No abstract

SUMMARYMicrovascular complications of insulin-dependent diabetes mellitus (IDDM) have been strongly associated with platelet abnormalities, whilst TNF-a has been implicated in the pathogenesis of this condition. However, at present it is not clear whether human circulating platelets express TNF-a or TNF receptors (TNF-R) or whether impaired expression of these molecules and of the TNF-reactive adhesion molecule ICAM-1 may be associated with platelet abnormalities in patients with IDDM. On this basis we investigated the platelet expression of these molecules in patients with IDDM complicated or uncomplicated by proliferative diabetic retinopathy (PDR) and in healthy subjects. We observed that the proportion of platelets staining for TNF-a was significantly higher in IDDM patients with active PDR than in patients without microvascular complications (P ¼ 0·0078), quiescent PDR (P ¼ 0·003) or healthy subjects (P ¼ 0·0013). Patients with active PDR also showed a higher proportion of platelets expressing TNF-RI (P ¼ 0·0052) and TNF-RII (P ¼ 0·015) than healthy controls or patients with quiescent PDR (P ¼ 0·009 and 0·0006, respectively). In addition, the percentage of ICAM-1 þ platelets was significantly higher in patients with active PDR than in patients with quiescent PDR (P ¼ 0·0065) or normal subjects (P ¼ 0·013). There was a direct correlation between platelet expression of TNF-a and that of TNF-R in PDR patients, indicating that platelet staining for TNF-a may be due to binding of this cytokine to its receptors. The results suggest that increased platelet expression of TNF-a, TNF-R and ICAM-1 in IDDM patients may constitute important markers of thrombocyte abnormalities during the development of microvascular complications of diabetes mellitus.

Hypoxic cells in tumours can be identified by exposing them to an immunologically identifiable 2-nitroimidazole (NITP) with a theophylline substituent which becomes bioreductively metabolised and binds to cellular macromolecules in the absence of oxygen. A range of monoclonal and polyclonal antibodies raised against theophylline or caffeine can identify cells containing bound adducts of NITP, in some cases with higher specificity than the standard product used. An alternative approach utilizes the very high specificity of FITC-avidin as a reagent to detect metabolic binding of a 2-nitroimidazole with a biotinylated side-chain (NIB), with the advantage of a single-step staining protocol. Both proliferating and hypoxic cell populations within tumours can be identified by simultaneous staining for incorporation of NITP and BrdUrd and this has shown that some cells incorporate both markers, suggesting that there is some overlap between the proliferating and hypoxic cell compartments.

The contribution of organic and psychogenic factors in the aetiopathogenesis of impotence was studied in a large number of diabetic males, to develop an algorithm for its management. We examined 110 consecutive patients who were referred to the Impotence Clinic of the Diabetes Centre. All patients were initially evaluated by a diabetologist and then underwent psychosexual assessment by a specialized psychiatrist. Patients with primarily organic disease were referred to a urologist for further management while those with psychogenic impotence received psychosexual counselling. Peripheral neuropathy was present in 71 (65%) and two or more autonomic tests were abnormal in 22 (20%) patients. Neuropathy was the only cause detected in 29 (27%) patients, the main cause in 22 (20%), and contributing, but not the main factor, in 20 (18%). Psychogenic factors were the only cause detected in 12 (11%) patients, the main cause in 26 (24%) and contributed in 19 (17%). Marital disharmony, medical treatment, and peripheral vascular disease were the main aetiopathogenic factors in the remaining cases. Psychosexual counselling resulted in successful intercourse in 17 (60%) out of the 24 treated patients and papaverine injections in 31 (61%) out of 56 treated patients. It is concluded that although organic factors are mainly responsible for the development of impotence in diabetic males, psychological factors contribute significantly and psychosexual assessment and counselling are essential adjuncts to its management. Treatment with papaverine injections is generally inexpensive and effective to overcome the multifactorial causes of erectile dysfunction in this population. An algorithm which may facilitate the investigation and treatment of impotent diabetic males is proposed.