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Biomedical subjects

N McGrath

Publications and source records attributed to N McGrath.

17 recordsLinked to original sources

HIV epidemic trend and antiretroviral treatment need in Karonga District, Malawi.

We describe the development of the HIV epidemic in Karonga District, Malawi over 22 years using data from population surveys and community samples. These data are used to estimate the trend in HIV prevalence, incidence and need for antiretroviral treatment (ART) using a simple mathematical model. HIV prevalence rose quickly in the late 1980s and early 1990s, stabilizing at around 12% in the mid-1990s. Estimated annual HIV incidence rose quickly, peaking in the early 1990s at 2.2% among males and 3.1% among females, and then levelled off at 1.3% among males and 1.1% among females by the late 1990s. Assuming a 2-year eligibility period, both our model and the UNAIDS models predicted 2.1% of adults were in need of ART in 2005. This prediction was sensitive to the assumed eligibility period, ranging from 1.6% to 2.6% if the eligibility period was instead assumed to be 1.5 or 2.5 years, respectively.

Adolescent↗

Community attitudes towards individuals living with HIV in rural KwaZulu-Natal, South Africa.

Antenatal sero-prevalence rates of 30% and more have been reported in KwaZulu-Natal since 1998 and over 50% of all adult deaths in 2000 were due to AIDS. Understanding the changing social and cultural attitudes to AIDS is important in providing contextual information to aid the design of interventions. This paper examines community attitudes towards individuals living with HIV. Eleven focus groups were conducted with men and women. Participants were asked to discuss how people living with HIV were treated within the family and community. The discussions were recorded and transcribed in isiZulu and then translated into English. These were coded using Nud*ist 6 software to identify key themes and sub-themes using content analysis. Gender and area differences were investigated. Generally participants expressed positive attitudes to the treatment of AIDS patients and felt that people living with HIV were being cared for within families. However, they reported more negative attitudes to those living with HIV by the general community and suggested these attitudes and acts of discrimination influenced disclosure. Discrimination included physical isolation and symbolism such as referring to them using a 'three finger' gesture. Participants also reported mixed responses to known HIV-positive individuals, ranging from sympathy to a lack of care, on the grounds that the person is certain to die. There are gender differences in terms of the attitudes towards people living with HIV. Compassion and hopelessness seem to be more common among women than men.

Adult↗

Socio-economic and demographic factors associated with prevalence of HIV infection among pregnant women in Dar es Salaam, Tanzania.

BACKGROUND: HIV/AIDS epidemic has become generalised in low resource settings in sub-Saharan Africa where 90% of all maternal-foetal transmission of HIV infection occurs. Global effort to scale-up pMTCT is underway, however, mechanisms to maximise screening of HIV- 1 positive women for Nevirapine treatment and other interventions, are not clear. OBJECTIVE: To identify socioeconomic and demographic characteristics associated with the prevalence of HIV- 1 infection among Tanzanian women. DESIGN: Cross-sectional study. SETTING: Four antenatal clinics in Dar es Salaam. RESULTS: HIV prevalence rate was 13.1 (95% confidence interval (CI): 12.7% - 13.5%) and it increased with increasing maternal age. Older age than 25, mid-arm circumference less than 25cm, geographic location, working in a public house, and partner's occupation were independently associated with higher prevalence of infection. Women in monogamous marriages were 77% less likely to be HIV infected compared to women with no regular partner. Similarly, women with more than five persons per household, and those who spent less on food had a significantly lower HIV prevalence. CONCLUSION: HIV infection is sufficiently widespread among women in Dar es Salaam suggesting that screening based on socioeconomic and demographic characteristics would miss a large proportion of the positives. There is need to increase facilities for counselling and testing using an opt-out approach for testing in all antenatal clinics in the city.

Adolescent↗

The effects of zidovudine in the subset of infants infected with human immunodeficiency virus type-1 (Pediatric AIDS Clinical Trials Group Protocol 076).

OBJECTIVE: To describe the effect of zidovudine on human immunodeficiency virus type 1 (HIV-1) and on the course of disease in infants who became infected while they and their mothers received zidovudine preventive therapy or placebo in Pediatric AIDS Clinical Trials Group Protocol 076. STUDY DESIGN: Observational substudy of a multicenter, randomized, double-blind, placebo-controlled trial. METHODS: We compared the progression of disease, timing of HIV-1 transmission, and the plasma HIV-1 RNA level in infected infants of mother-infant pairs who were randomly assigned to receive zidovudine (n = 14) or placebo (n = 43). The development of genotypic zidovudine resistance was assessed among infected infants in the zidovudine treatment group. RESULTS: In this limited study, zidovudine therapy during pregnancy and labor and in the neonatal period for 6 weeks failed to have a major effect on rapid progression of disease, timing of transmission, and viral replication in HIV-infected infants. When the zidovudine treatment regimen failed to prevent maternal-infant transmission of HIV-1, resistance to zidovudine did not develop during study treatment. CONCLUSIONS: Our study supports the safety of zidovudine use in pregnancy and in the newborn period but demonstrates the continued need for more potent antiretroviral treatment of the infected infant.

Acquired Immunodeficiency Syndrome↗

Homeologous plastid DNA transformation in tobacco is mediated by multiple recombination events.

Efficient plastid transformation has been achieved in Nicotiana tabacum using cloned plastid DNA of Solanum nigrum carrying mutations conferring spectinomycin and streptomycin resistance. The use of the incompletely homologous (homeologous) Solanum plastid DNA as donor resulted in a Nicotiana plastid transformation frequency comparable with that of other experiments where completely homologous plastid DNA was introduced. Physical mapping and nucleotide sequence analysis of the targeted plastid DNA region in the transformants demonstrated efficient site-specific integration of the 7.8-kb Solanum plastid DNA and the exclusion of the vector DNA. The integration of the cloned Solanum plastid DNA into the Nicotiana plastid genome involved multiple recombination events as revealed by the presence of discontinuous tracts of Solanum-specific sequences that were interspersed between Nicotiana-specific markers. Marked position effects resulted in very frequent cointegration of the nonselected peripheral donor markers located adjacent to the vector DNA. Data presented here on the efficiency and features of homeologous plastid DNA recombination are consistent with the existence of an active RecA-mediated, but a diminished mismatch, recombination/repair system in higher-plant plastids.

Base Sequence↗

Randomised trial of effects of vitamin supplements on pregnancy outcomes and T cell counts in HIV-1-infected women in Tanzania.

BACKGROUND: In HIV-1-infected women, poor micronutrient status has been associated with faster progression of HIV-1 disease and adverse birth outcomes. We assessed the effects of vitamin A and multivitamins on birth outcomes in such women. METHODS: In Tanzania, 1075 HIV-1-infected pregnant women at between 12 and 27 weeks' gestation received placebo (n=267), vitamin A (n=269), multivitamins excluding vitamin A (n=269), or multivitamins including vitamin A (n=270) in a randomised, double-blind, placebo-controlled trial with a 2x2 factorial design. We measured the effects of multivitamins and vitamin A on birth outcomes and counts of T lymphocyte subsets. We did analyses by intention to treat. RESULTS: 30 fetal deaths occurred among women assigned multivitamins compared with 49 among those not on multivitamins (relative risk 0.61 [95% CI 0.39-0.94] p=0.02). Multivitamin supplementation decreased the risk of low birthweight (<2500 g) by 44% (0.56 [0.38-0.82] p=0.003), severe preterm birth (<34 weeks of gestation) by 39% (0.61 [0.38-0.96] p=0.03), and small size for gestational age at birth by 43% (0.57 [0.39-0.82] p=0.002). Vitamin A supplementation had no significant effect on these variables. Multivitamins, but not vitamin A, resulted in a significant increase in CD4, CD8, and CD3 counts. INTERPRETATION: Multivitamin supplementation is a low-cost way of substantially decreasing adverse pregnancy outcomes and increasing T-cell counts in HIV-1-infected women. The clinical relevance of our findings for vertical transmission and clinical progression of HIV-1 disease is yet to be ascertained.

CD3 Complex↗

Herpes simplex encephalitis treated with acyclovir: diagnosis and long term outcome.

OBJECTIVES: The frequency and characteristics of the long term sequelae of herpes simplex encephalitis were assessed after treatment with acyclovir. METHODS: Patients were included if they were treated with acyclovir and the diagnosis of herpes simplex encephalitis was confirmed by culture of herpes simplex virus (HSV) from the brain, an increase in the CSF HSV antibody titre, or detection of HSV deoxyribonucleic acid in the CSF. Each patient's medical records were reviewed and surviving patients were interviewed and examined. RESULTS: A diagnosis of herpes simplex encephalitis was confirmed in 42 patients. Five patients (12%) died in the first month. Three patients (7%) had severe neurological sequelae and died after a longer interval. All but one of the 34 surviving patients had neurological symptoms, an abnormal neurological examination, or both. Twenty patients (48%) performed everyday activities as well as before herpes simplex encephalitis; nine patients (21%) were living independently, but were functioning at a lower level than before the illness; and five patients (12%) had a severe neurological deficit. Twenty nine of the 34 survivors were assessed six months to 11 years after herpes simplex encephalitis. The most common long term symptoms were memory impairment (69%), personality and behavioural abnormalities (45%), and epilepsy (24%). Short term memory impairment (70%), anosmia (65%), and dysphasia (41%) were the most common signs. CONCLUSIONS: Although acyclovir has reduced the mortality of herpes simplex encephalitis, 30% of this group of patients either died or had a severe neurological deficit. The other 70% of the patients regained independence in activities of daily living, but most of these people had persistent neurological symptoms, signs, or both.

Acyclovir↗

The long-term neuropsychological outcome of herpes simplex encephalitis in a series of unselected survivors.

This study sought to produce a cognitive profile of herpes simplex encephalitis (HSE) survivors from a large group of definitively diagnosed, acyclovir-treated participants. Results from 22 adults who underwent a battery of neuropsychological tests indicated anterograde memory dysfunction to be the most severe and common deficit (although the variation was great), with less severe and less frequent impairments in the areas of retrograde memory, executive functions, and language functioning. Overall, neuropsychological outcome was unimpaired in six participants, mildly impaired in thirteen, moderately impaired in one, severely impaired in two. Older participants and those with a lower level of consciousness before the start of treatment produced poorer scores on certain aspects of cognitive outcome (p < 0.05). A significantly better cognitive outcome was found in participants for whom there was a short delay (fewer than 5 days) between symptom onset and acyclovir treatment compared with those participants for whom there was a longer delay. The two children in the study had disparate results on most tests, the exception being those assessing memory functioning on which both children had scores at population norms. On a naming task designed to explore category-specific knowledge deficits, the adults as a group made more errors on pictures of living things than nonliving things (matched pair-wise for word frequency and visual familiarity), although this difference disappeared on a smaller subset of pictures also matched for visual complexity.

Acyclovir↗

Measures of prefrontal dysfunction after closed head injury.

Tasks sensitive to frontal lobe dysfunction (delayed response, delayed alternation, object alternation, and Wisconsin Card Sort) were administered to 20 patients with post-acute closed-head injury (CHI). Time since injury varied (6 to 280 months; mean, 48 months), as did length of coma (2 hr to 120 days; mean, 38 days). Compared to normal controls, CHI patients showed no deficits on delayed response tasks, but were impaired on delayed alternation, object alternation, and the Wisconsin Card Sort Test. Analyses of the performance profiles of the CHI patients suggested that they may have difficulty in establishing set (a consequence of damage to the orbitofrontal system).

Adult↗

Randomized study of the tolerance and efficacy of high- versus low-dose zidovudine in human immunodeficiency virus-infected children with mild to moderate symptoms (AIDS Clinical Trials Group 128). Pediatric AIDS Clinical Trials Group.

The current dosage of zidovudine for children is 180 mg/m2 every 6 h. To investigate whether a lower dosage was equally effective, human immunodeficiency virus (HIV)-infected children (3 months to 12 years) with mild to moderate symptoms were randomly assigned to receive either high-dose (180 mg/m2/dose) or low-dose (90 mg/m2/dose) zidovudine (double-blind). Treatments were compared with respect to neuropsychologic function, survival, clinical and laboratory evidence of disease progression, and safety and tolerance. Four hundred twenty-six HIV-infected children were enrolled; median time for receipt of study drug was 35 months. Zidovudine in either dose was well tolerated, with no difference in efficacy or tolerance by treatment group using any clinical or laboratory parameter. In children with mild to moderate disease, a reduction of zidovudine to 90 mg/m2/dose will result in substantial cost savings and should be the recommended dose.

AIDS Dementia Complex↗

A controlled trial of intravenous immune globulin for the prevention of serious bacterial infections in children receiving zidovudine for advanced human immunodeficiency virus infection. Pediatric AIDS Clinical Trials Group.

BACKGROUND: Serious bacterial infections are common in children infected with the human immunodeficiency virus (HIV). Studies performed before zidovudine became standard therapy found that intravenous immune globulin decreases the number of serious bacterial infections in these children. We designed a multicenter study to evaluate the efficacy of intravenous immune globulin in children with advanced HIV infection who were receiving zidovudine. METHODS: In a double-blind trial 255 children between 3 months and 12 years of age who had the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex were randomly assigned to receive either intravenous immune globulin (400 mg per kilogram of body weight) (n = 129) or placebo (0.1 percent albumin) (n = 126) every 28 days. All children received 180 mg of zidovudine per square meter of body-surface area orally four times daily. Treatment assignment was stratified according to whether the patients had a history of one or more serious bacterial infections, had previously been treated with zidovudine, or were currently receiving prophylaxis with trimethoprim-sulfamethoxazole. The median length of follow-up was 30.6 months. RESULTS: The estimated two-year rates of serious bacterial infections with confirmed pathogens were 16.9 percent for the immune globulin group and 24.3 percent for the placebo group (relative risk, 0.60; 95 percent confidence interval, 0.35 to 1.04; P = 0.07). The treatment effect was seen primarily among the 174 children who were not receiving trimethoprim-sulfamethoxazole prophylaxis at entry; the estimated two-year rates of infection were 11.3 percent for the immune globulin group and 26.8 percent for the placebo group (relative risk, 0.45; 95 percent confidence interval, 0.22 to 0.91; P = 0.03). For the 81 children who were receiving trimethoprim-sulfamethoxazole prophylaxis initially, the rates were 27.7 percent in the immune globulin group and 17.7 percent in the placebo group (relative risk, 1.26; 95 percent confidence interval, 0.44 to 3.66; P = 0.67). The two-year survival was similar in the two groups: 79.2 percent among immune globulin recipients and 75.4 percent among placebo recipients (P = 0.41). CONCLUSIONS: In children with advanced HIV disease who are receiving zidovudine, intravenous immune globulin decreases the risk of serious bacterial infections. However, this benefit is apparent only in children who are not receiving trimethoprim-sulfamethoxazole as prophylaxis.

AIDS-Related Complex↗

Severe vitamin D deficiency in Auckland.

AIMS: To study the presentation of severe vitamin D deficiency in Auckland and to determine if appropriate therapy was given. METHODS: Retrospective review of records of patients with very low plasma 25 hydroxyvitamin D concentrations (< or = 12.5 nmol/L or 5 micrograms/L). RESULTS: Fifty cases were identified over a two year period. 28 subjects had recognised risk factors for vitamin D deficiency (such as gastrointestinal disease or greatly reduced food intake). The majority of the other 22 subjects were elderly residents of rest homes or private hospitals. Low body weight and reduced mobility were common features of both groups. Increased plasma alkaline phosphatase activity and hypocalcaemia were the most frequent biochemical findings. Appropriate treatment with high dose calciferol had been given to only 28% of the subjects. CONCLUSIONS: Severe vitamin D deficiency does occur in Auckland despite its low latitude. Low body weight, reduced mobility and lack of sun exposure are particular risk factors. Appropriate therapy is cheap, safe and effective but many patients with severe vitamin D deficiency are being managed suboptimally.

Adolescent↗

It may be more significant than you think: BB air rifle injury to a child's head.

BB guns of 20 years ago were constructed of coils and springs which generated relatively little force, so that a projectile posed little threat of serious injury. Today, the coil and spring construction has been replaced by pump action pneumatic chambers which allow generation of muzzle velocities near 350 ft/sec. Speeds of 150 ft/sec and 200 ft/sec are required for skin penetration and bone penetration, respectively. We present a seven-year-old boy who suffered intracranial parenchymal injury from an air-powered BB gun projectile while playing with friends. We discuss literature which suggests these once-innocent toys are now harbingers of severe, if not fatal, injury.

Child↗

Emergency center laboratory evaluation of pediatric trauma victims.

Emergency center (ER) trauma evaluations often include leukocyte count (LC), serum amylase (SA), electrolytes (EL), and urine analysis. We reviewed records of 100 pediatric ER patients to determine utility of these tests in management of blunt injury. SA was evaluated in 65 patients and ranged from 30-146 U/L (mean 50.6 U/L); 14 patients with normal CT scans had SA from 30-68 U/L (mean 49.1 U/L). Six patients with intraabdominal or retroperitoneal injuries had SA from 30-130 U/L (mean 64.0 U/L), P = NS. LC was determined in 76 patients and ranged 2.3-28.3 k/ml (mean 13.8 k/ml). Patients with normal abdominal CT (12) had mean LC 14.8 k/ml (range 7.2-19.6 k/ml). Eight patients with injuries on CT had mean LC 14.4 k/ml (range 3.5-27.1 k/ml). ER, SA, and LC did not alter patient management. Thirty-four patients had serum sodium, 36 potassium, and 33 chloride and bicarbonate determinations. Sodium, potassium, and chloride levels were uniformly normal; bicarbonate and leukocyte counts were uniformly abnormal in initial evaluations. These changes are expected in response to severe injury and their determinations did not alter patient care. Combined laboratory urinarlysis (LA) and urine dipstick (DA) analysis for hematuria had sensitivity 75.0 per cent (specificity 81.6%). LA predicted injury with sensitivity 75.0 per cent (specificity 81.6%). DA predicted injury with sensitivity 60.0 per cent (specificity 79.2%). DA accurately represented LA results (sensitivity 100%, specificity of 94.5%). DA is a rapid and effective replacement of LA in evaluation of trauma patients in the emergency center.

Amylases↗