Association of an interleukin-1beta genetic polymorphism with altered brain structure in patients with schizophrenia.

OBJECTIVE: This study investigated the effect on brain morphology of an interleukin-1beta genetic polymorphism (C-->T transition at position -511) in patients with schizophrenia. METHOD: In vivo magnetic resonance imaging and genotype analysis were used in the examination of 44 male schizophrenic patients and 48 healthy male comparison subjects. RESULTS: No association between the interleukin-1beta polymorphism and schizophrenia was detected. Within the patient group, bifrontal-temporal gray matter volume deficits and generalized white matter tissue deficits in allele 2 carriers (genotype T/T or C/T) were found. In contrast, the interleukin-1beta polymorphism had no influence on brain morphology within the healthy subjects. CONCLUSIONS: The data suggest that allele 2 within the promoter region of the interleukin-1beta gene at position -511 contributes to structural brain alterations in patients with schizophrenia.

Evaluation of different recording parameters to establish a standard for flash electroretinography in rodents.

Different electrodes and stimulus protocols commonly used for electroretinography in rodent eyes were compared for convenience of use, degree of damage to corneal epithelium, and for magnitude of amplitude, reproducibility, left versus right eye accuracy, and reliability of recorded parameters of the flash electroretinogram (ERG). Adult C57BL/6 pigmented mice and albino Wistar rats were used to determine scotopic ERGs in response to Ganzfeld or strobe-light stimulation and light-adapted (photopic) ERGs recorded from both eyes at the same time. Test-retest data were used for statistical analyses to compare a monopolar gold-wire contact lens electrode (CLE), a cotton-wick silver-silver chloride electrode (CSCE), a DTL fiber electrode (DTLE), and a circular stainless steel wire electrode (SSE). Corneas were evaluated for abrasion after ERG recordings using fluorescein staining and also for the time taken, ease of insertion, and re-insertions required for the different electrodes. Compared to CSCE, DTLE, and SSE, the ERG potentials recorded by CLE had significantly larger scotopic amplitudes and oscillatory potentials under strobe or Ganzfeld stimulation and for light-adapted ERG b-wave amplitudes in both mice and rats. In analyzing test-retest data of scotopic ERG a-wave and b-wave amplitudes, the intraclass correlation coefficient showed the best agreement for the CLE (range 0.61-0.94) compared to the SSE (0.13-0.77), DTLE (0.02-0.69), and CSCE (0.12-0.51). In mice and rats, logistic regression analyses revealed significant correlations for amplitudes of most scotopic ERG parameters between contralateral eyes obtained with CLE and for some ERG components recorded by SSE. When comparing ERG amplitudes for stimulation by strobe or Ganzfeld, the difference was least with the CLE compared to DTLE, CSCE, or SSE. The time taken to insert the four different electrodes was greatest for the CLE in both mice and rats. The extent of corneal abrasion resulting from electrode use in mice was largest for the SSE followed by the CLE. However, in rats there was almost no corneal damage after ERG recordings with the CLE. Because of the stability of eye contact, the CLE allows ERGs to be determined over a longer recording session. Recording of scotopic and photopic (light-adapted) ERGs in rodents with monopolar gold-wire contact lens electrodes provides greater amplitudes and higher reproducibility when compared to other commonly used corneal electrodes. These electrodes are significantly better overall than others that were evaluated and should be considered for a standard protocol to monitor retinal function in rodent eyes.

Electroretinographic abnormalities in a rat glaucoma model with chronic elevated intraocular pressure.

The purpose of this study was to determine the ability of electroretinographic (ERG) measurements to document progression of the retinopathy in a rat glaucoma model. Thirty four rats with a chronic intraocular pressure (IOP) elevation induced in one eye by cautery of three episcleral/extra-orbital veins were studied in four separate groups. ERGs were recorded sequentially in Group A rats (n = 12) at baseline, and after approximately 20, 40 and 60 days of high IOP, and in three additional groups of rats (n = 6 or 10 per group) after approximately 58, 30 and 175 days of high IOP, respectively. Scotopic ERG parameters recorded simultaneously from both eyes in Group A rats were: a- and b-wave amplitudes, implicit times, oscillatory potential amplitudes (OPs) determined at three different light-flash intensities, and the light-adapted (photopic) ERG b-wave amplitude. In the other groups of rats, only scotopic ERG a-wave, b-wave and OP amplitudes were measured.In Group A rats that were followed sequentially, all the ERG parameters recorded with attenuated stimuli showed significant time-dependent changes in glaucomatous eyes relative to their contralateral normal eyes, with OPs showing the earliest significant difference after only 3 weeks of high IOP. When different groups of unilateral glaucomatous rats were compared beyond 8 weeks of elevated IOP only the OPs showed a continued decrease with time and good discrimination between glaucoma and normal eyes. Over a 25 week period of high IOP the scotopic OPs measured with attenuated light stimuli declined at the rate of approximately 1.5% per week and provided the best ERG measure to monitor progression of retinal pathophysiology in the vein-occlusion rat glaucoma model.

Retinal morphology and ERG response in the DBA/2NNia mouse model of angle-closure glaucoma.

PURPOSE: To document the time course of retinal dysfunction by scotopic electroretinography (ERG) and by quantitative morphology in eyes of the DBA/2NNia substrain of mouse (DBA) with inherited angle-closure glaucoma. METHODS: DBA and control C57BL/6J (C57) mice were studied by ERG recordings from 5 to 15 months of age, and by morphology from 1 to 14 months of age. Scotopic ERGs were simultaneously recorded from both eyes of dark-adapted anesthetized mice. Changes in the central neuronal retina were evaluated by quantitative morphometry performed on serial semithin sections of Epon-embedded eyes. RESULTS: When compared with normal C57 mice, DBA mice showed significant reductions of the a-wave and b-wave amplitudes by 7 to 8 months, and the decline continued as the animals aged. The b-wave implicit time in DBA mice showed a gradual prolongation beginning at 8 months of age, when compared with C57 mice. Logistic regression analyses revealed significant correlations in a- and b-wave amplitude reductions between ipsilateral and contralateral eyes of DBA mice at ages when ERG parameters were greatly altered. Morphologically, thinning of the whole retina was already evident in DBA mice at 4 months of age, but loss of ganglion cells and thinning of the outer plexiform layer were first seen in 7- to 8-month-old animals. These changes progressed to the end of the 13-month period studied. CONCLUSIONS: Progressive thinning of the outer retinal layers in DBA mice was found to correlate with decreases in ERG a- and b-wave amplitudes, both occurring from the age of 7 to 8 months onward. Similarities with the findings in human late-stage glaucomatous retinopathy indicate the relevance of this animal model in further glaucoma research.

Adhesio interthalamica in male patients with schizophrenia.

OBJECTIVE: The authors investigated whether absence of the adhesio interthalamica in patients with schizophrenia constitutes a marker of early developmental neuropathological changes. METHOD: Thirty male patients with schizophrenia and 30 healthy male subjects were recruited for study. Magnetic resonance imaging was performed, and the presence or absence of the adhesio interthalamica was determined for each subject. The length and volume of the third ventricle were also measured. RESULTS: No differences in the presence or absence of the adhesio interthalamica were found between patients with schizophrenia and normal comparison subjects. Patients without the adhesio interthalamica had significantly higher scores for negative symptoms than patients with the adhesio interthalamica. There was no correlation between absence of the adhesio interthalamica and length and volume of the third ventricle in either patients or comparison subjects. CONCLUSIONS: The findings suggest that patients with schizophrenia who do not have the adhesio interthalamica are characterized by more severe negative symptoms.

Precision of tibial cartilage morphometry with a coronal water-excitation MR sequence.

The aim of this study was to analyze the precision of tibial cartilage morphometry, by using a fast, coronal water-excitation sequence with high spatial resolution, to compare the reproducibility of 3D thickness vs volume estimates, and to test the technique in patients with severe osteoarthritis. The tibiae of 8 healthy volunteers and 3 patients selected for total knee arthroplasty were imaged repeatedly with a water-excitation sequence (image time 6 h 19 min, resolution 1.2 x 0.31 x 0.31 mm(3)), with the knee being repositioned between each replicate acquisition. After 3D reconstruction, the cartilage volume, the mean, and the maximal tibial cartilage thickness were determined by 3D Euclidean distance transformation. In the volunteers, the precision of the volume measurements was 2.3 % (CV%) in the medial and 2.6 % in the lateral tibia. The reproducibility of the mean cartilage thickness was similar (2.6 and 2.5 %, respectively), and that of the maximal thickness lower (6.5 and 4.4 %). The patients showed a considerable reduction in volume and thickness, the precision being comparable with that in the volunteers. We find that, using a new imaging protocol and computational algorithm, it is possible to determine tibial cartilage morphometry with high precision in healthy individuals as well as in patients with osteoarthritis.

Comparisons of the amplitude size and the reproducibility of three different electrodes to record the corneal flash electroretinogram in rodents.

To compare corneal electrodes commonly used in rodent eyes for repeat and left versus right eye accuracy and variability to record the flash electroretinogram (ERG). Animals studied were eight C57BL/6 mice and eight rats of the Wistar strain. Scotopic ERGs were recorded from eyes of dark-adapted anesthetized rodents to compare a custom-made gold-wire contact lens electrode (CLE), a cotton-wick silver-silver chloride electrode (SCLE), and a coiled stainless steel wire electrode (SSE). Compared to SCLE and SSE. the potentials recorded by CLE are characterized by significantly larger ERG amplitudes and oscillatory potentials in both rats and mice (p <0.0001). In analyzing test-retest data comparing the three different electrodes the coefficient of variation was smaller (range, 10.3-15.5%) and the interclass correlation coefficient (0.77-0.93) showed a better agreement for the CLE. Recording scotopic ERGs with custom-made gold-wire contact lens electrodes records large amplitudes and shows a good reproducibility and reliability to monitor retinal function in rodent eyes.

Corpus callosum size in schizophrenia--a magnetic resonance imaging analysis.

Previous MRI studies have shown differences in corpus callosum size between schizophrenic patients and controls. The corpus callosum (CC), as the main interhemispheric fiber tract, plays an important role in interhemispheric integration and communication. Though MRI studies suggest smaller CC in schizophrenia, there are still conflicting findings. Using in vivo magnetic resonance imaging, it was investigated whether the midsagittal area of CC differs between twenty-three right-handed male schizophrenic patients and twenty-three matched controls. Total CC area, five subregions of CC, total brain volume, gray and white matter were measured. No differences between schizophrenic patients and controls were found regarding all CC measurements, total brain volume, and gray matter tissue. However, a significant reduction of white matter tissue in the patient group emerged. There was no correlation between CC morphology and clinical variables such as age of onset, length of illness or symptom severity. Interestingly, five schizophrenic patients with a positive family history of schizophrenia showed significant reduction of the subregion C3, associated with a reduced total brain and gray and white matter volume. Significant reduction in the CC and its subregions was not confirmed in this group of patients with schizophrenia. In the subgroup of schizophrenic patients with a positive family history of schizophrenia, a significant reduction of the subregion corresponding to a part of the trunk of the CC was found.

Vestibular exercises improve central vestibulospinal compensation after vestibular neuritis.

OBJECTIVE AND BACKGROUND: Animal experiments have shown that central vestibular compensation of unilateral peripheral vestibular lesions can be improved by vestibular exercises. There are, however, no equivalent clinical studies on the efficacy of such specific physiotherapy on acute unilateral peripheral vestibular lesions in humans. DESIGN AND METHODS: To quantify the differential effects of specific vestibular exercises on central compensation in patients with an acute/subacute unilateral vestibular lesion (vestibular neuritis), we determined the time course of recovery of 1) the ocular torsion (OT) for the vestibulo-ocular system, 2) the subjective visual vertical (SVV) for perception, and 3) the total sway path (SP) values for postural control in 19 patients with and 20 patients without vestibular exercises. All patients had a persisting peripheral vestibular deficit for at least 30 days (statistical end point). RESULTS: Although normalization of OT and SVV was similar in the control and physiotherapy groups, the total SP values on day 30 after symptom onset differed significantly: 3.2 +/- 1.9 m/min in the physiotherapy group and 16.9 +/- 6.1 m/min in the control group (ANOVA, p < 0.001). CONCLUSIONS: This prospective clinical study suggests that specific vestibular exercises improve vestibulospinal compensation in patients with acute peripheral vestibular lesions.

In vivo reproducibility of three-dimensional cartilage volume and thickness measurements with MR imaging.

OBJECTIVE: Previous studies suggest that MR imaging is capable of providing accurate data on knee joint cartilage volume and thickness in vitro, but the reproducibility of these data in living subjects has not been analyzed rigorously. Our aim was therefore to determine the in vivo reproducibility of volume and thickness measurements from replicated data sets, applying three-dimensional (3D) postprocessing methods. SUBJECTS AND METHODS: Eight healthy volunteers were imaged six times at a resolution of 2 x 0.31 x 0.31 mm with a fat-suppressed fast low-angle shot 3D sequence, the knee being repositioned in between replicated examinations. Three-dimensional reconstructions of the articular cartilage surfaces were obtained from sagittal data sets, and the cartilage volumes were calculated. The thickness distribution was analyzed throughout the joint surfaces independent of the section orientation, using a previously validated 3D minimal-distance algorithm. RESULTS: In the volunteers, the coefficient of variation for replicated volume measurements ranged from 1.3% (patella) to 3.4% (lateral tibia), and the standard deviation of the individual cartilage volumes ranged from +/- 16% (lateral tibia) to +/- 22% (femur). The intraclass correlation coefficient ranged from .959 (lateral tibia) to .995 (patella). The interobserver evaluation was similar to the interscan reproducibility. The mean interscan deviation of the maximal cartilage thickness interval ranged from 0.1 to 0.3 cartilage thickness intervals (of 0.5 mm); only in rare cases did we record deviations greater than one thickness interval. CONCLUSION: MR imaging can be used to determine cartilage volume and thickness in the knee joints of living subjects with high precision, provided that a fat-suppressed gradient-echo sequence with adequate resolution and 3D digital image processing are used.

Risk factors for systemic fungal infections in liver transplant recipients.

The risk factors for systemic fungal infections were analysed retrospectively in 186 orthotopic liver transplant procedures performed in 152 patients between June 1985 and January 1993. The total incidence of systemic fungal infections was 16.5% (25/152). The incidence of disseminated candidiasis, aspergillosis, and combined candidiasis and aspergillosis was 6.5% (n = 10), 7.2% (n = 11) and 2.6% (n = 4), respectively. Mortality associated with systemic fungal infections was 80% (20 of 25 patients). There were ten cases of disseminated candidiasis, with 4 patients surviving, and 11 cases of invasive aspergillosis, with 1 patient surviving. All patients with combined systemic fungal infection died. To identify perioperative risk factors, 39 variables were used to compare patients with systemic fungal infections versus those without fungal infections. Fourteen variables were significantly associated with systemic fungal infections by univariate analysis. A consecutive logistic regression analysis revealed that the amount of fresh frozen plasma transfused due to poor initial function of the allograft and acute renal failure requiring hemofiltration were independently significant risk factors for systemic fungal infections. There was no statistical correlation between systemic fungal infections and the underlying liver disease, previous long-term corticosteroids and the postoperative immunosuppressive therapy. Risk factors identified in this study should be considered in the postoperative care of the individual liver transplant recipient. In our study a poor initial function of the hepatic allograft substantially increased the risk of systemic fungal infection.

[Manometric and clinical long-term outcome after grade III perineal rupture]. / Manometrische und klinische Langzeitresultate nach Dammriss III. Grades.

OBJECTIVE: To investigate the manometrical and clinical long-term results following a tear III. PATIENTS: 27 Primiparae with a tear III following a spontaneous vaginal delivery were retrospectively compared with 22 Primiparae without sphincter injury (follow-up: 27 months). METHODS: Water-Perfusion-Manometry and clinical assessment (modified Kelly-Score). Manometric parameter (at rest and during contraction): sphinctertone and - length, vectorvolume, radial asymmetry. Wilcoxon-Text (p < 0.05). RESULTS: Tear III patients showed a significant decrease in sphincter length and vector volume both at rest and during contraction. On clinical assessment there was no difference. CONCLUSION: A tear III weakens the anal sphincter by decreasing sphincter length and vector volume. This weakness can be demonstrated only manometrically but not clinically.

[Micrometastases in bone marrow of patients with cancers in the head and neck area]. / Mikrometastasen im Knochenmark von Patienten mit Karzinomen des Kopf-Hals-Bereiches.

Individual disseminated epithelial tumour cells were detected in bone marrow aspirates in 41 of 108 patients (37%) with squamous cell cancer of the head and neck region by an immunocytochemical technique based on monoclonal antibodies raised against the cytokeratin No. 19. In the clinical stage I (T1N0M0) tumour cells were detected only in 26.3% of the patients, whereas in stage IV (T4N0M0, T(all)N2-3M0, T(all)N(all)M1) almost twice as many patients (47.7%) presented with tumour cells in the bone marrow. Apparently, grade of differentiation of the tumour (grading) had no influence on the spread of single tumour cells. An influence of the different localisations of the primary tumour on tumour cell spread or the rate of tumour recurrence cannot as yet be discovered. Cytokeratin No. 19 expressing cells were not detectable in the bone marrow of 18 patients with non-malignant disease. Seventy-three patients were included in a follow-up study with a mean observation time of 25 months (range: 4-52 months). The presence of epithelial cells at the time of primary treatment appears to indicate a significantly higher risk of development of local or distant tumour recurrences (p = 0.01). Of 46 patients initially exhibiting no tumour cells in the bone marrow, only 14 had a clinical recurrence. Whereas 17 of 27 patients who presented with tumour cells in the bone marrow developed either a local tumour recurrence or distant metastases in different organs. Patients presenting with bone marrow tumour cells showed a significantly shorter disease-free survival than those without (p = 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)

[Prognostic scores in peritonitis: the Mannheim Peritonitis Index or APACHE II?]. / Prognosescores bei Peritonitis: Mannheimer Peritonitis-Index oder APACHE II?

Scoring systems are mandatory to quantify the severity of abdominal sepsis on the basis of objective criteria. The Mannheim Peritonitis Index (MPI) is a disease-specific score based on easy to handle clinical parameters. APACHE II is a large-scale general scoring system with acute physiological and chronic health parameters. To evaluate the prognostic value of both systems 108 patients with severe abdominal infection managed by open treatment entered a prospective study. 32 patients (29.6%) died, 23 of them due to sepsis and 9 from other causes. Both MPI and APACHE II scores correlated closely with mortality, with three and two significantly different classes, respectively. Statistical validation showed a sensitivity of 93% and a specificity of 16% for MPI, and 89% and 25% for the APACHE II. ROC curves were nearly parallel for both scores. In conclusion there was no significant difference in prognostic value between the scoring systems.

[The value of clinical parameters for determining the prognosis of peritonitis--validation of the Mannheim Peritonitis Index]. / Wertigkeit klinischer Parameter zur Prognosebeurteilung der Peritonitis--Validierung des Mannheimer Peritonitis-Index.

In order to evaluate the prognostic value of simple clinical parameters and the Mannheim Peritonitis-Index (MPI) 438 patients with abdominal infection entered a prospective study. 300 of them were managed by closed treatment with drainage, 138 by open treatment with planned relaparotomy. 63 patients (14.4%) died, 34 of them due to sepsis, 29 due to another cause. Stepwise logistic regression analysis showed only preoperative shock, concomitant disease and sepsis to be significant and independent factors leading to death. MPI had a strong correlation to mortality. Statistical validation showed a sensitivity of 88% and a specificity of 78% at the critical score of 26 points. The MPI is an easily documented prognostic index for peritonitis with high accuracy in individual prognosis.

[An increased risk of kinesitherapy in silent myocardial ischemia?]. / Erhöhtes Risiko der Bewegungstherapie bei stummer Myokardischämie?

The effect of three-week standardized physical training on exercise-induced ischaemia was investigated in patients with silent ischaemia after myocardial infarction. 24-hour monitoring and exercise ECGs before and after the period of physical training, were undertaken in 32 men (mean age 53.6 +/- 8.1 years) with angiographically proven coronary heart disease. The protocol of the standardized exercise included bicycle ergometry, gymnastics, breathing and movement exercises, as well as nonstandardized walking or hiking. Following the training period the number of ischaemic episodes fell from 90 to 72 for the group as a whole and that of the asymptomatic episodes from 79 to 64. The number and severity of ventricular arrhythmias were similar during silent and symptomatic ischaemia. There was a significant increase in duration of exercise until reaching the ischaemia threshold (mean exercise duration 4.7 +/- 2.1 vs 5.9 +/- 2.5 min; P = 0.0007). There was no increased risk concerning ventricular arrhythmias.