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Biomedical subjects

M Janssen

Publications and source records attributed to M Janssen.

At least 73 records · Page 4Linked to original sources

Controversies in preconditioning.

Preconditioning is an effective mean of protecting the heart against prolonged ischemia by pretreating it with a minor insult, and the present paper reviews various controversies in this highly active field of research. In many models, adenosine plays a role by triggering the activation of protein kinase C. It may work in conjunction with other agents, such as bradykinin, but the putative role of noradrenaline is uncertain. Regulation of the enzyme producing adenosine (i.e., 5'-nucleotidase) has been reported during preconditioning but, because its activity does not seem to be associated with infarct size, it is unlikely that the hydrolase plays a pivotal role. Controversial data have been published on the involvement of mitochondrial ATPase, which may be ascribed to the poor time resolution of the experiments described; however, we do not believe that either acidosis or tissue ATP are important factors in triggering preconditioning. The role of glycolysis in the preconditioning effect remains to be firmly established; opposite mechanisms are activated in low-flow and stop-flow protocols. Although species differences regarding preconditioning exist, they seem to be more of a quantitative than a qualitative nature. The phenomenon could be clinically relevant because evidence is accumulating that preconditioning may take place during bypass surgery and coronary angioplasty if longer balloon-occlusion times are used.

Adenosine↗

Bilateral adrenal enlargement as a first sign of systemic vasculitis.

In this case-report we describe the fatal outcome of systemic vasculitis. A 51-year-old man was hospitalised with constant abdominal pain, chest pain, anorexia, fatigue, weight loss, dyspeptic complaints, and a period of high fever at home. Bilateral adrenal enlargement was found without a plausible cause. Endoscopy revealed a reflux oesophagitis grade I, which was treated with famotidine. His complaints disappeared without further treatment. Five days after release from hospital the patient was re-admitted with subfebrile temperature followed by an Addison's crisis due to primary adrenal failure. Laboratory tests for systemic illness were all negative. He was treated with high-dose corticosteroids. Right adrenal biopsy revealed haemorrhage, possibly of older age. After 10 days he returned with severe kidney and heart failure. He was transported to another hospital for haemodialysis. Unfortunately the patient passed away because of cardiac arrhythmias. Postmortem investigation revealed inflammation of middle-sized and small arteries in the adrenal glands, heart, lung and thyroid. In the kidneys, mesangio-proliferative glomerulonephritis was found. A definite classification of the vasculitis could not be made because of the high-dose corticosteroids therapy. Possibly, the haemorrhage of both adrenal glands was caused by venous thrombosis due to the hypercoagulable state, which is often observed in vasculitis.

Adrenal Gland Diseases↗

INTERACT-CANCER. The development and evaluation of a computer-assisted course on communication skills for medical specialists in oncology.

One of the main problems in training medical specialists in communication skills is the fact that very few specialists participate in such courses. Most courses on communication skills are hard to combine with a busy medical practice because of the course attendance requirement on working days. Interact-Cancer has been developed to facilitate training in communication skills for medical specialists. It is an interactive, computer-assisted course, which fits relatively easily into the busy schedule of medical specialists in oncology because of its flexible character. The course can be followed individually by the participant in his/her own department at suitable periods of time. Interact-Cancer has introduced a new training method. In this study, the appeal of the method to the target group has been tested. Thirty-three medical specialists participated in Interact-Cancer. They evaluated the course as worthwhile, relevant to daily oncological practice, attractive and pleasant. They stated that the course brought inadequacies in their own behaviour to their attention and encouraged them to change their communicative behaviour.

Adult↗

Potentiation of phototactic suppression in Hermissenda by a chemosensory stimulus during compound conditioning.

Modifications of Hermissenda's phototactic behavior by compound pairings of light, scallop extract, and rotation were assessed. In general, the scallop extract potentiated phototactic suppression. Potentiation was dependent on (a) conjunctive presentations of scallop and light, (b) number of conditioning trials, and (c) scallop extract concentration. In related experiments, no second-order conditioning or sensory preconditioning of phototactic suppression was observed, indicating that within-compound associations did not contribute appreciably to potentiation. These results represent the first detailed analysis of compound conditioning in a mollusk using discrete presentations of well-characterized conditioned stimuli from distinct sensory modalities.

Animals↗

Sperm morphology assessment: diagnostic potential and comparative analysis of strict or WHO criteria in a fertile and a subfertile population.

This prospective study compared the diagnostic and predictive potential of sperm morphology assessments in a fertile vs. a subfertile population, evaluated in three different laboratories. The fertile population included 144 men who had recently fertilized their partners. As subfertile controls, 136 men with a history of subfertility for more than 12 months were used. All semen samples (280) were evaluated in three different centres in a blind fashion, without any patient information. The evaluation of sperm morphology was performed according to the criteria normally used in the different laboratories: WHO (1992) criteria for laboratory A, and Tygerberg strict criteria for laboratories B and C. Using ROC analysis, the predictive power of sperm morphology turned out to be different in the three laboratories (area under ROC curve: 69% for lab A, 72% for lab B and 78% for lab C). Using percentile 10 of the fertile population as the cut-off value for normality, we obtained the following results: 2, 1 and 5% for laboratories A, B and C, respectively. Using ROC analysis cut-off values with optimal specificity and sensitivity were 6, 1 and 10%, respectively. Although our data highlight a reasonable predictive power of sperm morphology in centres using different or the same criteria, cut-off values for normality were different, even when the same criteria were applied. These results stress the importance of standardization in sperm morphology evaluation and the need for examining a reference population in estimating the real threshold value in different laboratories.

Fertility↗

Longitudinal analysis of CD4 T cell counts, T cell reactivity, and human immunodeficiency virus type 1 RNA levels in persons remaining AIDS-free despite CD4 cell counts <200 for >5 years.

CD4 cell count, T cell reactivity, and human immunodeficiency virus type 1 (HIV-1) RNA load were examined in 10 persons remaining free of AIDS while CD4 cell counts were <200/mm3 for >5 years, so-called low CD4 cell count long-term survivors (low CD4 LTS), and 10 matched rapid and 10 matched intermediate progressors (AIDS within 1 and 1-3 years). Longitudinal analysis of CD4 cell count and T cell reactivity revealed slower declines in low CD4 LTS. HIV-1 RNA load was 1 log/mL lower in the low CD4 LTS compared with the rapid progressors, with a similar linear increase over time in low CD4 LTS and progressors of 0.1 log/year. There was considerable overlap between groups. The constant difference between low CD4 LTS and progressors probably reflects HIV RNA load early after infection, but low CD4 LTS and progressors show similar slopes of HIV-1 RNA load rise.

Acquired Immunodeficiency Syndrome↗

Semen parameters in a fertile versus subfertile population: a need for change in the interpretation of semen testing.

This prospectively designed study was conducted to compare a fertile and a subfertile population so as to define normal values for different semen parameters. Semen analyses were performed according to the World Health Organization (WHO) guidelines, except for sperm morphology (strict criteria). In the fertile population (n = 144), all patients had recently achieved pregnancy, within 12 months of unprotected coitus. As subfertile controls we examined semen samples from 143 consecutive men attending our infertility clinic during the same study period. Couples with tubal factor infertility and/or ovulatory disorders were excluded from our study. Using receiver operating characteristic (ROC) curve analysis we determined the diagnostic potential and cut-off values for single and combined sperm parameters. Sperm morphology scored best, with a value of 78% (area under the ROC curve). Summary statistics showed a shift towards abnormality for most semen parameters in the subfertile population. Using the 10th percentile of the fertile population as the cut-off value, the following results were obtained: 14.3 x 10(6)/ml for sperm concentration, 28% for progressive motility and 5% for sperm morphology. Using ROC analysis, cut-off values were 34 x 10(6)/ml, 45% and 10% respectively. Cut-off values for normality were different from those described in the WHO guidelines. Routine bacterial and non-bacterial cultures turned out to be of little prognostic value.

Adult↗

Treatment of male infertility due to sperm surface antibodies: IUI or IVF?

This prospectively designed study was aimed at comparing the results of two different treatment protocols in 29 infertile couples with proven male immunological infertility, i.e. a positive (>50%) mixed antiglobulin reaction (MAR) test (IgG and/or IgA). In the first protocol (group I, n = 14) couples were treated with ovarian stimulation/ intrauterine insemination (IUI), followed by in-vitro fertilization (IVF) if no pregnancy occurred after three IUI cycles. In the second protocol (group II, n = 15), patients were treated with IVF as a first choice procedure. The decision to follow protocol 1 or 2 was made by the couples after information about financial costs and expected success rates (according to the literature) for both treatment options. In group I, nine patients (64.3%) conceived after a maximum of three IUI cycles whereas seven patients (46.6%) of group II became pregnant during the first IVF cycle. The take-home baby rate per started IUI or IVF cycle was 27.3% (9/33) and 44.4% (16/36) respectively with a take-home baby rate of 64.3% after three IUI cycles and 93.3% after three IVF attempts. To conclude, both IUI and IVF yielded unexpectedly high pregnancy rates in this selected group of patients with long-standing infertility due to sperm surface (predominantly IgG) antibodies. Since cost benefit analysis comparing superovulation IUI with IVF may favour a course of four IUI cycles, we advocate superovulation IUI as the first line therapy in male immunological infertility.

Adult↗

Intrauterine insemination after ovarian stimulation with clomiphene citrate: predictive potential of inseminating motile count and sperm morphology.

This retrospective study aimed to evaluate the prognostic value of the inseminating motile count (IMC) and sperm morphology (using strict criteria) on success rates after homologous intrauterine insemination (IUI) combined with clomiphene citrate (CC) stimulation. A total of 373 couples underwent 792 IUI cycles in a predominantly (87.4%) male subfertility group. The overall cycle fecundity (CF) and baby take-home rate (BTH) was 14.6 and 9.9% respectively. The cumulative CF and BTH (per couple) after three cycles were 30.6 and 21.1% respectively. Overall, sperm morphology and IMC were of no prognostic value using receiver operating characteristic (ROC) curve analysis, but after classifying the study population into different subgroups according to IMC, sperm morphology turned out to be a valuable prognostic parameter in subgroup 1, i.e. IMC <1 x 10(6). In this subgroup, no pregnancies were seen when the morphology score was <4% and the mean value of sperm morphology was significantly different in the pregnant (8.3%) versus non-pregnant group (5.0%; P <0.05). The cumulative CF and BTH after three IUI cycles were comparable for all couples with the exception of those cases in which the IMC was <1 x 10(6) with a morphology score of <4% normal forms. We recorded only two twin pregnancies (2.5%) and no moderate or severe ovarian hyperstimulation syndrome. We conclude that in a selected group of patients without CC resistance and normal ovarian response following CC stimulation [maximum of three follicles with a diameter of >16 mm at the time of administration of human chorionic gonadotrophin (HCG)], IUI combined with CC-HCG can be offered as a very safe and non-expensive first-line treatment, at least with an IMC of >1 x 10(6) spermatozoa. In cases with <1 x 10(6) spermatozoa, CC-IUI remains important as a first-choice therapy provided the morphology score is > or =4%.

Adult↗

[Neuro-arthropathy, a painless but very destructive disorder of frequently one joint].

In a 38-year-old man who suffered from recurrent painless swelling of the right knee, neuroarthropathy was diagnosed, associated with tabes dorsalis. The patient was treated with a knee brace to stabilise the joint. Neuroarthropathy is a progressive degenerative joint disease caused by a central or a peripheral neurological disorder and causing denervation of the joint.

Adult↗

Glycoalkaloids selectively permeabilize cholesterol containing biomembranes.

The effects of the glycoalkaloids alpha-solanine, alpha-chaconine and alpha-tomatine on different cell types were studied in order to investigate the membrane action of these compounds. Hemolysis of erythrocytes was compared to 6-carboxyfluorescein leakage from both ghosts and erythrocyte lipid vesicles, whereas leakage of enzymes from mitochondria and the apical and baso-lateral side of Caco-2 cells was determined. Furthermore, the effects of glycoalkaloids on the gap-junctional communication between Caco-2 cells was studied. From these experiments, it was found that glycoalkaloids specifically induced membrane disruptive effects of cholesterol containing membranes as was previously reported in model membrane studies. In addition, alpha-chaconine was found to selectively decrease gap-junctional intercellular communication. Furthermore, the glycoalkaloids were more potent in permeabilizing the outer membrane of mitochondria compared to digitonin at the low concentrations used.

Adenylate Kinase↗

Randomised placebo-controlled study of stopping second-line drugs in rheumatoid arthritis.

BACKGROUND: A favourable benefit/risk ratio for treatment of rheumatoid arthritis (RA) with second-line drugs has been established only in short-term studies. The present investigation addresses the question of whether RA patients with a good response to long-term treatment with second-line drugs benefit from continuation of such treatment. METHODS: A 52-week randomised double-blind placebo-controlled multicentre study was conducted to assess the effect of stopping second-line therapy in 285 RA patients with a good long-term therapeutic response. The patients either continued the second-line drug (n = 142) or received a placebo (n = 143). The endpoint was a flare, defined as recurrence of synovitis. FINDINGS: At entry into the study median duration of second-line drug therapy was 5 years (range 2-33). At 52 weeks the cumulative incidence of a flare was 38% for the placebo group and 22% for the continued therapy group (p = 0.002). The risk of a flare was 2.0 times higher for patients receiving placebo than for those continuing the second-line drug (95% CI 1.27 to 3.17). The same trend was found for each second-line drug separately, with the exception of d-penicillamine. Side-effects that necessitated dose reduction or discontinuation occurred in 2 patients in each group. INTERPRETATION: Second-line drugs continue to be effective in RA patients who have responded well to initial treatment.

Anti-Inflammatory Agents, Non-Steroidal↗

High-dose ranitidine for the prevention of recurrent peptic ulcer disease in rheumatoid arthritis patients taking NSAIDs.

BACKGROUND: Continuous therapy with low-dose ranitidine (150 mg b.d.) is known to be effective for the prevention of recurrent nonsteroidal anti-inflammatory drug (NSAID)-associated duodenal ulcer but not for gastric ulcer. AIM: To investigate, in a double-blind placebo-controlled study, the preventive effect of a high dose of ranitidine (300 mg b.d.) on the recurrence of both duodenal ulcers and gastric ulcers in rheumatoid arthritis patients with a continuous need for NSAIDs. METHODS: Rheumatoid arthritis patients with a history of peptic ulcer disease were randomized to receive either ranitidine 300 mg b.d. or placebo for 12 months. Endoscopy was performed at study entry and after 6 and 12 months. End-point was the recurrence of gastric or duodenal ulcers. RESULTS: The study was stopped after a blinded interim analysis; at that time 10 of the 15 included patients in each treatment group were evaluable. Recurrent duodenal ulcers had occurred in four patients treated with placebo and none of the patients treated with ranitidine (Fisher's exact one-tailed P = 0.04; 95% CI, - 0.70 to -0.10). Recurrent gastric ulcers had occurred in six patients in the placebo group and three patients in the ranitidine group (Fisher's exact one-tailed P = 0.18; 95% CI, -0.72 to 0.12). Two patients in the placebo group had developed both duodenal ulcers and gastric ulcers. No adverse events were observed. CONCLUSIONS: High dose ranitidine is effective for the prevention of recurrent duodenal ulcer but not for recurrent gastric ulcer in rheumatoid arthritis patients taking NSAIDs.

Aged↗

Effects of fast clinostat treatment and microgravity on Vicia faba L. mesophyll cell protoplast ubiquitin pools and actin isoforms.

With parabolic rocket flights and fast clinostat treatments, the effect of microgravity on ubiquitin, ubiquitin-protein conjugates, and actin isoforms of Vicia faba mesophyll protoplasts was studied. Western immunoblotting with ubiquitin antibodies revealed that simulated and particularly, real microgravity influenced the amount of free ubiquitin and of 18, 19, and 40 kD ubiquitin conjugates by inducing strong oscillations in the proteins concentrations over time. Simulated microgravity and microgravity-phase during parabolic rocket flights resulted in a decrease of actin isoforms. Results obtained support the assumption, that microgravity and fast clinostat treatment have a direct effect on Vicia faba mesophyll protoplast metabolic activities.

Actins↗