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Biomedical subjects

R D'Souza

Publications and source records attributed to R D'Souza.

At least 19 recordsLinked to original sources
PubMed2006

In Vitro and In Vivo preparation evaluations of bleomycin implants and microspheres Prepared with DL-poly (lactide-co-glycolide).

In this investigation, poly(lactide-co-glycolide) (PLGA) gel implants and microspheric depot systems of bleomycin (BLM) were formulated and evaluated in vivo in mice bearing transplantable solid tumor (fibrosarcoma). The pharmacodynamic studies showed that both the formulations retarded tumor growth significantly (p<0.05) when compared to the control animals (without any drug treatment). Preliminary pharmacokinetic studies illustrated controlled release of the drug into the systemic circulation to elicit the anti-neoplastic action. The gel implants showed better release characteristics and greater pharmacodynamic action when compared to the microspheres, thus demonstrating the feasibility of employing biodegradable depot polymer gel matrix for chronic cancer therapy.

Animals↗
PubMed2005

Discontinuation of pegylated interferon plus ribavirin in patients who are not responding to therapy -- patients' views of early cessation of therapy.

BACKGROUND: Current therapy for chronic hepatitis C infection involves a course of pegylated interferon and ribavirin. Patients who do not show a virological response after 12 weeks of therapy have a low probability of sustained virological response and it is therefore recommended that such patients stop treatment. AIM: To assess patients' views of early treatment cessation. METHODS: We conducted a open-labelled study in three UK centres, in which patients with biopsy-proven chronic hepatitis C requiring therapy were offered the choice of a full course of therapy with 40 kDa pegylated interferon-alpha 2a plus ribavirin (24 or 48 weeks depending on viral genotype) or early cessation if therapy had failed after 12 weeks. RESULTS: Ninety-five participants were enrolled and the majority (69%) did not wish to discontinue therapy even if it had low probability of success. In this unselected UK population, very few patients (4%) did not achieve an early virological response with the 40-kDa pegylated interferon-alpha 2a plus ribavirin and two of the four early virological non-responders decided to continue therapy. CONCLUSION: Early discontinuation of 'ineffective' anti-viral therapy may prove less popular with patients than with health care providers, and further patient-directed education regarding the cost-effectiveness of therapy will be needed if early discontinuation of unsuccessful therapy is to be accepted by patients.

Adult↗
PubMed2005

An unusual form of autoimmune hepatitis in young Somalian men.

BACKGROUND: Significant diversity in disease severity has been identified for autoimmune disorders among different ethnic groups. Current knowledge of both the natural history and management of autoimmune hepatitis (AIH) has been derived from European or Japanese patients, and there is limited information about the disease in patients from other ethnic groups. AIMS: To assess the clinical, histological and immunological features of AIH in patients from Somalia and to determine their response to therapy. METHODS: Retrospective review of a cohort of young Somalian men with atypical AIH compared with a control group of European patients. RESULTS: The six Somalian men were younger at presentation (median age 37 (range 24-59) years) than the seven female and three male European controls (55 (34-54) years, P = 0.06). The Somalians had slightly more severe disease at presentation-median modified Ishak stage of 2.5 compared with 2 in Europeans (P = 0.61) and four (66%) had features of cholestasis compared with only one (10%) European patient (P = 0.04). Therapy with prednisolone and azathioprine was completely effective for eight of 10 Europeans but only one of seven Somalians (P = 0.04). Analysis of human leucocyte antigen types revealed differences between the Somalian and European patients, although these differences did not reach statistical significance. CONCLUSIONS: Somalian men with AIH present with cholestatic features and respond poorly to standard immunosuppressive regimes.

Adult↗
PubMed2005

Insulin resistance plays a significant role in liver fibrosis in chronic hepatitis C and in the response to antiviral therapy.

OBJECTIVES: To assess whether insulin resistance is associated with liver fibrosis in a group of patients with chronic hepatitis C virus (HCV) infection and whether there were any differences in insulin resistance between Asians and the indigenous Caucasian population. Secondly, to assess whether insulin resistance is associated with sustained virological response to antiviral therapy. METHODS: We determined insulin resistance in 59 (30 Caucasians; 29 Asians) consecutive patients with HCV prior to starting antiviral therapy. Insulin resistance was measured using the homeostasis model assessment of insulin resistance (HOMA-IR). The relationship between insulin resistance and biochemical, virological, and histological data together with response to antiviral therapy was assessed. RESULTS: In multivariable analyses, insulin resistance as measured using the HOMA-IR model correlated positively with the stage of fibrosis, with higher degrees of insulin resistance in those with greater degrees of fibrosis (p < 0.001). This significant relationship remained even after excluding cirrhotic patients, or after adjusting for other factors associated with fibrosis in univariable analyses. Insulin resistance was significantly higher in Asians than Caucasians (p= 0.004). Around half (55.6%) of patients completing a course of antiviral treatment had a sustained virological response. Multivariable logistic regression identified HCV genotype 3, lower fasting glucose levels, and lower aspartate transaminase (AST) levels as being associated with a higher odds of a sustained virological response. After adjusting for these variables, Asian ethnicity, higher fasting insulin levels, and higher HOMA-IR levels were all associated with a poorer virological response to therapy. CONCLUSIONS: Insulin resistance contributes to liver fibrosis in chronic HCV infection; this relationship is not genotypic specific. Asian patients had higher insulin resistance than Caucasians. Insulin resistance is also an important predictor of sustained response to antiviral therapy.

Adult↗
PubMed2004

Vitamin C for preventing and treating the common cold.

BACKGROUND: The role of oral vitamin C (ascorbic acid) in the prevention and treatment of the common cold has been a subject of controversy for at least sixty years. Public interest in the topic continues to be high and vitamin C continues to be widely sold and used as a preventive and therapeutic agent for this common ailment. OBJECTIVES: To discover whether oral vitamin C in doses of 200 mg or more daily, reduces the incidence, duration or severity of the common cold when used either as continuous prophylaxis or after the onset of cold symptoms. SEARCH STRATEGY: This updated review added to earlier searches, a full search of the following electronic databases: the Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2004); MEDLINE (January 1966 to June 2004); and EMBASE (1990 to June 2004). SELECTION CRITERIA: Papers were excluded if a dose less than 200 mg daily of vitamin C was used; if there was no placebo comparison; if methods of outcome assessment were inadequately described; and if the report did not record any of the three study outcomes (incidence, duration or severity) in sufficient detail to enter into the meta-analysis. Three criteria of study quality were assessed: Jadad scores, placebo distinguish-ability, and allocation concealment. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed trial quality. 'Incidence' of colds during prophylaxis was assessed as the proportion of participants experiencing one or more colds during the study period. 'Duration' was the mean days of illness of cold episodes and 'severity' of these episodes was assessed by days confined indoors, off work or school. or by symptom severity scores. MAIN RESULTS: Twenty-nine trial comparisons involving 11,077 study participants contributed to the meta-analysis on the relative risk (RR) of developing a cold while taking prophylaxis. The pooled RR was 0.96 (95% CI 0.92 to 1.00). A subgroup of six trials that involved a total of 642 marathon runners, skiers, and soldiers on sub-arctic exercises reported a pooled RR of 0.50 (95%CI 0.38 to 0.66). Thirty comparisons that involved 9,676 respiratory episodes contributed to the meta-analysis on common cold duration during prophylaxis . A consistent benefit was observed, representing a reduction in cold duration of 8% (95% CI 3% to 13%) for adult participants and 13.5% (95% CI 5% to 21%) for child participants. Fifteen trial comparisons that involved 7,045 respiratory episodes contributed to the meta-analysis of severity of episodes experienced while on prophylaxis. The pooled results revealed a difference favouring those on vitamin C when days confined to home and off work or school were taken as a measure of severity (p = 0.02), and when restricting to studies which used symptom severity scores (p = 0.16), and for the both measures of severity combined (p = 0.004). Seven trial comparisons that involved 3,294 respiratory episodes contributed to the meta-analysis of cold duration during therapy with vitamin C that was initiated after the onset of cold symptoms, and no significant difference from placebo was seen. Four trial comparisons that involved 2,753 respiratory episodes, contributed to the meta-analysis of cold severity during therapy and no significant difference from placebo was seen.In laboratory studies, differing methods of artificial transmission of virus to vitamin C or placebo treated volunteers in residential experiments gave different results. Volunteers infected by nasal installation showed small or no benefit from vitamin C, whereas a group who were infected more naturally, reported less severe symptom severity scores (p = 0.04). REVIEWERS' CONCLUSIONS: The failure of vitamin C supplementation to reduce the incidence of colds in the normal population indicates that routine mega-dose prophylaxis is not rationally justified for community use. But evidence shows that it could be justified in persons exposed to brief periods of severe physical exercise and/or cold environments. Also, the consistent and statistically significant small benefits on duration and severity for those using regular vitamin C prophylaxis indicates that vitamin C plays some role in respiratory defence mechanisms. The trials in which vitamin C was introduced at the onset of colds as therapy did not show any benefit in doses up to 4 grams daily, but one large trial reported equivocal benefit from an 8 gram therapeutic dose at onset of symptoms.

Administration, Oral↗
PubMed2001

Vitamin A for treating measles in children.

BACKGROUND: Measles is a leading cause of childhood morbidity and mortality. Vitamin A deficiency is a recognised risk factor for severe measles. The World Health Organization (WHO) recommends administration of an oral dose of 200,000 IU (or 100,000 IU in infants) of vitamin A per day for two days to children with measles in areas where vitamin A deficiency may be present. OBJECTIVES: The purpose of this review is to determine whether vitamin A when commenced after measles has been diagnosed, is beneficial in preventing mortality, pneumonia and other complications in children. SEARCH STRATEGY: MEDLINE and the Cochrane Library, Issue 4, 1999 were searched. SELECTION CRITERIA: Only randomized controlled trials in which children with measles were given vitamin A or placebo along with standard treatment were considered. DATA COLLECTION AND ANALYSIS: Studies were assessed independently by two reviewers. The analysis of dichotomous outcomes was done using the StatExact software package. Sub-group analyses were done for dose, formulation, age, hospitalisation and pneumonia specific mortality. Weighted mean difference with 95% CI were calculated for continuous outcomes. MAIN RESULTS: The relative risks (RR) and 95% Confidence Intervals (CI) are based on the estimates from the StatExact software package. There was no significant reduction in mortality in the vitamin A group when all the studies were pooled together (RR 0.60; 95% CI 0.32 to 1.12)(Statexact estimate). There was a 64% reduction in the risk of mortality in children who were given two doses of 200,000 IU of vitamin A (RR=0.36; 95% CI 0.14 to 0.82) as compared to placebo. Two doses of water based vitamin A were associated with a 81% reduction in risk of mortality (RR=0.19; 95% CI 0.02 to 0.85) as compared to 48% seen in two doses of oil based preparation (RR=0.52; 95% CI 0.16 to 1.40). Two doses of oil and water based vitamin A were associated with a 82% reduction in the risk of mortality in children under the age of 2 years (RR=0.18; 95% CI 0.03 to 0.61) and a 67% reduction in the risk of pneumonia specific mortality (RR=0.33; 95% CI 0.08 to 0.92). There was no evidence that vitamin A in a single dose of 200,000 IU was associated with a reduced risk of mortality among children with measles (RR=0.77; 95% CI 0.34 to 1.78). Sub-groups like age, dose, formulation, hospitalisation and case fatality in the study area were highly correlated and there were not enough studies to separate out the individual effects of these factors. There was a 47% reduction in the incidence of croup (RR=0.53; 95% CI 0.29 to 0.89), while there was no significant reduction in the incidence of pneumonia (RR=0.92; 95% CI 0.69 to 1.22) or of diarrhoea (RR=0.80; 95% CI 0.27 to 2.34). Duration of diarrhoea was measured in days and there was a reduction in its duration of almost two days WMD -1.92, 95% CI -3.40 to -0.44. Only one study evaluated otitis media and found a 74% reduction in its incidence (RR=0.26, 95% CI, 0.05 to 0.92). We did not find evidence that a single dose of 200,000 IU of vitamin A per day, given in oil-based formulation in areas with low case fatality, was associated with reduced mortality among children with measles. However, there was evidence that the same dose given for two days was associated with a reduced risk of overall mortality and pneumonia specific mortality. REVIEWER'S CONCLUSIONS: Although we did not find evidence that a single dose of 200,000 IU of vitamin A per day was associated with reduced mortality among children with measles, there was evidence that the same dose given for two days was associated with a reduced risk of overall mortality and pneumonia specific mortality. The effect was greater in children under the age of two years. There were no trials that compared a single dose with two doses, although the precision of the estimates of trials that used a single dose were similar to the trials that used two doses.

Adolescent↗
PubMed2001

Neurogenic pulmonary oedema induced by bacterial meningitis: a case report.

We report a case of neurogenic pulmonary oedema occurring in association with bacterial meningitis. An 87 year old man suddenly developed severe dyspnoea without cardiac failure (MUGA scan ejection fraction 47%). Radiographs showed pulmonary oedema. A few hours later he developed signs of meningitis and lumbar puncture suggested a partially treated bacterial meningitis. We suspect that the bacterial meningitis had induced neurogenic pulmonary oedema.

Aged↗
PubMed2001

Experience of a small British pacing centre between 1994 and 2000: some answers to the problem of low UK implantation rates.

Raigmore is a district general hospital offering a permanent pacemaker service to its catchment population of 233,500. This report reviews the pacemaker practice over a seven year period (1994 to 2000) and makes a comparison with the national database and other hospitals in the UK. The records of all patients receiving new implantions for the period under observation were reviewed retrospectively. Data collected included number of patients paced each year, age, sex, indications and complications. In the 84 months studied 3/71 patients received new permanent pacemakers (the mean age was 74 years and 51% were male). The most common presenting symptoms were syncope (62%), dizzy spells (24%), and heart failure (11.5%). The most common indication for permanent pacemaker insertion was complete atrioventricular block (58%) followed by sick sinus syndrome (20%). The implantation rate was 419.3/million population/year in 2000. Pacemaker modes used were appropriate and the early and late complication rates were low (2.7%). This current audit demonstrates continued growth of the service with low-complication rates and implantation rates which approach those in Western Europe and North America.

Aged↗
PubMed2001

Lessons to be learned: a case study approach a case study of the temporal onset of pulmonary hypertension with pre-existent cirrhotic portal hypertension.

We report the occurrence of pulmonary hypertension in a 37-year-old male patient with cirrhosis of the liver, portal hypertension and oesophageal varices. Although this is a rare combination, previous reports have shown that the association of portal and pulmonary hypertension is not coincidental; the temporal onset of primary pulmonary hypertension is hard to predict and our patient was asymptomatic for a number of years. The pathogenesis of portal hypertension leading to pulmonary hypertension is not known. Diagnosis is difficult because the clinico-pathological symptoms in both conditions are similar. Treatment is limited to calcium channel blockers, vasodilators, nitrous oxide and prostacyclin, although most patients will eventually require visceral transplantation.

Adult↗
PubMed2000

Antibiotics for preventing pneumonia in children with measles.

BACKGROUND: Measles causes more than a million deaths a year, of which most are children under five years of age who die from pneumonia. OBJECTIVES: The objective of this review was to assess the effects of antibiotics given to children with measles on reducing pneumonia or mortality, and to assess whether antibiotics should be given to all children with measles in communities with a high fatality rate. SEARCH STRATEGY: We searched MEDLINE (1966 - 1999), EMBASE (1980-1999) and the specialized trials register of the Acute Respiratory Infections Group in August 1999, and all relevant journals in the University of Melbourne medical library for the years 1935-46. SELECTION CRITERIA: Randomised or controlled trials of antibiotics for children with measles. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed trial quality. MAIN RESULTS: Six trials with 1304 children were included. All but one of the trials were unblinded, and randomisation was either not described or was by alternate allocation. In four studies, the incidence of pneumonia in the control group was similar to that in the antibiotic prophylaxis group; in the other two studies, the incidence of pneumonia was unusually high in the control group so these children had a higher complication rate than the antibiotic group. Four of the 764 children given antibiotics died compared with one of the 637 controls. REVIEWER'S CONCLUSIONS: The quality of the trials reviewed was poor, and they provide very weak evidence for giving antibiotics to all children with measles. Available evidence suggests that antibiotics should be given only if a child has clinical signs of pneumonia or other evidence of sepsis.

Anti-Bacterial Agents↗
PubMed2000

A pilot study of an educational service for rural mental health practitioners in South Australia using telemedicine.

Studies have found that rural patients want to be treated in their local hospitals. However, there have been difficulties with recruiting and retaining professionals in rural areas of Australia. Isolation, lack of professional development programmes, lack of academic programmes, lack of peer consultation and the need to travel long distances are some of the reasons identified in the National Rural Health strategy. A pilot service of educational programmes delivered by telemedicine was initiated and then evaluated. Forty-six community mental health workers from nine rural areas and 20 general practitioners from five rural areas participated. High satisfaction with the use of telemedicine was recorded by both groups. Telemedicine reduced the disincentives to rural practice, and also improved the professionals' competence and confidence in managing patients with psychiatric illness.

Education, Distance↗
PubMed2000

Telemedicine for intensive support of psychiatric inpatients admitted to local hospitals.

A service was developed to treat acute psychiatric inpatients in their local hospitals using telemedicine. This reduced the need for these patients to be transferred to a psychiatric facility in Adelaide. An evaluation of outcomes showed that it was possible to manage acute psychiatric patients in this manner, reducing costs of transport. In addition, patients were treated close to their homes. Patients rated their satisfaction with the service and the use of telemedicine very highly.

Adolescent↗
PubMed2000

Pharmacokinetic study of niosome encapsulated insulin.

Pharmacokinetic profile and hypoglycemic effect, after intraperitoneal injection of insulin and insulin encapsulated in niosomes were determined in diabetic rats. Niosomes (non-ionic surfactant vesicles) of different doses and different lipid compositions were prepared by lipid layer hydration method. Plasma samples were collected at specified time intervals and plasma concentration of insulin was determined by HPLC. Blood glucose level was estimated spectrophotometrically using commercial glucose assay kit. In vitro release and pharmacokinetic profile of niosomal formulation and free insulin were evaluated. Though there was a slight delay in the in vitro drug release due to cholesterol content in the niosomes, there was no difference between the two preparations when plasma levels were compared in vivo. Niosomes significantly reduced the blood glucose level in diabetic rats. Fall in blood glucose level was almost 92% of initial value. In case of the niosomal form the half-life of insulin was prolonged by 4 -5 hr in contrast to 2 hr for free drug. Niosomes maintained the plasma insulin level up to 12 hr, but free drug was cleared quickly. The area under the plasma concentration-time curve for niosomal forms was, 26.07 degrees +/- 0.99 mIU. hr/ml and for free insulin was 11.722 +/- 1.00 mIU. hr/ml. More than 80% of the drug was successfully encapsulated to give a formulation with sustained release characteristics. Entrapment efficiency increased with increasing lipid concentration and decreased with increasing drug concentration. The results showed that insulin entrapped in niosomes prolongs the existence of drug in the body therefore increasing its therapeutic value.

Animals↗
PubMed1999

Australia's notifiable diseases status, 1997. Annual report of the National Notifiable Diseases Surveillance System.

In 1997 there were 89,579 notifications to the National Notifiable Diseases Surveillance System. A notable feature of 1997 was the pertussis outbreak which peaked towards the end of the year and resulted in 10,668 cases being notified. The highest number of notifications received was for hepatitis C (unspecified) with 19,692 notifications; this is the first year for which data have been reported for New South Wales and South Australia for this disease category. The number of measles cases rose after the low number reported in 1996 but is still well below the number reported in the outbreak years of 1993 and 1994. Rubella notifications continued to decline in 1997. Notifications of Haemophilus influenzae type b appeared to have stabilised at a low rate, having declined markedly after introduction of the conjugated vaccine in 1992. The number of cases of campylobacteriosis remained steady after having risen for several years. Notifications of hepatitis A cases rose considerably, much of this being due to one outbreak in New South Wales. The number of cases of salmonellosis rose while shigellosis numbers dropped slightly. Notifications for chlamydial infection and gonococcal infection continued to rise, whilst those for syphilis continued to fall.

Australia↗
PubMed1998

Periapical inflammatory responses and their modulation.

Periapical inflammatory responses occur as a consequence of bacterial infection of the dental pulp, as a result of caries, trauma, or iatrogenic insult. Periapical inflammation stimulates the formation of granulomas and cysts, with the destruction of bone. These inflammatory responses are complex and consist of diverse elements. Immediate-type responses--including vasodilatation, increased vascular permeability, and leukocyte extravasation--are mediated by endogenous mediators, including prostanoids, kinins, and neuropeptides. Non-specific immune responses--including polymorphonuclear leukocyte and monocyte migration and activation, and cytokine production--are elicited in response to bacteria and their products. Interleukin-1 and prostaglandins in particular have been implicated as central mediators of periapical bone resorption. Chronic periapical inflammation further involves specific T- and B-cell-mediated anti-bacterial responses, and activates a network of regulatory cytokines which are produced by Th1- and Th2-type T-lymphocytes. Various naturally occurring and genetically engineered models of immunodeficiency are beginning to help elucidate those components of the immune system which protect the pulpal/periapical complex. Both specific and non-specific responses interface with and are regulated by the neural system. The modulation of these responses by immune response modifies, cytokine antagonists, and other novel therapeutic agents is discussed. As an experimental model, periapical inflammation has many advantages which permit it to be used in studies of microbial ecology and pathogenesis, host response, neuroimmunology, and bone resorption and regeneration.

Cytokines↗