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Biomedical subjects

R Nair

Publications and source records attributed to R Nair.

At least 55 records · Page 3Linked to original sources

Occlusive arterial disease in HIV-infected patients: a preliminary report.

OBJECTIVES: to preliminarily describe the clinical features and management of arterial occlusive disease in human immunodeficiency virus (HIV) infected patients. MATERIALS: twenty HIV positive patients with symptomatic large-vessel arterial occlusion treated by a tertiary vascular unit in a 3-year period. METHODS: retrospective review of clinical case records. RESULTS: patients were noted to be young (median age 37 years), with preponderance of males. Twelve patients had evidence of advanced HIV infection. All patients had critical ischaemia, involving the upper limbs in four and the lower limbs in 16. Coagulation abnormalities were noted in two cases. Operative intervention in 18 patients included revascularisation in seven. Thrombotic occlusion of normal-looking arteries was noted. Arterial biopsy revealed leucoIcytoclastic vasculitis indicative of HIV arteritis in three of five cases examined. CONCLUSIONS: initial experience with large-vessel occlusive disease in HIV positive patients suggests an underlying arteritic aetiology, with clinical and pathological features distinct from atherosclerosis. Further in-depth study is necessary to clarify the pathophysiological basis thereof.

Adolescent↗

International issues in the supply of tobacco: recent changes and implications for alcohol.

This paper reviews international issues in the supply of tobacco and tobacco products, including trade liberalization and globalization. The paper begins with a brief discussion of the theoretical foundations for trade and trade restrictions. This is followed by a description of the treatment of tobacco and tobacco products in recent multi-lateral, regional and bilateral trade agreements, as well as a short discussion of the recent globalization of the tobacco industry. Included in this description is a review of the empirical evidence on the impact of trade liberalization on tobacco use. The implications of two recently proposed international agreements--the Multilateral Agreement on Investments and the Framework Convention for Tobacco Control--are then discussed. The paper concludes by summarizing the theoretical and empirical evidence that shows clearly that trade liberalization has significantly increased tobacco use, particularly in low and middle-income countries, and follows this with a discussion of the lessons learned from tobacco for controlling alcohol supply.

Alcoholic Beverages↗

Finding nuclear localization signals.

A variety of nuclear localization signals (NLSs) are experimentally known although only one motif was available for database searches through PROSITE. We initially collected a set of 91 experimentally verified NLSs from the literature. Through iterated 'in silico mutagenesis' we then extended the set to 214 potential NLSs. This final set matched in 43% of all known nuclear proteins and in no known non-nuclear protein. We estimated that >17% of all eukaryotic proteins may be imported into the nucleus. Finally, we found an overlap between the NLS and DNA-binding region for 90% of the proteins for which both the NLS and DNA-binding regions were known. Thus, evolution seemed to have used part of the existing DNA-binding mechanism when compartmentalizing DNA-binding proteins into the nucleus. However, only 56 of our 214 NLS motifs overlapped with DNA-binding regions. These 56 NLSs enabled a de novo prediction of partial DNA-binding regions for approximately 800 proteins in human, fly, worm and yeast.

Animals↗

End-to-end diffusion on the microsecond timescale measured with resonance energy transfer from a long-lifetime rhenium metal-ligand complex.

We measured the end-to-end diffusion coefficient of an alkyl chain-linked donor-acceptor pair using the time-resolved frequency-domain decay of the donor. The donor was a rhenium metal-ligand complex with a mean decay time ranging from 2.1 to 7.9 microseconds in the absence of the Texas red acceptor. The decay time was used to measure the donor-to-acceptor distance distribution and the mutual diffusion coefficient. Using this long lifetime donor, it was easily possible to determine a diffusion coefficient near 2 x 10(-8) cm2/s and diffusion coefficients as low as 1.3 x 10(-9) cm2/s were measurable. Such long lifetime donors should be valuable for measuring the flexing of peptides on the microsecond timescale, domain motions of proteins and lateral diffusion in membranes. The availability of microsecond decay time luminophores now allows luminescence spectroscopy to be useful generally for studies of microsecond dynamics of biological macromolecules.

Biopolymers↗

Avascular necrosis of head of femur in a patient with acute promyelocytic leukemia.

Avascular necrosis (AVN) of head of the femur is associated with various pathological conditions and treatment modalities. We present a case of acute promyelocytic leukemia who was treated with all-transretinoic acid (ATRA), daunomycin, cytarabine and a short course of dexamethasone. He developed AVN of bone after 2 years of treatment. Whether this is related to ATRA is dealt with in the discussion.

Adult↗

Acute promyelocytic leukemia: all-trans retinoic acid (ATRA) along with chemotherapy is superior to ATRA alone.

This study was conducted to compare the results of treatment of acute promyelocytic leukemia (APL) with all-trans retinoic acid alone (ATRA) or a combination therapy of ATRA followed by chemotherapy. Forty-three patients treated between February 1992 and February 1996 were included in this study. Eighteen patients were treated with ATRA alone and 25 patients were treated with ATRA followed by chemotherapy. The cytogenetic analysis was done in 41 patients at presentation, following treatment, and at follow-up. A complete response (CR) was achieved in 13 (72%) patients on ATRA and 19 (76%) on ATRA followed by chemotherapy. Eleven of 13 patients with response to ATRA alone relapsed with median survival of eight months (range, 1 to 28). One patient died of hepatitis in CR and one patient is alive 2 years after diagnosis. In the combination therapy arm, 10 patients are in CR with a median follow-up of 22 months (range, 6 to 56 months). After achieving a CR, four patients died due to infections during chemotherapy therapy, and only 5 of 19 patients have relapsed. Major cytogenetic response was seen in 8 of the 10 patients in whom cytogenetic data was available after treatment with ATRA at the time of remission. Similarly, 13 of 15 for whom data was available showed a major cytogenetic response after treatment with ATRA plus chemotherapy. Prior to relapse, 80% of the patients had an increase in the percentage of t(15;17) cells in the marrow. Patients with a complete hematological response but no cytogenetic response relapsed within six months. Ten patients died prior to response evaluation. Two patients who received ATRA died of retinoic acid syndrome, one of pneumonia, and one of intracranial hemorrhage. Of the six patients on ATRA and chemotherapy, four died of retinoic acid syndrome (RAS), one of intracranial hemorrhage, and one of left ventricular failure. Only one patient is alive at 24 months following treatment with ATRA alone. The relapse-free survival is 42% at four years for patients treated with ATRA followed by chemotherapy. This trial is a historical comparison of ATRA alone and ATRA with subsequent combination chemotherapy. Nonetheless, the trial shows a significant improvement in the event free survival of patients receiving chemotherapy as consolidation following ATRA.

Adolescent↗

Diagnostic significance of papillary structures and intranuclear inclusions in Hurthle-cell neoplasms of the thyroid.

Papillary structures and intranuclear inclusions, features which are not ordinarily associated with Hurthle-cell lesions, are occasionally noted within Hurthle-cell-rich aspirates. The diagnostic significance of these features in this setting, if any, is unknown. The purpose of this study was to determine whether these features are diagnostically useful. Specifically, since fine-needle aspiration cytology cannot distinguish between Hurthle-cell adenoma and carcinoma, we wanted to know whether the presence of either feature might aid in preoperatively assessing the likelihood of carcinoma vs. adenoma. We identified 12 cases in which a diagnosis of Hurthle-cell lesion was made by thyroid fine-needle aspiration biopsy. All cases had subsequent surgery. For every case, all cytology slides were reviewed for the presence or absence of papillary structures and intranuclear inclusions, after which the findings were correlated with the final surgical pathological diagnosis. Seven of the 12 cases had identifiable papillary structures, ranging from cases where papillary structures comprised the predominant architectural pattern to cases where rare papillary structures were found amidst a predominance of sheets and single Hurthle cells. Four of the 12 cases had intranuclear inclusions. In all cases, intranuclear inclusions were uncommon. Of 6 cases that proved to be Hurthle-cell carcinoma, 5 had papillary structures on the antecedent fine-needle aspirate cytology, and 2 had intranuclear inclusions. Of 6 cases that proved to be Hurthle-cell adenoma, 2 had papillary structures, and 2 had intranuclear inclusions. Papillary structures had a sensitivity of 83% for the presence of carcinoma, a specificity of 66%, a positive predictive value of 71%, and a negative predictive value of 80% (P = 0.2). Intranuclear inclusions had a sensitivity of 33%, a specificity of 66%, and positive and negative predictive values of 50%. Papillary structures are more common in Hurthle-cell aspirates than previously recognized. Their presence is not diagnostic of carcinoma, but neither does their absence rule out carcinoma. However, when found, the likelihood of an ultimate diagnosis of Hurthle-cell carcinoma is increased. On the other hand, intranuclear inclusions, when rare, appear to have no diagnostic value.

Adenocarcinoma↗

Arterial aneurysms in patients infected with human immunodeficiency virus: a distinct clinicopathology entity?

Arterial aneurysms have only recently been associated with the human immunodeficiency virus (HIV). The clinical and pathological features of 10 HIV-positive patients with arterial aneurysms were retrospectively evaluated. These aneurysms were unusual in that they affected young black patients, occurred in atypical sites, and tended toward multiplicity. Surgery was performed in eight patients. Acute and chronic inflammatory changes were revealed by means of histologic examination of the aneurysm walls, with occlusion of the vasa vasora by inflammatory infiltrate or edema being a prominent feature. Culture of the aneurysm wall or thrombus yielded positive results in two patients. The association between HIV and aneurysms may be coincidental, caused by direct viral action or by bacterial infection resulting from immunosuppression. Implications for therapy are discussed, and the need for further study is highlighted.

Adolescent↗

Real-time optical imaging of experimental brain ischemia and hemorrhage in neonatal piglets.

Our objective was to study the development of experimental brain ischemia and hemorrhage by real-time optical imaging. Optical imaging is based on the ability of near infrared light to non-invasively penetrate through the intact scalp and skull and measure brain concentrations of oxy- and deoxyhemoglobin, dominant brain absorbers. Optical imaging was performed in 7 anesthetized, instrumented, and ventilated newborn piglets subjected to the injection of 0.3 cc of saline followed by 2 cc of blood into the left frontal subcortical brain region via a needle inserted through the skull with stereotactic guidance. The image-acquisition rate of 5.26 images per sec allowed for real-time imaging. The detection threshold of the imager at the estimated depth of 1-1.5 cm was approximately 70 microL for saline and approximately 40 microL for blood. The imager readily detected five subcortical hematomas and two large bilateral subarachnoid hemorrhages. The imager detected a global decrease in brain absorption associated with the volume-injection-related increase in intracranial pressure in the surrounding ipsilateral and contralateral brain. Any decrease in brain absorption is an equivalent to brain ischemia. This study demonstrates the capability of optical imaging in detecting brain ischemia and hemorrhage in real-time with high temporal and spatial resolution.

Animals↗

MALT lymphoma of nasal mucosa treated with antibiotics.

Mucosa associated lymphoid tissue (MALT) lymphomas occur in sites other than the gastrointestinal tract and in the early stages respond to treatment with antibiotics. We report a rare case of nasal mucosal MALT lymphoma which responded to treatment with antibiotics and has since then remained in remission.

Adult↗

Aneurysms of the persistent sciatic artery.

The persistent sciatic artery is a rare anatomical anomaly of the lower limb vasculature. It may be noted incidentally, or it may present with limb ischaemia or aneurysmal degeneration. Management entails exclusion of the aneurysm and vascular reconstruction. A case of bilateral persistent sciatic artery aneurysms and a review of the embryological development, clinical features, and management are reported. The persistent sciatic artery (PSA) may result from an aberration in the development of the arterial supply to the lower limb. It is a rare anomaly, with sporadic cases reported in the literature, few of which have been angiographically documented. A report of a patient treated at King Edward VIII Hospital, Durban, is presented here.

Adult↗

A randomized comparison of the efficacy and toxicity of epirubicin and doxorubicin in the treatment of patients with non-Hodgkin's lymphoma.

BACKGROUND: Combination chemotherapy consisting of methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisolone, and bleomycin (MACOP-B) has been frequently used for the treatment of non-Hodgkin's lymphoma. This randomized study was undertaken to assess the efficacy and toxicity of this regimen when either doxorubicin or epirubicin was used as the anthracycline drug. METHODS: Between April 1989 and December 1993, 211 previously untreated patients with intermediate grade and high grade non-Hodgkin's lymphoma were randomized to receive either doxorubicin (n=106) or epirubicin (n=105) with the MACOP-B regimen. These patients were followed through December 1996. Numerous clinical features predictive of response and survival were analyzed. Cardiac and noncardiac toxicity in the two treatment arms were compared. RESULTS: The median age of the patients was 48 years. Complete remission was experienced by 122 patients (58.3%); 62 patients (58.5%) achieved complete remission in the doxorubicin arm and 60 (58.1%) in the epirubicin arm. Response rates, time to treatment failure, relapse data, and overall survival were comparable between the two arms. Morbidity due to mucositis, vomiting, peripheral neuropathy, and cardiotoxicity were also comparable. The overall mortality was 10%. Mortality due to neutropenic sepsis was considerably higher among patients who received epirubicin (10 patients) than among those who received doxorubicin (5 patients). Cardiac evaluation revealed no difference in toxicity between the two arms. CONCLUSIONS: Epirubicin was as effective as doxorubicin in terms of patients' responses to therapy. There was no difference in cardiotoxicity between the two treatment arms. However, in this study, the mortality due to neutropenic sepsis was significantly higher among patients treated with epirubicin.

Adolescent↗

Acute results, complications, and effect of lesion characteristics on outcome with the solid-state, pulsed-wave, mid-infrared laser angioplasty system: final multicenter registry report. Holmium:YAG Laser Multicenter Investigators.

BACKGROUND AND OBJECTIVE: The solid-state, mid-infrared holmium:YAG laser (2.1 microm wavelength) is a relatively new percutaneous device that has recently been evaluated in a multicenter study. Because of its unique wavelength and photoacoustic effects on atherosclerotic plaques, this laser may be useful in treatment of symptomatic patients with coronary artery disease. This study sought to evaluate the safety and efficacy of mid-infrared laser angioplasty in the treatment of coronary artery lesions. PATIENTS AND METHODS: Laser angioplasty was performed on 2,038 atherosclerotic lesions in 1,862 consecutive patients with a mean age of 61 +/- 11 years. Clinical indications included unstable angina (69%), stable angina (20%), acute infarction (6%), and positive exercise test (5%). Complex lesion morphology included eccentricity (62%), thrombus (30%), total occlusion (27%), long lesions (14%), and saphenous vein grafts (11%). RESULTS: This laser catheter alone successfully reduced stenosis (>20%) in 87% of lesions. With adjunct balloon angioplasty, 93% procedural success was achieved. The presence of thrombus within the target lesion was a predictor of procedural success (OR = 2.0 [95% confidence interval 2.0, 4.0], P = .04). Bifurcation lesions (OR = 0.5 [95% confidence interval 0.2, 1.0], P = .05) and severe tortuosity of the treated vessel (OR = 0.4 [95% confidence interval 0.2, 0.9], P = .02) were identified as significant predictors of decreased laser success. Calcium within the lesion was associated with reduced procedural success (OR = 0.57 [95% confidence interval 0.34, 0.97], P = .03), and calcified lesions required significantly more energy pulses than noncalcified lesions (119 +/- 91 pulses vs. 101 +/- 86 pulses, respectively, P = .0002). Complications included in-hospital bypass surgery 2.5%, Q-wave myocardial infarction 1.2%, and death 0.8%. Perforation occurred in 2.2% of patients; major dissection in 5.8% of patients, and spasm in 12% of patients. No predictor of major complications was identified. Six-month angiographic restenosis was documented in 54% of patients, and clinical restenosis occurred in 34% of patients. CONCLUSION: Mid-infrared laser has a safety profile similar to that of other debulking devices. This laser may be useful in select patients presenting with acute ischemic syndromes associated with intracoronary thrombus; however, like other coronary lasers, it is limited by the need for adjunctive balloon angioplasty and/or stenting to achieve adequate final luminal diameter. No beneficial effects on reducing 6-month restenosis rates were observed.

Aluminum Silicates↗

The Canadian experience using plasma exchange for immune thrombocytopenic purpura. Canadian Apheresis Group.

The effect of plasma exchange (PE) for the treatment of acute immune thrombocytopenic purpura (ITP) was assessed both through an analysis of the use of PE for ITP in Canada from 1980 to 1997, and in a study of 23 patients with acute ITP. Thirteen of these 23 patients were treated by PE (10 were exchanged with albumin and three with FFP) plus prednisone and 10 were treated with prednisone alone. At the 6 month follow-up, 11 of 19 patients were considered complete responders and six were considered partial responders. The difference in response rates between the PE and prednisone groups was not statistically significant. All patients had platelet specific antibodies at the time of entry into the study. Antibody concentration was reduced following PE in 10 of the 12 patients tested, and a response to PE was seen in all 10 patients who had a reduction in the level of platelet antibody. In contrast, antibody levels did not change in the patients who received steroid treatment only. This observation suggests that antibody removal may be of direct benefit in patients with ITP. Analysis of our results indicated that PE increased the length of time before splenectomy but did not alter the need for splenectomy. Short term benefits of PE were accomplished with no increase in morbidity or mortality which confirms that PE is a safe procedure in patients with ITP.

Acute Disease↗

Synthesis and separation of potential anticancer active dihalocephalomannine diastereomers from extracts of Taxus yunnanensis.

Two diastereomeric 2",3"-dibromo cephalomannines and their two corresponding 7-epimers were obtained by treatment of extracts of Taxus yunnanensis with bromine solution under mild conditions. Treatment of the same extract with chlorine solution yielded four diasteromeric 2",3"-dichlorocephalomannines, with no 7-epimers. The diastereomeric mixtures were separated into the individual components by preparative HPLC on C18 reversed-phase silica gel. A more efficient analytical separation was obtained on a pentafluorophenyl-bonded phase. These reaction products were isolated and fully identified spectroscopically. Slight differences were observed in the NMR spectra of the 7-epimers when compared to their 7 beta-OH analogues. On the basis of a comparison of physicochemical data, the bromo compounds were identified as (2"R,3"S)-dibromo-7-epi-cephalomannine (3), (2"S,3"R)-dibromo-7-epi-cephalomannine (4), (2"R,3"S)-dibromocephalomannine (5), and (2"S,3"R)-dibromocephalomannine (6), and the chloro compounds as (2"R,3"R)-dichlorocephalomannine (7), (2"S,3"S)-dichlorocephalomannine (8), (2"R,3"S)-dichlorocephalomannine (9), and (2"S,3"R)-dichlorocephalomannine (10). Cytotoxic activity was tested against the NCI 60 human tumor cell line panel in comparison with paclitaxel (1), and encouraging results were obtained in some cases.

Antineoplastic Agents, Phytogenic↗

All trans retinoic acid with low dose cytosine arabinoside in the treatment of myelodysplastic syndrome.

The demonstration of synergistic interaction between differentiation inducing agents and DNA synthesis inhibitors suggests that these two groups act by two different mechanisms. We prospectively studied the response rate, response duration, survival, and toxicity in 10 patients with myelodysplastic syndrome (MDS) treated with all trans retinoic acid (ATRA) and low dose cytosine arabinoside (ara-C). These patients diagnosed between October 1993 and May 1995 were treated with ATRA (45 mg/M2/day) for 90 days followed by 90 mg/M2 on alternate day till Day 275; together with Ara-C (10 mg/m2) subcutaneously twice daily for 21 days for a total of 6 cycles. These patients were analyzed for response after 3 cycles of LD Ara-C and at the time of completion of therapy. Toxicity was recorded at the end of each cycle of Ara-C. There were 6 male and 4 female patients in the age range of 24 to 76 years. The morphological diagnosis was chronic myelomonocytic leukemia in 2, refractory anemia with excess blasts in 4 and refractory anemia with excess blasts in transformation in 4. Only 1 patient achieved a complete remission and 1 patient achieved a partial response. Four patients had progressive disease on treatment. One patient died of neutropenic sepsis and 1 of resistant thrombocytopenia and intracranial hemorrhage while on treatment. One patient refused further treatment after a minor clinical response and in 1 patient treatment was stopped due to toxicity. This data in a pilot study with a limited number of patient suggests that ATRA in combination with Ara-C has little effect in MDS.

Aged↗

Evaluation of a midwifery birthing center in the Canadian north.

An evaluation of a midwife-operated community birthing center was conducted to identify whether it would be safe, cost-effective, and psychologically and socially satisfying for Inuit women in one community in the Northwest Territories. Two nurse-midwives provided antenatal and postnatal care to all pregnant women and delivered those designated as 'low risk' for complications. Another community similar in size but with no community birthing was used for comparison of the three indices. Data were gathered on reproductive histories and pregnancy risk profiles of all women giving birth in a one-year period. The financial costs were calculated for those women transferred out to hospital for delivery and compared with those who stayed in the community. Pregnant women and their partners in both communities, health staff, and community members were interviewed for their feelings and concerns about the birthing services. Preliminary findings suggest that with experienced midwives community births are safe. A minimum of 25 births is required in the community for this project to be cost effective. The women who had their infants in the community expressed satisfaction for a number of reasons.

Arctic Regions↗