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Biomedical subjects

P Joseph

Publications and source records attributed to P Joseph.

At least 19 recordsLinked to original sources

Effect of vitamin A on hexachlorocyclohexane (HCH) toxicity in the rat.

1. Technical hexachlorocyclohexane (HCH) depleted hepatic stores of vitamin A in male albino rats to cause secondary vitamin A deficiency. 2. Toxicity of HCH in rats is augmented by dietary vitamin A-deficiency as evidenced by growth retardation, organ hypertrophies and alterations in the serum and liver levels of the marker enzymes of toxicity. 3. Supplementation of dietary vitamin A to the rats either in adequate (2000 IU/kg diet) or in an excess but not hypervitaminotic level (10(5) IU/kg diet) resulted in significant protection against the toxicity of HCH. 4. The activities of the hepatic xenobiotic metabolizing enzymes were generally low (with the exception of glutathione S-transferase) in the vitamin A-deficient rats compared to those of the vitamin A supplemented diet groups. 5. The results indicated that dietary vitamin A influences the response of male albino rats to HCH toxicity possibly by modulating the activities of hepatic xenobiotic metabolizing enzymes.

Animals

Inhibition of human term placental and fetal liver glutathione-S-transferases by fatty acids and fatty acid esters.

Glutathione-S-transferase (GST) activity from human term placenta and human fetal liver towards 1-chloro-2,4-dinitrobenzene as the second substrate was significantly inhibited by the saturated fatty acids, stearic (SA) and palmitic (PA) acids and fatty acid esters, ascorbyl stearate (Asc-S) and ascorbyl palmitate (Asc-P). The nature of inhibition of human placental GST was competitive towards CDNB with Ki values of 3.1, 10.0, 13.5 and 18.5 microM for Asc-S, Asc-P, PA and SA, respectively. The inhibitory effect of Asc-S on human term placental GST was reversible. I50 values for Asc-S, Asc-P, SA and PA were 15, 45, 83 and 78 microM, respectively, for partially purified human fetal liver GSTs and 21, 6, 88 and 117 microM, respectively, for partially pure rat liver GSTs. The evidence suggests that Asc-S, Asc-P, SA and PA are potent inhibitors especially of the pi-class of GST.

Animals

Role of vitamin A in the haematotoxicity of hexachlorocyclohexane (HCH) in the rat.

The haematotoxicity of technical hexachlorocyclohexane (HCH) (1000 ppm) was investigated in male albino rats fed with diet free of vitamin A or containing vitamin A at 2000 or 10(5) I.U./kg. Assessment of HCH-induced haematotoxicity at the end of the 7 weeks feeding period was done on the basis of haemoglobin content, total count of red blood cells and white blood cells and the differential counts of the white blood cells as well as by parameters such as packed cell volume, mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin content, prothrombin time and clotting time. In the rats fed with vitamin A-free diet containing HCH, significant reductions were noticed in the total white blood cells count, clotting time and prothrombin time indicating severe haematotoxicity. Differential count of the white blood cells of these rats revealed a non-significant reduction in the lymphocyte count. The only indication of haematotoxicity caused by hexachlorocyclohexane in the vitamin A supplemented rats was a slight but statistically significant reduction of the total count of white blood cells. These results demonstrate that the haematotoxicity of hexachlorocyclohexane in the rats is enhanced by vitamin A-deficiency and its supplementation particularly in excess but not at hypervitaminotic level is protective against the toxicity.

Animals

Intravenous or inhaled pentamidine for treating Pneumocystis carinii pneumonia in AIDS. A randomized trial.

OBJECTIVE: To evaluate the efficacy and toxicity of aerosolized pentamidine and of reduced-dose intravenous pentamidine for the treatment of mild to moderate Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN: Randomized open study with serial pulmonary function testing and measurement of pentamidine concentrations in plasma and bronchoalveolar lavage fluid. PATIENTS: Of 44 men and 1 woman with a mild to moderate first episode of P. carinii pneumonia (Pao2 greater than or equal to 7.3 kPa [55 mm Hg]), 23 received aerosolized pentamidine and 22, intravenous pentamidine. INTERVENTIONS: Pentamidine isethionate, 600 mg by inhalation using a Respirgard II nebulizer (Marquest Medical Products, Inc., Englewood, Colorado) or 3 mg/kg body weight intravenously, administered once daily for 2 to 3 weeks. MEASUREMENTS AND MAIN RESULTS: The planned 60-patient study was stopped after 45 patients had been enrolled. The rates (aerosolized compared with intravenous pentamidine) of initial failure, early recrudescence of symptoms, and relapse were 12% and 19% (difference, 7%; 99% confidence interval [CI], - 23% to 37%; P = 0.67), 35% and 0% (difference, 35%; CI, 13% to 58%; P = 0.02), and 24% and 0% (difference, 24%; CI, 4% to 49%; P = 0.03). The rates (aerosolized compared with intravenous pentamidine) of major toxicity were 0% (0 of 17 patients) and 10% (2 of 21 patients) (difference 10%; CI, -1% to 29%; P = 0.24). The mean (+/- SD) pentamidine concentration in bronchoalveolar lavage fluid for patients receiving aerosolized pentamidine was 96.6 +/- 65.1 ng/mL compared with 14.4 +/- 17.7 ng/mL for patients receiving intravenous treatment. Trough concentrations of pentamidine in plasma increased from 0 to 25.4 +/- 16.4, 56.5 +/- 26.1, and 61.1 +/- 56.0 ng/mL at the end of weeks 1, 2, and 3 of intravenous therapy, respectively. CONCLUSIONS: The data suggest that reduced-dose intravenous pentamidine was more effective than aerosolized pentamidine for treating mild to moderate P. carinii pneumonia. Systemic absorption during aerosolized therapy was minimal; daily doses of intravenous pentamidine resulted in increased accumulation of pentamidine in plasma.

Acquired Immunodeficiency Syndrome

Omental pedicle grafting in the treatment of postcardiotomy sternotomy infection.

Postcardiotomy sternal infection occurred in 20 (2%) of 1007 patients undergoing cardiac surgery between September 1985 and December 1987, a 10-fold increase over the preceding 33 months (4 [0.24%] of 1627 patients). Cultures were sterile in 5 patients and yielded staphylococci in 12 and a variety of bowel organisms in 3. The cause for the increased occurrence of sternal wound infection is unclear after multivariate analysis, although infections have precipitously dropped subsequent to changing to cefuroxime sodium antibiotic prophylaxis. Treatment has evolved to appropriate antibiotics and early débridement of involved sternum and cartilage. Rewiring the sternum is not attempted. If gross purulence is not present, primary closure is accomplished using muscle flaps (2 patients) or omental pedicle grafts (17 patients). In the presence of gross purulence, the wound is packed open for 5 days and then closed in the above fashion. Two patients required skin grafts for primary closure. The omental pedicle flap is preferred due to simplicity and improved coverage of the sternal defect inferiorly. Nineteen patients healed primarily. A superficial wound infection was drained in 1 patient. Midline incisional hernias developed in 3 muscular patients. Omentum is now harvested through a left subcostal incision. Hospital stay was under 2 weeks in 13 patients. One death occurred due to multisystem failure prior to completion of wound closure. In our experience, early sternal débridement and omental pedicle grafting with primary closure is appropriate therapy for postcardiotomy sternotomy infections. The presence of gross purulence may require 5 days of open packing prior to omental grafting. No significant complications occurred, and mortality was low. A left subcostal incision for omental harvesting is utilized to avoid the occurrence of delayed incisional hernias.

Cardiac Surgical Procedures

Impairment of cerebral function following cardiac and other major surgery.

Patients undergoing routine coronary artery surgery (N = 76) were compared with those undergoing other major operations (N = 29) in a prospective multidisciplinary study designed to define the incidence of neurological and psychological sequelae. The preoperative state of the carotid and vertebral arteries was defined by digital subtraction angiography. Changes in clinical neurological examination, detailed neuropsychological testing, psychiatric assessment and cerebral blood flow were measured. All preoperative studies were repeated 8 days and 8 weeks after surgery. Clinical neurological examination was repeated in addition on the 1st postoperative day. New focal neurological signs were found in 8% of the cardiac patients and none of the comparison group 24 h after operation (P = 0.9). Global transient neurological dysfunction occurred in 59% of the coronary group in the 1st postoperative day compared with 21% in other forms of surgery (P = 0.0007) but this correlated with postoperative narcotic and sedative drugs. A deterioration in neuropsychological performance was detectable in 73% of coronary cases at 8 days which was more likely to occur with increasing age, longer bypass time and lower perfusion pressure, but similar neuropsychological changes also occurred in 50% of the comparison group. By 8 weeks, there was a significant improvement in the cardiac patients (37%, P less than 0.001) but not in the other group. Cerebral blood flow was reduced at 8 days in the coronary bypass patients but not in the comparison group suggesting that the mechanism of cerebral change may be different in the two groups.

Adult

Zidovudine-induced fever.

Zidovudine (3'-azido-3'deoxythymidine, AZT, Retrovir) is the first antiretroviral drug to demonstrate clinical efficacy for symptomatic human immunodeficiency virus infection. In a large, placebo-controlled trial, nausea and hematologic toxicity, but not fever, occurred more frequently in zidovudine- than in placebo-treated patients. However, in an open label study, fever severe enough to halt zidovudine administration occurred in 10% of 70 acquired immune deficiency syndrome (AIDS) patients receiving the drug. We now describe three AIDS patients with severe zidovudine-induced fever in whom other causes of fever were excluded. Zidovudine-induced fever was confirmed in each case by drug rechallenge. Using an enzyme immunoassay, we detected IgM antibodies directed against a zidovudine-serum protein conformational determinant in one of these three patients. Neither IgG nor IgM anti-zidovudine antibodies were present in sera from the other two patients with zidovudine fever, from four AIDS patients who discontinued zidovudine for reasons other than fever, or from five AIDS patients who never received zidovudine. Zidovudine may cause fever as a severe adverse effect in patients with AIDS. Either type III or type IV hypersensitivity may mediate this reaction.

Acquired Immunodeficiency Syndrome

Response of blood and brain cholinesterase to dermal exposure of bromophos in the rat.

Response of cholinesterase to dermal exposure of acute, single and multiple doses of Bromophos in the female rat has been studied. Dose-response studies (50-4000 mg/kg body weight, 24 h exposure) showed that plasma cholinesterase was most sensitive to inhibition in vivo, followed by the brain and erythrocyte acetylcholinesterase. The ID50 values for the in vivo cholinesterase inhibition were 10.1, 576.1 and 1938.0 mg/kg body weight for the plasma, brain and erythrocytes, respectively. In time-course studies after a single sublethal dose of 1000 mg/kg body weight (24 h) of Bromophos, the serum and brain cholinesterase were rapidly inhibited reaching a maximum at 16 h. Recovery was complete in the case of serum at 14 days post-exposure, whereas the brain enzyme was not fully recovered at 21 days. In a subacute study, daily dermal application of 50 mg/kg body weight of Bromophos for 5 and 10 days, resulted in high inhibition of the serum cholinesterase and brain acetylcholinesterase, the former being more marked which was reversible after 10 or 15 days of post-exposure period. Very low levels of dermal exposure of Bromophos (10-50 mg/kg body weight) for 17 days caused pronounced depression of serum cholinesterase which completely recovered in 15 days after cessation of exposure suggesting that the serum cholinesterase could serve as the most sensitive diagnostic indicator of Bromophos exposure.

Animals

Cerebral consequences of cardiopulmonary bypass.

55 patients undergoing coronary-artery bypass surgery (CABS) and a comparison group of 20 patients having thoracic or major vascular surgery were investigated preoperatively and 8 days and 8 weeks postoperatively for changes in neuropsychological status, psychiatric state, cerebral blood flow, and neurological signs, this last being assessed also at 24 h. Major persisting neurological changes were rare, but minor abnormalities were significantly more common after CABS than after thoracic or vascular surgery. Neuropsychological deficits were common at 8 days in both CABS and comparison groups, and in about a third of all patients persisted at 8 weeks. Cerebral blood flow was reduced at 8 days in some CABS patients, but this was not significant for the group. Pre-existing cerebrovascular disease was not predictive, but low perfusion pressure and long bypass time were associated with postoperative deficits.

Adult

Temporomandibular joint: magnetic resonance imaging.

Magnetic resonance (MR) imaging of the temporomandibular joint was performed in two subjects using a 1.5 T experimental imaging system equipped with a 6.5 cm surface coil antenna. Normal and pathologic anatomy were demonstrated with exquisite detail. Anterior displacement of the joint meniscus was clearly visible in the symptomatic subject, consistent with arthrographic confirmation.

Adult

Contrast enhancement of spontaneous animal CNS tumors with gadolinium DTPA: a correlation of MRI with x-ray CT.

A visual comparison was made between both pre-contrast and post-contrast x-ray computerized tomographic images (X-CT) and magnetic resonance tomographic images (MRI) of spontaneous CNS tumors in three animals. The contrast agents, HypaqueR-76 (X-CT) and Gadolinium DTPA (MRI), were administered as an intravenous bolus injection. The parameters for comparison of pre- and post-contrast features included: lesion discrimination, demarcation, and intensity and pattern of enhancement. Necropsy specimens were included to correlate the anatomic fidelity of scan appearances for each modality and to establish a final diagnosis. There was good visual correlation of the lesion site with both X-CT and MRI. The intensity of lesion enhancement with the contrast reagents was similar for each modality but there were subtle differences in the pattern of enhancement. Overall, MRI in conjunction with the contrast agent Gadolinium DTPA, was as good or better at delineating the presence and extent of CNS tumors than contrast enhanced X-CT. Contrast agents may be necessary to provide increased lesion detectability and delineation when imaging with magnetic resonance.

Adenoma

Magnetic resonance imaging of postoperative patients with metallic implants.

Magnetic resonance imaging (MRI) examinations were reviewed in 10 postsurgical patients with metallic implants in the abdomen or pelvis. MRI scans in these patients were free of the streak artifacts commonly encountered in computed tomography. This represents a significant advantage in diagnostic imaging in postsurgical patients, and it suggests that MRI may be a valuable technique in the postoperative assessment of patients with extensive abdominal surgical clips or metallic prostheses.

Adolescent