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Biomedical subjects

J Harvey

Publications and source records attributed to J Harvey.

At least 109 records · Page 6Linked to original sources

Characterization of Listeria monocytogenes isolates by esterase electrophoresis.

Multiple bands of alpha-naphthyl-propionyl esterase (alpha NPE) activity observed following starch gel electrophoresis of cell extracts allowed 219 Listeria monocytogenes isolates from milk, nondairy foods, and clinical and veterinary sources to be assigned to 17 different alpha NPE types. Multilocus enzyme electrophoresis (MEE) analysis was used to obtain electrophoretic mobility data for alpha NPEs and nine other metabolic enzymes; on the basis of these data, the 219 strains were assigned to 59 electrophoretic types. Each of the methods separated the strains into two main groups, and there was extensive agreement on assignment of the strains to the groups. Although the method is less discriminatory than MEE, the usefulness of alpha NPE electrophoresis alone as a rapid, simple typing method for L. monocytogenes for certain purposes is indicated by agreement among alpha NPE, MEE, and restriction fragment length polymorphism types as molecular markers for persistent and transient L. monocytogenes strains found in sequential raw-milk and nondairy food samples obtained from different processors.

Animals↗

Physiologic definitions of obliterative bronchiolitis in heart-lung and double lung transplantation: a comparison of the forced expiratory flow between 25% and 75% of the forced vital capacity and forced expiratory volume in one second.

BACKGROUND AND METHODS: A comparison of the forced expiratory flow between 25% and 75% of the forced vital capacity (FEF25-75) and forced expiratory volume in 1 second (FEV1) was conducted for the detection of obstructive airway disease as an early manifestation of obliterative bronchiolitis. Pulmonary function tests performed on heart-lung and double lung transplant recipients between March 1981 and March 1983 were reviewed. Thirty patients were identified who showed progressive deterioration in pulmonary function after transplantation. Ratios determining proportionate decreases were calculated from measurements of absolute values for the FEF25-75 and FEV1 at the point when the FEF25-75 reached < 70% and < or = 30% of predicted, divided by baseline values obtained before the decline in function. Similar ratios were obtained for FEV1 and FEF25-75 at the point the FEV1 declined > or = 20% from its baseline value. RESULTS: Comparison of the ratios for the FEF25-75 and FEV1 at FEF25-75 values < 70% and < or = 30% of predicted and a similar comparison when the FEV1 declined > or = 20% from baseline showed a greater proportional decrease in FEF25-75 than FEV1 (p < 0.01). With the use of the FEF25-75, declines in airway function were detected earlier. After transplantation a decline in FEF25-75 to < 70% of predicted occurred approximately 112 days before a 20% decline a FEV1. CONCLUSION: The FEF25-75 is more sensitive than the FEV1 for the early detection of obliterative bronchiolitis. A presumptive diagnosis of obliterative bronchiolitis can be made with physiologic criteria, providing infection or acute rejection has been ruled out. When conducting epidemiologic studies or for vital statistics we propose that a decline in FEF25-75 to < 70% be used to define the onset of obliterative bronchiolitis.

Adult↗

Cancer in older persons in Scotland.

BACKGROUND: The average age in many populations in increasing. As the risk of most epithelial cancers increases with age, numbers of people with cancer can also be expected to grow. METHODS: Incidence data from the Scottish Cancer Registry for the period 1981-1990 were used to examine the size of the cancer burden in those aged 75 years and over. The future burden of cancer in Scotland was estimated by applying current age specific rates to population projections. Cancer survival in older cancer patients in Scotland was examined and comparisons made with other selected countries. The place of treatment of people under and over 75 in Scotland was investigated. RESULTS: Approximately 30% of the total cancer burden in Scotland and other countries occurs in the elderly. The total number of incident cases in Scotland in those aged 75 and over is estimated to rise by approximately 60% in males and 20% in females by 2029. A decline in survival is seen with increasing age. Older people with cancer in Scotland are less likely to be treated outwit their area of residence and are more likely to be admitted to institutions which admit small numbers of patients. CONCLUSIONS: Cancer in older persons contributes a significant proportion of the overall cancer burden. The burden of cancer in the elderly is likely to grow. More work needs to be done characterising cancer and its treatment in older persons.

Adolescent↗

Chemoradiation in advanced nonsmall cell lung cancer.

PURPOSE: Resectability, local control, and survival were evaluated in advanced stage nonsmall cell lung cancer treated with simultaneous chemoradiation therapy delivered in an accelerated, interrupted twice-a-day schedule. METHODS AND MATERIALS: Forty-seven consecutive patients with Stage IIIA or IIIB nonsmall cell lung cancer, consenting to participation in the study, received cisplatin, 30 mg/m2 for 3 days, etoposid, 80 mg/m2 for 3 days, and 5-fluorouracil, 900 mg/m2 for 4 days. Radiation therapy consisted of 2 Gy given twice a day for 5 days. Two weeks rest was planned between cycles. Patients were evaluated for resectability after the second cycle. Any patient with unresectable tumor received a third cycle of treatment. RESULTS: Forty-seven patients were evaluable for acute toxicity: eighteen (38%) required an extended rest period for esophagitis or low blood count; 3 (6%) had sepsis, of whom 1 (2%) expired. Three patients (6%) had multiple blood transfusions for low hemoglobin. Median follow-up is 23.6 months, with a range of 10-49 months. Nine patients (19%) failed locally; 15 (32%) had local and distant failure; 7 (15%) failed only at distant sites. Twelve patients (25.5%) are alive with no evidence of disease; 4 patients were lost to follow-up with disease. The 2-year actuarial survival is 49%, and the 4-year is 28.2%. CONCLUSION: Simultaneous chemoradiation is well tolerated with acceptable toxicity. The overall 2- and 4-year actuarial survival is somewhat better than that reported in the literature. Resectability in Stage IIIB patients was not increased with this regimen nor was any surgical specimen free of cancer. The 47% distant failure rate is not different from those reported by others.

Adult↗

Histological grading of breast carcinomas: a study of interobserver agreement.

Interobserver variation in the histological grading of breast carcinoma was investigated using the hypothesis that optimal fixation, more precise grading guidelines, some experience, the use of training and test sets, and a comparison of results with an expert group might allow higher levels of agreement. For the training sets sections from 50 consecutive cases of breast carcinoma received at the Sir Charles Gairdner Hospital (SCGH) and fixed in both B5 and buffered formal saline (BFS) were graded by consensus of three pathologists at the SCGH and independently by consensus of two pathologists at the Nottingham City Hospital (NCH) using a modified Scarff-Bloom-Richardson histological grading system with guidelines as suggested by NCH pathologists. The section quality and degree of preservation of nuclear morphology were judged by NCH pathologists to be superior for B5-fixed material. Complete agreement in grade between SCGH and NCH results was achieved for 83.3% of B5-fixed cases and 73.5% of BFS-fixed cases (P = .05) with relative disagreement rates (RDRs) of 0.15 and 0.29 and kappa statistic values of 0.73 and 0.58, respectively. Approximately 80% complete agreement was achieved for tubule formation, nuclear score, and mitotic count, with RDRs ranging from 0.19 to 0.27 and kappa values from 0.46 to 0.69. There was a consistent bias in the SCGH results toward a higher tubule score in both B5- and BFS-fixed material because of a difference in interpretation of cribriform or complex gland patterns and a consistent bias in SCGH results toward a lower nuclear size/pleomorphism score for B5 and BFS material. For the test set sections from 50 further consecutive cases of breast cancer fixed in B5 were examined using similar criteria but taking into account the sources of error shown by the training set. Approximately 80% complete agreement was again achieved for grade components and grade (RDRs, 0.18 and 0.72). Systematic bias was reduced in the test set, but no other improvement was observed. Of the tumors designated as grade I by NCH, 87.5% were called grade I tumors by SCGH in the B5 training set, 84.6% in the B5 test set, and 66.6% in the BFS training set. The levels of agreement shown in both the training and test sets were satisfactory and represented a significant improvement over our previous study, suggesting that experience and precise grading guidelines are of value. The similar levels of agreement in training and test sets suggest that reasonable results can be achieved without direct training by expert groups.(ABSTRACT TRUNCATED AT 400 WORDS)

Breast Neoplasms↗

Transplacental antibody transfer following maternal immunization with polysaccharide and conjugate Haemophilus influenzae type b vaccines.

Passive transfer of antibody to infants born to women immunized during the third trimester of pregnancy with a Haemophilus influenzae type b (Hib) vaccine (PRP polysaccharide or Hib conjugates PRP-D or HbOC) was studied in 50 mothers and infants and 47 nonimmunized mother-infant pairs. Geometric mean total PRP antibody by RIA was 1.2 micrograms/mL at delivery in unimmunized women and 21, 149, and 171 micrograms/mL in women who received PRP, PRP-D, and HbOC, respectively. Mean cord PRP antibody levels were 0.29, 3.0, 17.5, and 29.3 micrograms/mL for the corresponding groups. Postimmunization and cord PRP antibody levels were higher after maternal immunization with conjugate vaccines than with PRP vaccine (P < .01). PRP IgG1 subclass was transmitted more efficiently than IgG2 (56% vs. 35%, P < .01). The proportion of anti-PRP IgG transmitted from immunized mothers to infants correlated with time between immunization and delivery. Administration of PRP conjugate vaccines to women during pregnancy resulted in higher levels of PRP antibodies in infants than did polysaccharide or no vaccine.

Adult↗

Detection of occult bone marrow micrometastases in patients with operable lung carcinoma.

OBJECTIVES: A large proportion of patients with operable lung carcinoma (no evidence of systemic spread of tumor) develop metastatic disease after primary therapy. More sensitive and specific methods are needed to identify patients at highest risk for recurrence who may benefit most from adjuvant therapy, while sparing those patients who do not require such treatment. SUMMARY BACKGROUND DATA: Using epithelial-specific monoclonal antibodies, the authors have developed an immunocytochemical assay capable of detecting as few as 2 lung cancer cells in 1 million bone marrow cells. METHODS: The assay was used to test the bone marrow (from resected ribs) of 43 patients with primary non-small cell lung carcinoma who showed no clinical or pathologic evidence of systemic disease. RESULTS: Occult bone marrow micrometastases (BMMs) were detected in 40% of patients (17/43) with non-small cell lung cancer, including 29% (5/17) of patients with stage I or II disease and 46% of whom (12/26) had stage III disease. The median follow-up was 13.6 months. Patients with occult BMMs had significantly shorter times to disease recurrence compared with patients without BMMs (7.3 vs. > 35.1 months, p = 0.0009). Furthermore, for patients with stage I or II disease, the presence of occult BMMs was significantly associated with a higher rate of recurrence (p = 0.0004). CONCLUSIONS: The detection of occult BMMs identifies patients with operable non-small cell lung carcinoma who are at significantly increased risk for recurrence, independent of tumor stage, and may be useful in evaluating patients for adjuvant treatment protocols.

Antibodies, Monoclonal↗

The undergraduate medical curriculum: centralized versus departmentalized.

The authors describe the advantages and disadvantages of central governance of the undergraduate medical curriculum as contrasted with traditional departmental approaches, based upon their school's experience with a new centrally governed curriculum during the preceding four years. Central governance has more advantages, but also more costs, compared with traditional departmental approaches. Central governance does what it was intended to do: it provides rational and integrative mechanisms for ensuring a broad general education in medicine focusing on the doctor-patient relationship. It also provides an effective mechanism for dealing with "turf" and time issues in the curriculum while allowing for and encouraging changes and providing mechanisms for evaluating those changes. However, as the allocation of resources and rewards remains more departmentally than centrally based, a major challenge of central governance has been to help faculty resolve a "conflict of loyalty" (the sense of serving two masters) between school and department, particularly in the evaluation and reward of teaching. On balance, central governance provides a powerful means of introducing broad-based reforms into all elements of the undergraduate medical curriculum, but it requires ongoing collaboration with faculty and chairs to assist them in negotiating competing pressures and priorities as they strive to become excellent teachers.

Administrative Personnel↗

Cholesterol screening in the elderly: changing attitudes.

The purpose of this study was to assess an elderly population's (60-80 years old) attitudes toward health prevention and life-style change with a particular emphasis on cholesterol screening and management. A free cholesterol screen was offered to participants in exchange for completion of a 21-item questionnaire (including medical history, risk factors, attitudes on preventive health, eating patterns and demographic information). This study provides evidence for increasing awareness of elevated cholesterol levels as a risk factor for coronary heart disease. It also demonstrates that there is an attitude of willingness to modify dietary cholesterol and fat intake within this mobile elderly population.

Age Factors↗

Squamous cell carcinoma of the pyriform sinus: a nonrandomized comparison of therapeutic modalities and long-term results.

From January 1964 through December 1991, 408 patients with squamous cell carcinomas involving the pyriform sinus were treated at Washington University Medical Center. Their ages ranged from 29 to 83 years (mean, 62.3; median 59) and the male to female ratio was 5:1. The mean duration of symptoms prior to diagnosis was 3.9 months (range 1 to 32 months) and 89% had a smoking or ethanol history. Sixty-seven percent had T3 or T4 lesions and 87% were stage III or IV at presentation. Sixty-nine percent had neck metastases. The treatment strategy varied with respect to radiation and reconstruction. Prior to 1978, preoperative radiation (3.5 to 5000 cGy) was used. Postoperative radiation was given thereafter (600+ Gy). Since 1982, flap reconstruction (usually pectoralis major myocutaneous) has been used to close the partial laryngopharyngectomy (PLP) defect. Almost all N0 necks were treated by radiation or surgery and all N1-N3 lesions were treated by combined therapy. Pyriform tumors were subdivided into three groups: 1. one-wall lesions (n = 48), 2. medial-wall lesions which involved the aryepiglottic fold or supraglottis (N = 267), and 3. two- or three-wall lesions which extended to the pyriform apex or post-cricoid region (N = 93). Ninety-five patients had single-modality therapy and 302 had combined treatment. Two hundred seven patients had conservation surgery (PLP) and 157 had total laryngopharyngectomy alone or in combination with radiation. Thirty-three patients were treated by radiation alone. Eleven patients were excluded from the study because of distant metastases (TxNxM1) at presentation. The cumulative survival (NED) at 5, 10, 15, and 20 years was 56%, 35%, 31%, and 20%, respectively. The cumulative locoregional control rate was 71%. At 5 years (NED), the cure rates for one-wall lesions (73%) were better than for medial-wall lesions (63%) or 2- and 3-wall lesions (49%). One-wall lesions were smaller, medial-wall lesions behaved similar to supraglottic tumors, and two- or three-wall tumors behaved as hypopharyngeal tumors. The cure rates were related to T stage with T1 + T2 > T3 + T4 (28%). Neck metastases reduced the cure rate by 26% and N1 > N2-N3 by an additional 12%. Other factors contributing to therapeutic failure were distant metastases (17.7%), second primary tumors (6.2%; oropharynx and lung were most common), and intercurrent disease fatalities (9.5%). The secondary therapeutic salvage rate was 44% for surgery and 32% for radiation therapy. The therapeutic complication rate was 19% with 3.6% leading to fatality.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Integrin LFA-1 alpha subunit contains an ICAM-1 binding site in domains V and VI.

In order to identify a binding site for ligand intercellular adhesion molecule-1 (ICAM-1) on the beta 2 integrin lymphocyte function-associated antigen-1 (LFA-1), protein fragments of LFA-1 were made by in vitro translation of a series of constructs which featured domain-sized deletions starting from the N-terminus of the alpha subunit of LFA-1. Monoclonal antibodies and ICAM-1 were tested for their ability to bind to these protein fragments. Results show that the putative divalent cation binding domains V and VI contain an ICAM-1 binding site. A series of consecutive peptides covering these domains indicated two discontinuous areas as specific contact sites: residues 458-467 in domain V and residues 497-516 in domain VI. A three-dimensional model of these domains of LFA-1 was constructed based on the sequence similarity to known EF hands. The two regions critical for the interaction of LFA-1 with ICAM-1 lie adjacent to each other, the first next to the non-functional EF hand in domain V and the second coinciding with the potential divalent cation binding loop in domain VI. The binding of ICAM-1 with the domain V and VI region in solution was not sensitive to divalent cation chelation. In short, a critical motif for ICAM-1 binding to the alpha subunit of LFA-1 is shared between two regions of domains V and VI.

Amino Acid Sequence↗

Ocular injury secondary to periorbital use of stainless-steel wire and suture.

OBJECTIVE: To describe previously unreported ocular injuries from stainless-steel wire or suture used for facial skeletal or soft-tissue repair. PARTICIPANTS: Three patients who underwent orbital reconstruction (n = 2) or ptosis repair with excision of the orbiculus oculi (n = 1) were referred with signs and symptoms of ocular injury. INTERVENTIONS: Removal of the wires and sutures. RESULTS: Treatment resolved discomfort and irritation and diminished ocular motility, iritis, and bullous keratopathy but did not improve diminished vision in one of the patients. CONCLUSIONS: Occult ocular injury from misdirected or migrating stainless-steel wire should be considered in any case of ocular injury following orbital fracture or reconstructive repair when other disease processes are readily excluded. In these three cases, stainless-steel wire or suture impinged against or impaled the globe. The use of rigid plate fixation for orbital reconstruction or otherwise placing all stainless-steel wires and sutures outside the confines of the orbit would avoid such ocular injury.

Aged↗

Year-long weight loss treatment for obese patients with type II diabetes: does including an intermittent very-low-calorie diet improve outcome?

PURPOSE: To evaluate a year-long behavioral weight control program, used with and without an intermittent very-low-calorie diet (VLCD) in the treatment of type II diabetes mellitus. PATIENTS AND METHODS: Subjects (n = 93) were randomly assigned to 50-week treatment programs that used either a balanced low-calorie diet (LCD) of 1,000 to 1,000 kilocalories (kcal) per day throughout or included 2 12-week periods of a VLCD of 400 to 500 kcal per day alternating with the balanced LCD. Weight, glycemic control, blood pressure, and lipids were assessed at baseline, at the end of the year-long treatment, and at 2-year follow-up. RESULTS: Subjects in the VLCD program lost significantly more weight than did LCD subjects at the end of the 50-week program (14.2 kg versus 10.5 kg; P = 0.057) and remained off diabetes medication longer (P < 0.05). These benefits of the VLCD were due primarily to the first 12 weeks of the diet; the second diet maintained, but did not increase, these effects. Subjects in both groups experienced marked improvements in glycemic control and cardiovascular risk factors over the year-long program, but attendance declined in the latter weeks of treatment and weight was regained. There was also marked recidivism in both groups in the year following treatment. CONCLUSIONS: The intermittent VLCD improved weight loss and glycemic control, but these effects were quite modest and do not appear to justify the clinical use of an intermittent VLCD. Moreover, lengthening treatment to a full year did not prevent relapse. Thus, further research is needed to develop a successful approach to long-term weight control.

Adult↗