Cardiorespiratory Kinetics Determined by Pseudo-Random Binary Sequences - Comparisons between Walking and Cycling.

This study aims to compare cardiorespiratory kinetics as a response to a standardised work rate protocol with pseudo-random binary sequences between cycling and walking in young healthy subjects. Muscular and pulmonary oxygen uptake (V̇O2) kinetics as well as heart rate kinetics were expected to be similar for walking and cycling. Cardiac data and V̇O2 of 23 healthy young subjects were measured in response to pseudo-random binary sequences. Kinetics were assessed applying time series analysis. Higher maxima of cross-correlation functions between work rate and the respective parameter indicate faster kinetics responses. Muscular V̇O2 kinetics were estimated from heart rate and pulmonary V̇O2 using a circulatory model. Muscular (walking vs. cycling [mean±SD in arbitrary units]: 0.40±0.08 vs. 0.41±0.08) and pulmonary V̇O2 kinetics (0.35±0.06 vs. 0.35±0.06) were not different, although the time courses of the cross-correlation functions of pulmonary V̇O2 showed unexpected biphasic responses. Heart rate kinetics (0.50±0.14 vs. 0.40±0.14; P=0.017) was faster for walking. Regarding the biphasic cross-correlation functions of pulmonary V̇O2 during walking, the assessment of muscular V̇O2 kinetics via pseudo-random binary sequences requires a circulatory model to account for cardio-dynamic distortions. Faster heart rate kinetics for walking should be considered by comparing results from cycle and treadmill ergometry.

Influence of immunization with allogeneic spleen cells on the number of viable neonates in mice.

Female CBA/J (H-2k) mice mated with male DBA/2J (H-2d) mice show a high level of fetal resorption, which can be reduced by immunization with BALB/c (H-2d) spleen cells. The morphologically defined fetal resorption rate upon which evaluation of the outcome of pregnancy has previously been based in this strain combination is not equivalent to the rate of production of viable neonates.

Immunogenetic and serological investigations in nonpregnant and in pregnant women with a history of recurrent spontaneous abortions. German RSA/IVIG Study Group.

In the context of a controlled multicenter study on intravenous immunoglobulin (IVIG) treatment of patients with a history of unexplained recurrent spontaneous abortions (RSA), a number of controversial immunological parameters were evaluated prior to and during pregnancy with respect to their diagnostic and/or prognostic significance. A total of 390 serum samples from 52 patients were investigated. Sharing of 2 or more HLA (A, B, DR, DQ) antigens was significantly more frequent in RSA couples than in controls. The rate of cytotoxic or Fc-receptor (FcR)-blocking antibodies was not significantly lower in RSA patients than in individuals with normal pregnancies. Both tumor necrosis factor-alpha (TNF-alpha) levels and IgG anticardiolipin antibodies (IgG-ACA) were significantly increased in the patient group. While the occurrence of HLA sharing, cytotoxic/FcR-blocking antibodies and IgG-ACA did not correlate with the outcome of pregnancy, TNF-alpha levels were found to be significantly higher in patients with subsequent miscarriage than in those with successful pregnancy. IgG-ACA, if present, significantly decreased during the course of successful pregnancy but remained high in patients with subsequent abortion. It is concluded that the diagnostic and/or prognostic value of HLA sharing and cytotoxic/FcR-blocking antibodies has been overestimated while TNF-alpha and ACA levels are potential diagnostic markers and/or exhibit prognostic significance in subgroups of RSA patients.

[Preoperative cervix priming in the 1st trimester: initial clinical experiences with a combination of Pluronic F 127 and sulprostone]. / Präoperatives Zervix-priming im 1. Trimenon: erste klinische Erfahrungen mit einer Kombination von Pluronic F 127 und Sulproston.

A new gel with sulprostone was applied in a prospective randomized study in 70 patients who were scheduled for termination of 1st trimester pregnancy. Priming was carried out in two equal groups of 25 patients with 50 micrograms or 100 micrograms sulprostone gel respectively; in a control group of 20 patients the gelatinizing agent (Pluronic F 127) was used without sulprostone. The gel, which was produced immediately before the application, was applied intracervically with a semiflexible polyethylene catheter with a constant injection volume in a three-hour interval before the operation. A dilatation response--documented by the free patency of Hegar's dilatator which effortlessly passes the outer and inner uterine cervix--was seen in the therapy group; among these patients an average dilatation of the cervical canal of 8.2 mm (SD +/- 2.25) was achieved. This therapeutic effect was better in primiparae and multiparae compared with nulliparae (p less than 0.05). No statistically significant dose-effect correlation was found between the patients who had been treated with 50 micrograms sulprostone and those who had been treated with the 100 micrograms dosage. Among the side effects a dose-independent spastic lower abdominal pain was seen most frequently; it was noticed in 10 patients. Based on the results of this study it is concluded that cervical priming with sulprostone-pluronic gel can be regarded as a practicable method with a low rate of side effects for preoperative cervical priming in patients scheduled for termination of first trimester pregnancy.

[Primary cancer of Bartholin's gland]. / Das primäre Karzinom der Bartholinischen Drüse.

Carcinoma of Bartholin's gland is an extremely rare tumour representing approximately between 1% and 7% of the cases of cancer of the vulva. The aetiology of the tumour, which can be subdivided by means of light microscopy into squamous cell carcinoma, adenocarcinoma, adenoid cystic carcinoma and adenoacanthoma, remains unknown. Surgical and radiotherapeutic treatment is possible also in combination. If primary operative therapy is chosen, inguinal lymphadenectomy is required as usually suggested in all cases of cancer of the vulva; the metastatic involvement of the inguinal lymph nodes is regarded as the main prognostic determinant: if only one inguinal node has microscopic metastases, a five-year survival rate between 60% and 70% can be achieved in a selected operative group of patients. If more than four positive groin nodes are histologically diagnosed the survival rate - according to current results, not subdivided into different alternatives of therapy - is below 20%.

Intravenous immune globulin in recurrent abortion.

A specific effect of intravenous immune globulin (IVIG) on the outcome of pregnancy in patients with a history of habitual abortion has been postulated as an alternative to immunotherapy with allogeneic leucocytes. The results of different pilot studies have been promising, demonstrating a successful outcome of pregnancy in approximately 80% of treated patients. However, the evaluation and interpretation of the study results has to take into account that the probability of a successful pregnancy in women with a history of three spontaneous abortions is about 60% without treatment. Specific pharmacological effects therefore have to be verified in controlled studies in order to rule out psychological (placebo) effects. A specific therapeutic effect could not be verified in a German randomized, double-blind, multicentre trial in comparison to human albumin 5% which was used as a placebo. The result of another controlled study currently underway in the USA is expected.

Olfactory asymmetry in the rat brain.

Based on cytoarchitecture, myeloarchitecture, and physiological observations in the literature, two concentric strata are identified in the olfactory bulb of the albino rat. Stimulated by a report of physiologic asymmetry between the left and right bulb of the rodent brain, we parcelled the inner and outer strata of the olfactory bulbs of 16 albino rats and measured the volume of these olfactory subdivisions. The volume of the entire olfactory bulb was found to be significantly greater in the right hemisphere. This volume asymmetry was the result of a significantly larger right outer stratum. No significant asymmetry was demonstrated for the inner stratum. These findings are discussed in the light of some physiologic and anatomic properties of the olfactory bulb.

[Acute dermal gangrene: a postoperative complication. With an example from obstetrics]. / Die akute dermale Gangrän: Eine postoperative Komplikation. Mit einem Beispiel aus der Geburtshilfe.

In the anglo-american literature the acute dermal gangrene is characterized as a cutaneous syndrome of infectious etiology which is usually leading--postoperatively or after an injury--to necrotizing destructions of the cutis, subcutis, subcutaneous fat, fascia or muscle. Depending on the localization of the involved tissue a superficial progressive bacterial gangrene is distinguished from a more deeply localized necrotizing fasciitis. Diagnostic and therapeutic considerations of these extremely rare syndromes are described in connection with an obstetric case which has been seen by us recently.

Reduced immune phagocytosis of monocytes from neonates whose mothers produce HLA antibodies.

In vivo immune phagocytosis of neonatal monocytes was significantly correlated to the extent of maternal HLA immunization. Monocytes from all 15 neonates of mothers with HLA antibodies show reduced immune phagocytosis. In contrast, this holds true for monocytes from only 6 out of 13 neonates of mothers without detectable HLA antibodies. We infer the hypothesis that maternal HLA antibodies bind to mononuclear phagocytes of the fetus and of the fetal part of the placenta and thus cause inhibition of immune phagocytosis. Thereby, activation and secondary cell or tissue injury will not ensue and rejection of the fetal allograft is prevented in those pregnancies in which maternal alloimmunization occurs.

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.

[Diagnosis in patients with habitual abortion]. / Diagnostik bei Patientinnen mit habituellen Aborten.

Since promising immunological concepts for treatment of patients with three or more miscarriages have been introduced, an exact clarification of all possible etiological factors has become even more urgent, because an infection risk associated with leucocyte therapy cannot be ruled out. Own experiences with 47 couples with a history of habitual abortion who had been diagnostically evaluated in a special screening program in our hospital between 1985-1988 are discussed in the light of surveys of the recent literature. A critical revision of several factors which had been classified as etiological factors of habitual abortion in the past, seems important. While genetic factors are undoubtedly the most important cause of miscarriages in the first trimenon, the role of anatomical uterine anomalies (amongst our patients in 7 per cent), luteal insufficiency (among our patients in 9 per cent) and endometriosis cannot be evaluated with certainty yet because different diagnostic criteria have been established for diagnosis in the literature. Based on newly published data immunological factors seem to become etiologically more important; other anomalies, like infections or diabetes do not seem to be associated with an increased risk for habitual abortion. According to our experiences, habitual abortion may present as a problem involving different pathogenetic factors (among our patients in 79 per cent) so that sequential therapeutic steps may be required for treatment of a-possibly-multifactorial disease.

ACE inhibition and physical exercise: studies on physical work capacity, energy metabolism, and maximum oxygen uptake in well-trained, healthy subjects.

We investigated the effects of the angiotensin-converting enzyme (ACE) inhibitor trandolapril (2 mg/o.d.) on the physical work capacity (PWC), the received perception of exertion (RPE), as well as parameters determining physical performance (i.e., energy metabolism, lactate production, and oxygen uptake) in well-trained, healthy subjects. Twenty male sports students underwent a bicycle spiroergometry until exhaustion to determine maximum work load, maximum oxygen uptake, lactate threshold, and parameters of energy metabolism. The identical protocol was repeated after a 14-day treatment period with 2 mg of trandolapril o.d. or placebo. Treatment with the ACE inhibitor did not significantly alter maximum PWC, RPE, 4.0 mmol/L lactate threshold, heart rate, maximum oxygen uptake, plasma levels of total cholesterol, triglycerides, free fatty acids, glucose, insulin, cortisol, and human growth hormone. In the presence of the ACE inhibitor, the exercise-induced increase in systolic blood pressure was moderately (n.s.) blunted (204 +/- 7 versus 192 +/- 7 mm Hg). Treatment with the ACE inhibitor did not impair physical performance and RPE. This favorable profile of action was accompanied by no alterations in maximum oxygen uptake and parameters of energy metabolism at all levels of exercise intensity. Therefore, it may be concluded that antihypertensive treatment with an ACE inhibitor should be primarily considered in physically active patients.

Effect of a short maximal physical exercise on the eosinophil cationic protein.

Eosinophil cationic protein (ECP) has been shown to be a marker of eosinophil granulocyte activation. In 10 healthy young subjects the plasma concentrations of ECP were measured before and after a graded maximal bicycle exercise test. The analyses were carried out 30 min before and immediately before exercise, immediately after exercise and 20 and 45 min later. The post-exercise values were corrected for plasma volume changes which were calculated from hematocrit and hemoglobin values. Immediately post-exercise the ECP increased significantly (p < 0.01) from 1.25 +/- 0.28 at rest to 2.40 +/- 0.59 micrograms/l. Twenty and 45 min later the values normalized and significant differences from the pre-exercise values could no longer be measured. The results provide strong evidence for an activation of eosinophil granulocytes after a short maximal exercise.

Diagnostic and prognostic significance of anticardiolipin antibodies in patients with recurrent spontaneous abortions.

PROBLEM: The role of ACA in unexplained RSA is controversial. In the present study, diagnostic and prognostic aspects were investigated. METHOD: One hundred five nonpregnant patients with primary, 29 with secondary RSA, and 209 controls were investigated for IgG-ACA. Follow-up studies were done during pregnancy in 76 individuals. IgM-ACA were tested in a subset of patients. RESULTS: Elevated ACA levels were significantly more frequent in both patient groups (26 and 24%) than in controls (16%). However, there was no correlation of ACA with various parameters including pregnancy outcome. In ACA-positive patients with successful pregnancy a significant decrease of ACA values during pregnancy was observed, while ACA remained high in aborting patients. IgG- and IgM-ACA correlated well. CONCLUSIONS: Although the data from nonpregnant RSA patients does not allow diagnostic or prognostic conclusions to be drawn, sequential testing of ACA-positive individuals provides the possibility to foresee pregnancy outcome.

Reduction of the plasma concentration of C-reactive protein following nine months of endurance training.

An intense physical exercise induces an inflammatory reaction as demonstrated by the delayed increase in blood of acute phase proteins and among them of C-reactive protein (CRP). There is also evidence for a diminished acute phase reaction due to regular exercise suggesting a suppression of the inflammatory response through training. With this background CRP was measured by a sensitive enzyme immunoassay under resting conditions before and after 9 months of training in 14 subjects preparing for a marathon with the aim of studying the effect of training on the base-line CRP concentration. The mean distance run per week increased significantly from 31 +/- 9 km at the beginning to 53 +/- 15 km after 8 months of training (p < 0.01). The aerobic capacity rose significantly after training as demonstrated by the increase of running velocity during a maximal treadmill test from 3.82 +/- 0.29 m/s pre-training to 4.17 +/- 0.17 m/s post-training at a blood lactate concentration of 4 mmol/L (p < 0.01). In 10 of 12 runners base-line CRP was diminished after training in spite of a continuous increase of training intensity. The CRP median fell from 1.19 mg/L before to 0.82 mg/L after training (p < 0.05). Since intense physical exercise is known to be associated with an inflammatory reaction of muscles and tendons, the CRP decrease was unexpected. In 2 subjects the CRP concentration rose markedly because of a borrelia infection and a knee injury, respectively. These values were caused by a pathological condition and were not considered for the statistical evaluation. In 10 non-training control subjects the CRP median did not change significantly during the same 9 months period. The decrease of the CRP base-line concentration after training suggests that intensive regular exercise has a systemic anti-inflammatory effect. This is of particular interest with regard to several recent reports confering on the concentration of CRP in plasma a predictive value for the risk of cardiac infarction, venous thrombosis or stroke.

Prevention of recurrent spontaneous abortion by intravenous immunoglobulin.

Intravenous immunoglobulin (IVIG) treatment was attempted as a novel therapeutic approach for unexplained recurrent spontaneous abortions (RSA) occurring in the first trimester of pregnancy. Twenty women with a history of RSA were treated with IVIG during pregnancy. Therapy was commenced at week 5 of gestation with 1 dose of 0.5-0.6 g IVIG/kg body weight. Infusions were repeated every 3 weeks (0.3-0.4 g/kg) and terminated by week 22 to 24. Of 20 women, 11 delivered healthy infants at term. 5 women are still pregnant, 3 in the third trimester. Only 3 patients suffered abortions and 1 presented with ectopic pregnancy. The overall success rate was 82-86%. Thus, the therapeutic effect of IVIG is comparable to that of the conventional transfusion/vaccination regimen with allogeneic leukocytes, but avoids the risk of transmission of infections and/or HLA immunization, has no major adverse effects and is applicable to 'nonresponders'.

Blood glutathione status following distance running.

In 12 moderately trained subjects reduced glutathione (GSH) and oxidized glutathione (GSSG) as well as thiobarbituric acid reactive substances (TBARS) were measured in the blood before and during the first two hours and first two days after a 2.5-h run. The participants covered between 19 and 26 km (20.8 +/- 2.5 km, mean +/- SD). The running speed was between 53 and 82% of the speed at which blood lactate concentration reached 4 mmol/L lactate (67.9 +/- 8.2%, mean +/- SD) assessed during a previously performed treadmill test. Blood samples were collected 1 h before, immediately before, immediately after, 1 and 2 h after, as well as 1 and 2 days after the run. Immediately after exercise GSH was significantly decreased (p < 0.01) and GSSG significantly increased (p < 0.01). In all subjects the ratio of GSH to GSSG showed a marked decline to 18 +/- 4% (mean +/- SD) of the pre-exercise values (p < 0.01). One hour later the mean GSH and GSSG values returned to baseline. However, there were considerable inter-individual differences. In some subjects the GSH/ GSSG ratio overshot the pre-exercise levels, in others the ratio remained low even two hours after exercise. Compared with the pre-exercise values TBARS concentrations did not change significantly at any time point after exercise. The findings suggest that after prolonged exercise in moderately trained subjects a critical shift in the blood glutathione redox status may be reached. The changes observed were generally short-lived, the duration of which may have depended on the relative importance of reactive oxygen species generation by the capillary endothelial cells and neutrophil and eosinophil granulocytes after the end of exercise.

UVA1 irradiation induces deoxyribonuclease dependent apoptosis in cutaneous T-cell lymphoma in vivo.

Cutaneous T-cell lymphoma (CTCL) is a malignancy of mature T-cells, predominantly of the helper phenotype, that primarily invade the skin. Different photo- and chemotherapeutic treatments are known to be beneficial in early-stage CTCL. This observation has initiated prospective investigations into the efficacy of phototherapeutic regimens. The purpose of our study was to investigate the ability of medium-dose UVA1 phototherapy (60 J/cm2) to induce apoptosis (programmed cell death) in skin infiltrating T-cells of CTCL in vivo. We describe the results of three different staining methods for formalin-fixed, paraffin-embedded tissue sections. The in situ end-labeling (ISEL) procedure, nuclear staining using the DNA-binding fluorochrome Hoechst 33342, and immunohistochemistry using polyclonal antibodies against recombinant mouse deoxyribonuclease I (DNase I) demonstrated that UVA1 irradiation was able to induce marked apoptosis in CTCL. Thereby, ISEL and Hoechst staining clearly revealed DNA-condensation and nuclear fragmentation, accompanied by the formation of typical "apoptotic bodies". The accumulation of DNase I immunoreactivity in the cytoplasm of lymphocytes in UVA1 irradiated skin indicated that DNase I or DNase I-related endonucleases may have acted as apoptotic endonuclease(s) which were synthesized after UVA1 irradiation prior to their apoptotic elimination.