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Biomedical subjects

L Cox

Publications and source records attributed to L Cox.

At least 19 recordsLinked to original sources

Hyperproinsulinaemia in patients with myotonic dystrophy.

Hyperinsulinaemia is a reported feature of the inherited multisystem disorder myotonic dystrophy. This phenomenon has been attributed to a compensatory beta cell response to tissue insulin resistance. In this study, circulating concentrations of insulin, proinsulin, and split proinsulin molecules were determined after an overnight fast in ten patients with myotonic dystrophy using two-site monoclonal antibody-based immunoradiometric assays. Results were compared with ten healthy control subjects matched for age, gender, and body mass index. Oral glucose tolerance (75 g), as defined by World Health Organization criteria, was normal in all subjects. Fasting plasma immunoreactive insulin concentration, as determined using a conventional radioimmunoassay, was almost three times higher (p < 0.005) in the myotonic dystrophy patients than the healthy control subjects. By contrast, fasting concentrations (mean +/- SEM) of C-peptide (0.75 +/- 0.09 vs 0.52 +/- 0.03 nmol/l, p = 0.07) and immunoradiometrically-determined insulin (60 +/- 12 vs 38 +/- 4 pmol/l, p = 0.09) were not significantly different between the groups. Fasting concentrations of proinsulin (10.3 +/- 2.9 vs 1.6 +/- 0.3 pmol/l, p < 0.01), and 32-33 split proinsulin (7.8 +/- 2.5 vs 2.9 +/- 0.4 pmol/l, p < 0.05) were significantly elevated in the patients with myotonic dystrophy. Accordingly, the mean fasting proinsulin:insulin ratio, expressed as a percentage, was significantly increased in the myotonic patients (20 +/- 5 vs 4 +/- 1%, p < 0.01). The overall C-peptide response to the oral glucose challenge was significantly greater in the myotonic patients compared with the healthy control subjects (p < 0.001). These results provide corroborative evidence of increased beta-cell secretion in myotonic dystrophy.(ABSTRACT TRUNCATED AT 250 WORDS)

C-Peptide

Immunoradiometric assay of insulin, intact proinsulin and 32-33 split proinsulin and radioimmunoassay of insulin in diet-treated type 2 (non-insulin-dependent) diabetic subjects.

Plasma insulin, intact proinsulin and 32-33 split proinsulin measured by specific immunoradiometric assays and insulin and C-peptide measured by radioimmunoassay were measured during a constant infusion of glucose test in ten diet-treated subjects with a history of Type 2 (non-insulin-dependent) diabetes (termed diabetic subjects), mean fasting plasma glucose 6.0 +/- 1.0 mmol/l (mean +/- SD), and 12 non-diabetic control subjects. Immunoreactive insulin concentrations measured by radioimmunoassay were 33% higher than insulin and 16% higher than the sum of insulin and its precursors by immunoradiometric assay. The diabetic and non-diabetic subjects had similar fasting concentrations of insulin, intact proinsulin and 32-33 split proinsulin. The ratio of fasting intact proinsulin to total insulin was greater in the diabetic than the non-diabetic group 12.0% (6.8-21.0%, 1 SD range) and 6.3% (4.0-9.8%), respectively, p less than 0.01), though the groups overlapped substantially. After glucose infusion, diabetic and non-diabetic subjects had similar intact proinsulin concentrations (geometric mean 4.9 and 5.2 pmol/l, respectively), but the diabetic group had impaired insulin secretion by immunoradiometric assay (geometric means 55 and 101 pmol/l, p less than 0.05) or by radioimmunoassay C-peptide (geometric means 935 and 1410 pmol/l, p less than 0.05), though not by radioimmunoassay insulin (87 and 144 pmol/l, p = 0.12), respectively. Individual immunoradiometric assay insulin responses to glucose expressed in terms of obesity were subnormal in nine of ten diabetic subjects. Radioimmunoassay insulin and C-peptide gave less complete discrimination (subnormal responses in six of ten and eight of ten, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose

Sensitive amplified immunoenzymometric assays (IEMA) for human insulin and intact proinsulin.

Immunoenzymometric assays (IEMAs) for human insulin and intact proinsulin were developed using the amplification system developed by Johannsson et al. (Clin. Chim. Acta 148 (1985) 119-124) for the detection of the enzyme alkaline phosphatase. The detection limit of the assays was 0.8 pmol/l for proinsulin and 0.8 pmol/l for insulin whereas it was 1.8 pmol/l and 2.3 pmol/l respectively for the homologous immunoradiometric assays (IRMA). These assays are superior to immunoradiometric assays in terms of sensitivity, shelf-life of the labelled antibody and suitability for automation.

Alkaline Phosphatase

Duct carcinoma in situ of the breast: an analysis of local control after conservation surgery and radiotherapy.

Patients with duct carcinoma-in-situ are being treated with increasing frequency at our center. Between 1977 and 1988, 54 patients, including one with bilateral disease, opted for breast conserving surgery and radiation therapy. The median follow-up was 3 years (range 2-13 years). During this period, 10 patients (18%) had a recurrence in the breast; the local failure probability was 22% at 6 years (Kaplan-Meier). All patients had pre-biopsy mammograms, and in 67% this was the presenting abnormality. Thirty-three lesions (60%) required needle localization. Size, as determined by mammogram or pathology, was 2 cm or less in 60%, 2.1 to 4 cm. in 2%, and not measurable in the remainder. Close or involved margins were noted in 30% of patients who locally recurred, despite the fact that 50% had had a re-excision after their initial biopsy. Breasts which maintained local control had only 4% involved margins and re-excision was performed in only 20%. Radiation doses ranged from 4600 to 5200 cGy to the entire breast with tangential fields, followed by a boost dose in 73% of patients. No patient in the study has developed distant metastasis or died of breast carcinoma, but the local failure rate is of concern and has alerted our group to reexamine its treatment policy in patients with evidence of margin involvement. We continue to consider residual microcalcifications after surgery to be a contraindication to breast conservation.

Adult

Primary breast irradiation in large-breasted or heavy women: analysis of cosmetic outcome.

Treatment of early stage breast cancer with lumpectomy, axillary dissection, and radiation therapy is considered by many to be relatively contraindicated in heavy women or women with large or pendulous breasts. To quantitatively analyze this, we reviewed the cosmetic outcome in 257 patients. These patients were divided into "large" (89) and "average" (168) groups by one or more of the following criteria: weight greater than or equal to 80 kg, bra size greater than or equal to 40 in., cup size greater than or equal to D, and tangent separation greater than or equal to 23 cm. All patients were given cosmetic scores on a 1-10 scale by an independent observer for each of 8 cosmetic indices. These scores were analyzed at 1, 3, and 5 years follow-up (median 3 years). The average group scored higher than the large group on overall cosmesis (8.01 vs 7.34, p = 0.0004) and on 5 of 7 subindices (p = 0.0001 to 0.05) at 1 year. At 3 and 5 year follow-up only symmetry and retraction remained significantly different, favoring the average group. The largest difference noted at any point between the groups was 1.27 (retraction at 5 years, 8.54 vs 7.27, p = 0.0148). Therefore, although an inferior cosmetic result has been documented in the large group, we do not feel the magnitude of the difference mandates a change in our policy of offering all of these women breast-conserving therapy.

Adult

Arm edema in conservatively managed breast cancer: obesity is a major predictive factor.

To identify risk factors in the development of arm edema (AE) after conservative management of breast cancer, the authors prospectively measured differences in upper and lower arm circumference in 282 patients with stage I or II breast cancer who received radiation. AE was defined as a difference of 2.5 cm or more in either measurement between treated and untreated arms. Median follow-up was 37 months (range, 7-109 months). The crude frequency of AE overall was 19.5% (55 patients). In 21 patients (7.4%) AE was transient; 34 patients (12.1%) had persistent AE, which is the focus of this article. The 5-year actuarial incidence of persistent AE was 16%. The crude risk of persistent severe AE was 3.9%. Various factors were examined for their ability to enable prediction of AE. Treatment-related factors did not significantly enable prediction of AE, whereas factors related to patient size, such as body mass index, were strongly associated with both the frequency and severity of AE.

Adult

Correlates of drinking and drug use by higher education faculty and staff: implications for prevention.

The prevalence and frequency of drug and alcohol abuse among higher education faculty and staff is not known. Higher education is a cultural environment which, on the one hand, is stressful and, on the other, permits a high degree of autonomy. This relationship of stress and autonomy is predicted to produce drug and alcohol abuse. Information is gathered by anonymous, self-report questionnaires, on the frequency and prevalence of faculty and staff drug and alcohol use at a regional university. Responses show alcohol and drug use within the last year and month among four higher education occupational groups: faculty, administrators, clerical staff, and physical plant/custodial staff. While stress was found to be weakly correlated with some drug use in the last month, depression was consistently correlated with drug use and moderately correlated with suicidal thoughts and tendencies, as well as job dissatisfaction. Drug and alcohol abuse is a factor in behavioral problems that affect faculty/staff and can be addressed through Employee Assistance Programs.

Administrative Personnel

Growth hormone increases rate of pubertal maturation.

We have performed a retrospective analysis of the pubertal parameters of 134 children with isolated GH insufficiency on GH treatment and compared them to the standards of Tanner and to a recent longitudinal study of growth and development in the United Kingdom. The age at onset of puberty (13.0 years in boys, 12.1 years in girls) was found to be significantly delayed (Mann-Whitney p less than 0.001), but duration of puberty (1.5 years in both sexes) was shortened (Kolgomarov-Smirnov p less than 0.01). Skeletal maturity at the onset of puberty was not advanced excluding this as a contributory factor. There was no association between dose of GH administered and the pubertal parameters. The results suggest that GH accelerates the pubertal process.

Adolescent

Differentiation of benign and malignant local tumor recurrence after lumpectomy.

During a 5-year period, 28 women who had been treated conservatively for breast carcinoma had 29 reexcisions of the lumpectomy site because of suspicion of a recurrent malignant tumor. Biopsy results were benign in 19 cases and malignant in 10 cases. Sixteen of the 19 benign tumors had developed within 2 years after therapy. In 16 benign cases, a palpable lump developed at the scar and was found on biopsy to be fat necrosis or fibrosis. Seven of these cases had normal mammographic findings. Three women with abnormal mammographic findings but a normal breast examination had punctate microcalcifications develop at the scar; these were due to fibrosis in two and sclerosing adenosis in the other. Of the 10 malignant recurrent tumors, seven were palpable, four of which also were identifiable by mammography. Of seven mammographically identifiable recurrent tumors at the surgical site, four were palpable. Mammographic findings were a single mass in two cases, multiple masses in one, microcalcification in three, and a mass with microcalcifications in one. Malignant microcalcifications were all linear, irregular, and in one case branching. Mean time to recurrence in these 10 women was 3 years. This experience suggests that benign disease usually occurs at the scar within 2 years after the original therapy and when palpable may not show changes on mammography. When microcalcifications do occur, they are usually punctate.

Adult

The patients perception of her breast following radiation and limited surgery.

Seventy-four patients followed from 1 to 8 years post completion of breast-conserving surgery and radiation for early-stage breast cancer were asked to answer a questionnaire exploring their perception and awareness of the treated breast. The questionnaire was divided into several sections, including "Daily Activities", Pre-menstrual Changes", "Sexual Activities", and a summary "Satisfaction Index" section; when appropriate, comparisons were sought between the treated and untreated breasts. Preliminary results from this study indicate that 70% of all patients are aware of their treated breast in some way during everyday activities. The "Satisfaction Index" of this patient group is very high, with 75% rating their cosmetic result, and 81% their functional result "8" or higher on a scale of "0" to "10","10" indicating "best" or "normal".

Activities of Daily Living

Iridium-192 implants for primary breast cancer: experience with placement at the time of wide local excision.

An Ir-192 boost is a technique frequently used to deliver an additional dose of radiation therapy to the tumor bed following breast conserving surgery and combined with external beam radiation therapy to the entire breast for patients with early breast cancer. Traditionally these catheters are placed following completion of 4500-5000 cGy, as a separate procedure. This paper described a Pilot Study identifying placement of the catheters at the time of primary wide local excision, or re-excision in 52 patients. The key to the success of this technique is the achievement of complete hemostasis in the primary cavity, the presence of the radiation oncologist during the surgical procedure itself, and closure of the wound prior to placement of the catheters. Details of the technique, and preliminary patient results are presented.

Adult

Intraabdominal testis with yolk sac tumor in a 2-year-old child.

A case of a large yolk sac tumor in an undescended testicle in a 2-year-old child is presented. No such similar finding has been reported in a young child. Despite the large size of the primary tumor, the high level of serum alpha-fetoprotein and the relatively late clinical presentation, this was a stage I lesion, and the child responded to surgical resection of the tumor and chemotherapy.

Child, Preschool

Limited resection for breast cancer: a study of inked specimen margins before radiotherapy.

This is an analysis of tumor margins of 108 patients who underwent a limited resection for infiltrating breast cancer, prior to starting radiation therapy. This represented the initial resection (IR) in 75 patients, and a re-excision (RE) after biopsy elsewhere in 33 patients. All specimens were processed by the India ink method prior to frozen and paraffin section analysis. Overall, the incidence of involved margins was 28% for the IR group, and 15% for the RE group. No correlation was found with the axillary node status, or with the type of prior surgery in the RE group. The data suggest a correlation between increasing tumor size and margin involvement. Further surgery in the IR group with involved margins yielded negative margins in all cases; the finding of residual carcinoma was correlated with the type of secondary surgery, that is, further re-excision or mastectomy.

Biopsy