Irreducible Hernia With Unusual Content.

Chronic increase in the intravesical pressure secondary to bladder outlet obstruction can lead to the formation of bladder diverticulum. Bladder diverticulum may get pulled into the hernial sac and may become a component of the hernia. Here, we report the case of an elderly male who had an unusual presentation of urinary bladder diverticulum as the content in an obstructed inguinal hernia. Upon exploration, the bladder diverticulum was released from the inguinal canal and returned to the peritoneal cavity, following which conventional hernioplasty was done. Inguinal herniation of bladder diverticulum is an uncommon condition and can be perilous during surgery if not diagnosed preoperatively.

Assessment of Squalor in Migrant Colonies of Thiruvalla Province of Kerala, India using Rapid Survey Technique.

BACKGROUND: Domestic squalor refers to households that are extremely cluttered, in a filthy condition, and where the accumulation of items such as personal possessions, rubbish, excrement and decomposing food creates an environment that jeopardizes the health and wellbeing of the occupant(s). In India, an estimated 258 million are migrants. They are more likely to live in squalor due to inferior socio-economic status and no permanent residence. This poses a threat to the health of the migrants and the neighbors. OBJECTIVE: To assess the squalor and morbidity pattern among the migrants of Migrant colonies in Thiruvalla using Rapid survey technique. METHODOLOGY: The state of squalor in migrant colonies was assessed by Lot Quality Assurance Sampling Methodology using the Environment Cleanliness and Clutter Scale (ECCS). The sample size for each lot/colony was '14' dwellings according to LQAS table. The details were collected from 14 inhabitants of different dwellings of the same colony. The inhabitants were selected randomly and were excluded if he belonged to the same dwelling. Fifteen colonies were randomly selected to achieve the sample size of 210 (15*14). The study was done in Tiruvalla municipality. RESULTS AND CONCLUSION: Only two colonies (n = 15) were squalor free. Majority of the dwellings (n = 210) were having an ECCS score between 13 and 15. Common ailments affecting migrants include Common cold, Skin disorders, and dental caries and gastritis. Squalor was found in most of the migrant colonies as they are living in inhuman conditions.

Revisions in TB programme - boon or bane? A qualitative study exploring barriers and facilitators among health care workers in private and public sector, Kerala.

BACKGROUND: Despite many serious and organized efforts worldwide, Tuberculosis (TB) remains one of the major public health concerns in many countries. India accounts for more than one quarter of global TB cases and deaths each year. India's National Tuberculosis Elimination Programme (NTEP) is the largest TB control program in the world, placing more than 100,000 patients on treatment every month. There have been so many revisions in the programme guidelines in the last 5 years. As we are gearing up for TB elimination in India, knowledge regarding the barriers is very crucial in the successful undertaking of these revised guidelines. Exploring perceptions of health care workers, both from the private and public sector will help to design appropriate strategies at the field level. OBJECTIVE: To explore the barriers and facilitators among health care workers in the implementation of revised NTEP guidelines in a selected district of central Kerala. METHODOLOGY: This qualitative study was conducted among health care workers from all levels involved in the implementation of NTEP from private and public sector. Qualitative data was collected through Focus Group Discussions (FGD) and Key Informant Interviews using a topic guide till data saturation. All discussions were audio recorded with the consent of participants. Sociogram was plotted to confirm equal participation of interviewees. A total of 4 FGDs (2 from each sector) and 12 Key informant interviews (7 from public sector and 5 from private sector) were conducted after obtaining written consent from the participants. RESULTS: Overall awareness about revisions was found to be good. However, the study identified a "Gap between planners and implementers". Frequent nature of revisions without understanding the practical difficulties in the field, additional job responsibilities, inadequate knowledge among grass root level workers/private practioners in small clinics and increased side effects were the major barriers identified. In addition to that, insufficient logistics, not enthusiastic in learning revisions, fear of losing patients, delay in communication, decreased compliance with new regimen, increased out of pocket expenditure and grey areas in the current guidelines were also adversely affecting the successful implementation At the same time, facilitators like positive attitude and commitment of health care workers, introduction of M-health technology, strong public private partnership, inclusion of costly investigations in the revised guidelines, good administrative support, financial assistance, innovative initiatives like Treatment Support Groups (TSGs) and concept of Family Directly Observed Treatment Short-Course increased the effectiveness of the programme to a large extent. CONCLUSION: The study identified gaps in knowledge, attitude and practice of revised guidelines at the field level. Gap between 'Planners and implementers could impede the successful implementation of TB Elimination programme and needs to be addressed.

Post-treatment mortality after definitive chemoradiotherapy versus resection for esophageal cancer.

In efforts to better characterize incidence and predictors of 30- and 90-day mortality following operative versus nonoperative approaches for locally advanced esophageal cancer (EC), we conducted a novel investigation of a large, contemporary US database. The National Cancer Database was queried for newly-diagnosed T1-3N0-1 squamous cell or adenocarcinoma receiving surgical-based therapy (esophagectomy alone or preceded by chemotherapy and/or radiotherapy) versus definitive chemoradiotherapy (dCRT). Statistics included graphing cumulative incidences of mortality before and following propensity score matching (PSM), based on age-based intervals. Cox regression determined factors independently predictive of 30- and 90-day mortality. Of 15,585 patients, 9,278 (59.5%) received surgical-based therapy and 6,307 (40.5%) underwent dCRT. In the unadjusted population, despite nonsignificant differences at 30 days (3.3% dCRT, 3.6% surgical-based), the dCRT cohort experienced higher 90-day mortality (11.0% vs. 7.5%, P < 0.001). Following PSM, however, dCRT patients experienced significantly lower 30-day mortality (P < 0.001), with nonsignificant differences at 90 days (P = 0.092). Surgical-based management yielded similar (or better) mortality as dCRT in ≤70-year-old patients; however, dCRT was associated with reduced mortality in subjects > 70 years old. In addition to the intervention group, factors predictive for 30- and 90-day mortality included age, gender, insurance status, facility type, comorbidity index, tumor location, histology, and T/N classification. In summary, surgical-based therapy for EC is associated with higher 30-day mortality, which becomes statistically similar to dCRT by 90 days. Differences between surgery and dCRT were most pronounced in patients > 70 years of age. These data may better inform shared decision-making between multidisciplinary providers and patients.

The impact of postmastectomy and regional nodal radiation after neoadjuvant chemotherapy for clinically lymph node-positive breast cancer: a National Cancer Database (NCDB) analysis.

BACKGROUND: Following neoadjuvant chemotherapy (NAC), the optimal strategies for postmastectomy radiotherapy (PMRT) and regional nodal irradiation (RNI) after breast-conserving surgery (BCS) are controversial. In this analysis, we evaluate the impact of these radiotherapy (RT) approaches for women with clinically node-positive breast cancer treated with NAC in the National Cancer Database (NCDB). PATIENTS AND METHODS: Women with cT1-3 cN1 M0 breast cancer treated with NAC were divided into four cohorts by surgery [Mastectomy (Mast) versus BCS] and post-chemotherapy pathologic nodal status (ypN0 versus ypN+). Overall survival (OS) was estimated using the Kaplan-Meier method and RT approaches were analyzed using the log-rank test, multivariate Cox models, and propensity score-matched analyses. RESULTS: From 2003 to 2011, 15 315 cases were identified including 3040 Mast-ypN0, 7243 Mast-ypN+, 2070 BCS-ypN0, and 2962 BCS-ypN+ patients. On univariate analysis, PMRT was associated with improved OS for both Mast-ypN0 (P = 0.019) and Mast-ypN+ (P < 0.001) patients. On multivariate analyses adjusted for factors including age, comorbidity score, cT stage, in-breast pathologic complete response, axillary surgery, ypN stage, estrogen receptor status and hormone therapy, PMRT remained independently associated with improved OS among Mast-ypN0 [hazard ratio (HR) = 0.729, 95% confidence interval (CI) 0.566-0.939, P = 0.015] and Mast-ypN+ patients (HR = 0.772, 95% CI 0.689-0.866, P < 0.001). No differences in OS were observed with the addition of RNI to breast RT for BCS-ypN0 or BCS-ypN+ patients. Propensity score-matched analyses demonstrated identical patterns of significance. On subset analysis, OS was improved with PMRT in each pathologic nodal subgroup (ypN0, ypN1, and ypN2-3) (all P < 0.05). CONCLUSIONS: In the largest reported analysis of RT for cN1 patients treated with NAC, PMRT was associated with improved OS for all pathologic nodal subgroups. No OS differences were observed with the addition of RNI to breast RT.

Urate crystal degradation for treatment of gout: a nanoparticulate combination therapy approach.

The objective of the present work was to develop polymeric nanoparticles of uricase and aceclofenac (NSAID) and to incorporate them into gel, for delivering drugs to synovial joints, for effective treatment of Gout. Nanoparticles containing uricase and aceclofenac were prepared by double emulsion solvent evaporation method and emulsion solvent evaporation, using PLGA (50:50) as carrier, respectively. Process parameters were optimized using Taguchi L4 orthogonal array and L9 array, respectively. The formulations were characterized for particle size, entrapment efficiency, surface charge, in vitro drug release, ex vivo drug permeation, and urate crystal degradation activity. The particle size and entrapment efficiency for optimized batch was found to be 228.8 nm and 81.26% for uricase nanoparticles and 288.5 nm and 85.36% for aceclofenac nanoparticles, respectively. The developed nanoparticles formulations displayed zero order and Higuchi release kinetics with non-Fickian diffusion, respectively. The in vivo studies were performed in rabbit model. Topical application of gel containing polymeric uricase nanoparticles alone and a combination of both, uricase nanoparticles and aceclofenac nanoparticles in rabbit model test groups, provided complete removal of urate crystals and inflammation within 40 and 25 days of treatment, respectively. The combination treatment therapy resulted in effective treatment of gout due to degradation of crystals and anti-inflammatory response.

Natural history of asymptomatic gallstones: differential behaviour in male and female subjects.

OBJECTIVE: The natural history of asymptomatic (silent) gallstones has been inadequately studied. Existing information derives from studies based on oral cholecystography or relatively small sample sizes. We planned a retrospective cohort study in subjects with gallstones to determine conversion rates from asymptomatic to symptomatic. METHODS: We extracted data from computerised databases of one government hospital and two private clinics in Malaysia. Files were scrutinised to ensure that criteria for asymptomatic gallstones were fulfilled. Patients were called on telephone, further questioned to confirm that the gallstones at detection were truly asymptomatic, and asked about symptoms that were consistent with previously defined criteria for biliary colic. Appropriate ethical clearances were taken. RESULTS: 213 (112 males) patients fulfilled the criteria for asymptomatic gallstones and could be contacted. 23 (10.8%) developed pain after an average follow up interval of 4.02 years (range 0.1-11 years). Conversion rates from asymptomatic to symptomatic gallstones were high in the first two years of follow up, averaging 4.03±0.965 per year. Over time the conversion rates slowed, and by year 10 the annual conversion rate averaged only 1.38±0.29. Conversion rates were much higher for females compared to males (F:M hazard ratio 3.23, SE 1.54, p>z 0.014). The lifetime risks for conversion approached 6.15% for males, and 22.1% for females. CONCLUSION: In conclusion, asymptomatic gallstones are much more likely to convert to symptomatic in females than in males. Males in whom asymptomatic stones are discovered should be advised conservative treatment. Surgery may be preferable to conservative management if the subject is a young female.

Homozygous familial hypercholesterolemia.

We report a rare case of homozygous familial hypercholesterolemia (HoFH), a 22-year-old Malay woman who presented initially with minor soft tissue injury due to a cycling accident. She was then incidentally found to have severe xanthelasma and hypercholesterolemia (serum TC 15.3 mmol/L and LDL-C 13.9 mmol/L). She was referred to the Specialized Lipid Clinic and was diagnosed with familial hypercholesterolemia (FH) based on the Simon Broome (SB) diagnostic criteria. There was a family history of premature coronary heart disease (CHD) in that three siblings had sudden cardiac death, and of consanguineous marriage in that her parents are cousins. DNA screening of LDLR and APOB genes was done by Polymerase Chain Reaction (PCR), followed by Denaturing High Performance Liquid Chromatography (DHPLC). Homozygous mutation C255S in Exon 5 of her LDLR gene was found. There was no mutation was found in Exon 26 and Exon 29 of the APOB gene. This report is to emphasize the importance of identifying patients with FH and cascade screening through established diagnostic criteria and genetic studies in order to ensure early detection and early treatment intervention to minimize the risk of developing CHD and related complications.

Development of cellulosic polymer based gel of novel ternary mixture of miconazole nitrate for buccal delivery.

Aim of the present investigation was to develop cellulosic polymer based mucoadhesive antifungal gel comprising novel ternary mixture of miconazole nitrate (MN) for buccal delivery. Crosslinking of gel was made by adjusting pH with triethanolamine (TEA) and gel formulation was optimized on the basis of flux of MN (0.562-1.751 mg/cm(2)/h) calculated from ex vivo permeation study. Based on statistically validated polynomial equation and plotted response surfaces, B17 was found to be the optimum batch. Texture profile in terms of adhesiveness (3.24 ± 0.012 g), firmness (10.83 ± 0.067 g), spreadability (3.63 ± 0.033 mJ) and extrudability (35.6 ± 0.1 mJ) of B17 was evaluated using a novel instrumental approach. The texture parameters were found to be consistent over 90 days. Ternary mixture containing gel showed broader zone of growth inhibition (32.67-47.33 mm) in comparison to marketed formulation containing pure MN (17.50-40.33 mm) against selected strains of fungi. In conclusion, consistent and effective mucoadhesive antifungal gel of MN with extended residence time in oral mucosa was developed.

Prediction of blood loss during surgery on the lumbar spine with the patient supported prone on the Jackson table.

BACKGROUND CONTEXT: To date, many studies have examined the effects of one or several factors on blood loss during lumbar spine surgery. The nature and extent of the operation, patient position, blood pressure, and a variety of factors related to patient size have been touted as predictors of blood loss. PURPOSE: To measure multiple factors implicated as determinants of blood loss and develop a multivariable statistical model capable of predicting blood loss. STUDY DESIGN: An observational study of patients undergoing lumbar spine surgery in the prone position on the Jackson table. PATIENT SAMPLE: A total of 71 healthy adult men and women undergoing lumbar spine surgery in a university hospital setting. OUTCOME MEASURE: Blood loss during surgery. METHODS: We observed 35 surgeries and recorded demographic and body habitus data on each patient as well as surgical variables, blood pressure, and peripheral venous pressure. We measured bladder pressure intermittently as a surrogate for intra-abdominal pressure. We constructed a statistical model with the results and validated that model in a separate set of 36 subjects. RESULTS: The Jackson table supported all our patients regardless of body dimensions without causing an increase in bladder pressure. Blood loss during surgery averaged 1,167±998 mL (mean±1 standard deviation, range 32-3,745). The statistical model was able to account for about 75% of the variability in blood loss using four variables: the number of laminectomies, whether bone was harvested from the iliac crest, experience of the surgeon doing the initial exposure and closure, and distension of the epidural veins. Data on these variables that were collected in the validation study found a multiple correlation coefficient (R(2)) of 0.66 between predicted and observed blood loss. CONCLUSIONS: This is the first study to build a successful multivariable predictive model of blood loss during spine surgery. The Jackson table was effective in supporting patients with different body sizes and shapes, thus removing raised intra-abdominal pressure as an important factor.

Age, gender, and racial differences in incidence and survival in primary CNS lymphoma.

BACKGROUND: Primary central nervous system lymphoma (PCNSL) is a rare subtype of extranodal non-Hodgkin lymphoma that accounts for ~4% of newly diagnosed central nervous system (CNS) tumours. The objective of this study was to analyse the epidemiology, incidence, and outcome of these rare tumours. METHODS: Primary brain and CNS lymphoma cases were identified from the Surveillance, Epidemiology, and End Results (SEER) research data sets for the years 1980-2008 for analysis of trends in incidence and survival. SEER(*)Stat v. 7.0.4 software was used to analyse the data. RESULTS: The overall incidence rate of PCNSL was 0.47 per 100,000 person-years. The incidence was significantly higher in males compared with females, blacks aged 0-49 years at diagnosis compared with whites, and whites aged 50 years and older at diagnosis compared with blacks. After a significant decline in incidence between 1995 and 1999, incidence rates rose slightly; those aged 75+ years at diagnosis had the most dramatic increase in incidence rates over time. Five-year survival rates were significantly higher in whites compared with blacks aged 0-49 years at diagnosis, but was primarily driven by white women aged 0-49 years. CONCLUSION: There is an increase in incidence of PCNSL in the elderly, and elderly blacks have lower incidence compared with white population. Survival remains poor and is negatively dominated by factors associated with HIV infection and advanced age.

A novel technique for post-mastectomy breast irradiation utilising non-coplanar intensity-modulated radiation therapy.

The aim of this study was to investigate if non-coplanar intensity-modulated radiation therapy (IMRT) in the post-mastectomy setting can reduce the dose to normal structures and improve target coverage. We compared this IMRT technique with a standard partial wide tangential (PWT) plan and a five-field (5F) photon-electron plan. 10 patients who underwent left-sided mastectomy were planned to 50.4 Gy using either (1) PWT to cover the internal mammary (IM) nodes and supraclavicular fields, (2) 5F comprising standard tangents, supraclavicular fields and an electron field for the IM nodes or (3) IMRT. The planning target volume (PTV) included the left chest wall, supraclavicular, axillary and IM lymph nodes. No beams were directed at the right lung, right breast or heart. Mean dose-volume histograms were constructed by combining the dose-volume histogram data from all 10 patients. The mean PTV to receive 95% of the dose (V95%) was improved with the IMRT plan to 94.2% from 91.4% (p = 0.04) with the PWT plan and from 87.7% (p = 0.012) with the 5F plan. The mean V110% of the PTV was improved to 3.6% for the IMRT plan from 16.8% (p = 0.038) for the PWT plan and from 51.8% (p = 0.001) for the 5F plan. The mean fraction volume receiving 30 Gy (v30Gy) of the heart was improved with the IMRT plan to 2.3% from 7.5% (p = 0.01) for the PWT plan and 4.9% (p = 0.02) for the 5F plan. In conclusion, non-coplanar IMRT results in improved coverage of the PTV and a lower heart dose when compared with a 5F or PWT plan.

Biomarkers of oxidative stress and DNA damage in agricultural workers: a pilot study.

Oxidative stress and DNA damage have been proposed as mechanisms linking pesticide exposure to health effects such as cancer and neurological diseases. A study of pesticide applicators and farmworkers was conducted to examine the relationship between organophosphate pesticide exposure and biomarkers of oxidative stress and DNA damage. Urine samples were analyzed for OP metabolites and 8-hydroxy-2'-deoxyguanosine (8-OH-dG). Lymphocytes were analyzed for oxidative DNA repair activity and DNA damage (Comet assay), and serum was analyzed for lipid peroxides (i.e., malondialdehyde, MDA). Cellular damage in agricultural workers was validated using lymphocyte cell cultures. Urinary OP metabolites were significantly higher in farmworkers and applicators (p<0.001) when compared to controls. 8-OH-dG levels were 8.5 times and 2.3 times higher in farmworkers or applicators (respectively) than in controls. Serum MDA levels were 4.9 times and 24 times higher in farmworkers or applicators (respectively) than in controls. DNA damage (Comet assay) and oxidative DNA repair were significantly greater in lymphocytes from applicators and farmworkers when compared with controls. Markers of oxidative stress (i.e., increased reactive oxygen species and reduced glutathione levels) and DNA damage were also observed in lymphocyte cell cultures treated with an OP. The findings from these in vivo and in vitro studies indicate that organophosphate pesticides induce oxidative stress and DNA damage in agricultural workers. These biomarkers may be useful for increasing our understanding of the link between pesticides and a number of health effects.

Malignant ovarian mixed germ cell tumour: a rare combination.

Ovarian germ cell tumours are very rare and affect mainly young girls and women. Due to this, the conservation of reproductive potential is of great concern. One of the most remarkable advances in oncology is in the treatment of malignant ovarian germ cell tumours. Two histological groups are distinguished: dygerminomas, equivalent to testicular seminomas, and non-dysgerminomatous tumours. We report a case of a 30-year-old nulliparous woman who presented with persistent per vaginal bleeding and was found to have a malignant mixed germ cell tumour comprising of both embryonal carcinoma and choriocarcinoma.

Stem cell transplantation eliminates alloantibody in a highly sensitized patient.

Highly sensitized patients are forced to stay on transplant waiting lists for many years and ultimately may never find a donor. Peripheral blood stem cell (PBSC) transplantation may provide a strategy to decrease host alloreactivity through the production of a chimeric state. We investigated alloreactivity and chimerism in a highly sensitized 40-year-old patient with sickle cell disease who underwent a nonradiation based conditioning regimen consisting of fludarabine, ATG, and high dose melphalan, for allogeneic stem cell transplant. Host monocytes and lymphocytes became donor in origin by day 14. PRA, initially 100% pretransplant, fell to 0 by day 263. Anti-red blood cells antibody became undetectable by day 152. The use of a new nonradiation-based conditioning regimen enabled successful engraftment of allogeneic donor PBSCs and the elimination of alloantibody. As new less toxic conditioning regimens are developed, PBSC transplantation might provide a new solution to allosensitization.

Purified poloxamer 188 for treatment of acute vaso-occlusive crisis of sickle cell disease: A randomized controlled trial.

CONTEXT: Sickle cell disease (SCD) can cause severe painful episodes that are often thought to be caused by vaso-occlusion. The current therapy for these uncomplicated painful episodes includes hydration, oxygen, and analgesics. Purified poloxamer 188 may increase tissue oxygenation and thereby reduce inflammation, pain, and the overall duration of such painful episodes in patients with SCD. OBJECTIVE: To compare the duration of painful episodes in patients with SCD treated with purified poloxamer 188 to that of similar episodes experienced by patients who receive a placebo. DESIGN AND SETTING: Randomized, double-blind, placebo-controlled, intention-to-treat trial conducted between March 1998 and October 1999 in 40 medical centers in the United States. PARTICIPANTS: Two hundred fifty-five patients with SCD (aged 9-53 years) who had a painful episode sufficiently severe to require hospitalization and narcotic analgesics. INTERVENTION: Patients were randomly assigned to receive an intravenous infusion of purified poloxamer 188, 100 mg/kg for 1 hour followed by 30 mg/kg per hour for 47 hours (n = 127), or a matching volume of saline placebo (n = 128). MAIN OUTCOME MEASURE: Duration of the painful episode, from randomization to crisis resolution. RESULTS: Mean (SD) duration of the painful episodes was 141 (42) hours in the placebo group compared with 133 (41) hours in those treated with purified poloxamer 188, a 9-hour reduction (P =.04). Subset analyses indicated an even more pronounced purified poloxamer 188 effect in children aged 15 years or younger (21 hours; P =.01) and in patients who were receiving hydroxyurea (16 hours; P =.02). Finally, the proportion of patients achieving crisis resolution was increased by purified poloxamer 188 (65/126 [52%] vs 45/123 [37%]; P =.02). Similar results were observed in children aged 15 years or younger (22/37 [60%] vs 10/36 [28%]; P =.009) and in patients who were also receiving hydroxyurea (12/26 [46%] vs 4/28 [14%]; P =.02). CONCLUSIONS: A decrease in the duration of painful episodes and an increase in the proportion of patients who achieved resolution of the symptoms were observed when the purified poloxamer 188-treated patients were compared with the patients receiving placebo. However, the difference between these groups was significant but relatively small. In subgroup analysis, a more significant effect on both parameters was observed in children and in patients who were receiving concomitant hydroxyurea. It is important to confirm both of these observations in further prospective trials.

Short-term sequelae of minor head injury (6 years experience of minor head injury clinic).

PURPOSE: It is known that post-concussive symptoms may persist after mild head injury. However, the majority of those patients are denied follow-up or support. A minor head injury clinic was thus established in North Staffordshire Hospital in 1993 to address these problems. METHODS: Patients 16-65 years old attending hospital with minor head injury were invited to attend the clinic two weeks after presentation. A specialized brain injury nurse and/or assistant clinical psychologist assessed them. Patients with persistent symptoms were invited to a second assessment four weeks later. RESULTS: One thousand two hundred and fifty-five patients were invited for first assessment, the most common cause of head injury was assault (454) followed by road traffic accident (334). Six hundred and sixteen patients did not attend the first assessment; most of non-attendees were those who had been assaulted (281). Six hundred and thirty-nine patients attended, (472) were male, their mean age was 33. Forty-three per cent of them had history of recent alcohol intake. One third had had a previous head injury. Although 391 attendees were in regular employment, 219 patients were unable to return to work 2 weeks after discharge (56%), and 49 people were still off sick 6 weeks after the injury. The most common complaints at both assessments were fatigue, headache, dizziness, irritability, sleep disturbances, poor concentration and poor memory in that order. CONCLUSION: This study shows a significant number of patients with minor head injury still complaining of post concussive symptoms, which may contribute to a delay in return to work. The high incidence of non-attendance among the assaulted victims may indicate that this group needs to be more effectively targeted. Further study to look at the longer-term consequences of minor head injury is required in view of these findings.

Allogeneic stem cell transplantation for sickle cell disease. A study of patients' decisions.

Allogeneic stem cell transplantation is increasingly considered as a curative though risky treatment option for adults with sickle cell disease. Little is known about attitudes of adult patients and their health care providers regarding the risks and benefits of transplantation. A survey of 100 patients and their health care providers was undertaken. Assessment of risk was by a reference gamble paradigm. Comparison was made of the characteristics of those accepting substantial risk vs those not accepting risk, as well as assessment of agreement on risks recommended by health care providers and accepted by patients. Sixty-three of 100 patients were willing to accept some short-term risk of mortality in exchange for the certainty of cure. Fifteen patients were willing to accept more than 35% mortality risk. No differences in patient or disease-related variables were identified between those accepting risk and those not accepting risk. There was no agreement between the recommendations of health care providers and the risk accepted by patients. A substantial proportion of adults with sickle cell disease are interested in curative treatment, at the expense of considerable risk. The decision to accept risk is influenced by individual patient values that cannot be easily quantified and that do not correlate with the assessment of the health care provider. Given the substantial interest in curative therapy, education about and consultation for allogeneic stem cell transplantation in sickle cell patients should be encouraged.

Fludarabine-based conditioning for allogeneic transplantation in adults with sickle cell disease.

Although allogeneic transplantation can be curative for patients with sickle cell disease, the toxicity of conditioning regimens has precluded its use in adults with significant end-organ damage. Newer conditioning regimens have been developed that are less toxic and that may broaden the applicability of allogeneic transplantation in this disorder. We report two adults with end-stage sickle cell disease, who underwent allogeneic transplantation from an HLA-identical sibling donor after conditioning with fludarabine/melphalan and ATG. Both patients had been extensively transfused and one had multiple RBC antibodies. One of the patients also had end-stage renal disease, and was dialysis dependent. Engraftment occurred promptly in both patients. Both achieved 100% donor chimerism and both were free of pain crises after transplant. The first patient died of a respiratory failure related to chronic graft-versus-host disease (GVHD) on day 335 after transplantation. The second patient developed severe gastro-intestinal GVHD and TTP and died on day 147 after transplantation. Conditioning with fludarabine/melphalan and ATG followed by allogeneic stem cell transplantation resulted in prompt and reliable engraftment in adults with end-stage sickle cell disease. The incidence of severe GVHD was unacceptably high and may be related to the ethnicity of the patients or to the inflammatory state associated with pre-existing sickle cell disease.

2-deoxy 5-azacytidine and fetal hemoglobin induction in sickle cell anemia.

Augmentation of the fetal hemoglobin (HbF) levels is of therapeutic benefit in patients with sickle cell anemia. Hydroxyurea (HU), by increasing HbF, lowers rates of pain crisis, episodes of acute chest syndrome, and requirements for blood transfusions. For patients with no HbF elevation after HU treatment, augmentation of HbF levels by 5-aza-2'-deoxycytidine (5-aza-CdR, decitabine) could serve as an alternate mode of treatment. Eight adult patients participated in a dose-escalating phase I/II study with 5-aza-CdR at doses ranging from 0.15 to 0.30 mg/kg given 5 days a week for 2 weeks. HbF, F cell, F/F cell, gamma-globin synthesis ratio, complete blood count, and chemistry were measured. The average gamma-globin synthesis relative to non-alpha-globin synthesis prior to therapy was 3.19% +/- 1.43% and increased to 13.66% +/- 4.35% after treatment. HbF increased from 3.55% +/- 2.47% to 13.45% +/- 3.69%. F cells increased from 21% +/- 14.8% to 55% +/- 13.5% and HbF/F cell increased from 17% to 24%. In the HU nonresponders HbF levels increased from 2.28% +/- 1.61% to 2.6% +/- 2.15% on HU, whereas on 5-aza-CdR HbF increased to 12.70% +/- 1.81%. Total hemoglobin increased by 1 g/dL in 6 of 8 patients with only minor reversible toxicities, and all patients tolerated the drug. Maximum HbF was attained within 4 weeks of treatment and persisted for 2 weeks before falling below 90% of the maximum. Therefore 5-aza-CdR could be effective in increasing HbF in patients with sickle cell anemia who failed to increase HbF with HU. Demonstration of sustained F levels with additional treatment cycles without toxicity is currently being performed.