Epidemiology of neurosensorial deafness in the Foral Community of Navarra

Congenital deafness is a relatively frequent disorder that shows a heterogeneous aetiology. Knowledge and the control of some risk factors have decreased the incidence of acquired deafness and increased the relative importance of genetic cause. In an attempt to investigate the clinical relevance of congenital deafness and the mechanisms of prevention in our population, a clinical and genetic study of cases with neurosensorial deafness born in Navarra between 1975 and 1990 was carried out. A total of eighty-one cases were identified, giving an incidence of 0.8 per thousand. Thirty per cent of the cases showed deafness associated with defects. Cause of deafness was identified in seventy per cent of the cases with whom a detailed clinical and genetic study could be performed (n=50). Genetic factors were responsible for the disorder in more than half of these cases. The most frequent hereditary factor was of the autosomic recessive type. This was associated with a more severe form of hearing loss.     

Evidence for the involvement of 5-HT4 receptors in the 5-hydroxytryptamine-induced pattern of migrating myoelectric complex in sheep

1. The effects induced by 5-hydroxytryptamine (5-HT) on gastrointestinal myoelectric activity in conscious sheep were recorded through electrodes chronically implanted and analysed by computer. The 5-HT receptors and the cholinergic neuronal pathways involved in these actions were investigated.
2. The intravenous (i.v.) administration of 5-HT (2, 4 and 8 μg kg⁻¹ min⁻¹, 5 min) induced an antral inhibition concomitant with a duodenal activity front that migrated to the jejunum, followed by a period of intestinal inactivity. This myoelectric pattern closely resembled that observed in the phases III and I of the migrating myoelectric complex (MMC) in sheep. The 0.5 μg kg⁻¹ min⁻¹ dose evoked the same pattern in only two out of the six animals used. Likewise, the 1 μg kg⁻¹ min⁻¹ dose similarly affected four of the six animals. In addition, a transient stimulation was observed in the antrum and jejunum when the two highest doses were used.
3. The 5-HT₁ antagonist, methiothepin (0.1 mg kg⁻¹), the 5-HT₂ antagonists, ritanserin (0.1 mg  kg⁻¹) and ketanserin (0.3 mg  kg⁻¹), the 5-HT₃ antagonists, granisetron (0.2 mg kg⁻¹) and ondansetron (0.5 mg kg⁻¹), as well as the 5-HT₄ antagonist, {"type":"entrez-nucleotide","attrs":{"text":"GR113808","term_id":"238362519","term_text":"GR113808"}}GR113808 (0.2 mg kg⁻¹), did not modify the spontaneous gastrointestinal myoelectric activity. However, the cholinoceptor antagonists, atropine (0.2 mg kg⁻¹) and hexamethonium (2 mg kg⁻¹), inhibited gastrointestinal activity.
4. When these antagonists were injected i.v. 10 min before 5-HT (2 or 4 μg kg⁻¹ min⁻¹, 5 min), only {"type":"entrez-nucleotide","attrs":{"text":"GR113808","term_id":"238362519","term_text":"GR113808"}}GR113808, atropine and hexamethonium were able to modify the 5-HT-induced actions, all of them being completely blocked by the three antagonists.
5. Our data show that 5-HT initiates a MMC-like pattern in the gastrointestinal area in sheep through 5-HT₄ receptors. Furthermore, these actions are mediated by cholinergic neural pathways involving muscarinic and nicotinic receptors. However, our results do not indicate a role for either 5-HT₁, 5-HT₂ or 5-HT₃ receptors in the 5-HT-induced effects.

     

Prevalence and control of arterial hypertension in the south-east of Spain: A radical but still insufficient improvement

Stroke mortality rates in Spain are one of the highest in all of Europe. At the same time, the Murcia region (south-east Spain) shows, for both genders, the highest age-adjusted stroke mortality rates in all of Spain. The earliest available hypertension figure estimations for this area go back to 1981, when a high prevalence combined with an almost nonexistent control was detected. One decade later, updated prevalence estimations of hypertension are presented jointly with their degree of control and their association with other risk factors based on the results of a prevalence survey in a random population sample (n = 3,091). Arterial blood pressure was measured following the MONICA protocol, maintaining a tight quality control on between and within-observer variability. As hypertensive was considered as any person with systolic blood pressure (SBP) 140 mmHg or with diastolic blood pressure (DBP) 90 mmHg or with antihypertensive pharmacological treatment. Detected prevalence rises to 32.3% (CI 95%: 29.1%–35.5%) among males and to 23.7% (CI 95%: 21.4%– 26%) among females, maintaining its level regarding figures observed back in 1981. However, its control has been increased, especially among hypertensive women [from less than 5% in 1981 to 35% (95% CI: 32%–37.8%) at present]. Hypertension is strongly associated to hipercholesterolemia, overweight, obesity and diabetes (p < 0.01). On the contrary, it shows an opposite association with current smoking, higher educational level and leisure time physical activity (p < 0.01). The highest educational level was associated with better hypertension treatment and control. In summary, while hypertension prevalence is stabilized in our population, its control has improved in a measurable but still insufficient way. These results are in accordance with a decreasing trend in stroke mortality registered in the Murcia Region along the last decade.     

Poly (triethylenglycol monomethacrylate) and poly(glycerol monomethacrylate) cross-linked gel as potential viscoelastics for intraoperative use

Background: The highly swelling poly(glycerol monomethacrylate) gel (polyGLYMA) and hydrophilic polymer poly(triethylenglycol monomethacrylate (polyTEGMA) were tested as potential viscoelastics for intraopertive use in anterior segment surgery. Methods: PolyGLYMA was implanted into the anterior chamber in 5 rabbits, and 40% polyTEGMA in 16 rabbits. The eyes were enucleated 1 week to 3 months after the operation. The corneal endothelium was examined with specular microscopy, and then the whole eye histopathologically. Results: In all eyes of the polyGLYMA group, the clinical findings were characterized by a marked ciliary injection and severe secondary glaucoma, and the histologic ones by a marked inflammatory infiltration and thickening of Descemet's membrane in the anterior chamber angle. Specular microscopy revealed a decrease in the endothelial cell density and polymorphism of the endothelial cells. In the polyTEGMA group, the anterior segment and the fundus were physiologic all the time, and specular microscopy and histologic findings showed no degenerative and/or inflammatory changes. Conclusions: PolyGLYMA proved unsuitable for intracameral application in rabbits. The new polymer polyTEGMA is characterized by high biologic tolerance after its implantation into the anterior chamber of rabbits. PolyTEGMA 40% might be considered as a potential viscoelastic material in humans.     

Effects of acetylcholine, carbachol, and mannitol on rabbit corneal endothelial function as assessed by corneal deturgescence

Background: Anterior chamber miotic solutions are widely used in ophthalmic surgery to induce pupillary contraction. We investigated whether the acetylcholine, carbachol, or mannitol present in perfusing solutions can affect corneal endothelial function. Methods: Freshly dissected deepithelized rabbit corneas were mounted in a Dikstein-Maurice chamber at 36 °C. The endothelial sides were perfused with six solutions: (A) 55 mM (1%) acetylcholine Cl plus modified balanced salts; (B) control for A, with acetylcholine Cl replaced by sucrose; (C) 0.55 mM (0.01%) carbachol Cl plus balanced salts; (D) balanced salts solution (BS; control for C); (E) 3% mannitol plus modified balanced salts; and (F) modified balanced salts (control for E, with mannitol replaced by sucrose). Corneal thickness was followed for 3 h in each experiment. The effect of solution E did not differ from that of solution F. Results: The carbachol-containing solution produced a small increase in corneal thickness compared to the control solution, while the acetylcholine-containing solution resulted in corneal thickness lower than that in control preparations. Conclusion: From these data, acetylcholine is harmless to the endothelium, and may actually stimulate its fluid pump mechanism. Carbachol, on the other hand, appears to have a detrimental effect.     

Synthesis and biodistribution of peptide based 99mTc/186Re-MAGIPG-D612 monoclonal antibody in nude mice bearing colon cancer xenografts

A new bifunctional chelating agent MAGIPG was synthesized in good yield using Boc-p-nitro-phenylalanine as the starting material. 99mTc-labeled-MAGIPG-D612 conjugates reactive with human colon cancer were prepared in 3% to 15% yield with a radiochemical purity of 63% to 97%. 186Re-labeled MAGIPG-D612 conjugates were prepared with a 7% to 30% yield and a radiochemical purity of 82% to 98%. The biodistribution results demonstrate that these radioimmuno-conjugates selectively localized in LS174T human colon cancer xenografts.     

Potentiation by vasopressin of adrenergic vasoconstriction in the rat isolated mesenteric artery

1. The aim of the present study was to investigate in rat mesenteric artery rings whether low concentrations of vasopressin could modify the contractile responses to noradrenaline and electrical stimulation of perivascular nerves.
2. Vasopressin (10⁻¹⁰–10⁻⁷ M) caused concentration-dependent contractions (pD₂=8.36±0.09). The V₁-receptor antagonist d(CH₂)₅Tyr(Me)AVP (10⁻⁹–10⁻⁸ M) produced parallel rightward shifts of the control curve for vasopressin. Schild analysis yielded a pA₂ value of 9.83 with a slope of 1.10±0.14.
3. Vasopressin (3×10 ⁻¹⁰ and 10⁻⁹ M) caused concentration-dependent potentiation of the contractions elicited by electrical stimulation (2–8 Hz; 0.2 ms duration for 30 s) and produced leftward shifts of the concentration-response curve for noradrenaline. The V₁-receptor antagonist induced concentration-dependent inhibitions of potentiation induced by vasopressin. The selective V₁-receptor agonist [Phe^*, Orn⁸]-vasotocin (3×10 ⁻¹⁰ and 10⁻⁹ M) induced potentiation of electrical stimulation-evoked responses which was also inhibited in the presence of the V₁ antagonist (10⁻⁸ M). In contrast, the V₂-receptor agonist deamino-8-D-arginine vasopressin (desmopressin 10⁻⁸–10⁻⁷ M) did not modify the electrical stimulation-induced responses and the V₂-receptor antagonist [d(CH₂)₅, D-Ile^*, Ile⁴, Arg⁸]-vasopressin (10⁻⁸–10⁻⁷ M) did not affect the potentiation evoked by vasopressin.
4. In artery rings contracted by 10⁻⁶ M noradrenaline in the presence of 10⁻⁶ M guanethidine and 10⁻⁶ M atropine, electrical stimulation (2, 4 and 8 Hz) produced frequency-dependent relaxations which were unaffected by 10⁻⁹ M vasopressin but abolished by 10⁻⁶ M tetrodotoxin.
5. Vasopressin also potentiated contractions elicited by KCl and contractions induced by addition of CaCl₂ to KCl depolarized vessels. The augmenting effects were inhibited by the V₁ antagonist.
6. In the presence of the calcium antagonist nifedipine (10⁻⁶ M), vasopressin failed to enhance the contractile responses to electrical stimulation, noradrenaline and KCl.
7. The results demonstrate that low concentrations of vasopressin strongly potentiate the contractions to adrenergic stimulation and KCl depolarization. This effect appears to be mediated by V₁ receptor stimulation which brings about an increase in calcium entry through dihydropyridine-sensitive calcium channels.

     

Evaluation of in vitro activity of a new fluoroquinolone trovafloxacin (cp-99,219) compared with other anti-anaerobic antimicrobials against members of the Bacteroides fragilis group

The in vitro activity of a new fluoroquinolone, trovafloxacin (CP-99,219) was compared with that of ten other agents against 100 clinical isolates in the Bacteroides fragilis group. Trovafloxacin was the most active quinolone (MIC₉₀, 1 μg/ml) followed by sparfloxacin (MIC₉₀, 8 μg/ml), levofloxacin (MIC₉₀, 16 μg/ml) and ofloxacin (MIC₉₀, 32 μg/ml). Ciprofloxacin was the least active quinolone (MIC₉₀, 64 μg/ml). Metronidazole, chloramphenicol, imipenem and piperacillin/tazobactam, showed excellent activity with an MIC₉₀ of 1, 8, 0.25 and 16 μg/ml, respectively. Cefoxitin showed good activity and piperacillin was the least active compound. B. vulgatus and B. ovatus were the most resistant species to trovafloxacin among those of the B.fragilis group with an MIC₉₀ of 4 μg/ml while B. fragilis and B. thetaiotaomicron were the most susceptible (MIC₉₀, 1 μg/ml).     

Non-canonical mechanisms of antibiotic resistance

Although the current in vitro methods used for detection and analysis of the phenotypes of antibiotic resistance in the laboratory are well established, other resistance mechanisms of resistance exist which may escape detection using the standard approach. The present article reviews some of these mechanisms which are grouped under the term non-canonical mechanisms of antibiotic resistance. Such mechanisms include gene dosage, heterologous induction or selection, populational resistance and synergism between mechanisms of low resistance. The role of these mechanisms in the failure of therapy is discussed.