Human papillomavirus 16 (HPV16) and HPV52 E6-specific immunity in HIV-infected adults on combination antiretroviral therapy.

OBJECTIVES: Human papillomavirus (HPV)-associated cancers disproportionately affect those infected with HIV despite effective combination antiretroviral therapy (cART). The primary aim of this study was to quantify HPV16 and HPV52 E6-specific interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) T-cell responses, a correlate of protective immunity, in the first year following cART initiation and subsequently in those patients with suboptimal (sIR) and optimal (oIR) immune reconstitution. METHODS: Ninety-four HIV-infected patients were recruited to the study; a longitudinal cohort of patients recruited just prior to commencing cART and followed up for 48 weeks (n = 27), and a cross-sectional cohort (n = 67) consisting of patients with sIR (CD4 T-cell count < 350 cells/µL) and oIR (CD4 T-cell count > 500 cells/µL) after a minimum of 2 years on cART. Controls (n = 29) consisted of HIV-negative individuals. IFN-γ ELISPOT responses against HPV16 and HPV52 E6 were correlated to clinical characteristics, anal and oral HPV carriage, T-cell maturational subsets, markers of activation, senescence and T-regulatory cells. RESULTS: HPV16 and HPV52 E6-specific T-cell responses were detected in only one of 27 patients (3.7%) during the initial phase of immune recovery. After at least 2 years of cART, those who achieved oIR had significantly higher E6-specific responses (9 of 34; 26.5%) compared with those with sIR (2 of 32; 6.3%) (P = 0.029). Apart from higher CD4 T-cell counts and lower CD4 T-cell activation, no other immunological correlates were associated with the detection of HPV16 and HPV52 E6-specific responses. CONCLUSIONS: HPV16 and HPV52 E6-specific IFN-γ T-cell responses, a correlate of protective immunity, were detected more frequently among HIV-infected patients who achieved optimal immune recovery on cART (26.5%) compared with those with suboptimal recovery (6.3%).

Laboratory detection of strongyloidiasis: IgG-, IgG4 - and IgE-ELISAs and cross-reactivity with lymphatic filariasis.

Enzyme-linked immunosorbent assays (ELISAs) were developed for the detection of IgG, IgG4 and IgE antibodies against Strongyloides stercoralis. A commercial ELISA (IVD Research, USA) was also used, and the sensitivities and specificities of the four assays were determined. Serum samples from 26 patients with S. stercoralis infection and 55 patients with other infections or no infection were analysed. Sensitivities of the IgG4 , IgG, IgE and IgG (IVD) assays were 76.9%, 84.6%, 7.7% and 84.6%, respectively, while the specificities were 92.7%, 81.8%, 100% and 83.6%, respectively. If filariasis samples were excluded, the specificities of the IgG4 -ELISA and both IgG-ELISAs increased to 100% and 98%, respectively. A significant positive correlation was observed between IgG- and IgG4 -ELISAs (r = 0.4828; P = 0.0125). IgG- and IgG- (IVD) ELISAs (r = 0.309) were positively correlated, but was not significant (P = 0.124). Meanwhile there was no correlation between IgG4 - and IgG- (IVD) ELISAs (r = 0.0042; P = 0.8294). Sera from brugian filariasis patients showed weak, positive correlation between the titres of antifilarial IgG4 and the optical densities of anti-Strongyloides IgG4 -ELISA (r = 0.4544, P = 0.0294). In conclusion, the detection of both anti-Strongyloides IgG4 and IgG antibodies could improve the serodiagnosis of human strongyloidiasis. Furthermore, patients from lymphatic filariasis endemic areas who are serologically diagnosed with strongyloidiasis should also be tested for filariasis.

Resolution of adefovir-related nephrotoxicity by adefovir dose-reduction in patients with chronic hepatitis B.

BACKGROUND: Chronic hepatitis B patients (CHB) treated with adefovir were followed up to evaluate nephrotoxicity and its outcome. AIM: To assess the incidence of renal dysfunction during adefovir therapy in Asian patients and factors associated with it, and evaluate strategies to improve adefovir-related renal dysfunction and their impact on viral suppression. METHODS: Chronic hepatitis B clinic patients from a tertiary hospital on adefovir treatment, with their clinical and laboratory parameters were extracted from the hospital electronic clinical database in an observational study design. Patients were excluded if they had liver/renal transplant, baseline renal impairment or were on dialysis. Adefovir-related renal dysfunction was defined as adefovir-related abnormal serum creatinine (ARASC) > 125 µmol/L (males), >90 µmol/L (females); adefovir-related abnormal GFR <60 mL/min; and adefovir-related increased serum creatinine >0.5 mg/dL, without other known causes of nephrotoxicity. RESULTS: A total of 271/383 adefovir-treated patients were suitable for analysis and 33(12%) patients developed abnormal serum creatinine. Cumulative increase in proportion of patients with ARASC was 33.8% and GFR ≤60 mL/min was 38.3% by 6 years, while serum creatinine increase ≥0.5 mg/dL was 21.48% by 5 years. Using multivariate analysis, the only independent baseline predictor of ARASC was GFR ≤76.1 mL/min. Patients who had ARASC had similar levels of viral suppression to those who did not have ARASC. Those who had ARASC either continued adefovir (24%), switched therapy (24%) or had adefovir dose reduction (52%). ARASC resolved and GFR normalised in almost all patients after either switching therapy or reducing adefovir dose, with no difference between the two strategies (P = 0.737). Those with adefovir dose reduction had no significant increase in HBV DNA (P = 0.170). CONCLUSIONS: Adefovir-related renal dysfunction occurred in a significant number of adefovir-treated patients, but reduction of the dose led to renal improvement without compromising treatment efficacy.

Recurrent pancreatitis secondary to pancreatic ascariasis.

Ascaris lumbricoides infestations are endemic in tropical countries. Ascaris lumbricoides can occasionally cause biliary obstruction and result in obstructive jaundice or pancreatitis. We present a 34-year-old Bangladeshi woman with biliary ascariasis, resulting in recurrent pancreatitis. Her diagnosis was made with endoscopic retrograde cholangiopancreatography performed during an acute attack of pain.

Effect of fluoxetine on maximal electroshock seizures in mice: acute vs chronic administration.

There are no definite reports regarding the effects of chronic fluoxetine on animal models of epilepsy. Since chronically administered fluoxetine, in comparison to acutely administered fluoxetine has different effects on CNS, the present study was undertaken to investigate the effect of acute and chronic fluoxetine pretreatment, on a median anticonvulsant dose (ED50) of phenytoin in male ICR albino mice. Additionally, the effects of fluoxetine pretreatment on median convulsive current (CC50) in the presence and absence of phenytoin were investigated and results were compared. The maximal electroshock seizure (MES) test was used to estimate the ED50of phenytoin. The electroshock threshold test was used to estimate CC50. ED50and CC50values were calculated by probit analysis. The effects of the chronic and acute fluoxetine groups on the ED50of phenytoin were significantly different (P<0.05), and on CC50this difference was not statistically significant. Chronic fluoxetine insignificantly increased the ED50of phenytoin and decreased the CC50while acute fluoxetine decreased the ED50of phenytoin and increased the CC50. Our results indicate that chronic fluoxetine does not have an antiepileptic property and it may have dubious proconvulsant properties, contrary to acute fluoxetine.

Prognostic significance of retinopathy at presentation in adult acute leukemia.

Retinal changes are common in adult acute leukemia patients at presentation, but their prognostic significance is controversial. A 5-year study has been carried out with newly diagnosed acute leukemia patients aged 12-77 years. Seventy-seven cases (49 AML, 28 ALL) were studied prospectively for the presence of intraretinal hemorrhages (IRH), white-centered hemorrhages, cotton-wool spots, and macular hemorrhages. They were treated according to standard chemotherapy protocols, and then achievement of complete remission (CR) and the duration of overall survival (OS) were compared between the groups with and without these different retinal features. No association was found between the presence of any retinal abnormality and CR induction rate, although there was a trend to a lower CR rate among patients with IRH. The median OS of those with IRH was 72 days, compared with 345 days among those without IRH (p=0.002). A WBC at presentation greater than 50x10(9)/l and age greater than 40 years were also associated with shorter OS (p<0.0001 and p=0.0045, respectively). However, after regression analysis, IRH remained statistically significant as a poor prognostic indicator (p=0.01). We conclude that the presence of IRH is an indicator of poor prognosis in acute leukemia.

An application of the backcalculation method to estimate past HIV infection rates in Malaysia.

The method of backcalculation estimates past HIV infection rates from available AIDS incidence data and an estimate of the incubation period. The method is used on the Malaysian data to model the AIDS epidemic because it makes use of the Malaysian AIDS incidence data which is fairly reliable and is more reflective of the trend of the epidemic as compared to the HIV infection rate recorded. An application is made on the monthly AIDS incidence data in Malaysia from January 1995 until August 1996 released by the Ministry of Health, Malaysia using the backcalculation program from Bacchetti et al and the incubation period distribution from Brookmeyer to generate the current HIV infection rate for Malaysia (until August 1996).

Macular haemorrhage in adult acute leukaemia patients at presentation and the risk of subsequent intracranial haemorrhage.

Retinal changes are common in adult acute leukaemia patients at presentation, but whether they correlate with the risk of subsequent intracranial haemorrhage is unknown. A 4-year study has been carried out in 82 newly-diagnosed acute leukaemia patients, aged 12-77 years, who were studied prospectively for the presence of intra-retinal haemorrhages (IRH), white-centred haemorrhages (WCH), cotton-wool spots (CWS) and macular haemorrhages (MH). Groups with and without these features were compared for their risk of intra-cranial haemorrhage (ICH) within the first 30 d following diagnosis. There was no association between the incidence of ICH and the presence of IRH, WCH or CWS. However, 6/13 of those with MH developed ICH, compared to 6/69 of those without MH (relative risk 5.0, CI 95% [2.03-12.33], P=0.003). The only other identifiable risk factor for ICH was the M3 subtype of AML, but if the four cases of M3-AML were discounted from analysis, MH remained a highly significant risk factor for ICH. Patients with MH should be monitored intensively for the development of ICH, and receive priority in the allocation of platelets where these are in short supply.

Retinal findings in adult leukaemia: correlation with leukocytosis.

The associations between retinal findings and haematological parameters in acute leukaemia are controversial. Sixty-three newly-diagnosed acute leukaemia patients, aged 12-77 years, were studied prospectively for the presence of intra-retinal haemorrhages (IRH), white-centred haemorrhages (WCH), cotton wool spots (CWS) and macular haemorrhages (MH), Thirty-three patients (52.4%) showed at least one retinal abnormality. The prevalence of individual findings was: IRH (30 cases), WCH (20 cases), CWS (5 cases), MH (11 cases). In contrast to previous studies, there was no association between any of these retinal findings and the haemoglobin level or the platelet count. There was a higher median WBC in patients with IRH (68 x 10(9)/l) than in those without IRH (15.4 x 10(9)/l), P = 0.037. When the acute myeloblastic leukaemia cases were considered separately, an association was also found between higher WBC and the presence of WCH and CWS. There was no association between retinal findings and FAB type in the AML cases. We conclude that a high WBC may be at least as important as anaemia and thrombocytopenia in the pathogenesis of the retinopathy of acute leukaemia.

Prospective randomized study of radical versus four piles haemorrhoidectomy for symptomatic large circumferential prolapsed piles.

Twenty-eight patients (14 men, 14 women) with circumferential prolapsed piles were prospectively randomized to undergo either modified radical haemorrhoidectomy (group 1; 14 patients) or four piles haemorrhoidectomy (group 2; 14). The median duration of surgery was 30 and 10 min respectively in groups 1 and 2. After operation all patients in group 1 were continent compared with 12 of 14 in group 2. Two patients in group 2 developed an anal stricture requiring manual dilatation. Five patients in group 1 had wound dehiscence requiring secondary suture; three of these developed an anal stricture: two needed anal dilatation and one required anoplasty. Two patients in group 1 had residual anal skin tags, compared with nine in group 2. Two patients in group 2 had symptomatic residual piles, whereas none in group 1 had this problem. At 6 months, six patients in group 2 considered the results to be excellent, seven acceptable and one was disappointed. In group 1 two considered the operation to be excellent, ten acceptable and two were disappointed.

Colonic carcinoma with metastases to the tibialis anterior muscle--a case report.

Colorectal carcinoma usually spreads along predictable routes to the abdominal lymph nodes, liver and lungs. Documented cases of metastatic spread to skeletal muscle are uncommon. To the knowledge of the authors, only four cases have been previously reported in the literature. This is a report of a case of advanced carcinoma of the descending colon with metastases to the left tibialis anterior muscle. This case is unusual in that the patient first presented with a symptomatic secondary deposit and the primary lesion is only discovered after the histology of the left leg tumour is known.

Blunt abdominal trauma--injury assessment in relation to early surgery.

One hundred and thirteen patients sustaining blunt abdominal trauma over a 24-month period were retrospectively divided into three groups to assess parameters of three diagnostic methods and the time-lapse before implementing surgical treatment. Diagnosis was based in group A patients (n = 20) on physical findings, plain radiology, and blood and urine examinations. Diagnostic methods in group B patients (n = 35) and in group C patients (n = 58) were as in group A but with the addition of diagnostic peritoneal lavage (DPL) in group B or with the addition of diagnostic abdominal ultrasonography (DAU) in group C. Sixty-five patients underwent abdominal exploration. The time-lag from commencement of examination to surgery was 332.33 +/- 48.90 min, 251.82 +/- 29.08 min and 570.89 +/- 133.80 min respectively in groups A, B and C. It was significantly shorter in group B compared with group C (P = 0.03). DPL had a sensitivity of 95%, a specificity of 81% and an accuracy of 89% whilst DAU had a sensitivity of 79%, a specificity of 85% and an accuracy of 83% in detecting significant injury. The conclusion is that DPL in combination with DAU would facilitate early assessment and treatment of intra-abdominal injuries.

Outcome prediction in early management of severe head injury: an experience in Malaysia.

The outcome of 109 patients with severe head injury was studied in relation to clinical and computed tomographic (CT) criteria on admission, after resuscitation. Age, Glasgow Coma Score (GCS) and state of pupils strongly correlated with outcome. The presence of hypothalamic disturbances, hypoxia and hypotension were associated with an adverse outcome. The CT indicators associated with poor outcome were perimesencephalic cistern (PMC) obliteration, subarachnoid haemorrhage, diffuse axonal injury and acute subdural haematoma. The prognostic value of midline shift and mass effect were influenced by concomitant presence of diffuse brain injury. For the subset of patients aged < 20 years, with GCS 6-8 and patent PMC (n = 21), 71.4% correct predictions were made for a good outcome. For the subset of patients aged > 20 years, with GCS 3-5 and partial or complete obliteration of PMC (n = 28), 89.3% correct predictions were made for a poor outcome.

Investigation of the associations of a number of HLA antigens with psoriasis and psoriatic arthritis.

A method, using the GLIM computer package, for determining primary and secondary HLA associations with disease is described and is applied to data from patients with psoriasis and psoriatic arthritis.

The distributions of N and F: measures of HLA haplotype concordance.

Nonrandom inheritance of the two HLA haplotypes of Chromosome 6, available from each parent among siblings affected by certain diseases, has afforded evidence of HLA-linked disease-susceptibility genes. Two algebraically equivalent measures of HLA haplotype concordance (that is, the excessive sharing of certain haplotypes among affected siblings) are used for family studies designed to test whether or not there is significant evidence of the existence of an HLA-linked disease-susceptibility gene or for inferring the mode of inheritance when this is already believed to apply. The distributions of these measures are derived under the null hypothesis of random inheritance of HLA haplotypes, and there is a short discussion of the case in which inheritance of a diseased gene causes a change, from the purely random case, in the distribution of haplotype concordance among affected siblings.