Maternal characteristics and causes associated with refractory postpartum haemorrhage after vaginal birth: a secondary analysis of the WHO CHAMPION trial data.

OBJECTIVE: To assess the maternal characteristics and causes associated with refractory postpartum haemorrhage (PPH). DESIGN: Secondary analysis of the WHO CHAMPION trial data. SETTING: Twenty-three hospitals in ten countries. POPULATION: Women from the CHAMPION trial who received uterotonics as first-line treatment of PPH. METHODS: We assessed the association between sociodemographic, pregnancy and childbirth factors and refractory PPH, and compared the causes of PPH between women with refractory PPH and women responsive to first-line PPH treatment. MAIN OUTCOME MEASURES: Maternal characteristics; causes of PPH. RESULTS: Women with labour induced or augmented with uterotonics (adjusted odds ratio [aOR] 1.35; 95% CI 1.07-1.72), with episiotomy or tears requiring suturing (aOR 1.82; 95% CI 1.34-2.48) and who had babies with birthweights ≥3500 g (aOR 1.33; 95% CI 1.04-1.69) showed significantly higher odds of refractory PPH compared with the reference categories in the multivariate analysis adjusted by centre and trial arm. While atony was the sole PPH cause in 53.2% (116/218) of the women in the responsive PPH group, it accounted for only 31.5% (45/143) of the causes in the refractory PPH group. Conversely, tears were the sole cause in 12.8% (28/218) and 28% (40/143) of the responsive PPH and refractory PPH groups, respectively. Placental problems were the sole cause in 11 and 5.6% in the responsive and refractory PPH groups, respectively. CONCLUSION: Women with refractory PPH showed a different pattern of maternal characteristics and PPH causes compared with those with first-line treatment responsive PPH. TWEETABLE ABSTRACT: Women with refractory postpartum haemorrhage are different from those with first-line treatment responsive PPH.

Clinical practice patterns on the use of magnesium sulphate for treatment of pre-eclampsia and eclampsia: a multi-country survey.

OBJECTIVE: To characterise the current clinical practice patterns regarding the use of magnesium sulphate (MgSO4 ) for eclampsia prevention and treatment in a multi-country network of health facilities and compare with international recommendations. DESIGN: Cross-sectional survey. SETTING: A total of 147 health facilities in 15 countries across Africa, Latin America and Asia. POPULATION: Heads of obstetric departments or maternity units. METHODS: Anonymous online and paper-based survey conducted in 2015. MAIN OUTCOME MEASURES: Availability and use of MgSO4 ; availability of a formal clinical protocol for MgSO4 administration; and MgSO4 dosing regimens for eclampsia prevention and treatment. RESULTS: Magnesium sulphate and a formal protocol for its administration were reported to be always available in 87.4% and 86.4% of all facilities, respectively. MgSO4 was used for the treatment of mild pre-eclampsia, severe pre-eclampsia and eclampsia in 24.3%, 93.5% and 96.4% of all facilities, respectively. Regarding the treatment of severe pre-eclampsia, 26.4% and 7.0% of all facilities reported using dosing regimens that were consistent with Zuspan and Pritchard regimens, respectively. Across regions, intramuscular maintenance regimens were more commonly used in the African region (45.7%) than in the Latin American (3.0%) and Asian (22.9%) regions, whereas intravenous maintenance regimens were more often used in the Latin American (94.0%) and Asian (60.0%) regions than in the African region (21.7%). Similar patterns were found for the treatment of eclampsia across regions. CONCLUSIONS: The reported clinical use of MgSO4 for eclampsia prevention and treatment varied widely, and was largely inconsistent with current international recommendations. TWEETABLE ABSTRACT: MgSO4 regimens for eclampsia prevention and treatment in many hospitals are inconsistent with international recommendations.

Review on arsenic-induced toxicity in male reproductive system and its amelioration.

Arsenic is an environmental toxicant which causes mutagenic, teratogenic and carcinogenic defects. It is used as herbicide, fungicide and rodenticide and results in contamination of air, soil and water. Arsenic is also produced through burning of coal industries. The sludge of factories contaminates the fodder and drinking source of water of human and livestock. Arsenic binds thiol groups in tissue proteins and impairs the function of the proteins. This metal affects the mitochondrial enzymes and interrupts the production of energy. Oxidative stress and the generation of reactive oxygen species could also be a consequence of arsenic exposure. High arsenic level may suppress the sensitivity of gonadotroph cells to GnRH as well as gonadotropin secretion by elevating plasma levels of glucocorticoids. These ultimately lead to the development of gonad toxicity in animals and cause the reduction in sperm number, sperm viability and motility. Massive degeneration of germ cells and alterations in the level of LH, FSH and testosterone are also reported. The objective of this review was to find out the effects of arsenic-induced toxicity on male reproductive system in animals and its amelioration.

Clinical pharmacokinetic properties of magnesium sulphate in women with pre-eclampsia and eclampsia.

BACKGROUND: The pharmacokinetic basis of magnesium sulphate (MgSO4 ) dosing regimens for eclampsia prophylaxis and treatment is not clearly established. OBJECTIVES: To review available data on clinical pharmacokinetic properties of MgSO4 when used for women with pre-eclampsia and/or eclampsia. SEARCH STRATEGY: MEDLINE, EMBASE, CINAHL, POPLINE, Global Health Library and reference lists of eligible studies. SELECTION CRITERIA: All study types investigating pharmacokinetic properties of MgSO4 in women with pre-eclampsia and/or eclampsia. DATA COLLECTION AND ANALYSIS: Two authors extracted data on basic pharmacokinetic parameters reflecting the different aspects of absorption, bioavailability, distribution and excretion of MgSO4 according to identified dosing regimens. MAIN RESULTS: Twenty-eight studies investigating pharmacokinetic properties of 17 MgSO4 regimens met our inclusion criteria. Most women (91.5%) in the studies had pre-eclampsia. Baseline serum magnesium concentrations were consistently <1 mmol/l across studies. Intravenous loading dose between 4 and 6 g was associated with a doubling of this baseline concentration half an hour after injection. Maintenance infusion of 1 g/hour consistently produced concentrations well below 2 mmol/l, whereas maintenance infusion at 2 g/hour and the Pritchard intramuscular regimen had higher but inconsistent probability of producing concentrations between 2 and 3 mmol/l. Volume of distribution of magnesium varied (13.65-49.00 l) but the plasma clearance was fairly similar (4.28-5.00 l/hour) across populations. CONCLUSION: The profiles of Zuspan and Pritchard regimens indicate that the minimum effective serum magnesium concentration for eclampsia prophylaxis is lower than the generally accepted level. Exposure-response studies to identify effective alternative dosing regimens should target concentrations achievable by these standard regimens. TWEETABLE ABSTRACT: Minimum effective serum magnesium concentration for eclampsia prophylaxis is lower than the generally accepted therapeutic level.

Pre-eclampsia, eclampsia and adverse maternal and perinatal outcomes: a secondary analysis of the World Health Organization Multicountry Survey on Maternal and Newborn Health.

OBJECTIVE: To assess the incidence of hypertensive disorders of pregnancy and related severe complications, identify other associated factors and compare maternal and perinatal outcomes in women with and without these conditions. DESIGN: Secondary analysis of the World Health Organization Multicountry Survey on Maternal and Newborn Health (WHOMCS) database. SETTING: Cross-sectional study implemented at 357 health facilities conducting 1000 or more deliveries annually in 29 countries from Africa, Asia, Latin America and the Middle East. POPULATION: All women suffering from any hypertensive disorder during pregnancy, the intrapartum or early postpartum period in the participating hospitals during the study period. METHODS: We calculated the proportion of the pre-specified outcomes in the study population and their distribution according to hypertensive disorders' severity. We estimated the association between them and maternal deaths, near-miss cases, and severe maternal complications using a multilevel logit model. MAIN OUTCOME MEASURES: Hypertensive disorders of pregnancy. Potentially life-threatening conditions among maternal near-miss cases, maternal deaths and cases without severe maternal outcomes. RESULTS: Overall, 8542 (2.73%) women suffered from hypertensive disorders. Incidences of pre-eclampsia, eclampsia and chronic hypertension were 2.16%, 0.28% and 0.29%, respectively. Maternal near-miss cases were eight times more frequent in women with pre-eclampsia, and increased to up to 60 times more frequent in women with eclampsia, when compared with women without these conditions. CONCLUSIONS: The analysis of this large database provides estimates of the global distribution of the incidence of hypertensive disorders of pregnancy. The information on the most frequent complications related to pre-eclampsia and eclampsia could be of interest to inform policies for health systems organisation.

Overview of abortion cases with severe maternal outcomes in the WHO Multicountry Survey on Maternal and Newborn Health: a descriptive analysis.

OBJECTIVE: To summarise individual and institutional characteristics of abortion-related severe maternal outcomes reported at health facilities. DESIGN: Secondary analysis of data from the WHO Multicountry Survey on Maternal and Newborn Health. SETTING: 85 health facilities in 23 countries. SAMPLE: 322 women with abortion-related severe maternal outcomes. METHODS: Frequency distributions and comparisons of differences in characteristics between cases of maternal near miss and death using Fisher's exact tests of association. MAIN OUTCOME MEASURES: Individual and institutional characteristics and frequencies of potentially life-threatening conditions, and interventions provided to women with severe maternal outcomes, maternal near miss, and maternal death. RESULTS: Most women with abortion-related severe maternal outcomes (SMOs) were 20-34 years old (65.2%), married or cohabitating (92.3%), parous (84.2%), and presented with abortions resulting from pregnancies at less than 14 weeks of gestation (67.1%). The women who died were younger, more frequently without a partner, and had abortions at ≥14 weeks of gestation, compared with women with maternal near miss (MNM). Curettage was the most common mode of uterine evacuation. The provision of blood products and therapeutic antibiotics were the most common other interventions recorded for all women with abortion-related SMOs; those who died more frequently had antibiotics, laparotomy, and hysterectomy, compared with women with MNM. Although haemorrhage was the most common cause of abortion-related SMO, infection (alone and in combination with haemorrhage) was the most common cause of death. CONCLUSION: This analysis affirms a number of previously observed characteristics of women with abortion-related severe morbidity and mortality, despite the fact that facility-based data on abortion-related SMO suffers a number of limitations.

THE EFFECT OF TWO LEVELS OF COUNSELLING ON ACCEPTANCE, UPTAKE AND EARLY OUTCOMES OF POST-PLACENTAL INTRA-UTERINE CONTRACEPTIVE DEVICE.

OBJECTIVE: To determine the effect of two levels of counselling on the provision of Intrauterine Contraceptive Device (IUCD) at six weeks post-partum of the post-placental intrauterine device. SETTING: Embu Provincial General Hospital, Kenya. SUBJECTS: One hundred and thirty seven pregnant women at the gestation of 36 weeks to term, who attended Antenatal clinic and were followed until delivery and at six weeks post-partum. DESIGN: A randomised "open-label" clinical trial. RESULTS: One hundred and twenty seven study participants were enrolled and randomised to intensive (64 women) or routine FP counselling (63 women). Seventy eight per cent of women in the intensive FP counselled group and 66% in the routine FP counselled group accepted to have the post-placental IUCD inserted. There was no significant difference in uptake in the two-randomisation arms (p-value 0.232). Complications included expulsion (3.7%), allergic reaction (1.8%), pelvic infection (1.8%) and abdominal pain (1.8%).The post-placental IUCD is a favourable method with continuation rates (91%), client (88%) and reported partner (77%) satisfaction were notably high at six weeks. The most critical barrier to uptake was lack of trained medical personnel to insert the post-placental IUCD, which occurred in (60%) clients who had consented. CONCLUSION: The post-placental IUCD is an acceptable method among women irrespective of level of counselling. Intensive counselling did not significantly increase acceptance and uptake rates of post-placental IUCD insertion in comparison to routine counselling.

Perceived tutor benefits of teaching near peers: insights from two near peer teaching programmes in South East Scotland.

BACKGROUND AND AIMS: There is little evidence about the benefits to junior doctors of participating in teaching, or how to train doctors as teachers. We explore (through South East Scotland based teaching programmes): (a) How prepared do junior doctors feel to teach? (b) What junior doctors consider to be the main challenges of teaching? (c) What motivates the junior doctors to continue teaching, and what is the perceived impact of teaching on their professional development? METHODS AND RESULTS: 'Questionnaire 1', distributed at 'tutor training days', explored (i) attitudes towards teaching and (ii) tutors' preparedness to teach. 'Questionnaire 2', distributed after completion of a teaching programme, evaluated the tutor experience of teaching. RESULTS: Seventy-six per cent of tutors reported no previous teacher training; 10% were able to teach during allocated work hours. The strongest motivation for teaching was to help students with their learning and to develop teaching skills. Ninety one per cent of tutors felt more prepared to teach by the end of the programme. Tutors also improved their clinical skills from teaching. CONCLUSIONS: There is a body of junior doctors, who see teaching as an important part of their career, developing both teaching and clinical skills in the tutor. If teaching is expected of foundation doctors, rotas ought to be more flexible to facilitate both teaching and teacher training.

Rapid assessment of partograph utilisation in selected maternity units in Kenya.

BACKGROUND: Prolonged labour causes maternal and perinatal morbidity and mortality. Its sequela include obstructed labour, uterine rupture, maternal exhaustion, postpartum haemorrhage, puerperal sepsis, obstetric fistula, stillbirths, birth asphyxia and neonatal sepsis. These complications can be reduced by using the partograph to assess the progress of labour. The Ministry of Health, Kenya has adopted this tool for labour management in the country and the standardised partograph is recommended for use in all delivery units. OBJECTIVE: To determine the utilisation of the partograph in the management of labour in selected health facilities in Kenya. DESIGN: A descriptive cross sectional study. SETTING: Nine health facilities -ranging from a tertiary hospital to health centre, including public private and faith based facilities in four provinces in Kenya. RESULTS: All facilities apart from Pumwani Maternity Hospital and one health centre were using the partograph. The correct use was low, the knowledge on the use of the tool was average and there was minimal formal training being provided. Staff shortage was listed as the most common cause of not using the tool. Contractions were recorded 30-80%, foetal heart rate 53-90% and cervical dilatation 70-97%. Documentation of state of the liquor, moulding and descent as well as maternal parameters such as pulse, and blood pressure and urinalysis were minimally recorded. Supplies for monitoring labour such as fetoscopes and blood pressure machines were in short supply and sometimes not functional. Overall, the poor usage was contributed to staff shortages, lack of knowledge especially on interpretation of findings, negative attitudes, conflict between providers as to their roles in filling the partograph, and senior staff themselves not acting as role models with regards to the use, advocacy and implementation of the partograph. CONCLUSION: The partograph was available in most units. However, accurate recording of parameters to monitor the foetus, the mother and progress of labour as recommended was mostly not done. Shortage of staff, lack of knowledge, lack of team work, lack of supplies and negative attitude among healthcare providers were some of the obstacles noted to hamper partograph use.

Pseudomonas aeruginosa bacteremia over a 10-year period: multidrug resistance and outcomes in transplant recipients.

AIM: Transplant recipients are at risk for hospital-acquired infections (HAIs), including those caused by Pseudomonas aeruginosa. Of all HAIs, bloodstream infection (BSI) remains one of the most life-threatening. METHODS: Over a 10-year period, we studied 503 patients, including 149 transplant recipients, with pseudomonal BSI from the University of Pittsburgh Medical Center. Trends in antimicrobial susceptibility, risk factors for multidrug resistance (MDR), and outcomes were compared between transplant and non-transplant patients. RESULTS: Resistance to all antibiotic classes was significantly greater in pseudomonal blood culture isolates from transplant compared with non-transplant patients (P<0.001). Of isolates from transplant recipients (n=207), 43% were MDR, compared with 18% of isolates from non-transplant patients (n=391) (odds ratio [OR] 3.47; 95% confidence interval [CI] 2.34-5.14, P<0.001). Among all patients, independent risk factors for MDR P. aeruginosa BSI included previous transplantation (OR 2.38; 95% CI 1.51-3.76, P<0.001), hospital-acquired BSI (OR 2.41; 95% CI 1.39-4.18, P=0.002), and prior intensive care unit (ICU) admission (OR 2.04; 95% CI 1.15-3.63, P=0.015). Mortality among transplant recipients was 42%, compared with 32% in non-transplant patients (OR 1.55; 95% CI 0.87-2.76, P=0.108). For transplant recipients, onset of BSI in the ICU was the only independent predictor of mortality (OR 8.00; 95% CI 1.71-37.42, P=0.008). CONCLUSIONS: Transplant recipients are at greater risk of MDR P. aeruginosa BSI, with an appreciable mortality. Future management must concentrate on the implementation of effective preventative strategies.

Gestational thyrotoxicosis associated with emesis in early pregnancy.

OBJECTIVES: To determine the thyroid profile and the prevalence of gestational thyrotoxicosis among women with emesis during early pregnancy. DESIGN: A descriptive cross-sectional study. SETTING: Kenyatta National Hospital acute gynaecology ward and the ante-natal clinic. SUBJECTS: Seventy two women presenting with emesis up to 16 weeks gestation. MAIN OUTCOME MEASURES: The levels of FT3, FT4, TSH and beta-hCG during the first 16 weeks of gestation. Correlation between the thyroid hormones and beta-hCG as well as the severity of vomiting was also done. RESULTS: The point prevalence of gestational thyrotoxicosis was 8.3%. There was a significant positive correlation between beta-hCG levels and FT3 and FT4 (P-values < 0.05), and a significant negative correlation between beta-hCG and TSH (P < 0.05). Correlation between the severity of vomiting and the thyroid hormones as well as beta-hCG was not statistically significant. Patients' age ranged from 14-38 years (median 26). Majority of the women studied were at a gestation of 8 to 11 weeks (38.9%). Most patients (84.7%) had one to five episodes of vomiting per day. Peak beta-hCG was at 12-15 weeks gestation. CONCLUSIONS: Thyrotoxicosis does occur among women with emesis in pregnancy in this set-up. Screening for it may be beneficial to such women and also those with high serum beta-hCG levels above the median for the gestational age.

Contraceptive use among HIV infected women attending Comprehensive Care Centre.

OBJECTIVE: To determine contraceptive use among HIV infected women attending Comprehensive Care Centre at Kenyatta National Hospital. DESIGN: Hospital based cross-sectional descriptive study. SETTING: Comprehensive Care Centre (CCC), Kenyatta National Hospital. SUBJECTS: The study group was non-pregnant HIV positive women on follow up at the CCC. A total of 94 HIV infected women were interviewed between May 2006 and August 2006 through a pretested interviewer administered questionnaire. Consecutive women willing to participate in the study were interviewed. MAIN OUTCOME MEASURES: Current contraceptive use, contraceptive methods, source of contraception, reproductive intention and unmet need of family planning. RESULTS: The mean age of the respondents was 34 years, 47.9% were married, all had formal education and 74.6% were employed. Eighty six percent of the respondents did not have reproduction intentions in the next two years; however, only 44.2% of the respondents were using contraception. Condoms were the most popular (81.5%) contraceptive method. Female condom was used by 10.5% of the respondents. Norplant was the only long-term contraceptive method and was used by only 2.6%. Dual method of contraception was practiced by 13.5% of the respondents. Majority of the respondents obtained contraceptives from private sector (42.9%) with less than 10% getting them from CCC. The unmet need for family planning among the study group was 30%. Marital status and regular sexual partner were significantly associated with contraceptive use. CONCLUSION: Although majority of respondents did not have reproduction intentions in the next two years, use of contraception was low with only 44% being on a method. Use of long-term contraceptive methods was low among respondents. Majority of the respondents obtained contraceptives away from CCC. The unmet need for family planning was high at 30%.

Birth preparedness among antenatal clients.

OBJECTIVE: To evaluate birth preparedness and complication readiness among antenatal care clients. DESIGN: A descriptive cross- sectional study. SETTING: Antenatal care clinic at Kenyatta National Hospital, Nairobi, Kenya. SUBJECTS: Three hundred and ninety four women attending antenatal care at Kenyatta National hospital were interviewed using a pre-tested questionnaire between May 2006 and August 2006. Clients who were above 32 weeks gestation and had attended the clinic more than twice were recruited. Systematic sampling was used to select the study participants with every third client being interviewed. MAIN OUTCOME MEASURES: Health education on birth preparedness, knowledge of danger signs, preparations for delivery and emergencies. RESULTS: Over 60% of the respondents were counselled by health workers on various elements of birth preparedness. Eighty seven point three per cent of the respondents were aware of their expected date of delivery, 84.3% had set aside funds for transport to hospital during labour while 62.9% had funds for emergencies. Sixty seven per cent of the respondents knew at least one danger sign in pregnancy while only 6.9% knew of three or more danger signs. One hundred and nine per cent of the respondents did not have a clear plan of what to do in case of an obstetric emergency. Level of education positively influenced birth preparedness. CONCLUSIONS: Education and counselling on different aspects of birth preparedness was not provided to all clients. Respondents knowledge of danger signs in pregnancy was low. Many respondents did not know about birth preparedness and had no plans for emergencies.

Anti-proliferative or Cytopathic Potential of Thapsia garganica, Citrus sinensis, Citrus limon and Vinca rosea Extracts Against Human Embryonic Kidney Carcinoma Cell Line

ABSTRACT Objective: Developing anti-cancer drugs from natural products is receiving increasing interest worldwide due to limitations and side effects of anti-cancer drugs. The purpose of this study was to explore the anti-proliferative or cytopathic potential of natural compounds derived from plant sources as alternatives of synthetic compounds on human embryonic kidney carcinoma (HEK) cell line. Methods: In this study, aqueous and methanolic extracts were obtained from various plants, viz, Thapsia garganica, Citrus sinesis, Citrus limon and Vinca rosea. Extracts were serially diluted into 96-well microtitre plates and were screened for anti-proliferative potential against the HEK cell line via the neutral red dye uptake assay. Results: The findings revealed that methanolic extracts of T. garganica leaf and V. rosea leaf were the most effective as anti-proliferative or cytotoxic against the HEK cell line, with IC50 at 32-fold dilution of the extract. Conclusion: The extracts of T. garganic and V, rosea have been used as anti-proliferative drugs but after trial in experimental animals for being not toxic.

Long-term survival of patients with resistant lymphoma treated with tandem stem cell transplant.

Dose-intensive chemotherapy with autologous stem cell support is commonly used in resistant/refractory cases of Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL). The purpose of this study was to evaluate the role of tandem transplantation in these patients. We used non cross-resistant conditioning regimens with thiotepa, mitoxantrone and carboplatin (TMJ) followed by ifosphamide, carboplatin and etoposide (ICE) with autologous stem cell rescue in an attempt to maximize dose intensity and achieve long-term remission. Seventy-six patients were included in this study. Twenty-nine patients with HD and 47 with NHL underwent autologous stem cell transplant using TMJ as the conditioning regimen for the first transplant. Of these, 49 patients proceeded to the second transplant using ICE as the conditioning regimen. In 57 patients, only peripheral blood cells were used and in 11 patients both bone marrow and peripheral stem cells were used. Twelve patients died due to treatment-related toxicity. On an intent to treat basis, 32.14% of patients with HD refractory to initial or subsequent therapy survived long term as opposed to 12.76% of patients with NHL. With a median follow-up of 83 months (range 25 - 110 months), the median disease-free survival of patients with HD was 7 months, as opposed to 2 months for patients with NHL. Multivariate analysis identified that patients with HD had a superior outcome if they were less than 35 years of age and did not have B symptoms. Dose-intensive chemotherapy with tandem transplantation is an option in patients with resistant/refractory lymphoma who have very limited treatment options and poor prognosis.

Study of the effects of progesterone therapy on the stilboestrol-induced sensitivity of isolated uteri of hypophysectomized rats.

1. In intact rats progesterone (50 mg/kg) antagonized the effect of stilboestrol (100 mug/kg) on the vaginal smears and the uterine sensitivity. The uterine sensitivity to acetylcholine, oxytocin and 5-hydroxytryptamine was decreased by 6.8, 64 and 14.8 times, respectively, as compared with uteri removed after stilboestrol injections.2. Progesterone therapy in hypophysectomized rats also antagonized the effect of stilboestrol on the vaginal mucosa and on the uterine sensitivity to drugs. The sensitivity to acetylcholine, oxytocin and 5-hydroxytryptamine was decreased by 6.2, 50 and 14.5 times, respectively. Similar results were obtained on uteri removed from sham-hypophysectomized rats.3. On the basis of these results it is suggested that the hypophysis does not play any part in the desensitization of the myometrium to the oxytocic drugs and in the changes found in the vaginal mucosa after progesterone therapy.

High-dose chemotherapy and stem cell transplantation for patients with stage IV breast cancer without clinically evident disease: correlation of CD34+ selection to clinical outcome.

Forty-five patients with metastatic breast cancer without clinically evident disease were treated with thiotepa 750 mg/m2, mitoxantrone 40 mg/m2 and carboplatin 1000 mg/m2 followed by stem cell transplantation to determine the safety and efficacy of CD34+ selection of peripheral blood stem cells. Of these, 15 patients' (group I) stem cells were processed through Baxter Isolex 300 device for CD34+ selection, whereas 30 patients (group II) received unmanipulated stem cells. Toxicity, progression-free survival and survival were compared between these two groups. There was no difference in transfusion requirements, white cell count and platelet recovery and non-hematologic toxicity between the two groups. The survival of patients in group I was 27 months compared to 38 months in group II (P = 0.8). The progression-free survival was 12 months and 13.5 months for group I and group II patients, respectively (P = 0.6). Our results indicate that while there is no adverse effect, there is also no significant advantage of CD34+ selection in terms of progression-free survival and survival in patients with metastatic breast cancer without clinically evident disease. Bone Marrow Transplantation (2000).

High dose chemotherapy with thiotepa, mitoxantrone and carboplatin (TMJ) followed by autologous stem cell support in 100 consecutive lymphoma patients in a single centre: analysis of efficacy, toxicity and prognostic factors.

High dose chemotherapy with autologous stem cell transplant is often used in patients with Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) who either do not respond to, or relapse after conventional chemotherapy. There is no consensus on the "ideal" pretransplant conditioning regimen. In this study, we analyzed the results of 100 consecutive patients with HD and NHL who met our eligibility criteria and underwent autologous stem cell transplant at New York Medical College and Zalmen A. Arlin Cancer Institute. All patients received high dose chemotherapy with thiotepa, mitoxantrone and carboplatin (TMJ). One hundred patients, 37 with HD and 63 with NHL underwent autologous stem cell transplant using TMJ as a conditioning regimen. All patients with HD had chemo-sensitive relapse while 50 patients with NHL had chemo-sensitive relapse and 13 patients had first complete remission. The source of stem cells was bone marrow (18 patients), peripheral blood (50 patients) and both bone marrow and peripheral blood (32 patients). With a median follow up of 91 months (range 23-147 months), the median survival of patients with HD and NHL who underwent autologous stem cell transplant is 107 months and the 5 years disease free survival is 43%. Median survival of patients with HD and NHL is 87 and 107 months respectively. There were 4 transplant related deaths. Median survival of patients who had sensitive relapse at the time of transplant is 87 months while median survival has not been reached for patients who had first complete remission at the time of transplant. Multivariate analysis identified age>35 years (P=0.02) as a predictor for poor survival for the whole group as well as for patients with NHL (P=0.04). TMJ is a safe and effective regimen when used as a part of autologous stem cell transplant for patients with HD and NHL.

Treatment of external genital warts in men with imiquimod 2% in cream. A placebo-controlled, double-blind study.

OBJECTIVE: The purpose of this double-blind, placebo-controlled study was to evaluate the safety, clinical efficacy and tolerability of imiquimod (2%) in cream to cure external genital warts in males. METHODS: Preselected male patients (n=60) ranging between 18 and 50 years of age (mean 24.2) harbouring 558 lesions (mean 9.3) with clinical, histopathological and polymerase chain reaction (PCR) confirmed diagnosis of human papilloma virus (HPV) infection were randomized to two parallel groups. Each patient was allocated a precoded 25g tube, and instructions on how to apply the trial medication to their lesions at home once daily for three consecutive days per week (max. 12 application in 4 weeks). To evaluate the safety, clinical efficacy and tolerance, patients were exa-mined on a weekly basis. Cure was defined as the total elimination of treated warts with PCR, and Southern blot hybridization confirmed negative HPV DNA. RESULTS: By the end of the treatment, 40% (24/60) patients and 49.8% (278/558) warts were cured. Breaking the code revealed that imiquimod cream had cured 70% (21/30) patients and 86.8% of warts, while placebo healed three subjects and 28 warts (P=0.0001). Eleven patients (18.3%), predominantly in the imiquimod cream group, experienced mild to moderate, non-objective, drug-related side effects with no dropouts. The study was followed up for 18 months from the first day of the treatment, and among the 26 cured patients, one in the imiquimod cream group and two in the placebo had a relapse after 14 months. CONCLUSION: The study demonstrated that 2% imiquimod in cream with mild non-objective side effects is safe, tolerable and significantly more effective than placebo in curing external genital warts in males.