Correction: effect of neuroimaging studies on acute ischemic stroke.
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Brain Ischemia↗
Biomedical subjects
S Allen
Publications and source records attributed to S Allen.
In situ observation of streptavidin-biotin binding on an immunoassay well surface using an atomic force microscope.
Polystyrene microtitre wells are commonly used as supports for the enzyme-linked immunosorbent assay (ELISA) method of biomolecular detection, which is employed in the routine diagnosis of a variety of medical conditions. We have used an atomic force microscope (AFM) to directly monitor specific molecular interactions between individual streptavidin and biotin molecules on such wells. This was achieved by functionalising an AFM probe with biotin and monitoring the adhesive forces between the probe and a streptavidin coated immunoassay well. The results demonstrate that the AFM may be employed as an analytical tool to study the interactions between biomolecules involved in immunoassay systems.
Bacterial Proteins↗
Decreased bone mineralization in children with phenylketonuria under treatment.
Children with phenylketonuria (PKU) obtain a great deal of their protein and mineral intakes from synthetic elemental formulae devoid of phenylalanine. To assess the effect of such diets and/or the disease on bone mineralization, children with PKU were compared to normal children for many parameters of mineral homeostasis and bone mineralization. A total of 11 children with PKU of mean age 10.9 +/- 4.2 years were compared to a large group of normal control children mean age 11.4 +/- 4.2, and an age and sex matched subset (n = 11). Children with PKU had lower serum calcium (9.1 +/- 0.9 vs 10.4 +/- 1.9 mg/dl P < 0.01) amd magnesium (1.67 +/- 1.4 vs 2.07 +/- 0.16 mg/ dl, P < 0.001) but normal values for phosphorus, zinc, and copper. The percentage tubular reabsorption of phosphorus was increased in PKU (93 +/- 3% vs 88 +/- 6%, P < 0.05) suggesting a lower phosphorus intake and/or absorption. Serum 25-hydroxyvitamin D, parathyroid hormone and 1,25 dihydroxyvitamin D were similar in PKU and control children. Serum albumin and lean body mass by dual energy X-ray absorption were not different suggesting that protein intake was adequate. In the 11 pairs, a decreased bone mineral density was seen for the lumbar spine (0.61 +/- 0.15 vs 0.72 +/- 0.24 P < 0.05), and lower extremities (1.56 +/- 0.30 vs 1.87 +/- 0.56 P < 0.05) by paired t-test. Compared to the total controls and the paired controls, decreases were seen in markers of bone formation; bone alkaline phosphatase, (72 +/- 30 vs 126 +/- 43 P < 0.001), osteocalcin (10.7 +/- 3.4 vs 13.1 +/- 2.0 P < 0.05) and procollagen type I carboxyterminal propeptide. No differences were seen in the bone resorption markers tartrate resistant acid phosphatase and urine Ca/Cr. The changes noted could not be related after age correction to serum phenylalanine levels, protein intake, or mineral intakes. It is unclear whether deficits in bone mineralization relate to the disease process itself or its treatment.
Adolescent↗
Characterization of tobacco withdrawal symptoms: transdermal nicotine reduces hunger and weight gain.
The accurate assessment of both tobacco withdrawal and the impact of the nicotine patch on withdrawal may be compromised by attrition of subjects, or by subjects smoking during withdrawal. To reduce these occurrences, 211 participants were provided with intensive cessation counseling while trying to quit smoking with either nicotine (21 mg) or placebo transdermal patches. Subject attrition was low, with 80.5% of participants continuing through the 5-week study period. Abstinence rates were also high over this period (75% and 61% in active and placebo groups, respectively). In this multisite, double-blind trial, withdrawal severity was assessed using a nine-item daily self-report questionnaire, and abstinence was confirmed via CO monitoring. Abrupt smoking cessation increased multiple tobacco withdrawal symptoms/signs including craving for cigarettes, irritability, anxiety, appetite, sleep disruption, difficulty concentrating, restlessness, depression, and impatience. Treatment with transdermal nicotine reduced craving for cigarettes, anxiety, irritability, and appetite, as well as weight gain (1.85 versus 2.88 kg mean gain over 4 weeks in active and placebo groups, respectively).
Administration, Cutaneous↗
Lea's Shield: a study of the safety and efficacy of a new vaginal barrier contraceptive used with and without spermicide.
The purpose of this study was to evaluate the safety, efficacy and acceptability of Lea's Shield, a new vaginal contraceptive barrier device, when used with either spermicidal or non-spermicidal lubricant. One-hundred-eighty-five (185) women enrolled at six centers. Half were randomized to use the device with spermicide and half with a non-spermicidal lubricant. To be eligible, volunteers had to be 18-40 years old (inclusive), in good health with regular menses, sexually active in an ongoing relationship and at risk for pregnancy, and willing to use Lea's Shield as their sole means of contraception for six months. Participants were seen at admission, one week, one month, three months and six months. Gross cumulative life table rates were calculated for pregnancy and others reasons for discontinuation. Adverse experiences and responses to an acceptability questionnaire were evaluated. One-hundred-eighty-two (182) volunteers contributed data to the analysis of safety and 146 to that of contraceptive efficacy. The unadjusted six-month life table pregnancy rate was 8.7 per 100 women for spermicide users and 12.9 for non-spermicide users (p = 0.287). After controlling for age, center, and frequent prior use of barrier methods, the adjusted six-month life table pregnancy rate was 5.6 for spermicide users and 9.3 for non-spermicide users (p = 0.086), indicating that use of spermicide lowered pregnancy rates, although not significantly, during typical use. For purposes of comparison, it is important to note that this study differed from the cap/diaphragm and sponge/ diaphragm studies in that a high percentage (84%) of volunteers were parous. For reasons that are unclear, pregnancy rates among parous women using barrier contraceptives tend to be higher than among nulliparous women. Indeed, in this study there were no pregnancies among nulliparous users of Lea's Shield. Standardization of parity of this study population on those of the cap/diaphragm and sponge/diaphragm studies suggests that unadjusted pregnancy rates for this device would have been considerably lower (2.2 and 2.9 per 100 users of spermicide and non-spermicide, respectively) had the study been done using the populations of earlier studies. Since no directly comparative study has been done, these figures provide a tentative estimate of the relative efficacy of Lea's Shield compared with the sponge, cap, and diaphragm. There were no serious adverse experiences attributed to the use of Lea's Shield. Acceptability was very good. Seventy-five percent (75%) of women responded to an end-of-study questionnaire; 87% of these reported that they would recommend Lea's Shield to a friend. Lea's Shield is a new vaginal contraceptive that does not require clinician fitting. Pregnancy rates in this study compare favorably with other studies of barrier contraceptive methods including the cervical cap, diaphragm, and sponge, even though this study was done with greater rigor and with a greater percentage of parous women than previous barrier studies. Lea's Shield appears to be safe and very acceptable to study volunteers.
Adult↗
Influence of cooling on mesenteric vascular reactivity.
OBJECTIVES: Cardiopulmonary bypass has been shown to cause hypoperfusion of certain vascular beds leading to multiple system organ failure. It has been reported that the gut may be an important trigger. The underlying mechanism is not fully known, but vascular changes, particularly those due to cooling, could play a role. METHODS: We examined the effect of cooling (28 degrees C) and subsequent rewarming (37 degrees C) on the vascular reactivity of the rabbit mesenteric artery and abdominal aorta to a range of vasoactive substances using an in vitro organ bath apparatus. Cumulative concentration-responses of the agonists (noradrenaline, histamine, dopamine and potassium chloride) were examined at 37 degrees C, then repeated at 28 degrees C and then subsequently repeated after rewarming to 37 degrees C. RESULTS: All agonists were capable of inducing a constrictor response on the mesenteric artery and abdominal aorta. The results represent means +/- SEM. There was an increase in potency of noradrenaline at the lower temperature [from 5.6 +/- 0.1 (37 degrees C) to 6.0 +/- 0.1 (28 degrees C); Bonferroni-corrected P < 0.05; n = 10], which returned to normal [5.6 +/- 0.1 (37 degrees C)] following rewarming in the mesenteric artery. In contrast, there was a decrease in potency of noradrenaline in the aorta on cooling [6.5 +/- 0.1 (37 degrees C) to 6.2 +/- 0.1 (28 degrees C); Bonferroni-corrected P < 0.05; n = 8]. Neither histamine or dopamine showed any difference in potency at 28 degrees C or at 37 degrees C following rewarming in the mesenteric artery or aorta. There was no difference in the efficacy of the response of the mesenteric artery to noradrenaline as indicated by the maximum responses. However, the response to the highest dose of dopamine was increased on rewarming to 37 degrees C compared to control responses at 37 degrees C before cooling in the aorta [7.23 +/- 1.48 g vs 3.6 +/- 0.6 g; Bonferroni-corrected P < 0.05; n = 14]. Histamine contractions were attenuated at 28 degrees C and following rewarming to 37 degrees C in the mesenteric artery [5.5 +/- 0.5 g (37 degrees C) vs 2.2 +/- 0.2 g (28 degrees C); Bonferroni-corrected P < 0.05; n = 18], [5.5 +/- 0.5 g (37 degrees C) vs 2.32 +/- 0.5 g (37 degrees C rewarming); Bonferroni-corrected P < 0.05; n = 18]. CONCLUSIONS: We conclude that cooling elicits a heterogeneous responsiveness of the rabbit mesenteric artery and abdominal aorta to noradrenaline and dopamine which could have important implications for blood flow to mesenteric vascular beds during hypothermic cardiopulmonary bypass.
Adrenergic alpha-Agonists↗
Can the scientific method be applied to human interaction?
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Cognition Disorders↗
Effects of behavioral and pharmacological treatment on smokeless tobacco users.
The purpose of this study was to examine the effects of 2 mg of nicotine polacrilex versus placebo gum and of group behavioral treatment versus minimal contact on cessation of smokeless tobacco use. Participants (N = 210) were randomly assigned 1 of the 4 treatment conditions. Withdrawal symptoms were assessed throughout the treatment. Follow-up assessments were made at 1, 6, and 12 months posttreatment. Survival curve analysis showed that any of the 3 treatment groups involving group behavioral therapy or placebo gum were equally effective and superior to the minimal contact plus 2 mg of nicotine gum treatment in terms of abstinence. On the other hand, withdrawal symptoms were significantly reduced by nicotine gum, compared with placebo during the initial phases of cessation. The ineffectiveness of nicotine gum on treatment outcome may be attributed to its similarity with smokeless tobacco.
Adult↗
Clinical immunity to Plasmodium falciparum malaria is associated with serum antibodies to the 19-kDa C-terminal fragment of the merozoite surface antigen, PfMSP-1.
The development of an effective malaria vaccine depends upon identification of antigens that are targets of protective immune responses. An immunoepidemiologic approach has been used to investigate the relationship between antibody responses to a defined region of the major merozoite surface protein of Plasmodium falciparum (PfMSP-1 19) and resistance to clinical malaria in 2 populations of children from West Africa. After allowing for the confounding effects of age, antibodies to PfMSP-1 19 were shown the provide 40% protection against clinical malaria in children in Sierra Leone. In Gambian children, antibodies to one of the epidermal growth factor-like motifs of PfMSP-1 19 were strongly associated with resistance to both clinical malaria and high levels of parasitemia.
Animals↗
Management of chronic fatigue syndrome: case study.
1. Chronic fatigue syndrome (CFS) is a complex disorder marked by incapacitating fatigue of uncertain etiology which has resulted in a least a 50% reduction in activity and is of at least 6 months' duration. 2. Definitive diagnosis can be very challenging. Because no markers objectively identify the presence of CFS, diagnosis depends heavily on the presence of subjective complaints. 3. The current philosophy of CFS management is to use a multidisciplinary approach incorporating these rehabilitation goals: restore a sense of self efficacy and control; gradually increase physical activity; and decrease the restrictions imposed by CFS.
Fatigue Syndrome, Chronic↗
Malaria vaccine in children under 12 months of age.
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Animals↗
Finite-size corrections to the correlation function of the spherical model at d >= 4.
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Journal Article↗
Treatment of adult T-cell leukemia-lymphoma with a combination of interferon alfa and zidovudine.
BACKGROUND: Infection with the human T-cell lymphotropic virus type I, a retrovirus, can cause a distinctive cancer, adult T-cell leukemia-lymphoma. The median survival of patients with the acute and lymphomatous forms of the disease is short, despite the use of cytotoxic chemotherapy. METHODS: We treated 19 patients with acute or lymphomatous forms of adult T-cell leukemia-lymphoma with oral zidovudine (200 mg five times daily) and interferon alfa (Intron A, 5 to 10 million units subcutaneously each day). Seven of these patients had either relapsed after multiagent cytotoxic chemotherapy or failed to respond to that treatment. RESULTS: Major responses were achieved in 58 percent of the patients (11 of 19), including complete remission in 26 percent (5 of 19). Four patients in whom prior cytotoxic therapy had failed had major responses, two of which were complete remissions. Six patients have survived for more than 12 months, with the longest remission since the discontinuation of treatment lasting more than 59 months. CONCLUSIONS: The combination of zidovudine and interferon alfa has activity against adult T-cell leukemia-lymphoma, even in patients in whom prior cytotoxic therapy has failed. This regimen should be evaluated further for its role in the treatment of adult T-cell leukemia-lymphoma.
Adolescent↗
Acute agranular CD4-positive natural killer cell leukemia. Comprehensive clinicopathologic studies including virologic and in vitro culture with inducing agents.
BACKGROUND: A 63-year-old male presented with fever, a subcutaneous nodule, gingival hypertrophy, lacrimal gland enlargement, and no lymphadenopathy or hepatosplenomegaly, but had anemia, thrombocytopenia, and peripheral blood (PB) plus bone marrow (BM) involvement by leukemic cells. There was minimal response to multiagent chemotherapy and local radiotherapy, with a survival of 6.5 months from disease diagnosis. METHODS: The PB and/or BM leukemic cells were evaluated using electron microscopy (EM), immunohistochemistry, flow-cytometric immunophenotyping, cytochemistry, cytogenetics, Southern blot analysis for gene rearrangement and Epstein-Barr virus (EBV), polymerase chain reaction for EBV and human herpes virus-6 (HHV-6), and in vitro culturing with inducing agents. RESULTS: The leukemic cells were agranular and monocytoid, with a hairy cell-like bone marrow biopsy infiltrate. Myeloperoxidase (MPO) and alpha-naphthyl butyrate esterase staining was negative, and periodic acid-Schiff staining was positive by light microscopy. Electron microscopy showed MPO negativity and a lack of parallel tubular arrays. The immunophenotype was CD3-, CD56+, CD4+, CD8-, CD15+, TCR1-, and TCR2-, with germline immunoglobulin and T-cell receptor genes and an abnormal karyotype (44XY, 5q-, -13, 13q+, -15). No genomic material for EBV or HHV-6 was detected. Cell cultures with butyrate and N,N-hexamethylene bis-acetamide suggested the possible induction of tumor cells to express a T-cell immunophenotype. CONCLUSION: A case of clonal acute natural killer (NK) cell leukemia with an unusual morphology (agranular) and unique phenotype (CD3-, CD56+, CD4+, CD15+) is presented. Unlike as in other acute NK leukemias, EBV was negative; there was no evidence of HHV-6. The tumor cell, after culturing with differentiating agents, may have been induced to express a T-cell immunophenotype.
Acetamides↗
Intracellular folding of tissue-type plasminogen activator. Effects of disulfide bond formation on N-linked glycosylation and secretion.
The addition of N-linked core oligosaccharides to membrane and secretory glycoproteins occurs co-translationally at asparagine residues in the tripeptide sequon Asn-Xaa-Ser/Thr soon after translocation of the nascent polypeptide into the lumen of the endoplasmic reticulum. However, the presence of the sequon does not automatically ensure core glycosylation, as many proteins contain sequons that remain either unglycosylated or glycosylated to a variable extent. To investigate whether intracellular protein folding can influence sequon utilization, we have expressed tissue-type plasminogen activator (t-PA) in cell culture in the presence of mild concentrations of the reducing agent dithiothreitol to prevent co-translational disulfide bond formation in the endoplasmic reticulum. We show that conditions that prevent disulfide bond formation lead to complete glycosylation of a sequon that otherwise undergoes variable glycosylation in untreated cells. This demonstrated that folding and disulfide bond formation of t-PA determines its extent of core N-linked glycosylation. When dithiothreitol was removed from the cells, the reduced and overglycosylated t-PA formed disulfide bonds, folded, and was secreted. We also show t-PA present within cells is more susceptible to reduction with low concentrations of dithiothreitol than secreted t-PA.
Amino Acid Sequence↗
Classification of HIV infection and disease in women from Rwanda. Evaluation of the World Health Organization HIV staging system and recommended modifications.
OBJECTIVE: To develop a human immunodeficiency virus (HIV) staging system for sub-Saharan Africa on the basis of an evaluation of the World Health Organization (WHO) system and predictors of mortality. DESIGN: Prospective cohort study with 4 years of follow-up. SETTING: Kigali, Rwanda. PATIENTS: 412 HIV-infected women recruited from prenatal and pediatric clinics. MEASUREMENTS: Clinical signs and symptoms of HIV disease, laboratory assays (including complete blood count and erythrocyte sedimentation rate), and cumulative mortality. RESULTS: The WHO staging system includes a clinical and a laboratory axis. The clinical axis was revised by inclusion of oral candidiasis, chronic oral or genital ulcers, and pulmonary tuberculosis as "severe" disease (clinical stage IV); in addition, body mass index was substituted for weight loss in the definition for the wasting syndrome. The 36-month cumulative mortality was 7% for women in modified clinical stage I ("asymptomatic"), 15% for those in stage II, 19% for those in stage III, and 36% for those in stage IV (P < 0.001). The laboratory axis was revised by replacing lymphocyte count with hematocrit and erythrocyte sedimentation rate. The 36-month mortality was 10% for women in modified stage A ("normal" laboratory results) and 33% for those in stage B (erythrocyte sedimentation rate > 65 mm/h or hematocrit < 0.38) (P < 0.001). A single staging system combining clinical and laboratory criteria is proposed, with a 36-month mortality of 7% for women in combined stage I, 10% for those in stage II, 29% for those in stage III, and 62% for those in stage IV (P < 0.001). CONCLUSIONS: On the basis of this analysis, a staging system relevant for sub-Saharan Africa is proposed that reflects the range of HIV-related outcomes, has strong prognostic significance, includes inexpensive and available laboratory tests, and can be used by both clinicians and researchers.
AIDS-Related Opportunistic Infections↗
Male circumcision, sexually transmitted disease, and risk of HIV.
Our objective was to describe associations among male circumcision, behavioral and demographic variables, ulcerative and nonulcerative sexually transmitted disease (STD), and human immunodeficiency virus (HIV) infection via a cross-sectional study in Kigali, the capital of Rwanda. Our subjects were 837 married men who volunteered for HIV testing and counselling. Uncircumcised men had a relatively low-risk profile in that they reported fewer lifetime sexual partners and prostitute contacts than circumcised men and were more likely to live in rural areas with lower HIV prevalence rates. Uncircumcised men were also less likely to report a history of sexually transmitted disease (64% versus 73%, p = 0.01), although they were more likely to report genital ulceration (GUD) (24% versus 17%, p < 0.03) and to have inguinal adenopathy noted on physical exam (42% versus 29%, p = 0.009). Despite the low-risk profile, uncircumcised men had a higher prevalence of HIV infection than circumcised men (29% versus 21% HIV positive, p = 0.02), which was most marked in men reporting five or more lifetime sex partners (36% versus 23% HIV positive, p = 0.005) or contact with prostitutes (35% versus 23% HIV positive, p = 0.009). Circumcision remained a predictor of HIV infection in multivariate analyses (multivariate odds ratio 1.69, 95% confidence interval 1.16-2.47). Lack of circumcision is associated with a higher risk of HIV infection in Rwandan men. Further research is needed to determine whether this higher risk is due in part to poor hygiene or to complex mechanisms operating through the acquisition of other sexually transmitted diseases. Circumcision may be an appropriate risk reduction approach for men with known exposures to the virus when there are constraints to alternatives, such as condom use.
Adult↗
Characteristics of motor unit discharge in subjects with hemiparesis.
We studied the discharge rates and recruitment characteristics of single motor units in paretic and contralateral arm muscles of 6 hemiparetic subjects. Motor unit activity in biceps brachii was recorded at different elbow torques, and the activity related both to the mean level of surface electromyographic activity, and to the degree of weakness. In 3 of the 6 subjects, there were significant reductions in mean discharge rate of motor units in the paretic muscle. All 6 subjects showed compression of the range of motoneuron recruitment forces, and a failure to increase motor unit discharge rate during voluntary force increases in paretic muscles. These rate reductions could potentially alter the precise match of motoneuron properties to the mechanical properties of the innervated muscle fibers, and reduce the efficiency of muscle contraction. This reduction could lead, in turn to increased effort, to fatigue, and ultimately to a sense of weakness for voluntary force generation.
Adult↗