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Biomedical subjects

J Collins

Publications and source records attributed to J Collins.

At least 55 records · Page 3Linked to original sources

Cosmix-plexing: a novel recombinatorial approach for evolutionary selection from combinatorial libraries.

The efficiency of existing combinatorial biological library methods has been moderate in terms of the success rates, the affinities of the ligands selected and the time and effort involved in trying to optimize the initial leads. Although mimicking natural evolution, existing strategies take little notice of the importance of recombination within a selected population to generate increased diversity. We present an overview of our recent progress which has resulted in the successful development of such a strategy, which we designate cosmix-plexing. We incorporate recombination as a central feature in obtaining high success rates and high affinities, even for short monomer peptides, in a very short time. The method uses type II restriction enzymes to re-assort small hypervariable DNA cassettes from an intermediate pre-selected population (e.g. from a phagemid display library), while maintaining the original open-reading frame. Since, in the naive library, each cassette contains all possible combinations of the polypeptide sequences it encodes, much longer regions can be optimized than was possible with methods which depend on a simple selection from the naive library. Short peptides can now be rapidly selected, which exhibit the same, or higher, specificity and affinity for a defined target molecule, than (say) an antibody or even the natural ligand.

Amino Acid Sequence↗

The LPL S447X cSNP is associated with decreased blood pressure and plasma triglycerides, and reduced risk of coronary artery disease.

Linkage of the lipoprotein lipase (LPL) gene to blood pressure levels has been reported. The LPL S447X single nucleotide polymorphism (cSNP) has been associated with decreased triglycerides (TG), increased high density lipoprotein cholesterol, and a decreased risk of coronary artery disease (CAD), which may occur independently of its beneficial lipid changes. To investigate the relationship between LPL S447X cSNP and these parameters, we studied a cohort of individuals with familial hypercholesterolemia in whom blood pressures and information regarding the use of blood pressure lowering medications were available. Carriers of the S447X variant had decreased TG (1.21+/-0.47 vs. 1.52+/-0.67, p<0.001) and a trend towards decreased vascular disease (12.7 vs. 19.5%) compared to non-carriers. More interestingly, however, carriers of this cSNP had decreased diastolic blood pressure compared to non-carriers (78+/-10 vs. 82+/-11, p=0.002), evident in both men and women, youths and adults, with similar trends for systolic blood pressure. Furthermore, the decrease in blood pressure appeared independent of the decrease in TG (p=0.02), suggesting that the LPL protein may have a direct influence on the vascular wall. This suggests an additional mechanism whereby this variant may have protective effects, independent of changes in plasma lipid levels.

Adolescent↗

Cost-effectiveness of in vitro fertilization.

In vitro fertilization (IVF) is an effective but underutilized treatment for long-standing infertility. The median projected cost per IVF cycle in 2001 in the United States would be $9226 and $3531 in 25 other countries, based on previously published estimates. The cost per delivery arising from IVF cycles in 2001 in the United States would average $56,419, and $20,522 in eight other countries, based on previously published estimates. The cost-effectiveness of IVF has not been proven in three randomized controlled trials, but these trials are difficult to design and implement. Multiple gestation births significantly increase the cost of IVF treatment. IVF multiple births cost 36% more than the IVF cycles that gave rise to the multiple births. The uptake of IVF in most countries falls short of the minimum 1500 cycles per annum that would be needed per million population. Comparative international data indicate that infertile couples would increase their uptake of IVF services if the price were lower.

Adult↗

Macarthur model for ambulatory services.

The Macarthur Health Sector has embraced the concept of Ambulatory Care within all clinical streams. The Macarthur Model for Ambulatory Services is multi faceted and has sought to encompass and combine the best features of many established services throughout Australia and the world. The results is one integrated, cohesive model that allows patients multiple points of entry and exit. Ambulatory Care has developed an essential link in the continuum of care from acute 'illness' hospital-based to maintenance community 'health' care. The philosophy of shared responsibility between patient, carer, general practitioner and a hospital specialist team underpins the model developing in Macarthur.

Aftercare↗

A comparative study of metastatic renal cell carcinoma with correlation to subtype and primary tumor.

Clear cell (CRCC), papillary (PRCC) and chromophobe (CHRC) renal cell carcinoma (RCC) are the three most frequent subtypes of RCC. The rate and distribution of their metastatic lesions have not been well documented. We compared metastatic RCC according to subtype and primary tumor characteristics to better understand their behavior and to aid in the diagnosis of metastatic RCC. Pathology reports and clinical charts related to 283 CRCC, 48 PRCC and 13 CHRCC, including their respective sarcomatoid variants, were reviewed. A hundred and thirty-seven CRCC, 5 PRCC and 1 CHRCC with metastases were identified. CRCC and non-CRCC (PRCC and CHRCC) had different patterns of metastasis and primary tumor growth. CRCC metastases were predominantly distributed in lungs, bone, brain, lymph nodes, and adrenal glands. The associated primary CRCC measured 1.5 to 15 cm, were of all grades and stages, and were often associated with invasion of small or large veins. Three PRCC had regional lymph node metastases, 1 PRCC had both regional and mediastinal lymph node metastases. Bone metastasis was present in 1 case each of PRCC and CHRCC. One PRCC with metastasis solely to regional nodes measured 4 cm. The other 4 cases of PRCC with regional lymph node and/or distant metastases as well as the CHRCC with distant metastases were greater than 8 cm in diameter. In metastasizing and non-metastasizing non-CRCC, invasion of small veins was rare and invasion of renal veins was not seen. We cannot comment with any certainty on the metastatic behavior of CHRCC. In our experience, PRCC tend to loco-regional invasion with lymph node spread. They have a low potential for vascular invasion and distant metastases that likely occur only at late stages of the disease. CRCC has a propensity for vascular invasion and may be associated with distant metastasis at an early stage. Therefore, metastatic RCC at a distant location are most likely to be of CRCC origin than PRCC origin.

Adrenal Gland Neoplasms↗

Safer choices: reducing teen pregnancy, HIV, and STDs.

OBJECTIVES: This study evaluated the long-term effectiveness of Safer Choices, a theory-based, multi-component educational program designed to reduce sexual risk behaviors and increase protective behaviors in preventing HIV, other STDs, and pregnancy among high school students. METHODS: The study used a randomized controlled trial involving 20 high schools in California and Texas. A cohort of 3869 ninth-grade students was tracked for 31 months from fall semester 1993 (baseline) to spring semester 1996 (31-month follow-up). Data were collected using self-report surveys administered by trained data collectors. Response rate at 31-month follow-up was 79%. RESULTS: Safer Choices had its greatest effect on measures involving condom use. The program reduced the frequency of intercourse without a condom during the three months prior to the survey, reduced the number of sexual partners with whom students had intercourse without a condom, and increased use of condoms and other protection against pregnancy at last intercourse. Safer Choices also improved 7 of 13 psychosocial variables, many related to condom use, but did not have a significant effect upon rates of sexual initiation. CONCLUSIONS: The Safer Choices program was effective in reducing important risk behaviors for HIV, other STDs, and pregnancy and in enhancing most psychosocial determinants of such behavior.

Adolescent↗

Occupational exposure to solvents and male infertility.

OBJECTIVES: To determine whether, in a case-referent study of infertility patients, cases with low motile sperm count were more likely than referents to have had exposure to organic solvents. METHODS: Occupations of men attending fertility clinics in Canada were assigned codes reflecting probable exposure to organic solvents, at four grades of intensity, using a job exposure matrix previously developed. A case referent design was used, with cases being defined as men with <12x10(6)/ml motile sperm. Information from 656 men in manual work attending a single clinic in Montreal in 1972-91 was used for the main study. A separate analysis was conducted with information for 574 men in manual work attending 10 further clinics across Canada in 1984-7. RESULTS: In the Montreal series a significant association was found between intensity of exposure to solvents and clinical findings of <12x10(6)/ml motile sperm. Odds ratios (ORs), after allowing for confounding, were 2.07 (95% confidence interval (95% CI) 1.24 to 3.44) for moderate exposure to solvents and 3.83 (95% CI 1.37 to 10.65) for high exposure. In the second series of 568 men, the effect was confirmed at high exposure to solvents (OR 2.90, 95% CI 1.01 to 8.34) but not at moderate exposure (OR 1.01, 95% CI 0.53 to 1.92). CONCLUSIONS: Exposure to organic solvents is common both at work and in recreational pursuits. The results of this study suggest that efforts should be made to identify the compounds hazardous to male fertility, and if the risk is confirmed, to regulate their use.

Adult↗

Siblings, multiple births, and the incidence of allergic disease: a birth cohort study using the West Midlands general practice research database.

BACKGROUND: The presence of older siblings reduces the risk of developing hay fever, eczema and atopy, but findings for asthma have been inconsistent. Whether twins have a reduced risk of allergic disease is also unclear. We have investigated these questions in a birth cohort analysis of the West Midlands General Practice Research Database (GPRD). METHODS: Our birth cohort included 29,238 children. The incidence of allergic disease was examined according to the number of siblings, multiple births, and parental allergic disease and smoking habit using Cox regression. RESULTS: There was a dose related decrease in the incidence of eczema and hay fever with increasing number of older siblings (hazard ratio for children with three or more older siblings compared with none 0.70 (95% CI 0.64 to 0.76) for eczema and 0.67 (95% CI 0.52 to 0.86) for hay fever). In contrast, the presence of older siblings increased the incidence of asthma (HR 1.17, 95% CI 1.06 to 1.29), although this effect was strongly dependent on age of diagnosis. For children diagnosed over the age of 2 years the presence of older siblings was protective (HR 0.66, 95% CI 0.52 to 0.82), while below this age the reverse was true (HR 1.38, 95% CI 1.24 to 1.54). Members of a multiple birth had a reduced incidence of all three allergic diseases. Birth order and multiple birth effects were independent of sex, maternal age, consulting behaviour, and parental allergy and smoking habit. CONCLUSIONS: The presence of older siblings and being a member of a multiple birth appears to protect against the development of eczema, hay fever, and asthma diagnosed after the age of 2. In contrast, the presence of older siblings increases the incidence of early asthma.

Adolescent↗

Frequency and CT findings of recurrent disease after lung transplantation.

PURPOSE: To determine the frequency and computed tomographic (CT) findings of recurrence of the primary disease after lung transplantation at six North American lung transplantation centers. MATERIALS AND METHODS: Medical records of 1,394 lung transplant recipients were reviewed to identify patients with recurrent primary disease. Their CT scans and pathologic specimens were reviewed. RESULTS: The frequency of disease recurrence in the six transplantation centers was 1% (15 of 1,394 patients), including six previously reported cases. Sarcoidosis recurred in nine (35%) of 26 transplants and was the most common disease to recur. Three (33%) of nine patients with recurrent sarcoidosis had correlative findings at CT. When present, CT findings were usually different at recurrence compared with pretransplantation CT findings. CONCLUSION: A relatively small percentage of patients are at risk for recurrence of primary disease following lung transplantation. Sarcoidosis is the most common disease to recur.

Adult↗

Decreasing children's risk taking on the playground.

Playground mishaps are some of the most common sources of injury and are the leading killer of children. The present study used a multiple baseline design across three classrooms (N = 379 children). With minimal teaching and rewards, children decreased and maintained decreased risky playground behaviors on slides. Floor effects on climbers prevented the demonstration of similar effects. The decreases seen in risky slide behavior are discussed within the context of preventive safety training for playground injuries.

Child↗

Level 5 leadership. The triumph of humility and fierce resolve.

Boards of directors typically believe that transforming a company from merely good to truly great requires a larger-than-life personality--an egocentric chief to lead the corporate charge. Think "Chainsaw" Al Dunlap or Lee Iacocca. In fact, that's not the case, says author and leadership expert Jim Collins. The essential ingredient for taking a company to greatness is having a "Level 5" leader at the helm--an executive in whom extreme personal humility blends paradoxically with intense professional will. Collins paints a compelling and counter-intuitive portrait of the skills and personality traits necessary for effective leadership. He identifies the characteristics common to Level 5 leaders: humility, will, ferocious resolve, and the tendency to give credit to others while assigning blame to themselves. Collins fleshes out his Level 5 theory by telling colorful tales about 11 such leaders from recent business history. He contrasts the turnaround successes of outwardly humble, even shy, executives like Gillette's Colman M. Mockler and Kimberly-Clark's Darwin E. Smith with those of larger-than-life business leaders like Dunlap and Iacocca, who courted personal celebrity. The jury is still out on how to cultivate Level 5 leaders and whether it's even possible to do so, Collins admits. Some leaders have the Level 5 seed within; some don't. But Collins suggests using the findings from his research to strive for Level 5--for instance, getting the right people on board and creating a culture of discipline. "Our own lives and all that we touch will be better for the effort," he concludes.

Administrative Personnel↗

Comparison of cyclin A and MIB-1 expression in astrocytic tumors using image-based cell analysis system.

Traditional prognostic indicators for astrocytic tumors include tumor size, type, and histologic grade. Data suggest that tumor growth fraction assessed by MIB-1 is an important predicator of survival. Cyclin A, like MIB-1, is a recently described specific marker of proliferation, detectable primarily in S phase of the cell cycle as it undergoes progression to G2 phase. Thirty-seven cases of astrocytic tumors--14 cases of World Health Organization grade 1 and 2 (low grade tumors), 8 cases of grade 3 (anaplastic astrocytoma), and 15 cases of grade 4 (glioblastoma multiforme)--were simultaneously evaluated using routine paraffin immunohistochemical methods with commercial antibodies against MIB-1 and cyclin A. The results were quantitated using a Cell Analysis System (CAS) 200 image analyzer. The mean percentage positive nuclear area for MIB-1 was 3.32% in grade 1 and 2, 19.27% in grade 3, and 24.00% in grade 4 astrocytic tumors. Cyclin A showed a similar pattern of positivity in the same cases: 2.84% in grade 1 and 2, 16.27% in grade 3, and 24.88% in grade 4 astrocytic tumors. The data suggest that both proliferation markers correlated significantly with histologic grade. Cyclin A appears to be as good an indicator of brain tumor proliferation as MIB-1. Because cyclin A is detectable primarily in the S phase of the cell cycle, the fraction of cells positive for cyclin A should allow for a more accurate indicator of tumor progression.

Antigens, Nuclear↗

Visualization in the ipsilateral lymph nodes secondary to extravasation of a bone-imaging agent in the left hand: a case report.

Axillary or elbow lymph node visualization after subcutaneous infiltration of the bone-imaging agent on a routine bone scintigraphy has been reported. The prostate cancer patient in this case report underwent bone scintigraphy; in 3-h bone images, the lymph nodes in the wrist, elbow, and axillary regions were simultaneously visualized. This was caused by extravasation of the intravenous injection of bone-imaging agent in the dorsal part of the patient's hand.

Aged↗

An assessment of clinical guidelines for the management of acute pancreatitis.

BACKGROUND: Recent guidelines have been issued for the management of acute pancreatitis. The aim of this study was to audit the management of acute pancreatitis in one district general hospital, to determine the problems and benefits associated with the implementation of such guidelines. METHODS: Data were collected over the period 1991-1995 for all patients diagnosed as having acute pancreatitis who were admitted to one district general hospital. Data regarding severity grading, determination of aetiology and treatment of mild and severe pancreatitis were analysed in conjunction with the recommendations issued by the British Society of Gastroenterology Working Party on the management of acute pancreatitis in 1995. RESULTS: A total of 210 patients were admitted on 263 occasions; 16% of cases were severe but severity prediction was inaccurate. 56.1% had gallstone pancreatitis and 20.9% had idiopathic pancreatitis. Definitive treatment of gallstones was within the recommended time limit in only 70.1%. 27 patients experienced recurrent attacks of pancreatitis before definitive treatment of their gallstones, due either to inadequate investigation for gallstones after suboptimal ultrasound examination (n = 12) or to inappropriate delay before definitive treatment of gallstones (n = 15). Recommendations for the management of severe cases with early ITU/HDU admissions and CT scanning were not followed. 28 day mortality was 6.3%, median age of those dying was 80.5 years. CONCLUSIONS: Acceptable mortality can be achieved for acute pancreatitis despite failure to implement BSG guidelines for the management of severe acute pancreatitis. Inadequate investigation and treatment of gallstone disease leads to an unacceptable incidence of recurrent acute pancreatitis.

Acute Disease↗