The effect of dose increase of imatinib mesylate in patients with chronic or accelerated phase chronic myelogenous leukemia with inadequate hematologic or cytogenetic response to initial treatment.

PURPOSE: Imatinib mesylate is a tyrosine kinase inhibitor with high affinity for the BCR-ABL fusion protein expressed by the hematopoietic cells in chronic myelogenous leukemia (CML). Some patients with chronic-phase or accelerated-phase CML either relapse after an initial response or are refractory to imatinib, prompting us to evaluate the efficacy of dose increase in such patients. EXPERIMENTAL DESIGN: Twelve chronic-phase patients initially receiving 400 mg/day and 4 patients with accelerated phase initially receiving either 400 mg/day (two patients) or 600 mg/day (two patients) had their dose increased (14 to 800 mg/day and 2 to 600 mg/day) because of progressive disease (usually clonal evolution) or inadequate cytogenetic response after at least 1 year of therapy. RESULTS: Six patients had major cytogenetic responses after dose increase (3 complete and 3 partial). Two others had minor cytogenetic responses. Two patients with clonal evolution transiently lost the additional clonal aberrations. Almost all of the responses occurred within 6 months, and were typically 3-6 months in duration. However, 3 patients have continuing major cytogenetic responses of >18 months duration. Dose increase was well tolerated, with thrombocytopenia, mild leukopenia, and exacerbation of prior edema being the most common adverse events. CONCLUSIONS: Although increasing the dose of imatinib can benefit a subgroup of patients with CML with either an inadequate cytogenetic response or disease progression, our results suggest the majority will not have a sustained meaningful response, and that other options, such as allogeneic stem cell transplant or investigational therapies, also need to be considered at the time of dose increase.     

Prevalence of sexually transmitted diseases (STD) among women in a suburban Sudanese community

338 women with age ranging from 15 to 69 years in a suburban Sudanese community were randomly selected and studied. Urine sample, high vaginal swabs and blood samples were investigated for bacterial vaginosis, candidiasis, trichomoniasis, gonorrhoea, HIV and syphilis. The sensitivity and specificity of some laboratory tests were evaluated. Bacterial vaginosis was found in 17.2% of the subjects, candidiasis in 10.1%, trichomoniasis in 7.7%, gonorrhoea in 1.2%, HIV in 1.2% and syphilis in 0.9% of the subjects. The sensitivity and specificity of amine test as a criterion for diagnosing bacterial vaginosis was 58.6% and 73.2%, respectively. The respective values of clue cells in wet preparation were 43.1% and 99.6%. The vaginal discharge in women with bacterial vaginosis lacked pus cells unless associated with concurrent infection.     

Brainstem ischemia and preeclampsia.

Diffuse neurological manifestations of preeclampsia are due to endothelial involvement that lead to ischemia, hemorrhage, or edema. We analyzed clinical and radiological features and the course of brainstem ischemic strokes in a preeclampsia patient. We report a case of severe preeclampsia in a 30-year-old woman who was admitted 10 hr after a vaginal delivery at home. The pregnancy was at 39 wk, with no prenatal care. At her admission, she was conscious, and she had tetraparesia, swinging deep tendon reflex testing, drowsiness, and dysarthria; the BP was at 160/100 mmHg and 4 + proteinuria; magnetic resonance imaging revealed brainstem ischemic stroke. The evolution was favorable with symptomatic treatment. The patient was discharged on the 16th day; 2 months later she had a normal recovery. Brainstem strokes are rare. They are frequently due to hemorrhage; sometimes, they can also be ischemic. Their course is favorable.     

Physical activity combined with massage improves bone mineralization in premature infants: a randomized trial.

BACKGROUND: Osteopenia of prematurity is a known source for morbidity in preterm infants. Premature infants have shown favorable outcomes in response to massage and physical activity. Whether such intervention can stimulate bone formation or decrease bone resorption is yet to be determined. OBJECTIVE: To test the hypothesis that massage combined with physical activity can stimulate bone formation and ameliorate bone resorption in premature infants. DESIGN/METHODS: A prospective double-blinded randomized trial was conducted at the Neonatal Intensive Care Unit of Ain Shams University in Cairo, Egypt. Thirty preterm infants (28 to 35 weeks' gestation) were randomly assigned to either control group (Group I, n=15) or intervention group (Group II, n=15). Infants in the intervention group received a daily protocol of combined massage and physical activity. Serum type I collagen C-terminal propeptide (PICP) and urinary pyridinoline crosslinks of collagen (Pyd) were used as indices for bone formation and resorption, respectively. PICP and Pyd were measured at enrollment and at discharge for all subjects. t-Test, ANOVA and linear regression analysis were used for statistical analyses. RESULTS: There was no difference between groups I and II in gestational age (32.1+/-1.8 vs 31.5+/-1.4 weeks) or birth weight (1.429+/-0.148 vs 1.467+/-0.132 g). In the control group, serum PICP decreased over time from 82.3+/-8.5 to 68.78+/-14.6 (p<0.01), while urinary Pyd increased from 447.7+/-282.8 to 744.9+/-373.6 (p<0.01) indicating decreased bone formation and increased bone resorption, respectively. In the intervention group, serum PICP increased over time from 62.5+/-13.8 to 73.84+/-12.9 (p<0.01). Urinary Pyd also increased over time from 445.7+/-266.5 to 716.8+/-301.8 (p<0.01). In a linear regression model including gestational age and intervention, serum PICP increased significantly in the intervention group (regression coefficient 18.8+/-4.6, p=0.0001) while urinary Pyd did not differ between groups (regression coefficient=5.6+/-114.3, p=0.961). CONCLUSIONS: A combined massage and physical activity protocol improved bone formation (PICP) but did not affect bone resorption (Pyd). Pyd increased over time in both groups, possibly due to continuous bone resorption and Ca mobilization.     

The effect of different types of hysterectomy on urinary and sexual functions: a prospective study.

A prospective observational study was designed to evaluate the effect of the different techniques of hysterectomy on urinary and sexual function. One hundred and eighty-seven women aged 29-73 years and admitted for hysterectomy for various indications were recruited to the study. Women presenting primarily with major uterine prolapse and those requiring radical hysterectomy were excluded. Patients underwent one of four different techniques of hysterectomy: total abdominal, vaginal, laparoscopic or subtotal. All patients completed a standardised questionnaire addressing urinary and sexual symptoms and underwent urodynamic testing using the Lectromed 6000 System (Lectromed, Letchworth, Herts, UK) before and 6 months after surgery. Out of 187 women, 184 (98.4%) had completed data. Seventy-three patients (39%) had a total abdominal hysterectomy, 62 (34%) had vaginal, 38 (21%) had laparoscopic and 11 (6%) had subtotal hysterectomy. At 6 months after surgery, urinary symptoms occurred less frequently (P<0.01) and urodynamic studies remained unchanged. Moreover, patients reported significantly lower rates of stress incontinence (P=0.005), urgency (P=0.03) and deep dyspareunia (P<0.001) than before the operation, regardless of the hysterectomy technique used. The route of hysterectomy did not influence the outcome of surgery. We conclude that simple hysterectomy, whether performed abdominally, vaginally or laparoscopically, does not adversely affect urinary or sexual function at 6 months after surgery.     

Liver transplantation for hepatocellular carcinoma]

Hepatocellular carcinoma (HCC) is the most frequent primitive cancer of the liver. It mostly develops on cirrhotic livers. Orthotopic liver transplantation is the only treatment that definitively addresses both the metachronous occurrence risk of HCC and the underlying disease. Under Milan criteria, i.e. less than 3 nodules of 3 cm max in diameter, or 1 nodule of 5 cm maximum, OLT has been shown effective and provides with survival rates almost equal to those obtained with HCC free cirrhotic patients. In Rennes, 195 patients with early HCC on cirrhotic livers have been transplanted from January 1995 to June 2005. Global and disease free 8 years patient survival rates were 73 and 70%, respectively. These results were significantly altered when the recipient was female, the cirrhosis due to C virus and the patient of B blood group. Despite these excellent results, the principal limit to the application of transplantation for HCC remains the long period of time patients have to wait for a graft. During this period of time, growth of the tumour may drop the patient out of Milan criteria and subsequently from the waiting list. The role of chemoembolisation, liver resection and thermal ablation while the patient is waiting for a graft remains debatable.     

Are Essential Medicines in Malaysia Accessible, Affordable and Available?

Objective: To assess the pharmaceutical sector to know whether people have access to essential medicines. Setting: The study was conducted in 20 public health clinics, five public district drug stores and 20 private retail pharmacies selected randomly in five different areas randomly selected (four states and a federal territory). Method: The methodology used was adopted from the World Health Organization study protocol. The degree of attainment of the strategic pharmaceutical objectives of improved access is measured by a list of tested indicators. Access is measured in terms of the availability and affordability of essential medicines, especially to the poor and in the public sector. The first survey in the public health clinics and public district drug stores gathered information about current availability of essential medicines, prevalence of stock-outs and affordability of treatment (except drug stores). The second survey assessed affordability of treatment in public health clinics and private retail pharmacies. Main Outcome Measure Availability, stock-out duration, percent of medicines dispensed, accessibility and affordability of key medicines. Results The average availability of key medicines in the public health clinics for the country was 95.4%. The average stock-out duration of key medicines was 6.5 days. However, average availability of key medicines in the public district drug stores was 89.2%; with an average stock-out duration of 32.4 days. Medicines prescribed were 100% dispensed to the patients. Average affordability for public health clinics was 1.5 weeks salary and for the private pharmacies, 3.7 weeks salary. Conclusions: The present pharmaceutical situation in the context of essential medicines list implementation reflected that the majority of the population in Malaysia had access to affordable essential medicines. If medicines need to be obtained from the private sector, they are hardly affordable. Although the average availability of essential medicines in Malaysia was high being more than 95.0%, in certain areas in Sabah availability was less than 80.0% and still a problem.     

Quantitative variability in the biodistribution and in toxinokinetic studies of the three main alpha toxins from the Androctonus australis hector scorpion venom.

Scorpion stings represent a medical problem in numerous countries. The scorpion Androctonus australis hector produces three alpha toxins (Aah I to III), which are responsible for most of the lethality in mammals. These toxins act on sodium channel and do not cross-react immunologically. We used RIA and ELISA to measure the concentrations of these three toxins in plasma, urine and different organs after i.v. and s.c. injections of water extracts of venoms in rabbits or mice. In both animals, the toxins rapidly appeared in plasma after s.c. injection as it was previously described for the whole venom. However, the toxins disappeared from the blood more quickly than did other main components of the venom. Thus, serotherapy must be initiated immediately to prevent the toxin from reaching its target. We also detected the toxins in urine, kidneys, heart and lungs, but not in the brain. However, the concentration of Aah II was always lower than that of Aah I. Analysis of five samples of venom collected in different areas of southern Tunisia showed that a large polymorphism exists for the three toxins. This is yet another difficulty for serotherapy as there is no cross-antigenicity between them.     

Recurrence-free survival after radiofrequency ablation of hepatocellular carcinoma. A registry report of the impact of risk factors on outcome

BACKGROUND: Despite the high complete necrosis rate of radiofrequency ablation (RFA), tumor recurrence, either local tumor recurrence or new tumor formation, remains a significant problem. Purpose of this study is to evaluate the pattern and risk factors for intrahepatic recurrence after percutaneous RFA for hepatocellular carcinoma (HCC). METHODS: We studied 40 patients with 48 HCCs (< or = 3.5 cm) who were treated with percutaneous RFA. The mean follow-up period was 24.1 +/- 15.7 months. We evaluated the cumulative disease-free survival of overall intrahepatic recurrence, local tumor progression (LTP) and intrahepatic distant recurrence (IDR). Thirty host, tumoral and therapeutic risk factors were reviewed for significant tie-in correlation with recurrence: age; gender; whether RFA was the initial treatment for HCC or not; severity of liver disease; cause of liver cirrhosis; contact of tumor to major hepatic vessels and liver capsule; degree of approximation of tumor to the liver hilum; ablation time; degree of benign pre-ablational enhancement; sufficient safety margin; tumor multinodularity; tumor histological differentiation; tumor segmental location; maximum tumor diameter; degree of tumor pre-ablational enhancement at arterial phase CT, MRI or CT-angiography; and laboratory markers pre- and post-ablation (AFP, PIVKA II, TP, AST, ALT, ALP and TB). RESULTS: The incidence of overall recurrence, LTP and IDR was 65, 23 and 52.5%, respectively. The cumulative disease-free survival rates were 54.6, 74.8 and 78.3% at 1 year, 27.3, 71.9 and 46.3% at 2 years and 20, 71.9 and 29.4 at 3 years, respectively. Univariate and multivariate analysis showed that the significant risk factors for LTP were: tumor size > or = 2.3 cm, insufficient safety margin, multinodular tumor, tumors located at segments 8 and 5, and patient's age > 65 years (P < 0.05). No significant risk factor relationship for IDR could be detected. CONCLUSION: Our results would have clinical implications for advance warning and appropriate management of patients scheduled for RFA. Patients at risk of LTP should be closely monitored in the first year. Furthermore, regular long-term surveillance is essential for early detection and eradication of IDR.