Force recruitment during electrical nerve stimulation with multipolar intrafascicular electrodes

Experimentally, during electrical nerve stimulation, the influence is examined of two intrafascicular anodes on the force recruitment with one intrafascicular cathode. It is found that the anodes suppress recruitment and that this effect is more pronounced when the distance of the anodes to the cathode is decreased, or when the anodal currents are increased. The measured recruitment curve patterns can be qualitatively explained by a nerve stimulation model that calculates theoretical recruitment curves for intrafascicular multi-electrode configurations. Discrepancies between the experimental and the theoretical recruitment curves are seen, but these can be understood by taking into account a non-uniform fibre distribution.     

High survial rate of hamsters given intratracheal instillations of benzo[a]pyrene and ferric oxide and kept on a high {beta}-carotene diet

The study described in this paper was primarily conducted toidentify the cell types involved in the formation, progressionand regression of metaplastic changes in the respiratory tractepithelium of hamsters after intratracheal intubations withbenzo[a]pyrene Furthermore, the role of vitamin A and ß;-carotenein these processes was studied. In the course of the study aremarkable effect of dietary ß;-carotene on survivalof hamsters became a subject of investigation. Hamsters werefed diets with various levels of vitamin A or ß-caroteneand were treated intratracheally with a suspension of benzo[a]pyrenewith ferric oxide in saline. The tumour response of the respiratorytract was very low (2.8%) and hyper- and metaplasia of respiratoryepithelium were virtually absent. However, an interesting observationwas an exceptionally low mortality of only 2% after 69 weeksin the group of hamsters fed a high ß-carotene diet(1% w/w), whereas in the other groups mortality after 69 weeksamounted to 25%. Although the exact cause of death of most ofthe hamsters could not be established, a 40% reduction of lipidperoxidation in the livers was found in the high ß-carotenegroup. Moreover, In this group the degree and incidence of nephroslsand of focal mineralization of kidneys and heart were lowerthan in the other groups. These favourable effects of the highß-carotene diet may have contributed to the unusuallyhigh survival rate in hamsters fed this diet. Further studiesare planned to verify and study this observation.     

Use of commercially available cell culture inserts for primary culture and electrophysiologic studies of guinea pig gastric mucous epithelial cells

Summary The adherence, growth, and electrophysiologic properties of guinea pig gastric mucous epithelial cells were investigated using porous membrane filters. We also tested three commercially available Ussing-type chambers that were designed to be used with the various porous membrane supports. Overall, the 0.45-µm Falcon-Cyclopore porous membrane was found to be very favorable for the consistent attachment and growth of our cells. This same filter also gave good results in the detection of periodic acid Schiff-positive mucous glycoprotein and Nile red neutral lipid fluorescence in the gastric mucous cells. Our cells grew poorly on collagen-coated Costar-Snapwells and Millipore Millicell-CM porous filters. For measurement of transepithelial potential difference resistance, and short-circuit current, the Costar-Snapwell with the Costar-Snapwell Diffusion-chamber system was superior in design and operation when compared to the Costar Transwell-COL, Falcon-Cyclopore, or Anotec-Anocell porous inserts used with conventional Ussing-chambers. The gastric mucous cells grew best on ICN-Cellagen membranes, but these filters routinely detached from their plastic holder and therefore could not be used for Ussing-chamber studies. The large 24.5-mm, 0.40-µm pore size Costar-Transwell-COL and the 24.1-mm, 0.45-µm Falcon-Cyclopore membranes gave good results when used in a modified horizontal-chamber for microelectrode analysis of membrane potentials and resistances of the gastric mucous cell monolayers.     

Lymphocyte Populations and Cellular Immune Reactions in Juvenile Rheumatoid Arthritis

Ten patients with juvenile rheumatoid arthritis and age- and sex-matched healthy controls were investigated in pairs. The patients were found to have both normal proportions and normal absolute numbers of T lymphocytes, B lymphocytes, and the Fc-receptor-bearing lymphoid cells in peripheral blood. No abnormality of mitogen-induced lymphocyte transformation was observed. Lymphocyte-mediated cytotoxicity induced by phytohemagglutinin (PHA) or anti-target cell antibodies was also found to be normal. As in an earlier study, impaired delayed hyper-sensitivity by skin testing was observed in the patient group, thus indicating a dissociation between in vivo and in vitro parameters of lympboid cell function.     

Inhibition of Antibody-Dependent Human Lymphocyte-Mediated Cytotoxicity by Immunoglobulin Classes, IgG Subclasses, and IgG Fragments

The cytotoxicity of human peripheral blood lymphocytes against chicken erythrocytes sensitized by rabbit antibodies was inhibited by human immunoglobulin and immunoglobulin fragments. Myeloma proteins isolated in dimeric state or aggregated by heat treatment inhibited better than the corresponding monomeric proteins. Strong inhibition was observed with IgG1 and IgG3, and with IgG₂ after aggregation, while IgG₄ inhibited very little. No inhibition was found with IgM, IgA. IgD and IgE. The F(ab')₂. and Fab fragments of IgG inhibited poorly or not at all. While- considerable inhibition was observed with the Fc fragment, the pFc' fragment, which roughly corresponds to the C-terminal half of the Fc portion, showed little inhibitory capacity. A fragment isolated from IgG3, containing an extension of the N-terminal part of Fc (the Fch fragment), was an even better inhibitor than tin Fc fragment. The inhibitory capacity of the Fch and Fc fragments was greatly diminished following partial reduction and alkylation On the basis of the inhibitory pattern of IgG fragments, it is suggested that the region on the immunoglobulin molecule involved in binding to the Fc receptor of the effector lymphocytic cell may be located within the CH2 domain.     

Long-term adhesion and survival of dissociated cortical neurons on miniaturised chemical patterns

The influence of neuron-adhesive pattern geometry on long-term adhesion, survival and pattern compliance of cortical neuronal tissue was studied over a period of 15 days. The results are relevant for a successful, long-term integration of neuronal cells with electrodes from micro-electronic devices. Microwells (depth 0.5μm), with diameters of 25, 50, 100 and 150 μm and spacing distances of 15, 30, 60 and 90 μm, were etched in a neuron-repellent fluorocarbon (FC) layer and coated with neuron-adhesive polyethylenimine (PEI). Results showed that adhesion, survival and compliance to the underlying patterns were geometry-and time-dependent. After 1 day, adhesion was inversely proportional to the diameter of the microwells, thus favouring the 25 μm microwells. However, adhesion was best on 50 μm microwells after 15 days. Survival of neurons was limited on 25 μm microwells (viability function V(D, T) was 0.08), as opposed to the better survival on 150 μm microwells (V(D, T) was 0.25) after 15 days. In summary, the study shows that the chemical patterns with microwells of 150 μm diameter (90 μm spacing gap) are most suitable for application on neuro-electronic devices owing to the better long-term survival and high pattern compliance of the neuronal cells.     

Multivariate Markov chain analysis of the probability of pregnancy in infertile couples undergoing assisted reproduction.

BACKGROUND: Estimating the probability of pregnancy leading to delivery and the influence of clinical factors on that probability is of fundamental importance in the treatment counselling of infertile couples. A variety of statistical techniques have been used to analyse fertility data, many borrowed from survival analysis. METHODS AND RESULTS: We propose an alternative method of analysis which is based on a discrete time Markov chain approach, with states 'pregnancy (leading to a delivery)', 'not pregnant', and 'censored' and in which the transition probabilities are dependent both on the clinical characteristics of the patient and the treatment given. CONCLUSIONS: We believe that the method of analysis presented here may be preferable to standard analyses in that it better reflects the clinical situation, it is a truly discrete time analysis applied to a discrete time situation, it explicitly models the censoring process (a process which in itself provides information of interest to the physician) and can be readily extended to a variety of clinical situations.     

Striated intramural gallbladder lucencies on US studies: predictors of acute cholecystitis

Ultrasound scans of 51 consecutive patients with gallbladder wall thickening were reviewed, and specific sonographic features were correlated with surgical and clinical follow-up. Two patterns of thickening were identified as specific indicators of the presence or absence of acute cholecystitis. "Striated" wall thickening, consisting of several alternating, irregular, discontinuous, lucent and echogenic bands, was seen in eight of 13 patients (62%) with acute cholecystitis. This pattern was not encountered in any of the patients who did not have acute cholecystitis. Conversely, "three-layer" thickening, consisting of a single circumferential lucent zone between two relatively uniform echogenic layers, was seen in only one of 13 patients (8%) with acute cholecystitis but in 11 of 38 patients (29%) with other diagnoses. Other abnormalities, including the presence of intramural echogenic foci and wall irregularities, were more frequently seen in patients with acute cholecystitis but were not as helpful. Use of these features may suggest or help exclude a diagnosis of acute cholecystitis in those patients in whom the cause of gallbladder wall thickening is otherwise not apparent.     

The changing face of reoperative parathyroidectomy: a single-centre comparison of 147 parathyroid reoperations

IntroductionReoperative parathyroidectomy for persistent and recurrent primary hyperparathyroidism is dependent on radiology. This study aimed to compare outcomes in reoperative parathyroidectomy at a single centre using a combination of traditional and newer imaging studies.Materials and methodsRetrospective case note review of all reoperative parathyroidectomies for persistent and recurrent primary hyperparathyroidism over five years (June 2014 to June 2019; group A). Imaging modalities used and their positive predictive value, complications and cure rates were compared with a published dataset spanning the preceding nine years (group B).ResultsFrom over 2000 parathyroidectomies, 147 were reoperations (101 in group A and 46 in group B). Age and sex ratios were similar (56 vs 62 years; 77% vs 72% female). Ultrasound use remains high and shows better positive predictive value (76% vs 57 %). 99mTc-sestamibi use has declined (79% vs 91%) but the positive predictive value has improved (74% vs 53%). 4DCT use has almost doubled (61% vs 37%) with better positive predictive value (88% vs 75%). 18F-fluorocholine positron emission tomography-computed tomography and ultrasound-guided fine-needle aspiration for parathyroid hormone are novel modalities only available for group A. Both carried a positive predictive value of 100%. Venous sampling with or without angiography use has decreased (35% vs 39%) but maintains a high positive predictive value (86% vs 91%). Cure rates were similar (96% vs 100%). Group A had 5% permanent hypoparathyroidism, 1% permanent vocal cord palsy and 1% haematoma requiring reoperation. No complications for group B.ConclusionOptimal imaging is key to good cure rates in reoperative parathyroidectomy. High-quality, non-interventional imaging techniques have produced a shift in the preoperative algorithm without compromising outcomes.     

Economic evaluation of pharmaceuticals: a European perspective

In recent years there has been a large increase in the number of economic evaluations of pharmaceuticals. Many of these studies have been commissioned by individual pharmaceutical companies, in support of new or existing products. In 2 countries, Australia and Canada (in the province of Ontario), draft guidelines issued by the government have outlined the requirements for economic evaluations to be submitted in support of requests for reimbursement (government subsidy) of particular products. One consequence of the guidelines is that they clarify what is required, and in specifying the procedure for submission of dossiers, identify a clear audience for the economic evaluation. In contrast, the situation in Europe is diverse. A wide range of healthcare systems exist, including national health services and more liberal systems, involving a wide range of insurers and providers. European countries also differ widely in their approach to the pricing and reimbursement of pharmaceuticals. Because of this diversity, the nature, conduct and impact of economic evaluation in Europe is not clear. It is therefore difficult for pharmaceutical companies to develop appropriate strategies for economic evaluation and for analysts to decide on appropriate study methodology. This article reviews the nature of any official guidance or requirements for economic evaluation, the potential for use of economic evaluation, the range of studies carried out and the identifiable impacts. There is currently no official guidance in any country, although some countries are considering issuing guidelines. In some countries there is official encouragement to pharmaceutical companies to undertake studies, and where economic data have been presented they have been considered by the relevant committees. The potential uses of economic evaluation vary widely from country to country. These can be classified in terms of a potential role in undertaking national price negotiations, deciding on reimbursement status or copayment level, deciding on inclusion in local formularies or in treatment guidelines, or in improving prescribing decisions. Approximately 80 economic evaluations of pharmaceutical products have been conducted to date in Europe, covering a wide range of clinical areas. There are relatively few examples of identifiable effects of such studies. In part this is because it is often difficult to assess the part played by various items of data. Nevertheless, the overriding conclusion is that economic evaluation of medicines is likely to be more relevant in Europe in the future. The problem for the pharmaceutical industry is in determining when and how.