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Biomedical subjects

P Lynch

Publications and source records attributed to P Lynch.

At least 19 recordsLinked to original sources
PubMed1998

Accelerated recombinant protein purification process development automated, robotics-based integration of chromatographic purification and analysis.

Recovery of recombinant proteins from endogenous, host molecules can be an experimentally intensive and time-consuming task. Often the time to analyze material during development of recovery procedures is the rate-limiting step. Nowadays, modern techniques and equipment are being specifically engineered to make this effort much more efficient. We present a case study to illustrate how a new, automation tool, designed for easy, systematic methods development, can be used for very rapid process and analytical optimization. This tool uses robotics to integrate process development with rapid LC-based analysis requiring no user intervention. The methods and procedures described can be generalized to any recombinant protein recovery campaign.

Chromatography, High Pressure Liquid↗
PubMed1998

Palliation of malignant dysphagia and fistulae with coated expandable metal stents: experience with 101 patients.

BACKGROUND: Insertion of coated expandable esophageal stents is the preferred endoscopic palliative treatment for malignant dysphagia and digestive-respiratory fistulae. METHODS: One hundred one patients with malignant dysphagia and digestive-respiratory fistulae, 83 due to esophageal cancer and 18 due to metastatic disease, underwent placement of a coated expandable metal stent. Thirteen patients had a digestive-respiratory fistula. The stricture location (99 patients) was proximal in 11, mid in 29, distal in 37, and at the gastroesophageal junction in 24. The endoscopic appearance was exophytic in 80, infiltrative in 19, single ulcer in 1, and normal in 1. The mean stricture length was 6.7 cm. RESULTS: Initial stent placement was successful in 100 patients; a second stent was required in 1. The median dysphagia grade improved from 3.6 to 1.4 and sealing-off of the digestive-respiratory fistula was successful in all cases. The overall complication rate was 37.9%. Life-threatening complications occurred in 7.9%. There were no procedure-related deaths. During a mean follow-up of 201 days, 99 patients died-none from stent-related problems. CONCLUSIONS: This large series confirms the efficacy of the coated metal expandable stent in the palliation of malignant dysphagia and digestive-respiratory fistula with an acceptable complication rate.

Adult↗
PubMed1998

Perceived organizational support and police performance: the moderating influence of socioemotional needs.

Police patrol officers were surveyed to investigate how the strength of socioemotional needs affects the relationship between perceived organizational support (POS) and work performance. The association of POS with driving-under-the-influence arrests and speeding citations generally increased with strength of the needs for esteem, affiliation, emotional support, and social approval. Patrol officers with strong socioemotional needs, but not those with weak needs, showed a positive relationship between POS and performance. The findings are consistent with social exchange views that maintain (a) work effort is encouraged by the receipt of socioemotional resources, (b) POS fulfills a variety of socioemotional needs, and (c) the value of POS and the obligation to reciprocate with high performance increase with the strength of socioemotional needs.

Adult↗
PubMed1997

Recommendations for follow-up care of individuals with an inherited predisposition to cancer. II. BRCA1 and BRCA2. Cancer Genetics Studies Consortium.

OBJECTIVE: To provide recommendations for cancer surveillance and risk reduction for individuals carrying mutations in the BRCA1 or BRCA2 genes. PARTICIPANTS: A task force with expertise in medical genetics, oncology, primary care, gastroenterology, and epidemiology convened by the Cancer Genetics Studies Consortium (CGSC), organized by National Human Genome Research Institute (previously the National Center for Human Genome Research). EVIDENCE: Studies evaluating cancer risk, surveillance, and risk reduction in individuals genetically susceptible to breast and ovarian cancer were identified using MEDLINE (National Library of Medicine) and from bibliographies of articles thus identified. Indexing terms used were "genetics" in combination with "breast cancer," "ovarian cancer," and "screening," or "surveillance" in combination with "cancer family" and "BRCA1" and "BRCA2." For studies evaluating specific interventions, quality of evidence was assessed using criteria of the US Preventive Services Task Force. CONSENSUS PROCESS: The task force developed recommendations through discussions over a 14-month period. CONCLUSIONS: Efficacy of cancer surveillance or other measures to reduce risk in individuals who carry cancer-predisposing mutations is unknown. Based on expert opinion concerning presumptive benefit, early breast cancer and ovarian cancer screening are recommended for individuals with BRCA1 mutations and early breast cancer screening for those with BRCA2 mutations. No recommendation is made for or against prophylactic surgery (eg, mastectomy, oophorectomy); these surgeries are an option for mutation carriers, but evidence of benefit is lacking, and case reports have documented the occurrence of cancer following prophylactic surgery. It is recommended that individuals considering genetic testing be counseled regarding the unknown efficacy of measures to reduce risk and that care for individuals with cancer-predisposing mutations be provided whenever possible within the context of research protocols designed to evaluate clinical outcomes.

Antineoplastic Agents, Hormonal↗
PubMed1997

Recommendations for follow-up care of individuals with an inherited predisposition to cancer. I. Hereditary nonpolyposis colon cancer. Cancer Genetics Studies Consortium.

OBJECTIVE: To provide recommendations for cancer surveillance and risk reduction for individuals carrying mutations associated with hereditary nonpolyposis colon cancer (HNPCC). PARTICIPANTS: A task force with expertise in medical genetics, oncology, primary care, gastroenterology, and epidemiology convened by the Cancer Genetics Studies Consortium (CGSC), organized by the National Human Genome Research Institute (previously the National Center for Human Genome Research). EVIDENCE: Studies evaluating cancer risk, surveillance, and risk reduction in individuals genetically susceptible to colon cancer were identified using MEDLINE and bibliographies of articles thus identified. Indexing terms used were "genetics" in combination with "colon cancer," and "screening" in combination with "cancer family" and "HNPCC." For studies evaluating specific interventions, quality of evidence was assessed using criteria of the US Preventive Services Task Force. CONSENSUS PROCESS: The task force developed recommendations through discussions over a 14-month period. CONCLUSIONS: Efficacy of cancer surveillance or other measures to reduce risk in individuals who carry cancer-predisposing mutations is unknown. Based on observational studies, colonoscopy every 1 to 3 years starting at age 25 years is recommended for individuals known to have HNPCC-associated mutations. Endometrial cancer screening is also recommended, based on expert opinion concerning presumptive benefit. No recommendation is made for or against prophylactic surgery (ie, colectomy, hysterectomy); these surgeries are an option for mutation carriers, but evidence of benefit is lacking. It is recommended that individuals considering genetic testing be counseled regarding the unknown efficacy of measures to reduce risk and that care for individuals with cancer-predisposing mutations be provided whenever possible within the context of research protocols designed to evaluate clinical outcomes.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Bifunctional fusion between nerve growth factor and a transferrin receptor antibody.

The cDNAs encoding the variable regions of the heavy and light chains of a murine antibody specific for the human TfR were cloned and a human chimera (gamma1, kappa) was produced. A gene fusion was created by joining the 3' end of the coding region of the human nerve growth factor (NGF) precursor to the 5' end of the heavy chain variable region of the chimeric antibody. When expressed with the unmodified light chain in mammalian cells, the protein fusion is properly processed, assembled, and secreted. Subsequent purification and characterization established the uncompromised bifunctional activities of the protein, relative to the unmodified components, as demonstrated by its ability to both bind to the human TfR and induce neurite outgrowth in primary sympathetic or spinal ganglia and in trkA-transfected pheochromocytoma cells. The ability to generate biologically active NGF fused to a TfR targeting antibody, which was previously shown to cross the blood-brain barrier, may offer a novel way to deliver NGF and other neurotrophic factors to the central nervous system.

Animals↗
PubMed1997

Blood contacts in the operating room after hospital-specific data analysis and action.

BACKGROUND: There has been much work recently to quantify risk of blood exposures among operating room personnel. Little has been done to show the outcome of preventive strategies. Three hospitals implemented a variety of changes after detailed feedback on blood contact data. This report follows those hospitals to document changes in blood contact rates. METHODS: Each hospital reviewed detailed data on blood exposures and developed a range of strategies to reduce contacts. In a second data collection period, uniformly trained circulating nurses sought information during surgical procedures on blood contacts among staff. Data were collected on all blood contacts and surgeries during which they occurred. These data were then compared with data from the previous study period, before changes in practices. RESULTS: All blood contacts combined and in each hospital decreased significantly in the second data collection period. Percutaneous exposures also consistently decreased, but did not reach statistical significance. The distribution of types of contact changed, with percutaneous exposures representing a larger proportion of contacts seen in the second period. Similar anatomic locations, devices, and characteristics of surgeries were associated with blood contacts in both periods. DISCUSSION: Specific data provided to operating room personnel motivated the development of specific strategies, although the influence of feedback alone versus specific interventions can not be separated. Analysis and generation of hospital-specific data on blood exposures among operating personnel may have a positive influence in lowering the risk of blood exposures in this population group.

Blood-Borne Pathogens↗
PubMed1997

Perceived organizational support, discretionary treatment, and job satisfaction.

A diverse sample of 295 employees drawn from a variety of organizations was surveyed to investigate (a) whether the relationship between the favorableness of job conditions and perceived organizational support (POS) depends on employee perceptions concerning the organization's freedom of action and (b) whether POS and overall job satisfaction are distinct constructs. The favorableness of high-discretion job conditions was found to be much more closely associated with POS than was the favorableness of low-discretion job conditions. No such relationship was found between job conditions and satisfaction. To decide how much the organization values their contributions and well-being, employees distinguish job conditions whose favorableness the organization readily controls versus job conditions whose favorableness is constrained by limits on the organization's discretion.

Adult↗
PubMed1997

Medical planning--casualty treatment times at first and second line.

OBJECTIVE: To establish the average time taken to treat a seriously wounded battle casualty at First and Second Line (Role 1 and Role 2) according to the British Army Casualty Treatment Regimes under simulated conditions, and, in doing so, to assess whether British medical facilities are capable of meeting the medical planning directives of the Allied Command Europe Rapid Reaction Corps (ARRC). DESIGN: A casualty evacuation exercise, using standard ARRC medical planning data, deploying the war establishment of personnel and equipment of an armoured Battle Group Regimental Aid Post (RAP) and an armoured Field Ambulance. SUBJECTS: 200 simulated casualties, using 120 healthy soldiers dressed in expendable clothing and carrying a description of their injuries and clinical status. MAIN OUTCOME MEASURED: The time taken to treat simulated seriously wounded casualties at Role 1, the RAP and at Role 2, the Field Ambulance Dressing Station (DS). RESULTS: The mean treatment time at Role 1 was 28 minutes and at Role 2 was 17 minutes. CONCLUSION: Within the (large) caveat of simulation, as presently configured, the Field Ambulance (DS) is well able to cope with the casualty load expected of it by ARRC medical planners but the RAP of the armoured Battle Group is not.

Ambulances↗
PubMed1997

Coated expandable esophageal stents in the treatment of digestive-respiratory fistulas.

BACKGROUND: Malignant digestive-respiratory fistula (DRF) is associated with significant morbidity and mortality. In addition to the other recognized advantages of expandable stents, coated expandable stents can seal off DRF. METHODS: Eight men and five women, mean age 52 yr, with endoscopically and radiographically proven DRF were treated with the coated Wallstent (Schneider). Eleven had dysphagia, 11 postprandial cough, and two required mechanical ventilation. The DRF was proximal in four, mid-esophageal in seven, and distal in two. Two had a normal esophagus and 11 had stricture. RESULTS: Stent placement and DRF obliteration were successful in all. During a median follow-up of 157 days (range 30-423), no recurrent DRF were noted. The median dysphagia score improved from 3.4 to 1.3. Respiratory symptoms were corrected in all. A gastrostomy tube was required in three. The only complications were transient chest pain and foreign body sensation in three patients and constant sensation of belching in one. There was no procedure-related mortality. CONCLUSION: In this small group of patients, the coated Wallstent demonstrated excellent palliation of DRF with minimal morbidity and no mortality.

Adult↗
PubMed1997

Does chemoradiation therapy increase the incidence of complications with self-expanding coated stents in the management of malignant esophageal strictures?

BACKGROUND: Expandable stents offer excellent palliation of malignant dysphagia and digestive-respiratory fistula. There are insufficient data regarding factors that may affect the complication rate of expandable stents, but an association between previous treatment with chemotherapy and/or radiation therapy and stent-related life-threatening complications has been suggested. METHODS: We retrospectively analyzed our data on 60 patients; in all of them, a coated Wallstent had been successfully placed for malignant dysphagia and/or digestive-respiratory fistula. Our objective in this study was to determine the overall complication rate as well as whether previous or ongoing chemoradiation therapy increased the rate of life-threatening complications. RESULTS: Among 21 patients with no previous chemotherapy or radiation therapy, two (9.5%) had life-threatening complications (both had bleeding tumors; blood transfusions were required in two and endoscopic hemostasis in one). Among 39 patients who had had either radiation therapy, chemotherapy, or both, life-threatening complications occurred in three (8%). Two of the three had gastrointestinal bleeding (two received blood transfusions, and one had external radiation therapy), and in the third, an esophageal tear was treated with the stent. There was no procedure- or stent-related mortality in either group. CONCLUSIONS: Palliation of malignant dysphagia or digestive-respiratory fistulas with the coated Wallstent in patients with previous chemotherapy and/or radiation therapy is not associated with an increased risk of life-threatening complications.

Aged↗
PubMed1996

A randomised study of two doses of gemeprost in combination with mifepristone for induction of abortion in the second trimester of pregnancy.

Two regimens of the prostaglandin E1 analogue, gemeprost, in combination with mifepristone were compared in a randomised trial for termination of pregnancy between 12-19 weeks. Thirty-six hours after treatment with 200 mg mifepristone, women were allocated at random to receive either 4 x 1 mg (Group I) or 4 x 0.5 mg (Group II) gemeprost by vaginal pessary every 6 hours (n = 50 in each group). If abortion had not occurred after 24 h, 5 x 1 mg of gemeprost was administered every 3 h to both groups of women. Although the median abortion interval was slightly shorter in the 1 mg group (7.8 h vs. 8.4 h, p = 0.5), the cumulative abortion rates at 24 h were similar (98% vs. 96%). Women in Group I required significantly more gemeprost to induce abortion than Group II (p < 0.0001). Parous women in both groups required significantly less of the prostaglandin to induce abortion. In Group II, the median abortion interval was significantly longer in primigravidae than multigravidae (9.5 h vs. 6.1 h; p < 0.02). There were no significant differences between the groups in the incidence of vomiting, diarrhoea or the request for analgesia. The results suggest that in parous women, the dose of gemeprost can be reduced to 0.5 mg every 6 h within the first 24 h without loss of clinical efficacy.

Abortifacient Agents, Nonsteroidal↗
PubMed1996

Interobserver variability in endoscopic ultrasonography: a prospective evaluation.

BACKGROUND: Endoscopic ultrasonography (EUS) is an imaging modality that is now widely used to stage gastrointestinal malignancies. Few studies have addressed the issue of interobserver variability in the interpretation of EUS, particularly as it pertains to the staging of rectal carcinoma. METHODS: Twenty-six patients with a diagnosis of rectal carcinoma were evaluated prospectively by three endoscopists. One performed sigmoidoscopy, the second (primary endosonographer) performed an EUS staging examination with full knowledge of the patient history and sigmoidoscopic appearance of the lesion, and the third endoscopist (secondary endosonographer) performed EUS blinded to this information. The results of the respective examinations were then compared. RESULTS: When the EUS findings of the endosonographers were compared, T stage agreed in 88% of patients, with the following kappa coefficients: T1 (kappa = 0.00); T2 (kappa = -0.04); T3 (kappa = -0.05); T4 (kappa = 0.00). Interrator N stage agreed in 73% of patients (kappa = 0.42). CONCLUSION: Our study prospectively evaluated interobserver variation in staging rectal carcinoma by EUS. The protocol that was followed provides a useful template that eliminated potential observer bias. Fair agreement was demonstrated regarding lymph node assessment. Although the raters agreed in 88% of the patients, kappa statistic analysis did not reach significant agreement, due to this institution's preponderence of UT3 lesions. Thus, validation of our findings in a setting where a broader spectrum of disease is encountered is required.

Carcinoma↗
PubMed1996

Phase II trial of intravenous flourouracil and subcutaneous interferon alfa-2b for biliary tract cancer.

PURPOSE: To assess the efficacy of systemic intravenous-fluorouracil (5-FU) and subcutaneous recombinant human interferon alfa-2b (rIFN alpha-2b) in patients with measurable cancer of the biliary tree. PATIENTS AND METHODS: Thirty-five patients (25 with cholangiocarcinoma and 10 with gallbladder carcinoma) were registered onto this phase II protocol between 1992 and 1995. Patients received a continuous infusion of 750 mg/m2/d of 5-FU on days 1 through 5 through a centrally placed venous catheter and a subcutaneous injection of 5 MU/m2 of rIFN alpha-2b on days 1, 3, and 5. Treatment cycles were repeated every 14 days; one course of therapy included four treatment cycles. Disease status was assessed every 8 weeks. Dosages were lowered for grade III mucositis. Fourteen patients had prior treatment and, before initiating this therapy, 17 patients required decompression of the biliary tree. RESULTS: Eleven of 32 (34%) assessable patients had a partial response. The median time to disease progression was 9.5 months, and the median survival time 12 months. Grade III to IV toxic effects were granulocytopenia (14%), mucositis (20%), diarrhea (9%), and dermatitis (11%). Grade III to IV asthenia and fatigue were observed in 6% of patients. CONCLUSION: Drug tolerance was better among previously untreated patients. To achieve a complete response, additional chemotherapy or radiotherapy should be considered when liver resection or transplantation is not feasible. However, if these results can be reproduced by other investigators, the regimen should be studied for adjuvant treatment of gallbladder carcinoma incidentally identified in patients undergoing cholecystectomy.

Adult↗
PubMed1995

Value of serial carcinoembryonic antigen levels in patients with resectable adenocarcinoma of the esophagus and stomach.

BACKGROUND: Adenocarcinomas of the esophagus and the stomach are highly virulent and remain a major health problem worldwide; 5-year survival rates have not changed in the past 30 years. Recently, preoperative chemotherapy has been used to treat these adenocarcinomas. The authors evaluated the usefulness of serial serum carcinoembryonic antigen (CEA) levels in diagnosing these patients and compared the prognosis of patients with high or normal CEA levels. METHODS: Ninety consecutive patients with potentially resectable adenocarcinoma of the esophagus or stomach treated with preoperative chemotherapy were evaluated. Serum CEA levels were determined before registration, after each chemotherapy course, every 3 months for the first year after completion of all therapy, and every 6 months thereafter for 5 years. RESULTS: The CEA positivity rate before chemotherapy was 22.2% (20/90); after chemotherapy, it dropped to 10.9% (9/82). An increasing CEA level predicted relapse and correlated well with liver, lung, or pleural involvement in some patients. Most patients with peritoneal involvement did not show elevated levels of CEA. Clinical responses correlated with declining levels of CEA in the patients who showed a negative conversion in CEA level after chemotherapy. CONCLUSIONS: An elevated serum CEA level enabled early detection of relapse in the absence of clinical symptoms in patients with adenocarcinoma of the esophagus or the stomach. The level of CEA was also useful in monitoring the response to chemotherapy in patients who had a high CEA level before treatment. Although the pre- and postchemotherapy CEA-positive group had a higher relapse rate than that of other group, the CEA level did not predict resectability or survival. Future research with labeled monoclonal anti-CEA antibodies may prove useful for certain groups of patients.

Adenocarcinoma↗