Cytomegalovirus infections in seropositive patients after transfusion. The effect of red cell storage and volume

Antibody responses to cytomegalovirus (CMV) after red cell (RBC) transfusion were studied in 84 seropositive surgery patients and 82 seropositive oncology patients. The surgery patients were randomized to receive RBCs stored either 3 to 8 or 20 to 42 days after donation. Of 38 patients receiving RBCs stored 8 days or less, 3 developed a rise in titer (4-fold increase) of IgG antibody to CMV 8 to 12 weeks after transfusion. This rate of response (8%) did not differ significantly (p = 0.23) from that (16%) in the 46 patients receiving RBCs stored 20 to 42 days. Seropositive oncology patients were randomized to receive RBCs from seronegative or random donors. Five (19%) of 27 oncology patients receiving seronegative RBCs and 13 (23%) of 55 patients receiving random RBCs (mean, 2 seropositive RBC units/patient) developed a rise in titer of antibody to CMV. No CMV morbidity occurred in either patient group. For both patient groups, a rise in titer of antibody to CMV was associated with the number of transfused RBC units. These results confirm that CMV-seronegative RBCs are unnecessary for infrequently transfused seropositive patients. They also suggest that multiple transfusions of stored RBCs are as immunosuppressive as multiple transfusions of RBCs used within a few days after donation.     

Molecular basis of the heterogeneity of expression of glycosyl phosphatidylinositol anchored proteins in paroxysmal nocturnal hemoglobinuria

The purpose of these studies was to determine the molecular basis of the phenotypic mosaicism that is a defining feature of paroxysmal nocturnal hemoglobinuria (PNH). Analysis of T cell clones from a female patient revealed four distinct phenotypes based on surface expression of glycosyl phosphatidylinositol-anchored proteins (GPI-AP). When PIG-A (the gene that is mutant in PNH) from these clones was analyzed, four discrete somatic mutations were identified. Analysis of X chromosomal inactivation among the abnormal T cell clones was consistent with polyclonality. Together, these studies demonstrate that the phenotypic mosaicism that is characteristic of PNH is a consequence of genotypic mosaicism and that, at least in this case, PNH is a polyclonal rather than a monoclonal disease. That four distinct somatic mutations were present in a single patient suggests that in conditions that predispose to PNH PIG-A may be hypermutable.     

Correlation of P-glycoprotein expression and function in childhood acute leukemia: a children's cancer group study

Clinical drug resistance may be attributed to the simultaneous selection and expression of genes modulating the uptake and metabolism of chemotherapeutic agents. P-glycoprotein (P-gp) functions as a membrane-associated drug efflux pump whose increased expression results in resistance to anthracyclines, epipodophyllotoxins, vinca alkaloids, and some alkylating agents. This type of resistance occurs as both de novo and acquired resistance to therapy for leukemia. We have studied P- gp expression and function in childhood acute leukemias by developing a series of doxorubicin- and vincristine-selected CEM, T-cell lymphoblastoid cell lines that recapitulate the low levels of expression and resistance seen clinically. These cell lines have been used to develop flow cytometric assays for the semiquantitative measurements of P-gp expression with the MRK16 monoclonal antibody and P-gp function using the enhanced retention of rhodamine 123 in the presence of verapamil, a resistance modulator. Kolmogorov-Smirnov statistics, represented by the D measurement, are used to determine the difference in level of P-gp expression by comparing MRK16 staining to an IgG2a isotype control. When D is > 0.09, there is an excellent correlation (R = 0.82) between P-gp expression and function. The evaluation of 107 bone marrow specimens from 84 children with lymphoblastic or myelogenous leukemia showed a statistically significant (P = .004) increase in P-gp function at relapse. P-gp expression at relapse, however, approached but did not reach a significant level (P = .097). Using this methodology, we can identify patients with levels of P-gp expression and function that we can define clinically, as well as children with discordant multidrug resistance phenotypes. This study supports the role of P-gp-mediated drug resistance in childhood leukemia and confirms that P-gp expression and function are measurable in their leukemic blasts. These assays provide the means for the in vitro testing of resistance modulators and the monitoring of in vivo response to treatment with these agents.     

Relative carriage rates of nuclear dehydrogenating clostridia in two populations of different colorectal cancer risk

Carriage of nuclear dehydrogenating clostridia has been associated with colon cancer and implicated in its aetiology. This study has compared the carriage of these organisms in a British population at high risk for the development of colon cancer with a low risk Nigerian population. Clostridia were found in all of the stools from both populations. Nuclear dehydrogenating clostridia were only found in the stools of the British subjects (32%). These results support the suggestion that the carriage rate of nuclear dehydrogenating clostridia in a population is related to the risk of colon cancer.     

SUBACUTE HEPATIC FAILURE-A CLINICAL PROFILE

A combined experience of 37 cases of subacute hepatic failure encountered in five major gastroenterology centres over a period of ten years is discussed. Majority (65%) were males with average age of 38 years. Maximum (54%) were in 5th decade. Jaundice (100%), abdominal distention (38.7%), swelling feet (64%), fever (54%), abdominal pain (54%), exhaustion (78.3%) were the major presenting features. Jaundice and ascites were present in all cases. Pedal oedema (78.3%), hepatomegaly (54%), splenomegaly (32.4%) and encephalopathy (27%) were the other important clinical features. Hypoalbuminemia and prolonged prothrombin time were significant laboratory findings in addition to hyperbilirubinemia and elevated ALT and AST. Hbs Ag was detected in 46%. Major complications encountered were renal failure (48.7%), spontaneous bacterial peritonitis (43.2%), other infections (43.2%), encephalopathy (43.2%) and upper gastrointestinal bleed (22%). 54% died during stay in hospital. To conclude subacute hepatic failure is potentially fatal condition.KEY WORDS: Subacute hepatic failure, HBsAg, Jaundice     

EXPERIENCE WITH VIPERINE ENVENOMATION

Two hundred and twenty one cases of viperine envenomation, who presented to hospital without specific treatment, seen over an twenty five years period, have been presented. Mild, moderate and severe envenomation was encountered in 33 per cent, 47 per cent and 20 per cent respectively. Bites on feet and ankles were seen in 85.5 per cent of cases. The average time interval between bite and hospitalisation was 4.8 hours, range being 15 minutes to 7 days. Local swelling was observed in 97.7 per cent, hematuria in 62 per cent, mucosal haemorrhages in 24.8 per cent and haematemesis in 19 per cent of patients. Average Antisnake Venom (ASV) required in mild, moderate and severe envenomation was 50 ml, 147.5 ml and 324 ml respectively. Major complications observed were renal failure in 10, intracompartmental syndrome in 3, intracerebral bleed and septicaemia in 2 each. One patient each developed finger gangrene, osteomyelitis, perirenal haematoma, sinus bradycardia and uncontrolled bleeding. Blood transfusion was required in 32 patients. Reactions to ASV were seen in 12 patients and overall there were 5 deaths.KEY WORDS: Antisnake venom, Viperine envenomation     

Body Mass Index and obesity: Tailoring “cut-off” for an Asian Indian male population

Background: Obesity/overweight is a recognized risk factor for a host of disorders. The disease risk stratification is commonly based on the Quetelets Index (Body Mass Index-BMI), a surrogate measure of fatness. The currently used BMI cut-offs to classify people as overweight or obese in Armed Forces have been defined in studies on Caucasian populations. However, because of differences in body structure and composition in different ethnic, socioeconomic, cultural and regional groups the correspondence between BMI and body fat content varies between populations. We conducted this pilot study in the Indian Navy to define BMI cut-offs for overweight and obesity using body fat content derived from Skin Fold Thickness as the standard.