycin family are produced by a strain of Streptomyces flavogriseus MB 4638. Each of the six can be isolated in substantially pure form by column chromatography using Dowex 1, Amberlite XAD-2 and Biogel packings. The structures were established by comparison of the ultraviolet, proton magnetic resonance and mass spectral characteristics with those of thienamycin and its derivatives. All six compounds contain the carbapenem ring system which is also found in thienamycin. They differ from each other and from thienamycin by chemical modifications and/or stereoisomerism. Enzymatically deacetylated epithienamycin A has the properties of an isomer of thienamycin.

Anti-Bacterial Agents↗