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C Whalen

Publications and source records attributed to C Whalen.

At least 19 recordsLinked to original sources
PubMed2006

Introduction of an in-house PCR for routine identification of M. tuberculosis in a low-income country.

SETTING: National Tuberculosis (TB) Treatment Centre, Makerere University Medical School and Joint Clinical Research Centre, Kampala, Uganda. OBJECTIVE: To evaluate the introduction of a polymerase chain reaction (PCR) based assay for identification of the Mycobacterium tuberculosis complex (MTC) into routine practice. DESIGN: Routine diagnostic specimens were processed and inoculated into Bactec 12B vials and monitored daily. At a growth index (GI) > or =10, 0.5 ml of the 12B broth was removed and assayed with PCR. The same 12B vial was analyzed using the Bactec NAP method at GI > or =500. Vials at various levels of GI were included. Recurrent cost and time required to perform PCR and NAP were compared. RESULTS: Initially, 71 specimens were analyzed; of these, 68 were NAP-positive while 69 were PCR-positive for MTC. PCR resulted in a 75% reduction in cost for a single test compared with Bactec NAP. PCR has been successfully incorporated into routine practice, and 432 samples have been analyzed. In addition, isolates from solid media were also well identified by PCR. With PCR, more samples can be analyzed at a time, it is faster and is less labor intensive. CONCLUSION: PCR is a reliable and cheaper alternative for the identification of MTC.

Costs and Cost Analysis↗
PubMed2005

Kaposi's sarcoma in patients with and without human immunodeficiency virus infection, in a tertiary referral centre in Kenya.

The clinical features of Kaposi's sarcoma (KS), in patients with and without HIV infection, were investigated in a tertiary referral centre in Kenya between 1997 and 1999. Although 186 cases were identified prospectively, the data analysis was restricted to the 91 (49%) cases who had pathological confirmation of Kaposi's sarcoma and documented HIV serostatus. Among these 91 subjects (58% of whom were male), the age-group holding the largest number of KS cases was that of individuals aged 31-40 years; most of the paediatric cases were aged 6-10 years. The ratio of HIV-seropositives to HIV-seronegatives was 8.5:1 for the adult cases and 0.9:1 for the paediatric. Of the signs and symptoms of Kaposi's sarcoma seen at presentation, only peripheral lympadenopathy was found to be significantly associated with underlying HIV infection (P = 0.05). The median survival was 104 days. It is apparent that, as the HIV epidemic advances in regions of the world with endemic KS, the clinical presentation and natural history of the endemic KS are blending with those of the epidemic or AIDS-associated disease, leading to a reduction in the mean age of the cases and a nearly identical incidence in men and women. In regions of the world where patients have ready access to such chemotherapy, the impact of treatment with highly active antiretroviral drugs on the incidence and natural history of KS has been dramatic. It will be important to monitor the clinico-pathological features of KS in the developing world, as more active antiretroviral regimens become available in clinical practice there.

Adult↗
PubMed2005

Clinical characteristics of Burkitt's lymphoma from three regions in Kenya.

OBJECTIVES: To describe the clinical characteristics of Burkitt's lymphoma (BL) from three regions in Kenya at different altitudes with a view towards understanding the contribution of local environmental factors. DESIGN: Prospective cross-sectional study. SETTING: Kenyatta National Hospital and seven provincial hospitals in Kenya. METHOD: Histologically proven cases of Burkitt's lymphoma in patients less than 16 years of age were clinically examined and investigated. MAIN OUTCOME MEASURES: For every case the following parameters were documented: chief complaint(s); physical examination, specifically pallor, jaundice, oedema, lymphadenopathy, presence of masses, splenomegaly and hepatomegaly. Reports of evaluation of chest radiograph, abdominal ultrasound/scan, bone marrow aspiration, cerebral spinal fluid cytology, liver and kidney function tests, urinalysis, stool occult blood and full blood count results. Stage of disease was assigned A, B, C or D. Cases of BL from three provinces of Kenya with diverse geographical features were analysed: Central, Coast, and Western. RESULTS: This study documented 471 BL cases distributed as follows: Central 61 (males 39 and 22 females), M:F ratio 1.8:1; Coast 169 (111 males and 58 females), M:F ratio 1.9:1; and Western 241 (140 males and 101 females), M:F ratio 1.4:1. The major presenting complaints were: abdominal swelling--Central 36%, Coast 4% and Western 26%; swelling on the face--Central 31%, Coast 81% and Western 64%; and proptosis--Central 3%, Coast 1% and Western 9%. The mean duration of these complaints in weeks were Central 6.9, Coast 6.08, and Western 5.05. The initial physical finding was a tumour mass in 39%, 72% and 54% of cases for Central, Coast and Western respectively. Tumour stage at diagnosis was: stage A--Central 21%, Coast 43% and Western 34%; stage B--Central 10%, Coast 5% and Western 10%; stage C--Central 41%, Coast 34% and Western 30%; and stage D--Central 28%, Coast 17% and Western 26%. For the age and sex matched cases the results show that commonly involved sites were: abdomen--Central 35%, Coast 9% and Western 14%; jaw (mandible)--Central 24%, Coast 22% and Western 31%; maxilla--Central 6%, Coast 24% and Western 11%; and lymph nodes--Central 10%, Coast 4% and Western 8%. The disease stage was A--Central 33%, Coast 44% and Western 36%; stage B--Central 11%, Coast 10% and Western 27%; stage C--Central 39%, Coast 34% and Western 27%; and stage D--Central 21%, Coast 13% and Western 37%. CONCLUSION: This study shows that clinical features of childhood BL vary with geographical region. The variations are documented in proportion of jaw, maxilla, abdominal and lymph nodal sites involvement. The differences observed are potentially due to the local environmental factors within these provinces. BL cases from Western province had features, intermediate between endemic and sporadic. Coastal province BL cases were similar to endemic BL, while BL cases from Central province resembled more or less sporadic BL subtypes. Strategies to explain and investigate the local environmental factors associated with the observed differences may certainly contribute towards improved understanding and clinical management of BL.

Abdominal Neoplasms↗
PubMed2005

The diagnosis of childhood tuberculosis in an HIV-endemic setting and the use of induced sputum.

SETTING: A hospital in the capital city of Uganda. OBJECTIVES: To determine the proportion of positive induced sputum cultures among probable childhood tuberculosis (TB) cases, to describe the laboratory and radiological features of childhood TB in the context of human immunodeficiency virus (HIV), and to determine the prevalence of HIV infection in these patients. DESIGN: Cross-sectional descriptive study. METHOD: Seven hundred and fifty children with suspected TB were evaluated clinically, by chest radiography and by tuberculin test (Mantoux). Probable cases underwent sputum induction or lymph node biopsy, HIV testing and RNA-PCR tests. RESULTS AND CONCLUSION: The Mantoux test was positive in 55/121 (45%) of the patients; low sensitivity to Mantoux was associated with HIV infection (P = 0.000). Induced sputum yielded 12/101 (12%) positive smears of Mycobacterium tuberculosis and 30/101 (30%) positive cultures. Six of the eight lymph node biopsies were culture-positive, and the histology of seven samples was supportive of TB. Most of the children with probable and confirmed TB presented with similar signs, symptoms and chest radiography patterns, irrespective of HIV status. Elevated ESR had no significant role in the diagnosis of TB in children and even more so in the presence of HIV infection. The HIV infection rate was high among children with TB (49%).

Blood Sedimentation↗
PubMed2004

Burkitt's lymphoma in Kenya: geographical, age, gender and ethnic distribution.

OBJECTIVE: To show the geographical (Provincial), age, gender and ethnic distribution of Burkitt's lymphoma in patients in Kenya. DESIGN: A retrospective review of patients' records for the years 1988-1992 and a prospective evaluation of patients with BL between 1993 and 1997. These were descriptive and hospitals based studies. SETTING: Kenyatta National Hospital; Kenya's main referral and teaching hospital and seven provincial hospitals. MAIN OUTCOME MEASURES: For each tissue proven Burkitt's lymphoma case the following were required; province of birth and residence, tribe, age, sex, chief complains, physical examination findings, investigation results and tissues result confirming the diagnosis of BL. STATISTICAL METHOD: Mainly proportions were used to compare variables, however Pearson's liner correlation was used to assess the time trends. RESULTS: This study registered 1005 patients; 961 (95.6%) children and 44 (4.4%) adults. 0-14 years the age standardized incidence rate (ASR) of 0.83. Variations documented in the provinces' BL ASR range; 1.8 Coast to 0.23 Rift Valley and increasing yearly trend for both children and adults. The major tribes in Kenya consisted; Luo 29.5%. Luhya (24.1%) and Coastal (16.5%). No patient of Asian or European or Arab extraction was recorded in the study. The age distribution showed no case below two years, a rapid rise from three year 3 (5.6%), and peak at 6 (19.5%) for children and at 17 years (13.6%) years for the adult. Age group 5-9 years had the highest ASR. The male to female (M:F) ratios were; 1.5:1 and 1:1 in children and adults respectively, provincial ratios range; 2.6:1 in Nairobi to 1.2:1 in Nyanza, the tribes range; 3.5:1 in Somali to 1:1 in other tribes between 2 and 14 years old when also males were more than females. Peak time of presentation of symptoms was 4 weeks. Tumour sites were in children; jaw 51.6%, abdomen (25%), combined jaw and abdomen 13.8% and others 9.6% and adults; jaw (4.5%), abdomen (43.2%), combined jaw and abdomen (25%) and other sites (27.3%) 67.6% males and 42.4% female adults had HIV infection and disseminated BL disease. CONCLUSION: The study demonstrates that Burkitt's lymphoma is a childhood disease. The disease distribution is consistent with intermediate risk Burkitt's lymphoma level. Furthermore the distribution varied by province, tribe, age and gender. The variations could be due to environmental factors.

Abdominal Neoplasms↗
PubMed2004

Anatomical site predilections of non-Hodgkin's lymphoma in human immunodeficiency virus infection: a report on 54 cases.

OBJECTIVE: To identify and describe the primary anatomic sites of non-Hodgkin's lymphoma arising in the setting of Human Immunodeficiency Virus infection. DESIGN: Prospective (ongoing) study. SETTING: Kenyatta National Hospital a referral and teaching hospital in Kenya. SUBJECTS AND METHODS: Patients (n=54) with human immunodeficiency virus with associated non-Hodgkin's lymphoma managed at the Kenyatta National hospital from January 2001 to December 2003. Relevant clinical information obtained by medical history, physical examination and investigations. RESULTS: Of the 54 patients studied 29(54%) were males and 25(46%) females with median age 36 and range 20 to 61 years. Fifty (93%) had high grade and four (7%) intermediate grade lymphoma, the former had 15 (30%) Burkitt's and the rest large cell lymphoma. The stages at diagnosis were IV 35(65%), III 14(26%) and II 5(9%) and all had B symptoms. The primary sites at presentation to the hospital were peripheral nodes 16(30%), abdominal 15(28%), pectoral/chest wall 11(20%), central nervous system eight (15%) and systemic/generalised, four (7%). CONCLUSION: This study demonstrates that there were preferred anatomical sites of involvement by HIV associated non-Hodgkin's lymphomas and the finding of pectoral/ chest involvement in this series may not be coincidental. Further, this study suggests that anatomical sites predilection may be due to the tendency of viral associated malignancies to home to specific anatomic sites and also due to the anatomy of the lymphoreticular system. Studying virus pathogenesis in malignancies should consider also the anatomic sites involved.

Abdominal Neoplasms↗
PubMed2001

Adult Burkitt's lymphoma in patients with and without human immunodeficiency virus infection in Kenya.

Prior to the acquired immunodeficiency syndrome (AIDS) epidemic, one or two cases of adult Burkitt's lymphoma (BL) were seen annually at the Kenyatta National Hospital, the national referral medical center in Nairobi, Kenya. To investigate the influence of human immunodeficiency virus (HIV) infection in adult BL in Kenya, we conducted a national prevalence survey of all patients 16 years of age and older with BL. A systematic review of medical records of all patients diagnosed with BL between 1992 and 1996 was performed. The diagnosis of BL was based and confirmed on review of pathological material from time of original diagnosis. HIV serology was confirmed by enzyme-linked immunosorbent assay (ELISA). Twenty-nine adult patients with BL were identified during the 5-year study period. Of these patients, 17 (59%) were males, 12 (41%) were females, and the median age was 26 years. Nineteen patients (66%) with BL were HIV-seropositive. The proportion of men was similar in HIV-seropositive and -seronegative patients (58% vs 60%). HIV-seropositive BL patients were significantly older than seronegatives (median 35 vs 19.5 years, p < 0.001). HIV-seropositive patients uniformly presented with constitutional or B symptoms and advanced BL accompanied by diffuse lymph node involvement, whereas the clinical presentation of HIV-seronegative patients during this time period was reminiscent of the "typical" endemic pattern of disease with complete sparing of peripheral lymph nodes. The overall survival of HIV-seropositive cases was significantly worse than that of the HIV-seronegative cases; median survival in the HIV-seropositive patients was 15 weeks. There is an approximate 3-fold increase in the incidence of adult BL during the time period of this study, which is attributable to the AIDS epidemic. In this setting, patients often present with disseminated disease, diffuse peripheral lymphadenopathy and fever, the latter two of which heretofore have been commonly associated with non-lymphoproliferative disorders such as Mycobacterium tuberculosis and sexually transmitted diseases in Kenya. These observations warrant inclusion of AIDS-related BL in the differential diagnosis of the adult patient with unexplained fever and lymphadenopathy in Kenya. The corollary is that HIV infection is virtually excluded in an adult patient without peripheral lymphadenopathy and biopsy-proven BL.

Adolescent↗
PubMed2001

Activation of beta-chemokines and CCR5 in persons infected with human immunodeficiency virus type 1 and tuberculosis.

Tuberculosis (TB) in human immunodeficiency virus type 1 (HIV-1)-infected persons is associated with progression of HIV-1 disease. The expression of macrophage inflammatory protein (MIP)-1alpha and CCR5 was assessed in HIV-1-infected patients with pulmonary TB (HIV-1/PTB) and without PTB (HIV-1/C), PTB patients not infected with HIV-1 (PTB), and control subjects. Mycobacterium tuberculosis (MTB)-induced MIP-1alpha production was lower in peripheral blood mononuclear cells (PBMC) of HIV-1/PTB patients than in those of PTB patients (P< .05) and was lower in PBMC of HIV-1/C patients than in those of control subjects (P< .005). However, MIP-1alpha production was higher in PBMC of HIV/PTB patients than in those of HIV-1/C patients (P< .01). The pattern of MTB-induced RANTES production was similar to that of MIP-1alpha. However, MTB induced greater expression of mRNA for CCR5 in PBMC of HIV-1/PTB patients than in those of HIV-1/C patients (P< .04). Furthermore, the MTB-induced HIV p24 antigen level in PBMC of HIV-1/PTB patients with a CD4 cell count <500 cells/microL was higher (P< .05) than that in HIV-1/C patients. Thus, perturbations in chemokine pathways in HIV-1/PTB patients may accelerate HIV-1 disease.

AIDS-Related Opportunistic Infections↗
PubMed2001

Macrophage-activating cytokines in human immununodeficiency virus type 1-infected and -uninfected patients with pulmonary tuberculosis.

Tuberculosis (TB) is the most common opportunistic infection in human immunodeficiency virus type 1 (HIV-1)-infected patients globally and occurs throughout the course of HIV-1 disease. Here the production of interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha by peripheral blood mononuclear cells (PBMC) of HIV-1-infected versus -uninfected patients with newly diagnosed pulmonary TB (PTB) was compared. Findings were correlated with cytokine profiles, clinical presentation, and expression of inducible nitric oxide (iNOS). Most HIV-1/PTB patients with a CD4 cell count of 200-500 cells/microL had high IFN-gamma production and radiographic evidence of atypical PTB. Low IFN-gamma production and radiographic evidence of reactivated PTB characterized both HIV-1/PTB patients with a CD4 cell count >or=500 cells/microL and HIV-1-uninfected patients. TNF-alpha levels were similar in all HIV-1/PTB patients, regardless of CD4 cell count. Induction of iNOS in PBMC was low and was associated with low IFN-gamma production. These data underscore the potential pathogenic role of macrophage-activating cytokines in TB in HIV-1-infected patients.

AIDS-Related Opportunistic Infections↗
PubMed2001

High prevalence of carriage of antibiotic-resistant Streptococcus pneumoniae in children in Kampala Uganda.

There are few data on antibiotic-resistant Streptococcus pneumoniae in Uganda. A total of 191 healthy children in Kampala, Uganda were screened for nasopharyngeal carriage of S. pneumoniae; 118 (62%) of the children were carriers. Antimicrobial susceptibility and serotype of 115 strains was determined. Ninety-six (83.5%) of the isolates were of intermediate resistance to penicillin and 19 (16.5%) were susceptible. All strains were susceptible to cefotaxime. The rates of resistance to other drugs were trimethoprim-sulphamethoxazole (83.5%), tetracycline (28.7%) and chloramphenicol (10.4%). All strains were susceptible to rifampicin, erythromycin and clindamycin. Serogroups 6, 9, 14, 19 and 23 accounted for 80% of the isolates. These data show that the rate of carriage of antibiotic-resistant pneumococci by children is high in Kampala, Uganda.

Anti-Bacterial Agents↗
PubMed2001

Severity of human immunodeficiency virus infection is associated with decreased phase angle, fat mass and body cell mass in adults with pulmonary tuberculosis infection in Uganda.

Although coinfection with tuberculosis and human immunodeficiency virus (HIV) is emerging as a major problem in many developing countries, nutritional status has not been well characterized in adults with tuberculosis and HIV infection. We compared nutritional status between 261 HIV-positive and 278 HIV-negative adults with pulmonary tuberculosis in Kampala, Uganda, using anthropometry and bioelectrical impedance analysis. Among 163 HIV-positive and 199 HIV-negative men, intracellular water-to-extracellular water (ICW:ECW) ratio was 1.48 +/- 0.26 and 1.59 +/- 0.48 (P = 0.006) and phase angle was 5.42 +/- 1.05 and 5.76 +/- 1.30 (P = 0.009), respectively. Among 98 HIV-positive and 79 HIV-negative women, ICW:ECW was 1.19 +/- 0.16 and 1.23 +/- 0.15 (P = 0.11) and phase angle was 5.35 +/- 1.27 and 5.43 +/- 0.93 (P = 0.61), respectively. There were no significant differences in BMI, body cell mass, fat mass or fat-free mass between HIV-positive and HIV-negative adults. Among HIV-positive subjects, BMI, ICW:ECW, body cell mass, fat mass and phase angle were significantly lower among those with CD4(+) lymphocytes < or = 200 cells/microL compared with those who had > 200 cells/microL. In sub-Saharan Africa, coinfection with pulmonary tuberculosis and HIV is associated with smaller body cell mass and intracellular water, but not fat-free mass, and by large differences in ICW:ECW and phase angle alpha.

AIDS-Related Opportunistic Infections↗
PubMed1999

Placental membrane inflammation and risks of maternal-to-child transmission of HIV-1 in Uganda.

UNLABELLED: Prospective follow-up of 172 HIV-infected pregnant women and their infants was conducted at Mulago Hospital, Kampala, Uganda during 1990 to 1992. Information was collected on maternal immune status (CD4 counts or clinical AIDS), and concurrent infections with sexually transmitted diseases. Infants were observed on a follow-up basis to determine HIV infection, using polymerase chain reaction (PCR) under 15 months of age and enzyme immunoassay/Western blot for those older than 15 months. Placental membrane inflammation (chorioamnionitis and funisitis), and placental villous inflammation (villitis, intervillitis, and deciduitis) were diagnosed by histopathology. Mother-to-child HIV transmission rates were assessed, and adjusted odds ratios (OR) and 95% confidence intervals (95% CI) of transmission were estimated using women with no placental pathology or evidence of immune suppression as a reference group. RESULTS: The overall mother-to-child HIV transmission rate was 23.3%. Women with no placental membrane inflammation or immune suppression had a transmission rate of 11.3%; compared with 25.5% in women with placental inflammation and no immunosuppression (adjusted OR, 2.87; 95% CI, 1.04-7.90), and 37.0% in immunosuppressed women (OR, 3.07; 95% CI, 1.42-6.67). We estimate that 34% of HIV transmission could be prevented by treatment of placental membrane inflammation in nonimmunocompromised women. Transmission rates were 40.9% with genital ulcer disease (OR, 3.57; 95% CI, 1.28-9.66). Placental villous inflammation and artificial rupture of membranes did not increase transmission rates and cesarean section was associated with a nonsignificant reduction of risk (OR, 0.70; 95% CI 0.24-2.06). CONCLUSION: Placental membrane inflammation increases the rate of mother-to-child HIV transmission.

Blotting, Western↗
PubMed1999

Double-blind placebo-controlled study of concurrent administration of albendazole and praziquantel in schoolchildren with schistosomiasis and geohelminths.

A double-blind placebo-controlled study of the concurrent administration of albendazole and praziquantel was conducted in>1500 children with high prevalences of geohelminths and schistosomiasis. The study sites were in China and the Philippines, including 2 strains of Schistosoma japonicum, and 2 different regions of Kenya, 1 each with endemic Schistosoma mansoni or Schistosoma haematobium. Neither medication affected the cure rate of the other. There was no difference between the side effect rate from albendazole or the double placebo. Praziquantel-treated children had more nausea, abdominal pain, and headache but these side effects were statistically more common in children with schistosomiasis, suggesting a strong influence of dying parasites. The subjects were followed for 6 months for changes in infection status, growth parameters, hemoglobin, and schistosomiasis morbidity. In all 4 sites, a significant 6-month increase in serum hemoglobin was observed in children who received praziquantel, strongly supporting population-based mass treatment.

Adolescent↗
PubMed1999

The effect of human immunodeficiency virus-1 infection and stunting on measles immunoglobulin-G levels in children vaccinated against measles in Uganda.

BACKGROUND: Measles is an important public health problem in developing nations and there is concern that immune response to measles vaccination may be compromised by paediatric human immunodeficiency virus (HIV) infection. Therefore, this study investigated the relationship of immunoglobulin-G (Ig-G) antibody levels in children vaccinated against measles and HIV-1 infection. Further analysis was done to assess the influence of nutritional status on this relationship. METHODS: The authors measured HIV and measles antibodies in 243 vaccinated children aged 17-41 months from Kampala, Uganda. Children were from paediatric and HIV clinics. Potential confounders of this relationship included nutritional anthropometric measures, age at and time since vaccination, measles exposure, family crowding, vaccination clinic and gender. Univariable and multivariable analyses were used to study these associations. RESULTS: Fifty children (21%) were HIV infected. In univariable analysis, low measles antibody (<15 ELISA units/ml) was associated with HIV (P = 0.05; odds ratio (OR) = 1.86) and stunting (P = 0.06; OR = 1.68). Stunting, measured as height-for-age and defined as <-2 standard deviations of the reference population median, was a surrogate for chronic malnutrition. HIV was strongly associated with stunting (P = 0.0001; OR = 6.62). In multiple logistic regression, HIV was not associated with low measles antibodies; however, stunting (P = 0.04; OR = 1.81), and <3 children in the home (P = 0.01; OR = 1.96) were. Conversely, being male (P = 0.05; OR = 0.58), and measles in the home in the previous month (P = 0.04; OR = 0.33) were associated with high antibody levels. CONCLUSIONS: These findings suggest that HIV in Ugandan children immunized for measles may indirectly interfere with measles antibody levels by causing malnutrition, the latter being the direct cause. Programmes to improve childhood nutrition, especially for HIV-infected children, should accompany measles control programmes in developing nations for maximum benefit from measles vaccination. HIV infection per se should not change measles vaccination programmes.

Analysis of Variance↗
PubMed1998

Characterization of the recombinant extracellular domain of the neurotrophin receptor TrkA and its interaction with nerve growth factor (NGF).

Nerve growth factor (NGF) is the prototype of a family of neurotrophins that support important neuronal programs such as differentiation and survival of a subset of sympathetic, sensory, and brain neurons. NGF binds to two classes of cell surface receptors: p75LANR and p140TrkA. NGF binding to p140TrkA initiates the neuronal signaling pathway through activation of the tyrosine kinase activity, which subsequently results in a rapid signal transduction through a phosphorylation cascade. To examine this crucial signaling step in more detail, the TrkA extracellular domain polypeptide (TrkA-RED) was overexpressed in Sf21 insect cells and purified to homogeneity. The recombinant TrkA-RED is a 70 kDa acidic glycoprotein with a pI of 5.1, and mimics the intact TrkA receptor for NGF binding with a dissociation constant, Kd, of 2.9 nM. Thus, the recombinant TrkA-RED is functionally competent and can be used to elucidate the interaction of NGF and TrkA receptor. Circular dichroism difference spectra indicated that, upon association of NGF with TrkA-RED, a minor conformational change occurred to form a complex with decreased ordered secondary structure. Interaction between NGF and TrkA-RED was also demonstrated by size exclusion chromatography, light scattering, and chemical crosslinking with evidence for formation of a higher molecular weight complex consistent with a (TrkA-RED)2-(NGF dimer) complex. Association and dissociation rates of 5.6 x 10(5) M(-1) s(-1) and 1.6 x 10(-3) s(-1), respectively, were determined by biosensor technology. Thus, initiation of signaling may stem from NGF-induced receptor dimerization concomitant with a small conformational change.

Animals↗
PubMed1998

Comparison of three composite compliance indices in a trial of self-administered preventive therapy for tuberculosis in HIV-infected Ugandan adults. Uganda-Case Western Reserve University Research Collaboration.

Compliance with tuberculosis preventive therapy in a randomized placebo-controlled trial in 2736 HIV-infected Ugandans was measured using urinary isoniazid metabolite testing, clinic attendance, and self-report. Overall, 77% of urine tests were positive, subjects kept 85% of their scheduled visits while on therapy, and 69% reportedly never forgot to take their medication. Different strategies were used for constructing three composite compliance indices in active arms: (1) an unweighted index of the summed scores on scaled compliance measures; (2) a weighted index using weights obtained from a survey of experts on tuberculosis; and (3) a statistically weighted index using principal components analysis. Composite indices were evaluated for reliability, validity, and practical utility. Understanding of the regimen, study arm, subsequent follow-up, tuberculosis status, and urine spot-check result were associated with composite compliance scores. The unweighted index in this study performed as well as the weighted indices.

AIDS-Related Opportunistic Infections↗