Multiresistant Salmonella organisms in India.
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Anti-Bacterial Agents↗
Biomedical subjects
A Mehta
Publications and source records attributed to A Mehta.
An endocrine and pharmacokinetic study of four oral doses of formestane in postmenopausal breast cancer patients.
43 postmenopausal breast cancer patients were treated orally with the aromatase inhibitor formestane (4-hydroxyandrostenedione) at daily doses of 62.5, 125, 250 or 500 mg for 4 weeks followed by 250 mg daily for a further 4 weeks. For some patients, 62.5 mg did not suppress serum oestradiol levels maximally. The doses of 250 and 500 mg did not differ in their effectiveness. Oestrone levels were suppressed by all doses of formestane but no consistent changes of aldosterone, cortisol or 17-hydroxyprogesterone occurred. Serum levels of sex hormone binding globulin fell by about 15% during treatment with 250 mg formestane reflecting its minor androgenic activity. The maximum concentration and area under the curve of serum formestane levels after the first dose varied in an approximately linear manner with dose. It is concluded that formestane is an effective, specific suppressant of oestradiol levels via the oral route requiring no more than 250 mg to be given daily.
Administration, Oral↗
Chloramphenicol resistance in Salmonella typhi. Report from Bombay.
Chloramphenicol resistance to Salmonella typhi in 1989 was 16% in Hinduja Hospital. From Jan to June 1990, this resistance has increased to 81%. 74 strains of blood culture isolated of S typhi obtained from Jan to June were subjected to antibiotic sensitivity testing by disc diffusion technique of Kirby and Bauer 60 strains were found to show a block resistance tochloramphenicol, Ampicillin, Co-trimoxazole, Streptomycin, Tetracycline and Carbenicillin. All strains were sensitive to quinolones. Resistance was record and MIC done in 50 resistant strains by modified National Committee for Clinical Laboratory Standards [NCCLS] according to recommended break points and resistance to Chloramphenicol was confirmed. Of the 47 strains isolated, 34 had received treatment with either chlorampheniicol, Ampicillin or Cotrimoxazole in adequate dosages. In 39 of these 47 patients, Salmonella typhi was isolated after 14 days duration of fever. Plasmid analysis revealed presence of 100 megadalton plasmid in majority of cases. Most patients responded to fluoroquinolones but amongst the admitted patients complications such as Myoglobinuria in 2 cases, perforation in 4 cases, acute Renal failure in 2 cases and typhoid spine in 1 case were seen. Phage typing results of 19 strains were E-8, 0-6.
Chloramphenicol Resistance↗
Diagnosis and management of acute and chronic lung rejection.
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Graft Rejection↗
Oxalate decarboxylase from Collybia velutipes. Purification, characterization, and cDNA cloning.
The oxalate-degrading enzyme oxalate decarboxylase (EC 4.1.1.2), which is inducible by oxalic acid, was purified to homogeneity from a crude extract of Collybia velutipes, a basidiomycetous fungus. Two forms of the enzyme were resolved on chromatofocusing. The two isozymes were shown to be related by amino acid composition, peptide mapping, and immunological cross-reactivity. Peak A, eluting at pH 3.3, was used for further study; the Km was found to be 4.5 mM, and the Vmax was 166 mumol/min/mg. The subunit molecular mass of the glycosylated enzyme was 64 kDa, whereas the mass of the deglycosylated protein was 55 kDa. The enzyme showed an acidic pl, was very stable over a wide pH range, and was moderately thermostable. The cDNA encoding the enzyme was obtained by immunoscreening a lambda gt11 expression library. In vitro translation of hybrid-selected mRNA gave a 55-kDa protein. Genomic Southern hybridization indicated the oxalate decarboxylase is encoded by a single gene. The cDNA probe hybridized to a single 1.5-kilobase pair species of mRNA. The mRNA was shown to be induced by oxalic acid. A temporal relationship between enzyme activity and mRNA levels was observed, thus suggesting that the expression of oxalate decarboxylase is regulated at the transcriptional level.
Amino Acids↗
Stages of T-cell receptor protein expression in T-cell acute lymphoblastic leukemia.
In this study five monoclonal antibodies (MoAbs) to T-cell receptor (TCR) proteins (WT31, alpha F1, beta F1, TCR delta-1 and delta TCS-1) were used to identify discrete maturative stages in 40 cases of T-cell acute lymphoblastic leukemia (T-ALL). These MoAbs reacted exclusively with CD3+ T cells and did not label B-lineage and myeloid cells. In 17 of the 40 T-ALL cases studied the leukemic blasts lacked membrane and cytoplasmic TCR chains (group I). In 12 cases cells did not have membrane CD3/TCR but expressed cytoplasmic TCR proteins heterogenously: nine cases had cytoplasmic TCR beta chains (beta F1+, alpha F1-; group II), one case had cytoplasmic TCR alpha chains (alpha F1+, beta F1-; group III), and two cases were labeled by both alpha F1 and beta F1 MoAbs (group IV). The remaining 11 cases were mCD3+: nine were TCR alpha beta+ (group Va) and two exhibited TCR gamma delta (TCR delta-1+, delta TCS-1+; group Vb). The analysis of the TCR beta, -gamma, and -delta gene configurations in 23 of the 40 T-ALLs showed that: (1) the lack of TCR protein expression was due to the lack of TCR gene rearrangements only in one of nine cases; (2) five of five TCR beta+, TCR alpha- cases studied had germline TCR alpha genes (ie, no detectable TCR delta gene deletions); (3) seven of eight cases with TCR delta gene deletions expressed TCR alpha proteins, whereas in 12 of 20 of the T-ALLs with TCR beta gene rearrangements the synthesis of the corresponding protein occurred; only 2 of 16 cases with rearranged TCR delta genes expressed TCR delta chains. The T-ALL categories identified with anti-TCR MoAbs did not have additional characteristic phenotypic patterns and may correspond to the normal stages of T-cell development more precisely than those defined by other differentiation antigens.
Adult↗
Pharmacokinetics and pharmacodynamics of the aromatase inhibitor 3-ethyl-3-(4-pyridyl)piperidine-2,6-dione in patients with postmenopausal breast cancer.
The pyridylglutarimide 3-ethyl-3-(4-pyridyl)-piperidine-2,6-dione (PyG) is a novel inhibitor of aromatase that was shown to cause effective suppression of plasma oestradiol levels in postmenopausal patients. In four patients receiving oral doses of PyG (500 mg) twice daily for 3-4 days, oestradiol levels fell to 31.1% +/- 6.3% of baseline values within 48 h and remained suppressed during treatment. Of a further six patients who received oral PyG (1 g) as a single dose, five had quantifiable oestradiol levels. Oestradiol suppression was sustained for 36 h and recovery correlated with a fall of PyG concentrations below a threshold value of ca. 2 micrograms/ml. The pharmacokinetics of PyG were non-linear and, when fitted to the integrated Michaelis-Menten equation, yielded good parameter estimates for Co (21.7 +/- 1.82 micrograms/ml), Km (2.66 +/- 0.68 micrograms/ml) and Vmax (0.86 +/- 0.06 micrograms ml-1 h-1). On subsequent repeated dosing with PyG, both the Km (4.31 +/- 0.48 micrograms/ml) and the Vmax (1.83 +/- 0.13 micrograms ml-1 h-1) values increased and recovery from oestradiol suppression was more rapid, indicating that PyG induces its own metabolism.
Aminoglutethimide↗
Low-dose aminoglutethimide in postmenopausal breast cancer: effects on adrenal and thyroid hormone secretion.
Aminoglutethimide is effective in the treatment of breast cancer in postmenopausal patients as a result of its inhibition of aromatase. Its use is complicated by a number of endocrine side-effects which include the inhibition of thyroxine synthesis and inhibition of 11-steroid and 21-steroid hydroxylases. When aminoglutethimide is used at the conventional daily dose of 1000 mg in combination with 40 mg of hydrocortisone these effects can result in clinically significant hypothyroidism and increases in the serum levels of oestrone in response to stimulation of adrenocorticotropic hormone (ACTH). In the current study it was found that with twice daily treatment at the low dose of 125 mg aminoglutethimide plus 20 mg hydrocortisone there was no significant increase in oestrone levels after ACTH stimulation. In addition there was little effect on thyroid function: serum levels of triiodothyronine and thyroxine were unaffected whilst there was a marginally significant (P less than 0.05) increase in thyroid-levels were confined to those patients with pretreatment values greater than 2.5 mU/L, the most marked effect being in 1 patient whose pretreatment level was already outside the normal range.
17-alpha-Hydroxyprogesterone↗
The effect of the aromatase inhibitor, rogletimide (pyridoglutethimide), on guinea pig adrenal cell steroidogenesis and placental microsomal aromatase activity: comparison with aminoglutethimide and CGS 16949A.
A dispersed guinea pig adrenal system has been used to study the effect of the aromatase inhibitor rogletimide (RGL) on adrenal steroidogenesis. The ACTH-stimulated release of cortisol, 17-hydroxyprogesterone (17-OHP) and androstenedione (A) was measured following exposure of adrenal cells to RGL, or the other aromatase inhibitors aminoglutethimide (AG) and CGS 16949A. RGL at concentrations sufficient to cause 80-90% inhibition of placental microsomal aromatase had no effect on the release of all three steroids. In contrast, AG at 10(-5) M markedly reduced the output of all three steroids from these cells. CGS 16949A at 10(-6) M reduced the output of cortisol and increased the concentration of 17-OHP and A. These results indicate that RGL is unlikely to cause the suppression of cortisol synthesis which has been noted to occur with AG and CGS 16949A during the treatment of breast cancer patients.
Adrenal Glands↗
Endocrine, pharmacokinetic and clinical studies of the aromatase inhibitor 3-ethyl-3-(4-pyridyl)piperidine-2,6-dione ('pyridoglutethimide') in postmenopausal breast cancer patients.
The aromatase inhibitor, 'pyridoglutethimide' (PyG), has been shown previously to suppress serum oestrogen levels in postmenopausal breast cancer patients and to achieve clinical responses at a dose of 500 mg twice daily (b.d.). This report gives the results of a detailed pharmacokinetic and endocrine study of PyG in ten patients. Four doses were tested at intervals of 2 weeks in the following order: 200 mg b.d., 400 mg b.d., 800 mg b.d., 1200 mg b.d. Concentration-time profiles of serum levels of PyG were curvilinear in all patients probably reflecting a saturation of metabolic enzymes. During repeat-dosing metabolism was enhanced approximately 2-fold. Plasma levels of oestradiol were significantly suppressed by the lowest dose of PyG. Although higher doses appeared to achieve greater suppression this was not statistically significant in this small group of patients. There were no significant effects at any dose on the serum levels of cortisol, aldosterone, luteinising hormone, follicle stimulating hormone, prolactin, sex hormone binding globulin or thyroid stimulating hormone. There was a dose-related increase in 17 alpha-hydroxyprogesterone levels and a dose-related decrease in levels of dehydroepiandrosterone sulphate (DHAS). The androgens DHA, testosterone and androstenedione also were significantly suppressed with at least one of the doses of PyG. Synacthen tests did not support these changes being a result of inhibition of 17,20 lyase. It is possible that they are due to enhanced clearance of DHAS. Two patients experienced no toxicity throughout the study, whilst a total of four patients were withdrawn because of side-effects: one at 400 mg b.d., two at 800 mg b.d., and one at 1200 mg b.d. The most frequent side-effects were nausea and lethargy. One patient showed an objective response to treatment.
Aged↗
Calcium regulation of ciliary beat frequency in human respiratory epithelium in vitro.
1. The changes in ciliary beat frequency (CBF) of human nasal respiratory epithelial cells were measured in vitro with a photometric technique following exposure to either 4-bromo-calcium ionophore A23187 (4-Br-A23187) or trifluoperazine (TFP), an inhibitor of calmodulin-sensitive calcium-dependent protein kinases. Changes in intracellular free calcium concentrations in response to 4-Br-A23187 were studied using a fluorescent dye (Fura-2). 2. Addition of 10(-5) M-4-Br-A23187 caused a time-dependent (P less than 0.01) rise in CBF. The increment in CBF was statistically significant 10 min after challenge (+10%; P less than 0.01) and was sustained for at least 1 h, with maximal stimulation after 40 min (+ 18%; P less than 0.01). 3. Exposure to 10(-5) M-4-Br-A23187 caused an immediate increase in intracellular free calcium concentration, which preceded the rise in CBF. 4. TFP (10(-4) M) caused a reduction of baseline CBF (-10%; P less than 0.01) and prevented the expected rise when the cells were subsequently exposed to 10(-5) M-4-Br-A23187. 5. We conclude that: (1) calcium ionophore stimulates the CBF of human respiratory cells; (2) this effect is mediated through a calmodulin-sensitive system, since it is abolished in the presence of TFP; (3) the same pathway appears to control the basal CBF of these cells, since TFP also decreases CBF.
Adolescent↗
Hyperinsulinaemic hypoglycaemia in small for dates babies.
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Glucagon↗
Effect of cyclic AMP on ciliary activity of human respiratory epithelium.
In order to investigate the effect of cyclic adenosine monophosphate (cAMP) on ciliary beat frequency (CBF) in human respiratory epithelium, cells were brushed from the inferior nasal turbinates of three groups of ten subjects: awake adults (aged 20-34 yrs), anaesthetized children (2-15 yrs) and anaesthetized adults (19-61 yrs). Cells from the awake adults were also studied after storage for 24 h in tissue culture medium. CBF was measured in vitro with a photometric technique at room temperature (22.0 +/- 1.5 degrees C). Samples were mounted in a perfusion chamber and challenged with either control solutions, dibutyryl cAMP (10(-4) or 10(-3) M), or the cyclic nucleotide-dependent protein kinase inhibitor 1-(5-isoquinolinylsulphonyl)-2-methylpiperazine (H-7). Dibutyryl cAMP (10(-3) M) caused a significant increase in CBF in all groups studied: awake adults (+1.1 Hz; p less than 0.01), anaesthetized children (+1.2 Hz; p less than 0.01), anaesthetized adults (+1.2 Hz; p less than 0.01), stored cells (+1.1 Hz; p less than 0.01). This response was inhibited by preincubation with H-7 (10(-4) and 10(-3) M). It is concluded that cAMP is a regulator of ciliary activity in human respiratory epithelium.
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
Evidence against the involvement of nonenzymatic glycosylation in diabetic cardiomyopathy.
There is evidence to suggest that increased nonenzymatic glycosylation (NEG) occurs in hyperglycemic states such as seen in diabetes mellitus. In order to examine the hypothesis that the development of cardiomyopathy in diabetes results from an increased nonenzymatic glycosylation of cardiac sarcolemmal proteins, rats were made diabetic by an intravenous (IV) injection of streptozotocin (65 mg/kg). Twelve weeks after the induction of diabetes, animal showed significantly lower heart rate, left ventricular systolic pressure, rate of contraction (+dp/dt), and rate of relaxation (-dp/dt), whereas left ventricular diastolic pressure was markedly increased. Furthermore, cardiac sarcolemmal Na+, K+ adenosine triphosphatase (ATPase) activity was significantly decreased in diabetic rats. When examined in cardiac crude membranes, as well as in purified sarcolemmal membranes prepared by two different procedures, the levels of NEG did not differ between control and diabetic animals; however, NEG levels were increased in kidney and skeletal muscle. These results indicate that chronic diabetes is associated with functional and biochemical alterations in cardiac muscle and suggest that NEG of cardiac sarcolemma may not play any role in the development of diabetic cardiomyopathy.
Animals↗
A dose-comparative endocrine-clinical study of leuprorelin in premenopausal breast cancer patients.
Twelve premenopausal patients with advanced breast cancer were randomised to receive 3.75 or 7.5 mg of a slow release formulation of the luteinising hormone releasing hormone agonist leuprorelin once every 4 weeks. All patients were oestrogen receptor positive or unknown. Serum levels of gonadotrophins and oestrogens were suppressed markedly by both doses. All oestrogen values during treatment were within the postmenopausal range except for a single oestradiol level (274 pmol l-1) in one patient on the lower dose. There was no other indication that this lower dose was less effective as an oestrogen suppressant. There were two objective responders to the 3.75 mg dose and three to the 7.5 mg dose. Toxicity was confined almost entirely to hot flushes which occurred in 11/12 patients. We conclude that the slow release formulation of leuprorelin is effective in breast cancer treatment and that there is no major detriment to the use of the 3.75 rather than 7.5 mg dose.
Adult↗
Potency and selectivity of the non-steroidal aromatase inhibitor CGS 16949A in postmenopausal breast cancer patients.
A selective inhibitor of aromatase is widely sought for the treatment of postmenopausal women with breast cancer. CGS 16949A has been shown to be a highly selective, potent inhibitor of aromatase in vitro. Its potency as an oestrogen suppressant and its selectivity were examined by treating 24 postmenopausal patients with advanced breast cancer for 4 weeks with doses of 0.3, 1.0 and 2.0 mg twice daily. The study was conducted in two parts which compared the two lower doses and the two higher doses separately in a cross-over design protocol. All doses significantly suppressed serum oestradiol and oestrone levels below pretreatment levels. Cross-over analysis indicated that the 2.0 mg twice daily dose achieved significantly greater suppression of oestradiol levels than 0.1 mg twice daily but there was no significant differences between any of the doses in the suppression of oestrone. No significant effects were noted on serum levels of LH, FSH, SHBG, prolactin, testosterone, androstenedione, 17-hydroxyprogesterone or cortisol. For the four steroids this was true both for basal samples and those collected after Synacthen stimulation. However, serum aldosterone levels were significantly suppressed by 1.0 mg twice daily CGS 16949A and further suppressed by 2.0 mg twice daily. It is concluded that CGS 16949A is a potent oestrogen suppressant in postmenopausal patients but that its effect is not totally selective.
Aged↗
Nucleolar organizer regions, proliferative activity and DNA index in gastric carcinoma.
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Carcinoma↗