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Biomedical subjects

Jennifer Wells

Publications and source records attributed to Jennifer Wells.

11 recordsLinked to original sources

Range of normal neutrophil counts in healthy zimbabwean infants: implications for monitoring antiretroviral drug toxicity.

Mother-to-child HIV prevention trials in sub-Saharan Africa use the US National Institutes of Health Division of AIDS (DAIDS) grading scale to monitor hematologic toxicity. A recent study of nevirapine prophylaxis given for 6 months in breast-feeding Zimbabwean infants reported several cases of relative neutropenia in clinically well infants, raising concerns of drug toxicity. However, the DAIDS tables are based on normal blood counts for white infants, although there is evidence that black African infants may have lower absolute neutrophil counts (ANCs) than white infants. To establish normal hematologic values in black Zimbabwean infants and to quantify the apparent prevalence of relative neutropenia in this population, we evaluated HIV-uninfected healthy infants born to HIV-uninfected women at birth, 10 days, 6 weeks, 3, and 4 months of life. A physical examination and blood count were performed at each visit, and an HIV test was performed at the final visit. The ANC values were graded using the DAIDS table. A total of 145 healthy term infants satisfied the inclusion criteria. The mean ANC values for Zimbabwean infants were less than half of the corresponding standard values at all 5 time points (P < 0.0001). Using the DAIDS table in use at the time that the blood was collected, 57% of these healthy infants had relative neutropenia of any grade at birth, followed by 29% at day 10, 53% at 6 weeks, 32% at 3 months, and 37% at 4 months of life. Our data indicate that relative neutropenia exists in healthy black Zimbabwean infants. The guidelines for identifying toxicity were changed in December 2004. However, even by the new DAIDS tables, 43%, 23%, 24%, 42%, and 43% of these healthy babies had relative neutropenia at the time of the 5 visits. Future HIV prevention and treatment trials in sub-Saharan Africa should use normal hematologic values derived from African infants to avoid the overestimation of antiretroviral drug toxicity.

Anti-HIV Agents↗

Breast-milk shedding of drug-resistant HIV-1 subtype C in women exposed to single-dose nevirapine.

Single-dose nevirapine reduces intrapartum human immunodeficiency virus 1 type (HIV-1) transmission but may also select for nonnucleoside reverse-transcriptase inhibitor (NNRTI) resistance in breast milk (BM) and plasma. Among 32 Zimbabwean women, median 8-week postpartum plasma and BM HIV-1 RNA levels were 4.57 and 2.13 log(10) copies/mL, respectively. BM samples from women with laboratory-diagnosed mastitis (defined as elevated BM Na(+) levels) were 5.4-fold more likely to have HIV-1 RNA levels above the median. BM RT sequences were not obtained for 12 women with BM HIV-1 RNA levels below the lower limit of detection of the assay used. In 20 paired BM and plasma samples, 65% of BM and 50% of plasma RT sequences had NNRTI-resistance mutations, with divergent mutation patterns.

Anti-HIV Agents↗

Screening for psychological morbidity in HIV-infected and HIV-uninfected pregnant women using community counselors in Zimbabwe.

OBJECTIVE: To examine the prevalence of psychological morbidity in HIV-infected and uninfected pregnant women seeking antenatal care in Zimbabwe. METHODS: Pregnant women were screened for psychological morbidity at the initial antenatal care visit using the 14-item Shona Symptom Questionnaire (SSQ) before voluntary HIV counseling and testing (VCT). The primary outcome measure was "cases," as determined by a SSQ score of >or= 8. Demographic characteristics and HIV status were compared between cases and noncases to determine the risk factors for psychological morbidity. RESULTS: Of the 437 participants, psychological morbidity was detected in 73 (17%) women before undergoing VCT. Risk factors for psychological morbidity included having a spouse older than 35 years of age. HIV infection by itself was not a risk factor for psychological morbidity for women. CONCLUSIONS: There is a high burden of psychological morbidity among pregnant women in Zimbabwe. Mental health services should be integrated into antenatal care to improve psychological health for all women in Zimbabwe.

Adolescent↗

The promise of minocycline in neurology.

The capacity of minocycline to alleviate disease for several neurological disorders in animals is increasingly being recognised. Indeed, that one drug alone can attenuate the severity of disease in stroke, multiple sclerosis, spinal-cord injury, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis is astounding. In this review, we describe the evidence for the efficacy of minocycline in several animal models of neurological disease, discuss the mechanisms by which minocycline affects a range of neurological diseases with diverse causes, and introduce the emerging investigation of minocycline in clinical neurology. The encouraging results of minocycline in experimental neurology bode well for its therapeutic use in human neurological diseases.

Animals↗

Vision-specific health-related quality of life in age-related maculopathy patients presenting for low vision services.

Few studies have examined the effectiveness of low vision rehabilitation for age-related maculopathy (ARM) patients and its impact on vision-specific health-related quality of life (HRQoL). However, before a multi-site clinical trial can be conducted, appropriate outcome measures need to be identified for ARM patients who seek out low vision rehabilitation, including a vision-specific HR QoL instrument. The 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) was developed to assess vision-specific HRQoL for low vision patients, including those with ARM. This study examines the performance of the NEI VFQ-25 among ARM patients who seek out low vision services and examines its relationship with visual acuity and self-reported use of low vision aids. One hundred and twenty-seven patients were recruited from a University-affiliated low vision clinic. During two telephone interviews, subjects completed the NEI VFQ-25 and a short cognitive test and provided information on general health and use of low vision aids. Additional information on visual acuity and eye health were collected from the medical record. Our results indicate that ARM patients who seek out low vision services report significant impairment in their vision-specific HRQoL. Their NEI VFQ-25 scores were lower compared to other ARM and low vision rehabilitation samples previously studied. The VFQ subscales with the largest deficits were near and distance visual acuities and psychosocial issues (near vision, distance vision, role difficulties, dependency, social functioning, mental health). These subscale scores were lower for those with greater visual acuity impairment. The VFQ subscale scores most impacted by the disease had wide variability and were higher for those who used low vision aids, suggesting that the NEI VFQ-25 is suitable for measuring further decline and treatment-related improvements. Thus, it should be strongly considered for a multi-site clinical trial on the effectiveness of low vision rehabilitation.

Aged↗

Safety and trough concentrations of nevirapine prophylaxis given daily, twice weekly, or weekly in breast-feeding infants from birth to 6 months.

Despite the success of antiretroviral prophylaxis in reducing mother-to-child HIV-1 transmission, postpartum transmission through breast milk remains a problem. Antiretroviral administration to the infant during the period of breast-feeding could protect against postnatal transmission. An open-label phase 1/2 study was designed to assess the safety and trough concentrations of nevirapine (NVP) given once weekly (OW), twice weekly (TW), or once daily (OD) to HIV-exposed breast-feeding infants for 24 weeks. Following maternal dosing with 200 mg NVP orally at onset of labor, breast-feeding infants were randomized within 48 hours of birth to 1 of 3 regimens: arm 1, NVP given OW (4 mg/kg from birth to 14 days, upward arrow to 8 mg/kg from 15 days to 24 weeks), arm 2, NVP given TW (4 mg/kg from birth to 14 days, upward arrow to 8 mg/kg from 15 days to 24 weeks), and arm 3, NVP given OD (2 mg/kg from birth to 14 days, upward arrow to 4 mg/kg from 15 days to 24 weeks). Trough NVP concentrations and clinical and laboratory abnormalities were monitored. Of the 75 infants randomized (26 to OW, 25 to TW, and 24 to OD dosing), 63 completed the 32-week follow-up visit. No severe skin, hepatic, or renal toxicity related to NVP was observed. Neutropenia occurred in 8 infants. Trough NVP levels were lower than the therapeutic target (100 ng/mL) in 48 of 75 (64.0%) samples from infants in the OW arm, 3 of 65 (4.6%) samples in the TW arm, and 0 of 72 samples in the OD arm. Median (range) trough NVP concentrations were 64 ng/mL (range: <25-1519 ng/mL) with OW dosing; 459 (range: <25-1386 ng/mL) with TW dosing; and 1348 (range: 108-4843 ng/ml) with OD dosing. Our data indicate that NVP prophylaxis for 6 months was safe and well tolerated in infants. OD NVP dosing resulted in all infants with trough concentration greater than the therapeutic target and maintenance of high drug concentrations. A phase 3 study is planned to assess the efficacy of OD infant NVP regimen to prevent breast-feeding HIV-1 transmission.

Acquired Immunodeficiency Syndrome↗

Driving disability and dizziness.

PROBLEM: People with dizziness caused by vestibular (i.e., inner ear) disorders complain of difficulty driving. Physicians occasionally warn their patients with vestibular disorders not to drive. Few studies have asked patients about their driving performance, so little data are available. METHOD: Using the Driving Habits Questionnaire, the authors did structured interviews with people with several different vestibular disorders and with normal subjects. The self-reported crash rate and rate of citations for moving violations did not differ between the subject groups. RESULTS: Patients report reduced driving skills, particularly in situations when visual information is reduced, rapid head movements are used, and specific path integration or spatial navigation skills are needed.

Adult↗

Long-term effects of clomethiazole in a model of global ischemia.

The failure of neuroprotective drugs in clinical trials has raised questions about the predictive value of animal models. To address this issue we reexamined the efficacy of clomethiazole using functional and histological outcome measures in combination with long-term survival times. Gerbils were exposed to 5 min of global ischemia and received 400 mg/ml clomethiazole (via osmotic minipump) plus a bolus injection (60 mg/kg) 30 min after ischemia. Brain temperature was maintained at approximately 36.5 degrees C during ischemia and for the first 30 min after ischemia, and was monitored in all groups for 24 h. Subgroups of clomethiazole-treated gerbils had their temperatures regulated in the normothermic range while in other animals temperature was not controlled. Open-field habituation tests were conducted 5, 10, 30, and 60 days after occlusion. CA1 cell counts and CA1 slice recordings were done at the conclusion of behavioral testing. Clomethiazole significantly attenuated CA1 cell loss at 10-, 30-, and 60-day survival. A modest reduction in habituation deficits was evident only on Day 10 (P < 0.05). Similarly, field potential amplitude was not maintained in the rostral CA1 region. Clomethiazole produced mild hypothermia that developed over several hours. Based on short-term CA1 cell counts, clomethiazole provided significant histological protection with limited functional preservation. Neuroprotection disappeared when longer survival times (60 day) were employed and temperature confounds eliminated. These data demonstrate the necessity of utilizing more clinically relevant survival times and carefully monitoring/regulating postischemic temperature when assessing potential neuroprotective compounds.

Animals↗

Driving habits and health-related quality of life in patients with age-related maculopathy.

PURPOSE: To characterize the driving habits of persons with age-related maculopathy who present to a low-vision rehabilitation clinic and to examine how driving status relates to vision-specific health-related quality of life. METHODS: The Driving Habits Questionnaire, the National Eye Institute Vision Function Questionnaire-25, and the Life Space Questionnaire were administered via telephone interview to 126 patients with age-related maculopathy who presented to a low-vision clinic during the previous year and were either past or current drivers. RESULTS: Twenty-four percent of the sample reported being a current driver. Compared with those who stopped driving, current drivers were more likely to be male, younger, have better visual acuity and higher National Eye Institute Vision Function Questionnaire-25 scores. Drivers reported driving an average of 4 days and 10 miles per week. Over 50% of drivers reported that because of their vision, they had difficulty with or did not drive at all in rain, at night, on freeways or interstate highways, in heavy traffic areas, or during rush hour. Drivers and nondrivers did not differ in their life space, the spatial extent of their excursions into their environment. CONCLUSION: Some individuals who present to a low-vision clinic with age-related maculopathy do drive, although their driving exposure is low and they report avoiding challenging on-road situations. Driving status in age-related maculopathy appears to be related to better eye visual acuity and vision-specific health-related quality of life.

Activities of Daily Living↗

Impact of cataract surgery on motor vehicle crash involvement by older adults.

CONTEXT: Motor vehicle crash risk in older drivers is elevated in those with cataract, a condition that impairs vision and is present in half of adults aged 65 years or older. OBJECTIVE: To determine the impact of cataract surgery on the crash risk for older adults in the years following surgery, compared with that of older adults who have cataract but who elect to not have surgery. DESIGN, SETTING, AND PATIENTS: Prospective cohort study of 277 patients with cataract, aged 55 to 84 years at enrollment, who were recruited from 12 eye clinics in Alabama from October 1994 through March 1996, with 4 to 6 years of follow-up (to March 1999). MAIN OUTCOME MEASURE: Police-reported motor vehicle crash occurrence involving patients who elected to have surgery compared with those who did not. RESULTS: Comparing the cataract surgery group (n = 174) with the no surgery group (n = 103), the rate ratio for crash involvement was 0.47 (95% confidence interval, 0.23-0.94), adjusting for race and baseline visual acuity and contrast sensitivity. The absolute rate reduction associated with cataract surgery was 4.74 crashes per million miles of travel. CONCLUSIONS: In our sample, patients with cataract who underwent cataract surgery and intraocular lens implantation had half the rate of crash involvement during the follow-up period compared with cataract patients who did not undergo surgery. Cataract surgery thus may have a previously undocumented benefit for older driver safety, reducing subsequent crash rate.

Accidents, Traffic↗