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Biomedical subjects

J Clark

Publications and source records attributed to J Clark.

At least 37 records · Page 2Linked to original sources

Posterior distal cement extrusion during primary total hip arthroplasty: a cause for concern?

Manually operated injection systems are routinely used to deliver polymethyl methacrylate during cemented femoral component primary total hip arthroplasty (THA). The goal of cement delivery is to achieve sufficient intrusion of cement into the trabecular bone of the prepared femur so that the femoral component is securely bonded to the femur. We have observed posterior distal cement extrusion (PDCE), which appears to be secondary to too-successful pressurization. We sought to quantify and offer a possible explanation for this phenomenon. Eight patients with PDCE were identified, with an estimated incidence range of 0.90%, to 1.6% of primary cemented femoral component THA. All occurred in female patients of small stature. Endosteal canal diameters were also small, averaging 11 mm, 10 cm from the lesser trochanter. The PDCE occurred at an average distance of 9.8 cm from the midpoint of the lesser trochanter, and was most easily visualized on the lateral radiograph where it resided in the posterior soft tissues. Examination of 49 human femora showed 1 or more vascular channels in the posterior aspect of the femur in all specimens. The most proximal vascular channel averaged 10.1 cm distal to the lesser trochanter and had an average lumen diameter of 1 mm. The vascular channel contained an artery and 2 veins by histologic examination. We postulate that PDCE represents the escape of low-viscosity cement out of the vascular channel, and laboratory simulation supports this possibility. Because this finding has not previously been reported, we hoped that other centers will look closely for this phenomenon.

Aged↗

Loss of chromosome 10 is an independent prognostic factor in high-grade gliomas.

Loss of heterozygosity (LOH) for chromosome 10 is the most frequent genetic abnormality observed in high-grade gliomas. We have used fluorescent microsatellite markers to examine a series of 83 patients, 34 with anaplastic astrocytoma (grade 3) and 49 with glioblastoma multiforme (grade 4), for LOH of chromosome 10. Genotype analysis revealed LOH for all informative chromosome 10 markers in 12 (35%) of patients with grade 3 and 29 (59%) grade 4 tumours respectively, while partial LOH was found in a further eight (24%) grade 3 and ten (20%) grade 4 tumours. Partial LOH, was confined to the long arm (10q) in six and the short arm (10p) in three cases, while alleles from both arms were lost in four cases. Five tumours (one grade 3 and four grade 4) showed heterogeneity with respect to loss at different loci. There was a correlation between any chromosome 10 loss and poorer performance status at presentation (chi2 P = 0.005) and with increasing age at diagnosis (Mann-Whitney U-test P = 0.034) but not with tumour grade (chi2 p= 0.051). A Cox multivariate model for survival duration identified age (proportional hazards (PH), P= 0.004), grade (PH, P= 0.012) and any loss of chromosome 10 (PH, P= 0.009) as the only independent prognostic variables. Specifically, LOH for chromosome 10 was able to identify a subgroup of patients with grade 3 tumours who had a significantly shorter survival time. We conclude that LOH for chromosome 10 is an independent, adverse prognostic variable in high-grade glioma.

Brain Neoplasms↗

Students conducting consultations in general practice and the acceptability to patients.

OBJECTIVES: The General Medical Council has recommended that medical students should gain more experience in general practice. The study set out to determine patients' reactions to consultations conducted by a medical student alone prior to seeing their GP. DESIGN: A random sample of patients attending general practice surgeries in the Oxford area completed a questionnaire following consultation with a medical student. SETTING: Six general practice teaching surgeries. SUBJECTS: Fifth-year medical students. RESULTS: Of 130 responders 98% experienced no disadvantage in seeing the student; 35% considered that there were advantages in seeing the student; 98% said that they would be prepared to consult with a student again; 85% expressed no concerns about the gender of the student. CONCLUSIONS: The results of this study are very reassuring concerning the acceptability to patients of consulting with medical students and are more favourable than those reported for studies of students being present in consultations by GPs.

Education, Medical, Undergraduate↗

Severe cardiotoxicity during 5-fluorouracil chemotherapy: a case and literature report.

The chemotherapeutic agent 5-fluorouracil (5-FU) is a widely accepted part of many cancer treatment protocols. Its cardiotoxic potential is known, but considered uncommon and usually not life threatening, although some cases of severe cardiotoxicity related to 5-FU have been reported. The pathogenesis of cardiotoxicity caused by 5-FU is not clear. We report a case of sudden onset of severe cardiac failure, without ischemic symptoms or signs, during 5-FU treatment with serious consequences, in a previously healthy 23-year-old patient with squamous cell carcinoma of the tongue. Endomyocardial biopsy showed proliferation of the sarcoplasmic reticulum with marked vacuolization, similar to that found with doxorubicin cardiotoxicity. Because 5-FU cardiotoxicity is unpredictable and can have potentially fatal consequences, it requires, in our opinion, further clarification. With this well-documented case, including an endomyocardial biopsy, we hope to encourage additional efforts to investigate the pathophysiologic mechanisms of 5-FU cardiotoxicity.

Adult↗

Enhancing psychiatric nursing practice: role of an advanced practice nurse.

In response to demands for alternative health models that deliver cost-effective quality care, one large Midwestern medical center implemented a change in their nursing practice model. The change involved the introduction of unit-based nursing leadership teams that included advanced practice nurses (APNs). This article reports the findings from an investigation that employed a case study design to evaluate the process and outcomes of integrating an APN on a psychiatric unit with experienced nurses. Data collection methods included a nursing survey (n = 34), interviews with nine randomly selected nurses, and two multidisciplinary open forums. Consistent with the staff nurses' survey ratings of important advanced practice role functions, responses from the nursing interviews and open forums suggested nurses' professional development to be the most positive outcome. Role confusion was identified as a negative outcome. Recommendations for improved integration and use of APNs in today's psychiatric health environments were identified.

Hospital Units↗

A randomized prospective trial of amphotericin B lipid emulsion versus dextrose colloidal solution in critically ill patients.

BACKGROUND: Amphotericin B is the agent of choice for most invasive fungal infections in critically ill patients. It is associated with at least a 50% incidence of nephrotoxicity, despite prophylactic measures such as sodium loading. Newer formulations of amphotericin B are available but are costly and have unknown bioavailability in critically ill patients. Previous trials in neutropenic and critically ill patients have demonstrated that mixing amphotericin B with 20% lipid solution (Intralipid; Clintec Nutrition, Deerfield, III) may decrease nephrotoxicity. METHODS: In this randomized, prospective clinical trial, patients with positive fungal blood cultures, tracheal/sputum cultures or peritoneal cavity cultures were randomized to receive either 0.5 mg/kg per day of amphotericin B dextrose or 1.0 mg/kg per day of amphotericin B lipid emulsion. Duration of therapy was determined by the primary care team. Weekly 24-hour creatinine clearance was measured until 2 weeks after amphotericin B therapy was completed. RESULTS: The two groups were similar based on age, white blood cell count, serum creatinine, and creatinine clearance at the beginning of therapy. The group receiving amphotericin B lipid emulsion had significantly less decrease in creatinine clearance compared with controls, despite receiving significantly more amphotericin B. CONCLUSION: Amphotericin B lipid emulsion can be given at a higher total cumulative dose than amphotericin B dextrose with less nephrotoxicity.

Adult↗

Multi-institutional study of the angiogenesis inhibitor TNP-470 in metastatic renal carcinoma.

PURPOSE: Renal cell carcinoma is resistant to most chemotherapy, and only a minority of patients respond to immunotherapy. Its highly vascular nature suggests that antiangiogenesis therapy might be useful. We thus performed a phase II study of the fumigillin analog TNP-470 in previously treated patients with metastatic renal cell carcinoma. PATIENTS AND METHODS: Metastatic renal cell carcinoma patients with good organ function were entered onto the study through five separate institutions. There were no exclusion criteria for prior therapy. All patients were treated at a dose of 60 mg/m(2) of TNP-470 infused over 1 hour three times per week. RESULTS: Thirty-three patients were enrolled. Therapy was generally well tolerated, but asthenia, fatigue, vertigo, dizziness, sense of imbalance, and loss of concentration were common and severe enough to lead to therapy discontinuation in five patients. There was only one partial response of short duration (response rate, 3%, 95% confidence interval, 0% to 16%), but six patients (18%) remained on study for 6 or more months without toxicity or disease progression. CONCLUSION: Long-term therapy with TNP-470 has manageable toxicities and is feasible in patients with metastatic renal cell carcinoma but does not lead to any significant objective responses. Further studies in this population using TNP-470 schedules that produce more prolonged drug levels and clinical trial end points other than objective tumor regression may be indicated.

Adult↗

Femoral neck length and hip fracture risk.

To determine whether there are differences in femoral skeletal geometry in fracture-prone subjects when size, positioning diagnosis, and age are controlled, we compared femoral measurements made from the uninvolved hip on 119 plane anteroposterior pelvis radiographs of women without fracture to those of the contralateral hip in a group of 43 female patients with hip fractures (neck, 23; intertrochanteric, 20). The hip was imaged in a standardized position of rotation and adduction. Race, age, and musculoskeletal diagnosis were known. Subjects were grouped by diagnosis of the opposite hip condition (rheumatoid arthritis, osteoarthritis, and normal) and compared. Measurements were also analyzed as ratios to head diameter (HD), neck diameter (ND), and pelvic width. Femoral neck length (NL) was measured from skeletal preparations and imaged in controlled positions of abduction and external rotation. No differences were found between the neck and intertrochanteric fracture groups. The differences between the fracture group and the controls were a thinner femoral cortex (measured at a point one head radius below the lesser trochanter) a larger femoral head, and a larger femoral ND in the fracture group (p < 0.025). The difference in cortical thickness was still significant when scaled by size, but the ratio of HD to ND was equivalent in fractures and controls. No difference in femoral NL could be demonstrated. The experimental measurements showed that apparent NL is significantly position sensitive and this may explain previously reported differences in fracture-prone groups.

Aged↗

Syringe exchange in the United States, 1996: a national profile.

OBJECTIVES: This paper provides 1996 information on the status of US syringe exchange programs and compares these findings with data from our 1994 survey. METHODS: In November 1996, questionnaires were mailed to 101 syringe exchange programs. Program directors were contacted to conduct telephone interviews based on the mailed questionnaires. Data collected included number of syringes exchanged, syringe exchange program operations, legal status, and services offered. RESULTS: Eighty-seven programs participated in the survey. A total of 46 (53%) were legal, 20 (23%) were illegal but tolerated, and 21 (24%) were illegal-underground. Since 1994, there has been a 54% increase in the number of cities and a 38% increase in the number of states with syringe exchange programs. Eighty-four programs reported exchanging approximately 14 million syringes, a 75% increase from 1994. Syringe exchange programs also provided a variety of other services and supplies, and legal programs were more likely than illegal ones to provide these services. CONCLUSION: Despite continued lack of federal funding, syringe exchange programs expanded in terms of the number of syringes exchanged, the geographic distribution of programs, and the range of services offered.

Health Care Surveys↗

Extending the indications for breast-conserving treatment to patients with locally advanced breast cancer.

PURPOSE: Breast-conserving therapy (BCS) has generally been limited to T1 and T2 lesions because it has been thought impossible to achieve good local control with satisfactory cosmesis in patients with more advanced disease. However, many patients with T3 and T4 lesions will exhibit dramatic tumor downstaging with neoadjuvant chemotherapy. It is our hypothesis that for these patients BCS can be performed with good local control and cosmesis. METHODS AND MATERIALS: Between February 1991 and November 1995, 34 patients with T3/T4, N0-N2, M0 breast cancer completed treatment consisting of 90 mg/m2 of doxorubicin every 21 weeks x 4, surgery (a local excision if sufficiently downstaged, or mastectomy if not), high dose cyclophosphamide (CMF) every 2 weeks x 4, and radiation therapy. Radionuclide ventriculograms were performed on all patients pre- and postdoxorubicin, and at 6-12 months post radiation therapy. Patients were evaluated for toxicity, local control, cosmesis, disease-free and overall survival. RESULTS: Median follow-up is 30 months. 15/34 (44%) patients underwent BCS with only one local-regional failure and actuarial 3-year disease-free and overall survival of 77% and 88%. Cosmetic results were good to excellent in 80% of the patients. Left ventricular ejection fraction, which predictably declined following doxorubicin, did not further decline after radiation therapy. CONCLUSIONS: These results suggest that with this regimen a subset of patients with locally advanced breast cancer can preserve their breast with acceptable cosmesis without compromising local control or survival.

Adult↗

The design and synthesis of inhibitors of the cysteinyl protease, Der p I.

Prototype irreversible inhibitors of the cysteinyl protease Der p I were designed, synthesised and evaluated in vitro. Candidates were designed using a modular approach, whereby a peptide sequence was appended with known thiophilic moieties. This hinged on utilizing peptide sequences from substrate specificity data compiled using proprietary RAPiD technology.

Animals↗

Health-related quality of life in patients served by the Department of Veterans Affairs: results from the Veterans Health Study.

BACKGROUND: The Department of Veterans Affairs Health Care System (VA) is the largest integrated single payer system in the United States. To date, there has been no systematic measurement of health status in the VA. The Veterans Health Study has developed methods to assess patient-based health status in ambulatory populations. OBJECTIVES: To describe the health status of veterans and examine the relationships between their health-related quality of life, age, comorbidity, and socioeconomic and service-connected disability status. METHODS: Participants in the Veterans Health Study, a 2-year longitudinal study, were recruited from a representative sample of patients receiving ambulatory care at 4 VA facilities in the New England region. The Veterans Health Study patients received questionnaires of health status, including the Medical Outcomes Study Short Form 36-Item Health Survey; and a health examination, clinical assessments, and medical history taking. Sixteen hundred sixty-seven patients for whom we conducted baseline assessments are described. RESULTS: The VA outpatients had poor health status scores across all measures of the Medical Outcomes Study Short Form 36-Item Health Survey compared with scores in non-VA populations (at least 50% of 1 SD worse). Striking differences also were found with the sample stratified by age group (20-49 years, 50-64 years, and 65-90 years). For 7 of the 8 scales (role limitations due to physical problems, bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems, and mental health), scores were considerably lower among the younger patients; for the eighth scale (physical function), scores of the young veterans (aged 20-49 years) were almost comparable with the levels in the old veterans (>65 years). The mental health scores of young veterans were substantially worse than all other age groups (P<.001) and scores of screening measures for depression were significantly higher in the youngest age group (51%) compared with the oldest age groups (33% and 16%) (P<.001). CONCLUSIONS: The VA outpatients have substantially worse health status than non-VA populations. Mental health differences between the young and old veterans who use the VA health care system are sharply contrasting; the young veterans are sicker, suggesting substantially higher resource needs. Mental health differences may explain much of the worse health-related quality of life in young veterans. As health care systems continue to undergo a radical transformation, the Department of Veterans Affairs should focus on the provision of mental health services for its younger veteran.

Adult↗