Randomized controlled trial of the effectiveness of genetic counseling and a distance, computer-based, lifestyle intervention program for adult offspring of patients with type 2 diabetes: background, study protocol, and baseline patient characteristics.

Relatives of type 2 diabetic patients are at a high risk of developing type 2 diabetes and should be regarded as target of intervention for diabetes prevention. However, it is usually hard to motivate them to implement preventive lifestyle changes, because of lack of opportunity to take advises from medical professionals, inadequate risk perception, and low priority for preventive behavior. Prevention strategy for them therefore should be highly acceptable and suited for them. The parallel, three-group trial is now being conducted to investigate the effects of genetic counseling and/or a computerized behavioral program on the prevention of type 2 diabetes in that population. The preventive strategies used in this study could provide a novel solution to the numbers of genetically high-risk individuals, if found to be effective. The objective of this paper is to describe the background, protocol, and baseline patient characteristics of the trial.

Endoscopic treatment of refractory filarial chyluria: a preliminary report.

PURPOSE: We report our experiences treating 5 patients who had filarial chyluria using an endoscopic approach. MATERIALS AND METHODS: Two men and 3 women 47 to 83 years old with chyluria were treated with endoscopic coagulation using guide tube methods. Intrarenal pelvic instillation of silver nitrate was not effective in 4 patients and catheterization was impossible in 1. RESULTS: The responsible lesion was successfully coagulated in all 5 patients. Because the lesion was in the ruptured portion of the caliceal fornix, we thought that chyluria had arisen in the fragile portion of the fornix (fistulization). After endoscopic treatment there was no recurrence in any patient. CONCLUSIONS: Endoscopy is effective and minimally invasive therapy for filarial chyluria.

Thiopental attenuates relaxation and cyclic GMP production in vascular smooth muscle of endotoxin-treated rat aorta, independent of nitric oxide production.

As thiopental (thiopentone) suppresses cyclic GMP (cGMP) formation produced by nitric oxide donor drugs, we have tested if it suppresses cGMP formation and increases vascular tone after induction of calcium-calmodulin-independent nitric oxide synthase (iNOS). Rat aortic rings were treated with Escherichia coli lipopolysaccharide (LPS) 1 microgram ml-1 for 4 h, and the effects of thiopental on tension, cGMP concentrations and nitrite accumulation were determined. Thiopental 0.3 mmol litre-1 reduced the tension of phenylephrine-precontracted aortic rings before LPS treatment, but caused no significant effects on tension in the presence of L-arginine 10 mumol litre-1 after LPS treatment. L-Arginine 1 mumol litre-1 to 1 mmol litre-1 increased concentrations of cGMP in LPS-treated aorta in a concentration-dependent manner. This was reduced by thiopental 0.3-1 mmol litre-1. Treatment with L-arginine 1 mmol litre-1 increased concentrations of nitrite, the end product of nitric oxide; this was not affected by thiopental 1 mmol litre-1. We conclude that thiopental suppressed cGMP formation in iNOS-induced vascular smooth muscle without affecting nitric oxide production.

Suppression of acetylcholine-induced relaxation by local anesthetics and vascular NO-cyclic GMP system.

BACKGROUND: Local anesthetics have been demonstrated to attenuate acetylcholine-induced relaxation of vascular smooth muscle, but the mechanism responsible has not been elucidated. The present study was undertaken to ascertain whether this effect of local anesthetics is due to suppression of the vascular nitric oxide (NO)-cyclic GMP (cGMP) system. METHODS: Isolated rat aortae were cut into helical strips and mounted in bathing solution to measure isometric tension changes. They were precontracted with phenylephrine (0.3 microM) then exposed to cumulative concentrations of relaxants including acetylcholine, sodium nitroprusside (SNP) and papaverine, in the absence or presence of local anesthetics. Aortae for cGMP measurements were cut longitudinally into pairs of strips and bathed in the solution without tension. In the absence or presence of anesthetics, they were stimulated with acetylcholine or SNP, and the cGMP content of each strip was radioimmunoassayed. RESULTS: Acetylcholine-induced, endothelium-dependent relaxation of phenylephrine-precontracted aortae was attenuated by lidocaine (30-300 microM), tetracaine (10-30 microM), bupivacaine (10-100 microM) and ropivacaine (30-100 microM). SNP-induced relaxation was attenuated by lidocaine (300 microM), tetracaine (30 microM), bupivacaine (10-100 microM) and ropivacaine (30-100 microM). Papaverine-induced relaxation was attenuated by lidocaine (300 microM), bupivacaine (30-100 microM) and ropivacaine (30-100 microM), and augmented by tetracaine (30 microM). Cyclic GMP levels in acetylcholine-stimulated aortae were reduced significantly by lidocaine (300 microM), tetracaine (100 microM) and bupivacaine (300 microM) treatment, but not by ropivacaine (300 microM). SNP-stimulated cGMP levels were reduced by tetracaine (100 microM) but not by any other anesthetics at the concentrations tested. CONCLUSION: We conclude that lidocaine, tetracaine and bupivacaine suppress acetylcholine-stimulated formation of cGMP. However, the attenuation of acetylcholine-induced relaxation by local anesthetics is not totally ascribable to reduced cGMP levels.

Suppression of cyclic guanosine monophosphate formation in rat cerebellar slices by propofol, ketamine and midazolam.

PURPOSE: The nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) system is involved in glutamatergic neurotransmission. The current study determined the effects of propofol, ketamine and midazolam on rat cerebellar cGMP formation, attempting to clarify whether the effect was due to suppression of NO-cGMP system or to direct interaction with glutamatergic receptors. METHODS: Cerebellar slices, obtained from six- to eight-day-old Wistar rats, were pretreated with propofol (10 microM-1 mM), ketamine (10-100 microM) or midazolam (1-100 microM) for 30 min. and then stimulated with L-glutamate (3 mM), N-methyl-D-aspartate (NMDA, 0.1 mM), kainate (0.1 mM) or sodium nitroprusside (SNP, 0.3 mM) (n = 5-11 for each group). The levels of cGMP were determined by radioimmunoassay. RESULTS: None of the anaesthetics studied altered cGMP levels when no stimulant was given. Propofol (10 microM-1 mM) suppressed L-glutamate-, NMDA-, kainate- and SNP stimulated cGMP formation in a concentration-dependent manner, the sensitivity to propofol was in the order of NMDA > kainate > L-glutamate. SNP. Ketamine (10-100 microM) suppressed L-glutamate- and NMDA-stimulated cGMP formation, but did not suppress kainate- or SNP-stimulated cGMP formation. Midazolam (10-100 microM) did not affect NMDA-, L-glutamate- or SNP-stimulated cGMP formation, but suppressed kainate-induced formation. CONCLUSION: The inhibitory effects of propofol, ketamine and midazolam on cGMP formation in rat cerebellar slices are due mainly to interaction with receptors for excitatory amines, and not due to the suppression of nitric oxide synthase or guanylate cyclase activities.

Thiobarbiturates suppress depolarization-induced contraction of vascular smooth muscle without suppression of calcium influx.

We have studied the effects of barbiturates on vascular smooth muscle tension and cytosolic calcium concentrations ([Ca2+]i) in endothelium-denuded rat aortic rings, preloaded with fluo-3. Changes in [Ca2+]i were estimated by the fluorescence intensity of the calcium-bound form of fluo-3. In aortic rings under basal conditions, thiobarbiturates (thiopentone and thiamylal 100-300 mumol litre-1) increased [Ca2+]i, concomitantly with an increase in tension, although oxybarbiturates (pentobarbitone and secobarbitone up to 300 mumol litre-1) had no effect. Thiopentone (300 mumol litre-1)-induced increases in tension and fluorescence intensity were mean 25.1 (SD 3.2)% and 55.0 (6.0)%, respectively, of those induced by KCl 30 mmol litre-1 (n = 8, each). In KCl (30 mmol litre-1)-precontracted aortic rings, thiopentone decreased tension without reduction of [Ca2+]i, whereas pentobarbitone decreased tension and [Ca2+]i, KCl (30 mmol litre-1)-induced contraction was suppressed by pretreatment with all barbiturates (100-300 mumol litre-1); thiopentone 300 mumol litre-1 suppressed contraction to 64.8 (2.5)% (n = 6) and pentobarbitone 300 mumol litre-1 to 57.5 (2.2)% (n = 9). However, the increase in [Ca2+]i was suppressed by oxybarbiturates (pentobarbitone 300 mumol litre-1 to 77.9 (5.2) %; n = 9), but not altered by thiobarbiturates. These results suggest that thiobarbiturates and oxybarbiturates affect vascular smooth muscle differently and that the affected site in thiobarbiturate-induced vasodilatation is distal to regulation of [Ca2+]i.

[QOL and nursing care of a ventilator-assisted child at home].

QOL is the important issue for chronically ill children. We visited a girl, 8 years old and 24 hours dependent on a ventilator. We talked to her, and observed her daily life, mainly on the following points: (1) what she is doing; and (2) how often, and what kind of care she needs at school and at home. Then we discussed the problems, QOL and nursing care. She enjoyed her school life with her many friends, and received respiratory care, sanitary care, and other care for 11 hours and 19 minutes in average per day. 93.1% of the care was taken by her parents and volunteer care givers, so that they wanted to have nurses care for her. Many kinds of nursing care service were necessary as soon as possible.

Biosynthesis of Poly(3-Hydroxyalkanoic Acid) Copolymer from CO(inf2) in Pseudomonas acidophila through Introduction of the DNA Fragment Responsible for Chemolithoautotrophic Growth of Alcaligenes hydrogenophilus.

Pseudomonas acidophila is a bacterial strain producing a poly(3-hydroxyalkanoic acid) (PHA) copolymer from low-molecular-weight organic compounds such as formate and acetate. The genes responsible for PHA production were cloned in cosmid pIK7 containing a 14.8-kb HindIII fragment of P. acidophila DNA. With the aim of developing a means of producing a PHA copolymer from CO(inf2), cosmid pIK7 was introduced into a polymer-negative mutant of the chemolithoautotrophic bacterium Alcaligenes eutrophus PHB(sup-)4. However, the recombinant strain produced a homopolymer of 3-hydroxybutyric acid (polyhydroxybutyric acid) from CO(inf2). Since it was thought that the composition of the accumulated polymer might depend not on the PHA biosynthetic genes but on the metabolism of the host strain, a recombinant plasmid, pFUS, containing the genes for chemolithoautotrophic growth of the hydrogen-oxidizing bacterium A. hydrogenophilus was introduced into P. acidophila by conjugation. The recombinant plasmid pFUS was stably maintained in P. acidophila in the absence of chemolithoautotrophic or antibiotic selection. This pFUS-harboring strain possessed the ability to grow under a gas mixture of H(inf2), O(inf2), and CO(inf2) in a mineral salts medium, and PHA copolymer accumulation was confirmed by nuclear magnetic resonance spectral analysis. A gas chromatogram obtained by gas chromatography-mass spectrometry showed the composition of the polymer to be 52.8% 3-hydroxybutyrate, 41.1% 3-hydroxyoctanoate, and 6.1% 3-hydroxydecanoate. This is the first report of the production of a PHA copolymer from CO(inf2) as sole carbon source.

Modification of endothelium-dependent relaxation by propofol, ketamine, and midazolam.

Since volatile anesthetics, barbiturates, and local anesthetics have been reported to inhibit endothelium-dependent relaxation, we hypothesized that any drug with anesthetic action would suppress this relaxation. In the present study, using rat thoracic aortae, we attempted to determine whether nonbarbiturate intravenous anesthetics, including midazolam, propofol, and ketamine, suppress endothelium-dependent relaxation, and to clarify the mechanism(s) involved. Acetylcholine-induced, endothelium-dependent relaxation was significantly attenuated by propofol and ketamine, but was unaffected by midazolam. Sodium nitroprusside (SNP)-induced relaxation was attenuated by propofol, but not by midazolam or ketamine. The acetylcholine-stimulated 3',5'-cyclic guanosine monophosphate (cGMP) level was reduced by pretreatment with propofol and ketamine but not by midazolam, and that stimulated by SNP was reduced by propofol but not by ketamine or midazolam. We conclude that propofol and ketamine suppress endothelium-dependent relaxation, whereas midazolam has no influence. Moreover, the suppressive effect of ketamine on endothelium-dependent relaxation is mediated by suppression of nitrous oxide (NO) formation, whereas that of propofol may be mediated at least partly by suppression of NO function.

Inhibitory effects of anesthetics on cyclic guanosine monophosphate (cGMP) accumulation in rat cerebellar slices.

General anesthetics, including halothane, isoflurane, and barbiturates, suppress endothelium-dependent formation of 3',5'-cyclic guanosine monophosphate (cGMP) in the systemic and cerebral vasculature. The present study was conducted to determine whether these anesthetics have similar effects on the nitric oxide (NO)-cGMP system in the brain, and to elucidate the mechanism responsible. In rat cerebellar slices, formation of cGMP was suppressed by halothane after stimulation by N-methyl-D-aspartate (NMDA, 0.1 mM) and D-aspartate (1.0 mM) but not after stimulation by sodium nitroprusside (SNP, 0.3 mM). Isoflurane (2%) suppressed NMDA (0.1 mM)-stimulated, but not D-aspartate (1.0 mM)- and nitroprusside (0.3 mM)-stimulated formation of cGMP. In contrast, thiopental (0.1-1.0 mM) suppressed NMDA (0.1 mM)-, D-aspartate (1.0 mM)-, and nitroprusside (0.3 mM)-stimulated formation of cGMP. Treatment with aminophylline (0.1 mM), a phosphodiesterase inhibitor, did not influence the effect of thiopental, suggesting that the effect of thiopental was not mediated by activation of phosphodiesterase. D-Aspartate increases intracellular calcium, which in turn activates NO synthase, and nitroprusside generates NO without activation of NO synthase. Therefore, the present findings strongly suggest that halothane inactivates NO synthase (or related cofactors) without marked interaction with the NMDA receptor, that isoflurane may interact with the NMDA receptor, receptor-coupled G-protein, or calcium channels, and that thiopental suppresses guanylate cyclase activity.

Mechanisms of inhibition of endothelium-dependent relaxation by halothane, isoflurane, and sevoflurane.

Volatile anaesthetics inhibit endothelium-dependent relaxation, but the underlying mechanism(s) have not been clarified. In an attempt to elucidate the mechanism(s), we determined the effects of halothane, isoflurane and sevoflurane on relaxation induced by acetylcholine and sodium nitroprusside (SNP) and the cGMP formation elicited by exogenous nitric oxide (NO) and SNP in rat aortas. Acetylcholine (10(-7)-10(-5) M)-induced relaxation was attenuated by halothane (2%), isoflurane (2%) and sevoflurane (4%). SNP (10(-8) M)-induced relaxation was reduced by halothane (2%), but not by isoflurane (2%) or sevoflurane (4%). The cGMP level of NO-stimulated aorta was reduced by halothane (2%) and sevoflurane (4%), but not by isoflurane (2%). The cGMP level of SNP (10(-7) M)-stimulated aorta was reduced by halothane (2%), but not by isoflurane (2%) and sevoflurane (4%). We conclude that the mechanisms responsible for the inhibition of endothelium-dependent relaxation differ among anaesthetics. Isoflurane inhibits the relaxation mainly by inhibiting the formation of NO in the endothelium. In contrast, the effect of halothane on endothelium-dependent relaxation may be largely due to the inhibition of action of NO in the vascular smooth muscle and the effect of sevoflurane may be to inactivate NO or to inhibit the action of NO.

[Anesthesia and postoperative stroke in patients with previous cerebrovascular disease].

A retrospective study was performed to determine the incidence of perioperative stroke in patients with previous history of cerebrovascular disease (CVD). One hundred and seventy eight out of 20048 patients who underwent anesthesia and surgery during the period of 1985 to 1989 had history of prior CVD. Of them, 137 patients were managed with general anesthesia and 41 with regional anesthesia. Factors analyzed were interval between the prior CVD and the operation, intraoperative hemodynamic changes, perioperative changes in the hematocrit and urinary output, and postoperative neurological complications. Postoperative neurological complications occurred in 31 of the patients given general anesthesia (delayed awakening in 26, dementia syndrome in 6 and deterioration of paralysis in 1), whereas only one patient developed dementia syndrome postoperatively in those given regional anesthesia. None of the patients developed a postoperative stroke. There was no direct relationship between the factors analyzed and the incidence of postoperative neurological complications. Further studies are needed to identify more precisely factors contributing to the occurrence of cerebrovascular complication in a high risk patients.