Laminin-6 and laminin-5 are recognized by autoantibodies in a subset of cicatricial pemphigoid

To aid treatment choice in early stage of Hodgkin's disease, we analysed patients registered in the IDHD Database with clinical stages I or II Hodgkin's disease who were not staged with laparotomy and whose initial treatment was with radiotherapy alone. The factors analysed for outcome after first relapse included initial stage, age, sex, histology, number of involved areas, mediastinal involvement, E-lesions, B-symptoms, erythrocyte sedimentation rate, alkaline phosphatase, serum albumin and haemoglobin. As well as presentation variables, we analysed the disease-free interval after initial radiotherapy and the extent of disease at relapse. A total of 1364 patients with clinical stage I or II Hodgkin's disease were treated with initial radiotherapy, of whom 473 relapsed. The probability of survival 10 years after relapse was 63%. For cause-specific survival (CSS), both multivariate and univariate analysis identified the importance of age at presentation and histological subtypes. When all causes of death were considered, the multivariate analysis identified age as the only significant factor. The length of initial disease-free interval had no influence on prognosis after relapse, but the 169 patients with nodal relapse had a higher cause-specific survival than those with an extranodal component of relapse (74% versus 51% at 10 years, P < 0.005). Thus, the important factors for outcome after initial treatment with radiotherapy are those factors predicting the risk of relapse after initial treatment together with those predicting outcome after relapse, namely age, histologic subtype and extent of disease at relapse.     

Inhibition of Listeria monocytogenes on cold-smoked salmon by nisin and carbon dioxide atmosphere

The heat-stable enterotoxin of Escherichia coli binds to an intestinal receptor, guanylyl cyclase-C, and produces cGMP to induce diarrhea. Guanylin is an endogenous ligand of this receptor. In the present in vivo study, the intestinal water and ion secretion induced by mucosal application of 2 nmol/ml guanylin or 5 or 10 units/ml heat-stable enterotoxin into closed loops was compared in the rat. The characteristics of secretion induced by cAMP following intravenous perfusion of 1.2 nmol/100 g per h vasoactive intestinal peptide were compared to those induced by cGMP. Unidirectional Na+ and Cl- fluxes were estimated by addition of 22Na into the loop and i.v. injection of 36Cl. Guanylin induced less water and ion secretion than that produced by heat-stable enterotoxin in the colon, confirming the results of in vitro studies, and also in duodenum and ileum. The cAMP- or cGMP-mediated response had a similar pattern, i.e., an inhibition of Na+ absorption and an increase in anion secretion.     

Bilateral lower limb oedema due to a distended urinary bladder

A 91-year-old Chinese man developed bilateral lower limb oedema due to venous obstruction resulting from a distended urinary bladder. After the bladder was decompressed by urethral catheterisation, the bilateral lower limb oedema promptly subsided. Although a distended urinary bladder is a rare cause of bilateral lower limb oedema, it can be easily recognised by palpation of the lower abdomen and the relief of symptoms by urethral catheterisation is most rewarding.     

Usefulness of ictal and interictal 99mTc ethyl cysteinate dimer single photon emission computed tomography in patients with refractory partial epilepsy

OBJECTIVE: The aim was to investigate the feasibility of recording the electrical auditory brain stem response (EABR) evoked by electrical stimulation at the promontory (Prom-EABR) as a tool to assist selection of the ear for cochlear implantation in young children. STUDY DESIGN: The study group consisted of young children for whom the decision to proceed with implantation with the Nucleus mini 22-channel cochlear implant (Cochlear (UK) Ltd., London, UK) had already been made. SETTING: The Prom-EABR was recorded after the children had been anesthetised, but before the start of surgery. PATIENTS: A group of 25 children (11 boys and 14 girls), whose age at implantation ranged from 2 years 11 months to 6 years 8 months (mean age, 4 years 5 months), were investigated. INTERVENTION: Recordings of the Prom-EABR were used to determine which ear would receive the cochlear implant, providing there were no preexisting contraindications regarding selection of the ear. MAIN OUTCOME MEASURE: It has been suggested from earlier studies that the characteristics of the amplitude input/output (I/O) function of the EABR are related to neuronal survival. If the ear with the "better" I/O function is chosen for implantation, it might be expected that these children will perform better on average than those in whom the ear has been selected at random. RESULTS: Reliable recordings of the Prom-EABR were achieved in 40 ears (80%) of the 50 ears in the study. In 20 of the 25 children the technique was actively employed for selection of the ear for implantation. CONCLUSIONS: Recording of the Prom-EABR in the operating theater is a viable technique. Future analysis of long-term outcome measures of performance with the implant will confirm or dispute the benefit of ear selection using the Prom-EABR.     

Variability in cytotoxicity and fluoride release of resin-modified glass-ionomer cements

New-generation glass-ionomer cements contain resin to improve their restorative properties. These resin-modified glass-ionomer cements vary considerably in their chemistry, which could result in corresponding variability in their physical and biological properties. This study investigated the cytotoxicity and the fluoride release of two resin-modified glass ionomers, a conventional glass-ionomer cement, and a resin composite. Samples were prepared and extracted in distilled water for 1, 4, and 7 days; eluates were filtered and tested by means of 3T3 mouse fibroblasts. Cytotoxicity (MTT assay) values were low for all materials and extraction times, indicating minimal cytotoxicity of all materials (less than 30% inhibition). Cytotoxicity of one resin-modified glass ionomer was significantly higher than for the other materials (p < 0.001). One resin-modified glass ionomer and the conventional glass-ionomer cement released significantly more fluoride at each time interval (p < 0.001) than the other resin-modified glass-ionomer cement and the resin composite. Fluoride release and cytotoxicity were correlated (r2 = 0.60; p < 0.001), although the fluoride release does not account for the cytotoxicity observed. Cytotoxicity and fluoride release suggest that one hybrid behaved more like a conventional glass ionomer, and the other like a resin composite. These differences may have implications for material selection in specific clinical situations.     

Competency or incompetency--the dilemma

RATIONALE AND OBJECTIVES: Simplifying data collection and analysis should promote utilization management in review of examinations of the small bowel in the general practice. METHODS: A case control format with the generation of an odds ratio to answer sets of binary questions derived from annual examination data is shown. The positive examination results applied were compared with the literature as a cross-checking mechanism. The examination identified as most likely to be positive was recommended prospectively in a protocol for the following year. Two of 5 years are illustrated to emphasize the development of the methodology. RESULTS: Application of this model in testing its validity, since 1990 at Madigan Army Medical Center, allows for the generation of a new protocol each year to prospectively improve clinical definition. CONCLUSIONS: A 5-year analysis of small bowel examination protocols, subdivisions, and odds ratios, will be forthcoming. The 2 years illustrated show how strongly our practice was influenced in using enteroclysis or in using the small bowel follow through as the examination of choice in the various clinical categories of small bowel disease: (1) practice was influenced by protocol and (2) outcome was steered toward positive examinations.     

Pharmacokinetics of hyperimmune anti-human immunodeficiency virus immunoglobulin in persons with AIDS

Hyperimmune anti-human immunodeficiency virus immunoglobulin (HIVIG) is an intravenous immunoglobulin prepared from HIV-infected asymptomatic donors with a CD4 cell count greater than 400 cells/microl and a high titer of antibody to HIV-1 p24 protein. Twelve persons with AIDS received four doses of HMG (two at 50 mg/kg of body weight and then two at 200 mg/kg) every 28 days. Pharmacokinetics were evaluated by measurement of anti-p24 antibody. HIVIG was well tolerated, and all participants completed the study. Three subjects who were not receiving Pneumocystis carinii pneumonia (PCP) prophylaxis developed PCP. The mean value for HIVIG clearance was 3.02 ml/kg/day at 50 mg/kg and 3.65 ml/kg/day at 200 mg/kg (P = 0.027); the mean trough antibody titers (reciprocal units) were 1,442 and 4,428, respectively. This study indicates that high titers of anti-p24 antibody can be maintained with a monthly administration schedule of HIVIG and that short-term safety is acceptable. Comparisons to evaluate the therapeutic potential of HIVIG are justified.     

Evidence that levels of presenilins (PS1 and PS2) are coordinately regulated by competition for limiting cellular factors

Mutations in two related genes, PS1 and PS2, account for the majority of early onset cases of familial Alzheimer's disease. PS1 and PS2 are homologous polytopic membrane proteins that are processed endoproteolytically into two fragments in vivo. In the present report we examine the fate of endogenous PS1 and PS2 after overexpression of human PS1 or PS2 in mouse N2a neuroblastoma cell lines and human PS1 in transgenic mice. Remarkably, in N2a cell lines and in brains of transgenic mice expressing human PS1, accumulation of human PS1 derivatives is accompanied by a compensatory, and highly selective, decrease in the steady-state levels of murine PS1 and PS2 derivatives. Similarly, the levels of murine PS1 derivatives are diminished in cultured cells overexpressing human PS2. To define the minimal sequence requirements for "replacement" we expressed familial Alzheimer's disease-linked and experimental deletion variants of PS1. These studies revealed that compromised accumulation of murine PS1 and PS2 derivatives resulting from overexpression of human PS1 occurs in a manner independent of endoproteolytic cleavage. Our results are consistent with a model in which the abundance of PS1 and PS2 fragments is regulated coordinately by competition for limiting cellular factor(s).     

Whole-body kinetics and dosimetry of L-3--123I-iodo-alpha-methyltyrosine

BACKGROUND: Desflurane anesthesia can produce cerebral metabolic depression and increase cerebral blood flow. We evaluated the effect of desflurane on brain tissue oxygen pressure (PO2), carbon dioxide pressure (PCO2) and pH during neurosurgery. METHODS: Following a craniotomy, the dura was opened and a Paratrend 7 sensor, which measures PO2, PCO2, pH and temperature, was inserted into brain tissue. In 6 control patients in group 1, anesthesia was maintained constant with 3% end-tidal desflurane over 60 min, including a 30-min stabilization period. In group 2, 9 patients were ventilated with 3% desflurane under baseline conditions. After a 30-min stabilization period, baseline tissue gases and pH were measured and end-tidal desflurane was increased to 6% and then 9% for 15-min intervals. Mean arterial pressure (MAP) was maintained with intravenous phenylephrine. RESULTS: Under baseline conditions, cardiovascular and brain tissue measures were similar between the 2 groups. Increasing end-tidal desflurane from 3% to 9% produced burst-suppression EEG in all patients and significantly increased tissue PO2 and pH and decreased PCO2. No parameters changed significantly in the control group during steady-state anesthesia. CONCLUSION: These results show that 9% desflurane can improve brain tissue metabolic status before temporary brain artery occlusion if cerebral perfusion pressure is maintained. This may be particularly important in patients with symptoms of ischemia before surgery.