Immunological factors in endometriosis-associated reproductive failure: studies in fertile and infertile women with and without endometriosis

Immunopathophysiological mechanisms in endometriosis-associated reproductive failure were studied in appropriate populations: infertile and fertile women with and without endometriosis. The incidence of sera positive for any of the autoantibodies tested among infertile women with endometriosis (n = 25) was similar to that observed in the three control groups [unexplained infertility patients (n = 25) and fertile women with (n = 10) and without (n = 25) endometriosis]. The mean volume of peritoneal fluid was significantly elevated in women with endometriosis (both fertile and infertile) as compared with patients without endometriosis (fertile or infertile). The concentration of peritoneal fluid leukocytes and the percentage of cells positive for macrophage markers were significantly increased and the percentage of T lymphocytes significantly decreased in infertile women with endometriosis but not in patients with unexplained infertility and fertile women with endometriosis, as compared with fertile controls without endometriosis. Macrophages from infertile patients with endometriosis had higher sperm phagocytosis than did those from infertile women without endometriosis or fertile subjects with or without endometriosis. Incidences of serum and peritoneal fluid samples embryotoxic to the in-vitro development of 2-cell mouse embryos were significantly higher in infertile patients with endometriosis than in unexplained infertility patients and fertile women with or without endometriosis. It is concluded that immunological mechanisms of endometriosis-associated infertility exist but that these peritoneal immunological factors in infertile women with endometriosis are related to their subfertility rather than to the presence of ectopic endometrial implants. This is supported by the lack of immunological abnormalities observed among fertile women with endometriosis. These immunological abnormalities are lacking in patients with unexplained infertility.      

The ileoanal J pouch: radiographic evaluation

Endorectal ileoanal pull-through offers an attractive alternative to proctocolectomy and ileostomy for patients with ulcerative colitis, Gardner syndrome, and familial polyposis. To our knowledge, a careful radiographic analysis of the ileum, ileal pouch, and ileoanal anastomosis after ileoanal pull-through has not been reported. Thirty-two patients with ulcerative colitis, Gardner syndrome, and familial polyposis underwent colectomy, mucosal proctectomy, and endorectal ileoanal pull-through of a 15-cm ileal "J" pouch and loop ileostomy. Twenty-five (78%) of 32 of all the pouches radiographically demonstrated spiral folds extending from the middle of the pouch to the pectinate line. Other radiographic features included a mesenteric mass effect, pseudopolyps, and a central lucency that indicated intrapouch sutures. Radiographs provide useful information in the postoperative management of the ileal pull-through.     

A prospective study of the accuracy of preoperative computed tomographic staging of patients with biopsy-proven rectal carcinoma

From June 1983 to January 1986, 91 patients with biopsy-proven adenocarcinoma of the rectum had computed tomographic scans of the pelvis performed before treatment as part of a "sandwich" radiotherapy-surgery regimen. Two experienced diagnostic radiologists performed locoregional staging of all scans according to the University of California at San Francisco criteria; one of these radiologists repeated this staging at a later time to test the reproducibility of a single observer. Staging was performed without the use of any other radiographic studies or of any clinical information except the patients' age, sex, and the diagnosis of rectal carcinoma, to test the value of computed tomographic scans alone for staging. Agreement between the two stagings performed by the first observer was 51 percent, and interobserver agreement was only 37 percent. Agreement with Dukes' staging was only 33 percent. Therefore, preoperative pelvic computed tomographic scanning of primary rectal adenocarcinoma should not be relied upon for staging or for the selection of patients for treatment options.     

Ultraviolet exposure in the environment of welding work sites

It has been checked if the "limits of the acceptable doses of ultraviolet radiation of monochromatic radiation at the workplace" (NIOSH-standard of USA) are adhered to in the vicinity of welders' work stations in a factory hall. For recording of UV-doses polysulphon films have been used. According to these investigations non-welders are exposed to doses of UV-radiation which exceed the limits recommended by about eight times. Clinical examinations of these persons showed chronic damage of the external parts of the eyes in a higher percentage than in a control group. It is pointed to the necessity of taking protective measures to shield persons working in the vicinity of welding job sites from ultraviolet radiation.     

Effects of taprostene,a stable prostacyclin analogue,on haemodynamics,platelet function and arachidonate metabolism in healthy volunteers

Summary In order to assess the effect of taprostene on haemodynamics, platelet function and arachidonate metabolism in 4 healthy volunteers an intravenous infusion of 25 ng · kg^–1 · min^–1 was given for 6 h.During the infusion period systolic blood pressure dropped from 130 to 111 mm Hg and diastolic blood pressure from 77 to 69 mm Hg. The heart rate rose from 77 to 84 beats/min.During the taprostene infusion the slope and height of the ADP and collagen induced platelet aggregation curves were significantly inhibited and the sensitivity of platelets to PGI₂ and PGE₁ was increased.Plasma and serum thromboxane B₂, conversion of exogenous radiolabelled arachidonic acid, WU-test, circulating endothelial cell count, concentration of platelet factor 4, -thromboglobulin, malondialdehyde and the PGI₂-synthesis stimulating plasma factor did not show any clear drug-related alteration.It is concluded that infusion of taprostene 25 ng · kg^–1 · min^–1 caused measurable inhibition of platelet function ex vivo.     

Enhanced survival of glioma bearing rats following boron neutron capture therapy with blood-brain barrier disruption and intracarotid injection of boronophenylalanine

Boronophenylalanine (BPA) has been used for boron neutron capture therapy (BNCT) of brain tumors in both experimental animals and humans. The purpose of the present study was to determine if the efficacy of BNCT could be enhanced by means of intracarotid (i.c.) injection of BPA with or without blood-brain barrier disruption (BBB-D) and neutron irradiation using a rat brain tumor model. For biodistribution studies, F98 glioma cells were implanted stereotactically into the brains of Fischer rats, and12 days later BBB-D was carried out by i.c. infusion of 25% mannitol (1.373 mOsmol/ml), followed immediately by i.c. administration of 300, 500 or 800 mg of BPA/kg body weight (b.w.). At the 500 mg dose a fourfold increase in tumor boron concentration (94.5 g/g) was seen at 2.5 hours after BBB-D, compared to 20.8 g/g in i.v. injected animals. The best composite tumor to normal tissue ratios were observed at 2.5 hours after BBB-D, at which time the tumor: blood (T: Bl) ratio was10.9, and the tumor: brain (T: Br) ratio was 7.5, compared to 3.2 and 5.0 respectively for i.v. injected rats. In contrast, animals that had received i.c. BPA without BBB-D had T: Bl and T: Br ratios of 8.5 and 5.9, respectively, and the tumor boron concentration was 42.7g/g. For therapy experiments, initiated 14 days after intracerebral implantation of F98 glioma cells, 500 mg/kg b.w. of BPA were administered i.v. or i.c. with or without BBB-D, and the animals were irradiated 2.5 hourslater at the Brookhaven Medical Research Reactor with a collimated beam of thermal neutrons delivered to the head. The mean survival time for untreated control rats was 24 ± 3 days, 30 ± 2 days for irradiated controls, 37 ± 3 days for those receiving i.v. BPA, 52 ± 15 days for rats receiving i.c. BPA without BBB-D, and 95 ± 95 days for BBB-D followed by i.c. BPA and BNCT. The latter group had a 246% increase in life span (ILS) compared to untreated controls and a 124% ILS compared to that of i.v. injected animals. These survival data are the best ever obtained with the F98 glioma model and suggest that i.c. administration of BPA with or without BBB-D may be useful as a means to increase the efficacy of BNCT.     

Non-responsiveness to hepatitis B vaccination in haemodialysis patients: association with impaired TCR/CD3 antigen receptor expression regulating co-stimulatory processes in antigen presentation and recognition

The study was undertaken to evaluate the relationship betweennon-responsiveness to hepatitis B (HBV) vaccination in haemodialysedpatients and HBs antigen (Ag) presentation and recognition dependingon TCR/CD3 receptors expression. We have found that the causeof the blunted response to HBV vaccination is multifactorialand seems to be associated with the following: (1) A reducednumber of TCR/CD3 antigen receptor complexes on freshly isolateduraemic CD4 T cells, especially in non-responders. (2) The bluntedproliferative response of uraemic CD4 T cells isolated fromnon-responders and stimulated for 6 days by autologous monocytespresenting HBsAg was associated with the decreased density ofthe TCR/CD3 receptors. (3) Moreover, in uraemic non-respondersthe expression of adhesion and accessory molecules on monocytes(intercellular adhesion molecule-1/ ICAM-1, HLA-DR/Ia/) wassignificantly decreased following the culture with autologousmonocytes serving as HBsAg-presenting cells. CD4 molecules andlymphocyte function antigen-1ß /LFA-1ß/on helper-inducer T cells were increased before and after theculture. (4) These findings were also associated with a diminishedbinding capacity of IL-1ß and IL-6 to their receptorson helper-inducer T cells. (5) IL-2, IFN- and IL-4 productionwas decreased in uraemic non-responders, especially after 72h of the culture. (6) Inhibited proliferation of helper-inducerT cells in uraemic non-responders was only partially reversiblein the presence of exogenous IL-1ß, IL-6, IL-2 andIFN-. (7) HLA typing of uraemic non-responders was associatedwith extended haplotype: HLA A1, B8, DR3, DR7, DQ2.     

Congenital muscular dystrophy and severe central nervous system atrophy in two siblings

Severe degenerative features of the nervous system of a hitherto unknown kind, associated with a neuromuscular disorder with histopathological features of congenital muscular dystrophy, are reported in two female siblings. The clinical profile was characterized by generalized hypotonia followed by spastic tetraplegia, contractures, polyneuropathy, lack of cognitive development and progressive microcephaly. There was no involvement of the eyes. Neuropathological examination of the brain of one sibling, who died at the age of 30 months, revealed subtotal loss of neurons in the cerebral and cerebellar cortex and in the ventral pons, and secondary loss of myelin in the cerebral and cerebellar subcortical white matter. Sural nerve biopsy in the other sibling, who had a similar neurological affection, showed a lack of large myelinated fibers.This investigation is part of the research program Disorders of the Neuromuscular System of the University of Nijmegen     

The inhibitory modulation of guinea-pig intestinal peristalsis caused by capsaicin involves calcitonin gene-related peptide and nitric oxide

The effect of capsaicin-induced stimulation of afferent neurons on peristalsis and the possible neural mediators involved in this action were examined in the guinea-pig isolated ileum. The intraluminal pressure threshold for eliciting peristaltic waves was used to quantify facilitation (decrease in threshold) or inhibition (increase in threshold) of peristalsis. Capsaicin (0.1–1 M) caused an initial short-lasting stimulation of peristalsis followed by a prolonged inhibition of peristaltic activity. Capsaicin (1 M) was ineffective when the gut segments had been pretreated with 3.3 M capsaicin, which is indicative of an afferent neuron-dependent action of the drug. In contrast, the abolition of peristalsis caused by a high concentration of capsaicin (33 M) was fully reversible on removal and reproducible on readministration of capsaicin, a feature characteristic of a nonspecific depression of smooth muscle excitability. Baseline peristalsis and the excitatory/inhibitory effect of capsaicin (1 M) on peristalsis remained unaltered by a combination of the tachykinin NK₁ receptor antagonist ( + )-(2S, 3S)-3-(2-methoxybenzylamino)-2-phenyl piperidine (CP-99,994; 0.3 M) and the tachykinin NK₂ receptor antagonist L(-)-N-methyl-N[4-acetylamino-4-phenyl-piperidino-2-(3,4-dichlorophenyl)butyl]-benzamide (SR-48,968; 0.1 M). Further experiments, performed in the presence of a low concentration of atropine (10 nM) showed that the catcitonin gene-related peptide (CGRP) antagonist human -catcitonin gene-related peptide (8–37) [hCGRP (8–37); 10 M] attenuated the delayed inhibitory effect of capsaicin on peristalsis, but did not influence baseline peristaltic activity and the capsaicin-induced facilitation of peristalsis. Blockade of nitric oxide (NO) synthesis by N ^G-nitro-l-arginine methylester (l-NAME, 300 M) facilitated baseline peristaltic activity and reduced the delayed inhibition of peristalsis caused by capsaicin (1 M) without affecting the initial peristalsis-stimulating action of capsaicin. The effects of l-NAME were prevented by l-arginine (1 mM). The data of the current study indicate that capsaicin-sensitive afferent neurons do not participate in the neural pathways subserving peristalsis in the guinea-pig small intestine, but modulate peristaltic activity upon stimulation with capsaicin. The initial stimulant action of capsaicin on peristalsis is independent of tachykinins acting via NK₁ or NK₂ receptors, while the delayed capsaicin-induced depression of peristalsis involves CGRP and NO.     

Evaluation of abstracts submitted for the annual meeting of the German Neurosurgical Society 1999--unravelling a mystery

The evaluation for the abstracts submitted for the annual meeting of the German Neurosurgical Society together with the Swiss Neurosurgical Society in Munich 1999, is presented as it has developed during the meetings of the last years. 597 abstracts were reviewed by the 30 members of the review committee according to a 5 point grading system. Cut off for acceptance was a mean grading of 2.7 points. Abstracts better than 2.4 were accepted, abstracts worse than 2.7 were rejected. Experimental studies were judged slightly better than clinical studies: the mean grading of clinical and experimental studies was 2.55 +/- 0.5 vs. 2.72 +/- 0.6 (p < 0.02). All abstracts with a mean grading of 2.4-2.7 and a standard deviation > 1.0 were discussed in a meeting of the review committee. 353 abstracts were accepted. Some of the abstracts submitted for oral presentation had to be converted to poster presentations. Among others the decision was based on the grading of the abstract.