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Biomedical subjects

L Cox

Publications and source records attributed to L Cox.

At least 37 records · Page 2Linked to original sources
PubMed1993

Sézary syndrome with elevated serum IgE and hypereosinophilia: role of dysregulated cytokine production.

A 62-year-old man presented with a 4-year history of a pruritic erythematous rash. Initial workup was not diagnostic, and the rash was refractory to standard treatment. A complete blood cell count demonstrated a white cell count of 9100 cells/microliter with 61% polymorphonuclear neutrophils, 16% eosinophils, and 17% lymphocytes. A serum protein electrophoresis revealed an M spike identified as IgG kappa. His IgE level was 11,900 IU/ml. A bone marrow biopsy specimen demonstrated "atypical plasma cells" but was not diagnostic for myeloma. Peripheral blood smear was remarkable for highly convoluted lymphoid cells diagnostic for Sézary T cells. Consistent with this diagnosis, 89% of his peripheral blood CD2+ cells expressed CD4. The eosinophilia, elevated IgE level, and monoclonal gammopathy led to further investigations. Circulating adherent monocytes were 96% positive for presumed low-affinity IgE receptor expression as shown by surface IgE binding. In a 9-day lymphocyte coculture, the patient's T lymphocytes induced IgE production in vitro (1.25 ng/ml) by a normal donor's cultured B cells. A healthy donor's T cells failed to induce IgE production (0 ng/ml) in a similar culture system. In situ hybridization with an Sulfur-35-labeled cDNA probe revealed interleukin-4 mRNA expression by 84% and interleukin-2 mRNA expression by 62% of nonadherent peripheral blood mononuclear cells. Interleukin-5 mRNA was shown by reverse transcription and the polymerase chain reaction. These studies demonstrate a subject with Sézary T cell leukemia with hypereosinophilia and elevated IgE due to presumed enhanced interleukin-4 and interleukin-5 production by the Sézary T cells.

B-Lymphocytes↗
PubMed1993

Hyperproinsulinaemia in impaired glucose tolerance.

1. Basal circulating concentrations of islet B cell products were measured using two-site monoclonal antibody-based immunoradiometric assays after a 10 h overnight fast in a group of non-obese subjects with recently diagnosed impaired glucose tolerance (World Health Organization criteria). A group of healthy subjects with normal oral glucose tolerance matched for age and body mass index served as normal controls. 2. Fasting blood glucose concentration was normal in all subjects with mean (+/- SEM) levels of 5.1 +/- 0.2 and 4.8 +/- 0.2 mmol/l (P > 0.1) for the group with impaired glucose tolerance and the healthy control group, respectively. 3. There was no significant difference (P > 0.1) in fasting plasma insulin or C-peptide concentrations between the groups. 4. By contrast, the fasting concentration of intact proinsulin was nearly four-fold higher in the subjects with impaired glucose tolerance than in the matched healthy control subjects (4.5 +/- 1.0 versus 1.2 +/- 0.2 pmol/l, P < 0.005). 5. Similarly, the fasting plasma concentration of 32-33 split proinsulin in the subjects with impaired glucose tolerance was almost twice that of the control subjects (7.4 +/- 1.3 versus 3.9 +/- 0.8 pmol/l, P < 0.02). 6. In conclusion, fasting concentrations of proinsulin-like molecules are elevated in non-obese subjects with newly diagnosed impaired glucose tolerance. This observation is consistent with defective islet B cell proinsulin processing in this syndrome.

Glucose Intolerance↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1989

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↗
PubMed1988

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↗
PubMed1988

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↗