Effects of tolazamide and exogenous insulin on pattern of postprandial carbohydrate metabolism in patients with non-insulin-dependent diabetes mellitus. Results of randomized crossover trial

To determine whether therapy with exogenous insulin or sulfonylureas results in a postprandial pattern of carbohydrate metabolism in patients with non-insulin-dependent diabetes mellitus (NIDDM) that resembles that in nondiabetic individuals, we employed a dual-isotope technique combined with forearm catheterization to examine meal disposition in NIDDM patients, before and after 3 mo of therapy with tolazamide and after 3 mo of therapy with exogenous insulin, with a randomized crossover design. Results were compared with those observed in nondiabetic subjects. Although both forms of therapy improved chronic glycemic control (glycosylated hemoglobin concentration went from 9.6 +/- 0.7 to 7.6 +/- 0.5 and 7.1 +/- 0.2%, respectively, P less than .01), exogenous insulin resulted in a lower postprandial glycemic response than tolazamide (P less than .001). Both agents comparably increased (P less than .01) fasting and integrated postprandial insulin concentrations. However, the initial rate of postprandial increase was greater with exogenous insulin (P less than .05). Tolazamide (P less than .05) but not exogenous insulin increased postprandial C-peptide concentrations. However, tolazamide did not improve the deficient early insulin release. Both agents (P less than .05) lowered postabsorptive hepatic glucose release (from 2.8 +/- 0.3 to 2.3 +/- 0.2 mg . kg-1 . min-1), but not to normal rates (1.8 +/- 0.1 mg . kg-1 . min-1).(ABSTRACT TRUNCATED AT 250 WORDS)     

Cholinoceptor-mediated mechanical and electrical responses of rat oesophageal striated musculature. A comparison of two in vitro methods

1. Both muscarinic and nicotinic cholinoceptor agonists produce a contractile response of the rat oesophageal tunica muscularis externa (TME) in vitro. 2. The muscarinic receptor-mediated responses were confined to the distal 0.5 cm of the TME, which contains an admixture of smooth muscle. 3. Nicotinic receptor-mediated responses were obtained throughout the length of the TME striated musculature and consisted of a fast and slow component, representing TTX-sensitive contractions, associated with muscle action potentials, and electrically silent contractures, respectively. 4. Contractions were observed only in superfused preparations. 5. Contractures were resistant to changes in extracellular cation concentrations designed to eliminate generation of nerve and muscle action potentials or release of neurotransmitters.     

Pattern of postprandial carbohydrate metabolism and effects of portal and peripheral insulin delivery

The importance of portal insulin delivery in the regulation of postprandial carbohydrate metabolism is uncertain. To address this question, three groups of dogs were studied: one group in which pancreatic venous drainage was transected and reanastomosed (portal insulin delivery), one in which the pancreatic drainage was transected and anastomosed to the inferior vena cava (peripheral insulin delivery), and one that received only a sham operation. Plasma insulin was greater (P less than 0.05) during peripheral insulin delivery than in either the portal or sham groups, respectively, before and after meal ingestion. On the other hand, C-peptide concentrations did not differ between groups, resulting in a higher (P less than 0.001) insulin to C-peptide ratio in the peripheral group. This indicated that the hyperinsulinemia in the peripheral group was due to decreased insulin clearance rather than increased insulin secretion. Isotopically determined splanchnic uptake of ingested glucose, postprandial suppression of hepatic glucose release, incorporation of CO2 into glucose (a qualitative measure of gluconeogenesis), and total-body glucose uptake were virtually identical in all groups. Similarly, plasma lipid, beta-hydroxybutyrate, and lactate concentrations did not differ between groups. Our data indicate that, despite differences in systemic insulin concentration, portal and peripheral insulin delivery comparably regulate hepatic and extrahepatic carbohydrate metabolism after meal ingestion.     

Testicular microlithiasis: sonographic and clinical features.

Eleven cases of bilateral diffuse microlithiasis of the testes were evaluated sonographically. The presence of testicular microlithiasis was coincidental to the presence of testicular neoplasms (n = 2), nontesticular malignant lesion in the abdomen or chest (n = 2), subfertility (n = 2), varicocele (n = 1), epididymitis (n = 1), testicular maldescent (n = 1), scrotal trauma (n = 1), and transient scrotal pain (n = 1). Clinical follow-up suggested that testicular microlithiasis is an asymptomatic nonprogressive condition. Sonographic examination of testicular microlithiasis shows diffuse hyperechoic nonshadowing foci measuring 1-2 mm in diameter throughout both testes. The diagnosis of testicular microlithiasis was pathologically proved in five cases. In six cases, the diagnosis was made on the basis of the sonographic appearance (n = 6), clinical information and follow-up (n = 6), and radiologic demonstration of testicular microcalcifications (n = 3). The sonographic appearance of testicular microlithiasis is specific, and we believe that biopsy or orchiectomy in these cases is unnecessary.     

Cell cycling in bladder carcinoma determined by monoclonal antibody Ki67

Current methods of predicting prognosis in transitional cell carcinoma of the bladder fail to provide consistently reliable information about future tumour behaviour. The monoclonal antibody Ki67 recognises an antigen present in actively dividing cells and Ki67 reactivity has been shown to correlate with conventional prognostic indicators in several tumours. In this study, Ki67 antibody was used to determine the proportions of cells undergoing active division in 26 transitional cell carcinomas of the bladder. The proportion of cells stained in muscle invasive tumours (12.3 +/- 5.4%) was significantly greater than in superficial tumours (4.3 +/- 1.9%) and poorly differentiated tumours showed significantly greater proportions of cells staining compared with well or moderately well differentiated tumours. These results show that Ki67 reactivity correlates with high tumour stage and poor differentiation. Ki67 staining provides an easy method of determining tumour cell turnover that might provide additional prognostic information.     

Comparison of novel computer detectors and human performance for spike detection in intracranial EEG.

OBJECTIVE: Interictal spikes in intracranial EEG (iEEG) may correlate with epileptogenic cortex, but review of interictal iEEG is labor intensive. Accurate automated spike detectors are necessary for understanding the role of spikes in epileptogenesis. METHODS: The sensitivity, accuracy and reproducibility of three automated iEEG spike detectors were compared against two human EEG readers using iEEG segments from eight patients. A consensus set of detections was generated for detector calibration. Spike verification was calculated after both human EEG readers independently reviewed all detections. RESULTS: Humans and two of the three automated detectors demonstrated comparable accuracy. In four patients, automated spike detection sensitivity was >70% and accuracy was >50%. In the remaining four patients, EEG background morphology resulted in poorer performance. Blinded human verification accuracy was 76.7+/-6.6% for computer-detected spikes, and 84.5+/-4.1% for human-detected spikes. CONCLUSIONS: Automated iEEG spike detectors perform comparably to humans, but sensitivity and accuracy are patient dependent. Humans verified the majority of computer-detected spikes. SIGNIFICANCE: In some patients automated detectors may be used for mapping spike occurrences in epileptic networks. This may reveal associations between spike distribution, seizure onset, and pathology.     

Long-term follow-up of 500 patients with mild to moderate hypertension who had successfully completed a 3-month general practice study of a timolol-bendrofluazide combination ('Prestim')

A sample of 500 patients with mild to moderate hypertension, who had been successfully controlled on once daily timolol/bendrofluazide at the end of a 3-month general practice study, was followed up after approximately 1 year of treatment. Physicians who had participated in the trial were questioned on the current status of these patients. Out of 479 reports received, data showed that 358 (75%) patients were still normotensive 47 weeks after starting treatment with timolol/bendrofluazide and in a further 8 patients other antihypertensive agents had been added to this therapy. Of the 113 patients no longer receiving timolol/bendrofluazide, only 38 (7.9%) had stopped therapy due to adverse effects. It is concluded that the results are a further indication that timolol/bendrofluazide offers an acceptable and balanced long-term form of therapy in hypertension for both the patient and the physician.