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Biomedical subjects

R Mehta

Publications and source records attributed to R Mehta.

At least 127 records · Page 7Linked to original sources
PubMed1987

Amsacrine treatment of patients with supraventricular arrhythmias and acute leukemia.

Three patients with a history of supraventricular arrhythmia presented with relapse of acute leukemia. Two of the three patients were in sinus rhythm, receiving digoxin and/or verapamil daily. The third patient was in atrial fibrillation, but her heart rate was controlled with daily digoxin. All three patients received amsacrine without the occurrence of cardiac events. Although amsacrine may cause ventricular arrhythmias in the setting of hypokalemia, correction of the electrolyte abnormality permits its use in patients with a history of supraventricular arrhythmias.

Acute Disease↗
PubMed1987

Micronucleus formation induced in rat liver and esophagus by nitrosamines.

The rat hepatocarcinogen nitrosodimethylamine and the esophageal carcinogens nitrosomethylbenzylamine and nitrosomethylamylamine were shown to produce chromosomal damage, as manifested by micronucleus formation, in their target tissues. There was cross-reactivity in the two tissues, however, at high dose levels. Nitrosodiethylamine, which produces tumors in both the liver and esophagus in the rat, also produced micronuclei in both tissues.

Animals↗
PubMed1987

Synergistic antifungal activity and reduced toxicity of liposomal amphotericin B combined with gramicidin S or NF.

Amphotericin B (AmpB) disrupts membrane integrity by binding to sterols in fungal and mammalian cell membranes. The gramicidins, which form pores in all membranes but exhibit poor antifungal activity, are too toxic to mammalian cells to be used systemically. This study demonstrated synergistic antifungal activity of free and liposomal forms of AmpB when combined with the free and liposomal forms of gramicidin S and gramicidin NF against five Candida strains. In vitro erythrocyte lysis was prevented by using the liposomal forms of all drugs tested alone or in combination. Presumably, AmpB increases accessibility of the fungal cell membrane to the gramicidins, while liposome encapsulation decreases the rate of transfer of the drugs to the mammalian cell membrane. Liposome encapsulation of inactive or toxic drugs, used in combination with liposomal AmpB, may give new life to drugs previously believed to be inactive or too toxic for therapeutic consideration.

Amphotericin B↗
PubMed1987

A new regimen of amsacrine with high-dose cytarabine is safe and effective therapy for acute leukemia.

Amsacrine and high-dose cytarabine (HiDAc), when administered as single agents, are effective treatment of acute leukemia. When used in combination, a high remission rate is also possible. We treated 47 patients with acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), and blastic phase of chronic myelogenous leukemia (CML) with a combination of amsacrine and HiDAc. The patients received amsacrine 200 mg/m2 daily for three days and, concurrently, HiDAc 3 g/m2 over three hours once daily for five days. Of 20 evaluable patients with AML in relapse, there were 12 remissions; of seven additional patients with primary refractory AML, there were two remissions, and of 12 patients with ALL in relapse, there were eight remissions. The three patients with blastic phase CML and the three patients with biphenotypic leukemia did not respond. Nausea, vomiting, stomatitis, hepatic dysfunction, and diarrhea were common, but cutaneous, conjunctival, and significant cerebellar and cerebral side effects were absent. We conclude that this regimen is highly effective therapy for AML and ALL and is also safe, eliminating the major toxicities encountered with HiDAc.

Acute Disease↗
PubMed1986

Polymerized phospholipid vesicles containing amphotericin B: evaluation of toxic and antifungal activities in vitro.

We have prepared lipid vesicles (liposomes) composed of polymerized bis[12-(methacryloyloxy)dodecanoyl]-L-alpha-phosphatidylcholine (DPL) which contain the antifungal polyene antibiotic amphotericin B (AMB). It was necessary to devise a novel method for incorporating AMB into the liposomes subsequent to polymerization. The polymer liposome AMB was as effective as AMB in "conventional" liposomes in terms of inhibiting fungal growth in vitro. However, in contrast to "conventional" liposomes, the polymerized DPL vesicles did not protect mammalian cells against AMB induced toxicity.

Amphotericin B↗
PubMed1986

Acute and long term effect of nifedipine on pulmonary hypertension secondary to chronic obstructive airways disease.

To determine whether Nifedipine reduces pulmonary artery pressure and pulmonary vascular resistance in patients with hypoxic pulmonary hypertension, we have studied ten clinically stable patients with chronic obstructive airways disease following acute administration of sublingual Nifedipine 20 mg and also after three months long term treatment with Nifedipine tablets 20mg bd. In the acute study, Nifedipine significantly raised mean pulmonary artery pressure from 30.32 +/- 13.07 mm Hg to 34.15 +/- 14.33 mm Hg (p less than 0.001) and pulmonary wedge pressure from 6.15 +/- 5.09 mm Hg to 7.6 +/- 3.39 mm Hg (p less than 0.1). There was a significant fall in mean systematic artery pressure from 99.06 +/- 12.05 mm Hg to 89.47 +/- 10.04 mm Hg (p less than 0.005) and a rise in heart rate from 79 +/- 9.7 beats/minute to 85.45 +/- 13.46 beats/minute (p less than 0.5). There was a significant change in cardiac index from 2.96 +/- 0.76 l/min/m2 to 3.2 +/- 0.51 l/min/m2 p(less than 0.1). There was no statistically significant change in pulmonary vascular resistance from 5.06 +/- 3.45 mm Hg/l/min to 4.92 +/- 3.10 mm Hg/l/min. In the long term study, no statistically significant differences over the base line values were found in measurements of mean pulmonary artery and pulmonary wedge pressures, mean systemic artery pressure, cardiac index and PO2. There was a greater fall in pulmonary vascular resistance in comparison with the acute study. The pulmonary vascular resistance fell from 5.06 +/- 3.45 mm Hg/l/min to 4.24 +/- 2.31 mm Hg/l/min but did not achieve statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1985

Liposomal amphotericin B for the treatment of systemic fungal infections in patients with cancer: a preliminary study.

Twelve patients with hematologic malignancies complicated by fungal infections were treated with liposomal amphotericin B (L-AmpB). Nine patients were granulocytopenic; the three additional patients with normal granulocyte counts were immunosuppressed. All patients had biopsy findings or cultural evidence of the progression of their fungal infection while being treated with conventional amphotericin B. Doses of 0.8-1.0 mg/kg of L-AmpB were administered intravenously every 24-72 hr. Three patients had a complete remission, five had a partial remission, and four showed no improvements. A total of 161 doses of L-AmpB were administered. Fever and chills occurred on seven occasions. No hematologic or blood chemistry abnormalities related to L-AmpB treatment were observed.

Adolescent↗
PubMed1985

Selective toxicity and enhanced therapeutic index of liposomal polyene antibiotics in systemic fungal infections.

Incorporation of the polyene antibiotic amphotericin B (AMB) in liposomes results in a marked reduction in drug toxicity with no loss of antifungal potency. Nephrotoxicity, the dose-limiting side effect of AMB, is almost abolished when the drug is utilized in a liposomal carrier. Because of reduced toxicity, high doses of liposomal AMB can be used, resulting in superior therapy of systemic fungal infections in mice. The improved therapeutic index of liposomal AMB versus free AMB is also manifest in infected neutropenic animals. The reduced toxicity of liposomal AMB is due to a fundamental alteration in the interaction of the drug with mammalian cell membranes. AMB transfers effectively from donor liposomes to fungal cell walls and membranes and is thus toxic to fungi. By contrast, AMB does not transfer from liposomes to mammalian cells and thus is not toxic to these cells. Thus, the use of liposomal AMB may offer a marked improvement in the therapy of systemic fungal infection in cancer patients and other immunodebilitated individuals.

Amphotericin B↗
PubMed1985

Brainstem auditory evoked potentials in chronic renal failure and maintenance hemodialysis.

Brainstem auditory evoked potentials (BAEPs) were recorded in 36 chronic uremic patients maintained on hemodialysis and in 10 normal controls. Both absolute response latencies and central transmission times were affected. There were transitory increases in interpeak latencies of I-II and III-V that were reversed by dialysis. A permanent increase in wave III-V interpeak latency was not reversed by dialysis. Wave II-III interpeak latency was unaffected.

Adult↗
PubMed1985

Cortically evoked motor action potential in spinal cord injury research.

Somatosensory evoked potentials (SEPs) have been used extensively in the neurophysiological assessment of spinal cord integrity. However, SEPs mainly reflect the function of the dorsal column. In an effort to find a reliable method of assessing the integrity of the motor tracts for experimental purposes, we studied cortically evoked motor action potentials (CEMAPs). Twenty white rats used were anesthetized with ketamine, and extradural cortical stimulation was carried out through a parasagittal craniectomy posterior to the coronal suture. A single stimulus of 325 mV for a duration of 0.1 to 0.5 ms was used to obtain a motor action potential from the contralateral lower extremity. Complete transsection of the spinal cord abolished the CEMAP. A progressive increase in pressure applied to the spinal cord with a progressive increase in duration produced loss of the CEMAP. The selective motor tract study made possible by cortical stimulation makes this a good technique for studying the motor tracts in experimental work.

Animals↗
PubMed1984

Liposomal amphotericin B is toxic to fungal cells but not to mammalian cells.

Amphotericin B is an efficacious but extremely toxic anti fungal drug. Recently it has been shown that the incorporation of Amphotericin B in multilamellar liposomes results in a marked reduction in drug toxicity in mice with no loss of anti fungal potency. Until now, the mechanistic basis of the enhanced therapeutic index of liposomal Amphotericin B has been unclear. In this report, however, we show that the in vivo effects can be mimicked in vitro where free but not liposomal Amphotericin B causes lysis of erythrocytes while both free and liposomal drug kill fungal cells. These results suggest that the markedly improved therapeutic index of liposomal Amphotericin B is largely due to a fundamental alteration in the ability of the drug to interact with mammalian cell membranes rather than to alterations in pharmacokinetics or drug distribution.

Amphotericin B↗
PubMed1984

Acute renal failure following poisonous snakebite.

This study describes acute renal failure (ARF) following snakebite in humans and the effects of viperide venoms on the renal structure and function in subhuman primates. ARF developed in 45 of 157 patients with a history of snakebite admitted to the hospitals of the Postgraduate Medical Institute, Chandigarh, India. They were studied clinically, hematologically, and in 35 cases, for renal histopathology. All 45 were treated with antibiotics, and 8 received anti-snake venom. Ten cases had bilateral renal cortical necrosis (BRCN), eight of whom died; less severe acute tubular lesions (ATL) occurred in 23 patients, four of whom died (P less than .001). Sepsis was significantly more common with BRCN than ATL (P less than .05). No statistical difference was found between these groups in bleeding incidence, disseminated intravascular coagulation (DIC), hemolysis, or hypotension. Monkeys given lethal doses of viperide venom developed hypotensive shock, DIC, and hemolysis, with significantly reduced serum complement, and died within 24 hours. However, no renal functional changes or lesions were found. Monkeys given sublethal doses of viperide venom showed a significant increase in serum creatinine levels after 48 hours, and renal lesions were observed in a majority of animals. In conclusion, ARF in snakebite victims appears to be multifactorial in origin. Although hypotension, hemolysis, and DIC are likely to be important pathogenetic factors, a direct cytotoxic effect of the venom on the kidney in producing ARF cannot be excluded.

Acute Kidney Injury↗