Homocysteine, folate, methylation, and monoamine metabolism in depression.

OBJECTIVES: Previous studies suggest that folate deficiency may occur in up to one third of patients with severe depression, and that treatment with the vitamin may enhance recovery of the mental state. There are, however, difficulties in interpreting serum and red cell folate assays in some patients, and it has been suggested that total plasma homocysteine is a more sensitive measure of functional folate (and vitamin B12) deficiency. Other studies suggest a link between folate deficiency and impaired metabolism of serotonin, dopamine, and noradrenaline (norepinephrine), which have been implicated in mood disorders. A study of homocysteine, folate, and monoamine metabolism has, therefore, been undertaken in patients with severe depression. METHODS: In 46 inpatients with severe DSM III depression, blood counts, serum and red cell folate, serum vitamin B12, total plasma homocysteine, and, in 28 patients, CSF folate, S-adenosylmethionine, and the monoamine neurotransmitter metabolites 5HIAA, HVA, and MHPG were examined. Two control groups comprised 18 healthy volunteers and 20 patients with neurological disorders, the second group undergoing CSF examination for diagnostic purposes. RESULTS: Twenty four depressed patients (52%) had raised total plasma homocysteine. Depressed patients with raised total plasma homocysteine had significant lowering of serum, red cell, and CSF folate, CSF S-adenosylmethionine and all three CSF monoamine metabolites. Total plasma homocysteine was significantly negatively correlated with red cell folate in depressed patients, but not controls. CONCLUSIONS: Utilising total plasma homocysteine as a sensitive measure of functional folate deficiency, a biological subgroup of depression with folate deficiency, impaired methylation, and monoamine neurotransmitter metabolism has been identified. Detection of this subgroup, which will not be achieved by routine blood counts, is important in view of the potential benefit of vitamin replacement.

Multiple fractions daily for head and neck cancer: spinal cord effects and other late results.

Reports of late spinal cord damage after multiple fractions daily radiotherapy regimens for head and neck cancer are infrequent, but increasing. We have reviewed our experience of head and neck cancers treated thrice daily to examine this problem. Between 1982 and 1990, 65 patients with advanced head and neck cancer were treated by primary radiotherapy using three small fractions delivered on 5 days per week, with an inter-fraction interval of 3-4 hours during normal working hours. In 25 patients, the cervical spinal cord received > 39 Gy. In 13 patients, 39.6 Gy was given in 1.1 Gy fractions, and five received 41.8 Gy in 1.1 Gy fractions, two received 45.1 Gy in 1.1 Gy fractions and five received 45 Gy in 1.5 Gy fractions. Eleven of these patients have survived over 2 years, and can be assessed for late spinal cord damage. Ten of these received 1.1 Gy fractions with no cord damage. The only 2-year survivor whose cord received 45 Gy in 1.5 Gy fractions has developed mild, non-progressive long tract signs. Other late side effects were equivalent to those after conventionally fractionated radiotherapy. Tumour control was good, especially for the larynx. We feel that, for radiotherapy given with three small fractions daily and an inter-fraction interval of 3-4 hours, the spinal dose should not exceed 40 Gy.

Salvage laryngectomy after radical radiotherapy for laryngeal carcinoma.

Of 376 patients who were treated by radical radiotherapy for squamous carcinoma of the larynx, 56 subsequently underwent total laryngectomy. Residual or recurrent tumour was identified in 43 of the resection specimens, and necrosis alone in 13 cases, although a positive biopsy had been obtained in 3 of these prior to salvage laryngectomy. No disease related factors such as site or stage of the original tumour, or treatment related factors such as radiation type or dose, were found to be predictive of whether or not tumour was present. The clinical opinion of an experienced surgeon was found to have a positive predictive value of 0.86 for the presence of tumour. The fistula rate of salvage laryngectomy, 15 out of 56, was similar to that of other series. The actuarial cause specific 5-year survival for patients with tumour was 0.589, and for patients with necrosis only was 0.923. Intercurrent, smoking related disease was the cause of death in 16 of the 33 patients who have died.

Mastoid surgery in childhood.

The presenting features and operative findings in 105 patients aged 16 years or less undergoing mastoid surgery are reviewed. In 94% surgery was for chronic otomastoiditis, usually acquired, and associated with cholesteatoma in 64%. Post-operative otorrhoea persisted beyond 6 months in 44% and contralateral disease required some form of surgical procedure in 20%. Post-operative hearing thresholds were improved or unchanged in the majority of patients, most of whom underwent cortical or modified radical mastoidectomy. An improvement in the therapeutic results of mastoid surgery in childhood is clearly necessary, but requires a greater understanding of the aetiology of chronic middle ear disease.

Heparin and dihydroergotamine prophylaxis against thrombo-embolism after hip arthroplasty.

A prospective study involving 500 consecutive patients undergoing hip replacement was performed to find out whether a combination of heparin and dihydroergotamine was effective in preventing postoperative fatal and non-fatal emboli. Deep-vein thrombosis was demonstrated in 131 cases (26.2%), in 99 of whom thrombi were confined to the ipsilateral (operated) limb and in 13 to the contralateral limb; 19 patients developed bilateral thrombi. Nine patients (1.8%) died during the first four weeks after operation, before they were discharged from hospital; in one, major emboli were demonstrated in the right pulmonary artery. Three of the 500 patients developed non-fatal pulmonary emboli. Excessive bleeding occurred in 21 (4.2%) and in 19 of these prophylaxis was discontinued. Wound haematomas developed in 25 patients (5.0%); only six required evacuation but in none of these six did deep infection occur while in hospital; in three patients, however, the wound haematoma prolonged the stay in hospital. Thus the combination of heparin and dihydroergotamine proved an effective prophylaxis against pulmonary embolism in patients undergoing total hip replacement. The risk of bleeding complications is wholly acceptable when balanced against the advantages of the therapy.