Neonatal hearing screening--consequences for public health policy

In Germany 1-2 of every thousand newborns suffer from severe hearing impairment. The fatal consequences of this irreversible condition are avoidable only if therapy is started as early as possible--according to current US-American recommendations before the age of 6 months. In Germany children even with severe hearing loss are identified only when they are 21 months old (average figure). Universal hearing screening before the age of 3 months could be a useful measure to reduce the mean age of children at the time of diagnosis and so to give them a chance of an early and promising therapy. In the USA this has been recommended by the National Institute of Health since 1993.     

Pharmacological evaluation of a modified conflict procedure: punished drinking in non-water-deprived rats

Rationale: Conflict procedures used to detect anxiolytic-like activity of drugs often rely on maintaining strict schedules of water or food availability. It is ethically and practically desirable to reduce such states of deprivation in animal testing. Objective: The purpose of the present experiment was to develop and pharmacologically characterize a conflict drinking procedure that did not require the use of water-deprived animals. Methods: Rats were tested during daily sessions with alternating unpunished drinking (no tone: lick=sucrose solution) and signaled punished drinking (tone: lick=sucrose+shock) components, and developed individual steady baselines over a brief training period (approximately 3–4 weeks). The drugs tested i.p. were the positive allosteric modulators of γ-amino butyric acid_A (GABA)_A receptors, diazepam (0.03–30 mg/kg), chlordiazepoxide (0.03–30 mg/kg), lorazepam (0.03–10 mg/kg), zolpidem (0.3–10 mg/kg), pentobarbital (1–30 mg/kg), pregnanolone (1–30 mg/kg), and bretazenil (0.03– 10 mg/kg); the 5-hydroxy tryptamine_1A (HT)_1A-mediated anxiolytics, buspirone (1–10 mg/kg) and ipsapirone (1–17 mg/kg); and the negative controls d-amphetamine (0.3–3 mg/kg), haloperidol (0.01–0.3 mg/kg), morphine (0.3–17 mg/kg), and imipramine (0.3–30 mg/kg). Results: The experimental procedure was sensitive to increases in punished drinking by the GABA_A-positive modulators, consistent with their known or putative anxiolytic activity. Further, the 5-HT_1A-mediated anxiolytics increased punished drinking, although to a lesser extent and over a more narrow dose range than did the GABAergic drugs. In contrast, d-amphetamine, haloperidol, morphine, and imipramine failed to increase punished drinking up to doses that decreased unpunished drinking. Conclusions: The present results indicate that water deprivation is not a necessary condition to engender drinking conflict behavior or to obtain pharmacological effects similar to those obtained with other classical conflict procedures. Received: 23 November 1998 / Final version: 15 March 1999     

Expression of endothelial cell-derived nitric oxide synthase (eNOS) is increased during gastric adaptation to chronic aspirin intake in humans

BACKGROUND: Gastric adaptation to aspirin is well-documented. However, the mechanisms underlying the reduction of aspirin-induced mucosal damage despite continued ingestion of the drug remain poorly understood. METHODS: Eight healthy volunteers who received aspirin 1 g b.d. for 14 days were compared with eight placebo-dosed controls. Gastroscopy with mucosal biopsy was performed, and gastric mucosal blood flow was measured before and following 3, 7 and 14 days of aspirin treatment. At the same time points, tissue concentration and the content of prostaglandin E2 in the gastric juice were determined and expression of endothelial cell-derived nitric oxide synthase (eNOS) in mucosal biopsies was measured using Western blot analysis. RESULTS: Aspirin-induced mucosal damage that reached a maximum on day 3, declining significantly by day 14. Concomitantly, mucosal blood flow significantly increased on day 3 and returned to initial values on day 14. Aspirin intake led to a significant decrease in prostaglandin E2 concentration in the gastric mucosa and in gastric juice during the whole period of aspirin consumption. eNOS expression started to increase on day 7 in oxyntic mucosa and on day 3 in antral mucosa, reaching its highest values at the end of the consumption of aspirin. CONCLUSIONS: The human gastric mucosa adapts to prolonged aspirin intake, and this is accompanied by an increase in mucosal blood flow and reduced prostaglandin synthesis. Increase of mucosal eNOS expression might compensate for reduced prostaglandin synthesis and be responsible for gastric adaptation to chronic aspirin intake in humans.     

Assessment of left ventricular function: comparison between radionuclide angiography and semiquantitative two-dimensional echocardiographic analysis

Measurement of global left ventricular function is important in the follow-up of cardiac patients and is a good prognostic indicator in acute cardiac situations. We compared quantitative measurements of global left ventricular function made with radionuclide angiography (RNA) and contrast cardiac ventriculography (CVG) to visual semiquantitative estimates from two-dimensional echocardiographic images (2D-echo). Three hundred and thirty-nine consecutive patients who underwent RNA were assessed with 2D-echo within 3 months. In addition, 92 of these patients also underwent CVG (correlation of ejection fraction between CVG and RNA:r=0.82;P<0.0001). The RNA mean ejection fractions in the four 2D-echo groups (0=normal, 1=slightly, 2=moderate, or 3=severe reduced left ventricular function) differed markedly (P<0.0001); however, there was overlapping among the groups (2D-echo score/RNA ejection fraction: 0=57.3%±12.8%; 1=46.0%±12.9%; 2=29.6%±12.2%; and 3=24.6%±11.5%) and the difference between 2D-echo scores 2 and 3 was not significant. 2D-echo showed a good concordance in RNA classes (0=505; 1=35%–49%; 2=21%–34%; and 3=520% ejection fraction) 0 (133/166; 80%) and 3 (18/30; 60%) but low concordance in classes 1 (27/82; 33%) and 2 (21/61; 34%). For accurate assessment of global left ventricular ejection fraction, visual semiquantitative judgement of a 2D echocardiographic image is limited in comparison to CVG or RNA, especially in patients with a slight or moderate reduction in left ventricular ejection fraction.     

Radical cystectomy with or without adjuvant polychemotherapy for non-organ-confined transitional cell carcinoma of the urinary bladder: Prognostic impact of lymph node involvement

Objectives

To analyze the effectiveness of adjuvant polychemotherapy after radical cystectomy for nonorgan-confined transitional cell bladder cancer (Stages pT3b, pT4a, and/or pN1 or pN2).

Methods

Of 166 consecutive patients undergoing cystectomy at two institutions from 1987 to 1993, 80 received adjuvant polychemotherapy with methotrexate, vinblastine, and cisplatin plus doxorubicin (MVAC) or epirubicin (MVEC), whereas 86 had cystectomy only. The patients were evaluated for relapse-free survival and length of progression-free interval on the basis of follow-up data obtained in 1995 and 1996.

Results

Kaplan-Meier analysis revealed a significantly higher progression-free rate for patients after adjuvant chemotherapy (P=0.0002, log-rank test). With and without adjuvant chemotherapy, prognosis declined in a stepwise manner, depending on the extent of lymph node involvement. Nevertheless, the superior prognosis of the chemotherapy group could be demonstrated at each lymph node stage. Of the 166 patients, 49 had initially entered a prospective trial comparing adjuvant with no adjuvant treatment. That study was discontinued in December 1990 after an interim analysis revealed a significant prognostic advantage in favor of the 26 patients randomized to receive chemotherapy compared with the 23 control patients. Current follow-up data continue to demonstrate a significant improvement in progression-free survival in favor of patients randomized to receive adjuvant chemotherapy (P=0.0040). The follow-up period of patients living free of disease ranges from 58 to 96 months.

Conclusions

Adjuvant chemotherapy with MVAC/MVEC leads to significant prolongation of relapse-free survival and improvement of the definitive cure rate after radical cystectomy for locally advanced transitional cell carcinoma of the urinary bladder.     

Peri-operative elastase-α-1 proteinase inhibitor in patients with postoperative intervertebral discitis

Summary In a prospective study of 251 patients operated upon for lumbar disc herniation it has been investigated whether the preoperative and early postoperative values of Elastase--1 Proteinase Inhibitor (EPI) — an indicator of inflammatory processes — and C-reactive Protein (CRP) — a well known predictor of some postoperative complications — were correlated to the later development of discitis. Postoperatively discitis developed in 14 patients. A randomly choosen group of 15 complication-free patients out of the total of 251 cases was used as control group.Elevated EPI plasma values, especially in the pre-operative and first postoperative days, turned out to be significantly related to the likelyhood of later discitis development, but no such relation for the CRP plasma values could be established. Thus and early prediction of patients at risk for this complication seems to be possible by pre- and postoperative measurement of EPI. It could be justified —but its usefulness has yet to be proven — to give antibiotics prophylactically and other anti-inflammatory medication in patients with elevated pre- and postoperative EPI values.     

Clinical aspects and therapy of spontaneous under-anticoagulants-occurring intramural intestinal hemorrhages]

Massive spontaneous "anticoagulant" hemorrhage in the bowel wall may cause an acute abdomen with signs of intestinal obstruction within a few hours. An operative revision is indicated if a barium study is not possible to secure this rare diagnosis and therefore other much commoner causes of an acute abdominal illness are not to be excluded. While out of 42 patients, in whom the hemorrhagic segment was resected, only two died as a probable result of the operation, several cases are known where a survival without laparotomy was unimaginable. The dangers of a laparotomy should not, therefore, be overemphasized.     

Increased susceptibility of aged rats to hepatocarcinogenesis by the peroxisome proliferator nafenopin and the possible involvement of altered liver foci occurring spontaneously

We investigated the mechanism of the hepatocarcinogenic action of nafenopin (NAF), a nongenotoxic peroxisome proliferator. Groups of male rats aged 13 wk (designated "young") or 57 wk (designated "old") were fed NAF for 13 mo; additional groups received a basal diet or a phenobarbital (PB)-containing diet as positive control. The following results were obtained. (a) NAF produced numerous hepatocellular adenomas and carcinomas in old animals but very few in young animals. A similar result, although less pronounced, was seen with PB. Adenomas of PB-treated groups mostly consisted of eosinophilic and glycogen-storing cells. However, adenomas and carcinomas of NAF-treated livers were composed of weakly basophilic cells. (b) Phenotypically altered foci, evaluated in hematoxylin:eosin-stained sections, appeared spontaneously in untreated livers. The majority of these foci was either of the eosinophilic-clear cell or the tigroid cell type. In addition, we identified foci which are characterized by weak, diffuse cytoplasmatic basophilia. Their phenotype was similar to that of adenomas and carcinomas in NAF-treated rats. The number and size of eosinophilic-clear cell and of tigroid cell foci increased considerably with the age of the animals. At the end of the experiment, approximately 2.4% of liver tissue was occupied by focal cells. NAF, but not PB, treatment led to a selective increase in number and size of weakly basophilic foci. This subtype has previously been described as a likely precursor lesion for liver tumors induced by an aflatoxin B1-NAF initiation-promotion regimen (B. Kraupp-Grasl et al., Cancer Res., 50:3701-3708, 1990). These findings suggest that the peroxisome proliferator NAF leads to tumor development in aging rat liver by promotion of spontaneously occurring preneoplastic lesions. The type of lesion appears to be different from that promotable by PB.     

Comparative morphological studies on the incorporation of various cementless implanted artificial patellas]

Twelve uncemented, artificial patellar components clinically and radiologically without signs of loosening after an implantation period of 9-48 Months were investigated histologically and microradiographically. The components correspond to the system GSB-"old", GSB-"new", PCA and APS. Within the observed implantation period the artificial patellar components GSB-"old", GSB-"new" and PCA showed severe patho-morphological changes of the surrounding tissue and point to loosening. The dowel system according to APS shows after the longest period of time of 14 Months morphologically a fully bony encasement with wide spread direct contacts between the living bone and the metallic Titanium surface. The observation points urgently to the fact, that Polyethylene must not be in direct contact with the bony bed. On the basis of the patho-morphological reactions a partial armament of the polyethylene surface with metallic structures must be rejected as a general principle.     

Infection of the shunt system in children treated for hydrocephalus

From 1983 to 1988 25 infected shunt systems were found in 205 hydrocephalic children. Four children were treated successfully with antibiotics given into the shunt system and intravenously. Seventeen shunt systems had to be removed and Rikham reservoir or external drainage implanted. Antibiotics were given both into the ipsilateral ventricle and intravenously. In four children with "low dynamic" hydrocephalus the shunts were removed and antibiotics were given intravenously only. Six patients died, in eight neurological impairment developed.