Confidence intervals for biomarker-based human immunodeficiency virus incidence estimates and differences using prevalent data

Prevalent biologic specimens can be used to estimate human immunodeficiency virus (HIV) incidence using a two-stage immunologic testing algorithm that hinges on the average time, T, between testing HIV-positive on highly sensitive enzyme immunoassays and testing HIV-positive on less sensitive enzyme immunoassays. Common approaches to confidence interval (CI) estimation for this incidence measure have included 1) ignoring the random error in T or 2) employing a Bonferroni adjustment of the box method. The authors present alternative Monte Carlo-based CIs for this incidence measure, as well as CIs for the biomarker-based incidence difference; standard approaches to CIs are typically appropriate for the incidence ratio. Using American Red Cross blood donor data as an example, the authors found that ignoring the random error in T provides a 95% CI for incidence as much as 0.26 times the width of the Monte Carlo CI, while the Bonferroni-box method provides a 95% CI as much as 1.57 times the width of the Monte Carlo CI. Further research is needed to understand under what circumstances the proposed Monte Carlo methods fail to provide valid CIs. The Monte Carlo-based CI may be preferable to competing methods because of the ease of extension to the incidence difference or to exploration of departures from assumptions.

Airway and systemic inflammation and decline in lung function in patients with COPD

Study objective: Patients with COPD experience lower airway and systemic inflammation, and an accelerated decline in FEV. There is no evidence on whether this inflammation changes over time, or if it is associated with a faster decline FEV. Patient and design: a cohort of 148 COPD patients (100 men) was monitored daily for a median 2.9 years (interquartile range [IQR], 2.1 to 4.8). At recruitment median age was 68.5 years (IQR, 62.5 to 73.6) and FEV as percentage of predicted (FEV percent Pred) was 38.5 percent (IQR, 27.7 to 50.3). Results: During the study, the patients experienced 1,389 exacerbations, a median of 2.52/yr (IQR 1.48 to 3.96) and FEV declined by 40.2 mL/yr or as FEV percent Pred by 1.5 percent/yr. Concerning inflammatory markers, sputum interlukin (IL)-6 rose by 9 pg/mL, sputum neutrophil count rose by 1.64 x 10,000,000 cells per gram sputum per year, and plasma fibrinogen rose by 0.10 g/L/yr (all p, 0.05). Patients with frequent exacerbations (less than or equal to 2.52/yr) had a faster rise over time in plasma fibrinogen and sputum IL-6 of 0.063 g/L/yr (p= 0.046, n= 130) and 29.5 pg/mL/yr (p< 0.001, n=98), respectively, compared to patients with infrequent exacerbations (<2.52/yr). Using the earliest stable (nonexacerbation) measured marker, patients whose IL-6 exceeded the group median had a faster FEV percentPred decline of 0.97 percent/yr (p=0.001 and .40 percent/yr (p=0.014). respectively. Conclusions: In COPD, airway and systemic inflammatory markers increase over time; high levels of these markers are associated with a faster decline in lung function (AU)

Evaluation of Oestrogen and Progesterone Receptors and c-erbB-2 in Carcinoma of the breast in Trinidadian Women

One hundred and three consecutive cases of breast cancer in Trinidadian women were evaluated for steriod receptor status and c-erB-2 receptor along with conventional parameters including age, ethnicity, tumour size, histological type and grade, and lymph node status: The molecular markers were studied by immunohistochemistry (IHC) on paraffin sections. Tumour size > 2 cm was seen in 60 percent of the cases. Oestrogen receptor (ER), progestrone receptor (PR) and c-erbB-2 showed 54 percent, 46 percent, and 63 percent positivity, respectively. There was no correlation between c-erbB-2 and steroid receptors. Forty-one percent of cases showed double negativity for steriod receptors (ER-/PR-). No correlation was found between the markers and conventional parameters except for a negative correlation with the tumour grade. The high percentage of c-erbB-2 positivity and the high propotion of steriod receptor negativity suggest a need for studies on adjuvant therapy. Integration of selected markers with conventional parameters could help define sub-groups for treatment and pragnosis (AU)

The application of rapid analytical systems and sensors to the detection of cancers and other diseases

There is an advantage in combining knowledge of biosensor technology with that of immunological and molecular methods. This may enhance early diagnosis of cancers and other diseases and thus ultimately contribute to a better prognosis.(Au)

Risk factors associated with ischaemic stroke in Guadeloupe

We carried out a case control study at the University Hospital of Pointe-a-Pitre, Guadeloupe, during eight months. Seventy patients with ischaemic stroke and seventy age- and sex matched controls were involved. A standard questionnaire reported clinical characteristics and medical history. Seventy-six per cent of patients suffered from hypertension. Obesity and diabetes were more frequent in the case group than in the control group. Serum creatinine concentration (86 vs 74umol/l; p <0.001), total cholesterol (5.9 vs 5.2 mmol/l; p < 0.001), apolipoprotein B (1.2 vs 1.0 g/l' p < 0.001) and lipoprotein (a) (82 vs 48 mg/dl; p< 0.001) were significantly higher in patients than controls. Multiple logistic regression analysis revealed that in addition to serum creatinine, serum apolipoprotein B, hypertension, obesity, serum lipoprotein (a) and diabetes mellitus were associated independently and significantly with ischaemic stroke. These findings have implications for clinical practice and further research particularly with respect to serum creatinine concentration as a marker of renal damage from hypertension and as risk factor itself for cerebrovascular disease.(Au)

Childhood dermatitis in the tropics: with special emphasis on infective dermatitis, a marker for infection with human T-cell leukemia virus-I

Eczema in the tropics is a common problem. Although it is a major cause of discomfort among children worldwide, a warm tropical climate often has important repercussions for children with dermatitis. The original description by Sweet empahasized that interest in tropical eczemas extended to the English, as children of West Indian immigrants in England were affected. Likewise, immigrants may carry these disorders with them to the United States. In Jamaica, a tropical country, the largest and most populous of the English-speaking Caribbena islands, eczema is by far the most common skin disorder seen in children attending dermatology clinics. Reports from other Caribbean islands suggest that this is true for the region as a whole. In 1981, Alabi and La Grenade reported that from 1971 to 1975 eczema accounted for 46.7 percent of skin rashes seen in children at the University Hospital of the West Indies. Review of the period 1988 to 1993 showed that 52 percent of the 601 children who attended the skin clinic for the first time had eczema, confirming the earlier finding. In this latter review, atopic eczema was the most common type of eczema (52 percent), followed by seborrheic eczema (20 percent) and infective dermatitis (10 percent). The remaining 18 percent had a variety of unclassified eczemas including pityriasis alba, discoid eczema, acute vesicular eczema of the hands and/or feet, and hyperkeratotic eczema of the feet.(AU)

Differential patterns of serum biomarkers of immune activation in human T-cell lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis, and adult T-cell leukemia/lymphoma

Adult T-cell leukemia/lymphoma (ATL) and human T-cell lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) are associated with differing patterns of immune dysfunction. Biomarkers of immune activation may correlate with perturbations of immune function associated with these diseases. We conducted a pilot cross-sectionalstudy to assess four candidate biomarkers of immune activation, beta 2-microglobulin, neopterin, tryptophan, and kynurenine levels were assayed in storedsera from asymptomatic, human T-cell leukemia virus type I (HTL V-I) seronegative (HTLV-I-) and HTLV-I-seropositive (HTLV-I+) individuals, and ATL and HAM/TSP patients previously enrolled in seroepidemiological studies in Jamaica. Mean levels of beta 2-microglobulin, neopterin, and kynurenine were significantly elevated among ATL patients compared to the other study groups. Mean tryptophan levels were signigicantly lower among ATL and HAM/TSP patients than HTLV-I- and HTLV-I+ groups. No significant differences in biomarkers were found between HTLV-I- and HTLV-I+ groups. Among HAM/TSP patients, a significant association was found between elevated neopterin levels and symptoms of less than 4 years duration. In Cox proportional hazards regression modeling, neopterin and tryptophan were found to be independent predictors of survival among ATL patients. This study demonstrates a differential pattern of biomarkers of immune activation among ATL and HAM/TSP patients compared to HTLV-I- amd HTLV-I+ individuals. Neopterin and tryptophan may be useful clinical indicators of disease severity and prognosis among HAM/TSP and ATL patients. (AU)

Prevalence of antibodies to hepatitis C virus and other markers in Jamaica

Three population groups, 1500 blood donors, 513 antenatal women representing a normal population group and 250 sicklers representing a multiply transfused group were studied to determine the prevalence of hepatitis C viral (HCV) infection in Jamaica. The relationship to liver enzyme levels, hepatitis B infection, syphilis and HIV infection was also investigated. Sera were screened by enzyme-linked immunoassay (EIA) for anti-HCV C100-3 and subsequently tested by a supplementary second generation recombinant immunoblot assay (RIBA). In the blood donors, the prevalence of anti-HCV was low, 0.3 per cent - 0.4 per cent, the same level as that reported by several European countries. In the multiply transfused sicklers, the prevalence was more than seven times higher. No HCV infection was detected in the antenatal group. There was little correlation between HCV infection and surrogate markers alanine aminotransferase (ALT) and antibody to hepatitis B core antigen (anti-HBc) and no correlation with sexually transmitted diseases. (AU)

Field evaluation of baits and baiting strategies for delivering oral vaccine to mongooses in Antigua, West Indies

A field of study was conducted on Antigua, West Indies to determine the feasibility of delivering an oral rabies vaccine or population control agent to free-ranging mongooses (Herpestes javanicua). Two biomarkers (tetracycline hydrochloride [THCL] and Dupoint Oil Blue A dye) and two bait types (Dupont polymer fish meal and polyurethane foam) were used to bait three study sites. Four hundred polymer baits containing both biomarkers were distributed at 36 central point bait stations (11 baits/station) on an 80 ha study site (5 baits/ha); 69 percent of the mongoose population consumed one or more baits. Two thousand baits containing THCL and 400 baits containing DuPont dye were distributed on two additional 100 ha study sites (24 baits/ha). Polymer fish meal baits were used on the first site and polyurethane baits on the second site. Based on the presence of biomarkers in bone or soft tissue, 96 to 97 percent of the mongooses at both sites consumed at least one bait. We conclude that oral baiting of mongooses is a feasible method for delivery of vaccines for the control of rabies in this species (AU)

The selection of chemical markers in faeces for the identification of geophagia - abstract

Geophagia is the deliberate ingestion of soil and has been associated with geohelminthiasis, lead poisoning and other conditions of public health importance. It seems worthwhile therefore to investigate the extent of geophagia in the general population. One approach to the identification and quantification of geophagia would be to detect in faeces naturally occurring soil-specific chemical markers. These markers should exist in low concentration in food, water and other edibles, be of low bioactivity, and be excreted quantitatively in faeces. This study reports the selection of chemical markers common to Jamaican soils to be used as indicators of geophagia in the general population. Three common Jamaica soils were sterilised and placed in 1g gelatin capsules. Five volunteers were each asked to ingest 10 g of one of the soils with carmine (an inert gastrointestinal dye). A pre-ingestion faecal sample and all post-ingestion faecal samples were collected until no more carmine was seen in the faeces. The procedures was repeated for the other two soils. All faecal and soil samples were examined by Instrumental Neutron Activation Analysis (INAA). A total of 14 elements were found to be common to the three soils used in this study. Of these, dysprosium, europium, cerium, hafnium and thorium wer consistently detected in the post-ingestion faecals but not in the preingestion faecals. These five elements should make excellent markers of geophagia as they are present in insignificant levels in good compared to soil and seem to have low bioactivity. INAA has the highest sensitivity for dysprosium and europium and both have short processing time (30 minutes per sample). INAA and the use of dysprosium and/or europium as chemical markers would appear to be a promising basis for the detection of geophagia in the general population (AU)