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Biomedical subjects

A J Hall

Publications and source records attributed to A J Hall.

At least 55 records · Page 3Linked to original sources

Scedosporium endophthalmitis: two fatal disseminated cases of Scedosporium infection presenting with endophthalmitis.

The incidence of disseminated infection with Scedosporium species is increasing in patients with haematological malignancy. Two fatal cases are reported of patients with acute myeloid leukaemia and neutropenia who presented with Scedosporium endophthalmitis. Diagnosis of fungal infection was delayed as blood and vitreous cultures were positive only after 3 days in patient 1 and blood culture was positive at 7 days in patient 2. Despite antifungal therapy with amphotericin B and additional fluconazole in patient 2, both patients died of overwhelming fungal septicaemia. Post-mortem examination of the right globe in patient 1 showed haemorrhagic necrotizing chorioretinitis with numerous fungal hyphae in choroidal vessels, choroid, retina and vitreous. Scedosporium species are often resistant to conventional antifungal therapy including amphotericin B. Diagnosis is difficult and mortality in disseminated infection is high.

Acute Disease↗

Uveitis in Herpes zoster ophthalmicus.

BACKGROUND: Herpes zoster ophthalmicus (HZO) is a common condition occurring mostly in healthy people. Approximately 50% of HZO patients develop ocular complications, with iridocyclitis occurring in about 43%. This study aimed to identify the clinical features of uveitis secondary to HZO. METHOD: A retrospective case study was performed of consecutive patients with HZO and secondary uveitis seen in the past 10 years at the Royal Victorian Eye and Ear hospital as well as those seen in the private clinics of two ocular immunology consultants. The information collected included the time relationship between onset of rash and uveitis, duration and treatment of the uveitis, and rate and nature of ocular complications. RESULTS: Thirty-four patients fulfilled the enrolment criteria. The age range was from 24 to 83 years with an average age of 62.5 years. Of these, 28 patients (82%) were immunocompetent and six patients (18%) had underlying immunosuppression from various causes. Twenty-three patients had a uniphasic episode of uveitis and 11 patients (32%) had a chronic relapsing course of uveitis. The duration of the uveitis was variable, ranging from 1 week to 3 years, with 68% of episodes resolving within 2 months. Nineteen patients (56%) developed secondary glaucoma. Five of these patients (26%) required trabeculectomies to control their intraocular pressures. Three patients (9%) had bilateral ocular involvement and five patients (15%) had a reduction in final Snellen visual acuity of more than two lines. CONCLUSION: In this study, most patients were immunocompetent individuals. The course of the uveitis was generally uniphasic in nature and of a relatively short duration. There was a high incidence of secondary glaucoma with 15% of all patients requiring surgical intervention. The visual loss in the five patients was not directly related to the uveitis and secondary glaucoma but to other complications associated with HZO.

Adult↗

Changing causes of death in the West African town of Banjul, 1942-97.

OBJECTIVE: To determine trends in the causes of death in a West African town. Mortality caused by infectious diseases is reported to be declining while degenerative and man-made mortality factors are increasingly significant. Most mortality analyses for sub-Saharan Africa have involved extrapolation and have not been derived from community-based data. METHODS: Historical data on causes of death coded by physicians were analysed for the urban population of Banjul for the period 1942-97. As the calculation of rates is not possible in the absence of a reliable population denominator, age-standardized proportional mortality ratios (PMRs) for men and women by major groups of causes of death were calculated, using the 1942-49 data for reference purposes. FINDINGS: Most deaths were attributable to communicable diseases. There was a shift in proportional mortality over the study period: the contribution of communicable diseases declined and that of noncommunicable diseases and injuries increased. These trends were more marked among men than women. CONCLUSION: The data illustrate that while noncommunicable diseases and injuries are emerging as important contributors to mortality in sub-Saharan Africa, communicable diseases remain significant causes of mortality and should not be neglected.

Adult↗

Epidemiology of hepatitis B virus infection in the Middle East.

In this article, the epidemiology of hepatitis B (HBV) infection in the Middle East is reviewed. The prevalence of HBV carrier status in the region is considered and the modes of transmission of infection discussed. The risk factors associated with HBV infection are examined and preventive measures against HBV infection in countries of the region are presented. The review is based on information from two sources--publications in the international literature on the epidemiology of HBV infection in Middle East countries, identified by searching MEDLINE and POPLINE, and Middle East country and regional reports on viral hepatitis. It is evident that HBV infection is a serious public health problem in the region and many questions specific to the region remain unanswered. Community-based surveys are recommended as they provide more accurate information that can be generalized than hospital-based surveys.

Adult↗

Prevalence of antiviral drug resistance in untreated patients with cytomegalovirus retinitis.

The purpose of this study was to determine the prevalence of UL97 resistance mutations in cytomegalovirus (CMV) DNA amplified from the eyes of patients with AIDS and newly diagnosed CMV retinitis. Relevant segments of the CMV UL97 gene were amplified from vitreous humor, after which restriction digest screening was performed for resistance mutations at codons 460, 520, 591, 592, 594, 595, and 603. Mutations were confirmed by DNA sequencing. Vitreous from 21 eyes with AIDS-related non-CMV viral retinitis served as negative controls. CMV DNA was successfully amplified from 195 of 204 eyes. A resistance mutation was found in only a single eye, a T-->G mutation at base 1774, predicting a cysteine to glycine mutation at codon 592. The prevalence of UL97 resistance mutations in the eyes of patients with newly diagnosed CMV retinitis is very low.

AIDS-Related Opportunistic Infections↗

Aetiology, outcome, and risk factors for mortality among adults with acute pneumonia in Kenya.

BACKGROUND: Despite a substantial disease burden, there is little descriptive epidemiology of acute pneumonia in sub-Saharan Africa. We did this study to define the aetiology of acute pneumonia, to estimate mortality at convalescence, and to analyse mortality risk-factors. METHODS: We studied 281 Kenyan adults who presented to two public hospitals (one urban and one rural) with acute radiologically confirmed pneumonia during 1994-96. We did blood and lung-aspirate cultures, mycobacterial cultures, serotype-specific pneumococcal antigen detection, and serology for viral and atypical agents. FINDINGS: Aetiology was defined in 182 (65%) patients. Streptococcus pneumoniae was the most common causative agent, being found in 129 (46%) cases; Mycobacterium tuberculosis was found in 26 (9%). Of 255 patients followed up for at least 3 weeks, 25 (10%) died at a median age of 33 years. In multivariate analyses, risk or protective factors for mortality were age (odds ratio 1.51 per decade [95% CI 1.04-2.19]), unemployment (4.42 [1.21-16.1]), visiting a traditional healer (5.26 [1.67-16.5]), visiting a pharmacy (0.30 [0.10-0.91]), heart rate (1.64 per 10 beats [1.24-2.16]), and herpes labialis (15.4 [2.22-107]). HIV-1 seropositivity, found in 52%, was not associated with mortality. Death or failure to recover after 3 weeks was more common in patients with pneumococci of intermediate resistance to benzylpenicillin, which comprised 28% of pneumococcal isolates, than in those infected with susceptible pneumococci (5.60 [1.33-23.6]). INTERPRETATION: We suggest that tuberculosis is a sufficiently common cause of acute pneumonia in Kenyan adults to justify routine sputum culture, and that treatment with benzylpenicillin remains appropriate for clinical failure due to M. tuberculosis, intermediate-resistant pneumococci, and other bacterial pathogens. However, interventions restricted to hospital management will fail to decrease mortality associated with socioeconomic, educational, and behavioural factors.

Acute Disease↗

Environmental and genetic determinants of aflatoxin-albumin adducts in the Gambia.

Aflatoxins together with chronic hepatitis B virus (HBV) infection contribute to the high incidence of hepatocellular carcinoma in developing countries. An understanding of the mechanism of interaction between these factors would provide a strong rationale for developing effective prevention strategies. In this study in The Gambia we examined the effect of environmental (place of residence and timing of sample collection) and host factors (age, sex, HBV status and interindividual variations in carcinogen metabolising enzymes) in determining blood aflatoxin-albumin adduct levels in 357 individuals of whom 181 were chronic HBV carriers. Samples were analysed for aflatoxin-albumin adducts, HBV status and genotypes of glutathione S-transferase (GST) M1, GSTT1, GSTP1 and epoxide hydrolase (EPXH). Urine samples were analysed for 6beta-hydroxycortisol:cortisol ratio as a marker of cytochrome P450 (CYP) 3A4 activity. Adduct levels were significantly higher in subjects resident in rural [geometric mean adduct level 34.9 pg aflatoxin B1-lysine equivalent (28.5-42.8; 95%CI)/mg albumin] than in periurban areas [22.2 pg (14.9-33.4)/mg] and were approximately twice as high in the dry season [mid-February to March; 83.2 pg (53.3-130.8)/mg] than the wet [July to August; 34.9 pg (28.5-42.8)/mg]. In contrast, HBV status, CYP3A4 phenotype, GSTT1, GSTP1 and EPXH genotypes were not associated with aflatoxin-albumin adduct level. However, mean adduct levels were significantly higher in non-HBV infected subjects with GSTM1 null genotype. The main factors which affect aflatoxin-albumin adduct levels in this population are environmental, notably place of residence and timing of sample collection. This study further emphasises the priority to reduce aflatoxin exposure in these communities by primary prevention measures.

Adolescent↗

Femoral metastatic fractures treated with intramedullary nailing.

Between 1993 and 1998, 49 consecutive patients with impending or complete pathological fractures of the femur due to metastatic bone disease were treated with intramedullary nailing. Twenty-four were treated with a long Gamma nail and 32 with an AO nail with a cephalomedullary spiral blade. Both implants gave a good functional result with relief of pain and improved mobility with no difference in morbidity between either group (P>0.05).

Bone Neoplasms↗

Aortic wall tension as a predictive factor for abdominal aortic aneurysm rupture: improving the selection of patients for abdominal aortic aneurysm repair.

Aortic wall tension was determined in 40 patients to assess its predictive value in abdominal aortic aneurysm (AAA) rupture. A 3-year retrospective analysis of 243 patients with ruptured AAAs and 45 patients with intact AAAs was conducted. The 288 patient sample was limited to the 40 patients with an abdominal CT scan investigation. Aortic wall tension was calculated using blood pressure data and measurements from computerized tomographic (CT) images of 26 patients with intact AAAs and 14 patients with ruptured AAAs in accordance with LaPlace's Law for wall tension: P x R/W, where P = mean arterial pressure (MAP), R = radius of the vessel, and W = wall thickness of the vessel. The wall tension was approximated with the more readily accessible patient parameters of AAA diameter, MAP, height, and weight. This approximation was termed the body mass index (BMI)-pressure approximation for tension (BPAT), which is AAA diameter/BMI x MAP. Data were analyzed using one-sided t-tests, chi-squared tests, and a regression analysis for the relationship between aortic wall tension and the BPAT. AAA wall tension is a significant predictor of pending rupture. BPAT used to approximate the actual tension in the AAA wall is a more sensitive predictor of rupture than aneurysm diameter alone. A prospective study has been initiated to validate these conclusions.

Aorta, Abdominal↗

Primary prevention of hepatocellular carcinoma in developing countries.

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world with 80% of cases occurring in developing countries. The cancer is rapidly fatal in almost all cases with survival generally less than 1 year from diagnosis. The major risk factors for this cancer have been identified as chronic infection with hepatitis B (HBV) and hepatitis C (HCV) viruses and dietary exposure to aflatoxins. There is a safe and effective vaccine to prevent chronic HBV infection. Given estimates that approximately 70% of HCC in developing countries is attributable to HBV then vaccination could prevent more than 250,000 cases per year in these areas of the world. A major challenge now is to ensure the availability of vaccine in countries with endemic infection. Development of a vaccine against HCV is more problematic due to the genetic heterogeniety of the virus. However, with 24% of HCC in developing countries attributable to HCV (approximately 93,000 cases per year) a vaccine would make a major contribution to cancer prevention. Aflatoxins contaminate dietary staple foods (groundnuts, maize), are potent animal hepatocarcinogens and are carcinogenic in humans with particularly high risks in individuals with a concomitant infection with HBV. Reduction of exposure can be addressed at the community level either pre- or post-harvest by limiting fungal contamination of crops; approaches may involve low technology post-harvest measures to limit fungal growth or genetic engineering of crops to be resistant to fungal infection or toxin biosynthesis. An alternative measure is to modulate the metabolism of aflatoxins once ingested using chemopreventive agents e.g., oltipraz. The resources available in countries with endemic hepatitis infection and fungal contamination of foods are often severely limited. Clearly HBV vaccination has to be the priority in the reducing the incidence of HCC. However, there are currently 360 million chronic HBV carriers worldwide and HBV vaccine is still not incorporated into many national immunisation programs. Thus measures to reduce food spoilage by fungi and the associated dietary exposure to aflatoxins is also a desirable public health goal.

Aflatoxins↗

Early BCG vaccination and reduction in atopy in Guinea-Bissau.

BACKGROUND: It has been proposed that certain viral and bacterial infections in early childhood may prevent allergic sensitization, by inducing Th1-type immune responses. This has led to speculation that mycobacterial vaccines might, through their Th1-stimulating properties, also protect against atopy. OBJECTIVE: To investigate whether the prevalence of atopy is lower in children who have been vaccinated with BCG in infancy than in children who have not been vaccinated. METHODS: We measured skin test reactivity to three allergens (Dermatophagoides pteronyssinus, D. farinae and cockroach) in 400 children, aged 3-14 years, as part of a follow-up study to examine the immune sequelae of measles in an urban area of Bissau, the capital of Guinea-Bissau in west Africa. Information on childhood vaccinations, including BCG in infancy, was available from child records. Of these children, 271 had been vaccinated with BCG (according to records) and 53 had not been vaccinated (no record and no BCG scar). Atopy was defined in two ways, according to the presence of any allergen reaction > or = 2 mm and any reaction > or = 3 mm. RESULTS: Of the children who had received BCG vaccine, 57 (21%) were atopic (any reaction > or = 2 mm), compared with 21 (40%) of the unvaccinated children [odds ratio, after controlling for potential confounding factors, 0.19 (95% CI 0.06-0.59)]. When atopy was defined using the 3-mm criterion, the reduction in atopy associated with BCG was greater the earlier the age at vaccination, and the largest reduction was seen in children vaccinated in the first week of life. CONCLUSION: BCG vaccination given early in infancy may prevent the development of atopy in African children.

Adolescent↗

First, do no harm.

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Blood-Borne Pathogens↗

Hepatitis B infection and aflatoxin biomarker levels in Gambian children.

OBJECTIVES: To examine the relationship between hepatitis B virus (HBV) infection and biomarkers of aflatoxin exposure in West African children. METHODS: Sera from 444 children aged 3-4 years who were selected to be representative of their communities were analysed for aflatoxin-albumin (AF-alb) adducts and markers of hepatitis B infection. RESULTS: There was large interindividual variation in adduct levels (range: 2.2 to 459 pg AF-lysine eq./mg albumin). Adduct level was strongly correlated with season, with an approximately twofold higher mean level in the dry season than the wet. Geometric mean adduct levels in uninfected children, chronic carriers and acutely infected children were 31.6 (n = 404), 44.9 (n = 34) and 96.9 (n = 6) pg/mg, respectively. The relationship of AF-alb level to ethnicity, month of sampling and HBV status was examined in a multiple regression model. Month of obtaining the blood sample (P = 0.0001) and HBV status (P = 0.0023) each made a highly significant contribution to the model; the high AF-alb levels were particularly associated with acute infection. Elevated serum transaminase levels were significantly (P < 0.002) associated with HBV status, with acutely infected children having the highest levels. Ethnicity was not significantly associated with AF-alb adduct levels in the model (P = 0.09). CONCLUSIONS: HBV infection and month of sampling both significantly influence AF-alb adduct levels. The effect of seasonality on adducts was also observed in a previous study of 347 Gambian adults, although there was no correlation between adduct level and HBV status in that population. This difference between children and adults may reflect a more severe effect of HBV infection, particularly acute infection, in childhood on hepatic AF metabolism.

Aflatoxins↗

Effect of selective gastric intrinsic denervation on gastric motility in turkeys.

The effect of selectively denervating portions of the myenteric plexus on gastroduodenal (GD) motility was examined in domestic turkeys (Meleagris gallopavo). The neural network beneath the lateral or medial side of the isthmus between the glandular stomach and the muscular stomach was denervated by application of 1% benzalkonium chloride (BC). Image intensification radiology (IIR) was performed postsurgically on the research subjects to observe GD contractions and to analyze aberrations. Two trials were performed. The first employed temporal controls by checking GD motility in all treated birds before and after BC had taken effect. The second trial controlled for the trauma associated with the surgical procedure by applying 0.9% saline solution in lieu of BC in four turkeys. The normal GD contractions sequence as confirmed by these controls was thin muscle contraction, duodenal contraction and outflow, thick muscle contraction, and, finally, glandular stomach contraction. Ablation of the nerves beneath the medial or lateral side of the isthmus resulted in the same abnormality in GD motility, namely a lack of thick muscle contractions. These results indicate that the entire myenteric plexus associated with the isthmus must remain intact for proper GD motility to take place. Furthermore, it can be inferred that initiation and regulation of the thick muscle pair acts via nerves encircling the isthmus. Secondary regulatory mechanisms controlling GD motility may exist and should be tested through future investigation.

Animals↗

Validation of immune-complex enzyme immunoassays for diagnosis of pneumococcal pneumonia among adults in Kenya.

The efficacy of pneumococcal vaccines in protecting against pneumococcal pneumonia can feasibly be measured only with a diagnostic technique that has a high specificity (0.98 to 1.00) and a sensitivity greatly exceeding that of blood cultures (>0.2 to 0.3). In this context immune-complex enzyme immunoassays (EIAs) offer a novel, convenient diagnostic method, and we have investigated three such assays with appropriate study populations in Kenya. Sera from 129 Kenyan adults with pneumococcal pneumonia and 97 ill controls from the same clinics, but without pneumococcal disease syndromes, were assayed with immune-complex EIAs for pneumolysin, C-polysaccharide, and mixed capsular polysaccharides (Pneumovax II). At an optical density (OD) threshold yielding a specificity of 0.95, the sensitivities (95% confidence intervals) of the assays were 0.22 (0.15 to 0.30), 0.26 (0.19 to 0.34), and 0.22 (0.15 to 0.29), respectively. For pneumolysin immune complexes, human immunodeficiency virus (HIV)-positive patients had a higher mean OD than HIV-negative patients (639 versus 321; P < 0.0001), but stratification by HIV infection status did not alter the performance of this test. Combining the results of all three EIAs did not enhance the diagnostic performances of the individual assays. In Kenyan adults the sensitivities of the immune-complex EIAs could exceed that of blood cultures only at levels of specificity that were insufficient for the performance of vaccine efficacy studies.

Adult↗