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Biomedical subjects

R Mehta

Publications and source records attributed to R Mehta.

At least 73 records · Page 4Linked to original sources
PubMed1994

Repeated treatment with chimeric anti-CD4 antibody in multiple sclerosis.

We treated 21 multiple sclerosis patients with two to four doses of cM-T412, a chimeric monoclonal antibody against the CD4 antigen found on helper/inducer T lymphocytes. The mean number (+/- standard error) of circulating CD4 lymphocytes decreased from 888 (+/- 81) cells/mm3 at baseline to 246 (+/- 18) after treatment. At 1 year after the last treatment, the CD4 count had recovered to only 335 (+/- 32). The antibody had no effect on CD8 lymphocytes, B lymphocytes, or other leukocytes. Side effects were minimal. Despite the prolonged depletion of CD4 lymphocytes, no opportunistic infections occurred. Only 1 patient had a possible allergic reaction. Most patients were clinically stable, but a few progressed. We conclude that repeated treatment with cM-T412 is effective in reducing the number of circulating CD4 lymphocytes and has no limiting side effects.

Adult↗
PubMed1994

International Commission for Protection Against Environmental Mutagens and Carcinogens. Oxidative DNA damage--the effects of certain genotoxic and operationally non-genotoxic carcinogens.

A wide variety of oxidative DNA lesions are commonly present in untreated human and animal DNA. One of these lesions, 8-hydroxydeoxyguanosine, has been shown to lead to base mispairing (mutation) on DNA replication. Other lesions remain to be investigated in this respect. Oxidative DNA lesions on cell replication may, in appropriate circumstances, lead to proto-oncogene activation. Oxidative DNA damage, on fixation, may also lead to cytotoxicity followed by regenerative proliferation. The probable or possible importance of oxidative DNA damage is reviewed for various classes of carcinogens and natural processes, including metal ions, high-energy radiation, miscellaneous chemicals, tumor-promoting agents, polyhydroxyphenols/quinones, lipid metabolism, peroxisome proliferators and thyroid function. It is concluded that although the evidence needs considerable strengthening in many of these examples, the available information indicates the potential importance of oxidative DNA damage in the induction of tumors by these agents. It is also possible that non-cancerous degenerative diseases associated with aging are the result of the accumulation of lesions resulting from unrepaired oxidative DNA damage.

Animals↗
PubMed1994

Fitness to drive in patients with cirrhosis and portal-systemic shunting: a pilot study evaluating driving performance.

It has been suggested that some patients with cirrhosis are unfit to operate a motor vehicle. However, performance while driving a motor vehicle has not been evaluated in such patients. In this pilot study, we assessed the fitness to drive of stable individuals with cirrhosis and clinical evidence of portal hypertension, portal-systemic shunting and no prior history of hepatic encephalopathy. We examined 15 ambulatory patients with cirrhosis together with 15 age-, educational level- and driving experience-matched healthy controls. Neuropsychological testing was performed with the Reitan trail test, block design and digit symbol tests as well as visual reaction time. A driving test in the laboratory used a film to measure complex visual reaction time (reaction to road symbols) and threat recognition (accident avoidance). Driving on the road was assessed by a licensed Illinois state driving evaluator. Penalty points were given according to 11 standardized driving categories. As a group, patients with cirrhosis had no significant differences in their performance on a simulator or during actual driving conditions when compared to matched controls. Sixty-six percent of the subjects with cirrhosis had two or more abnormal neuropsychological tests, a criterion used to define the presence of subclinical encephalopathy. No deficiencies in simulated or real driving performance was seen when compared to patients with cirrhosis with normal neuropsychological tests. In this study, stable subjects with cirrhosis and evidence of portal hypertension, portal-systemic shunting, abnormal neuropsychological tests and no prior history of overt encephalopathy did not exhibit a major impairment in their fitness to drive.

Adult↗
PubMed1994

Outcome measurement in kidney disease.

The effects of chronic kidney disease have been difficult to quantify using traditional measures of mortality and biological processes. New approaches to the quantification of outcomes in kidney disease are required. A wide variety of methods have become available and are now in use in some studies. Psychometric approaches, such as the Sickness Impact Profile and the Kidney Disease Questionnaire, have been shown to be responsive to change in some clinical studies. In order to estimate the cost-effectiveness of investments in kidney disease, decision theory approaches are required. We argue that these decision theory approaches should be given serious consideration for inclusion in clinical trials and in the US Renal Data System.

Decision Theory↗
PubMed1994

Phase 1 clinical trial of chimeric monoclonal anti-CD4 antibody in multiple sclerosis.

We conducted an open trial of cM-T412, a chimeric monoclonal anti-CD4 antibody, in 29 patients with MS. This antibody caused a prompt and long-lasting depletion of circulating CD4 (helper/inducer) lymphocytes. The mean (+/- SE) CD4 count for the group decreased from 870 (+/- 66) cells/mm3 at baseline to 76 (+/- 11) 3 hours after treatment, and then increased to 425 (+/- 38) at 1 month after treatment and 475 (+/- 39) at 6 months after treatment. Numbers of CD8 (cytotoxic/suppressor) lymphocytes, B lymphocytes, granulocytes, and monocytes changed transiently but showed no significant long-term effects. The most common side effects were headache, nausea, myalgia, fever, and tachycardia occurring in the first few hours after treatment. No serious or unexpected infections or other significant adverse effects occurred. Kurtzke EDSS scores remained stable, and MRI scans showed less contrast enhancement 1 week after treatment. We conclude that treatment of MS patients with cM-T412 chimeric anti-CD4 antibody is well tolerated at the doses tested and produces a long-lasting, selective depletion of CD4 lymphocytes.

Adult↗
PubMed1993

Acute hepatic response to aflatoxin B1 in rats fed a methyl-deficient, amino acid-defined diet.

In order to evaluate the relative contribution of aflatoxin B1 (AFB1)-induced toxicity towards a methyl-deficient diet influenced AFB1 carcinogenesis, a no-observed-effect-level (NOEL) for AFB1, with reference to liver damage, was determined in rats fed a nutritionally complete amino acid-defined basal (CMS) diet or a choline-methionine-deficient (CMD) diet. After 3 weeks of dietary treatment, male Fischer 344 rats received a single, oral dose of AFB1 in the range of 100-600 pg/kg body weight. At 24, 48 and 72 h after AFB1 treatment, six serum biochemical parameters were analysed in parallel with histological examination of liver sections. In rats fed the CMS diet and receiving 250-600 micrograms/kg AFB1, serum levels of glutamyl oxalo-transaminase (SGOT), glutamyl pyruvic transaminase (SGPT), alkaline phosphatase (ALP) and total bilirubin increased, glucose levels decreased and gamma glutamyl transpeptidase (GGT) levels remained unchanged over the 72-h period following mycotoxin treatment. However, at 100 micrograms/kg AFB1, these serum parameters remained at control levels. Pathological examination of liver sections indicated no significant lesions at 100 micrograms/kg AFB1 confirming this as the non-necrogenic dose or NOEL in CMS diet group rats. In contrast, in CMD diet fed rats, serum or pathology data showed no obvious time- or dose-response to mycotoxin treatment, extensive hepatic lipidosis in response to dietary treatment being the only predominant lesion in this diet group. The milder response of CMD rat livers to a single dose of AFB1 suggest a possible reduction in the susceptibility of these livers to AFB1 toxicity.

Aflatoxin B1↗
PubMed1993

In vitro effect of indomethacin on polymorphonuclear leukocyte function in preterm infants.

Random motility and chemotaxis of polymorphonuclear leukocytes (PMN) was evaluated after in vitro exposure to 0, 300, 600, and 900 ng/mL (0.84, 1.68, and 2.52 mumol/L) of indomethacin. PMN were obtained from cord blood of 22 preterm infants of less than 37 wk gestation. For comparison, PMN were obtained from cord blood of seven healthy full-term infants and from venous blood of 10 normal adults. In preterm infants, a significant decrease of random motility and chemotaxis of PMN was noted at all three drug concentrations; impairment of PMN function was dose dependent in the three groups (p < 0.0001), with the greatest effect seen at 900 ng/mL (2.52 mumol/L). Significant impairment of random motility was noted in full-term infants when compared with adults at all indomethacin concentrations and in chemotaxis at 300 and 600 ng/mL (0.84 and 1.68 mumol/L). The study indicates that indomethacin has an adverse effect on PMN random motility and chemotaxis, which is more pronounced in preterm infants.

Adult↗
PubMed1993

Effect of maternal labor and mode of delivery on polymorphonuclear leukocyte function in healthy neonates.

In this study, effect of maternal labor and mode of delivery on polymorphonuclear leukocyte (PMN) chemiluminescence and random and chemotactic motility was evaluated in healthy full-term neonates. PMN were obtained from cord blood of three groups of neonates: group I, 24 vaginally delivered neonates; group II, 22 neonates delivered by elective cesarean section without labor; and group III, 18 neonates delivered by cesarean section after labor. In group III, six neonates were delivered by cesarean section for fetal distress with acidemia and 12 for failure of progression of labor. Peak chemiluminescence of PMN in group III was depressed compared with groups I and II (p < 0.01). There was no difference in the peak chemiluminescence of PMN from neonates in group I versus group II. Random motility of PMN in group III was increased compared with the random motility in groups I and II (p < 0.05). Chemotactic motility of PMN was comparable in all three groups. In group III, a negative correlation was noted between peak chemiluminescence of PMN and the duration of labor (p < 0.001), whereas no such correlation was observed in group I despite a similar duration of labor. There was no correlation between duration of labor and random and chemotactic motility of PMN in groups I and III. The results of this study indicate that labor and mode of delivery per se have no effect on PMN function and that factors other than labor such as fetal acidemia, fetal distress, arrested labor, or maternal administration of drugs may play a role in alteration of PMN function.

Cell Movement↗
PubMed1993

Perinatal mortality in caesarean section: a disturbing picture of unfulfilled expectations.

Indications for caesarean section had been studied in a 2-year period and the incidences were compared to that of the same 15 years back. Though there are more incidences of caesarean section, still perinatal death is a major concern to all. The study included a total of 291 perinatal deaths of which there were 208 early neonatal deaths and 83 stillbirths over a period of 2 years from January, 1990 to December, 1991. Caesarean section is being increasingly performed for foetal interest, but this study reveals that perinatal mortality is still high though cesarean section rate has increased in recent times.

Cesarean Section↗
PubMed1992

Portal-systemic shunting and the disruption of circadian locomotor activity in the rat.

To determine if the extent of portal-systemic shunting (PSS) influences the disruption of circadian function in chronic liver disease, locomotor activity was examined in two rat models with varying degrees of PSS, i.e., portal vein ligation (PVL) and end-to-side portacaval anastomosis (PCA). Animals were housed in individual activity cages under conditions of 12 hour light/12 hour darkness (weeks 0-3), then under conditions of constant dim light (weeks 4-7). Cages were equipped with running wheels connected to a continuous recorder, and daily tracings of running activity were recorded for 7 weeks. Computer analysis of wheel revolutions per hour with a chi 2 periodogram was used to calculate Qp, a measure of the amplitude of a circadian rhythm. The degree of PSS was measured by means of radioactive microspheres injected into the ileocolic vein and spleen. PVL rats were found to have PSS from the splenic and mesenteric territories of 88% and 27%, respectively; circadian periodicity was maintained in all PVL rats. PCA rats had complete shunting (greater than 99%) and showed a range of disrupted circadian rhythms from blunting of the amplitude to complete absence of the locomotor activity rhythm. This spectrum of disorganization occurred in spite of similar degrees of liver atrophy and weight gain. Whereas PCA in rats markedly disturbs the circadian rhythm of locomotor activity, animals with considerably less PSS from PVL exhibit normal behavior. The extent of PSS could be a variable affecting the expression of circadian rhythms in liver disease.

Animals↗
PubMed1992

Level of DNA double-strand break rejoining in Chinese hamster xrs-5 cells is dose-dependent: implications for the mechanism of radiosensitivity.

Rejoining of DNA double-strand breaks (dsb) was measured in a dsb repair-deficient mutant of CHO cells, xrs-5, after exposure to various doses of X-rays in the range between 15 and 50 Gy. For the experiments plateau-phase cultures were employed and dsb assayed by a pulsed field gel electrophoresis assay, the asymmetric field inversion gel electrophoresis (AFIGE). The half-times of dsb rejoining were larger in xrs-5 than in parental CHO cells and increased in both cell lines with increasing dose of radiation. The fraction of dsb remaining unrejoined after 240 min incubation at 37 degrees C was also higher in xrs-5 than in CHO cells, but decreased with decreasing dose of radiation. Although a decrease in the fraction of unrepaired dsb with decreasing dose has also been reported for repair-proficient cell lines, the extent of the phenomenon and its dependence on dose are entirely different in xrs-5 cells. We propose that this decrease in the fraction of unrejoined dsb with decreasing dose of radiation derives from the genetic alterations underlying the increased sensitivity to radiation of xrs-5 cells, and should be considered whenever results at the DNA level are correlated to results at the cell level. It is likely that similar responses will also be observed in other radiation-sensitive mutant cell lines deficient in dsb repair. There was no difference in the induction of dsb per Gy and dalton, as measured with AFIGE, between CHO and xrs-5 cells tested either in the exponential or in the plateau phase of growth.

Animals↗
PubMed1992

Liver DNA adducts in methyl-deficient rats administered a single dose of aflatoxin B1.

Using an 8 week Solt-Farber protocol with selection pressure (2-acetylaminofluorene/partial hepatectomy) applied during weeks 6 and 7, we have observed that a single oral administration of aflatoxin B1 (AFB1) to Fischer 344 rats on day 1 of the study, followed by a 3 week feeding regimen of either a methyl-deficient (CMD) or a basal (CMS) diet, results in a relative increase in hepatic preneoplastic lesions in CMD diet fed rats. It has previously been shown that a multiple dosing regimen with AFB1, started after 3 weeks of CMD diet, enhances tumor incidence. In the present study, the role of metabolic activation in the induction of preneoplastic lesions, and liver DNA adduct levels after the first dose of AFB1 in the tumorigenesis model have been investigated. AFB1-DNA adducts were determined at 2-168 h following a single non-necrogenic (100 micrograms/kg body wt) or necrogenic (600 micrograms/kg body wt) dose of AFB1 on day 1 or day 21 of a 3 week treatment with a complete basal or CMD diet. In all rats irrespective of dose, dietary treatment or time of AFB1 dosing, the patterns of adduct formation and repair did not change. In rats receiving AFB1 on day 1, total DNA adduct levels between the diet or dose groups were not significantly different, and quantitatively did not correlate with the observed increase in preneoplastic lesions, suggesting a contribution by additional factors in the initiation of these lesions. Administration of AFB1 on day 21, however, resulted in significantly reduced levels of total adducts at both dose levels in CMD diet fed rats compared to controls. Serum biochemistry data suggest that a prolonged exposure to CMD diet may cause pathological and/or biochemical alterations in hepatocytes with a resultant decrease in metabolic activation of AFB1, thus making it difficult to evaluate whether DNA damage is directly related to tumorigenesis.

2-Acetylaminofluorene↗
PubMed1992

Thermogenesis after surgery: effect of perioperative heat conservation and epidural anesthesia.

Body temperature, respiratory gas exchange, and plasma catecholamines were determined before and after surgery in three groups [control (C), warmed (W), and epidural (E) who received local anesthetic at T4-S5 dermatomes during and for 24 h after surgery] of patients undergoing colonic surgery under general anesthesia. At the end of surgery, group W were nursed in an ambient temperature of 28-30 degrees C, whereas the others were at 20-23 degrees C for a period of 24 h. Core (Tc) and dorsal hand temperature decreased during surgery in both C and E (P less than 0.05) but not in W. After surgery, Tc increased similarly in C and E and by a smaller amount in W. Plasma catecholamine concentrations increased significantly in C and W but not in E (P less than 0.001), with the greatest response occurring in C. Postoperative oxygen consumption and carbon dioxide production exceeded preoperative values (P less than 0.01) in C but not in W or E. After surgery, plasma albumin fell and C-reactive protein increased similarly in all three groups. Thus body heat conservation or epidural blockade attenuates or abolishes the rise in plasma catecholamines and oxygen consumption postoperatively but does not prevent the increase in Tc or the acute phase protein response.

Anesthesia, Epidural↗
PubMed1992

Localization and detection of ovarian follicular fluid protein in follicles of human ovaries.

Human ovarian follicular fluid protein has been partially purified and the active fraction designated as hGF2. Using specific polyclonal antiserum to hGF2, it was observed to be localized immunohistochemically in the granulosa cells of medium but not large follicles of human ovary. The hGF2 levels were estimated by ELISA in serum and follicular fluid of 10 gonadotropin-stimulated women recruited for IVF-ET programme. The results revealed a 3-fold increase in the concentration of hGF2 in follicular fluid compared to that in serum of these patients. These data indicate that the protein is secreted by granulosa cells and plays an important role in the regulation of follicular maturation and ovulation.

Chorionic Gonadotropin↗
PubMed1992

Gait in relation to ageing and idiopathic parkinsonism.

Distance/time measures of gait in 105 sufferers from idiopathic Parkinsonism, who were able to walk unaided, and 144 healthy controls were examined systematically. Those sufferers with overt fluctuations in control were assessed during their "therapeutic window". Free walking speed was lower for a given cadence in the sufferers, but reached a plateau whilst cadence could still be increased. Age, cognitive function and the range of passive hip flexion were important determinants of gait in them. Even minor degrees of cognitive impairment were associated with reduced free walking speed in sufferers: it appears unwise that they were prescribed more sedatives than the controls. The potential benefit of physiotherapy in maintaining joint flexibility was noted. The deficits in speed of individual sufferers, and hence the estimated potential for prophylaxis and treatment, were unrelated to age at presentation. There was no evidence for a limited period of responsiveness to levodopa therapy in this cross-sectional study.

Adult↗
PubMed1992

Zinc deficiency reduces hepatic cellular retinol-binding protein in rats.

Hepatic cellular retinol-binding protein (cRBP) levels were measured from the livers of four groups of Sprague-Dawley rats after three weeks of dietary treatment. The experimental group (n = 8) received a zinc-deficient (2.3 mg/kg dry powder) liquid diet ad libitum. A pair-fed control group (n = 8) received the same amount of liquid diet with supplemental zinc (60 mg/kg dry powder). Another control group (n = 8) received liquid diet ad libitum with supplemental zinc (60 mg/kg powder). A third control group (n = 7) received a pellet diet which also contained the same amount of zinc as the other control groups (60 mg/kg). Hepatic cRBP was reduced by more than 50% in the experimental group as compared to each of three control groups. It appears that zinc may be an essential element for the intra-cellular transport of vitamin A, in addition to its well-established role in the intercellular transport of vitamin A.

Animals↗