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Biomedical subjects

S Sherman

Publications and source records attributed to S Sherman.

At least 19 recordsLinked to original sources
PubMed2002

Sphincter of Oddi dysfunction: pancreaticobiliary sphincterotomy with pancreatic stent placement has a lower rate of pancreatitis than biliary sphincterotomy alone.

BACKGROUND AND STUDY AIMS: Patients with suspected or documented sphincter of Oddi dysfunction (SOD) who undergo standard biliary sphincterotomy have high rates of post-procedure pancreatitis. Approximately 75% of such patients have elevated basal pressures of the pancreatic sphincter. Biliary sphincterotomy (BES) on its own leaves the pancreatic sphincter unablated and may cause transient edema which aggravates the increase in pancreatic sphincter pressure. Combined pancreaticobiliary therapy (PBR), using pancreatic stenting in addition to sphincterotomy may therefore be safer. PATIENTS AND METHODS: The endoscopic retrograde cholangiopancreatography (ERCP) database was queried for patients with successful double-duct sphincter of Oddi manometry (SOM) who underwent BES alone or PBR between 1994 and 1997. The endoscopist had decided on the technique to be used. From 1995 to 1997 there was a general trend to do PBR. Pancreatitis was defined according to established criteria. RESULTS: The post-ERCP pancreatitis rate among all 436 SOD patients was 19.7%, while 256 patients with normal SOM results had a pancreatitis rate of 12.9%. The use of combined PBR was associated with a lower frequency of pancreatitis compared with BES alone (needle-knife over pancreatic duct stent, 14/131 patients, 10.7 %; pull-type pancreaticobiliary sphincterotomy plus pancreatic stent, 15/78 patients, 19.2%; BES alone, 52/184 patients, 28.3%). Episodes of moderate and severe pancreatitis were seen more frequently in the BES group. CONCLUSION: In SOD patients, post-ERCP pancreatitis rates remain high, but have improved with the addition of combined pancreaticobiliary sphincter therapy.

Case-Control Studies↗
PubMed2001

Double-blind, randomized trial of bupropion SR for the treatment of neuropathic pain.

OBJECTIVE: To evaluate the effectiveness and safety of bupropion sustained-release (SR) for the treatment of neuropathic pain. METHOD: This single-center, outpatient, randomized, double-blind, placebo-controlled, crossover study consisted of two phases. Forty-one nondepressed patients with neuropathic pain spent 6 weeks in each phase in random order and received identical tablets of 150 mg bupropion SR or placebo. Patients were instructed to take one tablet once daily for 1 week followed by one tablet twice daily for 5 weeks. RESULTS: While the patients took bupropion SR, neuropathic pain relief was improved or much improved in 30 (73%) patients, and one of these patients became pain-free. The mean average pain score at baseline was 5.7, which remained unchanged at the end of week 6 with placebo, but decreased by 1.7 points to 4.0 (p < 0.001) during therapy with bupropion SR. Pain relief with bupropion SR was significant at week 2 (p < 0.05) and continued throughout weeks 3 through 6 (p < 0.001). A significant decrease in interference of pain on quality of life was observed while patients were receiving bupropion SR compared with placebo. Side effects experienced with bupropion SR were not dose-limiting and consisted primarily of dry mouth, insomnia, headache, gastrointestinal upset, tremor, constipation, and dizziness. CONCLUSION: This placebo-controlled crossover trial showed that bupropion SR (150-300 mg daily) was effective and well tolerated for the treatment of neuropathic pain.

Adult↗
PubMed2001

Selenoprotein oxidoreductase with specificity for thioredoxin and glutathione systems.

Thioredoxin (Trx) and glutathione (GSH) systems are considered to be two major redox systems in animal cells. They are reduced by NADPH via Trx reductase (TR) or oxidized GSH (GSSG) reductase and further supply electrons for deoxyribonucleotide synthesis, antioxidant defense, and redox regulation of signal transduction, transcription, cell growth, and apoptosis. We cloned and characterized a pyridine nucleotide disulfide oxidoreductase, Trx and GSSG reductase (TGR), that exhibits specificity for both redox systems. This enzyme contains a selenocysteine residue encoded by the TGA codon. TGR can reduce Trx, GSSG, and a GSH-linked disulfide in in vitro assays. This unusual substrate specificity is achieved by an evolutionary conserved fusion of the TR and glutaredoxin domains. These observations, together with the biochemical probing and molecular modeling of the TGR structure, suggest a mechanism whereby the C-terminal selenotetrapeptide serves a role of a protein-linked GSSG and shuttles electrons from the disulfide center within the TR domain to either the glutaredoxin domain or Trx.

Amino Acid Sequence↗
PubMed2001

Endoscopic ultrasonography-guided fine-needle aspiration biopsy of suspected pancreatic cancer.

BACKGROUND: In many institutions, computed tomography (CT)-guided percutaneous fine-needle aspiration (FNA) has become the procedure of choice for biopsies of pancreatic mass lesions. This method of biopsy and others, such as endoscopic retrograde cholangiopancreatography (ERCP) cytology, are problematic because of a substantial false-negative rate. OBJECTIVE: To investigate the yield of endoscopic ultrasonography-guided FNA biopsies in patients who had negative results on CT-guided biopsy or negative cytologic findings on ERCP sampling. DESIGN: Prospective cohort study. SETTING: Tertiary care university medical center. PATIENTS: 102 patients (median age, 65 years; 58 men and 44 women) with suspected pancreatic cancer who fulfilled the above criteria were prospectively identified and underwent endoscopic ultrasonography-guided FNA biopsy. MEASUREMENTS: The operating characteristics of endoscopic ultrasonography-guided FNA for diagnosing pancreatic masses were determined. Surgical pathology or long-term follow-up (median, 24 months) was used to identify false-positive or false-negative results. RESULTS: Median mass size was 3.5 cm x 2.7 cm. A median of 3.4 passes were performed. Cytologic results on endoscopic ultrasonography-guided FNA biopsy were positive in 57 patients, negative in 37, and inconclusive or nondiagnostic in 8. No false-positive results were observed. A diagnosis of pancreatic cancer was subsequently confirmed in 3 patients who had tested negative (false-negative results) and 1 of the 8 patients with nondiagnostic results. Of these 4 patients, 3 had cytologic evidence of chronic pancreatitis on endoscopic ultrasonography-guided FNA biopsy. The 95% CI for the likelihood ratio for a positive test result contained all values greater than or equal to 9.7. The likelihood ratio for a negative test result was 0.05 (CI, 0.02 to 0.15). The posterior probability of pancreatic cancer after a definitely positive result was at least 93.5% by a conservative lower 95% confidence limit; after a definitely negative test result, it was 6.9%. The prevalence of pancreatic cancer was 59.8% (61 of 102 patients). Self-limited complications occurred in 3 of the 102 patients (2.9% [CI, 0.6% to 8.4%]). CONCLUSION: Endoscopic ultrasonography-guided FNA biopsy may play a valuable role in the evaluation of a pancreatic mass when results on other biopsy methods are negative but pancreatic cancer is suspected.

Aged↗
PubMed2001

Impact of endoscopic therapy on the survival of patients with primary sclerosing cholangitis.

BACKGROUND: Endoscopic measures such as balloon dilation can relieve obstruction and improve symptoms in patients with primary sclerosing cholangitis (PSC). However, the influence of repeated endoscopy to maintain biliary patency on the survival of patients with PSC is unclear. METHODS: This study evaluated the impact of endoscopic therapy on the survival of consecutive patients with PSC undergoing endoscopic therapy. During a 6-year period 63 patients underwent endoscopic therapy. After initial therapy, patients were followed for a median of 34 months. Endoscopic therapy primarily consisted of repeated balloon dilation of dominant biliary strictures. The observed survival of this cohort was estimated (Kaplan-Meier). The predicted survival of the cohort was estimated by using the Mayo Clinic survival model based on clinical information obtained within 3 months before first endoscopic therapy. The Mayo Risk Score was calculated by using the equation R = (0.03 Age, years) + (0.54 log(e) Bilirubin mg/dL) + (0.54 log(e) Aspartate aminotransferase U/mL) + (1.24 Bleed history) - (0.84 Albumin gm/dL). RESULTS: The observed survival over 5 years was significantly higher than the predicted 5-year survival (83% vs. 65%, respectively; p = 0.027). CONCLUSION: These data suggest that repeated endoscopic attempts to maintain biliary patency may improve the survival of patients with PSC and dominant strictures.

Adult↗
PubMed2001

Routes of drug administration, differential affiliation, and lifestyle stability among cocaine and opiate users: implications to HIV prevention.

Types of drugs used and routes of administration were assessed, and correlations to social affiliation, HIV status, and lifestyle stability were explored among 672 street-recruited drug users in Baltimore. Participants reported 63 patterns of drug use, which were categorized into five groups: (1) only sniff heroin; (2) smoke crack and may snort cocaine; (3) sniff heroin and smoke crack; (4) inject heroin and cocaine; and (5) inject heroin and cocaine, smoke crack, and may snort heroin. Social network analysis revealed that heroin sniffers and crack smokers both tended to associate with those with similar drug use patterns. High symptoms of drug dependence were observed among heroin users irrespective of mode of administration. Injectors reported higher rates of hospitalization compared to noninjectors even after adjusting for HIV status. Implications to HIV prevention and drug use transitions are discussed.

Adult↗
PubMed2001

Two dopamine genes related to reports of childhood retrospective inattention and conduct disorder symptoms.

The 7-repeat allele of the dopamine receptor D4 gene (DRD4) and the 10 repeat allele of the dopamine transporter gene (DAT1) have shown association and linkage with symptoms of attention deficit hyperactivity disorder (ADHD) in childhood. The parents of ADHD children (clinic group, n = 80 fathers and 107 mothers) and control children (control group, n = 42 fathers and 51 mothers) were the focus of this study. These parents reported retrospectively on their level of ADHD Inattention and Conduct Disorder symptoms in adolescence. In analyses of the relation of symptom levels to the DRD4 and DAT1 genotypes, fathers possessing the 7 repeat DRD4 allele had greater levels of both inattention and conduct disorder symptoms. Mothers with the 10/10 genotype had higher levels of inattention symptoms. Thus, genetic associations found in children may be replicable in their parents.

Adult↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

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↗