No significant effect of orally administered chemokine receptor 1 antagonist on intercellular adhesion molecule-3 expression in relapsing--remitting multiple sclerosis patients.

We investigated the expression of intercellular adhesion molecules ICAM-1 and ICAM-3 on peripheral blood mononuclear cells in a subgroup of 34 patients with relapsing-remitting multiple sclerosis who were treated orally with the chemokine receptor 1 antagonist BX 471 in a 16-week, randomised, double-blind, placebo-controlled phase II study. ICAM-1 and ICAM-3 expression was measured by flow cytometry at different time points during and after therapy and compared using multivariate analysis of variance and non-parametric Mann Whitney test. ICAM-3 expression on CD14( +) peripheral blood mononuclear cells was increased in the verum group under therapy, but did not differ significantly between the verum and placebo groups. Most likely, this trend represents a small epiphenomenon only mediated by receptor cross-talk and feedback mechanisms.

Significance of inflammation on standard semen analysis in chronic prostatitis/chronic pelvic pain syndrome.

The impact of defined urogenital inflammations on standard ejaculate parameters is still a matter of controversial debate. Basic spermiogram parameters has been analysed in patients with inflammatory and noninflammatory chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS-NIH IIIA/IIIB) with regard to indicators of inflammation in prostatic secretions and/or the ejaculate. A total of 112 consecutive patients symptomatic for chronic pelvic pain were included in the study. All of them underwent a 'four glass-test' including leukocyte determination in expressed prostatic secretions followed by ejaculate analysis according to WHO. The analysis included pH, volume, total sperm count, sperm density, motility, morphology (Shorr stain), vitality (eosin stain), and counting of peroxidase positive leukocytes (PPL). Patients were first subgrouped according to elevated leukocyte counts in prostatic secretions, and then according to the number of PPL in semen. Leukocytes neither in the prostatic secretions nor in the ejaculate were associated with reduced standard semen parameters. Our data supports previous results that elevated leukocyte counts in prostatic secretions and in ejaculate, as indicators of inflammation have no negative impact on total sperm count, sperm density, motility, morphology, and sperm vitality in patients with CP/CPPS.

Enhanced lymphocyte proliferation in patients with adrenoleukodystrophy treated with erucic acid (22:1)-rich triglycerides.

Lymphocytopenia and depression of natural killer cells have been observed in patients with adrenoleukodystrophy (ALD) treated with glycerol trioleate and glycerol trierucate ('Lorenzo's oil'). To investigate possible alterations of cellular immunoreactivity, we measured lymphocyte proliferation in response to mitogens (PHA, Con A, PWM, OKT3) in 27 patients on treatment and in 14 patients without treatment. In patients on treatment, lymphocyte proliferation in response to the mitogens PHA and Con A was significantly higher than in patients without treatment. Lymphocyte proliferation in patients without treatment was comparable to that of normal control lymphocytes. Additionally, we found increased concentrations of erucic acid, C22:1, in lymphocytes from patients with treatment. The enhanced proliferation of lymphocytes in response to mitogens is an indication of increased reactivity of cellular immunity to unspecific immunological stimuli. Long-term side-effects on cellular immunoreactivity have to be considered in ALD patients treated with Lorenzo's oil.

[Left ventricular heart volume determination with fast MRI in breath holding technique: how different are quantitative heart catheter, quantitative MRI and visual echocardiography?]. / Linksventrikuläre Herzvoluminabestimmung mittels schneller MRT in Atemanhaltetechnik: Wie unterschiedlich sind quantitativer Herzkatheter, quantitative MRT und visuelle Echokardiographie?

GOAL: Comparison of fast MRI, echocardiography (Echo), and ventricular angiography (Cath) in the assessment of left ventricular global function. METHODS: Fast MRI in short axis plane, biplane Cath, and 2D Echo were performed in 62 patients [35 coronary artery diseases, 16 acquired valvular diseases (VD), 9 dilated cardiomyopathies (DCM), 1 congenital heart disease and 1 heart transplantation]. Enddiastolic (EDV), endsystolic (ESV), stroke volumes (SV), cardiac output (CO), and ejection fraction (EF) were compared in MRI and Cath. EF was visually estimated in 2D Echo by an experienced observer. RESULTS: In comparison to MRI, Cath overestimated EF by 8.4%, and Echo underestimated EF by 5.6%. The limits of agreement between MRI and Cath in EF were +/- 23.8%, between MRI and Echo +/- 18%, and between Echo and Cath +/- 19.4%. Significant differences were found between Cath and MRI in EDV, SV, and CO, but not for ESV. The best agreement in EF was found in the group with DCM, the worst in the group with VD. CONCLUSION: Important systemic and random errors were found in the comparison of MRI, Echo, and Cath. For therapy decision and follow-up, the methods should not be exchanged unscrupulously.

Right ventricular volumes and ejection fraction with fast cine MR imaging in breath-hold technique: applicability, normal values from 52 volunteers, and evaluation of 325 adult cardiac patients.

Our goal was to establish right ventricular (RV) volume and ejection fraction (EF) values in normal volunteers with fast magnetic resonance (MR) imaging using a breath-hold technique, to assess the frequency and severity of RVEF abnormality in cardiac patients and to compare RV with left ventricular (LV) data. We performed simultaneously derived RV and LV fast cine measurements in 52 normals and 325 patients with coronary artery disease (CAD), acquired valvular disease (VD), cardiomyopathy (CM), or congenital heart disease (CHD). RVEF was reduced in 31% (102) of all patients, in 50% dilated CM, 39% CHD, 34% CAD, and 22% acquired VD patients. Solitary abnormally low RVEF was found in only 15/325 (5%) of all patients, whereas combined with LVEF deterioration in 87/172 (51%) patients. RVEF reduction was mild in 64%, moderate in 25%, and severe in 11%. Although RVEF correlated significantly (r = 0.55, P < 0.001) with LVEF, the predictive value of LVEF for RVEF was low. We conclude that RV volumes can be routinely assessed with fast MRI and should be performed in addition to LV evaluation in CHD, in right-sided VD, and in all patients with an abnormal LVEF.J. Magn. Reson. Imaging 1999; 10:908-918.

[The determination of left and right ventricular ejection and filling functions of the heart by fast cine MRT in the breath-hold technic in subjects]. / Bestimmung des links- und rechtsventrikulären Auswurf- und Füllungsverhalten des Herzens mittels schneller Cine MRT in Atemanhaltetechnik an Probanden.

PURPOSE: Evaluation and comparison of localized and global left and right ventricular ejection and filling with fast cine MR imaging in the breath-hold technique. MATERIALS AND METHODS: 10 healthy volunteers were examined with a 1.5 Tesla unit and phased-array-coil using a segmented FLASH-2D sequence in breath-hold technique. Peak ejection and peak filling rates [PER, PFR end-diastolic volume (EDV)/s)]. time to PER and PFR [TPER, TPFR ms] and time of end-systole [TSYS in % RR-interval] of all slices (complete-slice-evaluation) were evaluated and compared to three left ventricular and one right ventricular slices (reduced three-slice-evaluation). RESULTS: There were significant regional left ventricular differences of PER (p = 0.002) and PFR (p = 0.007), but not of TPER and TPFR. Ejection and filling indices of the left ventricular middle slice were closest to the overall evaluation of all sections. In the left-/right-side comparison the right ventricular PFR was higher than the left ventricular (5.1 and 4.2 EDV/s) and the right ventricular TPFR was earlier than the left (92.2 and 123.5 ms). CONCLUSIONS: With fast cine techniques, regional and global left and right ventricular ejection and filling indices can be evaluated in addition to the global heart volume indices. The three-slice-evaluation represents a comprehensive, clear and time-saving method for daily routine.

[Glare sensitivity of phakic and pseudophakic eyes]. / Untersuchungen zur Blendempfindlichkeit phaker und pseudophaker Augen.

BACKGROUND: Glare disability and appearance of halos may be side-effects of cataract, but were also described in patients with multifocal IOLs. The aim of this study was to compare glare sensitivity and halo size in phakic and pseudophakic eyes. PATIENTS AND METHODS: Contrast sensitivity without and with glare and halos around a light source were measured by means of a new computerized test in patients with cataract, monofocal IOLs, multizonal progressive and diffractive multifocal IOLs as well as in a younger control group of subjects with clear lenses. Glare acuity was measured at three different luminance settings. RESULTS: Patients with cataract showed the most important reduction in contrast sensitivity, noticed significantly larger halos and were more impaired in glare acuity than patients with monofocal or multizonal progressive IOLs. There was no significant difference in any criteria between these two pseudophakic groups. Subjects with a clear cristalline lens had statistically significant better results compared with all other groups. CONCLUSION: An increase in glare sensitivity and the appearance of halos are more important in patients with even minor cataracts than in any pseudophakic population. As a consequence of this study, night driving ability should be carefully examined in any pseudophakic patient, but also in any subject with even beginning cataract.

[Extraction of the deciduous anterior teeth and its consequences in children with the nursing bottle syndrome]. / Milchfrontzahnextraktion und ihre Folgen bei Kindern mit Nursing-Bottle-Syndrom.

On eighty children, whose rampant carious and predominant periapical diseased deciduous maxillary incisors had been formerly extracted, the outcomes of the early extraction were inspected in regard to the later development of the permanent teeth and the general state of health. For 68 children gypsum models were analysed, whether the early loss of deciduous incisors had led to deficiency of place in the front of the upper jaw. The early tooth extraction and conservation therapy resulted in a clear improvement of children's physical condition and ameliorated the starting situation of permanent teeth to be preserved healthy. The earlier the milk-incisors had to been extracted the greater was the danger of a belated eruption of the permanent incisors.

Influence of treatment with mouse immunoglobulin on the rate of viable neonates in the CBA/J x DBA/2 J model.

In the CBA/J (H-2k) x DBA/2J (H-2d) murine model, the protective value of pooled murine immunoglobulin i.p. was compared with that of serum taken 7 days after termination of CBA/J (H-2k) x BALB/c (H-2d) pregnancy. A control group of CBA/J females received treatment with autologous virgin serum. CBA/J females at 7 weeks of age were injected 3 days before mating with DBA/2J males and 3 days after sighting of the vaginal plug. An effect of treatment can be shown following IgG therapy (P less than 0.05). The highest rate of viable fetuses was documented in the immunoglobulin-treated females, while the rate of viable offspring did not differ in the two serum-treated animal groups.

Effects of positive end-expiratory pressure (PEEP) ventilation on the exocrine pancreas in minipigs.

The effect of positive end-expiratory pressure (PEEP) ventilation on the pancreas was studied in 22 anesthetized minipigs. Five pigs were treated with intermittent positive pressure ventilation (IPPV) for 21 h (Group I) and six pigs were treated with a PEEP of 15 cm H2O for 21 h (Group II). We next explored the influence of PEEP ventilation while stimulating the pancreas with Ceruletide, a synthetic cholecystokinin (CCK) analog, at 2.3 micrograms/kg per h.i.v. for 3 h. Ventilation with IPPV for 4 h (n = 5, group III) was compared with PEEP of 15 cm H2O for 4 h (n = 6, group IV). Changes in serum-lipase were observed in all groups. The average lipase level rose from 12.6 U/l to 67 U/l group I and from 15.1 U/l to 129.2 U/l in group II (P = 0.025 for group I vs group II). In group IV (PEEP and Ceruletide), the mean lipase level rose about six times more than in group III (IPPV and Ceruletide). The difference was significant (P less than 0.00005). By three-factor ANOVA analysis, effects due to the drug (P less than 0.000006) and to PEEP (P less than 0.038) as well as a threefold interaction could be demonstrated, i.e., using Ceruletide a greater PEEP effect on lipase than without the drug (P less than 0.023) took place. There were no significant histological changes of the pancreas in groups I and III. In group II (21 h PEEP), vacuolization of acinar cells was evident; on the ultrastructural level, indication was given that these vacuoles derived both from the Golgi apparatus and from fusion of individual zymogen granules. In group IV (PEEP and Ceruletide), the focal appearance of fatty-tissue necrosis and acinar cells as well as hemorrhage of the gland was observed. We conclude that PEEP ventilation impairs the function of the pancreas and produces even more deleterious effects when the gland is stimulated. These effects should be considered when PEEP is used in clinical practice in the treatment of acute pancreatitis.

[Statistical study of alcohol intoxicated female victims of sex offenses]. / Statistische Untersuchung alkoholisierter weiblicher Opfer von Sexualdelikten.

Comparing 133 presumable rape victims who underwent blood sampling after the event with 2446 alcoholized female traffic offenders it was found that both groups had a delinquency maximum between midnight and 2 a. m. and a delinquency minimum between 6 a. m. and 6 p. m. Most of the rape victims, however, were approximately 5 years younger than the traffic offenders, most of whom were about 25 years old. The time intervals between blood sampling and the event were longer in the case of the rape victims (4 to 20 hours) whereas most traffic offenders underwent blood sampling 1 to 2 hours after the event. At comparable maxima of the distribution curves of blood alcohol concentration (between 1.5% and 2%) that of the rape victims showed a shift to higher values. This is also illustrated by the mean values of blood alcohol concentration at the time of the event: the blood alcohol concentration of the rape victims was 2.24% and thus 0.45% higher than that of the traffic offenders, who averaged only 1.97%. The reason for this is probably to be seen in the different modes of back computation. By assigning 38 offenders to 35 victims it was possible to set up and compare 35 pairs. Comparing the blood alcohol concentrations of all 35 pairs it was found that the blood of the victims contained on average 0.4% more ethanol than the blood of the offenders (1.41% vs. 1.01%).

Quantitative assessment of long-term changes in insulin secretion after canine duct-obliterated pancreas transplantation.

In this study, we have quantitatively assessed the changes in insulin-secreting capacity after duct-obliterated segmental pancreatic autotransplantation in dogs. To this end, we have used a technique for the sampling of the complete and undiluted pancreatic venous blood with simultaneous flow measurement, by which means the actual insulin-secreting capacity was determined in a direct fashion. Histologic changes were analyzed in addition in order to address the underlying mechanisms of the changes in insulin-secreting capacity. Intraoperative glucose-stimulated insulin secretion of the left pancreatic lobe was measured before (group I, n = 8), at 6 weeks (group II, n = 5), and at 18-24 months (group III, n = 7) after duct-obliterated segmental pancreatic autotransplantation. At all 3 intervals, histologic analysis was performed. Since the experiments in groups I-III were performed under general anesthesia, a 4th group of dogs (group IV, n = 6) was studied in addition in order to determine the effect of general anesthesia on glucose metabolism. K-values appeared to be reduced to 1/5 and peripheral insulin response (AUC) to about 1/3 of the values obtained from fasting conscious dogs. Although all animals in groups I-III had normal fasting glucose levels and normal K-values at each test interval, a 75% reduction of insulin secretion after duct-obliterated transplantation was observed. Insulin secretion not only showed marked quantitative changes but significant qualitative alterations in glucose-stimulated insulin response were found. Disturbance of functional islet architecture appears to be the main causative factor in the decrease in insulin secretion. If applicable to man, our results indicate that especially the duct-obliterated graft, with its borderline endocrine capacity, is prone to loss of sufficient graft function by the damage induced by eventual rejection crises.

Effect of perioperative blood loss and perioperative blood transfusions on colorectal cancer survival.

Results of various studies suggest that the perioperative administration of blood transfusions in cancer patients operated upon for cure is associated with a diminished patient survival. Furthermore, recent results from our laboratory indicate that blood loss may also be capable of promoting tumor growth. In order to elucidate these findings a retrospective study was initiated towards the survival of 164 patients with colorectal carcinoma, operated upon for cure, at the University Hospital, Rotterdam. In 117 patients who perioperatively received blood transfusions the 5-year survival was 68%, as compared to 80% in the non-transfusion group (P = 0.039; Wilcoxon). The 5-year survival in the group of patients with a perioperative blood loss exceeding 500 ml (n = 88) was 70%, as compared to 73% in the group with a blood loss of 500 ml or less (not significant). Multivariate analysis, adjusting for 11 relevant parameters, showed that only tumor stage and the administration of blood transfusions were significantly associated with a decrease in survival. It is concluded that perioperative blood transfusions adversely affect colorectal carcinoma survival in this group of patients. Perioperative blood loss was not a significant prognostic factor.

A model for direct and quantitative assessment of pancreatic hormone secretion.

The usual parameters for the assessment of pancreatic endocrine function are oral or intravenous tolerance tests with various kinds of stimuli, generally glucose. Such tests provide information as to the pancreatic endocrine capacity in an indirect fashion, and the actual hormone output cannot be readily determined. The results are presented of a model in dogs with which the hormone producing capacity of the left lobe of the pancreas can be quantitatively assessed directly. The complete and undiluted venous blood from the left pancreatic lobe is sampled by cannulation of the splenic and the portal vein, under general anaesthesia. Removal of the right lobe is obligatory. With this model pancreatic blood flow, hormone secretion, and oxygen consumption can be studied after different sorts of stimuli. Moreover there is opportunity to determine the effect of various manipulations of the pancreas on its hormone secreting capacity directly.

[Measuring oxygen consumption in healthy infants and children and infants and children with heart diseases]. / Zur Messung des Sauerstoffverbrauchs bei gesunden und herzkranken Säuglingen und Kindern.

Oxygen consumption (VO2) must be known to calculate the hemodynamic parameters by Fick's principle. Often VO2 is not measured directly but calculated by nomograms. An open-system method was used for measuring oxygen consumption continuously in 140 healthy infants and children and 152 with congenital heart disease. The patients with heart disease were divided in three groups: I - with large left-to-right shunt (more than 40%), II - with a small left-to-right shunt, and III - without left-to-right shunt. In group I a significantly higher oxygen consumption was measured. There was also a difference in relation of indexed oxygen consumption to age between group I and all the other children. In a second part we compared two methods for determination of indexed oxygen consumption (VO2) in infants and children: measurement using an open system method estimation by using formulas. In healthy infants estimation showed higher values; but no difference was found in healthy children or those without significant left-to-right shunt. In children with congenital heart disease and large left-to-right shunt measured VO2 was significantly higher than the estimated values. No correlation was found in infants with large left-to-right shunt. But in these cases the exact calculation of the hemodynamic parameters would be of great importance. The results indicate that measurement rather than estimation of VO2 is necessary for calculation of hemodynamic parameters.

Granulocyte elastase as a sensitive diagnostic parameter of silent male genital tract inflammation.

Elastase, a specific inflammatory parameter of polymorphonuclear (PMN) granulocytes, was quantified with a sensitive enzyme immunoassay in the ejaculates of 188 patients consulting the andrological outpatient service. Correlations of the elastase concentrations to other parameters used up to now for the diagnosis of silent male genital tract inflammation were statistically evaluated by the CHI2-test. A correlation was found neither to the percentage of morphologically intact spermatozoa in the differential spermiocytogram and the total number of spermatozoa nor to the pH-value and viscosity of the ejaculate. However, release of elastase into the ejaculates was clearly associated with the occurrence of bacteria in native and stained smears or with the numbers of round cells present. Moreover, leukocyte counts in stained smears as well as an inflammation coefficient were highly significantly correlated to elastase concentrations. Obviously, quantification of granulocyte elastase in seminal plasma enables a rapid diagnosis of silent male genital tract inflammation, since even a single determination gives a reliable criterion and sequential determinations may allow the control of the course of the disease during therapy.

"Haemostasis time", a modified bleeding time test and its comparison with the Duke and Ivy/template bleeding times. I. Normal values, application in thrombocytopenic patients and evaluation of heparin and aspirin effects.

The occlusion time ("haemostasis time" - HT) of a thin, short cannula inserted into the cubital vein, was compared with the skin bleeding times of the Duke and Ivy/template techniques. 25 male and 25 female volunteers without a history of bleeding were divided into 5 equally large age groups ranging from 10 to over 50 years of age. They exhibited a range of 46 s-6 min 38 s (95% tolerance interval), while the Duke and Ivy/template bleeding times, which were simultaneously determined, corresponded to values given by other authors. HT is different from the skin bleeding times in that endothelium is replaced by a standard foreign surface which allows better standardization of the method. Similar results were obtained with HT compared to the skin bleeding times. These and a similar, non-significant heparin response with all three techniques suggest that HT is not more influenced by clotting factors than the Duke and Ivy/template bleeding times and, indeed, may be regarded as a bleeding time modification. HT, like both of the skin bleeding times, reflected lowered platelet counts and is even more sensitive in this respect. As tested in a group of 20 male and 20 female volunteers, HT showed a significant prolongation two hours after ingestion of 1 g aspirin. While male individuals exhibited longer bleeding times than females with the Ivy/template technique (sex-related difference p = 0.01), no male to female differences were found both with HT and the Duke bleeding time. HT is easy to perform, inexpensive, leaves no scars and is safe even for the patient with severe bleeding. Moreover, compared to the skin bleeding times, it permits a differential evaluation of vessel wall and tissue effects.