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Biomedical subjects

C Wright

Publications and source records attributed to C Wright.

At least 235 records · Page 13Linked to original sources

Primary mediastinal nonseminomatous germ cell tumors. A modern single institution experience.

Between 1976 and 1988, 31 patients with mediastinal nonseminomatous germ cell tumors (MNGCT) received initial cisplatin-based chemotherapy of uniform intensity. Eighteen of these patients (58%) obtained disease-free status; 11 with chemotherapy alone and seven with adjunctive surgery. Eleven have remained continuously free of disease. Two have had recurrence of teratoma and are disease-free after resection of teratoma at 12+ and 68+ months. Three patients developed recurrence of germ cell tumor. Three patients developed a hematologic malignancy. Of the 18 patients who obtained disease-free status, 15 remain alive and disease-free. Overall, 13 of the 31 patients and 24 other patients received salvage chemotherapy at Indiana University, Indianapolis, Indiana. Of these 37 patients, six obtained a disease-free status and four (11%) remain alive at 13+, 56+, 78+, and 122+ months, respectively. This series represents the largest series of patients with MNGCT ever reported. Analysis of these data and results from other recent series suggest that approximately 50% of patients with MNGCT will be cured with modern, intense cisplatin-based chemotherapy coupled with adjunctive surgery if needed.

Adult↗

Plasma exchange in progressive IgA nephropathy.

A therapeutic trial of plasma exchange was performed in 13 patients with documented progressive IgA nephropathy. Comparison of the rate of deterioration in renal function before, during, and after plasma exchange demonstrated significant improvement during plasma exchange. Seven patients had a slowed rate of deterioration by plasma exchange, but achieved a decrease in serum creatinine level. Favourable response was correlated with rapidity of deterioration preplasma exchange (P less than 0.01) and was apparent within 4 weeks of commencing therapy in those patients who responded. There was no overall difference between the deterioration rates pre- and postplasma exchange. In patients in whom creatinine decreased on plasma exchange, the initiation of subsequent dialysis was delayed.

Adolescent↗

Familial infantile nephrotic syndrome with ocular abnormalities.

Two siblings born from consanguineous parents experienced infantile nephrotic syndrome with ocular and neurological abnormalities; the boy also had a micropenis; both patients died before age 1 year. An initial renal biopsy followed by a two-step binephrectomy allowed good histological assessment of disease progression in one patient. The progression of the lesions was characterized by mesangial involvement, then an extensive extracapillary proliferation and tubular dilatations with a high mitotic activity of the epithelium and nuclei of unequal size. The main features involved major ultrastructural changes of the glomerular basement membrane. These two patients may represent a new disease entity or a severe form of diffuse mesangial sclerosis, with autosomal recessive inheritance.

Cataract↗

Role of transforming growth factor-alpha-related peptides in the autocrine/paracrine control of experimental breast cancer growth in vitro by estradiol, prolactin, and progesterone.

We have recently suggested that estradiol (E2), prolactin (oPrl), and progesterone (Pg) support the growth of the hormone-responsive N-nitrosomethylurea (NMU) rat mammary tumor in soft agar through autocrine/paracrine mechanisms. To gain insight into the nature of these hormonally regulated growth factors, we tested the ability of two monoclonal antibodies (MAb-425 and 528) directed against the epidermal growth factor receptor (EGF-R) to inhibit the colony-stimulating effects of conditioned media (CM) obtained from E2, oPrl, and Pg-treated NMU rat mammary tumors. Since both MAbs are specific for human EGF-R, MCF-7 breast cancer cells grown in soft agar in the absence of serum were used as our indicator system. Both MAb-425 and 528 totally abolished the colony-stimulating effect of genuine EGF, while having no agonistic/antagonistic action when added alone. Both MAb-425 and 528 markedly inhibited the colony-stimulating effect of rat mammary tumor E2-CM in a dose-dependent fashion. MAb-425 was also found to inhibit the growth-promoting action of Pg-CM, although this effect appeared to be somewhat less consistent and pronounced than that observed with E2-CM. In contrast, the colony-stimulating effect of Prl-CM was only rarely and, usually, modestly affected by the addition of either MAb-425 or 528. Our data suggest that in the NMU mammary tumor grown in soft agar, EGF/TGF alpha-related peptides are produced upon exposure to E2 and possibly Pg but only rarely following Prl administration. The possible role of these growth factors as mediators of hormonal effects in our experimental system remains to be established.

Animals↗

Disulfiram treatment of alcoholism.

PURPOSE: For 40 years, disulfiram has been the alcohol-aversive drug used most frequently by American physicians in the treatment of alcohol dependency disorders. We reviewed the clinical literature regarding the risks, benefits, indications, and efficacy of this controversial drug and summarized current knowledge of this therapy. CONCLUSIONS: Disulfiram will produce an aversive reaction with ethanol, usually at a dose between 250 mg/day and 500 mg/day, although some patients may not have an aversive reaction at this level. Cardiac, hepatic, and neurologic toxicity can also occur within this dosage range. If disulfiram is to be used, the patient must clearly understand the risks of drinking while taking the drug, and the physician and patient must agree about the need for continued clinical supervision and monitoring for efficacy and side effects. The physician must also recognize that disulfiram is only an adjunctive therapy and that continued support, supervision, and other therapeutic measures are required. Disulfiram is probably effective in reducing the frequency of alcohol consumption in the compliant patient over the short term (e.g., 6 months). Certain subgroups of patients, such as those who are older, those who are more socially stable, and those who are well-motivated, may experience a beneficial effect for longer periods. The drug may be most effective in reducing short-term alcohol consumption when the compliance of the patient is supervised, although consideration of this kind of therapy includes the practical problems of supervising the patient and concerns that the supervising person may be placed in a difficult position. Prescription of disulfiram without accompanying education, counseling, and concomitant alcoholism therapy is not beneficial. Disulfiram has no proven effect on the long-term outcome of alcoholism.

Alcoholism↗

Infertility and eating disorders.

Sixty-six consecutive infertility clinic patients were prospectively screened with the 26-item Eating Attitudes Test and a study questionnaire. Women identified as being at high risk for an eating disorder were then interviewed to confirm or refute the diagnosis. A total of 7.6% of infertility clinic women were found to suffer from anorexia nervosa or bulimia nervosa. If eating disorders not otherwise specified were included, a total of 16.7% of infertility patients were found to suffer from an eating disorder. Among infertile women with amenorrhea or oligomenorrhea 58% had eating disorders. Because women often fail to disclose eating disorders to their gynecologists and may appear to be of normal weight, it is recommended that a nutritional and eating disorder history be taken in infertility patients, particularly those with menstrual abnormalities. It has previously been shown that disorder eating and nutrition can affect menstruation, fertility, maternal weight gain, and fetal well-being.

Adult↗

Non-CS pre-erythrocytic protective antigens.

Three novel non-CS antigens have been identified on P. falciparum and P. berghei sporozoites and exoerythrocytic parasites. CSP-2 is a sporozoite surface protein common to P. falciparum and P. berghei that elicits antibody-mediated protection, and is also found within P. berghei EE parasites. LSA is a P. falciparum EE-specific antigen localized within the parasitophorous vacuole. LSA-2 is a P. berghei EE-specific antigen, localized on the parasitophorous vacuole membrane, that protected mice to P. berghei sporozoite challenge, and elicited cytotoxic T cells that killed P. berghei EE parasites in vitro.

Amino Acid Sequence↗

Pulmonary artery pressure changes during exercise and daily activities in chronic heart failure.

Long-term continuous pulmonary artery pressure monitoring was used to investigate pressure changes during different types of exercise and normal daily activities in patients with chronic heart failure. Nine men (mean age 55 years) with treated chronic heart failure underwent continuous pulmonary artery pressure measurement with use of a micromanometer-tipped catheter with in vivo calibration and frequency-modulated recording. The mean (+/- SD) maximal systolic pulmonary artery pressure (in mm Hg) was 59.4 +/- 26.1 on treadmill exercise, 54.9 +/- 30.6 on bicycle exercise, 52.5 +/- 26.1 walking up and down stairs and 43.5 +/- 23.9 walking on a flat surface. The mean maximal diastolic pressure (in mm Hg) was 27.8 +/- 14.6 on treadmill exercise, 25.5 +/- 14.9 on bicycle exercise, 24.9 +/- 14.8 walking up and down stairs and 20.4 +/- 12.5 walking on a flat surface. The increase in pulmonary artery pressure did not correlate with the severity of the limiting symptoms except during walking on a flat surface. All patients had marked postural changes in pressure, with the systolic pressure difference from lying to standing ranging from 8 to 25 mm Hg and the diastolic pressure difference ranging from 3 to 13 mm Hg. Eating meals caused an increase in pressure in three patients, but less than that when lying flat. There was an increase in pressure during urination in four patients equal to that when walking on a flat surface. None of these activities was associated with symptoms. Neither symptoms nor pulmonary artery pressure during maximal exercise is the same as during daily activities. This may restrict the value of maximal exercise tests in assessing patients with chronic heart failure.

Activities of Daily Living↗

Induction of type II T4-5'-monodeiodinase activity in brown adipose tissue in fasted mice.

In order to study the effect of starvation on brown adipose tissue (BAT) type II 5'-monodeiodinating activity (5'MDI), type II 5'MDI was measured in vitro in the presence of 20 mM dithiothreitol, 1 mM propylthiouracil, 2 nM thyroxine (T4) and appropriate amounts of 600 X g infranatant of BAT from fed control or 3 day fasted mice, with or without daily T4 replacement (1.2 micrograms/100 g bw) during starvation. I- released from 125I-T4 was measured by ion-exchange column chromatography. Activity of BAT 5'MDI was markedly elevated in the 3 day fasted group (133 +/- 28 fmol I-/h per mg protein vs. 26 +/- 6.4; p less than 0.05). Kinetic studies using BAT infranatant suggested that fasting-induced activity is associated with a similar change in the Vmax, but no demonstrable change in apparent Km of T4 monodeiodination. T4 replacement during fasting, which normalized both serum T4 and T3 in fed and 3 day fasted groups, did not stop the increase of BAT 5'MDI in the fasted group (p less than 0.01). The data suggest that: (1) the fasting-induced increase in BAT 5'MDI is due mainly to the changes in capacity rather than the affinity of the enzyme, and (2) the fasting-induced increase in BAT 5'MDI is not mediated entirely through changes in serum thyroid hormone concentration.

Adipose Tissue↗

Occupational outcome after military treatment for alcoholism.

Many studies measure the occupational outcome of alcoholism treatment utilizing reports from the patient and not from the employer. In an attempt to obtain an objective measure of occupational outcome, the authors used both supervisors' evaluations and clinical reports from aftercare personnel to observe 722 patients who completed a 6-week military inpatient alcoholism treatment program. Patients were observed for up to 2 years to determine prognostic indicators for post-rehabilitation personal and occupational success. Continuous abstinence from alcohol was seen in 77% of the study group, whereas satisfactory posttreatment occupational performance was observed in 90% throughout the study period. Military rank, successful inpatient program completion, and aftercare program adherence were good predictors of long-term outcome, whereas extent of prior treatment for substance abuse and Michigan Alcoholism Screening Test scores were not.

Adolescent↗

c-erbB-2 oncoprotein expression in mammary and extramammary Paget's disease: an immunohistochemical study.

Over-expression of the c-erbB-2 oncogene occurs in a proportion of human adenocarcinomas and in breast carcinoma is associated with poorer prognosis. Sections of formalin-fixed, paraffin-embedded tumour tissue from 22 patients with mammary and extramammary Paget's disease have been stained immunohistochemically using a monoclonal antibody (NCL-CB11) raised against a synthetic peptide from the C-terminal end of the predicted sequence of the c-erbB-2 protein product. All 12 cases of mammary Paget's disease showed membrane staining of intra-epidermal cells, indicating c-erbB-2 over-expression. Sections of underlying ductal breast carcinoma were available in nine cases; all nine tumours were c-erbB-2 positive and in eight the in situ component was of comedo or solid type. There was membrane staining of tumour cells in four of the 10 cases of extramammary Paget's disease; staining intensity was generally weaker than that observed in the cases of mammary disease. The possible implications of these findings for the histogenesis of both mammary and extramammary Paget's disease are discussed.

Breast Neoplasms↗

Cell cycling in bladder carcinoma determined by monoclonal antibody Ki67.

Current methods of predicting prognosis in transitional cell carcinoma of the bladder fail to provide consistently reliable information about future tumour behaviour. The monoclonal antibody Ki67 recognises an antigen present in actively dividing cells and Ki67 reactivity has been shown to correlate with conventional prognostic indicators in several tumours. In this study, Ki67 antibody was used to determine the proportions of cells undergoing active division in 26 transitional cell carcinomas of the bladder. The proportion of cells stained in muscle invasive tumours (12.3 +/- 5.4%) was significantly greater than in superficial tumours (4.3 +/- 1.9%) and poorly differentiated tumours showed significantly greater proportions of cells staining compared with well or moderately well differentiated tumours. These results show that Ki67 reactivity correlates with high tumour stage and poor differentiation. Ki67 staining provides an easy method of determining tumour cell turnover that might provide additional prognostic information.

Antibodies, Monoclonal↗

Recent achievements and adversities in anxious and depressed school age children.

Recent social achievements, friendship difficulties and life events were investigated for their relative effects on the probability of being a case of anxious or depressive emotional disorder. There are no significant differences between cases and controls for the presence of one or more recent social achievements. The probability of being a case is best predicted by a consideration of the independent effects of life events and the interactive (multiplicative) effects of the absence of recent social achievements with moderate to poor friendships. The absence of social achievements appears to exert significant risk for emotional disorder only in the presence of moderate to poor friendships. We have termed this an enhancing factor. There appears to be no greater probability of being anxious rather than depressed as a consequence of these factors or mechanisms occurring in the lives of school age children.

Achievement↗

Circadian variation of heart rate is affected by environment: a study of continuous electrocardiographic monitoring in members of a symphony orchestra.

Twenty four hour ambulatory ST segment monitoring was performed on 48 members (43 players and five members of the management/technical team) of the British Broadcasting Corporation (BBC) symphony orchestra without a history of cardiac disease. This period included final rehearsals and live performances (for audience and radio) of music by Richard Strauss and Mozart at the Royal Festival Hall (n = 36) and Rachmaninov and Tchaikovsky at the Barbican Arts Centre (n = 21). During the period of monitoring one person (2%) had transient ST segment changes. Mean heart rates were significantly higher during the live performances than during the rehearsals. Mean heart rates during the live performance of Rachmaninov and Tchaikovsky were significantly higher than during Strauss and Mozart in those (n = 6) who were monitored on both occasions. Mean heart rates in the management and technical team were higher than those of the players. The recognised circadian pattern of heart rate, with a peak in the morning waking hours, was altered similarly during both concert days, with a primary peak occurring in the evening hours and a lesser peak in the morning for both musicians and management/technical staff. This study showed that environmental factors are of primary importance in defining the circadian pattern of heart rate. This has important implications when identifying peak periods of cardiovascular stress and tailoring drug treatment for patients with angina pectoris.

Adult↗

The friendships and recent life events of anxious and depressed school-age children.

The number of moderate to severe undesirable life events and the quality of friendships were compared between a consecutive series of 100 children aged 7-16 years with emotional disorders and a series of community controls matched for age, sex, and social class. Undesirable events and friendship difficulties exerted independent direct effects of similar magnitude on the probability of developing emotional disorders; 33% of disturbed children experienced both adversities compared with 6% of controls. An additive interaction was found for the two factors. The results were uninfluenced by the sex or pubertal status of the subjects. There appears to be no greater probability of being anxious rather than depressed in the presence of life events, alone or in combinations with friendship difficulties. Recent undesirable life events and friendship difficulties arise through independent social pathways and may exert their effects through different psychological mechanisms.

Adolescent↗

Cervix and breast cancer incidence in immigrant Caribbean women.

Cervix and breast cancer incidence in 1978-82 was computed for immigrant and United States-born Black women in Brooklyn, New York. Compared to the national SEER (Surveillance, Epidemiology and End Results) rates, US-born and Haitian women had high rates of invasive cervical cancer, while English-speaking Caribbean immigrants had an average rate. However, while US-born women had an average rate of carcinoma in situ of the cervix, both immigrant groups had low rates. Both immigrant groups had low rates of breast cancer, whereas US-born Black women had an average rate.

Black People↗