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The Aspergillus nidulans genes chsA and chsD encode chitin synthases which have redundant functions in conidia formation [corrected and republished article originally appeared in Mol Gen Genet 1996 Jun; 251(4):442-50].

We previously isolated three chitin synthase genes (chsA, chsB, and chsC) from Aspergillus nidulans. In the present work, we describe the isolation and characterization of another chitin synthase gene, named chsD, from A. nidulans. Its deduced amino acid sequence shows 56.7% and 55.9% amino acid identity, respectively, with Cal1 of Saccharomyces cerevisiae and Chs3 of Candida albicans. Disruption of chsD caused no defect in cell growth or morphology during the asexual cycle and caused no decrease in chitin content in hyphae. However, double disruption of chsA and chsD caused a remarkable decrease in the efficiency of conidia formation, while double disruption of chsC and chsD caused no defect. Thus it appears that chsA and chsD serve redundant functions in conidia formation.

Amino Acid Sequence↗

[The treatment of imported Plasmodium falciparum malaria with halofantrine. Apropos of 59 case reports (corrected and republished article orginally printed in Med Trop (Mars) 1990 Jan-Mar;50(1):113-7)].

59 cases of Plasmodium falciparum malaria fever occurring in non-immune Caucasian subjects having got a correct chemoprophylaxis by chloroquine were treated by halofantrine (HALFAN). They were given 1500 mg divided in 3 doses of 500 mg every 6 hours from D1 to D8. All them were back from a malarial highly endemic zone with chloroquine resistance. Analysis of the main biological and clinical efficiency parameters displayed very satisfactory results: disappearances of fever (mean 22 H) and parasitemia (mean 36 H) are short. After two months of monitoring, no malaria recrudescence was noted. With an efficacy of 10 p.c. associated to a noticeable clinical and biological tolerance Halofantrine is a first-class treatment of chloroquine resistant malaria fever.

Adolescent↗

Atrioventricular nodal function in the immature canine heart [corrected and republished article orginally printed in Pediatr Res 1987 Nov;22(5):616-20].

Previous studies have suggested that the atrioventricular nodal functional refractory period in the neonate is equal to or shorter than that of the ventricle, providing little or no protection to the ventricle against rapid atrial rates and allowing closely coupled atrial beats to fall within the ventricular vulnerable period. We evaluated atrioventricular node function in 21 mongrel neonatal puppies, 3-15 days old, and 15 adult dogs utilizing intracardiac His bundle recording and stimulation techniques. The mean atrioventricular nodal functional refractory period (173.1 +/- 20.0 ms) exceeded both the ventricular effective refractory period (139.5 +/- 14.3) and ventricular functional refractory period (163.3 +/- 14.5) in the neonates. Furthermore, the atrioventricular node was the site of limiting antegrade conduction in all neonates. No ventricular arrhythmias were induced by atrial extrastimulation in any of the neonates. The site of conduction delay during atrial extrastimulation was confined to the atrioventricular node in 15/16 neonates (94%) while 1/16 (6%) had combined nodal and infranodal delay. The neonates developed Wenckebach, at significantly faster heart rates than the adults, but both groups developed Wenckebach at approximately twice the resting heart rate. Retrograde conduction was a consistent finding in the neonates. However, antegrade Wenckebach occurred at a significantly faster heart rate than retrograde Wenckebach suggesting different functional properties. Our data suggest that in the neonatal canine, the atrioventricular node functional refractory period is longer than both the ventricular effective refractory period and ventricular functional refractory period. Furthermore, the degree of protection offered by the neonatal atrioventricular node to the ventricle appears to be comparable to that of the adult.

Animals↗

Ectopic "high" origin of both coronary arteries from the left aortic wall: anatomic and postmortem angiographic findings.

Anatomic and postmortem angiographic findings of a previously unreported case of ectopic origins and unusual courses of the right coronary (RC) artery and the left coronary (LC) artery were demonstrated. This specimen was unique among 450 angiographies and 60 corrosion castings of the human hearts examined in this study. The ostium of the RC artery was pocket-like, located in the left aortic wall at roughly 180 degrees to the long axis of the ascending aorta and 19 mm above the rim of the sinotubular junction (SJ). Initially, the RC runs to the right and downward, passing high in the cleft between the aorta and the pulmonary trunk, thereby avoiding a possible compression from them. The ostium of the LC faced upward and originated from the left aortic wall 7 mm above the SJ. The LC ran to the left and downwards for 16 mm until its division. Histologically, the first 11 mm of the RC were elastic. This observation, together with its high course between the great vessels, combined to make this case benign. The best x-ray projections to show the characteristic findings of the present case were anteroposterior and lateral, which were of practical importance for the correct determination and interpretation of this case. The cardiac surgeon should be aware that high cannulation will be required to locate the RC to avoid accidentally cross-clamping or transecting the vessel during surgery where this anomaly may be encountered.

Adolescent↗

Single-day combined evaluation of regional myocardial perfusion and function at rest and peak exercise with 99mTc-MIBI in patients with coronary artery disease.

99mTc-labeled methoxy-isobutyl-isonitrile (MIBI) allows a simultaneous radionuclide assessment of regional heart function and perfusion. In this study the effectiveness of functional and perfusional images obtained with 99mTc-MIBI in the detection of coronary stenoses was compared with that of their combination. We studied 197 patients who underwent coronary angiography and a single-day radionuclide protocol including first pass angiography (multicrystal gamma camera) and single photon emission computed tomography, by means of 2 injections of 99mTc-MIBI at rest and at peak exercise. Fifteen patients had < 50% stenoses, 50 had 1-vessel, 69 2-vessel and 63 3-vessel disease, for a total of 377 pathological major coronary vessels; 129 patients had previous myocardial infarction. Functional images, perfusional tomograms and their combination showed the same sensitivity (98%) and specificity (80%) in detecting coronary patients. Regional sensitivity and specificity of the combined analysis achieved 87% and 82%, respectively, vs. 94% (p < 0.005) and 60% (p < 0.001) of functional images, and 88% (p = N.S.) and 74% (p < 0.05) of perfusional tomograms. Thus, the combined analysis of regional functional and perfusional abnormalities increased significantly the specificity in the detection of coronary stenoses, in comparison with the separate evaluation of function and perfusion, achieving also a slightly higher diagnostic accuracy (85%, vs. 81% and 83%, respectively). The results confirm that a single-day protocol simultaneously assessing regional myocardial function and perfusion with 99mTc-MIBI represents a rapid and effective diagnostic method, that allows the physician to assess the presence and functional importance of coronary stenoses in less than 4 hours.

Coronary Disease↗

[The dilatation technique with the novel trocar system for minimally invasive implantation of intramedullary nails at the proximal femur].

A new technique of a minimally invasive approach to the proximal femur was developed for the management of per- and subtrochanteric fractures using intramedullary nail blade systems. For creating the entry portal at the proximal femur a transcutaneously applied Kirschner-wire is used. Subsequently, a new developed trocar system (TNS) for the protection of the soft tissue during reaming procedures is placed via a small cutaneous incision. The reaming of the femoral shaft can be performed through this trocar system. A new targeting jig especially adapted to the gliding nail was used in this first series. From December 1998 to June 1999 12 patients were treated with this new technique in the Department of Trauma Surgery of the Philipps-University in Marburg. The mean age of the 8 female and 4 male patients was 78 (+/- 12) years. The majority of the total group were old patients with a mean ASA score of 3-4. Relevant intraoperative complications using the new dilatation approach were not observed. All patients were mobilised after few days. Postoperative complications or infections were not found. In the clinical practice of the management of per- and subtrochanteric femoral fractures the new dilatation approach has proved to be more comfortable and minimally invasive than the standard technique existing to date.

Aged↗

[The endoleak problem in endoluminal therapy].

Endovascular treatment of aortic aneurysms with stent grafts was performed increasingly in recent years. The most frequent complication after endovascular therapy of aortic aneurysms is an endoleak. In case of a persistent endoleak, diameter of the aneurysm is increasing with a high risk of aneurysm ruptur. Diagnostic tools are spiral computed tomography and angiography. Spiral computed tomography is the most sensitive method for the diagnosis of an endoleak ad should be performed with a biphasic acquisition. In- and outflow of sidebranches can be identified correctly with selective angiography in 86%. Perigraft endoleaks should be treated in any case. Patent side branches generally are observed over a period of 6 months. After 6 months approximately half of these endoleaks are thrombosed. Is there an increasing of the diameter of the aneurysm or any changing in the morphology of the aneurysm there is an indication for embolisation of these sidebranches of the aneurysmal sac. Preinterventional embolisation of patent sidebranches is under discussion. Type I endoleaks can be managed by additional stent-graft implantation or coil embolisation. In case of type II endoleaks in- ad outflow vessels should be embolised with coils. Therapy of type III endoleak is performed mostly by additional stent-graft placement. The total incidence of secondary interventions in the Eurostar-study was nearly 10% per year.

Aortic Aneurysm, Abdominal↗

Influence of the polyol pathway on norepinephrine transporter reduction in diabetic cardiac sympathetic nerves: implications for heterogeneous accumulation of MIBG.

PURPOSE: Cardiac scintigraphic studies using 123I-labeled metaiodobenzylguanidine ([123I]MIBG) have demonstrated heterogeneous myocardial accumulation of MIBG in diabetes. The accumulation has been found to correlate with a heterogeneous decrease in the expression of norepinephrine transporter (NET). In diabetic peripheral nerve tissue, polyol pathways are activated and cause nerve dysfunction and degeneration. However, there has been little research on the polyol pathway and cardiac sympathetic nerves. Therefore, to assess the influence of the polyol pathway on cardiac sympathetic nervous function, we investigated the regional accumulation of MIBG and NET protein expression in diabetic model rats treated with aldose reductase inhibitor (ARI) for the blockade of polyol pathways. METHODS: Rats were given a single intravenous injection of streptozotocin (n=76, STZ-D rats). Starting the day after STZ injection, ARI was administered daily to 42 of the rats for 4 weeks (ARI-D rats). To assess the cardiac sympathetic nervous function, [125I]MIBG autoradiographic experiments were carried out. Finally, NET protein expression was assessed with a saturation binding assay. RESULTS: The myocardial sorbitol concentration was significantly higher in STZ-D rats than in ARI-D rats. There was no heterogeneous accumulation of MIBG in ARI-D rats. There was a heterogeneous decrease of NET expression in STZ-D rats, but not in ARI-D or control rats. CONCLUSION: The gathered data indicate that the enhanced polyol pathway correlates with the decrease in regional cardiac sympathetic nervous function, and this impairment may lead to the reduction of NET protein in cardiac sympathetic nerves of the diabetic inferior wall.

3-Iodobenzylguanidine↗

The substance P receptor antagonist CP-96,345 interacts with Ca2+ channels.

The nonpeptide substance P receptor antagonist CP-96,345 was found to displace binding to Ca2+ channel binding sites labelled with either [3H]desmethoxyverapamil or [3H]diltiazem and to enhance [3H]nitrendipine binding. Unlike the substance P receptor antagonist activity of CP-96,345, these effects on Ca2+ channel binding sites were neither stereoselective nor species-dependent. It is concluded that CP-96,345 may act as an antagonist of L-type Ca2+ channels in addition to being a potent NK1 receptor (substance P) antagonist.

Animals↗

Estrogen and progesterone activate spinal kappa-opiate receptor analgesic mechanisms.

Rats and humans manifest elevated response thresholds to aversive stimuli during gestation and parturition. This pregnancy-associated antinociception is mediated, in part, by a spinal cord dynorphin/kappa antinociceptive system. Simulating the maternal pregnancy blood concentration profile (in non-pregnant animals) of 17-beta-estradiol (E2) and progesterone (P) produces an opioid antinociception which closely approximates that of actual pregnancy. The current study was initiated in order to determine whether sex steroid-induced antinociception involves a spinal cord kappa-opiate receptor-coupled system (as does the antinociception of actual gestation). Additionally, sex steroid modulation of the intrathecal (i.t.) antinociceptive effectiveness of a kappa agonist was investigated. The opioid antinociception associated with simulating the pregnancy blood concentration profile of E2 and P (hormone-simulated pregnancy, HSP) is significantly antagonized by i.t. administration of nor-binaltorphimine, an antagonist highly specific for the kappa-opiate receptor. This indicates that exposure (of non-pregnant animals) to the pregnancy blood profile of E2 and P activates a spinal cord kappa-opiate receptor analgesic system, as occurs during actual gestation. Furthermore, during HSP, antinociceptive responsiveness to i.t. U50,488H (kappa-selective) is significantly enhanced (approximately 40%). This effect is abolished in animals treated concomitantly with steroid hormones and systemic naltrexone or i.t. nor-binaltorphimine. In contrast to the effects of steroid treatment on antinociceptive responsiveness to i.t. U50,488H, no alteration in antinociceptive responsiveness to i.t. sufentanil was observed on day 19 of HSP over all doses tested (0.1-1 nmol). Thus, during HSP (and actual gestation), a less robust constituent of intrinsic opioid pain-attenuating systems in the spinal cord is recruited.

Animals↗

Engaging needles: a simple technique for arthroscopic side-to-side rotator cuff repair.

We present a simplified technique for the side-to-side arthroscopic rotator cuff repair. The instruments required for this technique are a 45 degrees Suture Lasso (SL; Arthrex, Naples, FL) and a 17F spinal needle (SN). With the arthroscope in the lateral portal, the SL is inserted through the posterior cannulas to grab healthy tissue at the posterior margin of the cuff. Through the anterior cannulas or through a skin puncture, the SN is inserted to catch healthy tissue at the anterior margin. Once both instruments are through the tissues, we manipulate them to make their tips converge. Because the SN diameter is small, it is very easy to engage its tip into the SL tip. Once engaged, a No. 1 PDS monofilament suture is easily passed through both instruments. When the suture comes out of the SL handle, both instruments can be pulled out, leaving the suture in place. Using a suture retriever clamp, the sutures are retrieved through a cannula for knot tying. This technique can be repeated as many times as necessary to place enough sutures in a side-to-side fashion to achieve the repair.

Arthroscopy↗

Glucose utilization is suppressed in the gut of insulin-resistant high fat-fed rats and is restored by metformin.

It has been recently suggested that the small intestine (SI) has the capacity to contribute to endogenous glucose production (EGP), in addition to the liver and kidney. The aim of this work was: (1) to estimate the role of SI glucose fluxes in glucose homeostasis in insulin resistance states (induced by high-fat (HF) feeding); (2) to assess the effect of metformin, an anti-diabetic molecule, on these fluxes. Rats were fed for 6 weeks on a HF-diet, supplemented or not with metformin (HF-Met) at a daily dosage of 50 mg/kg during the last week. We combined arterio-venous glucose balance measurements and isotopic dilution techniques to separate basal intestinal glucose uptake (IGU) and release (IGR). Contrary to what was observed in control starch-fed rats, IGU was negligible in HF-fed rats: 0.6 +/- 2.4 micromol/kg min (mean +/- S.E.M., n = 9). It was restored to a level close to that of control rats in the HF-Met group: 13.0 +/- 6.7 micromol/kg min (mean +/- S.E.M., n = 9, p < 0.05 compared to the non-treated group). Similarly, IGR was close to zero in HF-fed rats (-3.8 +/- 2.6 micromol/kg min), but was significant in HF-Met rats (7.4 +/- 4.4 micromol/kg min, p < 0.05 compared to non-treated rats). These data strongly suggest that the impairment of glucose uptake in the SI might be a crucial feature of insulin resistance states and that a key beneficial effect of metformin in these situations might be to restore a normal glucose metabolism in this tissue.

Animals↗

Factors affecting regression of mitral regurgitation following isolated coronary artery bypass surgery.

OBJECTIVE: Fate of MR following CABG is variable. Predictors of MR regression following CABG alone are not known. METHODS: From our surgical registry, CABG patients with both pre-operative and post-operative resting echocardiograms at our institution were screened. Of the 523 patients identified, 92 had 3+ (n = 65) or 4+ (n = 27) MR on the pre-operative echocardiogram on a 0-4 scale, who had isolated CABG. MR regression was correlated with clinical, operative, electrocardiographic and echocardiographic variables. RESULTS PATIENT CHARACTERISTICS: age 68+/-11 years, 62% male, and LVEF 37+/-15%. MR grade decreased from 3.3+/-0.5 to 2.3+/-1.2 post-CABG. Residual 3 or 4+ MR post-CABG was present in 43 (47%) patients. Regression of MR (n = 49) was associated with reductions in LV end-diastolic (P = 0.006) and end-systolic (P = 0.0005) dimensions, improvement in LVEF (P = 0.01), longer cross-clamp time (P = 0.04), use of beta-blockers (P = 0.04) and lower presence of CVA as a possible marker of lower atherosclerotic burden (P = 0.03). There was a trend towards increased mortality (P = 0.3) with residual 3-4+ MR over a mean follow-up of 3.9 years. CONCLUSIONS: In nearly half of patients with 3-4+ MR, MR does not regress with CABG alone. Residual MR may be associated with increased mortality. Regression of MR is related to LV size reduction and improvement in LV function. Presence of myocardial viability, adequate revascularization, lack of excessive atherosclerotic burden and therapy with beta-blockers and ace-inhibitors may be critical for MR regression following CABG alone.

Adrenergic beta-Antagonists↗

The GC-MS detection and characterization of reticuline as a marker of opium use.

Reticuline (a precursor of opium alkaloids) was detected and characterised as its trimethylsilyl ethers, acetyl esters and methyl ethers by GC-EIMS and GC-CIMS in opium and the urine of opium users after hydrolysis by acid or beta-glucuronidase as coextractive of morphine. Because this compound cannot be detected in heroin and poppy seeds, it is suggested as a differentiating marker between opium and heroin use, opium and poppy seeds use, or opium and "pharmaceutical" codeine use in cases when opiate use has been confirmed by detection of morphine and codeine in the urine. As well as being a constituent of opium, reticuline in the urine of opium users may also result from the metabolic demethylation of the three other benzyltetrahydroisoquinoline opium alkaloids: codamine, laudanosine and laudanine.

Alkaloids↗