PubMed Health⌕ Search

Biomedical subjects

A L Crombie

Publications and source records attributed to A L Crombie.

At least 19 recordsLinked to original sources
PubMed2001

A ring expansion-annulation strategy for the synthesis of substituted azulenes. Preparation and Suzuki coupling reactions of 1-azulenyl triflates.

[structure: see text]. A new strategy for the synthesis of substituted azulenes is reported, based on the reaction of beta'-bromo-alpha-diazo ketones with rhodium carboxylates. The key transformation involves intramolecular addition of a rhodium carbenoid to an arene pi-bond, electrocyclic ring opening, beta-elimination, tautomerization, and trapping to produce 1-hydroxyazulene derivatives. The synthetic utility of the method is enhanced by the ability of the triflate derivatives to participate in Suzuki coupling reactions, as illustrated in a synthesis of the antiulcer drug egualen sodium (KT1-32).

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1995

Natural history of thyroid associated ophthalmopathy.

BACKGROUND: The natural history of thyroid associated ophthalmopathy is poorly documented, although it is widely thought that many cases improve spontaneously with time. This has important implications in the management of patients and is also a critical factor when assessing the effects of different treatments. OBJECTIVE: To document the natural history of thyroid associated ophthalmopathy, 59 patients were studied longitudinally and the severity of eye disease documented at regular intervals. METHODS: Fifty-nine patients with thyroid associated ophthalmopathy who had not received immunosuppressive or surgical treatment for their eye disease, were recruited from a combined thyroid-eye clinic. They were assessed at presentation and at 3-6-monthly intervals for a median of 12 months. The eyes were assessed by separate and objective measurements relating to the status of the eyelids, cornea, extraocular muscles, proptosis and optic nerve function. In addition, a scoring system based on the above measurements was used to grade the overall severity of eye disease. RESULTS: Thirteen patients (22%) improved substantially, 25 patients (42.4%) showed minor improvement, 13 patients (22%) did not change, and 8 patients (13.5%) deteriorated progressively, to the extent that immunosuppressive treatment was considered to be necessary. CONCLUSIONS: A significant proportion of patients with thyroid associated ophthalmopathy (64.4% in the present series) improve spontaneously so serial assessment plays an important part in deciding which patients require immunosuppressive treatment. These findings also support the view that clinical trials designed to test the efficacy of new treatments in thyroid associated ophthalmopathy should be scrupulously controlled to allow for the natural tendency towards remission.

Adolescent↗
PubMed1993

Age and gender influence the severity of thyroid-associated ophthalmopathy: a study of 101 patients attending a combined thyroid-eye clinic.

BACKGROUND: The pathogenesis of thyroid-associated ophthalmopathy is thought to be autoimmune, although environmental and genetic factors are also considered to be important. As the morbidity of thyroid-associated ophthalmopathy is considerable and treatment often unsatisfactory, there a need to identify possible predisposing factors. OBJECTIVE: The study was undertaken in order to ascertain the relationship between age, gender and severity of thyroid-associated ophthalmopathy. PATIENTS: One hundred and one consecutive patients with thyroid-associated ophthalmopathy who presented over a period of 5 years to a combined thyroid-eye clinic. METHODS: Patients were assessed by grading their inflammatory signs and degree of diplopia, and by measurement of exophthalmos, palpebral aperture, differential intraocular pressure, and visual acuity. On the basis of the above an ophthalmopathy index was devised to grade the overall severity of eye disease. RESULTS: The mean age was 49.2 years (SD 13.4), the female-to-male ratio was 4.05, and mean ophthalmopathy index 6.49 (SD 3.3). Optic nerve compression was present in 9.9% of patients. There was a positive relationship between age and ophthalmopathy index (P < 0.001); after correcting for age, males had an average ophthalmopathy index 41% greater than that of females. CONCLUSION: There is an association between severity of thyroid-associated ophthalmopathy and (i) advancing age and (ii) female-to-male ratio, which has not been previously described. Patients over the age of 60 (particularly males) with Graves' disease appear to be at risk of developing severe eye disease.

Age Factors↗
PubMed1990

Azathioprine in the treatment of thyroid-associated ophthalmopathy.

Azathioprine is used in the treatment of thyroid-associated ophthalmopathy, but its effectiveness has not been evaluated. In the present study 20 patients with moderately severe ophthalmopathy were recruited; 10 patients received azathioprine and the other 10 matched patients served as controls. During the treatment period (lasting 1 year) and 1 year later, no changes were detected in exophthalmometer readings, visual acuity or measurement of palpebral aperture. Differential intraocular pressure fell with time in both groups. Azathioprine treatment did not significantly influence these parameters, although it did induce significant decrease in thyroid microsomal antibodies and in thyroid-stimulating hormone binding inhibiting immunoglobulin index. The study demonstrates that thyroid-associated ophthalmopathy of moderate severity, often improves with time without treatment. Azathioprine is not an effective treatment for patients with moderately severe thyroid-associated ophthalmopathy. The study emphasises the necessity for an adequately matched control population in the evaluation of therapy.

Azathioprine↗
PubMed1988

Intravenous methylprednisolone in the treatment of Graves' ophthalmopathy.

Eleven euthyroid patients with severe Graves' eye disease were treated with intravenous methylprednisolone and followed up for six months or more by ophthalmological assessment, orbital computed tomography (CT), photographs, and antibody measurements. Papilloedema resolved in the single patient in whom it was present; visual acuity was abnormal in seven eyes initially and in only one eye after treatment; the intraocular pressure differential, which reflects muscle dysfunction, was initially abnormal in 18 eyes but showed a progressive and distinct improvement; nine patients showed substantial improvement in inflammatory signs. Exophthalmos improved early after treatment, but this improvement was not maintained. Orbital CT showed a pronounced reduction in the bulk of eye muscles after treatment in eight of nine patients. Autoantibodies to the thyroid stimulating hormone receptor declined. Adverse effects were trivial. Thus eight patients showed a clear response to intravenous methylprednisolone as judged by ophthalmic assessment and CT scan. The two patients who showed little response and one who had none all had a long history (more than a year) of ophthalmopathy. Results were better than those with oral steroids and adverse effects less. Treatment of Graves' eye disease is more likely to be effective if given early; patients should be referred promptly to specialist centres, where treatment with intravenous methylprednisolone should be considered.

Adult↗
PubMed1986

The long-term effects of megavoltage radiotherapy as sole or combined therapy for large prolactinomas: studies with high definition computerized tomography.

The long-term sequelae of external pituitary irradiation alone or in combination with surgery and/or bromocriptine therapy have been studied in 14 patients with large prolactinomas over an observation period of 6-22 years (mean 13 years). Galactorrhoea was abolished in four of the five females with this symptom, but menstrual disturbance persisted in five of six patients. Sexual function was normal without sex hormone replacement in only one of the eight males after treatment. Neurological deficits were abolished or improved by treatment in all 9 patients with this presentation. Serum prolactin levels declined after treatment (P less than 0.001) and fell to within the normal range off bromocriptine therapy in six of the 14 patients at a mean of 9 years (range 5-17 years) after radiotherapy. All patients had anterior pituitary deficiency of some degree at reassessment, and 13 required replacement treatment. Serial skull radiographs revealed remineralization of the fossa floor in five patients and a decrease in fossa size in three. All five patients who did not also have surgery had evidence of tumour shrinkage without bromocriptine treatment (on CT scan or metrizamide cisternography). Fourth generation CT scans on completion of the study revealed a decrease in tumour mass in all patients, with varying degrees of empty sella in 13 and a cystic intrasellar tumour in the remaining one. Residual tumour was demonstrated in 10 patients, three of whom had normal serum prolactin levels, while one patient without visible tumour had persistent hyperprolactinaemia. Radiotherapy, alone or in combination with surgery and bromocriptine, effectively decreases prolactin secretion and tumour size in patients with large prolactinomas at the expense of other anterior pituitary function. Circulating prolactin levels are a poor marker of residual tumour volume.

Adolescent↗
PubMed1983

Hyperprolactinemia. Long-term effects of bromocriptine.

Patients with hyperprolactinemia may be managed by pituitary surgery or irradiation, bromocriptine treatment, or a combination of these methods, and some patients remain untreated. Little is known of the long-term consequences of some of these therapeutic regimens. Forty-six hyperprolactinemic patients (40 female and six male) managed solely with bromocriptine or no treatment over a period of 12 months to six years were therefore evaluated in this study. Nine patients with radiologically normal pituitary fossae were untreated and 10 received bromocriptine, 7.5 to 10 mg daily, while 20 patients with radiologic evidence of a pituitary tumor were treated with bromocriptine, generally 10 to 20 mg daily. Patients were assessed clinically, biochemically, and radiologically before treatment and at least six weeks after discontinuation of therapy. A further seven patients were similarly assessed before and after eight bromocriptine-induced pregnancies. Symptoms persisted in the untreated group of nine patients, although menstruation returned in four of the females with previous amenorrhea; serum prolactin levels remained elevated, other pituitary function did not change, and pituitary fossae remained normal radiologically. In all patients treated with bromocriptine, symptoms improved irrespective of radiologic findings on the pituitary, and were abolished in 67 percent during treatment associated with a decrease in serum prolactin levels in all, and a return of levels to within normal limits in 80 percent of patients. Persistent side effects were usually dose-related, but remained troublesome in 13 percent. Bromocriptine-induced tumor regression was evident radiologically in all patients with suprasellar tumor tissue and in some with purely intrasellar adenomas. This effect occurred rapidly and persisted or increased throughout follow-up. On discontinuation of treatment, prolactin levels remained significantly lower than before therapy (mean 2,934 versus 5,052 mU/liter, p less than 0.05) but were within the normal range in only two patients. Other pituitary function was unaltered, or improved in some patients with definite tumors. Bromocriptine-induced pregnancy produced no permanent change in clinical, biochemical, or radiologic status. Long-term bromocriptine treatment for hyperprolactinemia is thus highly effective in alleviating symptoms and suppressing prolactin secretion, and induces persistent tumor regression on treatment without deterioration of other pituitary function in patients with macroadenomas. On discontinuation of therapy, however, hyperprolactinemia usually recurs, and treatment may therefore need to be continued for years.

Adult↗
PubMed1980

An evaluation of supervoltage orbital irradiation for Graves' ophthalmopathy.

Twenty patients with moderately severe ophthalmopathy due to Graves' disease or ophthalmic Graves' disease were treated by supervoltage orbital radiotherapy generated by a linear accelerator. Seven patients (35%) showed some response within 3 weeks of the treatment, four patients (20%) improved minimally while nine patients (45%) were unchanged. Improvement was noted mainly in soft tissue changes while proptosis decreased in only four patients. With one exception, ophthalmoplegia did not improve after the radiotherapy. The benefit obtained with the treatment was not impressive.

Adult↗
PubMed1976

Study on a family with anderson--Fabry's disease and associated familial spastic paraplegia.

A family in the north-east of England with Anderson--Fabry's disease is presented. Alpha-galactosidase activity in plasma and white cells was significantly reduced in three adult male members of the family. One of them had an abnormal chromosome karyotype pattern with an extra Y chromosome (47,XYY) and he was clinically less severely affected than his brothers. Coincidentally five other members of the family suffered from a form of familial spastic paraplegia.

Adult↗