Prevalence and Factors Associated with Acute Kidney Injury among Malaria Patients in Dar es Salaam: A Cross-Sectional Study.

INTRODUCTION: Falciparum malaria still remains as a major cause of morbidity and mortality worldwide. Acute kidney injury is a known complication of malaria, and it is reported to occur in up to 40% of adult patients with severe falciparum malaria in endemic regions like sub-Saharan Africa. OBJECTIVES: To determine the prevalence and factors associated with acute kidney injury among falciparum malaria patients in a tertiary level private hospital in Dar es Salaam. METHODOLOGY: In a cross-sectional study design, 104 adults with falciparum malaria were enrolled consecutively over 6 months from April to September 2015. The diagnosis of acute kidney injury (AKI) in these patients was established using the KDIGO classification criteria. The prevalence of AKI was obtained at 48 hours from admission and at day 7. Different sociodemographic and clinical parameters which were associated with acute kidney injury at 48 hours and at day 7 were identified by hypothesis testing using chi squared tests followed by multivariate logistic regression analysis. Factors with a p value less than 0.05 were considered significant. RESULTS: The participants were predominantly males 65.4% (68/104) and a third (36.5% (38/104)) were between 46 and 65 years. The prevalence of AKI among malaria patients at 48 hours was 26% (27/104). The prevalence of AKI among malaria patients at day 7 was 18.3% (19/104). On multivariate logistic regression, we found that factors that were significantly associated with AKI at 48 hours were male sex (OR 127, CI 3.4-4700, P = 0.008) and hemoglobin <7.5g/dl (OR 36.5, CI 1.7-797.7, P = 0.022), and factor associated with AKI at day 7 was baseline platelet count <25×103 per mm3 (OR 77.8 CI 1.045-5798.6, P = 0.048). Only two patients needed hemodialysis (1.9%) and there were no deaths. CONCLUSION: Acute kidney injury is a common complication in patient with falciparum malaria. When managed well it has an excellent prognosis and necessitates dialysis in only a minority of patients. Male sex and hemoglobin is associated with AKI at 48 hours and baseline platelet count is associated with AKI at 7 days.

The management of carcinoma of the anal canal by external beam radiotherapy, experience in Vancouver 1971-1988.

From 1971 to 1988 72 cases of carcinoma of the anal canal were treated by external beam radiotherapy, most commonly by 5000 cGy in 20 fractions given over 4 weeks. The actuarial survival at 5 years was 66% and the disease specific survival 78%. Nine patients had inguinal node metastases at diagnosis; their 5-year disease specific survival was 75%. 63 patients were inguinal node negative at presentation; their 5-year disease specific survival was 78%, by UICC 1987 staging: T1 71%, T2 88%, T3 41%, T4 42%. 17 patients developed local recurrence; 10 were suitable for abdominoperineal (AP) resection which was successful in 7. The probability of local control was related to T stage. 13 patients were left with a colostomy because of recurrence, 2 had a colostomy for radiation damage and 4 had their local recurrence managed palliatively, without a colostomy. As a result, 53 of the 72 patients (74%) were left with a functional anus. Severe late complications occurred in 6 (8%).

Endotoxin reduces maximal oxygen consumption in hepatocytes independent of any hypoxic insult.

OBJECTIVE: The cause of the metabolic disturbances in sepsis remains uncertain, but there is increasing evidence suggesting that haemodynamic changes are not solely responsible. We addressed the question of whether endotoxin has a significant effect on cellular oxygen metabolism, independent of confounding haemodynamic defects. DESIGN: Prospective, controlled experimental study. SETTING: University Laboratory. MODEL: Human hepatocyte cell line. METHODS: The oxygen consumption rate (OCR) was calculated from the fall in oxygen tension in a sealed cuvette containing Hep G2 cells in suspension. The oxygen tension was measured by porphyrin phosphorescence half-life analysis. Resting OCR was measured in control cells and after 1, 6 and 24 h of endotoxin exposure. In a second series of experiments, resting and maximal OCR was measured after 6 and 24 h of endotoxin exposure and in control cells using the addition of a mitochondrial uncoupler (FCCP); this uncouples the respiratory chain from ATP synthesis, thereby removing negative feedback and allowing the respiratory chain to work at maximal rate. RESULTS: Endotoxin caused a rise in resting OCR at 1 h which was significant by 6 h but had returned to control values by 24 h. Maximal OCR also increased at 6 h, however exposure to endotoxin for 24 h significantly reduced maximal OCR compared to the control cells. CONCLUSIONS: Endotoxin has complex effects on cellular energy metabolism causing an initial rise in the oxygen consumption rate and a significant limitation in oxygen consumption capacity at 24 h. These complex effects would be in keeping with the varied responses seen in patients.

Iron depletion and anaemia: prevalence, consequences, diagnostic and therapeutic implications in a developing Pakistani population.

The prevalence of iron deficiency anaemia in Karachi, Pakistan, was examined in a group of 100 children, aged 2 to 6 years, and 200 adult females, aged 17 to 35 years. Anaemia, defined as a haemoglobin level less than 11.5 g/dl, was present in 47% of the children and 30% of the adult females. The majority of subjects had normal red cell counts and MCV, but haematocrit and MCH were below normal in one-quarter of the children and one-third of the adult females. More than half of both children and adult females had serum ferritin levels below normal. Many also had elevated iron binding capacity and reduced serum iron levels. Iron deficiency may be superimposed on folate deficiency in this population. The potentially serious consequences and higher prevalence of iron deficiency anaemia in children and women of childbearing age demand greater efforts toward diagnosis and eradication in developing countries.

PIP: Iron deficiency anemia has more serious consequences on the health of people in developing than developed nations. In Karachi Pakistan 300 subjects were examined to determine the prevalence of iron deficiency anemia: 100 children (49 males and 51 females) aged 2-6 years; 100 females aged 17-21 years with no history of pregnancy; and 100 females aged 25-35 with at least 1 prior pregnancy. Most subjects came from the lower to middle income groups, with only 10% from the higher income bracket. Blood samples were taken to measure serum ferratin, serum iron, total iron binding capacity (TIBC), red cell indices and films. Results showed that anemia was present in 47% of the children, a 30% of the adult females. More than half of both children and adult females had serum ferritin levels measuring below normal. Elevated iron binding capacity and reduced serum iron levels were found in many subjects. In the children, iron deficiency may be superimposed on folate deficiency. As a result, low levels of serum ferritin go hand in hand with iron depletion, and this is directly dependent upon the diet and socioeconomic conditions of the populace.

'Moderate-risk' ovarian cancer (stage I, grade 2; stage II, grade 1 or 2) treated with cisplatin chemotherapy (single agent or combination) and pelvi-abdominal irradiation.

We placed patients with invasive epithelial ovarian cancer into four distinct prognostic groups: 'low', 'moderate', 'high' and 'extreme' risk. The 'moderate-risk' group contained all residual negative, stage I and II patients with two exceptions: stage Ia or b, grade 1 cancers and grade 3 cancers. They were treated with primary surgery, usually including bilateral salpingo-oophorectomy, hysterectomy and omentectomy. Chemotherapy was then given (cisplatin at 100 mg m-2 every 2 weeks for three cycles) followed by pelvi-abdominal irradiation (2250 cGy in 10 fractions to the pelvis and 2250 cGy in 22 fractions to the whole abdomen including pelvis). An early cohort with ascites or positive washings instead received six cycles of cisplatin and cyclophosphamide at 75 mg m-2 and 600 mg m-2 every 4 weeks with the same pelvi-abdominal irradiation sandwiched between cycles 3 and 4. One-hundred and nine patients were treated between November 1983 and December 1989. Median follow-up was 4.7 years (range 0.7-9 years). The 5-year actuarial overall and failure-free survivals were 81% and 76%, respectively. Chronic toxicity, although usually minor, included 15% with peripheral neuropathy or ototoxicity and 23% with chronic abdominal complaints. Our combined-modality results are similar to those obtained by other centers utilizing either pelvi-abdominal irradiation alone or cisplatin-based chemotherapy alone.

Platinum plus cyclophosphamide plus radiotherapy is superior to platinum alone in 'high-risk' epithelial ovarian cancer (residual negative and either stage I or II, grade 3, or stage III, any grade).

Patients with epithelial ovarian cancer (EOC) referred to our institution are stratified into risk groups based on their stage, grade and presence of residual cancer, with a specific treatment policy for each group. One-hundred and thirty-one patients with no visible residual tumor following primary surgery and either stage I, grade 3; stage II, grade 3; or stage III, any grade EOC were treated between November 1983 and the end of December 1991. Regimen A (cisplatin 75 mgm-2 and cyclophosphamide 600 mgm-2 intravenously every 4 weeks for 6 cycles with abdominopelvic irradiation between cycles 3 and 4) was used until April 1989 and was then replaced with Regimen B (cisplatin 75 mgm-2 intravenously every 3 weeks for 6 cycles). The 5-year actuarial overall and failure-free survivals were 78% and 64% respectively. Multivariate analysis identified increasing stage and treatment with Regimen B as independent adverse prognostic factors for failure-free survival. The importance of treatment regimen reached statistical significance for the stage I patients (P = 0.04) but not stage II (P = 0.11) or stage III (P = 0.79). It is possible to undertreat EOC as shown by the inferior results achieved with Regimen B (single agent cisplatin) compared to Regimen A (cisplatin-cyclophosphamide, irradiation). This effect of treatment regimen was particularly important for the lower-stage patients. Our postulate is that treatment resistant clones are less regularly present in lower-stage patients, and that a certain minimum amount of treatment is required to eliminate all the sensitive cancer.

Carcinoma of cervix, the King Faisal Specialist Hospital & Research Center experience--the need for screening for cervical cancer in developing countries.

The King Faisal Specialist Hospital and Research Center opened in 1975 to provide specialized medical treatment to the citizens of Saudi Arabia and to promote prevention of disease through research and education. It is a national and middle eastern tertiary care hospital for oncology and a principle center for radiation therapy in Saudi Arabia. In this retrospective study, 504 patients with carcinoma of the cervix were analysed. Of the 504 patients, 410 received treatment with curative intent, which comprised radical surgery alone, radical radiation alone or combination surgery and radiation. The overall 3, 5 and 10 years survival of all 504 patients was 64%, 55% and 40%, respectively and for 410 patients treated with curative intent it was 74%, 61% and 51%, respectively. Multivariate analysis, using the Cox regression method, showed that the stage of the disease is the only significant prognostic factor influencing relapse-free survival. Stage for stage, treatment outcomes at King Faisal Specialist Hospital and Research Center match those achieved in the First world, but two-thirds of patients (rather than one-third) present with advanced disease at diagnosis. Therefore, any improvement in overall outcomes will require earlier diagnosis, achievable only through an effective screening program in the Kingdom of Saudi Arabia and similarly in the other Third world countries where patients present with advanced stage disease.

Laboratory diagnosis of iron deficiency in a developing country, Pakistan.

In developing countries, such as Pakistan, laboratories do not routinely screen for iron deficiency unless the patient presents with symptoms of anaemia. Efforts to prevent the often serious consequences of iron depletion are hampered in developing countries by the expense and impracticality of routinely screening patients using bone marrow examination. Assays for serum iron concentrations, total iron-binding capacity or haemoglobin and examinations of blood films, although more practical, cannot detect the earliest stages of iron deficiency. Serum ferritin appears to be a sensitive, early indicator of iron deficiency and can be easily and relatively inexpensively determined using an immunoassay kit. In the present study, serum ferritin levels were determined using immunoassay and compared to blood films, serum iron levels and total iron-binding capacity values in 300 apparently healthy Pakistanis. In the early stages of iron deficiency, serum ferritin appeared to be a sensitive measure of iron depletion.