Influence of hypo- and hyperglycaemia on plasma leptin concentrations in healthy women and in women with polycystic ovary syndrome.

BACKGROUND: Insulin resistance and obesity play an important role in the pathogenesis of polycystic ovary syndrome (PCOS). It is known that experimentally induced insulin resistance diminishes the stimulatory effect of insulin on leptin secretion. It is not yet known whether the long-term insulin resistance as found in PCOS patients alters the leptin response to hypo- and hyperglycaemia. METHODS: We induced hyper- and hypoglycaemia by glucose clamp technique in 7 patients with PCOS and 20 healthy controls. After a plasma glucose level of 8.8 mmol/l was reached, the plasma glucose level was reduced stepwise to 6.8, 4.8 and 2.8 mmol/l. RESULTS: The PCOS patients required lower glucose infusion rates to reach the glycaemic targets (P < 0.05). Serum insulin and C-peptide concentrations increased significantly during the clamp compared with the baseline in both groups (P < 0.001 for insulin, and P < 0.001, P < 0.005 for C-peptide control and PCOS, respectively) and increased significantly more in PCOS patients compared with the control group (both P < 0.05). Basal leptin levels were significantly higher in the PCOS group than in the control group (P = 0.005). In the controls, the leptin concentration increased significantly during the clamp (P < 0.001 for each glycaemic target), whereas in the PCOS group, leptin secretion increased only during hypoglycaemia (P = 0.04). CONCLUSIONS: Compared with the healthy controls, the response of leptin secretion to hyper- and hypoglycaemia was diminished in PCOS patients. Changes in leptin secretion seem not to be caused by hyper- and hypoglycaemia, but rather by hyperinsulinaemia. Reduced insulin sensitivity seems to be responsible for the diminished leptin response, which might contribute to the obesity found in PCOS patients.

Excitatory stimulation of neurons in the arcuate nucleus inhibits gastric acid secretion via vagal pathways in anesthetized rats.

It is well established that autonomic control of gastrointestinal function is modulated by central autonomic neurotransmission. In this context it has been shown that gastrointestinal motility and secretion can be modulated by exogenous neuropeptides microinjected into the paraventricular nucleus of the hypothalamus (PVN). Furthermore, there is considerable evidence suggesting that neurons projecting from the arcuate nucleus (Arc) to the PVN may be the source of endogenous neuropeptide release in the PVN. This poses the question whether stimulation of neurons in the arcuate nucleus, e.g. by an excitatory amino acid, alters gastrointestinal function. In the present study, we investigated the effect of an excitatory amino acid, kainate, microinjected into the arcuate nucleus on gastric acid secretion in urethane-anesthetized rats. Kainate (140 pmol/rat) bilaterally microinjected into the Arc induced an significant inhibition of pentagastrin (PG) stimulated (16 mg/kg per h) gastric acid secretion throughout an observation period of 120 min after microinjection. Microinjection of kainate into hypothalamic areas outside the arcuate nucleus did not modify gastric secretion. Bilateral cervical vagotomy blocked the effect of kainate injected into the Arc on PG-stimulated gastric acid secretion. These data show that gastric secretory function can be modulated by stimulation of neuronal activity in the Arc via efferent vagal pathways. The results suggest that the arcuate nucleus is a forebrain area involved in the CNS regulation of gastrointestinal function.

I(f) current mediates beta-adrenergic enhancement of heart rate but not contractility in vivo.

BACKGROUND: The hyper-polarization-activated "I(f)" current in the sinoatrial (SA) node participates in the spontaneous diastolic depolarization responsible for pacemaking function. Both sympathetic and parasympathetic control of heart rate is thought to involve modulation of I(f). This study tested whether beta-adrenoceptor activation of heart rate, but not contractile state, could be reduced by blockade of I(f) channels in the intact, anesthetized pig. METHODS: Both isoproterenol (ISO, 0.1 micrograms/kg/min i.v. for 5 min) and norepinephrine (NE, 0.3 micrograms/kg/min i.v. for 5 min) were used sequentially to activate beta-adrenoceptors in five metomidathydrochloride-anesthetized pigs. Left ventricular pressure and dP/dt, aortic blood pressure and cardiac output were measured. I(f) channels were then blocked selectively with 0.3 mg/kg i.v. zatebradine (ULFS49) and the test doses of ISO and NE were repeated. Following a further high dose (10 mg/kg, i.v.) of zatebradine, the test doses of ISO and NE were repeated once again. RESULTS: Before I(f) blockade, ISO and NE elicited reproducible increases in both heart rate and left ventricular dP/dt. Whereas NE caused an increase in both systolic (56%) and diastolic (53%) aortic pressure and a modest heart rate increase (22%), ISO caused a decrease in diastolic aortic pressure (-22%) and a marked increase in heart rate (81%). Low dose zatebradine reduced basal heart rate from 98 +/- 6 to 66 +/- 3 bpm, p < 0.05; cardiac output fell by 20%, stroke volume increased by 18% and total peripheral resistance was unchanged. ISO after low-dose zatebradine still elicited marked increases in heart rate (66 +/- 3 to 105 +/- 5 bpm, p < 0.05) and left ventricular dP/dt (774 +/- 94 to 3364 +/- 206 mmHg/s, p < 0.05) and reduced aortic diastolic pressure (37 +/- 2 to 33 +/- 1 mmHg, p < 0.05). NE after low-dose zatebradine increased heart rate (73 +/- 4 to 89 +/- 5 bpm, p < 0.05), left ventricular dP/dt (810 +/- 95 to 3372 +/- 196 mmHg/s, p < 0.05) and both systolic and diastolic aortic pressures. High dose zatebradine caused no further reduction in heart rate (77 +/- 4 vs 82 +/- 6 bpm, NS) but left ventricular dP/dt decreased (798 +/- 92 to 418 +/- 50 mmHg/s, p < 0.05) as did both systolic and diastolic aortic pressures. Subsequent administration of ISO had no effect on heart rate but increased left ventricular dP/dt from 418 +/- 50 to 3468 +/- 256 mmHg/s (p < 0.05) and systolic aortic pressure increased from 58 +/- 7 to 90 +/- 3 mmHg (p < 0.05). NE administered after high dose zatebradine also increased left ventricular dP/dt (580 +/- 54 to 2608 +/- 182 mmHg/s, p < 0.05) while heart rate fell (86 +/- 4 to 74 +/- 6 bpm, p < 0.05). Both systolic and diastolic aortic pressures increased substantially during the NE infusion after high dose zatebradine. CONCLUSION: Zatebradine dose-dependently inhibits beta-adrenoceptor-mediated heart rate increases while leaving beta-adrenoceptor-mediated increases in myocardial contractile state intact. This observation can be explained by a selective blockade of the hyperpolarization-activated current I(f) by low concentrations of the drug.

[Principles of acute management of the severe diving accident]. / Grundlagen der Akutversorgung des schweren Tauchunfalles.

The basics of the acute management of severe diving accidents are outlined by means of 25 patients (20 patients presented with decompression sickness, 5 suffered from a barotrauma of the lungs with consecutive air embolism) treated at our facilities. Contrary to widespread notion, disturbed vital functions have to be treated by intensive care measures, prior to the definite recompression therapy. These are: (1) Treatment of generalized or localized tissue hypoxia secondary to bubble-generation; (2) puncture of a (valvular-) pneumothorax after a pulmonary barotrauma; (3) haemodynamic stabilization when cardiac or spinal shock is present; (4) improvement of the rheological situation. When vital functions are unstable or endangered, these patients must not be transported in a monoplace chamber. This type of chamber does not leave any access to the patient in case of a deteriorating status. Since the severe diving accident mostly turns out to be a problem of intensive care medicine in close combination with the recompression therapy, the continuous integration of the recompression protocol with a comprehensive intensive care therapy is considered crucial.

Transcutaneous electric nerve stimulation (TENS) in the therapy of chronic facial pain. Preliminary report.

Chronic facial pain remains a therapeutic problem. We report on 29 patients (37 nerves involved), who were treated with transcutaneous electric nerve stimulation (TENS). Pain reduction was achieved in 27 patients (93%) while in 5 patients it was possible to stop the treatment because they were constantly free from pain. Two patients did not respond to TENS therapy. It was possible to reduce or discontinue the use of analgesics in 79% of the cases. There were no severe side effects. Therefore, TENS should be seen as a simple, safe and effective method of treatment for many forms of chronic facial pain, as opposed to other invasive surgical procedures.

Indications and treatment of keratoconus using epikeratophakia.

Nineteen patients with keratoconus underwent epikeratophakia by one of the authors (DSD) and were followed from 3 to 29 months. Patient selection criteria included contact lens failure, and minimal or no central corneal scarring. Uncorrected visual acuity improved by three or more Snellen lines in 13 of 19 patients (68%). Postoperatively, after more than 6 months follow-up, 81% of the patients had best-corrected visual acuity of 20/40 or better. A mean flattening of 4.73 diopters (D) occurred on keratometry readings. There was a mean decrease in refractive cylinder of 2.84 D. Spherical equivalent refraction showed a mean decrease in myopia of 4.64 D. Five patients had postoperative refractive cylinder greater than 4 D requiring relaxing incision(s). With some patients having been followed for more than 2 years, no recurrences of keratoconus have been noted. In properly selected patients, epikeratophakia can effectively be used to treat keratoconus and thus avoid potential intraocular surgical complications and immunogenic phenomena.

Secondary intraocular lens implantation vs epikeratophakia for the treatment of aphakia.

We analyzed retrospectively the results of 30 consecutive secondary intraocular lens implantations and 30 epikeratophakia procedures performed by one surgeon for adult aphakia. Specific indications for epikeratophakia were criteria that excluded patients as candidates for intraocular implants. Follow-up of all patients was at least six months. Preoperative and postoperative uncorrected and best corrected visual acuity and endothelial cell counts, as well as power predictability and complications rates, were compared. Preliminary results indicated that postoperative visual acuity, power predictability, and endothelial cell counts were comparable for the two groups. There were, however, fewer sight threatening complications associated with epikeratophakia, and complications in these patients were successfully reversed by removal and replacement of the lenticule.