Peginterferon {alpha}-2b and ribavirin therapy in chronic hepatitis C genotype 4: impact of treatment duration and viral kinetics on sustained virological response.

BACKGROUND: The response rates and duration of peginterferon alpha (PEG-IFN-alpha) and ribavirin combination therapy in chronic hepatitis C genotype 4, the prevalent genotype in the Middle East and Africa, are poorly documented. AIMS: To compare the efficacy and safety of 24, 36, or 48 weeks of PEG-IFN-alpha-2b and ribavirin therapy in chronic hepatitis C genotype 4. METHODS: In this prospective, randomised, double blind study, 287 patients with chronic hepatitis C genotype 4 were randomly assigned to PEG-IFN-alpha-2b (1.5 mug/kg) once weekly plus daily ribavirin (1000-1200 mg) for 24 weeks (group A, n = 95), 36 weeks (group B, n = 96), or 48 weeks (group C, n = 96) and followed for 48 weeks after completion of treatment. Early viral kinetics and histopathological evaluation of pre- and post treatment liver biopsies were performed. The primary end point was viral clearance 48 weeks after completion of treatment. RESULTS: Sustained virological response was achieved in 29%, 66%, and 69% of patients treated with PEG-IFN-alpha-2b and ribavirin for 24, 36, and 48 weeks, respectively, by intention to treat analysis. No statistically significant difference in sustained virological response rates was detected between 36 and 48 weeks of therapy (p = 0.3). Subjects with sustained virological response showed greater antiviral efficacy (epsilon) and rapid viral load decline from baseline to treatment week 4 compared with non-responders and improvement in liver histology. The incidence of adverse events was higher in the group treated for 48 weeks. CONCLUSION: PEG-IFN-alpha-2b and ribavirin for 36 or 48 weeks was more effective in the treatment of chronic hepatitis C genotype 4 than treatment for 24 weeks. Thirty six week therapy was well tolerated and produced sustained virological and histological response rates similar to the 48 week regimen.

Serum levels of endothelin-1 (ET-1), interleukin-2 (IL-2) and amino-terminal propeptide type III procollagen (PIII NP) in patients with acute and chronic filariasis.

Filariasis, a mosquito-borne parasitic disease, is a worldwide health problem. There is still, some controversial concerning the diagnosis of acute and chronic infections. The serum levels of endothelin-1 (ET-1), interleukin-2 (IL-2) and amino-terminal propeptide Type III (PIII NP) was measured in patients with acute and chronic filariasis as compared with controls. The ET-1, IL-2 and PIII NP levels were significantly high in chronic cases than in acute. On the other hand, the serum levels of IL-2 and PIII NP were significantly high in acute cases than in the controls. These three immuno-mediators play role in the pathogenesis of filariasis particularly. The chronic cases. So, these mediators can be used as markers for diagnosis of human cases infected with chronic and acute filariasis.

Evaluation of the IgG4 in Egyptian bancroftian filariasis.

The IgG4 response against antigen extracts from Wuchereria bancrofti microfilariae and Dirofilaria immitis adult worms was determined by ELISA in 65 Egyptian adult male patients suffering from different clinical manifestations of W. bancrofti infection. They were divided into microfilaremic (n-35) and amicrofilaremic (n = 30) and these divisions were subdivided into early asymptomatic, hydrocele and late chronic elephantiasis subgroups. The IgG4 responses were significantly higher in early asymptomatic patients whether microfilaremic or amicrofilaremic than in hydrocele or in chronic elephantiasis (P < 0.05) & (P < 0.001) respectively. The IgG4 response was slightly higher in microfilaremic than in amicrofilaremic subjects. The mean OD value of IgG4 among the microfilaremics against the microfilaria antigen in early asymptomatic patients (0.840 nm) was lower than the IgG4 response against the adult antigen in the same group (0.960 nm), while among the early asymptomatic amicrofilaremics it was the same (0.690 nm) in both microfilaria and adult antigens.

Chironomid potent allergens causing respiratory allergy in children.

Generally speaking, chironomids contain potent inhalant allergens. The skin prick tests with chironomid crude extract (Chironomus (C.) calipterus) were positive in 20 out of 25 children with respiratory allergy. The skin prick tests with house dust mite crude extract (Dermatophagoides pteronyssinus) were positive in 3 of these 20 chironomoid positive skin tests. Chironomid-specific IgE-ELISA were demonstrated in the sera of 17 (85%) of the chironomid skin positive patients. These 17 patients gave negative skin prick test to house dust mite crude extract. It is concluded that chironomid allergens should be considered when dealing with human respiratory allergy caused by arthropods.

Assessment of splenic functions in patients with hepato-splenic schistosomiasis using non-invasive techniques.

This study was carried out on forty cases, classified into 3 groups; group I: 10 healthy controls subjects, group II: 20 patients with hepatosplenic schistosomiasis and group III: 10 bilharzial patients who underwent total splenectomy. All cases were subjected to clinical examination, abdominal ultrasonography, rectal snips and laboratory investigations which included: stool and urine analysis, complete blood picture, IHAT for bilharziasis, liver function tests, viral markers, estimaton of T-lymphocyte subpopulations (CD(+)3, CD(+)4, & CD(+)8) by flow Cytometry, silver stained blood films to detect argyrophilic inclusions and 99mTc sulphur colloid splenic scan which was applied to group II only. The present results revealed varying degrees of hypersplenism (anaemia, leukopenia & thrombocytopenia) in GII. Seventy percent of this group was positive for HbsAg, HCV or both in association with schistosomiasis. Abnormal red blood cells (acanthocytes, target cells, pitted cells & normoblasts) and inclusion bodies (Howell Jolly bodies, argyrophilic inclusions & pappenhiemer bodies) were detected with different values in GIII. CD(+)4 cells were moderately reduced in GII while they were markedly decreased in GIII. CD(+)8 cells were elevated in GII and returned nearly to the normal values in GIII with decrease in number of total T-lymphocytes. Most patients of GII showed marked squestration of 99mTc labelled R.B.Cs. in the spleen with reversed hepatic/splenic ratio (normally hepatic/splenic ratio is over two). IHAT showed positivity in 90% of patients in GII while it was 50% in GIII. Although total splenectomy improved the haematological pattern and the cytopenias, which are prominent features in hepatosplenic schistosomiasis, yet the immunological profile was still altered. So, it is recommended to perform segmental splenectomy with retention of a normal mass of functioning residual spleen to preserve more immunological function and to protect against life-threatening occurrence of post-splenectomy sepsis.

A study of some changes of cell-mediated immunity in protein energy malnutrition.

This work was done to assess both monocytic and lymphocytic functions and to identify their role in the altered immunocompetence in protein energy malnutrition (PEM). This was accomplished through the evaluation of the phagocytic function and the in vitro production of interleukin 1 and interleukin 2 (IL-1 and IL-2) from cultured mononuclear cells. Forty patients with PEM within the age of (5-20 months) and twenty normal healthy subjects of matched age and sex were studied. They were subjected to complete blood picture, total serum protein, serum albumin, C3, C4, monocyte phagocytic function and in vitro production of both IL-1 and Il-2 from cultured mononuclear cells. Patients were graded on the basis of their clinical findings into three groups: Marasmic, marasmic kwashiorkor and Kwashiorkor. The study revealed that monocyte phagocytosis, complement components, in vitro production of IL-1 and IL-2 were significantly lower in the patients group when compared to normal control group, this increase was most obvious in the marasmic Kwashiorkor and Kwashiorkor groups. In addition, mononuclear cells from the infected patients produced less IL-1, Il-2 although the total leucocytic count was significantly increased than in the non-infected patients, indicating a functional rather than numerical cellular impairment. It was concluded that both monocytic and lymphocytic functions were impaired in PEM. This functional impairment may be involved in the failure of development of specific immune response and predisposed to increased susceptibility to infection in these patients.

Pregnancy outcome after laparoscopic fimbrioplasty in nonocclusive distal tubal disease.

OBJECTIVE: To determine pregnancy rates (PR) after fimbrioplasty and salpingostomy in nonocclusive distal tubal disease. To evaluate the relative impact of various factors using contemporary statistical analysis. DESIGN: Prospective cohort. SETTING: Tertiary institutional infertility clinic. PATIENTS(S): Infertility patients. INTERVENTION(S): Fimbrioplasty and salpingostomy. MAIN OUTCOME MEASURE(S): Cumulative PR, monthly fecundity rates, monthly probability of pregnancy, crude PR, and cure rates. RESULTS(S): Thirty-five percent of patients conceived with a cure rate of 72.2%, monthly probability of pregnancy of 3.9%, and monthly fecundity rate of 3.9%. Cumulative PRs were 22%, 35%, and 58% at 6, 12, and 24 months, respectively. Pairwise comparisons (unilateral, bilateral, or either) failed to detect any statistical difference between the salpingostomy and fimbrioplasty groups. Salpingostomy patients initially may have a higher tendency to become pregnant but appear to lose that advantage after the first few months. When patients with tubo-ovarian adhesions are excluded from the analysis, patients who underwent a bilateral salpingostomy as their sole procedure had better outcome compared with those who only underwent bilateral fimbrioplasty. There was no significant association between pregnancy outcome and the presence of endometriosis, other infertility factors, or tubo-ovarian adhesions. The staging of adnexal adhesions and endometriosis did not predict pregnancy outcome. CONCLUSION(S): Laparoscopic fimbrioplasty and salpingostomy are clinically efficacious for the treatment of nonocclusive distal tubal disease. After accounting for statistical interactions of various factors among them, no particular association with pregnancy outcome could be identified. This illustrates the need for a revision of the classification of patients with distal tubal disease.

Pregnancy rates after operative endoscopic treatment of total (neosalpingostomy) or near total (salpingostomy) distal tubal occlusion.

OBJECTIVE: To determine the efficacy of the endoscopic treatment of complete distal tubal occlusion or moderate to severe tubal phimosis and to analyze outcome using contemporary statistical methodologies. DESIGN: Prospective cohort analysis. SETTING: Tertiary-care institution. PATIENTS: One hundred thirteen consecutive patients undergoing a neosalpingostomy or salpingostomy. INTERVENTIONS: KTP/532 laser (Laserscope, Santa Clara, CA) laparoscopy. Additional infertility factors were treated postoperatively. MAIN OUTCOME MEASURES: Crude pregnancy rate (PR), monthly fecundity rate, monthly probability of pregnancy, cure rate, and cumulative PRs. Outcome was compared on the basis of the surgical procedure performed. The impact of endometriosis as well as other fertility factors was analyzed. RESULTS: Twenty-three patients conceived yielding a crude PR of 20.4%, a monthly fecundity rate of 2.6%, a monthly probability of pregnancy of 6.4%, and a cure rate of 52.4%. There were six ectopic pregnancies (5.3%). A significant difference was found among the cumulative pregnancy curves. The cumulative pregnancy curve for unilateral salpingostomy differed significantly from that of unilateral neosalpingostomy. Patients with endometriosis and no other infertility factors had a significantly better cumulative pregnancy curve compared with patients without endometriosis or other factors as well as compared with patients with no endometriosis but with other infertility factors. Patients undergoing bilateral neosalpingostomy had a cure rate of 9.0% whereas patients undergoing bilateral salpingostomy had a cure rate of 34.2%. CONCLUSIONS: Operative endoscopy yields PRs that are comparable to those reported in the literature for laparotomy. The presence of complete bilateral distal tubal occlusion has a negative impact on outcome.

A randomized trial of three oral contraceptives: comparison of bleeding patterns by contraceptive types and steroid levels.

OBJECTIVE: Our purpose was to determine the relationship between bioavailability of contraceptive steroids and bleeding patterns. STUDY DESIGN: A randomized clinical trial evaluated 192 women on 50 micrograms of ethinyl estradiol and 1.0 mg of norethindrone (OC1), 35 micrograms ethinyl estradiol and 1.0 mg of norethindrone (OC2), and 35 micrograms ethinyl estradiol and 0.5 mg norethindrone (OC3) over nine cycles. RESULTS: Intermenstrual bleeding rates were higher for OC3 when compared with OC1 (p = 0.01). The number of intermenstrual bleeding days was highest for OC3 (p = 0.001) and higher for OC2 when compared with OC1 (p < 0.006). The onset of withdrawal bleeding occurred faster in OC3 patients (p < 0.02). Bioavailability of both contraceptive steroids as measured by baseline values and 1-hour slopes did not correlate with bleeding patterns at 3, 6, and 9 months of use. CONCLUSION: These data suggest that differences in biologic responses associated with pill use cannot be explained solely on the basis of these particular hormone measurements.

PIP: Breakthrough bleeding as a side effect of oral contraceptive (OC) use is considered one of the primary causes if discontinuation of oral contraceptives. In this study, the incidence and pattern of vaginal bleeding is examined and correlated with biologic responses and plasma steroid bioavailability. Between October 1, 1985 and October 15, 1987, subjects were randomly selected from eligible women beginning OC use as patients of the Department of Gynecology and Obstetrics at the Johns Hopkins Medical Institutions. Women were grouped by type of OC as follows: 1) 67 women taking 50 micrograms of ethinyl estradiol and 1.0 mg of norethindrone (OC1);l 2) 61 women taking 35 micrograms of ethinyl estradiol and 1.0 mg of norethindrone (OC2); and 3) 64 women taking 35 micrograms of ethinyl estradiol and .5 mg of norethindrone (OC3). Estrogen and progesterone concentrations in plasma were measured on the 21st day during the third, sixth, and ninth cycles. The samples was taken 24 hours after ingestion of the pill for day 20, and 1 hour after taking the pill on day 21. An extensive interview was also conducted for all study participants. Bleeding was recorded for any amount of bleeding occurring during days 2 through 21, and during days 21 through 28. Cycles were omitted where pills had been forgotten by the patient. An initial slope was calculated with the 1 hour value level and subtracting the 0 hour level over the actual time interval. Linear regression analysis was used to compare the slopes and bleeding days. Of the 316 women enrolled, 61% (192) completed the study. The findings were that the incidence of intermenstrual bleeding was not statistically different among the various preparations. For 59 patients eliminated from the study, 24% experienced intermenstrual bleeding. Those lose to follow-up were not among those unwilling to tolerate their bleeding pattern. There was similar incidence of other side effects among all three preparations: .5% amenorrhea of dysmenorrhea, 7% nausea, 16% headache, 26.5% depressed mood, 16.6% breast tenderness, and 44.3% acne. The low-dose OC3 had the statistically highest rates of intermenstrual bleeding. The bleeding patterns are described. Bleeding patterns were higher than those previously reported in the literature. Further research might focus on controlling for factors such as hormone-binding globulin capacity.

KTP/532 laser laparoscopy in the treatment of endometriosis-associated infertility.

OBJECTIVE: To determine the clinical effectiveness of the KTP/532 laser in treating endometriosis-associated infertility and to analyze the impact of additional infertility factors on outcome. DESIGN: Prospective cohort analysis of 74 consecutive patients followed up to 24 months after surgery. SETTING: Tertiary institutional infertility clinic. MAIN OUTCOME MEASURES: Cumulative pregnancy rates (PRs), monthly fecundity rates, monthly probability of pregnancy, crude PRs, and cure rates. RESULTS: Thirty-eight percent (28) of patients conceived with a mean +/- SE time to conception of 7.2 +/- 0.8 months. The cure rates were 74% for the total patient sample, 51% for stage I, 69% for stage II, and 64% for stage III disease. Patients who had a cervical factor (P = 0.05), who underwent intrauterine insemination (P = 0.03), who received human menopausal gonadotropin (P = 0.03), or who had additional infertility factors (P = 0.02) had significantly lower crude PRs. The presence of additional infertility factors (P less than 0.02) and intrafimbrial adhesions (P less than 0.01) had a significant impact on cure rates. In the absence of additional factors, 60% (12) of patients with stage I and II conceived. When additional factors were excluded, the overall cure rate was 80%. CONCLUSION: The results indicate that the KTP/532 laser is an effective tool for the treatment of endometriosis-related infertility. The high prevalence of subtle adhesions may lend further impetus to operative laparoscopy for stage I and II disease. Additional infertility factors may adversely affect outcome.

Primary papillary serous carcinoma of the peritoneum: a case of complete remission of bulky peritoneal disease after chemotherapy.

Peritoneal papillary serous carcinoma is a rare tumor that involves the surface of the pelvic and/or abdominal peritoneum. Long-term survival among patients with this tumor has been rare. Most patients with this cancer have been treated with debulking surgery and postoperative chemotherapy. A case of incompletely resected peritoneal papillary serous carcinoma with a complete response to cisplatin-based chemotherapy is reported. Subsequent laparotomy revealed no residual tumor. This case suggests that primary chemotherapy may be successful in treating unresectable primary papillary serous tumors of the peritoneum.

Hepatitis D anti-bodies in some HBs Ag positive in Saudis at Riyadh.

This study was done on 212 male and female Saudi blood donors and those visiting the Outpatient Clinics in Al Ali General Hospital during the years 1987 to 1990. None of them had history of hepatitis and all were clinically free. The prevalence of anti-Delta Ab in hepatitis B surface antigen (HBs Ag) carriers was 17.6%. The existence of closely linked family ties and joint family systems, result in close contact between patients and other members of the family and hence the high prevalence rate in normal population (8%). Vaccination against Hepatitis B virus may be particularly necessary.

Effects of maternal sickle cell haemoglobinopathy on pregnancy.

In order to determine the significant factors which may contribute to complications in pregnant mothers with sickle cell haemoglobinopathy, a study was considered on 100 mothers (35 SS and 65 AS) and the results were compared with 20 control women with normal haemoglobin electrophoretic pattern. The incidence of vaso-occlusive was significant in mothers with sickle cell disease. Furthermore, it was observed that high levels of fetal haemoglobin did not have any beneficial effect in patients with sickle disease during vaso-occlusive episodes.

Chlamydial infection in Riyadh, Saudi Arabia.

Sera of patients attending a genitourinary clinic, gynaecological clinic in Al Ali General Hospital, Riyadh, Saudi Arabia and from males and females without overt genital diseases were tested for the presence of antichlamydial antibodies using an immuno-fluorescence test. Antibodies for Chlamydia trachomatis were found in 66 (46%) of 145 male patients and 72 (35%) of 200 female patients attending a genitourinary clinic and gynaecological clinic respectively and in two (2%) of 100 men and in none of 100 women without genital diseases. These results suggest that the prevalence of chlamydial infection in Saudi Arabia among both men and women is high. Since serious complications can follow chlamydial genital infection, further work has to be done in this field.