Therapeutic biliary endoscopy.
Therapeutic biliary endoscopy is continuing to evolve; some small but important developments were seen during the last year. Competing techniques are continuing to develop.
Biliary Tract Diseases↗
Biomedical subjects
S Sherman
Publications and source records attributed to S Sherman.
Endoscopic drainage of malignant hilar obstruction: is one biliary stent enough or should we work to place two?
Explore the source record for details and available documents.
Cholestasis↗
Roux-en-Y internal drainage is the best surgical option to treat patients with disconnected duct syndrome after severe acute pancreatitis.
BACKGROUND: Roux-en-Y (RNY) internal drainage has been our primary surgical strategy to definitively treat disconnected duct syndrome in patients after severe acute pancreatitis (SAP). This study compares the results of internal drainage with the results of distal pancreatectomy-splenectomy (DPS) performed in a contemporaneous group of patients. METHODS: For 5 years (June 1995 to June 2000), 27 consecutive patients with disconnected duct syndrome after SAP were identified: 13 treated with internal drainage and 14 with DPS. Fistula characteristics, operative management, and clinical outcome were analyzed. Comparisons between groups were made with the Student t test and Fisher exact test, with statistical significance defined as P <.05. RESULTS: Age, sex, etiology of pancreatitis, comorbid diseases, and prior operations were similar between groups. Internal drainage required less operative time (211 +/- 37 vs 269 +/- 88 minutes, P =.04), blood loss (735 +/- 706 vs 2757 +/- 3062 mL, P =.03), and transfusion requirements (0.69 +/- 1.7 vs 4.21 +/- 8.0 units, P =.05). Clinical outcomes--as measured by postoperative complication rate, reoperation rate, fistula recurrence rate, and death rate--were similar between groups. CONCLUSIONS: RNY internal drainage, when technically feasible, is the best surgical option to treat disconnected duct syndrome after SAP.
Acute Disease↗
Stages of Reproductive Aging Workshop (STRAW).
A select group of clinicians and investigators met recently for the express purpose of developing a staging system for female reproductive aging. The group also addressed the confusing and redundant nomenclature that is commonly used to describe the late reproductive years. A summary and recommendations are presented.
Aging↗
Impact of pancreatic head resection on direct medical costs in patients with chronic pancreatitis.
OBJECTIVE: To quantitate disease-specific hospital-based medical costs in 34 patients with chronic pancreatitis before and after treatment by either duodenal-preserving pancreatic head resection (DPPHR) or pylorus-preserving pancreaticoduodenectomy (PPPD). SUMMARY BACKGROUND DATA: Pancreatic head resection in selected patients with chronic pancreatitis provides pain relief and improves quality of life, but the effect on healthcare costs is unknown. METHODS: This observational cohort study comprised 34 selected patients with chronic pancreatitis followed up exclusively at the authors' institution treated by either DPPHR or PPPD between 1992 and 1997. RESULTS: Twenty-one patients had DPPHR and 13 had PPPD. Patients in the PPPD group were slightly older, but other clinical characteristics were similar. Before surgery, the mean number of admissions per patient per year, days in the hospital per patient per year, and disease-specific hospital-based medical costs per patient per year were not significantly different between groups. After surgery, those three variables were similar between the groups but significantly less than preoperative values. Pain control remained significantly improved after 36 months of follow-up. CONCLUSIONS: In selected patients with chronic pancreatitis, DPPHR and PPPD are equally effective in providing long-term pain relief and decreasing disease-specific hospital-based costs.
Adult↗
Endoscopic ultrasound-guided celiac plexus block for managing abdominal pain associated with chronic pancreatitis: a prospective single center experience.
OBJECTIVE: In our previous randomized trial, we suggested a possible role for endoscopic ultrasound (EUS) guided celiac plexus block in the treatment of abdominal pain associated with chronic pancreatitis. The purpose of this study was to evaluate our prospective experience with EUS-guided celiac plexus block for controlling pain attributed to chronic pancreatitis, including follow-up on response rates and complications. METHODS: All subjects enrolled had documented chronic pancreatitis by ERCP and EUS criteria and presented with chronic abdominal pain unresponsive to current treatment options. All were treated with EUS-guided celiac plexus block under the guidance of linear array endosonography using a 22-gauge FNA needle (GIP, Mediglobe Inc., Tempe, AZ) inserted on each side of the celiac area, followed by injection of 10 cc bupivacaine (0.25%) and 3 cc (40 mg) triamcinolone on each side of the celiac plexus. Individual pain scores, based on a visual analog scale (0-10), were determined preblock and postblock by a nurse at 2, 7, 14 days and monthly thereafter. Subjects also rated their overall comfort level during the EUS procedure. RESULTS: EUS-guided celiac plexus block was performed in 90 subjects (40 males, 50 females) having a mean age of 45 yr (range 17-76 yr) between July 1, 1995 and December 30, 1996. A significant improvement in overall pain scores occurred in 55% (50/90) of patients. The mean pain score decreased from 8 to 2 post EUS celiac block at both 4 and 8 wk follow-up (p < 0.05). In 26% of patients there was persistent benefit beyond 12 wk, and 10% still had persistent benefit at 24 wk, including three patients who were pain-free between 35 and 48 wk. Younger patients (<45 yr of age) and those having previous pancreatic surgery for chronic pancreatitis were unlikely to respond to the EUS-guided celiac block. Three patients experienced diarrhea post EUS celiac block, which resolved in 7-10 days; however, it is unclear whether this diarrhea was due to the block or to refractory disease. A cost comparison between the EUS ($1200) and CT ($1400) techniques shows the EUS celiac block to be less costly and perhaps more cost efficient in a subset of subjects. CONCLUSIONS: EUS-guided celiac plexus block appears to be safe, effective, and economical for controlling pain in some patients with chronic pancreatitis. Younger patients (<45 yr) and those having prior pancreatic surgery for chronic pancreatitis do not appear to benefit from this technique. Prophylactic antibiotics should be considered if acid suppressing agents are being taken.
Abdominal Pain↗
Opportunities for future research.
Remarkable progress has been made in SERM development. Profiles of new SERMs indicate great potential for efficacy in the prevention and treatment settings, in more than one physiological system, and with improved risk/benefit ratios. The concept of what is achievable with respect to broad-spectrum disease prevention and what constitutes an "ideal" SERM is likely to undergo considerable reevaluation over time. The development of new, more broadly efficacious SERMs will require continued exploration of the effects of estrogen at the cellular and molecular level in tissues and physiologic systems throughout the body. A better understanding is needed of the mechanisms of the biological actions that are mediated through major forms of the estrogen receptor. High priority must be placed on elucidation of the role of the coregulators of estrogen receptor (ER) action. The quest for a SERM(s) with the "optimal clinical profile" also constitutes a major research challenge with respect to designing clinical trials that are simultaneously parsimonious with respect to time, monetary, and human resources and yet capable of delivering unequivocal outcomes with respect to primary end points. A vigorous research effort is needed to identify highly sensitive and specific surrogate measures to facilitate future clinical studies. Research to identify and validate relevant measures of safety is also essential to inform the risk/benefit balance and, thus, the ultimate usefulness of SERMs and their potential for long-term use. Future advances in the modulation of ER action are likely to have profound effects--not only on diseases and conditions known (or later discovered) to be related to estrogen action, but on the development of paradigms for understanding and modifying the action of other nuclear hormone receptors in the prevention and treatment of additional age- and disease-related pathologies.
Alzheimer Disease↗
Executive summary: Stages of Reproductive Aging Workshop (STRAW).
A select group of investigators attended a structured workshop, the Stages of Reproductive Aging Workshop (STRAW), at Park City, Utah, USA, in July 2001, which addressed the need in women for a staging system as well as the confusing nomenclature for the reproductive years.
Aging↗
Preventing and treating osteoporosis: strategies at the millennium.
Osteoporosis has been defined as "a progressive systemic disease characterized by low bone density and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture." Osteoporosis and the consequences of compromised bone strength--particularly vertebral and hip fractures--are a significant cause of frailty, and increased morbidity and even mortality and hence are a serious and costly public health problem in the elderly population. However, due to remarkable advances in basic and clinical research and in drug design, development, and testing, a number of efficacious, evidence-based options are available for the prevention and treatment of osteoporosis. These options extend far beyond estrogen/progestin therapy and include lifestyle and dietary changes such as increasing weight-bearing activity, enhancing calcium and vitamin D intake, as well as incorporating pharmacologic agents such as the bisphosphonates and selective estrogen receptor modulators (SERMs) such as raloxifene. In addition to its efficacy in increasing bone mineral density and reducing vertebral fractures by almost 40% in women with osteoporosis, the SERM raloxifene appears to promote a cardioprotective profile and to offer some protection against breast cancer. The potential of raloxifene to prevent or delay the development of a number of chronic diseases of aging such as osteoporosis, cardiovascular disease, and perhaps even Alzheimer's disease has stimulated the development and refinement of subsequent generations of SERMs aimed at maximizing beneficial effects in a wide variety of tissues while eliminating deleterious outcomes and side effects.
Diphosphonates↗
Conclusions: Considerations regarding SERMs.
The "considerations" addressed in this section consist of a number of thought-provoking issues and unresolved questions that emerge from the papers in this volume. The evidence for tamoxifen carcinogenicity in animal models and, to a more restricted extent, in humans has led some investigators to question whether SERMs are ready or appropriate for clinical testing--specifically, in a disease prevention setting involving healthy but high-risk individuals. There is, however, inconsistency in both efficacy and toxicity--specifically, carcinogenicity--between animal models and humans, leading others to question the value of basing the decision to proceed with clinical studies on preclinical results in animals. Although the molecular basis for SERM action is rapidly being clarified, the cellular activity of these agents is still elusive. We discuss the view that the efficacy of tamoxifen in breast cancer is based on its treatment of "occult cancers," or small collections of cancer cells that are not clinically apparent, not only in the context of prevention but also in the treatment setting. As part of our approach that assumes estrogen activity to be the foundation upon which SERM development is being modeled, we discuss the inconsistency between the epidemiologic data and prospective randomized data with respect to the relationship between estrogen use and cardiovascular disease. The need to validate surrogate markers of SERM action is discussed in relation to bone but is clearly relevant to all disease sites. The semantics used in describing SERM action as agonistic or antagonistic in relation to estrogen at various target sites has been inconsistent, especially in the clinical context. We attempt to dissect out some of the inconsistencies in semantics in the hope that this will contribute to improved communication of data resulting from SERM research. In the clinical arena, we begin with the premise that the large, simple randomized trial offers the optimal design for the testing of SERMs. In view of limited resources, however, we counter this position with alternative, if less desirable, approaches to the clinical format for SERM testing. Finally, we explore the process by which statistically meaningful results from clinical trials are extrapolated into the specific drug indications that apply to clinical practice.
Animals↗
Sphincter of Oddi dysfunction: diagnosis and treatment.
Explore the source record for details and available documents.
Calcium Channel Blockers↗
Structural effects of O-glycosylation on a 15-residue peptide from the mucin (MUC1) core protein.
To study the effect of O-glycosylation on the conformational propensities of a peptide backbone, the 15-residue peptide PPAHGVTSAPDTRPA (PPA15) from the MUC1 protein core and its analogue PPA15(T7), glycosylated with alpha-N-acetylgalactosamine on Thr7, were prepared and investigated by NMR spectroscopy. The peptide contains both the GVTSAP sequence, which is an effective substrate for GalNAc-T1 and -T3 transferases, and the PDTRP fragment, which is a well-known immunodominant epitope recognized by several anti-MUC1 monoclonal antibodies. Useful structural results were obtained in water upon decreasing the temperature to 5-10 degrees C. The sugar attachment slightly affected the conformational equilibrium of the peptide backbone near the glycosylated Thr7 residue. The clustering of low-energy conformations for both PPA15 and PPA15(T7) within the GVTSAP and APDTRP fragments revealed structural similarities between glycosylated and nonglycosylated peptides. For the GVTSAP region, minor but distinct clusters formed by either PPA15 or PPA15(T7) conformers showed distinct structural propensities of the peptide backbone specific for either the nonglycosylated or the glycosylated peptide. The peptide backbone of the APDTRP fragment, which is a well-known immunodominant region, resembled an S-shaped bend. A similar structural motif was found in the GVTSAP fragment. The S-shaped structure of the peptide backbone is formed by consecutive inverse gamma-turn conformations partially stabilized by hydrogen bonding. A comparison of the solution structure of the APDTRP fragment with a crystal structure of the MUC1 peptide antigen bound to the breast tumor-specific antibody SM3 demonstrated significant structural similarities in the general shape.
Acetylgalactosamine↗
Digit preference in year at menopause. Data from the study of women's health across the nation.
PURPOSE: To assess possible digit preference in self-reported year at natural menopause, and to determine whether equal proportions is an appropriate reference distribution.METHODS: Data are from the cross-sectional telephone interview from the Study of Women's Health Across the Nation (SWAN), a multi-site, multi-ethnic study of women aged 40-55. Analyses included 2151 naturally menopausal respondents, who were asked the year their periods stopped. Using a chi-square test, we compared the distribution of the terminal digit for year of final menstrual period (FMP) to an equal proportions (EP) distribution assigning 10% probability of each of the 10 digits. Departures from EP, however, may be accurate and may reflect the observed age distribution of subjects rather than digit preference. Thus, we stratified by year of interview to determine if the distribution was the same across years-suggesting digit preference-or if it varied systematically. We then estimated an expected distribution of terminal digit for year of FMP, using prospectively collected data (not subject to digit preference or recall bias) from the Massachusetts Women's Health Study, applied to the SWAN age distribution. The SWAN terminal digit distribution was compared with this expected distribution.RESULTS: Terminal digit for year at FMP exhibited a strong departure from EP (chi(2) = 841.60, p < 0.001), with highest frequencies for digits 4 and 5. Stratifying by year of interview, the distribution was shifted one digit in 1997 compared with 1996, consistent with unbiased reporting. Using the expected distribution as the reference reduced the chi-square statistic by a factor of 7 (chi(2) = 119.51, p < 0.001).CONCLUSIONS: The distribution of terminal digits for reported year at FMP was far from uniform, but departures from EP were consistent with results expected from an independent prospective study. These results suggest that EP may not be an appropriate reference for studies of digit preference, particularly those with a restricted age range.
Journal Article↗
Bias associated with study protocols in epidemiologic studies of disease familial aggregation.
The effect of selection bias has not been well evaluated in epidemiologic studies which focus on familial aggregation. The authors illustrate this type of bias for a reconstructed cohort study. With the reconstructed cohort design, cases and controls are first selected from the population and their relatives form the exposed and unexposed cohorts, respectively. The recurrence risk ratio (RRR) is calculated to assess and measure familial aggregation. The ways of utilizing information from relatives affects the estimate of RRR, and the authors show that a traditional method used in epidemiologic studies can yield a severely biased estimate of the RRR. However, this traditional approach can give approximately unbiased estimates under special conditions. A novel selection approach is proposed which yields an unbiased estimate of RRR. In conclusion, when relatives are identified through cases or controls, they should be included and counted in the study cohorts each time a case or control is selected, even if they or other family members have already been included.
Bias↗
Endoscopic measurement of pancreatic tissue perfusion in patients with chronic pancreatitis and control patients.
BACKGROUND: Pancreatic blood flow is diminished in experimental models of acute and chronic pancreatitis. We attempted to develop a safe and reliable technique for its measurement in patients and to examine blood flow in patients with chronic pancreatitis and in control subjects. METHOD: Pancreatic blood flow was measured using the hydrogen gas clearance technique and an endoscopically placed platinum ductal electrode. Pancreatic blood flow was measured in 12 patients with chronic pancreatitis diagnosed clinically and radiographically, and in 11 control patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) for non-pancreatic pathology. RESULTS: Patients with chronic pancreatitis had a significantly lower pancreatic blood flow compared with control patients (51.5 versus 91.7 mL/min/100 gm, p < 0.01). With secretin stimulation pancreatic blood flow increased in two control patients, whereas this notable rise was not seen in three patients with chronic pancreatitis. CONCLUSIONS: Measurement of pancreatic blood flow with an endoscopically placed electrode is relatively safe and simple to perform. The scarring and vascular fibrosis associated histologically with chronic pancreatitis is reflected in lower pancreatic blood flow.
Adult↗
Triple-tissue sampling at ERCP in malignant biliary obstruction.
BACKGROUND: Procurement of cytologic samples by brushing is common practice at endoscopic retrograde cholangiopancreatography (ERCP) but has low sensitivity for cancer detection. Limited data are available on other techniques, including endoluminal fine-needle aspiration and forceps biopsy. This series reviews the yield of these three stricture sampling methods. METHODS: In this prospective study, patients with biliary obstruction with a clinical suspicion of malignancy underwent triple-tissue sampling at one ERCP session. Final cancer diagnosis was based on all sampling methods plus surgery, autopsy, and clinical follow-up. Tissue specimens were reported as normal, atypia, or malignant. RESULTS: A total of 133 patients were evaluated: 104 had cancer and 29 had benign strictures. Tissue sampling sensitivity varied according to the type of cancer; the highest yield was seen in ampullary cancers (62% to 85%). The cumulative sensitivity of triple-tissue sampling in the cancer patients was as follows: sensitivity was 52% if atypia was considered benign and 77% if it was considered malignant. The addition of a second or third technique increased sensitivity rates in most instances. No serious complications occurred from the tissue sampling methods. CONCLUSIONS: Tissue sampling sensitivity varied according to the type of cancer. Combining a second or third method increased sensitivity; general use of at least two sampling methods is therefore recommended.
Adult↗
Down syndrome: genetic recombination and the origin of the extra chromosome 21.
Despite the clinical importance of trisomy 21, we have been ignorant of the causes of meiotic nondisjunction of chromosome 21. Recently, however, genetic mapping studies of trisomy 21 families have led to the identification of the first molecular correlate of human nondisjunction; i.e. altered levels and positioning of meiotic recombinational events. Specifically, increases in 0 exchange events or in distal-only or pericentromeric exchanges are significantly increased in trisomy 21-generating meioses. These observations have led to the idea that chromosome 21 nondisjunction requires 'two hits': first, the establishment in prophase I of a 'vulnerable' bivalent and second, abnormal processing of the bivalent at metaphase I or II.
Chromosomes, Human, Pair 21↗
Effectiveness of tizanidine in neuropathic pain: an open-label study.
The purpose of this research trial is to assess the effectiveness and tolerability of tizanidine in neuropathic pain. In an open-label study, patients with neuropathic pain received 1 to 4 mg of tizanidine once daily for 7 days, followed by weekly dose escalation of 2 to 8 mg to his/her effective or maximum tolerated dose or a maximum of 36 mg over an 8-week period. Treatment effects were assessed, using average weekly pain scores as well as biweekly scores for patient global assessment of pain relief, the neuropathic pain scale, and wisconsin brief pain inventory. Frequency and severity of adverse events were examined also. Twenty-three patients were enrolled. The mean average weekly pain score at baseline was 6.9, which decreased by 1.7 points at the end of week 8 to 5.2 (p < or =.01). A total of 15 patients (68%) reported that their pain relief was improved or much improved with tizanidine therapy, and 2 of these patients became completely pain-free. The following neuropathic pain qualities were significantly lower at week 8 compared with baseline: intense, sharp, hot, dull, cold, sensitive, unpleasant, and deep pain. There was a significant decline in pain quantity and interference of pain on quality of life from baseline to week 8. The mean effective or maximum tolerated dose was 23 mg/day (range 6 to 36 mg/day). Side effects consisted primarily of dizziness/lightheadedness (52%), drowsiness (48%), fatigue/weakness (43%), dry mouth (39%), gastrointestinal upset (30%), and sleep difficulty (22%). One patient developed significant elevation in liver function tests (LFTS) With symptoms at week 4. Tizanidine therapy was discontinued. LFTS returned to normal in 3 weeks. Tizanidine might be an effective treatment for neuropathic pain, offering an alternative for patients poorly responsive to other medications. A larger, randomized placebo-controlled trial is recommended. In addition, comparative studies with alternative agents should be sought.
Journal Article↗