Clinicopathological review of ocular surface squamous neoplasia in Malawi.

BACKGROUND: Ocular surface squamous neoplasia (OSSN) is the most common cause of malignancy of the conjunctiva. Variable clinical presentation means that invasive malignant OSSN is often difficult to discriminate from other similarly presenting differential diagnoses which can be managed more conservatively. AIMS: Identification of clinical factors associated with a histopathological diagnosis of conjunctival squamous cell carcinoma (SCC). METHODS: Prospective consecutive case series of suspected OSSN cases presenting at two hospitals in Central Malawi over a 1 year period. A pro forma was completed assessing preidentified clinical variables. Suspected lesions underwent excisional biopsy followed by histopathological investigation. RESULTS: Fifty-eight patients were recruited. Mean age was 35.8 (range 22-62). 51 cases of histopathologically confirmed OSSN were found. 30 (50%) patients were confirmed HIV seropositive which rose to 86.67% in invasive SCC. Larger size of tumour (p=0.008), male gender (p=0.025) and HIV seropositivity (p=0.010) were associated with invasive SCC pathology. CONCLUSIONS: A clinicopathological study of OSSN has not previously been performed in Malawi. The association of HIV with SCC corresponds to previous reports from sub-Saharan Africa. A new finding in our study is a relationship between larger tumour size and invasive lesions confirmed by histopathology. When integrated into a clinical decision-making model, tumour area provides a simple clinical measure for ophthalmic practitioners to use in order to differentiate higher risk OSSN from more benign pathology. The higher risk lesions can subsequently be treated with greater surgical care and undergo closer follow-up.

An unusual presentation of an amoebic liver abscess: the story of an unwanted souvenir.

This case was rather unusual with regard to the disease presentation. The patient had non-specific symptoms of weight loss and general malaise, without any history of preceding diarrhoea or dysentery. It is important to be aware of the epidemiology of the disease, and to relate it to patients presenting with symptoms suggestive of amoebiasis. We discuss the recommended investigations and management options for these patients based on the current guidelines/evidence.

Two-wavelength fundus autofluorescence and macular pigment optical density imaging in diabetic macular oedema.

PURPOSE: To evaluate the application of 488 and 514 nm fundus autofluorescence (FAF) and macular pigment optical density (MPOD) imaging in diabetic macular oedema (DMO) and to demonstrate the typical imaging features. PATIENTS AND METHODS: A hundred and twenty-five eyes of 71 consecutive patients with diabetic retinopathy who underwent examination at a specialist university clinic employing a modified Heidelberg Retina Angiograph, using two different light sources of 488 and 514 nm wavelength, were retrospectively reviewed. MPOD images were calculated using modified Heidelberg Eye Explorer software. All images were evaluated by two independent masked graders. Features from FAF and MPOD images were correlated with optical coherence tomography (OCT) imaging findings and inter-grader variability, sensitivity and specificity were calculated using OCT as reference. RESULTS: Sixty-seven eyes had DMO on OCT. The inter-grader variability was 0.84 for 488 nm FAF, 0.63 for 514 nm FAF and 0.79 for MPOD imaging. Sensitivity and specificity for detection of DMO were 80.6 and 89.7% for 488 nm FAF; 55.2 and 94.8% for 514 nm FAF; and 80.6 and 91.4% for MPOD imaging. In 488 nm FAF and MPOD imaging, DMO was better visualised in comparison with 514 nm FAF imaging, P<0.01. MPOD revealed displacement of macular pigment by intraretinal cysts. CONCLUSION: MPOD imaging, and particularly its combination with 488 nm and 514 nm FAF, provides a valuable addition to OCT in the evaluation of DMO and is clinically useful in rapid en-face assessment of the central macula.

Management of peritoneal carcinomatosis secondary to metastatic cancer of unknown primary in men.

Peritoneal seeding of cancer cells leading to peritoneal carcinomatosis (PC) is an ominous finding that has primarily been described in women with underlying ovarian malignancy. It is also a common development in patients with gastrointestinal malignancy and may sometimes occur in the absence of a known, identified primary malignancy. Peritoneal carcinomatosis resulting from a cancer of unknown primary (CUP) is a rare and ill-defined entity, and as a result, there is no clear guidance on the most effective management strategy for this group of patients. The indiscriminate use of numerous investigations in an attempt to identify a primary malignant focus is discouraged. A subjective approach to the patient, with the aim of identifying patients who would benefit from therapeutic management and those who should be managed with palliative intent, should be employed. Aggressive therapeutic measures such as cytoreduction, peritonectomy and hyperthermic intraoperative intraperitoneal chemotherapy may offer some long-term survival, but selection of appropriate patients is essential. Large randomized studies are needed in patients with PC secondary to CUP to determine the efficacy of such treatment options. Studies into the pathogenesis and molecular pathways of this condition are required to improve understanding and guide development of novel therapeutic strategies.

The aetiology and associations of conjunctival intraepithelial neoplasia.

AIM: To summarise the main causes and associations of conjunctival intraepithelial neoplasia (CIN) found in the literature to date. METHOD: Literature search using Ovid databases on the NHS Scotland E-library, Medline, and the Cochrane Library. The internet search engine Google Scholar was also used to identify relevant articles. RESULTS: The main causes and associations of CIN in the literature are sun exposure and distance from the equator; human papillomavirus infection, increased p53 expression, and HIV seropositivity. It has been found that in HIV positive individuals CIN is on the increase with people being affected with more aggressive tumours at younger ages. CONCLUSION: Given that CIN is becoming more common in HIV infected populations and that it has the potential to cause severe disability, it is important to improve our understanding of the condition. Early identification of CIN by an understanding of its aetiology and associations may enable the implementation of preventative measures to reduce its incidence and potentially lead to the diagnosis and further management of conditions such as HIV. Young people presenting with CIN in particular may benefit from HIV testing.

Pancytopenia in Zimbabwe.

BACKGROUND: There has been little systematic study of the clinical spectrum of pancytopenia, and the optimal diagnostic approach to pancytopenia remains undefined. METHODS: The authors studied 134 hospitalized pancytopenic patients in Zimbabwe in both consecutive and nonconsecutive fashion. RESULTS: The most common cause of pancytopenia was megaloblastic anemia, followed by aplastic anemia, acute leukemia, acquired immunodeficiency syndrome (AIDS), and hypersplenism. Severe pancytopenia was usually due to aplastic anemia. Patients with aplastic anemia and acute leukemia were usually children, whereas those with megaloblastic anemia were adults. Moderate to severe anemia was noted throughout the series, but was most striking in patients with megaloblastic anemia, aplastic anemia, and acute leukemia. The mean corpuscular volume (MCV) was elevated in most patients with megaloblastic hematopoiesis, aplastic anemia, and acute nonlymphocytic leukemia. Normal or low MCV values were noted in almost one third of patients with megaloblastic anemia. Anisocytosis, poikilocytosis, macroovalocytosis, microcytosis, fragmentation, and teardrop erythrocytes were more prominent on the blood films of patients with megaloblastic anemia. CONCLUSIONS: Megaloblastic anemia, aplastic anemia, and AIDS are the most common causes of pancytopenia in Zimbabwe. Aplasia is the most frequent cause of severe pancytopenia. The authors have formulated tentative guidelines for the evaluation of pancytopenic patients in this setting.

African iron overload and hepatocellular carcinoma (HA-7-0-080).

Although HLA-linked hemochromatosis greatly increases the risk for hepatocellular carcinoma in people of European ancestry, iron overload in Africa is not thought to be etiologically related to this malignancy. To determine if African iron overload may be associated with hepatocellular carcinoma, we reviewed 320 consecutive diagnostic liver biopsies processed at the University of Zimbabwe from 1992 to 1994 and we selected for analysis 215 biopsies from adults that were suitable for the histological assessment of hepatocellular iron. Subjects were stratified according to hepatocellular iron grades of 0-2+ (normal levels to mild siderosis; n = 183) and grades of 3+ and 4+ (distinctly elevated levels consistent with iron overload; n = 32). Thirty-six subjects had hepatocellular carcinoma. Logistic regression modeling revealed a significant association between iron overload and hepatocellular carcinoma after adjustment for age, sex and and the presence of portal fibrosis or cirrhosis (p = 0.041). The odds of hepatocellular carcinoma in subjects with iron overload was 3.1 (95% confidence interval of 1.05-9.4) times that of subjects without iron overload. While we could not test for exposure to viral hepatitis or to aflatoxins in this study, our findings suggest that iron overload may be a risk factor for hepatocellular carcinoma in Africa.

Evidence of genetic transmission in African iron overload.

Iron overload in Africa was previously regarded as purely due to excessive iron in traditional beer, but we recently found evidence that transferrin saturation and unsaturated iron binding capacity may be influenced by an interaction between dietary iron content and a gene distinct from any HLA-linked locus. To determine if serum ferritin follows a genetic pattern and to confirm our previous observations, we studied an additional 351 Zimbabweans and South Africans from 45 families ranging in size from two to 54 members. Iron status was characterized with repeated morning measurements of serum ferritin, transferrin saturation, and unsaturated iron binding capacity after supplementation with vitamin C. For each measure of iron status, segregation analysis was consistent with an interaction between a postulated iron-loading gene and dietary iron content (P < .01). In the most likely model, transferrin saturation is 75% and serum ferritin is 985 micrograms/L in a 40-year-old male heterozygote with an estimated beer consumption of 10,000 L, whereas the saturation is 36% and serum ferritin is 233 micrograms/L in an unaffected individual with identical age, sex, and beer consumption. This segregation analysis provides further evidence for a genetic influence on iron overload in Africans.

Traditional beer consumption and the iron status of spouse pairs from a rural community in Zimbabwe.

To examine the relationship between dietary iron exposure through the consumption of traditional beer and the presence of iron overload in black Africans not related by birth, we studied 28 husband and wife pairs from a rural Zimbabwean community. Lifetime traditional beer consumption was estimated by questioning subjects and iron status was assessed by repeated measurements of serum ferritin and transferrin saturation in subjects who were fasting and had received vitamin C supplementation. Each of the 56 study subjects had an estimated lifetime traditional beer consumption >1,000 L. The mean +/- standard deviation (SD) concentration of iron in the supernatants of nine samples of traditional beer from the community was 46 +/- 10 mg/L. Four of 28 men (14.3%) and no women had the combination of an elevated serum ferritin and a transferrin saturation >70%, suggestive of substantial iron overload. Significant correlations were not found between the iron status of the husbands and their wives or between dietary iron exposure and iron stores. Our findings suggest that dietary iron exposure may not fully explain the development of iron overload in Africans and are consistent with the hypothesis that an iron-loading gene may also be implicated in pathogenesis.

Tuberculosis and iron overload in Africa: a review.

Both pulmonary tuberculosis and dietary iron overload are common conditions in sub-Saharan Africa. The incidence of tuberculosis has increased markedly over the last decade, primarily as a result of the rapid spread of infection with the human immunodeficiency virus (HIV). Dietary iron overload affects up to 10% of adults in rural populations and is characterized by heavy iron deposition both in parenchymal cells and in macrophages. Mycobacterium tuberculosis grows within macrophages and, at the same time, the antimicrobial function of macrophages is important in the body's defence against tuberculosis. In vitro, the loading of macrophages with iron reduces the response of these cells to activation by interferon-gamma and diminishes their toxicity against micro-organisms. In the clinical setting, dietary iron overload appears to increase the risk for death from tuberculosis even in the absence of the acquired immunodeficiency syndrome. The combination of dietary iron overload and infection with the HIV, with impaired function of both macrophages and T-cells, may make patients especially vulnerable to tuberculosis. It is possible that the prevention and treatment of dietary iron overload could contribute to the control of tuberculosis in African populations.

The epidemiology and prophylaxis of hepatitis B in sub-Saharan Africa: a view from tropical and subtropical Africa.

There are approximately 50 million chronic carriers of hepatitis B virus (HBV) in Africa, with a 25% mortality risk. In sub-Saharan Africa, carrier rates range from 9-20%. Many studies have suggested that HBV transmission in Africa occurs predominantly in childhood, by the horizontal rather than the perinatal route. The exact mode of transmission is uncertain but probably involves percutaneous infection through saliva or traces of blood, as well through unsterile needles, tribal scarification, and other possible vehicles. Compared with adult HBsAg carriers in the Far East, those in Africa have a low rate of HBeAg positivity, which may account for the relatively low rates of perinatal infection. It is also possible that African infants are less susceptible to perinatal HBV infection compared with their Asian counterparts. Alternatively, it may be that African infants are indeed infected with HBV at birth but, for genetically determined reasons, have persistently negative tests for a number of years until the virus is reactivated. In view of the high HBV carrier rates in the general population, universal immunisation of all infants is recommended. Ways of incorporating the hepatitis B vaccine into the Expanded Programme on Immunisation in each country are being evaluated.

High prevalence of Enterocytozoon bieneusi infections among HIV-positive individuals with persistent diarrhoea in Harare, Zimbabwe.

Infection with the microsporidian parasite Enterocytozoon bieneusi may be a major cause of prolonged diarrhoea in individuals also infected with human immunodeficiency virus (HIV). The parasite has been reported from Europe, Australia and the Americas, with a prevalence of 7-29%. Faecal specimens were obtained from 202 adults and 106 children in Harare, Zimbabwe, all of whom were in hospital and had diarrhoea. HIV serology was available for 119 adults: 106 were HIV seropositive. There were clinical grounds for suspecting HIV infection in 23 of the remaining patients. E. bieneusi was identified in specimens from 13/129 patients (10%) for whom HIV infection was indicated by serology and/or clinical signs, 1/60 patients (2%) of uncertain HIV status, and 0/13 seronegative patients. 18/106 children were HIV seropositive and 12 were not; HIV serology was not available for the remainder, but 19 were strongly suspected of being infected with HIV on clinical criteria. E. bieneusi was not detected in samples from any child. As is common in Zimbabwe, the prevalence of other parasites in faecal specimens was low and, amongst patients with proven or suspected HIV infection, E. bieneusi was the most prevalent parasite identified, particularly in patients with diarrhoea of over 4 weeks duration.

Helicobacter pylori in endoscopy patients in Zimbabwe: value of enzyme-linked immunosorbent assay and a rapid urease test.

Biopsy and serum specimens were obtained from 95 patients undergoing endoscopy at the University of Zimbabwe Medical School. Common presenting features were epigastric pain, bleeding and dyspepsia. Ulcers were detected in 16 patients (17%), and were more common in men (24%) than in women (7%). Histological examination of biopsies showed that all 95 patients had spiral-shaped organisms that were indistinguishable microscopically from Helicobacter pylori, though the numbers of organisms varied considerably. There was evidence that the degree of inflammation in the mucosa was related to the numbers of H. pylori-like organisms (HPLO) present. Fifty-one biopsy specimens (55%) gave a positive rapid urease test (RUT), with colour change occurring within 4 h. In all but one case, the gastric mucosa from these patients contained moderate to numerous HPLO. We defined the 'gold standard' of H. pylori-associated gastritis as the presence of both moderate to numerous HPLO and moderate to severe inflammation in the gastric mucosa. Using these criteria, RUT had a sensitivity of 67% and a specificity of 68%. Sera from 92 patients were tested for immunoglobulin G antibodies reactive with a glycine-extract antigen of H. pylori, using an enzyme-linked immunosorbent assay (ELISA). Sera giving an indeterminate reaction in the ELISA were also tested by Western blotting. In all, 36 sera (39%) gave a positive ELISA or Western blot reaction. There was poor correlation between serology and RUT results, with only 57% of biopsy specimens from seropositive patients giving a positive RUT, compared with 45% from seronegative patients. Positive serology was found in only 35 patients (61%) with histological evidence of H. pylori-associated gastritis, and the specificity of the test was only 54%. When used in combination with the RUT result, however, 79% of patients with a positive RUT and positive serology had histological evidence of H. pylori-associated gastritis. There was a general trend for increased seroprevalence in patients with mild to moderate atypia. These findings indicate that serology, using an antigen derived from the type strain of H. pylori, is unreliable in detecting H. pylori infection in Zimbabwe. Current studies are aimed at characterizing antigens from organisms isolated from Zimbabwean patients.

Fine needle aspiration cytology in the diagnosis of hepatocellular carcinoma.

Fine needle aspiration (FNA) of the liver without ultrasound guidance was performed on 110 patients with hepatocellular carcinoma (HCC). The median age was 52 years, with a range of 16 to 86 years. There were 90 males and 20 females (a male: female ratio of 4.5:1), with a median age of 51.5 years (range 16 to 86 years) and 55.5 years (range 17 to 72 years) respectively. FNA was reported as showing malignancy in 92 (84 pc, 95 pc CI 77 to 91 pc) patients; 80 (73 pc) were definite HCC, 12 (11 pc) were malignant unspecified, seven (6 pc) were suspicious of malignancy, seven (6 pc) had no malignant cells and four (4 pc) were non-diagnostic. The only complication observed was dizziness in one patient. We conclude that FNA of the liver for the diagnosis of HCC is a safe, simple and accurate procedure which can be undertaken in settings that would otherwise not be suitable for formal liver biopsy.

Vitamin B12 deficiency is the primary cause of megaloblastic anaemia in Zimbabwe.

In a study of the pathogenesis and clinical features of megaloblastic anaemia in southern Africa, we evaluated 144 consecutive Zimbabwean patients with megaloblastic haemopoiesis. Vitamin B12 deficiency was diagnosed in 86.1% of patients and was usually due to pernicious anaemia; isolated folate deficiency accounted for only 5.5% of cases. Anaemia was present in 95.8% of patients; the haemoglobin (Hb) was < or = 6 g/dl in 63.9%. Neurological dysfunction was noted in 70.2% of vitamin B12-deficient patients and was most striking in those with Hb values > 6 g/dl. Serum levels of methylmalonic acid, homocysteine, or both, were increased in 98.5% of patients. Vitamin B12 deficiency is the primary cause of megaloblastic anaemia in Zimbabwe and, contrary to textbook statements, is often due to pernicious anaemia. Isolated folate deficiency is less common. As reported in industrialized countries 75 years ago, anaemia is almost always present and often severe. Neurological dysfunction due to vitamin B12 deficiency is most prominent in patients with mild to moderate anaemia.

Endoscopic sclerotherapy in Zimbabwe.

Fifty consecutive patients presenting with upper gastrointestinal haemorrhage caused by oesophageal varices were subjected to endoscopic sclerotherapy during the period April 1989 to December 1991. Portal hypertension was caused by alcoholic liver cirrhosis in 22 (44pc), Hepatitis B induced liver cirrhosis in seven (14pc), cryptogenic liver cirrhosis in three (six pc), bilharzial portal fibrosis in 17 (34pc) and extrahepatic portal obstruction in one (two pc). Acute bleeding was controlled in 12 out of 13 patients, five of whom with a fresh bleed and eight who rebled while on the endoscopic sclerotherapy regimen. All patients were treated on a weekly sclerotherapy regimen. Reduction in variceal size of two or more grades was achieved in all 30 patients who had completed at least four or more endoscopic sclerotherapy courses with total eradication of varices in 27 (90pc). Three patients died. All deaths were caused by progressive hepatic encephalopathy. Complications usually seen were retrosternal pain, fever, dysphagia and oesophageal ulceration. There were no fatal complications. The study shows that endoscopic sclerotherapy is effective not only in controlling acute bleeding but also in preventing rebleeding. We recommend a weekly schedule for the early eradication of varices.

HIV infection and Salmonella septic arthritis.

Human immunodeficiency virus (HIV) infection predisposes to bacterial infection at may sites but septic arthritis is notably uncommon. An HIV seropositive patient who presented with oligoarticular septic arthritis due to Salmonella enteritidis and who responded poorly to antibiotic therapy and repeated aspiration of involved joints is described. Unusual features included the clinical presentation of septic arthritis in more than one joint, a protracted clinical course with radiological destruction of the hip, bone marrow suppression induced by cotrimoxazole, and death thought to be due to a gastropathy induced by non-steroidal anti-inflammatory therapy at a time when the septic arthritis appeared to have responded to treatment. Cure of Salmonella septic arthritis in HIV infected patients may be difficult and require aggressive prolonged treatment. Septic arthritis should be considered in the differential diagnosis in a patient with HIV infection and arthritis.