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Biomedical subjects

C J O'Brien

Publications and source records attributed to C J O'Brien.

At least 37 records · Page 2Linked to original sources

Changing trends in the management of carcinoma of the oral cavity and oropharynx.

Two groups of patients with squamous cell carcinoma of the oral cavity and oropharynx treated by radical surgery were studied. Special emphasis was placed on analysing changing trends in reconstruction and the management of the mandible and their influence on complication rates, length of hospital stay and tumour control rates. Group 1 consisted of 97 patients treated between 1980 and 1984 and Group 2 consisted of 153 patients treated between 1987 and 1991. Anatomical distribution of cancers and clinical stages were similar in the two groups. The major trends identified were: (i) the increasing use of free flaps for reconstruction (0 in Group 1, 41% in Group 2); (ii) more conservative mandibular resection and the increasing use of mandibular swing procedures (1% in Group 1, 16% in Group 2) rather than segmental mandibular resection (44% in Group 1, 13% in Group 2); (iii) fewer procedures per patient (2.6 per patient in Group 1, 1.2 per patient in Group 2); and (iv) a decrease in mean duration of hospital stay from 34 to 16 days and fewer complications. Patients in Group 2 also had a lower rate of local recurrence of cancer when compared with patients in Group 1 (19 vs 29%).

Carcinoma, Squamous Cell

Naevoid basal cell carcinoma (Gorlin's) syndrome.

The multiple naevoid basal cell carcinoma syndrome (Gorlin's syndrome) is an inherited multisystem disorder which affects not only the skin, but also the skeletal system and a variety of other tissues and organs. This is a report of the case of a 29 year old woman who presented with multiple advanced basal cell carcinomas. On the basis of a literature review, guidelines for management are suggested and the importance of early diagnosis and regular follow-up is emphasized.

Adult

Comprehensive treatment strategy for oral and oropharyngeal cancer.

This prospective nonrandomized study analyzes the effectiveness of the following treatment protocol for oral and oropharyngeal cancers: (1) radical initial surgery; (2) elective modified or selective neck dissection for NO necks; (3) jaw preservation unless gross invasion is present; (4) radial forearm freeflap reconstruction; (5) elective tracheotomy; (6) postoperative radiotherapy unless previously given; and (7) active oral rehabilitation. Between 1987 and 1992, 75 patients (55 men and 20 women) with a median age of 58 years had this treatment. Fifteen had been previously treated with radiotherapy. Clinical stages of untreated patients were as follows: 4 patients, stage I; 25 patients, stage II; 12 patients, stage III; and 19 patients, stage IV. Ten patients had segmental jaw resection, 26 had a marginal mandibulectomy, and 26 had a jaw swing. There were no operative deaths, and only one flap (1.2%) failed. Median times for oral feeds and hospital stay were 8 and 17 days, respectively. Forty-four patients had postoperative radiotherapy. Median follow-up time is 30 months, and locoregional control is 95% for previously untreated patients and 54% for previously treated patients. Thirteen patients have died of disease, 8 with locoregional recurrence and 5 with distant metastases alone. We conclude that this treatment strategy is highly effective in previously untreated patients but less effective in salvaging patients in whom radiotherapy has failed.

Adult

Clinical tolerance to three 5-aminosalicylic acid releasing preparations in patients with inflammatory bowel disease intolerant or allergic to sulphasalazine.

The clinical tolerance to three 5-aminosalicylic acid (5-ASA) releasing preparations (mesalazine, olsalazine and balsalazide) was assessed in a consecutive series of 43 patients with inflammatory bowel disease who were intolerant to sulphasalazine. The relative contributions to the side-effects of sulphasalazine made by its two components, 5-ASA and sulphapyridine, were also assessed in these patients. Thirty-nine (91%) patients were able to tolerate at least one of the three 5-ASA preparations. Only four (9%) patients were intolerant to all preparations, having adverse reactions previously experienced with sulphasalazine and presumably related to 5-ASA rather than sulphapyridine. The clinical tolerance to mesalazine (63%), olsalazine (70%) and balsalazide (70%) was similar, and tolerance to one drug only was found in nine (18%) patients. The commonest adverse reactions associated with 5-ASA preparations were gastrointestinal. Diarrhoea was a problem in five patients during treatment with olsalazine and three each while on mesalazine and balsalazide. Allergic reactions from 5-ASA preparations were uncommon; of ten patients with rash following sulphasalazine only one developed a rash with mesalazine. The results of this study indicate that the vast majority of patients with inflammatory bowel disease can be managed with at least one of these four 5-ASA containing preparations and that the side-effects of sulphasalazine are multifactorial in aetiology, some being due to the parent molecule, and some to one of its two metabolites, 5-ASA and sulphapyridine.

Aminosalicylic Acids

Limitations of radiotherapy in the definitive treatment of squamous carcinoma of the tonsillar fossa.

Between 1970 and 1990, 104 patients with squamous cell carcinoma (SCC) of the tonsil were treated. The median age was 58 years and 80% of patients were males. Distribution among clinical stages was: stage I, 19 patients; stage II, 12 patients; stage III, 23 patients; and stage IV, 48 patients. More than 70% of patients had initial radiotherapy as definitive treatment irrespective of stage, reflecting the treatment philosophy over much of this period. The overall survival rate was 26% at 5 years, with survival being significantly affected by T stage, clinical stage and age. Clinical node status did not significantly affect survival rates. Good local control of T1N0 cancers was achieved with radiotherapy alone, but patients with more advanced cancers did poorly. We have now moved away from a non-selective policy and use initial surgery combined with postoperative radiotherapy in most patients, reserving radiotherapy alone for mainly early tonsil cancers.

Adult

Familial coexistence of achalasia and non-achalasic oesophageal dysmotility: evidence for a common pathogenesis.

In five of seven siblings of healthy parents, dysphagia developed during adolescence or early adult life. A barium swallow was normal in one patient but showed appearances considered to be consistent with achalasia in all others. Oesophageal manometry was successfully performed in four of the five patients, including the patient with symptoms but normal radiological appearance. One patient had achalasia, two had oesophageal body motor dysfunction associated with a hypertensive, but normally relaxing lower oesophageal sphincter, and one had diffuse oesophageal spasm alone. The occurrence of three different oesophageal dysmotility disorders within members of a single sibship suggests that these conditions are intimately related and probably genetically determined as an autosomal recessive trait.

Adolescent

Experience with 998 cutaneous melanomas of the head and neck over 30 years.

Between 1960 and 1990, a total of 998 patients were treated at the Sydney Melanoma Unit for cutaneous melanoma of the head and neck. There were 595 male and 403 female patients, with a median age of 53 years. The most common primary lesion site was the face (47%), followed by the neck (29%), scalp (14%), and ear (10%). Histologic types were as follows: superficial spreading 30%, nodular melanoma 28%, lentigo maligna melanoma 16%, and other 26%. All patients underwent surgical treatment. Primary closure of wounds was achieved in 52% of patients, and excision margins were 2 cm or less in 45%. A total of 152 patients had therapeutic neck dissections, and 234 had elective neck dissections. The overall local recurrence rate was 13%, and this was significantly influenced by increasing tumor thickness and Clark level. The recurrence rate in the neck after neck dissection was 24%, and the rate of parotid recurrences was 14%. Melanoma-specific survival was 77% at 5 years and 66% at 10 years for the entire group. By univariate analysis, survival varied significantly with age, tumor thickness, ulceration, anatomic sub-site, histologically positive nodes, and the presence of distant metastases. A diagnosis of lentigo maligna melanoma and elective lymph node dissection both appeared to improve survival. With multivariate analysis, all of these factors remained significant prognostic factors except elective node dissection, which lost its beneficial influence.

Female

Elemental diet in steroid-dependent and steroid-refractory Crohn's disease.

Sixteen patients with Crohn's disease who had symptoms uncontrolled by high-dose steroids (n = 11) or symptoms invariably appearing on reduction or withdrawal of immunosuppressive therapy (n = 5) were treated with elemental diet. After 4 wk of dietary treatment, 10 patients were in remission and off all medication. Seven continued to be well without treatment for a minimum of 6 months, and four for at least 1 yr. No patient who subsequently relapsed had further steroid-refractory symptoms. Of the six patients failing to respond to elemental diet, four with steroid-refractory disease required early resective surgery for symptom relief, and two continued with steroid therapy, one in much reduced dosage. Elemental diet can bring about a sustained remission in many patients with Crohn's disease dependent on or refractory to corticosteroids, and reduce the need for surgical intervention.

Adolescent

Aerobic work capacity in patients with chronic fatigue syndrome.

OBJECTIVE: To determine the aerobic work capacity of patients with the chronic fatigue syndrome and compare it with that of two control groups, and to assess the patients' perception of their level of activity before and during illness. DESIGN: A symptom limited exercise treadmill test with on line gas analysis and blood sampling was used. Subjects were assessed by one investigator, who was blind to the group which they were in. SETTING: Department of medicine, Royal Victoria Hospital, Belfast. SUBJECTS: 13 Patients (10 women, three men) who fulfilled the diagnostic criteria for chronic fatigue syndrome. Two control groups of similar age, sex, and body weight: 13 normal subjects (10 women, three men) and seven patients (five women, two men) with the irritable bowel syndrome. MAIN OUTCOME MEASURES: Aerobic work capacity as assessed by several variables such as length of time on treadmill, heart rate, and biochemical measurements; Borg score; and visual analogue scores of perceived level of physical activity. RESULTS: The patients with the chronic fatigue syndrome had a reduced exercise capacity compared with that of the other subjects, spending a significantly shorter time on the treadmill. They had a significantly higher heart rate at submaximal levels of exertion and at stage III exertion had significantly higher blood lactate concentrations. Using a Borg score, they showed a significantly altered perception of their degree of physical exertion with a mean score of 8.2 compared with 6.6 and 5.3 for the normal subjects and patients with the irritable bowel syndrome respectively. Using a visual analogue scale they indicated that they had a greater capacity for activity before illness than had the patients with the irritable bowel syndrome, but the scores were not significantly different between the two groups. Both groups of patients indicated reduced activity at the time of testing. Normal controls and patients with the irritable bowel syndrome aspired to a greater level of activity than their current level, but the patients with the chronic fatigue syndrome aspired to a level similar to that which they had had before their illness. CONCLUSIONS: Patients with the chronic fatigue syndrome have reduced aerobic work capacity compared with normal subjects and patients with the irritable bowel syndrome. They also have an altered perception of their degree of exertion and their premorbid level of physical activity.

Adult

Demonstration of Epstein-Barr virus in primary brain lymphoma by in situ DNA hybridisation in paraffin wax embedded tissue.

Tumour tissue from 29 patients with primary brain lymphoma was reviewed to determine if there was an aetiological association between Epstein-Barr virus and polyclonal and monoclonal lymphoproliferations. The morphology and immunophenotype in 24 patients for whom paraffin wax embedded tissue was available were studied. A high grade pleomorphic tumour morphology with plasmacytoid features was seen in 13 tumours. Because of the large number of pleomorphic lymphomas, all tumours were examined for the presence of the Epstein-Barr virus genome using in situ DNA hybridisation. A panel of three biotinylated probes to different sequences in the Epstein-Barr virus genome was used. Positive hybridisation with one or more probes was shown in tumours from 11 patients. The remaining tumours gave no hybridisation signal. There was no correlation between positive hybridisation and morphological subtype or clinical outcome.

Adolescent

Aperistaltic oesophageal disorders unmasked by severe post-fundoplication dysphagia.

Two patients were referred because of persistent dysphagia which developed for the first time after Nissen fundoplication. Investigations, including oesophageal manometry, demonstrated the presence of achalasia in one case, confirmed histologically, and aperistaltic oesophagus associated with an underlying connective tissue disorder in the other case. Our observations highlight the importance of assessing oesophageal motility before referring patients for anti-reflux surgery and illustrate the effect of such surgery on patients in whom oesophageal dysmotility was not suspected.

Connective Tissue Diseases

Increased interleukin 2 receptor expression in post-gestational women: relationship to impaired glucose tolerance and islet cell antibodies in pregnancy.

Fifteen women with positive islet cell antibodies were identified in a group of 115 consecutive patients found to have impaired glucose tolerance in pregnancy. These subjects were postulated to be at increased risk of later developing type 1 diabetes mellitus. They were examined post--partum for HLA types known to be associated with this disease and for any increase in Interleukin 2 receptor expression or alteration of T cell subsets of possible relevance to its pathogenesis. Fifteen women negative for islet antibodies and with normal glucose tolerance during previous pregnancy and 15 women with a normal fasting plasma glucose who had never been pregnant were studied as controls. Using flow cytometric techniques a significant increase in both the number and proportion of activated (Interleukin 2 receptor, CD25) lymphocytes in the peripheral blood of women who had islet cell antibodies and previous impaired glucose tolerance in pregnancy was found (0.14 +/- SE 0.03 x 10(9)/l; 7.1 +/- 1.1%) when compared with normal parous controls (0.09 +/- 0.01 x 10(9)/l; 4.2 +/- 0.6%), p less than 0.01 x 10(9)/l; showed significant increases when compared with nulliparous controls (0.04 +/- 0.01 x 10(9)/l; 2.1 +/- 0.2%), p less than 0.01. No differences were detected between the three groups with respect to total T-lymphocytes (CD3), helper T-lymphocytes (CD4), suppressor cytotoxic T-lymphocytes (CD8), or the inducer of suppressor (Leu 3+/Leu 8+) subset of T-lymphocytes. Three women persistently islet cell antibody positive, two of whom were HLA DR4, showed impaired glucose tolerance at the time of lymphocyte subset analysis, while two further patients, one DR3 and the other DR4, had developed type 1 (insulin-dependent) diabetes. No correlation between increased Interleukin 2 receptor expression and glucose intolerance was demonstrated. We conclude that islet cell antibody positive women with impaired glucose tolerance during pregnancy are at increased risk of later developing type 1 diabetes but that heightened immune activation present in these women is in part a post-pregnancy phenomenon.

Adolescent

Patterns of cellular immune responses to thyrocyte membrane antigens and specific immunoregulatory defects in autoimmune thyroid disease.

Although Graves' disease (GD), Hashimoto's thyroiditis (HT) and idiopathic myxoedema (Myx) are clinically distinct autoimmune thyroid diseases, previous studies using crude thyroid preparations as a source of antigens have failed to identify differences in cellular immune responses. In this study, we have assessed cellular immunity in patients with these disorders to two antigen preparations (derived from thyroid gland and cervical fat) enriched in cell membranes and known to share a functional TSH receptor. Using an indirect T-lymphocyte migration inhibitory factor (T-LIF) assay, T-cell immunity to thyroid membranes was demonstrated in 11/11 patients with GD, 4/5 with HT and 4/5 with Myx, but in none of 18 patients with chronic active hepatitis (another organ-specific autoimmune disease) or sixteen healthy controls. In contrast, T lymphocytes responsive to adipocyte membranes were detected only in patients with GD. TSH binding inhibiting antibodies were found exclusively in six patients with GD, and thyroid stimulating antibodies in five of these patients. In co-culture experiments designed to study the activity of antigen-specific suppressor T cells, low numbers of T cells from 6/6 normal controls, 4/4 patients with HT and 5/5 patients with myxoedema suppressed the response to adipocyte membranes of T lymphocytes from patients with Graves' disease. The results of this study demonstrate different patterns of T-cell reactivity to thyroid antigens in patients with Graves' disease, Hashimoto's thyroiditis and myxoedema and suggest that cellular immunity to the TSH receptor is restricted to patients with Graves' disease and associated with a defect in the specific immunoregulatory control of this response.

Adolescent

Correlation of morphology, immunophenotype, and flow cytometry with remission induction and survival in high grade non-Hodgkin's lymphoma.

A series of cases of high grade non-Hodgkin's lymphomas has been studied by morphology (110 cases), immunocytochemistry (90 cases), using reagents reactive in fixed paraffin-embedded tissue, and flow cytometry (77 cases). B-cell tumours constituted 67.0 per cent of the total, T-cell tumours 22.0 per cent, and unclassified cases 8.8 per cent. Immunocytochemistry revealed two anaplastic carcinomas. Of the 77 cases studied by flow cytometry, 67.5 per cent were diploid and 32.5 per cent DNA aneuploid. T-cell tumours were more likely to be diploid than B-cell tumours, though the difference did not reach statistical significance. T-cell tumours had a significantly lower proliferative index (%S + G2) than B-cell tumours (P = 0.002). The overall remission induction rate was 68 per cent and actuarial 3-year survival 47 per cent. There was a trend for cases with %S + G2 less than 22 per cent to survive longer (P = 0.07). This trend became statistically significant when aneuploid cases were added to the high PI group (P = 0.04). No correlation was seen between morphological or immunophenotypic groups and remission induction rates or survival.

Adolescent

Morphologic and immunophenotypic characterization of primary brain lymphomas using paraffin-embedded tissue.

Primary lymphomas of the brain constitute about 1% of all primary intracranial neoplasms, but recent studies suggest an increasing incidence. Most cases are associated with an immunosuppressed state. We reviewed 29 cases of primary brain lymphoma from the Yorkshire Health Authority Region between 1970 and 1988 and found a striking increase in incidence over this period. No overt evidence of immunosuppression was found in any case. All were non-Hodgkin's in type and were classified morphologically using Kiel criteria and immunophenotypically using a panel of antibodies. Cryo-preserved tissue was available in five cases for parallel immunophenotyping. The majority of tumours were high-grade lymphomas together with three of lymphoplasmacytoid type. Thirteen tumours showed a striking pleomorphic morphology with plasmacytoid features. A reactive, predominantly perivascular monomorphic T-cell population was seen in all tumours. Most tumours were of B-cell lineage. No cases of Hodgkin's disease, T-cell or histiocytic lymphoma were present. Light chain restriction was present in only 46% of cases. The results of tumour immunophenotyping on cryostat sections were comparable with those from paraffin blocks. Our study emphasizes the value of a panel of antibodies reactive in paraffin-embedded tissue, allowing simultaneous evaluation of morphology and immunophenotype, and suitable for small biopsies received from stereotactic procedures.

Adolescent

Morphological and immunohistological study of testicular lymphomas.

We have studied normal testis, seminomas and malignant lymphomas of the testis using routine stains and a panel of antibodies directed against lymphoid and basement membrane antigens. The results show that normal testis contains, at most, a minor population of T-lymphocytes: seminomas contain mixed T- and B-cell populations with a predominance of B-lymphocytes; and most primary lymphomas are B-cell tumours of large centroblastic type. Solid testicular lymphomas presenting secondarily to acute lymphoblastic leukaemias showed intact seminiferous tubular basement membranes with predominantly interstitial lymphomatous infiltrates, whereas the tubules in primary cases were over-run by lymphoma cells and basement membranes were disrupted.

Antibodies, Monoclonal