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Biomedical subjects

M Duggan

Publications and source records attributed to M Duggan.

At least 19 recordsLinked to original sources
PubMed1991

Bronchial mucus hypersecretion in acute quadriplegia. Macromolecular yields and glycoconjugate composition.

In acute quadriplegia we have noted that about one in five patients develops unexplained production of markedly excessive and tenacious bronchial mucus. Spontaneous recovery from mucus hypersecretion usually occurs within weeks to months. Mucus samples collected from 12 patients have been found to be abnormal. Macromolecular contents of single aspirates yielded as much as 500 mg. Analytical ultracentrifuge analysis showed the mucus to contain considerable epithelial glycoprotein (GP) of typical buoyant density; its amino acid and carbohydrate compositions were characteristic of the GP from hypersecretory bronchial mucus such as in chronic bronchitis and cystic fibrosis. In five patients studied after recovery from hypersecretion, there tended to be relatively less GP. The mucus samples contained a high density glycoconjugate (GC): this had sugars of GP but also reacted positively with a monoclonal antibody to keratan sulfate. Its amino acid composition was different from that of GP: threonine was lower and glycine was higher than in GP. In mucus from one patient who died, chondroitin sulfate ABC and hyaluronic acid were identified as well. This suggests proteoglycans are involved in the pathophysiology of mucus hypersecretion. The sudden onset and spontaneous recovery of hypersecretion suggests that it is not due to gland hypertrophy. We speculate that in acute quadriplegia it is due to disturbed neuronal control of bronchial mucus gland secretion, perhaps related to initial disappearance and later reappearance of peripheral sympathetic nervous system tone.

Acute Disease↗
PubMed1991

Epstein-Barr viral genome in lymph nodes from patients with Hodgkin's disease may not be specific to Reed-Sternberg cells.

A possible etiologic role for Epstein-Barr virus (EBV) in Hodgkin's disease (HD) was investigated by probing for EBV genome in 52 biopsy specimens involved with HD and 43 hyperplastic lymph node specimens. Using dot-blot hybridization (Bam HIW probe), Southern blot hybridization (Xho I probe), and polymerase chain reaction analyses, 27%, 27%, and 58% of the nodes with HD were positive for EBV genome, respectively, as compared to 16%, 14%, and 43% in the hyperplastic lymph nodes. Clonal and nonclonal episomal EBV and linear replicating EBV genome were present in both conditions. Immunoglobulin heavy chain gene rearrangements were found in two clonal and two nonclonal EBV-positive HD cases, but not in the lymphoid hyperplasia cases. These findings and other recent reports showing EBV genome in benign lymphoid cells by in situ hybridization in Hodgkin's disease suggest that the characteristics of EBV infection in HD could be explained by the reactive cellular milieu, especially in the setting of defective immunity. The identification of EBV genome in Reed-Sternberg cells may, therefore, be a nonspecific phenomenon.

Gene Rearrangement↗
PubMed1991

High frequency of antithrombin 3 and protein C deficiency following autologous bone marrow transplantation for lymphoma.

To investigate the possibility that a hypercoagulable state develops during autologous bone marrow transplantation (BMT), we measured levels of circulating natural anticoagulants and fibrinolytic proteins before and weekly during the hospital course of 18 patients undergoing autologous BMT for Hodgkin's and non-Hodgkin's lymphoma. Patients received either weekly (standard dose group) or daily (high dose group) vitamin K supplements with their total parenteral nutrition. By day 14 there had been a significant drop in protein C activity (mean of 95% of normal to 52%), protein C antigen (mean of 105% of normal to 70%), and antithrombin 3 activity (111% of normal to 83%), and an increase in fibrinogen (471-621 mg/dl) and tissue plasminogen activator (6.9-13.8 ng/ml). No changes were seen in free or total protein S, plasminogen activator inhibitor, prothrombin time or partial thromboplastin time. The decreases in protein C and antithrombin 3 persisted through day 28 after transplantation. The drop in protein C correlated strongly with decrease in serum albumin, suggesting impaired synthesis of these proteins by the liver. No differences were seen in any of these parameters between the standard and high dose groups. Deficiencies in anticoagulant proteins antithrombin 3 and protein C and a rise in fibrinogen without a concomitant improvement in fibrinolytic variables create a potentially hypercoagulable state which may contribute to the thrombotic complications of autologous BMT.

Adult↗
PubMed1990

A Veterans Administration Cooperative Study of biphasic calcium phosphate ceramic in periodontal osseous defects.

One hundred thirty-seven V.A. patients were randomized to one of three treatment groups to evaluate the efficacy of biphasic calcium phosphate (BCP) ceramic in the treatment of periodontal osseous defects. This material was tested against both autogenous bone implant and open flap curettage procedures. Baseline probing attachment level, Navy plaque index, and gingival index were recorded for all patients. These parameters were monitored for 3 years. At the end of this period, 101 patients had completed the study. Although the plaque and gingival indices steadily increased with time, there were no statistically significant differences among the treatment groups. Patients in the ceramic group had a gain in attachment level of 1.0 mm; those in the curettage group, 0.9 mm; and 0.4 mm for those in the bone implant group. Although the BCP patients had a greater gain, the difference was not statistically significant. In this veteran population, not only did BCP patients fail to outperform those in the control groups, all three treatment groups were similarly ineffective.

Adolescent↗
PubMed1989

Chromosomal abnormalities in Hodgkin's disease.

Numerous neoplastic states have associated or causal cytogenetic abnormalities. In some cancers, specific chromosomal abnormalities appear to correlate with the clinical characteristics and prognosis. Cytogenetic analysis of Hodgkin's disease is thought to be technically difficult and only a small number of cases with evaluable results have been reported. We have attempted cytogenetic studies of lymph nodes from 37 patients with Hodgkin's disease. In 29 of the 37 patients (78%), successful chromosomal analysis was accomplished. Chromosomal abnormalities were found in 13 patients (45%); five of these patients had been previously treated with chemotherapy. Numerical changes were found in all patients, most commonly involving chromosomes 5, 9, 15, 18, 22, X, and marker chromosomes. Seven patients also had structural abnormalities. The breakpoints 4q32-34, 6q24, 12q13, 12q23-24, and 13p11-13 were each seen in at least two patients. All but two patients had an admixture of normal cells. Three patients had two or more clones, and one had subclones. No statistically significant correlations between chromosomal abnormalities and clinical characteristics were demonstrated, although the number of patients in each subgroup was small. We conclude that chromosomal studies of Hodgkin's disease are likely to be successful. Additional studies are needed to correlate the karyotypical abnormalities in Hodgkin's disease with clinical and biological characteristics.

Adolescent↗
PubMed1988

Laser vaporization of vaginal intraepithelial neoplasia.

Laser vaporization was used to treat 27 women diagnosed at the Tom Baker Cancer Centre, Calgary, Alberta, Canada, as having vaginal intraepithelial neoplasia. The diagnosis was established after review of vaginal cytologic examination and a histologic biopsy. Treatment was performed with a carbon dioxide laser unit attached to an operating microscope. All but three patients had general anesthesia for the purpose of treatment. Tissue destruction was accomplished to a depth of 2 to 3 mm. Patients were followed up for an average of 14.4 months with regular colposcopy, cytologic evaluation, and biopsy when persistent or recurrent disease was suspected. Failure of therapy was defined as evidence of intraepithelial neoplasia in any one of these three parameters. Four patients required a second treatment. After one or two treatments the success rate of therapy was 78%. In our institution, laser vaporization with the patient under general anesthesia on an outpatient basis is the treatment of choice for vaginal intraepithelial neoplasia.

Ambulatory Surgical Procedures↗
PubMed1988

Angiotensin-converting enzyme inhibitors. Mercaptan, carboxyalkyl dipeptide, and phosphinic acid inhibitors incorporating 4-substituted prolines.

Analogues of captopril, enalaprilat, and the phosphinic acid [hydroxy(4-phenylbutyl)phosphinyl]acetyl]-L-proline incorporating 4-substituted proline derivatives have been synthesized and evaluated as inhibitors of angiotensin-converting enzyme (ACE) in vitro and in vivo. The 4-substituted prolines, incorporating alkyl, aryl, alkoxy, aryloxy, alkylthio, and arylthio substituents were prepared from derivatives of 4-hydroxy- and 4-ketoproline. In general, analogues of all three classes of inhibitors with hydrophobic substituents on proline were more potent in vitro than the corresponding unsubstituted proline compounds. 4-Substituted analogues of captopril showed greater potency and duration of action than the parent compound as inhibitors of the angiotensin I induced pressor response in normotensive rats. The S-benzoyl derivative of cis-4-(phenylthio)captopril, zofenopril, was found to be one of the most potent compounds of this class and is now being evaluated clinically as an antihypertensive agent. In the phosphinic acid series, the 4-ethylenethioketal and trans-4-cyclohexyl derivatives were found to be the most potent compounds in vitro and in vivo. A prodrug of the latter compound, fosinopril, is also being evaluated in clinical trials.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1988

Pyoderma gangrenosum or cutaneous lymphoma: a difficult clinical diagnosis.

Pyoderma gangrenosum is frequently associated with an underlying condition such as ulcerative colitis or a myeloproliferative syndrome. However, lymphoproliferative malignancies have only rarely been seen concurrently with pyoderma gangrenosum. We present the case of a patient with small lymphocytic lymphoma who noted a slowly enlarging skin ulcer that was clinically consistent with pyoderma gangrenosum. Examination of a biopsy specimen showed infiltration of the skin with lymphoma cells as well as deeper necrotic material and thrombosis of vessels that were infiltrated by lymphoma. This case illustrates the difficulty of differentiating pyoderma gangrenosum from cutaneous lymphoma clinically.

Diagnosis, Differential↗
PubMed1979

Severe ulcerative herpes of mouth and eye following measles.

Malnourished children in the north of Nigeria who had had a severe attack of measles were prone to deep ulcers of the mouth and eyes. Herpes simplex virus was isolated from 17 of 25 of the mouth ulcers which were erosive, slow to heal and caused much suffering and loss of weight. Herpes virus was also identified, either by immunofluorescent staining or viral culture, in the corneal scrapings of the eye ulcers from 16 of 34 children. These ulcers healed slowly in two to six weeks leaving damaging scars which impaired vision and caused blindness in some cases. It is suggested that measles leads to profound depression of cell mediated immunity in malnourished children with the consequence that secondary herpes simplex infections become abnormally severe and erosive.

Body Weight↗
PubMed1979

Ischaemic heart disease-an hypothesis to integrate the role of insulin, fibre and sucrose.

The theory that a high dietary cholesterol and saturated fat intake has an aetiological role in coronary artery disease is inadequate. So are those theories based upon insulin, upon refined carbohydrate and upon dietary sucrose. An alternate hypothesis is presented. Central to it is prolonged hyperinsulin-aemia. This, acting synergistically with the changes in lipide metabolism secondary to the effects of dietary fibre and sucrose, is crucial to atherogenesis. There is abundant evidence for an association of insulin and vascular changes, both in vitro and in epidemiological studies. Laboratory and epidemiological evidence also exists for an effect of fibre and soluble carbohydrate on cholesterol synthesis and excretion, both as itself and as bile acid. A scheme is presented to demonstrate these complex inter-relationships and their role in vascular diseases.

Animals↗
PubMed1975

Meningococcal antigen in diagnosis and treatment of group A meningococcal infections.

Meningococcal antigen was measured by countercurrent immunoelectrophoresis in the blood and cerebrospinal fluid of 200 patients with group A meningococcal meningitis. Antigen was detected in the blood of 27 (13.5 per cent) patients. These patients had a worse prognosis and a higher incidence of allergic complications, such as arthritis and vasculitis, about 5 days after the start of antibiotic treatment. Antigen was found in the CSF of 129 (67.5 per cent) patients); antigen often persisted in the cerebrospinal fluid despite antibiotic treatment before admission. A combination of immunoelectrophoresis and routine bacteriologic study was used in the diagnosis of 162 (84.8 per cent) patients with meningococcal meningitis. High levels of antigen and a slow antigen disappearance were associated with neurologic damage. The antigen is stable and may be detected from specimens of cerebrospinal fluid dried on filter paper.

Antigens, Bacterial↗
PubMed1973

Trial of chloramphenicol for meningitis in northern savanna of Africa.

In a controlled trial chloramphenicol proved as effective and much cheaper than penicillin for the treatment of group A meningococcal meningitis in Zaria, Nigeria. A short course of five days cured most patients. Adults and older children were soon able to take chloramphenicol by mouth, which reduced the cost and simplified treatment.It is suggested that chloramphenicol is a suitable alternative to sulphonamides for the treatment of meningococcal meningitis in those parts of Africa where the organism is sulphonamide-resistant.

Administration, Oral↗