Radiolabeled antibody therapy in non-Hodgkins lymphoma: radiation protection, isotope comparisons and quality of life issues

Anti-CD20 antibodies radiolabeled with I-131 tositumomab (Bexxar) or Y-90-Ibritumomab tiuxetan (Zevalin), are similarly efficacious in treating chemotherapy-refractory non-Hodgkin's lymphoma. The relative merits of both radioimmunoconjugates with respect to practical issues, including radiation exposure risk, the advantages and disadvantages of the respective isotopes and other parameters that could affect a patient's quality of life are also important. I-131-labeled antibody treatment often requires inpatient hospitalization due to the inherent risk of exposure from gamma emissions, and patients and families should follow detailed instructions to prevent undue exposure. Other issues relevant to patients and medical staff include: (1) the need for dosimetry to calculate effective therapeutic doses of I-131-labeled anti-B1 (Bexxar) compared with the lack of correlation of dosimetry with marrow toxicity for IDEC-Y2B8 (Zevalin), (2) determining the acute and long-term toxic effects of each agent, (3) time commitments for nuclear medicine staff and patients along with the relative ease of administration, and (4) cost considerations. A more challenging future issue will be to determine the optimal use of Bexxar and Zevalin alone and in combination in ways that will significantly affect patient outcome without compromising quality of life. The recent demonstration of significant response rates in patients having chemotherapy-refractory Non-Hodgkin's Lymphoma (NHL) using both on I-131- and Y-90-labeled anti-CD20 antibodies with minimal toxicity has stimulated comparison of I-131 tositumomab (Bexxar) and Ibritumomab tiuxetan (Zevalin) in terms of radiation safety requirements, the advantages and disadvantages of both radionuclides, and quality-of-life (QOL) issues. Therefore, in this review, we attempt to compare the relative merits of (Bexxar and Zevalin) and address important practical considerations that may influence patient and physician choices regarding treatment using these agents.     

Aetiology of male urethritis in patients recruited from a population with a high HIV prevalence

The aetiology of urethritis, the significance of potential pathogens and the relation of urethritis to HIV infection were determined in 335 men (cases) with and 100 men (controls) without urethral symptoms. Urethral swab specimens were tested for different organisms by PCR or by culture for Neisseria gonorrhoeae. The prevalence of N. gonorrhoeae and Chlamydia trachomatis was 52 and 16%, respectively. The potential pathogens: Mycoplasma genitalium, Ureaplasma urealyticum, Trichomonas vaginalis and herpes simplex virus (HSV), were present in 5, 36, 6 and 6% of the cases respectively. M. genitalium was the only potential pathogen associated with microscopic urethritis. After excluding gonococcal infections, U. urealyticum was more frequent in symptomatic patients, while the prevalence of T. vaginalis was similar among cases and controls. These results strongly suggest an a etiological role for M. genitalium in male urethritis, a possible role for U. urealyticum, but not for T. vaginalis. The control group, with 97% genital ulcer disease patients, was not suitable for the investigation of the role of HSV. The sero-prevalence of HIV was 45%. Current infections were not associated with HIV. However, a history of previous urethral discharge was associated with HIV in a multivariate analysis and supported the hypothesis that non-ulcerative sexually transmitted diseases facilitate HIV transmission.     

Social inequalities and disability in older men: prospective findings from the British regional heart study

The independent association of socio-economic position with self-reported disability was assessed. The effect of home and car ownership as additional indices of socio-economic position within occupational social classes was explored. Data from a prospective study of a cohort of 7735 men aged 40-59 years at recruitment and representative of the occupational social class distribution of middle-aged men in Great Britain were used. Men were selected from one general practice in each of 24 towns in England, Wales and Scotland in 1978-1980. The present study concerns 5773 (88.4% of those able to take part) men aged 52-73 years at follow up in 1992 who completed the disability section of a postal questionnaire. A quarter (1453) of men reported disability. Socio-economic position measured as both occupational class (social class I vs. V: age-adjusted OR 5.0, 95% CI 3.4-7.5) and ownership of home and car (both vs. neither: age-adjusted OR 2.8, 95% CI 2.3-3.4) showed a graded relationship with likelihood of reporting disability in 1992. Within all social class groups, those owning both home and car had a lower risk of disability than those who owned neither, even after adjustment for a wide range of risk factors. Men from manual occupations were more likely than those in non-manual occupations to report disability on developing chronic diseases. The relationship between socio-economic position and severe, but not milder, disability appeared to be independent of disease status. Socio-economic position is a strong predictor of disability in later life independent of a wide range of lifestyle factors and presence of diagnosed disease. The likelihood of reporting disability between and within social class groups is influenced by material wealth.     

A double-blind, randomized, placebo-controlled study to assess the efficacy of ketoconazole for reducing the risk of ovarian hyperstimulation syndrome

OBJECTIVE: To evaluate the role of ketoconazole in prevention of ovarian hyperstimulation syndrome (OHSS) in women with the polycystic ovary syndrome (PCOS) undergoing ovarian stimulation with gonadotropins. DESIGN: Prospective, randomized, double-blind, placebo-controlled study. SETTING: University hospitals.One hundred nine women with PCOS who were referred for treatment with gonadotropins. INTERVENTION(S): Fifty patients were randomly assigned to receive two ampoules of hMG beginning on day 2 or 3 of the cycle and ketoconazole (50 mg every 48 hours) starting on the first day of hMG treatment. Fifty-one patients received the same amount of hMG plus one tablet of placebo every 48 hours. MAIN OUTCOME MEASURE(S): Follicular development, E(2) level, and pregnancy rate. RESULT(S): The total number of hMG ampoules and duration of treatment to attain ovarian stimulation were higher among ketoconazole recipients. The serum E(2) level and number of patients with dominant follicles on day 9 of the cycle were greater in placebo recipients. Serum E(2) level and total number of follicles at the time of hCG administration did not differ between the two groups. The cancellation rate and OHSS rate were similar in the two groups. CONCLUSION(S): Ketoconazole does not prevent OHSS in patients with PCOS who are undergoing ovarian stimulation. It may reduce the rate of folliculogenesis and steroidogenesis.     

Sperm MTT viability assay: a new method for evaluation of human sperm viability

Purpose : MTT (3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay is commonly used as a cell proliferation assay. The objective of this study was to evaluate the capability of MTT assay to discriminate between viable and nonviable sperms and compare its efficiency with E&N (eosin and nigrosin) and HOST (hypo-osmotic swelling test). Methods : MTT assay was modified to obtain optimal result for assessment of sperm viability. After standardization of method, MTT, E&N, and HOST were carried out simultaneously on 57 semen samples from patients referring to Isfahan Fertility and Infertility Center. The correlation coefficient between these tests and sperm motility was calculated using the SPSS statistical program. Specificity and sensitivity of each test was also obtained. Results : The optimal conditions for sperm MTT viability assay were 2 h after addition of sperm to MTT in HAM'S F10 + 25 mM HEPES + 10% HSA at 37°C and pH 7.4–7.45. Inter- and intra-assay coefficients of variations were 9 and 7%, respectively. The sensitivity and specificity for sperm MTT viability assay, E&N, and HOST were 97, 98, and 99%, and 100, 100, and 83% respectively. High significant correlations were obtained between sperm MTT viability assay, E&N, HOST and motility. Conclusions : Sperm MTT viability assay can be used as a diagnostic test for discrimination of viable sperms from sperm population.     

Lay perceptions of a 'natural' menopause. Cross sectional study of the British Women's Heart and Health Study

Health practitioners and researchers define a natural menopause as one not due to a hysterectomy or oophorectomy. In a large cross sectional study of postmenopausal women, we found that the majority of women who report that their menopause was not natural gave a gynaecologic reason. However, 3% gave a major life event, such as divorce or bereavement. Age at menopause for women who had had a hysterectomy/oophorectomy was the same as that of women who reported that their periods has stopped because of a major life event—on average six years younger than that of women who described their menopause as natural. We suggest that women whose periods stop 'naturally' (from a medical perspective) but at a relatively young age perceive this as unnatural and search for an explanation for the early cessation of their menses.     

A prospective,double-blind,randomized, placebo-controlled clinical trial of bromocriptine in clomiphene-resistant patients with polycystic ovary syndrome and normal prolactin level

OBJECTIVE: To evaluate the effects of administration of bromocriptine combined with clomiphene citrate (CC) in CC-resistant patients with polycystic ovary syndrome (PCOS) and normal prolactin (PRL) level. DESIGN: Prospective double-blind, placebo-controlled, randomized. SETTING: Referral university hospitals. PATIENTS: One hundred women with PCOS and normal PRL who failed to ovulate with a routine protocol of CC. INTERVENTIONS: Treatment group received 150 mg of CC from day 5 to 9 and 7.5 mg bromocriptine continuously, with hCG 10,000 units on day 16 or 17. Control group received the same protocol of CC combined with placebo. MAIN OUTCOME MEASURES: Follicular development, hormonal changes, ovulation rate, pregnancy rate. RESULTS: Follicular development (follicular size greater than 15 mm) was observed in 12 (25.5%) and 8 (15.1%) women in the treatment and placebo group, respectively (p = 0.29). The serum prolactin level was within normal limits in all patients before treatment. After 3 and 6 months of treatment with bromocriptine, there was a significant decrease in serum level of prolactin (p = 0.000001). No significant differences were seen in ovulation, pregnancy rate, or serum levels of FSH, LH, DHEAS, and progesterone between treatment and placebo groups after treatment. CONCLUSIONS: The only significant effect of long-term bromocriptine therapy in CC-resistant women with PCOS was to lower the serum PRL concentration. It is also concluded that 10%-15% of patients with PCOS experienced occasional ovulatory cycles and pregnancy whether or not they were on treatment.