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Biomedical subjects

R Gopalan

Publications and source records attributed to R Gopalan.

At least 19 recordsLinked to original sources

Hepatitis B-related polyarteritis nodosa complicated by pulmonary hemorrhage.

A 34-year-old man presented with fever, weight loss, paresthesia, abdominal pain, and hypertension. He had hepatitis B antigenemia, with negative antineutrophil cytoplasmic antibody, antinuclear antibody, and antiglomerular basement membrane serology results. Renal arteriography showed multiple intrarenal microaneurysms. In spite of therapy with antiviral agents (lamivudine, famciclovir), prednisone, cyclophosphamide, and plasmapheresis, renal function deteriorated. He later developed rapidly progressive dyspnea and hemoptysis. Diffuse alveolar hemorrhage was confirmed by bronchoscopy. He died of respiratory failure. The cause of pulmonary hemorrhage in this case of polyarteritis nodosa is unclear, but may include underlying capillaritis, cocaine-induced pulmonary hemorrhage, or recurrent attacks of malignant hypertension.

Adult↗

Tranilast in the Therapy of Coronary Artery Disease.

Restenosis after percutaneous intervention remains a significant clinical problem. Although stent implantation has significantly reduced the rate of restenosis by approximately 25% to 33%, intimal hyperplasia within stents still limits long-term vessel patency. The clinical sequelea of this neointimal proliferation is more pronounced in certain patient subgroups, eg, patients with diatbetes mellitus, diffuse disease, smaller vessels, chronic total occlusions, and lesions located in saphenous vein bypass grafts. Pharmacologic agents studied to date have failed to prevent restenosis. Tranilast, a novel anti-inflammatory agent, interferes with the proliferation and migration of vascular smooth muscle cells (VSMCs) induced by platelet-derived growth factor and transforming growth factor beta-1. Basic and preliminary clinical studies conducted with tranilast in Japan have shown encouraging results in terms of reducing restenosis. The Prevention of Restenosis with Tranilast and its Outcomes study (PRESTO), a double-blind, placebo-controlled study (n = 11,500), will test the efficacy of two doses (300 and 450 mg twice a day) of tranilast administered for 1 and 3 months compared with placebo. The primary objective is to compare the composite clinical event rate (death, myocardial infarction, or the need for ischemia-driven target vessel revascularization) after 9 months in patients treated with tranilast or placebo. Angiographic and intravascular ultrasound studies will be peformed in order to assess the effects of tranilast on angiographic restenosis and the volume of intimal hyperplastic tissue. If successful, tranilast will be the first drug to reduce angiographic and clinical restenosis.

Journal Article↗

Tuberculin skin test reactivity, anergy, and HIV infection in hospitalized patients. Longcope Firm of the Osler Medical Housestaff.

PURPOSE: Detection of latent tuberculosis infection is an important step in the control of tuberculosis because high-risk persons may be given preventive therapy. The value of tuberculin skin testing in individuals with human immunodeficiency virus (HIV) infection, however, is limited by anergy. We evaluated the prevalence of tuberculin skin test reactivity, anergy, and HIV infection in a group of hospitalized patients in an area where both tuberculosis and HIV infection are prevalent. PATIENTS AND METHODS: Three hundred fifty-one patients consecutively admitted to a medical service of a large urban teaching hospital were enrolled in the study. All those with no documented history of a positive tuberculin skin test were evaluated on admission with purified protein derivative (PPD) by the Mantoux test, and with anergy testing using a multiple-puncture device. HIV testing was offered to all patients who did not have a known history of HIV infection, and was performed when informed consent was obtained. RESULTS: Forty-one patients (12%) had a documented history of a positive PPD. Of the remaining 310 patients, 62 (20%) had a PPD response of > or = 10 mm induration. Fifty-two (15%) of the 351 patients were HIV positive. None of the HIV-infected patients was PPD positive. Anergy was found in 63% of the HIV-infected patients and 28% of the HIV-seronegative patients. Independent risk factors for a positive PPD included age > 55, male sex, and hypertension. HIV infection, current steroid use, and a history of cancer were associated with a negative PPD. Independent risk factors for anergy included HIV infection, current corticosteroid use, renal failure pneumonia, and a history of cancer. Of the 62 new PPD-positive patients, 30 (48%) were candidates for chemoprophylaxis. Additionally, 30 (63%) of 48 HIV-seropositive patients who were completed testing were anergic and might be candidates for chemoprophylaxis. Almost all of the patients eligible for chemoprophylactic therapy would have been detected if only patients at increased risk for developing tuberculosis were screened. CONCLUSIONS: Tuberculosis infection, HIV infection, and anergy were common in patients admitted to this medical service. Interpretation of PPD reactivity was confounded by a high prevalence of anergy, particularly in HIV-infected patients. A large proportion of patients tested were candidates for chemoprophylaxis. Routine tuberculin skin testing with anergy testing for high-risk patients on admission to the hospital is useful for identifying patients who might benefit from prophylaxis to help control the spread of tuberculosis.

Adult↗

Fatiguing isometric contraction of hind-limb muscles results in the release of immunoreactive neurokinins from sites in the rostral medulla in the anesthetized cat.

Antibody-coated microprobes were used to determine whether immunoreactive neurokinins (irNK) were released from sites in the brainstem during fatiguing isometric contractions of the triceps surae muscles in cats anesthetized with alpha-chloralose. Contractions were generated by stimulating the tibial nerve using a microprocessor-controlled stimulator. Microprobes were inserted into the periaqueductal grey (P 0.5-1.0 mm) or the medullary brainstem (either 3.0 or 3.5 mm rostral to the obex) prior to, during and following fatiguing contractions. No release of irNK was detected from the periaqueductal grey as a result of fatiguing isometric contractions. When probes were inserted 3.0 mm rostral to the obex, a basal release of irNK was detected from the medulla but this was inhibited during isometric contractions from sites corresponding to the lateral tegmental field. When probes were inserted into the more rostral site in the medulla (3.5 mm rostral to the obex), irNK were released in response to contractions from sites corresponding to lateral reticular nucleus, ventral regions of the nucleus tractus solitarius and the medial vestibular nucleus. No irNK were released from this site (3.5 mm rostral to obex) either during passive leg flexing, during nerve stimulation following gallamine injection and muscle paralysis or during stimulation of the central end of the cut tibial nerve. These results demonstrate that neurokinins are released from discrete sites in the medulla in response to fatiguing muscle contractions and suggest that tachykinin neurons may be a component of the pathways regulating blood pressure during ergoreceptor activation.

Anesthesia↗

Community-acquired pneumonia: impact of immune status.

This cross-sectional and prospective one year study evaluated adults admitted to an inner city hospital with community-acquired pneumonia. The study used extensive diagnostic methods to evaluate the etiologies of community-acquired pneumonia in hospitalized patients with differing immunologic status. Of 385 study patients, concurrent problems associated with immunosuppression were noted in 221 (57%) patients, 180 of whom were human immunodeficiency virus (HIV)-infected. The five most common causes of community-acquired pneumonia were: Streptococcus pneumoniae, Pneumocystis carinii, aspiration, Hemophilus influenzae, and gram-negative bacilli. Only 8.3% of patients had either Legionella, Chlamydia pneumoniae or Mycoplasma pneumoniae. Despite use of state-of-the-art diagnostic techniques, no diagnosis was made in 46 of 180 (25.6%) HIV-infected patients, 56 of 164 (34.1%) immunocompetent patients, and 20 of 41 (48.8%) non-HIV-infected immunosuppressed patients. The diagnostic yield of pre-antibiotic sputum culture for conventional bacteria was 99/155 (63.9%) compared to 52 of 169 patients (32.7%) with adequate post-antibiotic sputum culture (p < 0.0001). Although S. pneumonia continues to be the most commonly identified etiologic agent of community-acquired pneumonia, it is surpassed by P. carinii in the HIV-infected patient population. The apparent decline in the frequency of S. pneumoniae in our series presumably reflects administration of antibiotics prior to procurement of sputum culture. The paucity of atypical agents in this study support the current American Thoracic Society guidelines for selective use of macrolide therapy in immunocompetent adults hospitalized with community-acquired pneumonia.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Related Opportunistic Infections↗

Racial differences in the use of drug therapy for HIV disease in an urban community.

BACKGROUND: Guidelines for drug therapy in human immunodeficiency virus (HIV) disease are based primarily on the stage of the disease. To determine whether sociodemographic characteristics of patients influence drug therapy in practice, we analyzed the use of antiretroviral therapy and prophylactic therapy for Pneumocystis carinii pneumonia (PCP) in an urban population infected with HIV. METHODS: All patients presenting for the first time to our HIV clinic from March 1990 through December 1992 were enrolled. Data on sociodemographic and clinical variables and on drug use were collected at the time of presentation and after six months. We asked whether patients with CD4+ cell counts of 500 or less per cubic millimeter were receiving antiretroviral therapy at the time of presentation, and whether patients with CD4+ cell counts of 200 or less per cubic millimeter were receiving PCP prophylaxis. RESULTS: Among the 838 patients enrolled, 656 (79 percent) were blacks, 167 (20 percent) were non-Hispanic whites, and 15 (2 percent) were Asian or Hispanic descent or were not racially classified. There were no racial differences in the stage of HIV disease at the time of presentation. However, there were racial disparities in the receipt of antiretroviral therapy: 63 percent of eligible whites but only 48 percent of eligible blacks received such therapy (P = 0.003). PCP prophylaxis was received by 82 percent of eligible whites but only 58 percent of eligible blacks (P < 0.001). There were no significant differences in the receipt of drug therapy with respect to age, sex, mode of HIV transmission, type of insurance, income, education, or place of residence. In a logistic-regression analysis, race was the feature most strongly associated with the receipt of drug therapy. When blacks were compared with whites, the adjusted relative odds were 0.59 (95 percent confidence interval, 0.38 to 0.93) for the receipt of an antiretroviral agent and 0.27 (95 percent confidence interval, 0.13 to 0.56) for the receipt of PCP prophylaxis. CONCLUSIONS: Among patients infected with HIV, blacks were significantly less likely than whites to have received antiretroviral therapy or PCP prophylaxis when they were first referred to an HIV clinic. This disparity suggests a need for culturally specific interventions to ensure uniform access to care, including drug therapy, and uniform standards of care.

AIDS-Related Opportunistic Infections↗

Detection of immunoreactive substance P-like substances from cat brainstem sites during fatiguing isometric contractions.

Isometric contractions were generated on the left hindlimb muscles from adult cats (n = 11) anesthetized with alpha-chloralose (75 mg/kg) to determine whether immunoreactive substance P (irSP) was released from either the right periaqueductal grey (PAG) or ventrolateral medulla (VLM), sites shown to be involved with the integration of the muscle pressor response. The release of immunoreactive SP was measured using SP antibody-coated microelectrodes that were inserted into the PAG or the VLM during periods of rest, fatiguing isometric contractions and post-contraction. Mean arterial pressure increased by 78 +/- 11 mmHg during the contractions. There was a release of irSP from sites in the medulla during the contractions compared to the non-contraction periods but none was detected from the PAG in response to muscle stimulation. These results provide further evidence that SP-like substances may be involved with the central integration of the muscle pressor response.

Amino Acid Sequence↗

Maternal estimates of developmental age in preschool children.

OBJECTIVE: To investigate the accuracy of maternal estimates of developmental age in preschool children with suspected developmental delay. METHODS: In a sample of 139 preschool children, aged 5 to 60 months, mothers were asked before evaluation to estimate the developmental age of their child. Maternal estimates were converted to a developmental quotient (DQ) and compared with results from standardized tests of cognitive functioning, adaptive abilities, expressive and receptive language, and visual-motor skills. RESULTS: A high correlation was found (r = 0.82; p < 0.0001) between maternal-estimate DQ and actual DQ (mean of test scores). Most mothers estimated within 15% of their child's actual functioning, and 84% of mothers estimated within +/- 5 months of actual functioning. Multiple regression found no factors that would identify mothers who were more or less accurate in estimating developmental age. Maternal-estimate DQ was sensitive (83%) and specific (83%) for mental retardation. CONCLUSION: Maternal estimates provide an accurate measure of developmental functioning and could be successfully incorporated into routine developmental surveillance of preschool children.

Child Development↗

Net costs from three perspectives of using low versus high osmolality contrast medium in diagnostic angiocardiography.

OBJECTIVES: We conducted an economic analysis to assess the extent to which a reduction in adverse drug reactions induced by low osmolality compared with high osmolality contrast media during diagnostic angiocardiography would result in savings to hospitals, society and third-party payers that would offset the substantially higher price of low osmolality contrast medium. BACKGROUND: Substitution of low osmolality for high osmolality contrast media in the approximately 1 million diagnostic angiocardiographic procedures performed each year in the United States could substantially increase health care costs. Cost-effectiveness estimates should include savings that might occur through reduced costs of managing adverse drug reactions. METHODS: In a randomized clinical trial of 505 persons under-going diagnostic angiography with either high osmolality or low osmolality contrast medium, we measured and compared 1) material costs of contrast media, and 2) costs from three perspectives of incremental resources used to manage contrast-related adverse drug reactions. We also performed sensitivity analyses to examine the effect of different assumptions with regard to relative risk, absolute risk and costs of adverse drug reactions on estimates of net cost of use of high osmolality and low osmolality contrast media. RESULTS: One-hundred thirty-seven (54.2%) of 253 patients receiving high osmolality contrast medium and 44 (17.5%) of 252 patients receiving low osmolality contrast medium experienced adverse drug reactions. The average cost (from society's perspective) of resources used to manage adverse drug reactions per patient undergoing angiography was significantly (p = 0.0001) greater for high osmolality (mean $249) versus low osmolality (mean $92) contrast medium. Differential costs (from the hospital's perspective) were $67 greater for high osmolality contrast medium. Charges and professional fees (from the payer's perspective) were $182 greater for high osmolality (mean $312) than for low osmolality (mean $130) contrast medium (p = 0.42, NS). The higher differential and average costs of managing adverse drug reactions with high osmolality contrast medium offset 33% and 75%, respectively, of the $207 difference in mean material costs, but these estimates are sensitive to infrequent high cost cases. CONCLUSIONS: Although low osmolality contrast medium is not cost-saving in diagnostic angiocardiography, its higher price is partially offset by lower management costs of adverse drug reactions. The cost offset for the hospital is lower than that for society and may not be realized by third-party payers. These methods and results may be useful in establishing clinical and payment guidelines for use of alternative contrast media in diagnostic angiocardiography.

Angiocardiography↗

Clinical Adaptive Test/Clinical Linguistic Auditory Milestone Scale in early cognitive assessment.

Correlations between the Clinical Adaptive Test/Clinical Linguistic Auditory Milestone Scale (CAT/CLAMS) and the Bayley Scales of Infant Development--Mental Scale (BSID) were examined in 61 infants and toddlers with suspected developmental delay. Highly significant correlations were found between the two instruments. Gender, race, and gestational age did not influence the relationship between CAT/CLAMS and BSID scores. The CAT/CLAMS was both sensitive (88%) and specific (67%) for mental retardation (BSID < 70). The CAT/CLAMS correlates with the BSID and can be used as an instrument for detecting cognitive delay.

Child, Preschool↗

A rare wandering splenic cyst removed with laparoscopic assistance.

This is a report of the first case of a true cyst arising in a wandering spleen. Laparoscopic splenectomy was attempted. The spleen was mobilized under laparoscopic control and the cyst aspirated. Dissection of the pedicle was technically feasible. However, the procedure was aborted due to uncontrollable bleeding from a moderate-sized artery. Although the whole procedure was not completed laparoscopically, laparoscopic assistance facilitated extirpation of the spleen through a 5-cm oblique left iliac fossa incision in a minimally invasive fashion.

Adult↗

Safety and cost effectiveness of high-osmolality as compared with low-osmolality contrast material in patients undergoing cardiac angiography.

BACKGROUND AND METHODS: Low-osmolality contrast agents produce fewer hemodynamic and electrophysiologic alterations during cardiac angiography, but they are 20 times more expensive than high-osmolality contrast agents. In a randomized, double-blind trial comparing a nonionic low-osmolality contrast agent (Omnipaque 350) with a high-osmolality agent that does not avidly bind calcium (Hypaque 76) in 505 patients undergoing cardiac angiography, we determined the incidence of minor, mild, moderate, and severe adverse reactions, identified risk factors for such reactions, and evaluated the cost effectiveness of various strategies for the use of contrast material. RESULTS: The 253 patients who received a high-osmolality contrast agent were three times more likely to have a moderate adverse reaction (95 percent confidence interval for the relative risk, 1.6 to 5.5) but no more likely to have a severe reaction (95 percent confidence interval, 0.2 to 2.3) than the 252 patients who received a low-osmolality agent. All 10 severe reactions occurred in patients who were older than 60 years or had unstable angina. Patients with these characteristics were also 3.5 times more likely (95 percent confidence interval, 1.8 to 6.8) to have a moderate reaction (44 of 310 patients, or 14 percent) than those without either characteristic (8 of 195 patients, or 4 percent). We estimated that the incremental cost of each moderate reaction avoided would be $1,698 with a strategy that involved giving a low-osmolality contrast agent only to patients who were over 60 years of age or had unstable angina, instead of giving a high-osmolality agent to all patients. The incremental cost per moderate reaction avoided by giving a low-osmolality contrast agent to all patients rather than only to those over 60 or with unstable angina would be $5,842. CONCLUSIONS: The use of contrast agents with low rather than high osmolality during cardiac angiography reduces the risk of moderate, but not of severe, adverse reactions to the agent used. A strategy of reserving low-osmolality contrast agents for use in patients at high risk for adverse reactions would be more cost effective than one requiring their use in all patients.

Age Factors↗

Evaluation of a model curriculum on substance abuse at The Johns Hopkins University School of Medicine.

Beginning in 1985, The Johns Hopkins University School of Medicine developed a model curriculum on alcohol abuse to enhance the education of medical students in issues related to the abuse of alcohol and other drugs. By 1987, preclinical courses (given in years one and two) reflected the goals of the curriculum; however, integration of the curriculum into the clinical courses (given in years three and four) was only partially successful. This paper reports on nine annual surveys of students (the classes of 1989-1992) that were conducted from 1987 to 1990 to measure the effects of the curriculum, using previously validated instruments to record the students' knowledge, attitudes, beliefs in role responsibility, and confidence in clinical skills. Significant improvements occurred in the students' attitudes, beliefs in role responsibility, and confidence in skills during their preclinical years. These positive changes were stronger, and better sustained during the clinical years, in students who participated in special programs or elective courses focusing on substance abuse; the positive changes were not always sustained in other students. The authors suggest that enhanced experiential sessions, elective programs, and greater emphasis during the clinical years on issues relating to substance abuse are necessary for maintaining the desirable educational outcomes of a substance abuse management curriculum, and that an intensive program against a backdrop of curriculum reform is a useful model.

Baltimore↗

Nephrotoxicity of high-osmolality versus low-osmolality contrast media: randomized clinical trial.

The comparative frequency of and risk factors for nephrotoxicity with low-osmolality contrast medium (LOM) versus high-osmolality contrast medium (HOM) were investigated. A randomized, double-blind clinical trial was conducted in patients undergoing diagnostic angiocardiography (n = 430) or contrast material-enhanced body computed tomography (CT) (n = 499). Nephrotoxicity was defined as an increase in serum creatinine level that was greater than both 33% and 0.4 mg/dL (40 mumols/L) above the baseline level within 48 hours after the radiologic procedure. The frequency of nephrotoxicity was similar in patients who received LOM versus those who received HOM: 13 of 479 (2.7%) versus 13 of 450 (2.9%), respectively (P = .87), overall; 4.4% versus 4.0% in angiocardiography patients (P = .84); and 1.2% versus 2.0% in body CT patients (P = .35). Factors associated (P less than .05) with increased risk of nephrotoxicity were insulin-dependent diabetes, baseline serum creatinine level greater than 1.5 mg/dL (130 mumols/L), concurrent use of furosemide, and angiocardiographic examination. Patients who have preexisting renal insufficiency may be at higher risk for nephrotoxicity with HOM than with LOM.

Angiocardiography↗

Publication bias in clinical research.

In a retrospective survey, 487 research projects approved by the Central Oxford Research Ethics Committee between 1984 and 1987, were studied for evidence of publication bias. As of May, 1990, 285 of the studies had been analysed by the investigators, and 52% of these had been published. Studies with statistically significant results were more likely to be published than those finding no difference between the study groups (adjusted odds ratio [OR] 2.32; 95% confidence interval [Cl] 1.25-4.28). Studies with significant results were also more likely to lead to a greater number of publications and presentations and to be published in journals with a high citation impact factor. An increased likelihood of publication was also associated with a high rating by the investigator of the importance of the study results, and with increasing sample size. The tendency towards publication bias was greater with observational and laboratory-based experimental studies (OR = 3.79; 95% Cl = 1.47-9.76) than with randomised clinical trials (OR = 0.84; 95% Cl = 0.34-2.09). We have confirmed the presence of publication bias in a cohort of clinical research studies. These findings suggest that conclusions based only on a review of published data should be interpreted cautiously, especially for observational studies. Improved strategies are needed to identify the results of unpublished as well as published studies.

Bias↗