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Biomedical subjects

R J McCormack

Publications and source records attributed to R J McCormack.

At least 19 recordsLinked to original sources

Murine T-lymphocytes express vasoactive intestinal peptide receptor 1 (VIP-R1) mRNA.

Vasoactive intestinal peptide (VIP), a neuropeptide present in primary and secondary lymphoid organs has been previously reported to inhibit IL-2 and IL-4 production as well as the proliferation of mitogen- or antigen-stimulated T-cells. Binding studies suggested that the immunoregulatory effects of VIP are mediated through specific VIP-binding sites present on lymphocyte subpopulations. Here we report on the expression of VIP-R1 mRNA in various murine lymphocyte subpopulations. By using RT-PCR. RNase protection assay, cDNA cloning, and sequence analysis, we show that stimulated and unstimulated murine spleen cells, thymocytes. CD4+ and CD8+ T-cells express VIP-R1. The VIP-R1 fragment amplified from murine brain, thymocytes, spleen cells and CD4+ T-cells share identical nucleotide sequences, and a high degree of homology with the corresponding nonlymphoid rat and human VIP-R1 sequences. The expression of VIP-R1 in thymocytes and peripheral lymphocytes, and especially in the CD4+ T-cell subset supports the idea that VIP produced or released locally in the lymphoid microenvironment could directly affect cytokine production and proliferation of T-lymphocytes.

Animals↗

An mRNA homologous to interleukin-1 receptor type I is expressed in cultured rat sympathetic ganglia.

Interleukin-1 (IL-1) induces substance P (SP) gene expression in cultured rat superior cervical ganglion (SCG) explants. In order to study the molecular mechanism of this action of IL-1, the presence of an interleukin-1 receptor (IL-1R) activity and the identity of an mRNA homologous to known IL-1R sequence was determined in SCG. The SP increase is blocked by recombinant IL-1 receptor antagonist protein, so IL-1 must be interacting with a specific receptor. We have cloned cDNA homologous to IL-1R type I from rat SCG using a reverse transcription-polymerase chain reaction (RT-PCR). The resulting cDNA sequence is strongly homologous with mouse and human IL-1R cDNA of the T cell and fibroblast type (type I; encoding an 80-kDa protein). mRNA specific for IL-1R can be readily detected in intact SCG by quantitative RT-PCR and S1 hybridization. However, the level of IL-1R mRNA increases 3-6-fold by 2 days in culture. This increase is independent of the presence of dexamethasone, IL-1 beta or IL-1 receptor antagonist protein ligands. The increase of IL-1R following explantation, a model of nerve injury, may provide a mechanism linking inflammatory signalling to neuronal phenotypic changes.

Amino Acid Sequence↗

Multiple-dose pharmacokinetics and safety of rufloxacin in normal volunteers.

The pharmacokinetics and safety of rufloxacin were evaluated in a double-blind, placebo-controlled study. Two groups of 16 healthy volunteers were given a single oral loading dose of 400 or 600 mg of rufloxacin on day 1 of the study. A single daily maintenance dose of 200 or 300 mg was then administered for a further 9 days; in addition, four subjects in each group received placebos. Rufloxacin levels in plasma and urine were determined by high-performance liquid chromatography. Following the initial dose, the mean (+/- standard error of the mean) peak concentrations of rufloxacin in plasma were 3.35 +/- 0.12 micrograms/ml in the 400-mg group and 4.54 +/- 0.19 micrograms/ml in the 600-mg group. They were generally reached 2 to 3 h after dosing. At the end of treatment, maximum levels in plasma rose to 4.51 +/- 0.15 and 7.20 +/- 0.25 micrograms/ml in the 400-mg and 600-mg groups, with a mean extent of accumulation (fold) of 3.1 +/- 0.1 and 3.3 +/- 0.1. For the 400-mg and 600-mg groups, the elimination half-lives were 40.0 +/- 1.5 and 44.0 +/- 1.3 h, mean residence times were 57.8 +/- 2.2 and 63.7 +/- 1.8 h, apparent volumes of distribution were 132 +/- 4 and 139 +/- 5 liters, and apparent total body clearance were 39 +/- 1 and 44 +/- 4 ml/min, assuming complete bioavailability. Of the total dose administered, the percentages excreted in urine were 49.6 +/- 1.3 and 51.1 +/-2.1%, with renal clearances of 21 +/- 1 and 22 +/- 2 ml/min, for the 400-mg and 600-mg groups. On the whole, the treatments were well tolerated, but some minor adverse events (mainly headache, insomnia, or abdominal discomfort) were reported for 7 subjects on abnormalities were detected in the laboratory examinations or in ocular function tests. This study shows that a 200-mg daily oral dose of rufloxacin preceded by a loading dose of 400 mg are well tolerated and produce steady-state concentrations in plasma above the MIC for most susceptible pathogens.

Adult↗

Persistence of ductus arteriosus with left to right shunt in the older patient.

Eight hundred and four patients with persistence of the ductus arteriosus were seen in Edinburgh between 1940 and 1979. Thirty-seven of them reached the age of 50 years, and in 32 the shunt was exclusively from left to right. Fifteen of the 32 were subsequently treated surgically. None of the 32 was lost to follow-up. Duration of clinical observation averaged 17 years and extended to over 30 years in eight patients. Their features have been correlated with those from reports of 48 comparable patients in an attempt to clarify the management of the persistent ductus in the older patient. Impairment of left ventricular function is shown as the major risk, even when the ductus is small. Bacterial endarteritis is infrequent. Surgical treatment carries greater risk than in childhood and early adult life but usually reduces heart size and restores exercise tolerance. Left ventricular dysfunction, however, occasionally vitiates the benefits; symptoms are then incompletely relieved and death from heart failure may occur months or years after operation. Experience in older patients thus emphasises the value of elective operation in childhood, however well the child, however trivial the shunt. It is concluded that in older patients, the presence or the development of symptoms or cardiac enlargement are almost always indications for surgical treatment. As age increases, especially by the eighth decade, medical treatment may be preferable. Continued follow-up of symptomless patients without cardiomegaly is important because increase in heart size usually precedes further deterioration which can then be prevented by timely surgical treatment.

Adult↗

Intrabronchial metastases from renal carcinoma with recurrent tumour expectoration.

Three patients are described who presented to their doctors with a history of coughing up pieces of tissue. These took the form of large bronchial casts and consisted of intrabronchial deposits of clear cell carcinoma. In one patient the pulmonary symptoms preceded the finding of a primary renal carcinoma by four years. The other two patients had undergone nephrectomy for renal carcinoma 13 and four years previously. Expectoration of intrabronchial tumour should alert the physician to the possibility of metastasis from clear cell carcinoma of the kidney.

Adenocarcinoma↗

Regression of multiple pulmonary varices after mitral valve replacement.

A 30-year-old woman with severe mitral insufficiency had large, rounded opacities at the right hilus as seen on her chest x-ray film. These were shown to be varicosities of the right pulmonary veins by pulmonary angiography and by direct injection of contrast medium from a Brockenbrough catheter, which entered the varices from the left atrium. A year after mitral valve replacement there was complete regression of the venous dilatations. When a pulmonary varix is detected there is associated heart disease in 40% of cases. Mitral valve disease (usually mitral insufficiency) is the cardiac abnormality in 27%. This would indicate that pulmonary varix is a complication of mitral insufficiency. Four patients who have undergone valve replacement for mitral reflux have shown regression of the caricosities, suggesting that relief of mitral insufficiency will reduce or eliminate the risk of varix rupture.

Adult↗

Surgical management of bronchial carcinoma invading the chest wall.

In a 20-year period (1958-77) 43 patients underwent combined pulmonary and chest wall resection for bronchial carcinoma with local invasion of the thoracic wall. The clinical data, symptoms, surgical procedures, pathology, and results are reviewed. Pain was the usual presenting symptom. The operative mortality was 16%, respiratory complications causing most of the postoperative morbidity and mortality. These complications were less common after pneumonectomy. Long-term survival was achieved in only three cases with a corrected three-year survival rate of 10%. The survivors had certain pathological and operative features in common that may have prognostic significance. Recurrent carcinoma was responsible for most late deaths. Despite the poor overall prognosis, surgical management provided reasonable palliation and occasionally resulted in prolonged disease-free survival.

Adult↗

Aetiology of unresolved pneumonia.

Preoperative histological or cytological confirmation of a diagnosis of bronchogenic carcinoma is not always possible, so occasionally non-neoplastic lesions are resected. Of these lesions a significant number are described by pathologists as 'unresolved pneumonia'. We studied the case notes and histopathology of 30 patients from whom lung had been resected and which had been classified as pneumonia. Other non-neoplastic lesions, such as pulmonary infarction, bronchiectasis, and tuberculosis, were excluded. All had a preoperative diagnosis of probable bronchial carcinoma. On review very few appeared to be the consequence of an infective, pneumonic episode. In 11, foreign material was identified, including one typical example of a paraffinoma. Aspiration of foreign material may lead to a localised lesion which simulates carcinoma of the bronchus both clinically and radiographically.

Bronchial Neoplasms↗

Intrathoracic neural tumours.

The experience of one regional thoracic surgical unit in managing intrathoracic neural tumours over a 25-year period is presented. Neural tumour was diagnosed in 55 patients, of whom 41 were asymptomatic. In 11 patients complete resection was not achieved--the reasons for this and its effect on the outcome of the patient are discussed. There were 52 posterior mediastinal and three lateral chest wall tumours. The pathological distribution was as follows--benign nerve sheath tumours (neurofibroma, neurilemoma) 39, ganglioneuroma 13, and neuroblastoma 3. One neurofibroma recurred as a neurosarcoma six years after its apparently complete resection and was removed by an extensive resection at reoperation. One neuroblastoma recurred within the spinal canal four years after incomplete excision at thoracotomy--this patient died subsequently of widespread metastatic neuroblastoma. No other tumour is known to have recurred.

Adolescent↗

The malignancy of bronchial adenoma.

The literature on bronchial adenoma has been reviewed and controversy found to exist about certain aspects of these tumors, particularly their malignancy. A retrospective study of 79 cases managed in Edinburgh since 1946 is presented. Seventy-one were of the carcinoid type, 7 were adenoid cystic carcinomas, and there was a single example of mucoepidermoid carcinoma. All types show a definite malignant potential, greatest in the rare mucoepidermoid tumor and least in the common carcinoid variety. Adenoid cystic carcinoma occupied an intermediate position in frequency and malignancy.

Adenoma↗

Hiatus hernia.

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Adolescent↗