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Biomedical subjects

J Connolly

Publications and source records attributed to J Connolly.

At least 109 records · Page 6Linked to original sources

Functional expression of two neuronal nicotinic acetylcholine receptors from cDNA clones identifies a gene family.

A family of genes coding for proteins homologous to the alpha subunit of the muscle nicotinic acetylcholine receptor has been identified in the rat genome. These genes are transcribed in the central and peripheral nervous systems in areas known to contain functional nicotinic receptors. In this paper, we demonstrate that three of these genes, which we call alpha 3, alpha 4, and beta 2, encode proteins that form functional nicotinic acetylcholine receptors when expressed in Xenopus oocytes. Oocytes expressing either alpha 3 or alpha 4 protein in combination with the beta 2 protein produced a strong response to acetylcholine. Oocytes expressing only the alpha 4 protein gave a weak response to acetylcholine. These receptors are activated by acetylcholine and nicotine and are blocked by Bungarus toxin 3.1. They are not blocked by alpha-bungarotoxin, which blocks the muscle nicotinic acetylcholine receptor. Thus, the receptors formed by the alpha 3, alpha 4, and beta 2 subunits are pharmacologically similar to the ganglionic-type neuronal nicotinic acetylcholine receptor. These results indicate that the alpha 3, alpha 4, and beta 2 genes encode functional nicotinic acetylcholine receptor subunits that are expressed in the brain and peripheral nervous system.

Amino Acid Sequence↗

Current status of conservative surgery and radiotherapy as primary local treatment for early carcinoma of the breast.

Since it is now recognized that breast cancer is commonly a systemic disease at presentation, it is clear that local treatment is limited to providing local tumor control, and that effective systemic therapy is required for the eradication of micrometastatic disease. We here review the current status of conservative surgery and radiotherapy in the treatment of early breast cancer. Results from retrospective studies support the view that this combination is highly effective in achieving local control and maintaining good cosmetic results. Results at five and ten years from prospective trials indicate that survival using this approach is comparable to that of mastectomy. Though further follow-up is required, we do not believe that a large survival difference in favor of either approach will emerge.

Antineoplastic Combined Chemotherapy Protocols↗

Breast relapse following primary radiation therapy for early breast cancer. I. Classification, frequency and salvage.

Primary radiation therapy has become an accepted alternative to mastectomy for patients with early breast cancer. In order to improve the results of this treatment, we performed an analysis of failure on 366 clinical Stage I or II invasive breast carcinomas treated with primary radiation therapy. With a median follow-up of 52 months, there have been 30 recurrences in the treated breast, for a 5 year actuarial local recurrence rate of 9%. The recurrence rate was much higher for patients having less-than-excisional biopsy than for those undergoing excisional biopsy (35% vs. 7%, p less than 0.0001). Failures in the treated breast have been categorized as: true recurrence (TR), directly at the site of the primary; marginal miss (MM), at the edge of the boosted volume; and elsewhere in the breast (E). For patients having excisional biopsy, the actuarial probability of a true recurrence at 5 years was 4%. The risk of a true recurrence was related to the dose given to the primary site with rare true recurrences seen with doses greater than 6000 rad. The probability of a marginal miss at 5 years was 4%, and was not related to the dose or volume of the boost used. The probability of a recurrence elsewhere in the breast at 5 years was 1%. In patients treated with excisional biopsy and a total primary dose over 6000 rad, the probability of a local recurrence at 5 years was 4 and 10% for clinical Stage I and II patients respectively. These results indicate that primary radiation therapy provides a high likelihood of local tumor control and our analysis of failure suggests methods for decreasing each type of local recurrence.

Adult↗

Psychological, nutritional and physical status of olympic road cyclists.

Six members of the Irish Olympic Road Cycling Squad underwent a comprehensive medical, nutritional, psychological and biochemical assessment in January 1983. They were given specific medical and dietary recommendations and were reassessed in January 1984 after a period spanning the competitive racing season. The cyclists' diets at both sessions were comparable and generally conformed with recommended daily intakes. Supplementary ingestion was unnecessary to attain recommended daily intakes of vitamins. Serum levels of HDL-cholesterol increased and triglyceride decreased during the period of the study. The squad had characteristics indicating traits of self-sufficiency, toughness and practical mindedness. At the second assessment there was evidence of heightened ambition and competitiveness and an improvement in mood states with reduced ratings for confusion and tension.

Adult↗

Intraductal carcinoma of the breast: results of treatment with excisional biopsy and irradiation.

Between 1976 and 1983, 40 women with intraductal carcinoma of the breast without invasion underwent excisional biopsy and irradiation as an alternative to mastectomy. The median age was 53 years (range, 28 to 77 years) and the median follow-up time since initiation of radiation was 44 months (range, 14 to 97 months). Twenty-seven patients presented with a palpable mass; in 13 patients the tumor was detected only by mammography. A limited axillary dissection was performed in 13 patients, and all lymph nodes removed were negative. Treatment was administered to the breast and adjacent chest wall to a dose of 4,600 to 5,000 rad, with 26 patients also receiving a boost dose of 1,000 to 2,000 rad to the site of the primary. Four patients have developed a recurrence in the treated breast, at 17, 19, 35, and 63 months after the beginning of radiation therapy. The 5-year actuarial rate of local recurrence is 10%. Three of the recurrences were in those four patients who presented with a nipple discharge and a central primary. In two cases, the recurrence consisted of only intraductal carcinoma; in the other two, both intraductal and invasive cancer were found. All four patients with recurrence underwent mastectomy and are well without evidence of distant metastases at 1, 12, 15, and 15 months since mastectomy. Cosmetic results were excellent. No patient has developed distant metastases. Since the number of patients treated is small and the period of follow-up is short, one must be cautious in the interpretation of these results. Nonetheless, the treatment of intraductal carcinoma of the breast by excision and irradiation appears to give acceptable local control and excellent survival when suitable precautions of patient selection and evaluation are taken.

Adult↗

Life's happenings and organic disease.

There is a widespread belief among people and their doctors that what happens in life contributes to the cause of not only altered mood states but also organic lesional disease. Finding out whether it is true, with all the rigour of scientific method is a challenging task.

Accidents↗

Radiotherapy for prostate carcinoma: the JCRT experience (1968-1978). II. Factors related to tumor control and complications.

We have analyzed treatment failure and complications as a function of radiotherapy technique and other factors in 229 patients irradiated for prostate carcinoma from 1968-1978. Thirty-four patients (15%) developed clinical evidence of local-regional recurrence. In about one-quarter of these recurrences, there was a component of ureteral obstruction, possibly due to marginal miss in the seminal vesicles. Although different parameters of treatment technique were not significantly correlated with local failure, there was a trend toward higher failure rates for Stage B and C patients when the length and/or width of the conedown field was less than 8 cm (p = 0.27 and 0.25, respectively). As in other recent studies, patients with Stage C disease who had undergone trans-urethral resection of the prostate had a lower disease-free survival rate than patients who had only needle biopsy (39 vs. 65% at 5 years, p = 0.055). The use of larger initial fields treating the pelvic lymph nodes did not result in better local tumor control or better overall control. However, the use of larger fields did result in a higher rate of significant complications (8.7 vs. 1.6% for fields greater than or equal to 150 cm2 or less than 150 cm2, respectively, p = 0.013). In view of the higher complication rate and the absence of convincing evidence of benefit for whole pelvic treatment, irradiation of all pelvic lymph nodes can be questioned.

Carcinoma↗

Radiotherapy for localized prostate carcinoma.

We reviewed the radiation therapy treatment experience for localized prostate carcinoma at the Joint Center for Radiation Therapy from 1968-1978 (N = 229 patients, median follow-up of 5 years). Actuarial 5 (and 8) year survival rates for clinical Stage A (N = 25), B (N = 85), and C (N = 88) disease were 96% (82), 77% (63), and 61% (38). The corresponding 5 (and 8) year relapse-free survivals were 84% (67), 68% (61), and 53% (36). Actuarial rates of clinical local failure at 5 (and 8) years were 0%, (0), 12% (20), and 15% (30) for Stage A, B, and C respectively. There was a suggestion of a decrease in the force of local and overall recurrence after 8 years, although further follow-up will be necessary for confirmation. Among 42 patients who underwent pelvic lymphadenectomy followed by irradiation, lymph node status appeared to be a strong predictor of distant failure (9% (3/32) failures for node (-) patients compared to 70% (7/10) for node (+) patients). Twenty-nine patients received radiotherapy after radical prostatectomy for clinically palpable (Stage B and C) tumor. Only one of 16 patients treated post-operatively because of microscopic or gross residual disease has developed recurrence. By contrast, only 2 of 13 patients irradiated because of clinical local tumor recurrence remain alive and free of disease. We conclude that radiation therapy can provide effective long-term local control of prostate carcinoma, but that the ultimate radiocurability of the disease is not yet known.

Adenocarcinoma↗

ERPs and psychopathology. II. Biological issues.

We have briefly covered important issues and considerations in four topic areas likely to be of use to the ERP researcher who is also interested in biological psychiatry. We cannot ignore diagnosis because of its basic role in the field of psychiatry. Although there are reliability problems, especially in the field of psychiatric diagnosis, ERPs may help in the painstaking task of validating diagnosis based on behavioral observation. In addition, the ERP researcher can use diagnosis to obtain potentially more homogeneous samples of patients so as to reduce between-subject error variance in studies. We have considered research areas like PET scan and CT scan which provide data of more anatomical precision than ERPs for deep neurological sites. While the potential may be there, it is essentially unrealized as yet. Finally, neurochemistry and psychopharmacology seem to be the areas most likely to bear fruit in the immediate future. If this potential is to be realized, it is necessary to formulate new questions and a new methodology to handle these questions. An important question, for example, is whether a biological profile is a more useful criterion than a behavioral profile for predicting response to pharmacological intervention. In biological psychiatry, this question is a human suffering issue of considerable importance.

Antipsychotic Agents↗

Immunocompetence in patients with prosthetic graft infection.

The immunologic competence of 12 patients with advanced and fulminating prosthetic graft infections was studied. Critical deficiencies were noted in the immune status of all the patients. Enhancement of immune responses with accelerated recovery occurred in 8 of the 12 patients who received total parenteral nutritional support. The four patients who exhibited anergy and were not given the benefits of supplemental nutrition endured a prolonged convalescence, and two subsequently died. This study brought to our attention not only the prevalence of depressed host resistance in these critically ill individuals with advanced prosthetic graft injections but also the benefits of adjunctive parenteral nutritional support in combination with the more conventional modes of therapy, including antibiotics, surgical removal of the septic nidus, and bypass to restore arterial continuity.

Aged↗

Paraganglioma of the falciform ligament: a case report.

A single case of an extra-adrenal paraganglioma removed at laparotomy from the falciform ligament of a 16 year-old girl is reported. Whilst extra-adrenal paragangliomata have been frequently documented in specific sites in relation to the vascular axis, the occurrence of these tumours in other areas is rare. This is the first report of a paraganglioma occurring within the falciform ligament in the midline in apposition to the anterior abdominal wall.

Adolescent↗

Effect of propranolol and phenothiazines on electrodermal orienting and habituation in schizophrenia.

Bilateral electrodermal orienting responses were measured to repeated auditory stimuli in schizophrenic patients and controls. In 3 studies phasic activity to moderate intensity sounds of patients on no drugs or phenothiazines was predominantly hyper- or hypo-responsive. Controls showed moderate or slow habituation. Propranolol was found to facilitate habituation in slow habituators and to reinstate responses in half of non-responders, especially when given as the sole drug. The effects seldom had a counterpart in changes in non-specific responses or levels of skin conductance. Modulatory influences on stimulus and response processing and on lateral asymmetries in responses may underlie propranolol's efficacy in treating schizophrenia.

Acoustic Stimulation↗

Accident proneness.

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Accident Proneness↗