The ileoanal J pouch: radiographic evaluation

Endorectal ileoanal pull-through offers an attractive alternative to proctocolectomy and ileostomy for patients with ulcerative colitis, Gardner syndrome, and familial polyposis. To our knowledge, a careful radiographic analysis of the ileum, ileal pouch, and ileoanal anastomosis after ileoanal pull-through has not been reported. Thirty-two patients with ulcerative colitis, Gardner syndrome, and familial polyposis underwent colectomy, mucosal proctectomy, and endorectal ileoanal pull-through of a 15-cm ileal "J" pouch and loop ileostomy. Twenty-five (78%) of 32 of all the pouches radiographically demonstrated spiral folds extending from the middle of the pouch to the pectinate line. Other radiographic features included a mesenteric mass effect, pseudopolyps, and a central lucency that indicated intrapouch sutures. Radiographs provide useful information in the postoperative management of the ileal pull-through.     

The role of surgery in transmitting ≪ post-transfusion hepatitis ≫

The role of surgery as an additional risk in transmitting post-transfusion hepatitis was investigated in a retrospective study on acute hepatitis occurring in 77 transfused patients, 293 transfused and operated patients and 243 hepatitis cases with history of surgery without transfusion.Hepatitis A patients admitted to the same centres in the same period were utilized as controls. In transfused patients the percentage of NANB hepatitis was higher than that of type B (61.0% vs. 36.4%), while in the operated not transfused group the percentage of type B was twice that of type NANB (63.4% vs. 32.5%).In transfused and operated cases intermediate values were observed. The age-adjusted measures of association between exposures and the different hepatitis types showed a lack of effect of transfusion and a dominant role of surgery in transmitting type B hepatitis. In contrast, NANB post-transfusional cases were actually a mixture of post-transfusional and post-surgical cases, since both these exposures were found to be significantly associated with the disease.Our results suggest that studies on the incidence and the etiology of post-transfusion hepatitis should take into account the risk of surgical exposure which might have occurred.Corresponding author.     

Immunohistochemical detection of p140trkA and p75LNGFR neurotrophin receptors in neuroblastoma

In neuroblastoma, high levels of mRNA for p14h ^trkA and p75 ^LNGFR neurotrophin receptors are predictive of favorable outcome. Their evaluation by Northern blot, however, requires substantial amounts of tissue and this prevents their routine evaluation as well as the possibility for multicenter studies to be easily carried out. In an attempt to overcome these limitations, the feasibility and reliability of determining both neurotrophin receptors on cryostat sections by immunohistochemistry were assessed, and these findings were compared to those obtained from Northern blot analysis. Primary tumor samples from 28 untreated patients at all stages were evaluated by using H10 anti-p140 ^trkA and ME20.4 anti-p75 ^LNGFR mAbs. Although weak, positiveimmunostaining was found in 9 of 28 tumors for p140 ^trkA and in 5 of 28 tumors for p75 ^LNGFR . As compared to Northern blot, the concordance rate was 79% (22 of 28 cases) for p140 ^trkA (p < 0.05) and 71% (20 of 28 cases) for p75 ^LNGFR (p < 0.05). No case negative for Northern blot was found to be positive with immunohistochemistry. Since only high mRNA levels for both receptors have been shown to be clinically relevant, their immunohistochemical detection, although less sensitive than Northern blot, can be just as sufficient and reliable as a prognostic tool, and possibly with a better cost-benefit ratio.     

P0.1 is a useful parameter in setting the level of pressure support ventilation

Objective The purpose of this study was to investigate whether changes in breathing pattern, neuromuscular drive (P0.1), and the work involved in breathing might help to set the individual appropriate level of pressure support ventilation (PSV) in patients with acute respiratory failure (ARF) requiring ventilatory assistance.Design: A prospective, interventional study.Setting An 8-bed multidisciplinary intensive care unit (ICU).Patients Ten patients with ARF due to adult respiratory distress syndrome (ARDS), sepsis or airway infection were included in the study. Chronic obstructive pulmonary disease (COPD) patients with acute exacerbation were excluded. None of these patients was in the weaning process.Interventions We found a level of pressure support able to generate a condition of near-relaxation in each patient, as evidenced by work of breathing (WOB) values close to 0 J/l. This level was called PS 100 and baseline physiological measurements, namely, breathing pattern, P 0.1 and WOB were obtained. Pressure support was then reduced to 85%, 70% and 50% of the initial value and the same set of measurements was obtained.Measurements and results Flow ( ) was measured by a flow sensor (Varflex) positioned between the Y-piece of the breathing circuit and the endotracheal tube. Tidal volume was obtained by numerical integration of the flow signal. Airway pressure (P_aw) was sampled through a catheter attached to the flow sensor. Esophageal pressure (P_es) was measured with a nasogastric tube incorporating an esophageal balloon. The esophageal balloon and flow and pressure sensors were connected to a portable monitor (CP 100 Bicore) that provided realtime display of flow, volume, P_aw and P_es tracings and loops of P_es/V, P_aw/V and /V relationships. The breathing pattern was analyzed from the flow signal. Patient work of breathing (WOB) was calculated by integration of the area of the P_es/V loop. Respiratory drive (P 0.1) was measured at the esophageal pressure change during the first 100 ms of a breath, by the quasiocclusion technique. When pressure support was reduced, we found that the respiration rate significantly increased from PS 100 to PS85, but varied negligibly with lower pressure support levels. Tidal volume behaved in a similar way, decreasing significantly from PS 100 to PS85, but hardly changing at PS 70 and PS 50. In contrast, WOB and P 0.1 increased progressively with decreasing pressure support levels. The changes in WOB were significant at each stage in the trial, whereas P 0.1 increased significantly from PS 100 at other stages. Linear regression analysis revealed a highly positive, significant correlation between WOB and P 0.1 at decreasing PSV levels (r=0.87), whereas the correlation between WOB and ventilatory frequency was less significant (r=0.53). No other correlation was found.Conclusions During pressure support ventilation, P 0.1 may be a more sensitive parameter than the assessment of breathing pattern in setting the optimal level of pressure support in individual patients. Although P 0.1 was measured with an esophageal balloon in the present study, non-invasive techniques can also be used.     

AMPA receptors shape Ca2+ responses in cortical oligodendrocyte progenitors and CG-4 cells

Intracellular calcium signals triggered by glutamate receptor activation were studied in primary cortical oligodendrocyte lineage cells and in the oligodendrocyte cell line CG-4. Glutamate, kainate, and AMPA (30-300 μM) increased [Ca ²⁺]_i in both types of cells at the stage of oligodendrocyte progenitors (O-2A; GD3⁺) or pro-oligodendroblasts (04⁺). The peak amplitude of Ca²⁺ responses to glutamate receptor agonists was significantly larger in cortical cells. In CG-4 and in cortical cells, the majority (more than 90%) of bipolar GD3⁺ or multipolar 04⁺ cells responded to kamate. In all the cells analyzed, kainate was more efficacious than AMPA and glutamate. The percentage of bipolar or multipolar cells responding to glutamate was significantly lower in the CG-4 cell line than in primary cultures. Cellular responses typical of metabotropic glutamate receptor activation were observed in 20% of the cortical O-2A progenitors, but in none of the CG-4 cells. The AMPA-selective antagonist GYKI 52466 blocked kainate-induced Ca²⁺ responses in cortical O-2A cells. The selective AMPA receptor modulator cyclothiazide (30 μM) greatly potentiated the effects of AMPA (30-100 μM) on [Ca ²⁺]_i in cortical and CG-4 cells. Our findings indicate that Ca²⁺ responses in cells of the oligodendrocyte lineage are primarily shaped by functional AMPA receptors. © 1995 Wiley-Liss, Inc.

1 This article is a US Government work and, as such, is in the public domain in the United States of America.

     

Acute and nongenomic effects of testosterone on isolated and perfused rat heart

Gonadal steroid hormones influence vascular tone and the development of hypertension. There are sex differences in the incidence of cardiovascular diseases, and great attention has been placed on the study of estrogen cardiovascular effects. However, there are only a few reports on the effects of testosterone on the vasculature. It is commonly accepted that the mechanism of the action of steroid hormones on target tissues is mediated through the binding of hormones to cytoplasmic or nuclear receptors. However, some studies indicate that steroid action can be extremely rapid and therefore unlikely to be through a genomic mechanism. The purpose of this study was to assess the effect of intravascularly confined testosterone on an isolated rat heart to demonstrate acute and possibly nongenomic effects of the steroid. Our results show that testosterone blocked the adenosine vasodilator effect and increased vascular resistance, even when its presence was restricted to the coronary vascular lumen. These effects were exerted rapidly and possibly through nongenomic mechanisms.     

Indications and limits of the exercise test in chronic heart failure

Assessment of exercise capacity has been widely used in the evaluation of chronic heart failure (CHF), both to define the severity of the syndrome and to assess the changes induced by therapy. Various exercise tests and protocols can be used. The simple stress test using the exercise bicycle or the treadmill can give useful indications only in patients with severe or lower functional reductions. Maximum exercise duration usually depends on the patient's and the physician's motivation. The addition of respiratory gas exchange measurements, maximum oxygen consumption (VO(2)) or anaerobic threshold, increases the exactness of the assessment of the exercise limitation in CHF. VO(2) maximum provides an objective marker of aerobic capacity and it is biased by neither the patient nor the physician. This technique, however, requires the patient to exercise to exhaustion, and it is somewhat subjective and not indicative of normal daily exercise routine. The anaerobic threshold is a useful way of evaluating adaptability to submaximal efforts and the impact of the therapy on the daily performance. Nevertheless, it is significantly influenced by the fitness level and it has a reduced prognostic capability compared to VO(2) maximum. Submaximal exercise tests discriminate particularly between patients with severe CHF. The major limits are the influence of the patient's motivation and its limited validation in terms of reproducibility and prediction in controlled surveys.     

Chick gonadogenesis following early surgical bursectomy

Left ovaries of bursectomized chick embryos were examined on the 17th day of incubation in comparison to normal and sham-operated controls, by histological and histochemical observations. The results show that in bursectomized embryos the cortex appears irregulary developed, with a significant decrease in the mean thickness and in the percentage of the secondary sex cords in the total cortical area. Furthermore, the germinal epithelium appears thicker and the subcortical medulla and the tunica albuginea more compact. The greater activity of the enzyme ⁵–3-hydroxysteroid dehydrogenase ( ⁵3HSD) found in ovaries of bursectomized embryos (histochemical method) could be related to an endocrine dismetabolism affecting the cortical development. On the basis of these results and those of other authors, some hypotheses are advanced. In particular, an action of the bursal factor on GTH receptors could be the factor responsible of the enhanced steroidogenic activity altering the hormonal environment.     

Hybrid Pharmacokinetic Models to Describe Anti-HIV Nucleoside Brain Disposition Following Parent and Prodrug Administration in Mice

Brain delivery of active anti-HIV compounds is important for successful treatment of the AIDS patient. As an initial step in predicting human brain drug concentrations, hybrid pharmacokinetic models were developed to characterize the disposition of anti-HIV nucleosides following parent and prodrug administrations in mice. Mouse data were obtained following intravenous administration of 3-azido-2,3-dideoxyuridine (AZddU or AZDU), 3-azido-3-deoxythymidine (AZT), and their dihydropyridine prodrugs (AZddU-DHP and AZT-DHP). Exponential equations were fitted to the serum concentration–time data for each species, including the pyridinium ion moieties, and subsequently used in differential mass balance equations describing the brain dynamics of each compound. Model parameters for the mass balance equations were estimated by various techniques, including the utilization of in vitro data. In general, model-predicted brain concentrations agreed with the observed data. Similar data in larger animals will permit scale-up of the current model to predict human brain drug concentrations.