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Biomedical subjects

C Flowers

Publications and source records attributed to C Flowers.

At least 19 recordsLinked to original sources

Randomised trial of vitamin A supplementation in pregnant women in rural Malawi found to be anaemic on screening by HemoCue.

OBJECTIVE: To assess the effects of vitamin A supplementation in women with anaemia during pregnancy. DESIGN: Single-centre randomised controlled trial. SETTING: Rural community in southern Malawi, central Africa. POPULATION: Seven hundred women with singleton pregnancies at 12-24 weeks measured by ultrasound scan and with haemoglobin <11.0 g/dl by HemoCue screening method. Analysis was by intention to treat. All received iron and folate, and sulphadoxine/pyrimethamine for antimalarial prophylaxis. METHODS: Women were randomised to receive oral supplementation with daily 5000 or 10,000 iu vitamin A, or placebo. MAIN OUTCOME MEASURES: Anaemia, as assessed by Coulter counter, severe anaemia, iron status and indices of infection. RESULTS: Vitamin A deficiency was, in this rural population, less common than predicted. Vitamin A supplementation had no significant impact on anaemia, severe anaemia, iron status and indices of infection. Vitamin A stores were less likely to be depleted at the end of pregnancy in supplemented groups. CONCLUSIONS: Vitamin A supplementation programmes to reduce anaemia should not be implemented in similar antenatal populations in rural sub-Saharan Africa unless evidence emerges of positive benefit on substantive clinical outcomes. Introducing public health interventions of unknown benefit and with unclear biological mechanisms can divert scarce resources from clinical and social interventions more likely to impact maternal mortality.

Administration, Oral↗

Clinical and magnetic resonance imaging regression of progressive multifocal leukoencephalopathy in an AIDS patient after intensive antiretroviral therapy.

A 36-year-old homosexual man with 6 months of visual symptoms and headaches had right homonymous hemianopia, mild new learning impairment, and alexia with agraphia. The initial brain magnetic resonance imaging (MRI) scan was reported consistent with left occipital infarction. Subsequent MRI demonstrated abnormal demyelination in subcortical white matter and deep parieto-occipital white matter bilaterally, but primarily left. Human immunodeficiency virus testing and cerebrospinal fluid polymerase chain reaction for JC virus DNA were both positive, consistent with progressive multifocal leukoencephalopathy (PML) with AIDS. His clinical status steadily deteriorated, and MRI white matter abnormalities worsened despite high-dose antiretroviral therapy. After the antiretroviral regimen was intensified by the addition of a protease inhibitor, rapid clinical and radiographic improvement occurred with subsequent MRI studies revealing only residual left parieto-occipital encephalomalacia. PML in AIDS patients has been associated with a nearly uniformly poor prognosis until recent reports of improved outcomes after highly active antiretroviral therapy. This patient with PML and AIDS similarly showed a robust clinical and MRI response to intensive antiretroviral combination therapy, which has been maintained for more than 3 years.

AIDS-Related Opportunistic Infections↗

Nonmyeloablative hematopoietic cell transplantation. Replacing high-dose cytotoxic therapy by the graft-versus-tumor effect.

Conventional allografting produces considerable regimen-related toxicities that generally limit this treatment to patients younger than 55 years and in otherwise good medical condition. T cell-mediated graft-versus-tumor (GVT) effects are known to play an important role in the elimination of malignant disease after allotransplants. A minimally myelosuppressive regimen that relies on immunosuppression for allogeneic engraftment was developed to reduce toxicities while optimizing GVT effects. Pre-transplant total-body irradiation (200 cGy) followed by post-transplant immunosuppression with cyclosporine (CSP) and mycophenolate mofetil (MMF) permitted human leukocyte antigen (HLA)-matched sibling donor hematopoietic cell engraftment in 82% of patients (n = 55) without prior high-dose therapy. The addition of fludarabine (90 mg/m2) facilitated engraftment in all 28 subsequent patients. Overall, fatal progression of underlying disease occurred in 20% of patients after transplant. Non-relapse mortality occurred in 11% of patients. Toxicities were low. Grade 2-4 acute graft-versus-host disease (GVHD) associated with primary engraftment developed in 47% of patients, and was readily controlled in all but two patients. Donor lymphocyte infusions (DLI) were not very effective at converting a low degree of mixed donor/host chimerism to full donor chimerism; however, the addition of fludarabine reduced the need for DLI. With a median follow-up of 244 days, 68% of patients were alive, with 42% of patients in complete remission, including molecular remissions. Remissions occurred gradually over periods of weeks to a year. If long-term efficacy is demonstrated, such a strategy would expand treatment options for patients who would otherwise be excluded from conventional allografting.

Adult↗

Criterion-related validity of the Marital Disaffection Scale as a measure of marital estrangement.

The Marital Disaffection Scale was administered, along with measures of positive feelings towards spouse, problem-drinking behavior of spouse, workaholic behavior of spouse, and marital status, to 323 female members of the American Counseling Association. Scores on the Marital Disaffection Scale showed significant inverse correlations (r = -.94) with positive feelings towards spouse and (rpb = -.63) with marital status. Scores on the Marital Disaffection Scale showed significant positive relationships (r = .36) with spouse's problem drinking behavior and (r = .48) with workaholic behavior of spouse. The results support the use of the Marital Disaffection Scale as a measure of emotional estrangement in marriage.

Adult↗

Serum transferrin receptors in detection of iron deficiency in pregnancy.

A prospective hospital-based study was conducted to evaluate the efficacy of serum transferrin receptors in the detection of iron deficiency in pregnant women. The iron status of 100 pregnant women with single uncomplicated term pregnancies in the first stage of labor was established using standard laboratory measures. These included complete hemogram, red cell indices, serum iron, percent transferrin saturation, and serum ferritin. In addition, serum transferrin receptor (STFR) was estimated. The results of 81 women with complete laboratory profiles were analyzed. Thirty-five (43.2%) women were anemic (hemoglobin <11 g/dl). Hemoglobin (Hb) showed a significant correlation with MCH, MCHC, serum iron, and percent transferrin saturation, suggesting that the anemia was likely to be due to iron deficiency. The mean STFR level was 18.05+/-9.9 mg/l in the anemic women and was significantly raised (p<0.001) compared with that of the nonanemic women. STFR correlated significantly with Hb (p<0.001), MCH (p<0.05), MCHC (p<0.01), serum iron (p<0.01), and percent transferrin saturation (p<0.01) and also showed a highly significant correlation with the degree of anemia. Serum ferritin in these women did not correlate with Hb, and only 54.4% of the women had levels <12 ng/ml, which does not reflect the true prevalence of iron deficiency. Serum transferrin receptor estimation is thus a useful measure for detecting iron deficiency in pregnancy.

Adult↗

Schizophrenia, monoamine oxidase activity, and cigarette smoking.

Reduced monoamine oxidase activity has been proposed as a marker for vulnerability to schizophrenia. Reduced monamine oxidase activity has also been shown to occur in cigarette smokers. This study compared monamine oxidase activity level in a matched group of patients with schizophrenia who smoked with a group who did not. Lower levels of monoamine oxidase activity were found in the smokers and this is the likely explanation for the low levels hypothesized as a marker for schizophrenia.

Adult↗

The Caco-2 cell culture system can be used as a model to study food iron availability.

To assess the usefulness of the Caco-2 cell culture system as a model to study the availability of dietary iron, preliminary experiments were performed to determine the optimal conditions for iron uptake and transport. Iron uptake of radioactive ferrous sulfate was optimal at pH 5.5 using a 2:1 molar ratio of ascorbic acid to iron and a 1-h incubation time. Under these experimental conditions, we studied the effect on iron uptake of adding supernatants from homogenates of different meat sources, soybean protein isolates, egg albumen and bovine serum albumin. Iron uptake was 6.3 +/- 1.7% from meat, which was significantly greater (P < 0.001) than the values of 1.2 +/- 0.3% from soybean protein, 1.3 +/- 0.3% from egg albumen and 0.8 +/- 0.1% from bovine serum albumin. Iron uptake was also significantly higher from digested meat samples than from undigested meat when the protein concentration was equalized. Measurements of iron uptake and protein concentration from fractions obtained after preparative isoelectric focusing of meat and soybean protein extracts showed two peaks of higher protein concentration and iron uptake in meat, apparently not found in soybean protein, that contained the factor(s) responsible for the higher iron uptake by the cells. In view of these observed similarities with iron absorption studies in humans, we conclude that the Caco-2 cell culture system is a useful in vitro model to study food iron availability.

Ascorbic Acid↗

Serum transferrin receptor levels in the evaluation of iron deficiency in the neonate.

Iron deficiency anemia (IDA) is a major global problem. Early onset of iron deficiency in developing countries makes it imperative to identify iron deficiency in neonates. Most conventional laboratory parameters of iron status fail to distinguish neonates with iron deficient erythropoiesis. Serum transferrin receptor (STFR) levels are a recent sensitive measure of iron deficiency and the present study was carried out to evaluate the usefulness of cord serum transferrin receptors in identifying iron deficient erythropoiesis in neonates. A complete hemogram, red cell indices, iron profile: serum iron (SI), percent transferrin saturation (TS%) and serum ferritin (SF) was carried out in 100 full-term neonates and their mothers at parturition. Cord and maternal STFR levels were estimated using a sensitive enzyme-linked immunosorbent assay (ELISA) technique. Anemic women had a significantly lower SI, their TS% and high STFR levels suggesting that iron deficiency was responsible for the anemia. In the neonates of iron deficient mothers, cord SI, TS% and cord ferritin were not significantly different from those of neonates born to non-anemic mothers. Cord STFR level correlated well with hemoglobin (Hb) and laboratory parameters of iron status, and its level was significantly higher in neonates born to anemic mothers than in those born to non-anemic mothers. It was the only laboratory parameter to differentiate between neonates born to anemic and non-anemic mothers. Therefore, STFR is a sensitive index of iron status in neonates and identifies neonates with iron deficient erythropoiesis.

Adolescent↗

IMPACT: an object-oriented graphical environment for construction of multimedia patient interviewing software.

This paper describes our software for rapid construction of multimedia computer interviews. The program, which we call IMPACT, was designed to measure preferences for health outcomes using the standard gamble and other decision analytic techniques. IMPACT is also a multimedia shell program that allows researchers to interactively construct patient interviewing instruments without programming or scripting. It supports the integration of text, graphics, synthesized speech, digital sound and QuickTime movies into interviewing instruments through a point-and-click interface. IMPACT also supports branching logic and randomizing the presentation order of materials within an instrument. This allows customization of the presentation based on patient responses and facilitates experimental designs. Validation studies show that preference assessments performed using IMPACT have high test-retest reliability (r = 0.83, n = 96). Post-test surveys (n = 52) show that most subjects understand valuation methods (86%) and believe that the explanations provided were clear (96%) and that methods were reasonable (80%). The majority of subjects thought the preference assessment methods were not difficult to use (53%) and would have been comfortable using such methods for medical decisions (53%).

Computer Graphics↗

Nigral degeneration in acquired immune deficiency syndrome (AIDS).

Using stereological techniques we have estimated the volume density of melanin and counted the number of pigmented and non-pigmented neuronal cell bodies in the pars compacta of the substantia nigra of 12 autopsied patients with acquired immune deficiency syndrome (AIDS) who did not have inflammation or necrosis of the midbrain or clinical parkinsonism. The total number of neuronal cell bodies was 25% lower in AIDS (P less than 0.01) than in 12 age-matched controls, although the volume density of neuronal melanin did not differ from that of controls because the percentage of pigmented cell bodies was higher (P less than 0.01) and the cell bodies were more fully packed with melanin in AIDS. Also, the expected increase with age of the volume density of neuronal melanin (P less than 0.02) and the percentage of pigmented neurons (P less than 0.01) occurred in the controls but not in AIDS patients. Importantly, our histopathological examination showed unequivocal nigral degeneration with neuronal loss, small neuronal cell bodies packed with melanin, reactive astrocytosis and extra-cellular melanin in the AIDS patients but not in controls. Our study shows that a subclinical nigral degeneration is common in AIDS and could possibly explain the heightened susceptibility of some patients to drug-induced parkinsonism.

Acquired Immunodeficiency Syndrome↗

The causes of bone scintigram hot spots in fluoride-treated osteoporotic patients.

We previously described new bone formation in fluoride-treated osteoporotic patients. Since then, several investigators have contended that fluoride-induced "hot spots," as seen on bone scintigrams, represent stress fractures. To further evaluate this issue we analyzed scintigrams, radiographs, and quantitative computer tomography (CT) scans of the spine and femoral condyles from 129 patients, obtained before and during therapy. Hot spots, new or of increased intensity, were more than twice as common in the weight-bearing peripheral skeleton than in nonweight-bearing sites (p less than 0.001). The hot spots were usually diffuse, multiple, bilateral, and mostly seen early in therapy, a pattern quite different from that expected of stress fractures. Previously, we postulated that mechanical stress and fluoride act synergistically to stimulate new bone formation. If this hypothesis were correct, we would expect to see a greater increase in femoral condyle bone density in patients with hot spots. Consistent with this hypothesis, patients who developed hot spots in the knees had a greater increase in condylar density (22 +/- 2.5 vs. 9 +/- 3.3 mg/cc) than those without hot spots and stress fractures were not seen in either group. Additionally, patients with more than 5 hot spots in the peripheral skeleton had greater increases in spinal and condylar density than those with fewer than 5 hot spots. Finally, stress fractures were found in less than 2% of our patients. While we do not exclude the possibility that some additional patients may have had stress fractures, our data support the hypothesis that the great majority of hot spots seen on the scintigrams are the sites of new bone formation.

Adult↗

The relationship of "high risk" mammographic patterns to histological risk factors for development of cancer in the human breast.

In the UK Trial for the Early Detection of Breast Cancer in Nottingham, 119 women were identified as having fibrocystic change with epithelial hyperplasia or in situ carcinoma. Their mammograms were classified according to Wolfe's criteria and the corresponding histology for each patient was classified for degrees of epithelial hyperplasia, atypia and in situ neoplasia using Page's criteria. A control population of patients presenting for breast screening was used to represent the general population. No correlation was found between the four mammographic Wolfe patterns, N1, P1, P2 and DY and histological evidence of epithelial hyperplasia, atypia or in situ carcinoma. A further study was carried out to determine histological features of Wolfe pattern, using radiological examination of resected breast tissue. The variation in Wolfe pattern was related to the distribution of fibrous and adipose tissue in the breast interlobular stroma and appeared to have no relationship to epithelial parenchymal content. This information does not support the hypothesis that radiographic densities of P2 and DY patterns correspond to high risk epithelial proliferation.

Breast↗

Duodenal iron proteins in idiopathic hemochromatosis.

This study was undertaken to assess the relationship between iron absorption and the concentration of duodenal iron proteins in normal subjects and patients with idiopathic hemochromatosis (IH). Biopsies were obtained endoscopically from the duodenum in 17 normal subjects, 3 of whom were mildly iron deficient, and 7 patients with untreated IH. The absorption of both heme and nonheme iron was increased in IH despite a 20-fold elevation in serum ferritin. Immunoassays using MAb were used to measure transferrin, H-rich ferritin, and L-rich ferritin in mucosal samples. Mucosal transferrin concentrations in normal subjects did not correlate with either iron status or iron absorption, indicating that mucosal transferrin plays no physiological role in iron absorption. Mucosal transferrin was significantly lower in IH, presumably because of a decrease in mucosal transferrin receptors. Mucosal H and L ferritin concentrations were directly related to body iron stores and inversely related to iron absorption in normal subjects. In IH, mucosal H and L ferritin failed to increase in parallel with the serum ferritin, but were appropriate for the level of iron absorption. The relationship of mucosal H/L ferritin in IH did not differ from that observed in normal subjects. Our findings indicate that the major abnormality in duodenal iron proteins in IH is a parallel decrease in the concentration of H- and L-rich ferritin. It is not evident whether this is the result or the cause of the absorptive abnormality.

Adult↗

Adolescent suicide attempters presenting to a pediatric facility.

This study profiles the characteristics of adolescent suicide attempters and the treatment they received in a pediatric emergency room (ER). A retrospective chart review of 4,072 adolescents seen in the ER at a children's hospital (CH) from July 1984 to June 1985 was undertaken. Twenty-seven adolescents who had deliberately injured themselves were identified. The average age was 14 years 7 months (range 11-19 years). Fifty-two percent of the patients were white and 78% were female. Ingestion was the most common method (78%), followed by attempted hanging (11%), and wrist laceration (7%). After evaluation by a pediatrician in the ER, 30% of the patients were treated and released, 11% were transferred directly to a psychiatric hospital, and 59% were admitted to the CH, with an average hospital stay of 1.88 days. Once hospitalized, consultations from psychiatry (81%), social service (50%), psychology (19%), and neurology (6%) were obtained. At the time of discharge from either the ER or CH, the patients had a variety of plans for ongoing care, with 52% being referred to outpatient counseling, 37% being transferred to a psychiatric hospital, and 11% having no documented plan for ongoing care. These results demonstrate that the evaluation of suicidal adolescents cared for in a pediatric facility may be episodic and suggest the need for a comprehensive program to approach the problem.

Adolescent↗