Biomedical subjects
Publications and source records attributed to Y Sultan.
Some factor VIII concentrates cause downregulation of the immune system in HIV-positive haemophilia patients. This effect appears to be related to the purity of the concentrate, but not to its method of preparation. The optimum purity for preventing downregulation is not known at present.
An increase in the incidence of Salmonella typhi strains resistant to chloramphenicol, ampicillin and trimethoprim-sulfamethoxazole causing enteric fever in Egyptian children stimulated the evaluation of alternative drugs. Children with positive blood cultures were treated with cefixime, ceftriaxone or aztreonam, and the efficacy, safety and cost of these regimens were evaluated and compared. Cefixime (7.5 mg/kg) was given orally twice daily to 50 children for 14 days, ceftriaxone (50 to 70 mg/kg) was given im once daily for 5 days to 43 children and aztreonam (50 to 70 mg/kg) was given im every 8 hours for 7 days to 31 children. Children in the 3 groups were comparable with regard to age, sex, duration and severity of illness before admission. All children were cured. A significant difference (P < 0.05) in duration of treatment before becoming afebrile seemed to favor ceftriaxone (3.9 days) over aztreonam (5.5 days) and cefixime (5.3 days). During the 4-week follow-up period relapses occurred in 3 (6%) children in the cefixime group, in 2 (5%) in the ceftriaxone group and in 2 (6%) in the aztreonam group. Safety and efficacy were comparable for all 3 drugs. Ceftriaxone was most cost-effective on an inpatient basis, because of a more rapid clinical cure, and cefixime was the most cost-effective on an outpatient basis, because of drug cost.
The development of factor VIII inhibitors is one of the most serious complications of repeated transfusions in haemophilia patients, but it is not clear why the complication develops only in some haemophiliacs. This paper discusses the nature of FVIII inhibitors, their occurrence and detection, and outlines treatment procedures for haemophilia patients who show FVIII inhibitors.
UNLABELLED: Interferon (alpha-IFN) exerts a modulating effect on the immune system. Kupffer cells of the liver play an important immunological role by their uptake of various agents and particles, including colloids. We sought to discover if alpha-IFN could enhance the colloid uptake function of the Kupffer cells. The effect of alpha-IFN therapy on radioisotope scans of the liver was studied in 20 patients with chronic liver disease due to hepatitic C virus (HCV) infection who received therapy at a dose of 3 million IU for 6 mo, in another 20 patients who received the same therapy for 12 mo and in matched control groups (10 patients with HCV infection for each study group) who did not receive alpha-IFN. METHODS: A 99mTc-sulfur colloid scan of the liver was obtained for each group before and after therapy and, for control subjects, at the start and end of the study periods. The liver-to-spleen geometric mean ratio of colloid uptake was assessed. RESULTS: In the first study group, the mean rate of improvement in the liver-to-spleen ratio was 48% in 70% of patients, compared to 8% in 20% of controls (p < 0.05). In the second study group, mean liver-to-spleen ratio was 88% in 85% of patients, compared to 12% in 40% of controls (p < 0.001). CONCLUSION: Alpha-IFN therapy appears to enhance the colloidal uptake function of Kupffer cells, which adds a new dimension to the immunomodulatory effect of interferon.
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In France, since 1988, factor VIII concentrate are prepared by ion exchanged chromatography from plasma cryoprecipitate. The final product is a very high purity factor VIII with a specific activity (SA) between 150 and 250 IU/mg of proteins. Viral inactivation is obtained after solvent detergent method with TNBP and Tween 80. Since 1989 hemophilia B patients are treated with a factor IX preparation purified from a prothrombin complex concentrate and after solvent detergent inactivation. Factor IX concentrate is a high purity product with a SA of 50 to 100 U/mg of protein.
Biospecific functional polymers, i.e., polymers randomly substituted with specific chemical functional groups, were designed to interact with living systems. Interactions between polystyrene sodium sulfonate (PSSO3Na) and insulin secreting RINm5F cells have been previously described. For the sake of comparison, interactions of PSSO3Na with human umbilical vein endothelial cells (HUVEC) were studied. In this case, the interaction is indirect, i.e., mediated by a binding protein, fibronectin (Fn). This was evidenced by HUVEC culture on Fn precoated PSSO3Na microcarriers. The interactions between PSSO3Na and HUVEC result in a biologically normal proliferation of cells and synthesis and secretion of Von Willebrand Factor (VWF). These results show that different biospecific interactions may occur between cells in culture, binding proteins and polymers randomly substituted with suitable functional groups. HUVEC, when cultured on heparin-like microcarriers, behave differently from other cells like RINm5F, whose interaction with the same polymers is not mediated by binding proteins.
OBJECTIVE: To evaluate whether HLA-B35 influences progression to AIDS in HIV-seropositive subjects with haemophilia. DESIGN: Retrospective (before 1985) and prospective (after 1985) follow-up of a group of French haemophiliacs. METHODS: We studied 144 seropositive patients with moderate or severe haemophilia A or B or von Willebrand's disease. Enzyme-linked immunosorbent assay was used to screen patient sera for total HIV antigen and core p24 antigen antibodies. All patients were typed for HLA A, B and C antigens in the same laboratory. Time of seroconversion was estimated to be the mid-point between the last seronegative test and the first seropositive test. AIDS-free survival curves were constructed using the Kaplan-Meier estimate and differences in survival analysed using the Mantel-Cox test. The Cox proportional hazards model was used to adjust for confounding variables. RESULTS: Median follow-up after seroconversion was 8.7 years (range, 3.5-10.7 years). By the end of the study, six HLA-B35-positive patients and 12 HLA-B35-negative patients had progressed to AIDS. Individuals with HLA-B35 showed a significantly faster rate of progression to AIDS over the follow-up period than HLA-B35-negative individuals (hazard ratio, 2.72; P = 0.037). After adjusting for type and severity of haemophilia, CD4 cell count at first seropositive test, age at seroconversion, and zidovudine treatment before AIDS, the hazard ratio was 2.74 (P = 0.045). CONCLUSION: HLA-B35 is a risk factor for more rapid progression to AIDS in subjects with haemophilia.
A study was conducted to determine the etiology of acute hepatitis among 261 children (age range 1-11 years) living in Cairo, Egypt. A blood sample was obtained from each subject when initially evaluated and a questionnaire was used to collect demographic and risk factor data. Sera were tested by enzyme immunoassay for acute hepatitis A (anti-hepatitis A virus IgM), hepatitis B (anti-hepatitis B core antigen IgM and hepatitis B surface antigen [HBsAg]), hepatitis C (total anti-HCV), delta hepatitis (total anti-delta), and cytomegalovirus infection (anti-CMV IgM). In addition, hepatitis E virus (HEV) infection was diagnosed using a new Western blot technique to test patients with non-A, non-B hepatitis for anti-HEV IgM. Among 261 children, acute hepatitis A was diagnosed in 85 (32.6%) patients, acute hepatitis B in 19 (7.3%), delta hepatitis in 3 (1.1%), mixed hepatitis A and B infection in 2 (0.8%), CMV infection in 1 (0.4%), hepatitis E in 58 (22.2%), and non-A, non-B hepatitis of unknown type in 51 (19.5%). Forty-two (16.1%) subjects had HBsAg without other markers of acute infection. Risk factor analysis indicated that patients living in homes not connected to a municipal source of water were at increased risk of hepatitis E infection. These data provide additional evidence that hepatitis E virus is a common cause of acute sporadic hepatitis in children living in Egypt.
A total of 7,809 patients with meningitis or encephalitis were admitted to the Abbassia Fever Hospital in Cairo, Egypt from November 1, 1966 to April 30, 1989. The etiology was Neisseria meningitidis (mostly group A) in 27.3% of the patients, Mycobacterium tuberculosis in 19.7%, Streptococcus pneumoniae in 7.3%, and Haemophilus influenzae in 4.1%. Almost 27% of the cases had purulent meningitis but without detectable etiology; however, the epidemiologic data suggest that most of these had meningococcal meningitis. Encephalitis was suspected in 12.5% of the patients. Most of the meningococcal, pneumococcal, and Haemophilus cases occurred during the winter months. The number of meningococcal and culture-negative purulent cases per year reached a maximum three times during the 22.5 years of this study. There were more males than females in all etiologic groups, with the ratio for the total patient population being 1.6:1. The average age ranged between 11.7 and 16.5 years for all groups except for Haemophilus patients, who had a mean age of 2.5 years. The mortality rate was almost 55% for tuberculous patients and was approximately 40% for both pneumococcal and Haemophilus patients; it was 8.5% in patients with meningococcal disease.
Cefixime in a dose 20 mg/kg/day, orally, divided into two doses 12 h apart for a minimum of 12 days, was administered to 50 children with proven S. typhi septicaemia. Forty four of the patients were infected with strains of S. typhi resistant to multiple antibiotics including chloramphenicol, ampicillin and trimethoprim-sulfamethoxazole. All patients responded rapidly to treatment and were cured clinically and bacteriologically. Fever subsided within a mean of 5.3 days (range 3-8 days). Only two of the 50 patients treated relapsed during the 8 week follow-up period. No serious adverse reactions attributable to the drug were observed. Cefixime proved to be an effective oral drug in this open treatment trial and was associated with minimal side effects. It may provide a therapeutic alternative to the treatment of Salmonella infection with organisms multi-resistant to the standard drug regimens. Its oral formulation may provide an efficient alternative to parenteral therapy in less severely ill patients who can tolerate oral feeding.
Clinical efficacy of plasma-derived products with factor VIII--bypassing activity in patients with factor VIII inhibitors is difficult to evaluate. It is also difficult to predict efficacy by coagulation assay. A test of thrombin generation in defibrinated plasma and in the presence of activated platelets was used to test the bypassing activity of the most currently used products (activated prothrombin complex concentrate from various origins, prothrombin complex concentrate, and factor VIIa). The bypassing activity was evaluated in the absence and presence of tissue factor. In plasma with inhibitor, activated prothrombin complex concentrate elicited dose-dependent thrombin formation, whereas prothrombin complex concentrate and factor VIIa induced only minimal thrombin activity. Addition of tissue factor in the assay elicited thrombin generation in the presence of factor VIIa and prothrombin complex concentrate and allowed additional thrombin formation in the presence of activated prothrombin complex concentrate. Although it is hazardous to extend results of in vitro testing to clinical efficacy, our study sheds some light on the mechanism of action of the various substances used to treat bleeding episodes in patients with factor VIII inhibitors.
A cooperative study between the 37 centers of the French Hemophilia Study Group was undertaken to establish the prevalence of inhibitor patients in the French hemophilia population. The prevalence reported in the literature varies widely from 3.6% to 17.5%. Some of the studies are dealing with a small number of patients and inhibitor patients are reported either to the total number of hemophiliacs or to the severely affected ones. The French study provided information concerning 3,435 hemophiliacs and showed a prevalence of 6.2% for the overall population. Prevalence of inhibitors was found to be 7% in the population of hemophilia A patients and 12.8% in the population of severely affected ones. The prevalence of inhibitors in the population of hemophilia patients was 2% and 4% in the population of severely affected hemophilia B patients. The cooperative study also showed that 47.5% of inhibitors are detected before 10 years of age and that 82% of inhibitor patients are high responders. Analysis of inhibitor detection in patients under the age often showed that there was a peak in the population of 2 years old children. Although not comparable to the present study the high incidence of inhibitors with ultrapurified and recombinant FVIII reported in previously untransfused patient may be borne in mind.
Therapeutic preparations of polyspecific IgG obtained from plasma pools of a large number of normal donors (IVIg) express anti-idiotypic activity against a wide spectrum of natural and disease-associated autoantibodies. The present study investigated the origin of anti-idiotypic activity against autoantibodies to factor VIII. The neutralizing activity of pools of IgG against patients' anti-factor VIII autoantibodies was not influenced by the presence of individuals with natural anti-factor VIII antibodies among donors contributing to the pool. A higher frequency of neutralizing antibodies against anti-factor VIII autoantibodies was found in aged donors as compared with young adults and in pools of IgG from multiparous women as compared with IgG from random donors. Pooling IgG from several donors synergistically enhanced the inhibitory activity of the pools. Thus, a neutralizing activity against anti-factor VIII autoantibodies was detected in pools of IgG of as few as two to four donors of whom individually tested IgG did not exhibit inhibitory activity against anti-factor VIII autoantibodies. These observations suggest that aged donors and multiparous women may be privileged sources for the anti-idiotypic activity of IVIg against autoantibodies and emphasize that the expression of anti-idiotypic activity in IVIg results from a synergistic participation of anti-idiotypes from each donor contributing to the pool.
Spontaneous inhibitors of factor VIII (FVIII) are pathogenic IgG autoantibodies of restricted isotypic heterogeneity found in the plasma of patients presenting with bleeding episodes and low levels of FVIII. We now report the presence of a natural FVIII-neutralizing activity in 85 of 500 plasma samples (17%) from healthy donors. FVIII-inhibitory activity was present in F(ab')2 fragments of purified IgG and was dose-dependent. The titer of anti-FVIII antibodies in normal plasma ranged between 0.4 (threshold of detection) and 2.0 Bethesda units. Anti-FVIII IgG was also detected in normal plasma by using an ELISA. Anti-FVIII antibodies from healthy individuals did not exhibit restricted isotypic heterogeneity. Mean levels of FVIII activity did not differ significantly between individuals with and without detectable anti-FVIII antibodies in plasma. Natural anti-FVIII IgG inhibited FVIII activity in pools of normal plasma and in plasma of certain donors in the pool but did not inhibit FVIII activity in autologous plasma. These observations demonstrate that polyclonal IgG antibodies against procoagulant FVIII are present in healthy individuals. The antibodies are natural IgG autoantibodies and/or antibodies directed against epitopes associated with a so far unidentified allotypic polymorphism of the human FVIII molecule.
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Age-prevalence and age-intensity data of Echinococcus granulosus hydatid cysts in sheep populations were collected in an abattoir in the Xinjiang Uygur Autonomous Region, People's Republic of China. The frequency distribution of the larval cysts per sheep was empirically described by the negative binomial model, with parameter k being 0.5273. A mathematical model for the life cycle of E. granulosus was applied to the collected data and the results show that the infection pressure on sheep was 0.4362 (female) or 0.4119 (male) infections per year, the mean number of cysts increased linearly by 0.8824 (female) or 0.9971 (male) cysts every year and acquired immunity was too low to depress this rate of increase. According to certain definitions of steady states for taeniid populations, it was concluded that at least in some parts of Xinjiang, the life cycle of E. granulosus was and may still be in an endemic steady state. Consequently, the regular dog-dosing program would readily drive the infection from an endemic state towards extinction.
The objective of this study was to see if determination of uterine artery velocity waveforms between 20 and 30 weeks in lupus pregnancy and the antiphospholipid syndrome (APS) have a good predictive value for later fetal distress before labor, intrauterine growth retardation, and preeclampsia. Uterine and umbilical artery blood flow velocity waveforms were determined in 21 pregnancies complicated by systemic lupus erythematosus (SLE): 12 with antiphospholipid antibodies (aPL), 9 without aPL. We also studied 7 pregnancies with APS. This retrospective study was running from January 1st 1986 to July 31st 1991, at the Port-Royal Maternity, Paris, France. Abnormal uterine artery blood flow velocity waveforms were found in 10 out of 28 pregnancies at the first examination performed between 20 and 30 weeks gestational age. All the later adverse fetal and neonatal events were predicted by an abnormal uterine artery blood flow velocity waveform. From the 7 cases of fetal distress diagnosed during pregnancy, 6 were predicted by abnormal uterine waveforms and all of these pregnancies resulted in induced delivery before 32 weeks of gestational age. Twelve pregnancies with aPL and normal uterine artery waveforms were uncomplicated. Only 1 out of 7 pregnancies with abnormal uterine artery waveform and aPL ended without complication. Determination of uterine artery flow velocity waveform is a good adjunct to the management of pregnancies complicated by SLE or aPL. This determination has a better predictive value than the presence of aPL.