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Biomedical subjects

N Agarwal

Publications and source records attributed to N Agarwal.

At least 181 records · Page 10Linked to original sources

Effect of acute sublethal and chronic administration of DDT (chlorophenotane) on brain lipid metabolism of rhesus monkeys.

Either a single oral dose of 1,1,1-trichloro-2,2-bis-(p-chlorophenyl) ethane (DDT), 150 mg/kg body weight or a long-term chronic dose of the pesticide, 10 mg/kg body weight daily for 100 days was administered to rhesus monkeys and the level of various lipid classes was studied in the brain. A significant decrease was observed in total lipid, unesterified cholesterol and phospholipid (PL) level. Individual PL fractions showed a generalized pattern of reduction, so also did the cholesterol (chol)/PL ratio. Sphingomyelin (SM) registered a significant increase, while no significant alteration was observed in the brain galactolipid and ganglioside level. Lipid lowering effect of DDT was more pronounced in the chronic group. Lipids associated with the myelin sheath were found to be more resistant to pesticide injury, while cholesterol and PL metabolism were more affected.

Animals↗

Energy expenditure in chronic alcoholics with and without liver disease.

Chronic alcoholism activates metabolic pathways, resulting in wasteful expenditure of energy (Pirola and Lieber, J Nutr 1975;105:1544-8). To study this hypothesis, we measured oxygen consumption (VO2), carbon dioxide production (VCO2), and resting energy expenditure (MREE) utilizing indirect calorimetry in 8 chronic alcoholics with (group I) and 11 chronic alcoholics without (group II) clinical or biochemical evidence of alcoholic liver disease. Seven healthy volunteers served as controls. A statistically increased MREE was observed in group II subjects (p less than 0.05, MREE 999.7 +/- 111.4 kcal X day X m2) as compared to normals (MREE 842.3 +/- 42.1 kcal X day X m2) and group I subjects (MREE 813.4 +/- 101.4 kcal X day X m2). VO2 and VCO2 were also significantly higher (p less than 0.05) in group II than in group I and normals. The predicted resting energy expenditure as calculated by the Harris-Benedict equation was similar in both groups and normals. Theories to explain the increased MREE in group II subjects are presented.

Adult↗

Increased risk of colorectal cancer following breast cancer.

Identification of population groups at increased risk for colorectal cancer is important for deriving maximum benefit from screening procedures. A retrospective analysis of 7605 patients with cancer treated between 1958 to 1982 revealed that the colorectum was the site of metachronous primary in 38 patients (15 males and 23 females). The risk factor of developing the metachronous multiple primary cancer was determined by comparing the observed number of second primary malignancy with the expected number based on person years of observation, age, sex, and site specific incidence rates. Incidence of metachronous colonic cancer was twice the expected number and was the highest following a primary in the breast. This increased risk (2.0) is of equal magnitude as noted following primary colon cancer (1.7). Advanced metachronous colonic lesions were seen more often following breast cancer than following colon cancer. Since carcinoma of the breast is the leading cancer in women, it is urged that the follow-up management of such patients include the same aggressive screening program as that recommended for those with colorectal cancer.

Breast Neoplasms↗

Factors influencing DRG 210 (hip fracture) reimbursement.

The effect of prospective payment system (PPS) on reducing cost and quality of care is still unknown. Fifty-two patients (mean +/- SD, 82.0 +/- 6.5 years) with hip fracture classified as DRG 210 (hip and femur procedures except major joint, age greater than 69 years and/or complication and/or comorbidity), treated by compression nail were separated into four groups: Group I--no comorbidity, no complications; Group II--no comorbidity but had complications; Group III--with comorbidity but no complications; and Group IV--with both comorbidity and complications. Compared to length of stay (LOS) in Groups I, II and III (mean 26 days), Group IV had significantly increased LOS (mean, 61.5 days) and 81% of the 16 who were day outliers (L.O.S. greater than 40 days). Patients without comorbidity (I & II) even if they did develop complications were not financial losers. Those with comorbidity appear to be high-cost patients as they invariably end up with complications (78%), and reimbursement for Group IV was significantly less, resulting in net loss of this DRG. Our finding demonstrates the importance of preventing complications in patients with comorbidity. Present DRG reimbursement guidelines do not provide sufficient attention to LOS implications of both comorbidity and complications. Ideally, they should be considered as separate factors within the DRG category.

Aged↗

Simplified prognostic criteria in acute pancreatitis.

Simplified prognostic criteria (SPC) have been developed for evaluating patients with acute pancreatitis. The criteria based on easily measured biologic and clinical variables were evaluated on all 76 patients with acute pancreatitis treated over a 2-year period. Results were compared with Ranson's early objective sings. All the SPC within 48 h of admission correlated significantly (p less than 0.001) with increased incidence of complications. Of the 11 early objective signs only four--fall in hematocrit, serum calcium, PO2, and fluid sequestrations--were associated with significantly increased complications. The incidence of complications, 48%, seen in patients with one or more SPC was comparable to the 50% seen in patients with three or more Ranson's early objective signs. The results suggest that SPC is a simple, easily applicable gauge that gives valuable assessment of the severity of acute pancreatitis.

Acute Disease↗

Comparison of bentiromide test and rice flour breath hydrogen test in the detection of exocrine pancreatic insufficiency.

Bentiromide test (BT) has been recently approved in the United States for screening patients with chronic pancreatitis for exocrine insufficiency. A few reports have suggested that the rice flour breath hydrogen test (RFBHT)--i.e., breath hydrogen analysis after rice flour ingestion--may also be useful in diagnosing exocrine pancreatic insufficiency. We conducted this study to compare the diagnostic value of these two tests in chronic alcoholic (n = 14) and nutritional or tropical (n = 6) pancreatitis. False-positive results were not noted with either of these two tests in 12 healthy volunteers. BT was positive in 28.6% of patients with chronic alcoholic pancreatitis and in 16.7% of patients with tropical pancreatitis. In comparison, RFBHT was almost twice as sensitive as BT in detecting insufficiency in patients with alcoholic pancreatitis (50 vs. 28.6%) and four times as sensitive in patients with tropical pancreatitis (66.7 vs. 16.7%). Only one patient in our study had a positive BT but a negative RFBHT. We recommend RFBHT as a simple, safe, and inexpensive test in screening patients for exocrine pancreatic insufficiency.

4-Aminobenzoic Acid↗

Clinical zinc deficiency during long-term total enteral nutrition.

Zinc deficiency during long-term total parenteral nutrition has been well reported in the literature. However, there is limited information available on zinc deficiency occurring during total enteral nutrition. Two cases of clinical zinc deficiency in patients on long-term enteral feedings are presented. Nutritional assessment of these two patients on admission revealed hypoalbuminemic malnutrition. Nutritional support in the form of nasogastric tube feedings were initiated in both patients due to altered mental status. The formula used was Ensure (Ross Labs, Columbus, OH), which provided greater than 150% of the RDA for zinc. However, four months and seven months after initiation of adequate nutritional support, both patients developed skin rashes around the groin and under the breasts and axilla. Serum zinc levels were depressed in both patients, to 42 and 54 mg/dL, respectively (normal for the authors' laboratory, 66 to 120 mg/dL). Supplementation with zinc sulfate 220 mg per day via nasogastric tube resulted in disappearance of the rash with return of serum zinc to normal levels. The authors suggest close observation of patients on long-term enteral nutrition for clinical manifestation of zinc deficiency, especially an unexplained skin rash. Further studies are needed to establish minimum daily zinc requirements in patients on long-term enteral feedings.

Aged↗

Isolation and characterization of a Na-H antiporter-deficient mutant of LLC-PK1 cells.

LLC-PK1 is an established cell line derived from pig kidney epithelium; it differentiates in vitro to form a polarized epithelial sheet, capable of the vectorial transport of solutes and water. We have used a modification of the "proton-suicide" method of Pouyssegur et al. (Proc. Natl. Acad. Sci. USA. 81:4833-4837, 1984) to isolate a mutant of LLC-PK1 cells that is deficient in Na-H antiporter activity. The mutant grows normally at pH 7.0 and above in the presence and absence of bicarbonate; at pH 6.5, however, it requires bicarbonate for growth. Alkalinization of the cytoplasm by the Na-H antiporter thus appears to be essential for growth at acidic pH in the absence of bicarbonate. The antiporter is also essential for the formation of domes (a consequence of vectorial water transport) in the absence of bicarbonate.

Amiloride↗

Delayed sternal closure as a safe adjunct to support biventricular failure after open heart surgery.

Over a four-year period, 22 patients of 2495 undergoing open heart surgery sustained severe biventricular failure (BVF) and would not tolerate primary sternal closure. Reasons for BVF included intraoperative injury, perioperative infarction, global dysfunction, cardiopulmonary edema, and intractable arrhythmia. Mechanical assist devices were required in nine patients. Average cardiac index fell to 1.1 L/min/m2 with attempts to close the chest, then stabilized at 1.9 with the sternum open and only soft tissue closed. After 3 to 11 days, cardiac index rose to 2.5 when assist devices were removed, inotropic agents decreased, and the sternum closed. Three early deaths (5-12 days) were caused by progressive biventricular failure. Five later deaths (19-64 days) were associated with renal and respiratory failure, superinfection, and sepsis. All of these required tracheostomy. Survival of 14 patients was not related to early low cardiac output, preoperative status, timing of sternal closure, or age, but was associated with early recovery of respiratory function without need for tracheostomy, avoidance of renal failure, and satisfactory alimentation. Sternal infection occurred in three patients, resulting in one death. The hospital stay ranged from 12 to 230 days. There was one death resulting from respiratory failure 14 months postoperatively. Our findings show that delayed sternal closure lessens early cardiac instability during BVF, helps allow recovery, and does not produce long-term disability.

Journal Article↗

The metabolic cost of breathing in critical surgical patients.

Twenty ventilator-dependent patients, 14 male and six female, age 47.9 +/- 14, status post polytrauma (14), emergency surgery (three), and coronary artery bypass (three) were evaluated to compare measured energy expenditure (MEE) between the intermittent mandatory ventilation mode (IMV) and assist mode ventilation (AMV) utilizing indirect calorimetry. The MEE was then compared to the predicted basal energy expenditure (PEE) utilizing the Harris-Benedict equation (HBE) and appropriate correction factors dependent on disease and injury status (mean 1.65 +/- 0.24). The mean oxygen consumption (VO2) (IMV) was 347.5 +/- 54.6 ml/min; (VO2) (AMV) was 307.1 +/- 51.4 ml/min (p less than 0.001). The mean MEE (IMV) was 2,380 +/- 369 kcal/day; MEE (AMV) was 2,128 +/- 342 kcal/day (p less than 0.05). The mean predicted energy expenditure (PEE) was 2,731 +/- 416 kcal/day. The IMV mode required 11.6% more pulmonary work when compared to AMV (VO2 IMV - VO2 AMV). The PEE overestimated caloric needs in ventilator-dependent patients by 12.8% on IMV and 22.1% on AMV. The MEE (IMV) required 10.7% more energy than MEE (AMV). Assist mode ventilation resulted in decreased work of breathing and decreased energy expenditure, and the (HBE) inaccurately predicted caloric needs in ventilator dependent patients.

Adult↗

Assessment of nutritional and metabolic status of paraplegics.

Nutritional and metabolic assessment using anthropometric, biochemical, immunological, and indirect calorimetric techniques was performed on 17 healthy paraplegic males with a mean age of 44.2 +/- 14.6 years and mean duration of injury of 17.8 +/- 12.3 years. Significant differences in energy expenditure were observed; only 29.4 percent were normometabolic [measured resting energy expenditure: (MREE) 90-110 percent of predicted resting energy expenditure (PREE)], 35.3 percent were hypermetabolic (MREE greater than 110 percent of PREE) and 35.3 percent were hypometabolic (MREE less than 90 percent of PREE). Obesity (weight greater than 110 percent ideal body weight) was maximum in hypometabolic patients (83.3 percent) due to the imbalance between caloric intake and energy expenditure (p less than 0.05). None of the patients had normal values for all four objective measurements of nutritional assessment (albumin, transferrin, total lymphocyte count, and cutaneous hypersensitivity). Mild malnutrition was evidenced in 47 percent of patients; 53 percent of patients demonstrated some index of moderate malnutrition. We conclude that nutritional therapy based on measurements of energy expenditure instead of predictive equations will benefit these patients. A larger long-term study is needed to determine the ideal predictive measurements of nutritional assessment with their optimal cutoff values applicable to the spinal cord-injured patient.

Adult↗

Toilet facilities in a large Indian teaching hospital.

While assessing the total medical care provided by any large hospital in a community, hardly any stress is laid on the sanitary facilities which the hospital provides and which form such an integral part of every hospital patient. We studied the toilet facilities of M.L.B. Medical College, Jhansi. They seem to be adequate for the ambulant patient but are insufficient for the bedridden and for those who have weak legs. The findings are discussed.

Activities of Daily Living↗

Studies on the mechanism of action of local anesthetics on proton translocating ATPase from Mycobacterium phlei.

We have measured the inhibitory potencies of local anesthetics (procaine, lidocaine, tetracaine and dibucaine) on ATP-mediated H+-translocation, Ca2+-transport and ATPase activity in membrane vesicles from Mycobacterium phlei. Procaine and lidocaine up to 1 mM concentration did not inhibit ATP-dependent H+-translocation, Ca2+-transport and ATPase activity. However, tetracaine and dibucaine at 0.2 mM concentration caused dissipation of the proton gradient, measured by the reversal of the quenching of fluorescence of quinacrine, and inhibition of active Ca2+-transport. Tetracaine (1 mM) inhibited membrane-bound ATPase activity without affecting solubilized F1-ATPase activity. Studies show that these local anesthetics do not prevent the inactivation of F0-F1 ATPase by dicyclohexylcarbodiimide (DCCD). Binding of [14C]DCCD to F0-proteolipid component remained unchanged in the presence of tetracaine indicating that DCCD and tetracaine do not share common binding sites on the F0-proteolipid sector. The inhibition of H+-translocation and membrane-bound ATPase activity by tetracaine was substantially additive in the presence of vanadate.

Anesthetics, Local↗

Purification and functional properties of the DCCD-reactive proteolipid subunit of the H+-translocating ATPase from Mycobacterium phlei.

Interaction of N,N'-dicyclohexylcarbodiimide (DCCD) with ATPase of Mycobacterium phlei membranes results in inactivation of ATPase activity. The rate of inactivation of ATPase was pseudo-first order for the initial 30-65% inactivation over a concentration range of 5-50 microM DCCD. The second-order rate constant of the DCCD-ATPase interaction was k = 8.5 X 10(5) M-1 X min(-1). The correlation between the initial binding of [14C]DCCD and 100% inactivation of ATPase activity shows 1.57 nmol DCCD bound per mg membrane protein. The proteolipid subunit of the F0F1-ATPase complex in membranes of M. phlei with which DCCD covalently reacts to inhibit ATPase was isolated by labeling with [14C]DCCD. The proteolipid was purified from the membrane in free and DCCD-modified form by extraction with chloroform/methanol and subsequent chromatography on Sephadex LH-20. The polypeptide was homogeneous on SDS-acrylamide gel electrophoresis and has an apparent molecular weight of 8000. The purified proteolipid contains phosphatidylinositol (67%), phosphatidylethanolamine (18%) and cardiolipin (8%). Amino acid analysis indicates that glycine, alanine and leucine were present in elevated amounts, resulting in a polarity of 27%. Cysteine and tryptophan were lacking. Butanol-extracted proteolipid mediated the translocation of protons across the bilayer, in K+-loaded reconstituted liposomes, in response to a membrane potential difference induced by valinomycin. The proton translocation was inhibited by DCCD, as measured by the quenching of fluorescence of 9-aminoacridine. Studies show that vanadate inhibits the proton gradient driven by ATP hydrolysis in membrane vesicles of M. phlei by interacting with the proteolipid subunit sector of the F0F1-ATPase complex.

Adenosine Triphosphatases↗

An improved cathepsin-D substrate and assay procedure.

Ten analogs of the peptide A-Phe(NO2)-Phe-Val-Leu-B were synthesized and tested as substrates for cathepsin D and pepsin. The best substrate found for cathepsin D, Phe-Ala-Ala-Phe(NO2)-Phe-Val-Leu-OM4P (kcat = 2.9 s-1; Km = 7.1 microM), has the largest kcat/Km value (408 mM-1 s-1) reported to date for this enzyme. The effect of peptide structure on solubility and kinetic parameters is discussed. The peptide provides a useful new substrate for continuous assay of cathepsin D.

Cathepsin D↗