Studies of chemical and biological properties of 99mTc-DMS (dimercaptosuccinic acid) — Renal imaging agent

Studies of the chemistry of preparation of tin chelate 2.3-dimercaptosuccinic acid (DMS) complexed with ^99mTc with respect to its biological properties have been made. We have varied molar ratio of reactants (DMS:Sn/II/), concentration of Sn-DMS chelate and pH of ^99mTc-DMS injection solution and examined their influence on biodistribution. Biodynamics of labeled solution at time intervals of from 0.5 to 4 h have also been measured. Animal experiments were carried out on mice and rats.Radiochemical purity was checked by paper chromatography, thin-layer chromatography, and gel-filtration through Bio-Gel P-2.A sterile, pyrogen-free lyophilized kit for labeling, stable for 6 months, was made on the basis of achieved results.The results of its clinical application are also reported.Report presented at the I European Congress of Nuclear Medicine, Lausanne, May 12/15, 1976     

Severity of illness scores and the outcome of acute tubular necrosis

The outcome of patients with acute renal failure (ARF)due to acute tubular necrosis (ATN) was evaluated inthis study. Two hundred and twenty-two patients witha mean age of 55.l ± 17.7 years (range 19–97years; male 153, female 69) who developed ATN in theperiod from July 1991 through January 1997 werestudied. Patients were divided into four groupsaccording to their APACHE II scores at the time of thediagnosis of ATN. Group I included patients with anAPACHE II score of 14 or less (n = 70), Group II with ascore of 15–18 (n = 52), Group III with a score of 19–23(n = 58), and group IV with a score of 24 or above(n = 42). The mean APACHE II score for each of the fourstudy groups was 11 ± 0.4, 16 ± 0.2, 20 ±0.2, and 29 ± 0.7, respectively. Patient survivalwas evaluated by the Kaplan-Meier analysis withcensorship at 12 months. Survival rates at 180 dayswere 67%, 47%, 39%, and zero%, for group I through IV respectively, χ² = 27.99, p < 0.0001,with a median survival of >365, 120, 31, and 11days, for groups I through IV, respectively. For patients with oliguria (n = 88) survival at 180days was 23% vs. 58% for patients without oliguria(n = 134), p < 0.0001, median survival 13 vs. 364 d.Six months survival of those who required dialysis(n = 79) was 25% vs. 58% for those whom dialysis wasnot needed (n = 143), p = 0.001, median survival 15 vs.364 d, respectively. In patients with sepsis (n = 58),6 months survival was 35% vs. 50% for those withoutsepsis (n = 164), p = 0.013, median survival 14 vs. 169 d. In patients who required mechanical ventilation(n = 72), 6 months survival was 17% vs. 62% for those whodid not need respiratory support (n = 150), p = 0.0001,median survival 13 vs. > 365 d, respectively. Finally, 6 months survival in patients with one(kidney only), two, three, and four organ failure was76, 30, 11, and zero percent, respectively, p = 0.0001,median survival > 365, 16, 11, and 12 days,respectively. We conclude that the use of the APACHE II score forthe stratification of the severity of illness could beof clinical utility in predicting mortality inpatients with ATN. Other predictors of poor prognosisinclude the need for dialysis, the presence ofoliguria, the need for mechanical ventilation, thepresence of sepsis, and the number of failed organs. This revised version was published online in August 2006 with corrections to the Cover Date.     

Mixed hematopoietic chimerism at day 90 following allogenic myeloablative stem cell transplantation is a predictor of relapse and survival.

We retrospectively analyzed the prognostic significance of mixed chimerism and associated clinical parameters in 80 patients following unmanipulated allogenic stem cell transplantation. Chimerism studies were performed on marrow aspirates using fluorescent in situ hybridization and variable number tandem repeats techniques at day +30, day +90 and +12 months. The median overall survival (OS) was 24 months (range, 1-56 months). Mixed chimerism was found in 23, 28 and 14% of patients at day +30 (1 month), +90 (3 months), and +12 months, respectively. Day +30 chimerism studies failed to provide any prognostic information. Day +90 mixed chimeras (MC) had significantly higher relapse rates compared to day +90 complete chimeras (CC) at 6 months (P=0.03) and 18 months when compared to MC (P=0.03) following transplant. The median OS in day +90 MC and day+90 CC were, respectively (95% CI, 2-35 months), compared to 47 months (95% CI, 20-74 months) (P=0.02). In conclusion, chimerism studies on day +30 could be reserved for patients who fail to demonstrate engraftment. Day +90 MC had higher relapse rates and lower OS, and therefore may be considered for novel therapies and future studies.     

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.