Links across disabilities: unveiling associations between functional domains.

BACKGROUND: Persons with disabilities experience higher risks of mortality as well as poorer health as compared to the general population. The aim of this study is to estimate the correlations between functional difficulties across several domains in six countries. METHODS: National census data with questions on disability from six countries (Mauritius, Morocco, Senegal, Myanmar, Vietnam, and Uruguay) was used in this study. We performed logistic regressions to assess the extent to which having a functional difficulty in one domain is correlated with having a functional difficulty in each of the other domains and report weighted odds ratios (ORs) overall and within age-groups ('18-44' years and '45+' years). Models adjust for age, sex, and location (rural or urban). Sensitivity analyses around different choices of predictors and response variables were conducted. FINDINGS: For all countries, reporting a functional difficulty in one domain was consistently and significantly positively correlated with reporting a functional difficulty in other domains (overall) and for each of the two age-groups considered - '18-44' years and '45+' years. All ORs were greater than one. Cognition, mobility, and hearing were the domains that were the most correlated ones with other domains. The highest pairwise correlations were for i/ hearing and cognition; ii/ mobility and cognition. Results were robust to changing the severity thresholds for functional difficulties. Across countries, Uruguay, the only high-income country among the six countries under study, had the lowest correlations between functional domains. CONCLUSIONS: There are consistent positive associations in the experience of functional difficulties in various domains in the six countries under study. Such correlations may reflect barriers to social services including healthcare services and resources (e.g. assistive devices) that may lead to an avoidable deterioration of functioning across domains. Further research is needed on the trajectories of functional difficulties and on structural barriers that people with functional difficulties may experience in their communities and in healthcare settings in particular. This is important as some functional difficulties may be preventable.

Current Trends in Compensation for Fellowship in Minimally Invasive Gynecologic Surgery Graduates: A 6-Year Follow-Up.

STUDY OBJECTIVE: To present updated information regarding compensation patterns for Fellowship in Minimally Invasive Gynecologic Surgery (FMIGS)-graduated physicians in the United States beginning practice during the last 10 years, focusing on the variables that have an impact on differences in salary, including gender, fellowship duration, geographic region, practice setting, and practice mix. DESIGN: An online survey was sent to FMIGS graduates between March 15, 2019 and April 12, 2019. Information on physicians' demographics, compensation (on the basis of location, practice model, productivity benchmarks, academic rank, and years in practice), and attitudes toward fairness in compensation was collected. SETTING: Online survey. PARTICIPANTS: FMIGS graduates practicing in the United States. INTERVENTION: E-mail survey. MEASUREMENTS AND MAIN RESULTS: We surveyed 298 US FMIGS surgeons who had graduated during the last 10 years (2009-2018). The response rate was 48.7%. Most of the respondents were women (69%). Most of the graduates (84.8%) completed 2- or 3-year fellowship programs. After adjustment for inflation, the median starting salary for the first postfellowship job was $252 074 ($223 986-$279 983) (Table 1). The median time spent in the first job was 2.6 years, and the median total salary at the current year rose to $278 379.4 ($241 437-$350 976). The median salary for respondents entering a second postfellowship job started at $280 945 ($261 409-$329 603). Significantly lower compensation was reported for female FMIGS graduates in their initial postfellowship jobs and was consistently lower than for that of men over time. Most FMIGS graduates (59.7%) reported feeling inadequately compensated for their level of specialization. CONCLUSION: A trend toward higher self-reported salaries is noted for FMIGS graduates in recent years, with significant differences in compensation between men and women. Among obstetrics and gynecology subspecialists, FMIGS graduates earn significantly less than other fellowship-trained physicians, with median salaries that are lower than those of generalist obstetrics and gynecology physicians.

Comparison of Industry-Leading Energy Devices for Use in Gynecologic Laparoscopy: Articulating ENSEAL versus LigaSure Energy Devices.

STUDY OBJECTIVE: To compare 2 laparoscopic bipolar electrosurgical devices used in total laparoscopic hysterectomy (TLH). An articulating advanced bipolar device (ENSEAL G2; Ethicon Endo-Surgery, Cincinnati, OH) and an electrothermal bipolar vessel sealer (LigaSure; Medtronic, Minneapolis, MN) were analyzed for differences in surgeon perception of ease of instrument use and workload using the NASA Raw Task Load Index (RTLX) scale. A second objective was to examine differences in operative time, estimated blood loss (EBL), and perioperative complication rates between the 2 devices. DESIGN: Single-institution, single-blinded, randomized controlled trial (Canadian Task Force classification I). SETTING: Division of Minimally Invasive Gynecologic Surgery in a university hospital. PATIENTS: Eligibility required planned TLH, over age 18 years, and able to give informed consent; exclusions were stage III or IV endometriosis, known gynecologic malignancy, and early decision for conversion to laparotomy. One hundred seventy-eight patients screened, 142 enrolled, 2 withdrew, and 140 completed the study. Patients were followed 1 month postoperatively. INTERVENTIONS: Preoperative randomization to articulating advanced bipolar device or electrothermal bipolar vessel sealer to be used during TLH. MEASUREMENTS AND MAIN RESULTS: At the end of each hysterectomy the primary surgeon completed an ergonomic assessment tool, the RTLX. Results were analyzed to detect differences in workload between the 2 devices. For each case the time to ligation of the bilateral uterine arteries, EBL, and complications (including device failure, blood transfusion, or other injury) were recorded. Statistical analysis was performed using the t test for normally distributed data, χ2 test for categorical data, and Mann-Whitney U-test for nonparametric data. There were no differences in age, body mass index, parity, prior surgery, uterine weight, race, indication, pathology, and comorbidities between the 2 groups. A statistically significant increase in RTLX scores (p < .0001), device failures (p = .0031), and time to ligation of bilateral uterine arteries (p = .0281) was noted in the articulating device group. No significant differences in EBL or complication rates were noted between the groups. CONCLUSIONS: The articulating advanced bipolar device was shown to have a statistically significant increase in surgeon-perceived workload and rate of device failure when used in TLH; however, clinical and surgical outcomes were equivalent.

Identifying the Rate-Limiting Step in Total Laparoscopic Hysterectomy in a Training Hospital.

STUDY OBJECTIVE: To identify the lengthiest step of total laparoscopic hysterectomy (TLH) in a teaching hospital and to determine which clinical factors affect the duration of this step. SETTING: The University of Louisville Hospital. DESIGN: Single institution retrospective case series. METHODS AND MAIN RESULTS: This is a retrospective chart and video review that included 135 benign, elective TLHs performed at The University of Louisville. TLH was divided into 5 steps: (1) insertion of laparoscopic ports and adhesiolysis to restore normal anatomy; (2) identification of the ureter and resection of adnexal structures to transection of the round ligament; (3) transection of the round ligament to transection of the uterine artery; (4) lateralization of the uterine vessel pedicle to completion of colpotomy; and (5) completion of vaginal cuff closure. The random intercept and slope model was used to identify the lengthiest step of TLH, and the backward elimination procedure was used to evaluate which clinical factors affected this step. Mean ± SD total length of TLH was 81 ± 30 min. The lengthiest step was colpotomy, with a mean duration of 24 ± 13 min. Uterine weight significantly increased the length of time required for colpotomy (p = .001). The primary energy source (ultrasonic scalpel vs monopolar hook) used to perform colpotomy did not influence the length of time (p = .539 vs p = .583). Uterine weight (p < .001) and adhesiolysis (p = .003) significantly increased the total time of TLH. CONCLUSIONS: At a teaching institution where surgeries are performed by residents and fellows, colpotomy is the lengthiest step of TLH and is influenced by uterine weight. This finding may reflect the training levels of the surgeons performing these cases and the learning curve associated with a challenging surgical skill. Further research should focus on simulation models and/or tools for colpotomy that may result in greater efficiency in the operating room.

Management of Acute Pulmonary Embolism: Consensus Statement for Indian Patients.

Pulmonary embolism (PE) is an important cause of morbidity and mortality among hospitalized patients. Although the exact epidemiology of PE is not known in India, Some of the studies show that more frequently it is missed and not managed appropriately leading to significant cardiovascular morbidity and mortality. Justification and purpose: Indian guidelines for the diagnosis and treatment of acute PE are not yet formulated. The objective of this consensus statement is to propose a diagnostic and management approach for acute PE in India. PROCESS: A working group of 15 experts in the management of acute PE (cardiologists, pulmonologist, haematologist, emergency specialist and intensivists). This consensus statement makes recommendations for diagnosis and management for PE based on literature review, including Indian data.

2013 consensus statement for early reperfusion and pharmaco-invasive approach in patients presenting with chest pain diagnosed as STEMI (ST elevation myocardial infarction) in an Indian setting.

UNLABELLED: In India, the prevalence of ST elevation myocardial infarction (STEMI) is rising exponentially leading to cardiovascular morbidity and mortality. Despite advancement in reperfusion therapy (pharmacologic and interventional), the overall utilization, system of care and timely reperfusion remains suboptimal. JUSTIFICATION AND PURPOSE: Alarming treatment delays exist in patients presenting with chest pain observed in real-world and published evidences. Time to diagnose STEMI and initiation of reperfusion therapy at various first medical contacts in India is variable mandating immediate attention. We intend to provide evidence based explicit recommendations for practicing clinicians about time-dependent early management and the concept of pharmaco-invasive (PI) approach, contextualized to the situation in India. PROCESS: Pre-prepared guidance document by expert steering committee was discussed and commented by over 150 experts representing from 16 states in India at regional level. The moderators of these meetings arrived at a consensus on the evaluation and management of STEMI patients by PI approach to improve clinical outcomes. RECOMMENDATIONS: In addition to patient awareness and education for early symptom identification, education is required for general practitioners and physicians/intensivists to implement early time dependent STEMI management. Percutaneous Coronary Intervention (PCI) is the gold standard, yet it remains inaccessible to majority of patients, hence early reperfusion by initial use of fibrinolytics is recommended followed by coronary intervention. Fibrinolytics are easily available, economical and evaluated in several clinical studies and hence we recommend a PI approach (early fibrinolysis followed by PCI 3-24 hours later). We recommend a time guided 'Protocol/Plan of Action' for early fibrinolysis and implementing a PI approach at the level of general practitioners, non-PCI hospitals/nursing homes with intensive care facility and in PCI capable centers. For STEMI patients with symptom duration < 6 hours, we suggest administration of fibrinolytics either tenecteplase (Grade1A), reteplase (Grade1B), alteplase (Grade1C) or streptokinase (Grade 2B) alongside contemporary adjunctive medical therapy for PI approach. The aim of this Consensus Statement is * To provide explicit recommendations for practicing clinicians about the early management of STEMI and concept of pharmaco-invasive approach * To provide recommendations based on the best available evidences, contextualized to the situation in India. It must be recognized that even when randomized clinical trials have been undertaken, treatment options may be limited by resources. The Cardiocare STEMI experts realize that the recommended diagnostic examinations and treatment options may not be available or affordable in all parts of India. Cost-effectiveness is becoming an increasingly important issue when deciding upon therapeutic strategies. As always with guidelines/consensus statement, they are not prescriptive. Clinical scenario and patients vary so much from one another that individual care is paramount, and there is still an important place for clinical judgment, experience, and common sense. The mandate of the Cardiocare STEMI expert consensus is to recommend evidence-based standards of care, related targets and strategies for implementation of standards in the management of STEMI. CONTEXT AND USE: This document should be taken as consensus recommendations by qualified experts, not as rigid rules. It comprises of published evidence and may not cover every eventuality; new evidence is published every day. Furthermore, this should not be used as a legal resource, as the general nature cannot provide individualized guidance for all patients under all clinical circumstances.

Role of omega-3 ethyl ester concentrate in reducing sudden cardiac death following myocardial infarction and in management of hypertriglyceridemia: an Indian consensus statement.

INTRODUCTION: Sudden cardiac death (SCD) is the most lethal manifestation of heart disease. In an Indian study the SCDs contribute about 10% of the total mortality and SCD post ST elevation myocardial infarction (MI) constitutes for about half of total deaths. OBJECTIVE: Given the limitations of existing therapy there is a need for an effective, easy to use, broadly applicable and affordable intervention to prevent SCD post MI. Leading cardiologists from all over India came together to discuss the potential role of n-3 acid ethyl esters (90%) of eicosapentaenoic acid (EPA) 460 mg & docosahexaenoic acid (DHA) 380 mg in the management of post MI patients and those with hypertriglyceridemia. RECOMMENDATIONS: Highly purified & concentrated omega-3 ethyl esters (90%) of EPA (460 mg) & DHA (380 mg) has clinically proven benefits in improving post MI outcomes (significant 15% risk reduction for all-cause mortality, 20% risk reduction for CVD and 45% risk reduction in SCD in GISSI-Prevenzione trial) and in reducing hypertriglyceridemia, and hence, represent an interesting option adding to the treatment armamentarium in the secondary prevention after MI based on its anti-arrhythmogenic effects and also in reducing hypertriglyceridemia.

Effect of Supplemental Parenteral Nutrition Versus Enteral Nutrition Alone on Clinical Outcomes in Critically Ill Adult Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Enteral nutrition (EN) is considered the first feeding route for critically ill patients. However, adverse effects such as gastrointestinal complications limit its optimal provision, leading to inadequate energy and protein intake. We compared the clinical outcomes of supplemental parenteral nutrition added to EN (SPN + EN) and EN alone in critically ill adults. Electronic databases restricted to full-text randomized controlled trials available in the English language and published from January 1990 to January 2019 were searched. The risk of bias was evaluated using the Jadad scale, and the meta-analysis was conducted using the MedCalc software. A total of five studies were eligible for inclusion in the systematic review and meta-analysis. Compared to EN alone, SPN + EN decreased the risk of nosocomial infections (relative risk (RR) = 0.733, p = 0.032) and intensive care unit (ICU) mortality (RR = 0.569, p = 0.030). No significant differences were observed between SPN + EN and EN in the length of hospital stay, hospital mortality, length of ICU stay, and duration of mechanical ventilation. In conclusion, when enteral feeding fails to fulfill the energy requirements in critically ill adult patients, SPN may be beneficial as it helps in decreasing nosocomial infections and ICU mortality, in addition to increasing energy and protein intakes with no negative effects on other clinical outcomes.

Consensus and development of document for management of stabilized acute decompensated heart failure with reduced ejection fraction in India.

AIM: Ensuring adherence to guideline-directed medical therapy (GDMT) is an effective strategy to reduce mortality and readmission rates for heart failure (HF). Use of a checklist is one of the best tools to ensure GDMT. The aim was to develop a consensus document with a robust checklist for stabilized acute decompensated HF patients with reduced ejection fraction. While there are multiple checklists available, an India-specific checklist that is easy to fill and validated by regional and national subject matter experts (SMEs) is required. METHODOLOGY: A total of 25 Cardiology SMEs who consented to participate from India discussed data from literature, current evidence, international guidelines and practical experiences in two national and four regional meetings. RESULTS: Recommendations included HF management, treatment optimization, and patient education. The checklist should be filled at four time points- (a) transition from intensive care unit to ward, (b) at discharge, (c) 1st follow-up and (d) subsequent follow-up. The checklist is the responsibility of the consultant or the treating physician which can be delegated to a junior resident or a trained HF nurse. CONCLUSION: This checklist will ensure GDMT, simplify transition of care and can be used by all doctors across India. Institutions, associations, and societies should recommend this checklist for adaptability in public and private hospital. Hospital administrations should roll out policy for adoption of checklist by ensuring patient files have the checklist at the time of discharge and encourage practice of filling it diligently during follow-up visits.

Pre-Transplant Marital Status and Hematopoietic Cell Transplantation Outcomes

Background: Evidence about the impact of marital status before hematopoietic cell transplantation (hct) on outcomes after hct is conflicting. Methods: We identified patients 40 years of age and older within the Center for International Blood and Marrow Transplant Research registry who underwent hct between January 2008 and December 2015. Marital status before hct was declared as one of: married or living with a partner, single (never married), separated or divorced, and widowed. We performed a multivariable analysis to determine the association of marital status with outcomes after hct. Results: We identified 10,226 allogeneic and 5714 autologous hct cases with, respectively, a median follow-up of 37 months (range: 1-102 months) and 40 months (range: 1-106 months). No association between marital status and overall survival was observed in either the allogeneic (p = 0.58) or autologous (p = 0.17) setting. However, marital status was associated with grades 2-4 acute graft-versus-host disease (gvhd), p < 0.001, and chronic gvhd, p = 0.04. The risk of grades 2-4 acute gvhd was increased in separated compared with married patients [hazard ratio (hr): 1.13; 95% confidence interval (ci): 1.03 to 1.24], and single patients had a reduced risk of grades 2-4 acute gvhd (hr: 0.87; 95% ci: 0.77 to 0.98). The risk of chronic gvhd was lower in widowed compared with married patients (hr: 0.82; 95% ci: 0.67 to 0.99). Conclusions: Overall survival after hct is not influenced by marital status, but associations were evident between marital status and grades 2-4 acute and chronic gvhd. To better appreciate the effects of marital status and social support, future research should consider using validated scales to measure social support and patient and caregiver reports of caregiver commitment, and to assess health-related quality of life together with health care utilization.

Therapeutic experience of ticagrelor in Indian patients with acute coronary syndrome: A non-interventional, prospective, and observational study.

OBJECTIVE: This observational study was designed to understand the usage pattern of ticagrelor in real-life clinical practice among a large number of acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG), or medical management (MM). The study also recorded clinical events, i.e., bleeding, dyspnea, and cardiovascular (CV) events, reported by the investigator during the follow-up period. METHODS: The ACS patients aged ≥18 years hospitalized for ACS and were prescribed ticagrelor upon discharge or ≤1 month and patients who underwent PCI, CABG, or MM for ACS were enrolled. The subjects were followed up for a period of up to 12 months. The data were collected on a case report form. RESULT: The study recruited 2997 subjects from 49 sites in India. Approximately half of the ACS subjects had ST segment elevation myocardial infarction (48.9%), and PCI was used as management in 92.4% subjects. The mean (±SD) duration of use of ticagrelor was 314 (±110.2) days over a period of 12 months. Of 136 subjects (4.5%) who experienced any clinical events, CV deaths were reported in 20 (0.7%), myocardial infraction in 19 (0.6) subjects and ischemic stroke in 23 (0.8%) subjects, and severe dyspnea was reported in 68 (2.2%) subjects. Out of 33 bleeding cases, 25 (0.8%) subjects had thrombolysis in myocardial infarction (TIMI) minimal, seven (0.2%) had TIMI minor, and one TIMI major. Platelet inhibition and patient outcomes (PLATO) major was reported in two subjects and CABG bleed in one subject. The incidence of PLATO defined major and minimal bleeding were lower in subjects undergoing fibrinolysis than overall population. CONCLUSION: Ticagrelor has been used across ACS types and in different management strategies in real world settings in India. The incidence of clinical events was lower as compared with data in literature. ClinicalTrials.gov Identifier: NCT02408224.

Estrus induction and fertility response following different treatment protocols in Murrah buffaloes under field conditions.

AIM: The aim of this study was to evaluate the efficacy of three different treatment protocols for estrus induction and conception rate in postpartum anestrus buffaloes during breeding season under field conditions. MATERIALS AND METHODS: The 47 postpartum anestrus buffaloes of the 2nd to 6th parity were divided into three groups. Group 1 (n=16): Buffaloes received cosynch treatment, that is, buserelin acetate 10 µg on day 0 and 9, cloprostenol 500 µg on day 7 followed by fixed-time artificial insemination (FTAI) at the time of second buserelin acetate and 24 h later. Group 2 (n=15): Buffaloes received norgestomet ear implant subcutaneously for 9 days, estradiol benzoate 2 mg on the day of implant insertion (day 0), pregnant mare serum gonadotropin (PMSG) 400 IU and cloprostenol 500 µg on day 9 followed by AI at 48 and 72 h after implant removal. Group 3 (Cosynch-plus, n=16): Buffaloes received Cosynch protocol as per Group 1 except an additional injection of PMSG 400 IU (i.m.) was given 3 days before the start of protocol and FTAI done at the same time of Group 1. Pregnancy diagnosis was performed after 45 days of AI. RESULTS: The estrus induction response following the treatment was 81.3%, 100%, and 93.7% in Group 1, 2, and 3, respectively. The buffaloes of Group 1, 2, and 3 expressed intense (38.4%, 60% and 46.6%, respectively) and moderate estrus (46.1%, 26.6%, and 40%, respectively). The conception rates in Group 1, 2, and 3, at FTAI and overall including subsequent estrus were 37.5% and 62.5%, 53.3%, and 66.6%, 56.3%, and 75%, respectively. CONCLUSION: All the three treatment protocols can be effectively used for induction of estrus with acceptable conception rate in postpartum anestrus buffaloes during breeding season under field conditions. However, Cosynch-plus (similar to Cosynch protocol except addition of PMSG, 400 IU 3 days before the start of first buserelin acetate administration) protocol results comparatively better pregnancy rate.

Adnexal masses requiring reoperation in women with previous hysterectomy with or without adnexectomy.

OBJECTIVES: To characterize the etiologies of adnexal masses requiring reoperation in women with prior hysterectomy and to compare incidence and pathology of these masses based upon whether total, partial or no adnexectomy was performed at time of hysterectomy. In addition, the average time interval between hysterectomy and reoperation for a pelvic mass is ascertained. STUDY DESIGN: A single-institution, retrospective review spanning 10 years. Using pertinent ICD-9 and CPT codes, women with a history of hysterectomy who underwent a subsequent surgery for an adnexal or pelvic mass were identified. RESULTS: Over ten years, 250 women returned for gynecologic surgery due to a pelvic mass after prior hysterectomy. Most had undergone hysterectomy only (76%). 64.8% of these women had masses of ovarian origin, 12.4% were tubal in origin, 20% of masses involved both the ovary and tube and a small proportion arose from non-gynecologic processes. 18% of these women had a malignancy; 80% were ovarian and 6.7% originated from the fallopian tube. Patients having had a prior hysterectomy and bilateral salpingectomy returned soonest (p<0.0001) and patients with malignant masses returned after the longest time intervals (HR 0.41, p<0.0001). CONCLUSIONS: The majority of adnexal masses requiring reoperation after hysterectomy are gynecologic in origin, benign, and arise from the ovary. Women returning with malignant masses after hysterectomy present after longer time intervals.

Spatial regulation of DELTA expression mediates NOTCH signalling for segmentation of Drosophila legs.

The Notch (N) signalling pathway is recruited for segregation of cell fates in a number of Drosophila tissue types. We show here that N dependent segmentation of Drosophila legs is regulated by a dynamic pattern of expression of its ligand, DELTA (DL). During third larval instar and early stages of pupation, high levels of DL expression is seen in stripes of cells in the leg imaginal discs which later form the proximal borders of leg joints. These domains also displayed heightened Dl enhancer activity. During subsequent stages of pupation, following segmentation of the leg primordium, DL expression becomes uniform throughout these segments barring the joints. We further show that regulatory Dl mutations or mis-expression of DL abolish leg segmentation. Domains of N signalling for segmentation of legs of flies are thus set up by a stringent spatial regulation of expression of its ligand at the segment border. Further, a comparable role of DL in antennal development reveals a common paradigm of DL-N signalling for segmentation of appendages in flies.

Reasons why patients fail screening in Indian breast cancer trials.

INTRODUCTION: An increased number of screen failure patients in a clinical trial increases time and cost required for the recruitment. Assessment of reasons for screen failure can help reduce screen failure rates and improve recruitment. MATERIALS AND METHODS: We collected retrospective data of human epidermal growth factor receptor (HER2) positive Indian breast cancer patients, who failed screening for phase 3 clinical trials and ascertained their reasons for screen failure from screening logs. Statistical comparison was done to ascertain if there are any differences between private and public sites. RESULTS: Of 727 patients screened at 14 sites, 408 (56.1%) failed screening. The data on the specific reasons for screen failures was not available at one of the public sites (38 screen failures out of 83 screened patients). Hence, after excluding that site, further analysis is based on 644 patients, of which 370 failed screening. Of these, 296 (80%) screen failure patients did not meet selection criteria. The majority -266 were HER2 negative. Among logistical issues, 39 patients had inadequate breast tissue sample. Sixteen patients withdrew their consent at private sites as compared to six at public sites. The difference between private and public sites for the above three reasons was statistically significant. CONCLUSION: Use of prescreening logs to reduce the number of patients not meeting selection criteria and protocol logistics, and patient counseling to reduce consent withdrawals could be used to reduce screen failure rate.

Development and characterization of Haemophilus influenzae type b conjugate vaccine prepared using different polysaccharide chain lengths.

Capsular polysaccharide conjugates of Haemophilus influenzae type b (Hib) are important components of several mono- or multi-valent childhood vaccines. However, their access to the most needy people is limited due to their high cost. As a step towards developing a cost effective and more immunogenic Hib conjugate vaccine, we present a method for the preparation of Hib capsular polysaccharide (PRP)-tetanus toxoid (TT) conjugates using optimized PRP chain length and conjugation conditions. Reactive aldehyde groups were introduced into the polysaccharides by controlled periodate oxidation of the native polysaccharide, which were subsequently covalently linked to hydrazide derivatized tetanus toxoid by means of reductive amination. Native polysaccharides were reduced to average 100 or 50kDa polysaccharide and 10kDa oligosaccharides in a controlled manner. Various conjugates were prepared using Hib polysaccharide and oligosaccharide yielding conjugates with polysaccharide to protein ratios in the range of 0.25-0.5 (w/w) and free saccharide levels of less than 10%. Immunization of Sprague Dawley rats with the conjugates elicited specific antibodies to PRP. The low molecular weight PRP-TT conjugates were found to be more immunogenic as compared to their high molecular weight counterparts and the PRP-TT reference vaccine.

Nitrate cross-tolerance: effect of sublingual isosorbide dinitrate and nitroglycerin during sustained nitrate therapy.

In a randomized, single-blind, crossover study, 10 patients with stable, exercise-induced angina pectoris were studied during sustained therapy with oral isosorbide dinitrate (ISDN). Circulatory changes and exercise performance were evaluated before and 6 hours after therapy with oral ISDN. One-half hour after this therapy, sublingual ISDN or nitroglycerin (NTG) was administered and exercise testing repeated. Treadmill walking time 6 hours after oral ISDN was similar to the control value. Subsequent administration of sublingual ISDN improved walking time from 429 +/- 156 to 513 +/- 166 seconds (p less than 0.005), whereas after NTG improved from 411 +/- 159 to 480 +/- 158 second (p less than 0.005). The improvement in walking time with ISDN (23%) and NTG (18%) and the absolute walking times were not different. The standing systolic blood pressure decreased from 124 +/- 23 to 112 +/- 22 mm Hg (p less than 0.02) after therapy with sublingual ISDN and 122 +/- 23 to 110 +/- 24 mm Hg (p less than 0.005) after administration of NTG. This study demonstrates that (1) during sustained ISDN therapy, walking time returns to control values by 6 hours; (2) administration of either sublingual ISDN or NTG results in significant circulatory changes and improvement in walking time; and (3) the changes in circulatory and exercise variables after administration of NTG in patients taking sustained ISDN therapy cannot be taken as evidence of an absence of cross-tolerance between these agents.

Marked ST elevation after successful PTCA for acute myocardial infarction.

Prompt reperfusion of acutely ischemic myocardium appears to be the rational way of reversing ischemic injury and limiting the extent of eventual necrosis. Recent advances in emergency coronary bypass surgery, percutaneous transluminal coronary angioplasty (PTCA) and thrombolytic therapy have provided methods for effective treatment of acute myocardial infarction. However, several observations indicate this issue is more complex. Although blood flow must be restored to ischemic myocardium if it is to survive, animal experiments suggest potential deleterious effects associated with this reperfusion. These deleterious effects may be associated with unstable ST segments reported early after acute infarct thrombolysis. Though recurrent coronary occlusion cannot be excluded, reperfusion injury in this setting of coronary artery patency must be considered. This case illustrates this proposed reperfusion injury reflected as "tombstone" ST segment elevation in a patient following successful acute infarct PTCA.

Right coronary arteriocameral fistula into the right ventricle. An inspiratory accentuation of continuous murmur: a case report.

A case of a right coronary artery fistula into the right ventricle is presented. The clinical diagnosis was based on the presence of a continuous murmur best heard in the epigastrium, which increased in intensity and duration on inspiration . This report stresses the importance of this sign in the localization of the arterial fistula to the right ventricle. To the best of our knowledge, there are no previous reports of this sign.

Coronary artery spasm in the transplanted human heart. A case report.

This report describes a patient manifesting spontaneous and catheter-induced coronary artery spasm in a transplanted, denervated heart. This diagnosis should be considered in patients undergoing posttransplant coronary angiography. Intracoronary nitroglycerin should routinely be administered prior to coronary artery injections during posttransplant angiography.