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Biomedical subjects

K Lawrence

Publications and source records attributed to K Lawrence.

At least 19 recordsLinked to original sources
PubMed2001

A simian human immunodeficiency virus with a nonfunctional Vpu (deltavpuSHIV(KU-1bMC33)) isolated from a macaque with neuroAIDS has selected for mutations in env and nef that contributed to its pathogenic phenotype.

Previous studies have shown that passage of nonpathogenic SHIV-4 through a series of macaques results in the selection of variants of the virus that are capable of causing rapid subtotal loss of CD4(+) T cells and AIDS within 6-8 months following inoculation into pig-tailed macaques. Using a pathogenic variant of SHIV-4 known as SHIV(KU-1bMC33), we reported that a mutant of this virus with the majority of the vpu deleted was still capable of causing profound CD4(+) T cell loss and neuroAIDS in pig-tailed macaques (McCormick-Davis et al., 2000, Virology 272, 112-116). In this study, we have analyzed the tissue-specific changes in the env and nef in one macaque that developed neuroAIDS (macaque 50 O) and in three macaques that developed only a moderate or no significant loss of CD4(+) T cells and no neurological disease (macaques 50 Y, 20220, 20228) following inoculation with DeltavpuSHIV(KU-1bMC33). Sequence analysis of the gp120 region of env isolated from lymphoid tissues (lymph node and spleen) of macaques 50 Y, 20220, and 20228 revealed no consensus amino acid substitutions. In contrast, analysis of the gp120 sequences isolated from lymphoid and CNS tissues (parietal cortex, basal ganglia, and pons) of macaque 50 O revealed numerous amino acid substitutions. The significance of the amino acid substitutions in gp120 was supported by neutralization assays which showed that the virus isolated from the lymph node of macaque 50 O was neutralization resistant compared to the parental SHIV(KU-1bMC33). Analysis of changes in the nef gene from macaque 50 O revealed in-frame deletions in Nef that ranged from 4 to 13 amino acids in length, whereas the nef genes isolated from the other three macaques revealed no deletions or consensus amino acid substitutions. Inoculation of the virus isolated from the lymph node of the macaque which developed neuroAIDS, SHIV(50OLNV), into four pig-tailed macaques resulted in a severe loss of the circulating CD4(+) T cells within 2 weeks postinoculation, which was maintained for up to 20 weeks postinoculation, confirming that this virus had indeed become more pathogenic in pig-tailed macaques. Taken together, these observations suggest that DeltavpuSHIV(KU-1bMC33) has a low pathogenic phenotype in macaques but that individual pig-tailed macaques can select for additional mutations within the Env and Nef which can compensate for the lack of an intact Vpu and ultimately increase its pathogenicity.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Posttransplant diabetes mellitus in pediatric thoracic organ recipients receiving tacrolimus-based immunosuppression.

BACKGROUND: Posttransplantation diabetes mellitus (PTDM) is a well-known complication of tacrolimus-based immunosuppression in both adult and pediatric solid organ recipients. The "natural history" of diabetes in the pediatric thoracic transplant population has not yet been described. METHODS: We identified all pediatric thoracic transplant patients receiving tacrolimus-based immunosuppression who developed PTDM. Medical records were reviewed, with a particular focus on the clinical course of PTDM and its relationship to drug weaning. RESULTS: Diabetes developed in 24 of 143 (17%) 30-day survivors of heart (12/96, 13%) and heart-lung/lung (12/ 47, 26%) transplantation. In 17 (71%) patients, the immunosuppressive regimen at the onset of PTDM also included maintenance corticosteroids. Seventeen patients demonstrated glucose intolerance before the onset of diabetes. Nine patients (38%) developed diabetes during pulsed corticosteroid therapy. Median time of onset after transplantation was 9.0 months. All patients required s.c. insulin for glucose control. The median follow-up from transplant was 49.9 months. There was a significant decrease in mean tacrolimus dosage (P<0.01), tacrolimus level (P<0.04), and steroid dosage (P<0.02) from onset of PTDM to most recent follow-up. Despite this significant reduction in immunosuppression, only 3/24 (13%) patients were successfully weaned off insulin. CONCLUSIONS: Diabetes mellitus is a common complication in pediatric thoracic transplant patients receiving tacrolimus-based immunosuppression. Insulin dependence in our population rarely resolved, even after lowering tacrolimus and steroid doses. Discontinuation of steroids did not guarantee resolution of diabetes.

Adolescent↗
PubMed2001

Heat shock protein-56 is induced by cardiotrophin-1 and mediates its hypertrophic effect.

Cardiotrophin-1 (CT-1) is an interleukin-6 family cytokine with known protective and hypertrophic effects in the heart. Previous studies have shown that CT-1 treatment increases heat shock protein 70 (hsp70) and heat shock protein 90 (hsp90) levels in cardiac cells. Due to the known protective effects of hsp90 and hsp70, induction of these proteins may be involved in the protective effects of CT-1. We show here that heat shock protein 56 (hsp56), also known as FK506 binding protein 59 (FKBP59), is induced by CT-1 treatment at both the mRNA and protein levels. It has been demonstrated previously that, unlike hsp70 and hsp90, hsp56 overexpression does not protect cardiac myocytes against stressful stimuli. The other known effect of CT-1 is hypertrophy, an increase in cell size without cell division, which occurs in many cardiac pathologies. We investigated the role of hsp56 in the hypertrophic response of primary neonatal rat cardiac myocytes, using overexpression with transiently transfected plasmid vectors and Herpes viral vectors. Overexpression of hsp56 caused a significant increase in cardiac cell size and protein:DNA ratio. Hsp27, hsp70 and hsp90 overexpression had no effect on cell size. An antisense construct to hsp56 reduced hsp56 levels when transiently transfected and blocked the hypertrophic effect of CT-1. This is the first time that a hypertrophic effect has been demonstrated for a heat shock protein and demonstrates that CT-1-induced hypertrophy involves a specific hsp, which is not involved in its protective effect.

Animals↗
PubMed2000

A reduced estimate of the number of kilometre-sized near-Earth asteroids.

Near-Earth asteroids are small (diameters < 10 km), rocky bodies with orbits that approach that of the Earth (they come within 1.3 AU of the Sun). Most have a chance of approximately 0.5% of colliding with the Earth in the next million years. The total number of such bodies with diameters > 1 km has been estimated to be in the range 1,000-2,000, which translates to an approximately 1% chance of a catastrophic collision with the Earth in the next millennium. These numbers are, however, poorly constrained because of the limitations of previous searches using photographic plates. (One kilometre is below the size of a body whose impact on the Earth would produce global effects.) Here we report an analysis of our survey for near-Earth asteroids that uses improved detection technologies. We find that the total number of asteroids with diameters > 1 km is about half the earlier estimates. At the current rate of discovery of near-Earth asteroids, 90% will probably have been detected within the next 20 years.

Earth, Planet↗
PubMed2000

Cardiotrophin-1 reduces stress-induced heat shock protein production in cardiac myocytes.

Cardiotrophin-1 (CT-1) can induce expression of the protective heat shock proteins (hsps) in cardiac cells. We show here that, unlike the stress induced accumulation of hsps, the effect of CT-1 is not accompanied by increased hsp mRNA levels and is insensitive to the RNA synthesis inhibitor actinomycin D, suggesting that it occurs at the post-transcriptional level. Pre-treatment with CT-1 reduces the ability of heat shock to induce hsp expression and this effect occurs at the transcriptional level. Hence, CT-1 and stress induce the hsps via different pathways which can antagonise one another. The mechanisms of these effects and their potential impact on the use of CT-1 as a cardioprotective agent are discussed.

Blotting, Western↗
PubMed2000

Sonographic evaluation of the thenar compartment musculature.

The thenar region was studied with ultrasonography in 10 healthy volunteers. All thenar muscles could be identified and their course followed entirely. In addition, their function could be assessed by scanning during unresisted or resisted active movements. Standard approach, normal appearance, and dynamic tests for each muscle are described.

Adolescent↗
PubMed1999

Utilization of health care resources by obese Canadians.

BACKGROUND: The prevalence of obesity in Canada has been increasing in recent years. Using data from the National Population Health Survey (NPHS), the authors determined the prevalence of obesity among Canadians, the associated comorbidities and the patterns of resource utilization by obese people. METHODS: The NPHS, a cross-sectional survey conducted in 1994, was administered to 17,626 Canadians 12 years of age or older who were not long-term residents of hospitals or long-term care facilities and were not residing on First Nations reserves or Canadian Armed Forces bases, or in the Yukon and Northwest Territories. For the authors' analysis, the study population consisted of 12,318 Canadians aged 20-64 years who were not pregnant and for whom the body mass index (BMI) had been calculated. The prevalence of comorbidities, health status index scores, self-esteem, self-rated health, restriction of activity, health care resource utilization (physician visits, disability days, admissions to hospital and medication use) were determined for obese people (BMI of 27 or greater) and nonobese people. RESULTS: The NPHS data revealed that 35.2% of men and 25.8% of women in Canada were obese in 1994. Obese respondents were more likely than nonobese respondents to suffer from stress (adjusted odds ratio [OR] 1.20, 95% confidence interval [CI] 1.11-1.31), activity restrictions (adjusted OR 1.39, 95% CI 1.26-1.54) and a number of chronic comorbidities. Obese respondents were also more likely to consult with physicians (adjusted OR 1.32, 95% CI 1.22-1.43), be prescribed a number of medications and to require excess disability days (adjusted OR 1.22, 95% CI 1.08-1.36). INTERPRETATION: Obesity represents a substantial burden on the health of Canadians and on Canada's health care resources.

Adult↗
PubMed1998

Analysis of Canadian population with potential geographic access to intravenous thrombolysis for acute ischemic stroke.

BACKGROUND AND PURPOSE: We sought to identify the Canadian population with potential access to intravenous tissue plasminogen activator within 3 hours of onset of acute ischemic stroke. METHODS: Assuming that 60 minutes is needed for stroke recognition, emergency room evaluation, and administration of tissue plasminogen activator, 120 minutes remain for transport, using a 3-hour treatment window. Ambulance databases were analyzed for transport times of 60, 90, and 120 minutes and were found to correspond to transport distances of 32, 64, and 105 kilometers (20, 40, and 65 miles), respectively. Using Geographical Information System (GIS) software, these radii were overlaid on thematic maps of Canadian hospitals identified as having a third- or fourth-generation CT and with a neurologist and an emergency physician on staff. Analysis was then performed on complete Canadian census data from 1991 and the interim 1996 census count. RESULTS: 67.3%, 78.2%, and 85.3% of the total Canadian population were within 32, 64, and 105 kilometers, respectively, of an identified hospital. For individuals >/=65 years of age, 64.4%, 77.0%, and 85.7% were within the respective radii. Complete analysis by age, ethnic origin, and gender are detailed. CONCLUSIONS: In the model described, a substantial percentage of the Canadian population has geographic access to a hospital potentially capable of delivering intravenous thrombolysis for acute ischemic stroke. GIS analysis can identify both population groups and rural areas with limited access to thrombolytic stroke treatment. A coordinated emergency medical service response for stroke is advocated to maximize coverage, as a 60-minute delay in emergency room arrival eliminated 5.1 million people from potential treatment.

Acute Disease↗
PubMed1998

Stability of diltiazem in whole blood: forensic implications.

The stability of diltiazem (DTZ) in whole blood and in postmortem samples was investigated. In the first study, an aliquot of outdated Red Cross blood with sodium fluoride added as a preservative was spiked with DTZ and stored for one year under three separate conditions: room temperature, 4 degrees C, and -20 degrees C. DTZ and one of its major metabolites, desacetyldiltiazem (DAD), were quantitated at given intervals during this period. In the second study, case postmortem blood samples (n = 36) that exhibited different degrees of putrefaction were spiked in a similar fashion and the stability of DTZ was determined after storage at 4 degrees C for 92 days. DTZ and DAD were extracted as bases, using mild pH conditions to prevent the hydrolysis of DTZ, and quantitated by an HPLC system equipped with a diode array detector and a Supelcosil LCDP column, 5 microns, 250 mm x 4.6 mm inside diameter. Approximately 50% of DTZ was lost in the Red Cross blood stored at room temperature and 4 degrees C, after 19 and 124 days, respectively. This was associated with concomitant appearance and comparable increase in DAD concentration, presumably due to the in vitro hydrolysis of DTZ to DAD. No significant loss of DTZ was observed in the -20 degrees C samples. Similar changes in DTZ and DAD concentrations were seen in postmortem blood samples stored at 4 degrees C for 92 days, though notably, the extent of loss of DTZ varied from complete to negligible. The data suggest that the potential for in vitro conversion of DTZ to DAD should be considered for proper interpretation of postmortem DTZ/DAD findings. Several cases examined in this laboratory will be used to discuss other forensic implications.

Adult↗
PubMed1997

A shorter form health survey: can the SF-12 replicate results from the SF-36 in longitudinal studies?

BACKGROUND: The SF-36 is a generic health status measure which has gained popularity as a measure of outcome in a wide variety of patient groups and social surveys. However, there is a need for even shorter measures, which reduce respondent burden. The developers of the SF-36 have consequently suggested that a 12-item sub-set of the items may accurately reproduce the two summary component scores which can be derived from the SF-36 [the Physical Component Summary Score (PCS) and Mental Health Component Summary Score (MCS)]. In this paper, we adopt scoring algorithms for the UK SF-36 and SF-12 summary scores to evaluate the picture of change gained in various treatment groups. METHODS: The SF-36 was administered in three treatment groups (ACE inhibitors for congestive heart failure, continuous positive airways therapy for sleep apnoea, and open vs laparoscopic surgery for inguinal hernia). RESULTS: PCS and MCS scores calculated from the SF-36 or a sub-set of 12 items (the 'SF-12') were virtually identical, and indicated the same magnitude of ill-health and degree of change over time. CONCLUSION: The results suggest that where two summary scores of health status are adequate than the SF-12 may be the instrument of choice.

Adult↗
PubMed1997

Evaluation of index and profile measures of health status in a randomized controlled trial. Comparison of the Medical Outcomes Study 36-Item Short Form Health Survey, EuroQol, and disease specific measures.

OBJECTIVES: The authors compare two generic measures of health status with disease-specific measures in a randomized controlled trial of transurethral resection of the prostate with laser vaporization prostatectomy for benign prostatic hypertrophy. METHODS: Patients entered into the trial completed the following questionnaires prior to treatment and at follow-up at 3 months and 1 year. The Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) is a generic measure that produces an eight-dimension profile as well as two summary measures of health status (the physical component score and the mental component score). The EuroQol provides two single index measures of health status; one intended to convey the utility (or lack of) that an individual derives from his or her own health state compared with alternative states and a second simple visual analog scale "thermometer" of health status. The American Urological Association symptom score and the Bothersome index are disease-specific indices of health status for use specifically with benign prostatic hypertrophy patients. RESULTS: The EuroQol indicates no statistically significant improvements with time for either arm of the trial. The SF-36 physical and general health perceptions domains indicates statistically significant improvements for the transurethral resection of the prostate arm alone at 3 months and 1 year, as do the physical summary score at the 3-month follow-up visit. The effect sizes of these improvements, however, are small, using standard criteria. In contrast, statistically significant differences are found with time for both transurethral resection of the prostate and laser prostatectomy on both disease-specific measures, which also indicate statistically significant superior outcome for the transurethral resection of the prostate arm compared with the laser arm. CONCLUSIONS: The results indicate that the disease-specific measures are more sensitive to change than the generic measures of outcome. Possible explanations for this are discussed.

Follow-Up Studies↗
PubMed1997

Oral administration of tylosin phosphate for treatment and prevention of proliferative enteropathy in pigs.

OBJECTIVE: To evaluate the efficacy of orally administered tylosin phosphate for prevention and treatment proliferative enteropathy (PE) in pigs. ANIMALS: Crossbred pigs weaned at 24 days of age. PROCEDURE: Pigs were challenge exposed with an inoculum of Lawsonia intracellularis strain LR189/5/83. Seven control pigs received buffer solution. Of 33 challenge-exposed pigs, 8 were untreated. Two groups of challenge-exposed pigs were dosed orally with tylosin phosphate via a 2% stabilized premix, starting with 100 or 40 ppm 4 days before challenge exposure and continuing for 16 days, when the dose was reduced to 40 or 20 ppm, respectively, which was continued for 12 more days. Another group of challenge-exposed pigs was dosed orally with 100 ppm of tylosin phosphate commencing 7 days after challenge exposure and continuing for 21 days. Pigs were euthanatized and necropsied 4 weeks after challenge exposure. RESULTS: The 8 untreated pigs had reduced weight gain, 3 of them had moderate diarrhea 3 weeks after challenge exposure. Five pigs had gross lesions of PE at necropsy. Seven pigs had histologic lesions of PE with numerous L intracellularis organisms. None of the pigs in the control, nonchallenge-exposed, or the 3 groups given tylosin phosphate before or after challenge exposure had clinical signs or lesions of PE. CONCLUSION AND CLINICAL IMPLICATIONS: Tylosin phosphate can be effective for prevention and for treatment of PE, using reported dosing schedules. We can experimentally induce PE, using the pure culture challenge-exposure model, for use in testing of treatments.

Administration, Oral↗
PubMed1997

Quality of life in patients undergoing inguinal hernia repair.

Inguinal hernia repair is one of the most common surgical procedures undertaken in the NHS. Despite this, no previous work has examined quality of life in this patient group. This study examines quality of life preoperatively and at 3 and 6 months postoperatively in 140 patients undergoing inguinal hernia repair in the context of a randomised controlled trial of laparoscopic versus open hernia repair. Surgery was undertaken on a day case basis, and quality of life was assessed using the Short Form 36 (SF36). In the initial phase of the study, 57% of those screened for suitability met the study inclusion criteria and were randomised. No significant differences were found between laparoscopic and open hernia repair in terms of quality of life at 3 and 6 months postoperatively. No difference was found between 3 and 6 month scores, suggesting that patients had already made a good recovery by 3 months. A significant improvement was found between preoperative and postoperative scores, with the greatest change arising on dimensions assessing pain, physical function, and role limitation owing to physical restriction. After standardising for age, sex, and social class, a comparison of the hernia patients to population norms for the SF36 was consistent with improvement from preoperative to postoperative assessment. This study has demonstrated the improvement in quality of life in patients undergoing elective inguinal hernia repair by experienced surgeons on a day case basis. It has also demonstrated the feasibility of assessing quality of life using generic measures in this patient group. Further work in this area is required. Ultimately, the priority given to elective inguinal hernia repair will depend on how the demonstrated benefits compare with those derived from other elective surgical procedures.

Adolescent↗
PubMed1997

Pharmaceutical policies in Canadian family medicine training. Survey of residency programs.

OBJECTIVE: To determine whether family medicine residency training programs have formal policies regarding interactions between residents and the pharmaceutical industry, to identify existing practices, and to find out what issues in industry-physician interaction are addressed during the 2-year core curriculum training in Canada. DESIGN: Mailed survey using a questionnaire. SETTING: The 16 Canadian residency training programs in family medicine. PARTICIPANTS: Program directors of all 16 Canadian family medicine residency training programs replied. MAIN OUTCOME MEASURES: Number of programs with formal pharmaceutical policies; number of programs offering formal curriculum coverage of related topics in the field; program practices regarding industry sampling, detailing, sponsorship, and access. RESULTS: Only four of the 16 programs have formal policies or guidelines. Topics generally covered in core curriculum included critical appraisal (13/16) and cost trends (11/16). Few programs address determinants of prescribing (5/16), marketing techniques (4/16), provincial drug access programs (6/16), or the Canadian Medical Association guidelines on physician-industry interaction (5/16). Industry presence and sponsorship in family medicine training is notable, and screening is limited. Great variation exists, and programs are interested in future initiatives. CONCLUSIONS: Family medicine training in Canada is attempting to address pharmaceutical issues. Interest is strong, but these issues need to be given more emphasis.

Canada↗
PubMed1996

An economic evaluation of laparoscopic versus open inguinal hernia repair.

BACKGROUND: The rapid and widespread introduction of minimal access surgery has major implications for the National Health Service. It cannot be assumed that replacing an open procedure with a minimal access alternative will be cost-effective. Laparoscopic inguinal hernia repair is a procedure for which the potential economic benefits are particularly unclear. It is currently being adopted in many centres, although limited evidence on its clinical and cost-effectiveness exists. METHODS: This economic comparison of laparoscopic versus open hernia repair was undertaken on data collected on 104 patients undergoing surgery on a day case basis, in the context of a randomized controlled trial. RESULTS: The mean total health service cost of laparoscopic repair was 1074 pounds versus 489 pounds for open repair [mean difference in total health service costs 583 pounds; 95 percent confidence interval (CI) 265 pounds-904 pounds]. This difference was largely accounted for by the difference in theatre costs. Laparoscopic repair remained significantly more expensive for most but not all of the scenarios explored in the sensitivity analysis. The direction of the cost-effectiveness ratio was not sensitive to assumptions about long-term recurrence. Neither was it sensitive to halving the operating time in the laparoscopic arm of the trial. When both operating time and the costs of consumables were reduced, laparoscopic repair remained more expensive, but results for this scenario did not achieve statistical significance on this sample size. CONCLUSIONS: Laparoscopic hernia repair appears an expensive option in most plausible situations. Furthermore, many uncertainties still exist about long-term outcome after the procedure and about the conditions necessary to maximize cost-effectiveness. Large-scale randomized studies to evaluate laparoscopic hernia repair are currently under way to address these issues. We suggest that further evidence is awaited before this technology is further diffused.

Adolescent↗
PubMed1996

Relationship between health status and postoperative return to work.

BACKGROUND: Time back to work or normal activity is often regarded as an outcome measure of interest after surgery. It has recently been used as a way of quantifying the benefits of minimal access surgery. However, the extent to which variation in time back to normal reflects differences in health status is unclear. METHODS: The relationship was examined in 140 patients recovering from inguinal hernia repair. A multi-dimensional measure of health status, the Short Form 36 (SF-36), was administered preoperatively, and at ten days and six weeks postoperatively. The relationship between scores on the SF-36 dimensions and return to normal activity was examined using correlation statistics and stepwise regression. RESULTS: Health status dimensions measuring role limitation owing to physical restriction at 10 days and 6 weeks, and role limitation owing to mental problems at ten days were associated with time to return to normal on univariate analysis. Social class was also strongly associated. Using stepwise regression these two dimensions of health status together explained 33 per cent of the variance in time to normal. Other factors unrelated to health status clearly contributed to this outcome. CONCLUSION: Time back to normal activity postoperatively is influenced by a number of factors unrelated to health status and is an unreliable proxy for it. Time to normal is therefore, not a good outcome measure for quantifying the benefits of surgical interventions. Claims currently being made to justify investment in some minimal access interventions should be interpreted in the light of this.

Activities of Daily Living↗