Alternate current biosusceptometry for the assessment of gastric motility after proximal gastrectomy in rats: a feasibility study.

BACKGROUND: This study proposes an experimental model to assess the consequences of gastric surgeries on gastric motility. We investigated the effects of proximal gastrectomy (PG) using a non-invasive technique (alternate current biosusceptometry [ACB]) on gastric contractility (GC), gastric emptying (GE), and orocecal transit (OCT) after the ingestion of liquids and solids in rats. METHODS: Twenty-four male rats were subjected to gastric motility assessment before and after the PG procedure. The GE and OCT results are expressed as the mean time of gastric emptying (MGET) and cecum arrival (MCAT). The GC recordings are presented as the frequency and amplitude of contractions. KEY RESULTS: Mean time of gastric emptying after solid meals were significantly different (p < 0.001) between control and PG (113 ± 5 to 99 ± 6 min). Mean time of cecum arrival ranged from 265 ± 9 to 223 ± 11 min (p < 0.001) and 164 ± 9 to 136 ± 17 min (p < 0.050) for solid and liquid meals, respectively. The assessment of GC showed that surgery decreased the phasic frequency (4.4 ± 0.4 to 3.0 ± 1.1 cpm, p < 0.050) and increased the amplitude of contractions (3.6 ± 2.7 to 7.2 ± 3.0 V/s, p < 0.050). No significant difference was found in tonic frequency. CONCLUSIONS & INFERENCES: The ACB system was able to assess GE, OCT, and GC in gastrectomized rats. Overall, PG accelerated GE and gastrointestinal transit, likely due to the increase in both intragastric pressure and amplitude contraction. Our data presented an efficient model to investigate functional consequences from gastric surgeries that will allow further studies involving different procedures.

[Malignant fibrous histiocytoma of the penis]. / Malignes fibröses Histiozytom des Penis.

According to the most recent World Health Organization (WHO) guidelines a diagnosis of malignant fibrous histiocytoma (MFH) should be made only for lesions composed of tumor cells without evidence of a specific line of differentiation. This is therefore a diagnosis by exclusion which is why the name of undifferentiated high-grade pleomorphic sarcoma (UPS) should be preferred. Soft tissue sarcomas currently have an incidence in all body regions of approximately 20 cases per 1 million inhabitants per year. Soft tissue tumors of the penis represent approximately 5 % of all penile tumors and the incidence of penile sarcomas is estimated to be approximately 0.6-1 case per 100,000 patients. Only seven cases have so far been reported in the literature. This article describes the case of a 61-year-old Caucasian male who presented with a painless mass sited in the upper part of the corpus cavernosa. An incisional biopsy with a subsequent investigation using an extensive immunohistochemical panel were performed and a high-grade undifferentiated pleomorphic sarcoma or pleomorphic storiform MFH was diagnosed. In addition to the case report a literature review is presented to elaborate the discussion on the differential diagnoses of these kinds of lesions.

Perceived changes and minimum clinically important difference of the Neurological Fatigue Index for multiple sclerosis (NFI-MS).

The determination of the minimum clinically important difference (MCID) is an important aspect of scale development. The Neurological Fatigue Index for multiple sclerosis (NFI-MS) was administered before and after expected change or stability in fatigue in 208 multiple sclerosis (MS) patients. The overall change scores of the NFI-MS accorded with perceived direction of change; importantly, no change was seen when none was perceived. Using the interval level NFI-MS scores, the largest MCID equated to 2.49 points on the Summary scale, 2.36 points on the Physical scale, 0.84 points on the Cognitive scale, 0.97 on the Diurnal Sleep scale and 1.95 on the Nocturnal Sleep scale. Our conclusion is that the NFI-MS responds as expected to changes in fatigue and has desirably small MCID scores.

Safinamide: from molecular targets to a new anti-Parkinson drug.

Ideal treatment in Parkinson's disease (PD) aims at relieving symptoms and slowing disease progression. Of all remedies, levodopa remains the most effective for symptomatic relief, but the medical need for neuroprotectant drugs is still unfulfilled. Safinamide, currently in phase III clinical trials for the treatment of PD, is a unique molecule with multiple mechanisms of action and a very high therapeutic index. It combines potent, selective, and reversible inhibition of MAO-B with blockade of voltage-dependent Na+ and Ca2+ channels and inhibition of glutamate release. Safinamide has neuroprotective and neurorescuing effects in MPTP-treated mice, in the rat kainic acid, and in the gerbil ischemia model. Safinamide potentiates levodopa-mediated increase of DA levels in DA-depleted mice and reverses the waning motor response after prolonged levodopa treatment in 6-OHDA-lesioned rats. Safinamide has excellent bioavailability, linear kinetics, and is suitable for once-a-day administration. Therefore, safinamide may be used in PD to reduce l-dopa dosage and also represents a valuable therapeutic drug to test disease-modifying potential.

Anti-allodynic effect of NW-1029, a novel Na(+) channel blocker, in experimental animal models of inflammatory and neuropathic pain.

NW-1029, a benzylamino propanamide derivative, was selected among several molecules of this chemical class on the basis of its affinity for the [(3)H]batracotoxin ligand displacement of the Na(+) channel complex and also on the basis of its voltage and use-dependent inhibitory action on the Na(+) currents of the rat DRG (dorsal root ganglia) sensory neuron. This study evaluated the analgesic activity of NW-1029 in animal models of inflammatory and neuropathic pain (formalin test in mice, complete Freund's adjuvant and chronic constriction injury in rats) as well as in acute pain test (hot-plate and tail-flick in rats). Orally administered NW-1029 dose-dependently reduced cumulative licking time in the early and late phase of the formalin test (ED(50)=10.1 mg/kg in the late phase). In the CFA model, NW-1029 reversed mechanical allodynia (von Frey test) after both i.p. and p.o. administration (ED(50)=0.57 and 0.53 mg/kg), respectively. Similarly, NW-1029 reversed mechanical allodynia in the CCI model after both i.p. and p.o. administration yielding an ED(50) of 0.89 and 0.67 mg/kg, respectively. No effects were observed in the hot-plate and tail-flick tests up to 30 mg/kg p.o. The compound orally administered (0.1-10 mg/kg) was well tolerated, without signs of neurological impairment up to high doses (ED(50)=470 and 245 mg/kg in rat and mice Rotarod test, respectively). These results indicate that NW-1029 has anti-nociceptive properties in models of inflammatory and neuropathic pain.

Complement C1q is dramatically up-regulated in brain microglia in response to transient global cerebral ischemia.

Recent evidence suggests that the pathophysiology of neurodegenerative and inflammatory neurological diseases has a neuroimmunological component involving complement, an innate humoral immune defense system. The present study demonstrates the effects of experimentally induced global ischemia on the biosynthesis of C1q, the recognition subcomponent of the classical complement activation pathway, in the CNS. Using semiquantitative in situ hybridization, immunohistochemistry, and confocal laser scanning microscopy, a dramatic and widespread increase of C1q biosynthesis in rat brain microglia (but not in astrocytes or neurons) within 24 h after the ischemic insult was observed. A marked increase of C1q functional activity in cerebrospinal fluid taken 1, 24, and 72 h after the ischemic insult was determined by C1q-dependent hemolytic assay. In the light of the well-established role of complement and complement activation products in the initiation and maintenance of inflammation, the ischemia-induced increase of cerebral C1q biosynthesis and of C1q functional activity in the cerebrospinal fluid implies that the proinflammatory activities of locally produced complement are likely to contribute to the pathophysiology of cerebral ischemia. Pharmacological modulation of complement activation in the brain may be a therapeutic target in the treatment of stroke.

[Videolaparoscopic cholecystectomy. Experience, evolution, and comparison of techniques]. / Colecistectomia videolaparoscopica. Esperienza, evoluzione e tecniche a confronto.

The paper broadly outlines the technique of laparoscopic cholecystectomy used by the authors to treat patients suffering from calculosis of the gallbladder. Basing their comments on the French school, the authors review the literature to identify those innovations introduced by individual operators in elation to the original technique which have enabled this method to be extended to those cases complicated by acute cholecystitis, VBP calculosis or sequelae from abdominal surgery. The most important innovations include the use of a laparoscope with oblique 30-degrees vision, which is extremely useful during the dissection of Calot's triangle since it allows VBP to be identified with greater ease and precision, above all in the event of phlogistic sequelae enclosing the peduncle. In addition, laparoscopic suture or ligation using Roeder's running-knot, used by the Dundee school to treat the cystic duct and artery, presents considerable advantages compared to the conventional use of metal clips. The authors also emphasise the growing return to intraoperative cholangiography which is routinely performed by some authors and is of value in identifying anatomic anomalies, iatrogenic lesions and VBP calculi unnoticed by preoperative tests. A second innovation which is highlighted consists of the treatment of choledocholithiasis during the course of laparoscopic cholecystectomy, in addition to pre- and postoperative endoscopic papillo-sphincterotomy.

Evidence for a direct vasoconstrictor effect of big endothelin-1 in the rat kidney.

Inhibition of endothelin-1 (ET-1)-converting enzyme has been suggested as a strategy for blocking ET-1-mediated vasoconstriction. However, it is unclear whether its putative substrate, bigET-1, is an inactive precursor. Thus, we compared in the rat the effects of ET-1 and bigET-1 on renal vascular resistance (RVR) in vitro (isolated perfused kidney, n = 15) and in vivo (Doppler shift technique, n = 23) when injected i.v. or in the rat renal artery (i.a.), before and after metalloprotease inhibition with phosphoramidon (30 mg/kg i.v.). In vitro, the ET-1/bigET-1 potency ratio for the RVR increase was 175; in vivo (i.v.) it was approximately 7 (ED50: 99 and 692 pmol/kg, respectively; P < 0.01). Unlike that of ET-1, the bigET-1 effect started slowly (peak effect at 15 min). On i.a. injection, the ED50 of ET-1 was lower but that of big ET-1 was unchanged (ED50: 28 and 706 pmol/kg, respectively). Moreover, the effect of i.a. bigET-1 on RVR was biphasic, with a dose-related rapid increase followed by a slowly developing further rise. Phosphoramidon completely inhibited the hemodynamic effects of i.v. bigET-1, but abolished only the second phase of the response when given i.a. It also significantly enhanced the effect of ET-1. We conclude that in the rat: (1) bigET-1 may affect RVR by both a direct effect and through phosphoramidon-sensitive conversion to ET-1; (2) the direct vasoconstrictor effect of bigET-1 might be expressed during endothelin-converting enzyme inhibition; (3) metalloproteases are involved in ET-1 degradation.

[The prevalence of smoking in psychiatric patients. The effect of "institutionalization"]. / La prevalenza del fumo di tabacco nei pazienti psichiatrici. L'influenza dell'istituzionalizzazione.

The prevalence and other parameters concerning tobacco smoking were assessed in 100 outpatients with psychiatric disorders of axis I and II, according to DSM-III R criteria, and compared with those of 85 male psychiatric inpatients with forensic problems, recruited in a psychiatric hospital. The use of tobacco smoking was increased in psychiatric outpatients vs. the general pupulation and was very heightened in schizophrenic, as reported in earlier investigations; in the forensic sample both schizophrenic and non schizophrenic patients showed a very high prevalence. Therefore, the factor "institutionalization" does not modify the prevalence of tobacco smoking in schizophrenic--whose "smoking disposition" appears independent of the different social environments--while increasing the use in non schizophrenic patients. The positive correlation between tobacco smoking and schizophrenia is largely supported by these data and demands further investigation of its pathophysiologic mechanisms.

[Chronic dialysis and forcing of the ability to fantasize. Evaluation of the alexithymic phenomenon in a group of dialyzed patients]. / Dialisi cronica e coartazione della capacità fantasmatica. Valutazione del fenomeno alexitimico in un gruppo di soggetti dializzati.

In order to evaluate personality modifications toward greater concreteness and a consequent reduction of fantasizing in subjects undergoing chronic haemodialytic treatment, the Shalling Sifneos Personality Scale (S.S.P.S.) was administered to a group of patients undergoing dialysis and to two control groups: one consisting of patients with chronic hepatitis and the other of healthy subjects. The S.S.P.S. measures the alexithymic traits of the personality. Subjects undergoing dialysis scored significantly higher than chronic hepatitis patients and healthy subjects; the latter group had the lowest scores. The alexithymic score, moreover, appears to be directly correlated with the duration of dialysis. It is suggested that the prominence of the alexithymic phenomenon may be related to defense mechanisms against recurrent anguish about dying and to the tendency to assume certain characteristics of the particular therapeutic regimen, such as concreteness and rationality, so as to be able to tolerate the aggressive aspects of the treatment.

Echocardiographic and clinical correlations in systemic hyper-tension.

Echocardiographic measurements in 47 asymptomatic hypertensive patients were correlated with duration and severity of blood pressure elevation and with optic fundoscopic findings. These observations were also compared with electrocardiographic and chest roentgenographic measurements. Echo left ventricular wall thickness (LVWT) correlated best with duration of known hypertension. For 22 recent hypertensive patients the LVWT mean was .9 +/- .3 cm whereas mean LVWT for 25 patients hypertensive for five or more years was 1.3 +/- .2, (p less than or equal to .01). More severe initial diastolic pressure and the presence of hypertensive fundi also correlated with increased wall thickness. Increased left atrial diameter (greater than or equal to 2 cm m2) was observed primarily in the presence of longstanding disease. ECG and cardiothoracic ratio by xray did not correlate highly with the echo abnormalities. These observations suggest that echocardiography may be a sensitive and early means of recognizing cardiac changes in hypertensive patients.