Factor VIII-von Willebrand factor requires calcium for facilitation of platelet adherence

The role of divalent cations in platelet adherence to deendothelialized human arteries in flowing blood was investigated in an annular perfusion chamber. Spreading of platelets on the subendothelium was impaired below 30 microM of free Ca2+ ions (Ca2+). When Ca2+ was replaced by Mg2+, adherence was unchanged in perfusates without exogenous factor VIII-von Willebrand factor (FVIII-vWF), but the ability of FVIII-vWF to support platelet adherence was lost. Binding of FVIII-vWF to the vessel wall was independent of divalent cations, but bound FVIII-vWF was only able to mediate adherence after exposure to Ca2+. Pretreatment of FVIII-vWF with the calcium chelator EGTA (10 mM) resulted in loss of the ability to facilitate platelet adherence, while the ristocetin cofactor activity remained intact. Full restoration of the ability to mediate platelet adherence could only be obtained by prolonged dialysis against Ca2+ in the millimolar range. These data indicate that divalent cations have at least two separate roles to play in supporting platelet adherence: (1) platelet spreading on the subendothelium requires Ca2+ or Mg2+; (2) FVIII-vWF should be exposed to Ca2+ to obtain its optimal biologic activity in supporting platelet adherence.     

Maternal and Neonatal Factors Adversely Affecting Breastfeeding in the Perinatal Period

Background

Despite its known advantages, breastfeeding rates are low world over. Large number of factors affect breastfeeding. This study was designed to detect maternal and neonatal factors that adversely affect breastfeeding in the perinatal period.

Methods

A prospective, single-blinded study was conducted on randomly chosen mother-infant pairs in the maternity ward of a tertiary care service hospital. Only full term singletons born by normal vaginal delivery were studied. The B.R.E.A.S.T observation score and time spent by the infant at the mother''s breast were primary outcome variables. Maternal age, gravida, para status and education level were recorded. Birth weight, sex, gestation age of the infant and time interval from birth to observation were also recorded. Initial univariate analysis followed by multivariate analysis was performed using SPSS ver 7.5 software.

Results

A total of 54 mother-infant pairs formed the study group; 19(35.2%) were primigravidas. Primigravidas status of the mother led to significantly lower scores (p<0.04; 95% CI 0.10 to 3.62) as did maternal age < 26 years (p<0.04; 95% CI 0.2. to 3.46) on univariate analysis. Low birth weight (<2500 g) was the only neonatal factor that significantly lowered breastfeeding scores (p<0.02;95%Cl 0.56 to 6.31). On multivariate analysis only primigravida status was significantly associated with lower scores (p<0.02). The alpha value of the study was 5% and the power was 74%. Time spent by infant on breast was not significantly different between primigravida and non-primigravida mothers.

Conclusion

Primigravida status adversely affects breastfeeding scores; therefore counseling and support should be focused on this group. Extra care should also be taken to ensure adequate breastfeeding by younger mothers and in those with low birth weight infants. Larger studies with long-term follow up will be able to identify other factors and dertermine the effects of focused counseling and support in the perinatal period upon long-term breastfeeding rates.Key Words: Breastfeeding, Primigravida, Counseling     

Efficacy and Toxicity Profile of Methotrexate Chloroquine Combination in Treatment of Active Rheumatoid Arthritis

Background

The present study was conducted to study the efficacy and toxicity profile of methotrexate chloroquine combination in treatment of active rheumatoid arthritis.

Methods

24 patients of rheumatoid arthritis confirming to revised American Rheumatism Association (ARA) criteria were studied prospectively for twenty months. Clinical evaluation was made every 3 months. Clinical disease variables measured at each visit were number of joints with swelling, number of joints with tenderness and pain, duration of morning stiffness and physician and patient assessment of disease activity. Blood counts, liver function tests and other adverse effects due to drugs were monitored every 2 months.

Results

10 patients demonstrated more than 50% improvement. 4 patients withdrew from study, 2 because of excessive nausea and vomiting and 2 because of noncompliance. Other side effects noted were hyperpigmentation, photosensitivity, skin rashes, raised transaminases and stomatitis.

Conclusion

Methotrexate chloroquine combination has good efficacy and toxicity profile. Gastrointestinal side effects are most common and usually responsible for the discontinuation of the drugs.Key Words: Rheumatoid arthritis, Methotrexate, Chloroquine, Efficacy, Toxicity     

Ethics roundtable debate: Child with severe brain damage and an underlying brain tumour

A young person presents with a highly malignant brain tumour with hemiparesis and limited prognosis after resection. She then suffers an iatrogenic cardiac and respiratory arrest that results in profound anoxic encephalopathy. A difference in opinion between the treatment team and the parent is based on a question of futile therapy. Opinions from five intensivists from around the world explore the differences in ethical and legal issues. A Physician-ethicist comments on the various approaches.     

Quality of life (QOL) assessment of MIP (mitomycin, ifosfamide and cisplatin) chemotherapy in advanced non-small cell lung cancers (NSCLC)

BACKGROUND: Quality of life (QOL) assessment has emerged to measure and quantify the balance between treatment benefit and toxicity, and has a value in predicting response and overall survival in cancer patients. METHODS: From July 1995 to February 1997, 38 symptomatic patients with advanced non-small cell lung cancer (NSCLC) were treated with MIP chemotherapy (mitomycin 6 mg/m2, ifosfamide 3000 mg/m2 and cisplatin 50 mg/m2 on day 1 every 3 weeks). Patients were assessed for QOL including physical well-being, general symptoms and lung cancer-specific symptoms, as well as objective response. RESULTS: The overall response rate was 38.9% (14/36, all were partial response) and the median duration of response was 3.5 months [95% confidence interval (CI) 2.0-4.0]. The median duration of overall survival was 7 months (95% CI 5.9-8.5). The overall improvement of QOL was 58.3% with 21 patients feeling better on treatment. The toxicity of chemotherapy was mild, mainly nausea/vomiting and minimal alopecia. Using multiple clinical predictors of survival (age, histology, stage, performance status), only change of QOL emerged significantly (P = 0.0007). CONCLUSIONS: MIP had an endurable response and low toxicity profile, and provided good QOL. Integral QOL data in our study provided the strong prediction of survival in advanced NSCLC. Further experienced QOL study will provide greatly enhanced outcome data in clinical trials.      

A combination of misoprostol and estradiol for preoperative cervical ripening in postmenopausal women: a randomised controlled trial

Objective  To compare the impact of 1000 μg of self-administered vaginal misoprostol versus self-administered vaginal placebo on preoperative cervical ripening after 2 weeks of pretreatment with estradiol vaginal tablets in postmenopausal women prior to day-care operative hysteroscopy.
Design  Randomised, double-blind, placebo-controlled sequential trial.
Setting  Norwegian university teaching hospital.
Population  Sixty-seven postmenopausal women referred for day-care operative hysteroscopy.
Methods  The women were randomised to receive either 1000 μg of self-administered vaginal misoprostol or self-administered vaginal placebo on the evening before day-care operative hysteroscopy. All women had administered a 25-μg vaginal estradiol tablet daily for 14 days prior to the operation.
Main outcome measures  Primary outcome: preoperative cervical dilatation at hysteroscopy. Secondary outcomes: difference in dilatation at recruitment and before hysteroscopy, number of women who achieved a preoperative cervical dilatation of 5 mm or more, acceptability, complications and adverse effects.
Results  The mean cervical dilatation was 5.7 mm (SD, 1.6 mm) in the misoprostol group and 4.7 mm (SD, 1.5 mm) in the placebo group, the mean difference in cervical dilatation being 1.0 mm (95% CI, 0.2–1.7 mm). Self-administered vaginal misoprostol of 1000 μg at home on the evening before day-care hysteroscopy is safe and highly acceptable, although a small proportion of women experienced lower abdominal pain.
Conclusions  One thousand micrograms of self-administered vaginal misoprostol, 12 hours prior to day-care hysteroscopy, after 14 days of pretreatment with vaginal estradiol, has a significant cervical ripening effect compared with placebo in postmenopausal women.