Tailoring Antireflux Surgery: A Randomized Clinical Trial

A hypothesis has been formulated that mandates the adjustment of antireflux surgery to either a total or a partial wrap depending on the motor function of the esophagus to avoid dysphagia and other obstructive complaints. This hypothesis has been tested in a randomized, clinical trial where 106 chronic gastroesophageal reflux patients were allocated to either a total Nissen-Rossetti (n= 53) or a Toupet partial posterior (n= 53) fundoplication, irrespective of their preoperative esophageal motor function. All patients were followed at least 3 years, during which time none had a relapse of moderate to severe reflux symptoms. Motor dysfunctions defined as peristaltic amplitude ≤ 30 mmHg in the distal third and failed primary peristalsis with or without > 20% simultaneous contractions were noted in 67 patients preoperatively, but these patients did not have a specific symptom profile (e.g., dominated by obstructive symptoms) nor did seven patients with “aperistaltic esophagus.” The incidence of dysphagia decreased from 20% preoperatively to 8% (mild) at 3 years after the operation with no difference between the surgical procedures. We were unable to demonstrate a relation between preoperative manometric findings and postoperative symptoms when assessed in the total group or when subdivided by the type of fundoplication (r < 0.3). Flatulence occurred more frequently among those with a total fundic wrap (p < 0.01). When patients representing motor dysfunction (see above) were specifically analyzed, we again observed no difference in outcome between those having a total or a partial fundic wrap. In conclusion, the concept of tailoring antireflux surgery based on the preoperative motor function of the esophagus in patients with chronic gastroesophageal reflux disease was not supported by the results of this clinical trial.     

Exit of the retinal central vascular trunk and extent of para-papillary atrophy]

PURPOSE: To evaluate whether the position of the central retinal vessel trunk exit on the lamina cribrosa spatially correlates with the location of parapapillary atrophy in glaucoma. METHODS: Color stereo optic disc photographs of 79 patients with primary or secondary open-angle glaucoma and 53 normal subjects were morphometrically evaluated. We determined the position of the central retinal vessel trunk exit on the lamina cribrosa surface and measured the area of parapapillary atrophy in four 90 degrees quadrants. RESULTS: After correction for normal values, the beta zone area of parapapillary atrophy in the glaucoma eyes was significantly larger, when measured in the disc quadrant most distant to the central retinal vessel trunk exit than as if measured in the quadrant containing the vessel trunk exit. CONCLUSIONS: Position of the central retinal vessel trunk exit on the lamina cribrosa influences the location of parapapillary atrophy in glaucoma. The longer the distance to the central retinal vessel trunk exit, the more enlarged is parapapillary atrophy.     

Localised retinal nerve fibre layer defects in chronic experimental high pressure glaucoma in rhesus monkeys

AIM: To evaluate prospectively in an experimental model of chronic high pressure glaucoma whether the concept of a mainly diffuse pattern of optic nerve damage holds true for high pressure glaucoma. METHODS: The study comprised nine eyes of nine rhesus monkeys (Macaca mulatta) with a mean age of 17.7 (SD 3.1) years (range 13-23 years). Experimental glaucoma was produced by multiple applications of argon laser to the trabecular meshwork. Applanation tonometry was regularly performed and fundus photographs, which were taken serially, were used for retinal nerve fibre layer (RNFL) assessment and morphometric optic disc analysis. Six monkeys, in which arterial hypertension and atherosclerosis had additionally been induced several years before elevation of intraocular pressure, did not show any sign of diffuse loss or localised defects of the RNFL before initiation of glaucoma. RESULTS: Compared with the same eyes at baseline, localised RNFL defects had developed in eight (89%) eyes. It included all three eyes (100%) of the monkeys without arterial hypertension/arteriosclerosis, and five of the six monkeys (83%) with arterial hypertension/arteriosclerosis. Four eyes had multiple localised RNFL defects. In all eyes, diffuse RNFL loss was additionally present. CONCLUSIONS: Besides diffuse loss of RNFL, localised RNFL defects were present in almost all eyes of monkeys with chronic experimental high pressure glaucoma. Challenging the concept that a mostly diffuse type of optic neuropathy occurs in high pressure glaucoma, the results suggest that, in high pressure glaucoma, at least a mixture of localised and diffuse pattern of optic nerve damage prevails.     

Accommodative facility training with a long term follow up in a sample of school aged children showing accommodative dysfunction

The primary aim of this project was to study the effect of flip lens-training on the accommodative function in a group of children with accommodative dysfunction and subjective symptoms such as asthenopia, headache, blurred vision, and avoidance of near activity. We also wanted to measure the accommodative facility among the children in comparison with a control group. Another aim of the study was whether flip lens-training increased accommodative facility, and to find out if it also had a positive effect on their asthenopia and related problems also in long term. Following the training period the accommodative facility and accommodative function significantly increased and two years after finishing the training period no child had regained any subjective symptoms and the objective findings were almost the same as at the end of facility training period. These results suggest that accommodative facility training is an efficient method built on loss of symptoms among children with accommodative infacility. This revised version was published online in July 2006 with corrections to the Cover Date.     

Development of receptoral responses in pigmented and albino guinea-pigs (Cavia porcellus)

We describe the postnatal development of the electroretinogram (ERG) receptoral response in the guinea pig. In addition, the time course and nature of maturation was compared between albino and pigmented strains to consider the role that melanogenesis might have in this process. Electroretinograms were collected on groups of albino and pigmented animals from postnatal day (PD) PD1 to PD60. A-wave amplitudes and implicit times were extracted from filtered data (0–75 Hz). Receptoral components were modelled using the delayed gaussian model of Hood and Birch [1] fitted as an ensemble to the raw data. Guinea pigs show saturated amplitudes (Rm_P3) that are 50% of adult values at birth, these mature by PD12. Receptoral delay (t_d) also undergoes some postnatal maturation, while phototransduction gain (log S) is adult-like at birth. Albino animals had significantly (p<0.05) larger Rm_P3 and log S across all ages. Guinea pigs have significant postnatal development in their receptoral response. Maturation of Rm_P3 implies a postnatal increase in rod outer segment length. Whereas the adult values of log S implies a mature phototransduction process at birth. We argue that the likely cause for the larger log S of albino eyes is compatible with theories of increased levels of internal light. Whereas the larger Rm_P3, even after allowing for increased light effectiveness, may reflect a lower ocular resistance in albino eyes due to their lower levels of melanin. Furthermore, decreased Rm_P3 and log S with age is observed in the pigmented group only and is consistent with increased ocular resistance due to melanin development in this strain. This revised version was published online in July 2006 with corrections to the Cover Date.     

Reliability of Doppler color flow mapping in the identification and localization of multiple ventricular septal defects

The purpose of this study was to compare Doppler color flow mapping with angiography and surgical observation for detection of multiple ventricular septal defects (VSDs). Only patients with elevated pulmonary ventricular pressure were included. Among 137 patients with VSDs, 38 multiple defects were identified in 25 patients echocardiographically, 34 multiple defects in 24 patients angiographically, and 21 multiple defects in 17 patients surgically. Using surgical observation as the reference standard, the sensitivity of echocardiography for identifying patients with multiple VSDs was 17 of 17 (100%) and for angiography 15 of 17 (88%). The sensitivity of echocardiography for identifying all multiple VSDs seen at operation was 19 of 21 (90%) and of angiography was also 19 of 21 (90%). In many patients, use of both techniques may no longer be necessary.     

Pharmacokinetics of methotrexate in leukemia cells: Effect of dose and mode of injection

A lumped compartmental model has been derived to predict methotrexate concentration as a function of time for L1210 cells in BD2F ₁ female mice at doses ranging from 3 mg/kg to 400 mg/kg. Using standard methods of parameter estimation as well as experimental determinations, an integrated approach was derived to account for the differences between the subcutaneous (s.c.) and intraperitoneal (i.p.) modes of injection. It was found that a single generalized forcing function can be used to fit plasma concentration after s.c. injection for all doses. Adequate fits (average error<20% while the standard deviation of experimental determinations was±22%) of L1210 cell data after s.c. injection were obtained. The best results were for a maximum facilitated influx constant V_max of 0.424 g/min/ml, a Michaelis influx constant K_m of 1,42 g/ml, and a first-order efflux constant of 0.047 min^–1.The model simulations were not sensitive to V_max, K_m,and so long as the ratio V_max/was approximately 9g/ml. The values of V _max ,K _m ,and which were obtained from our analysis of the in vivodata can be explained on the basis of previously performed in vitroexperiments. The parameters obtained from modeling the s.c. data were then applied for i.p. injection data. The resulting fits were adequate (average error<20% while the standard deviation of experimental determinations was±22%). A single generalized forcing function for drug concentration in the peritoneal cavity after i.p. injection for all doses was derived. The application of these results enables the prediction of methotrexate concentration in neoplastic cells at other doses after either s.c. or i.p. injection.     

Pets for the mentally ill

After studying the historical importance of the domestic animal through the ages and the role of the "pet" animal in the contemporary world, the authors present an analysis of the literature dealing with the function of the animal in child development and the use of animals as therapeutic "tools". The author's then consider, based on a series of observations, the relationship certain mentally ill patients may establish with one or several pet animals and the significance this object relation may have for the patient : animals become invested as counter depressive or delusional objects, auxiliary means for identification and projection, symbiotic relationship, as well as encouraging feeling of security and responsibility.     

Interleukin-2 and interferon-alpha2b as a daily alternating schedule in advanced renal cell cancer

Summary Interferon-alpha (IFN-) and interleukin-2 (Il-2) are effective as single agents in metastatic renal cell cancer (RCC) with response rates of 15–30%. Additionally, IFN- is assumed to act synergistically with Il-2 in the induction of lymphokine-activated killer cells. (LAK cells) in vitro. With the aims of increasing the response rate by combining both cytokines and of reducing side effects, we started a clinical trial with a daily alternating schedule of 10×10⁶ units/m² s.c. rIFN-_2b (Essex, Munich, FRG) and 3×10⁶ Cetus units/m² rIL-2 (EuroCetus, Frankfurt, FRG) in the form of 1 h infusions over a period of 14 days. Patients found to have progressive disease after two cycles of therapy were withdrawn from the study; patients with stable disease or better received two further cycles.Of the 27 patients included in the study, 22 (16 male, 6 female) are evaluable for response. In 1 patient with multiple pulmonary metastases complete remission was achieved, in 5 patients partial remission, and in 2 a minor response. The schedule was practicable; the main side effects were influenza-like symptoms, fatigue and hypotension. Some patients suffered from arthralgias and erythemas up to 3 weeks after finishing the therapy cycle. On the whole, the side effects seem to be less severe than those arising from schedules using continuous Il-2 infusions.This work was supported by Grant No. 01GA8802 of the Bundesministerium für Forschung und Technologie (BMFT)