Neurogenic bladder after operation of rectal cancer

Of the patients who had had a urodynamic examination during the five year period from 1982 to 1987 in our clinic, 48 patients underwent operations for rectal cancer prior to the study. In 35 of them, the operation mode was known. If the pelvic nerve is damaged by operative modes for rectal cancer, urinary disturbances of severe kinds may occur. In spite of such disturbances, 71.4% of those who had had excision of the low anterior part and 51.9% of those with Miles' operation could be weaned from the clean intermittent self-catheterization and take up spontaneous urination. Even in patients who developed severe dysuria, if catheterized at an early stage, many of them could urinate by abdominal pressure with in several months after operation, without the aid of a catheter. This transition took place mostly within one year after operation. When a patient develops dysuria after radical surgery for rectum cancer, treatment mainly with self-catheterization is an effective method at present.     

Representativity of endomyocardial biopsies: a theoretical approach based on quantitative light microscopy

To create a model for studying the regional variation in the histologic structure of left ventricular myocardium and the representativity of samples from endomyocardium in predicting the state of myocardium as a whole, 12 human hearts (3 normal and 9 pathological) were investigated with histoquantitative methods. Ten small endomyocardial areas representing biopsy sites (mean area on section 0.94 mm2) were delineated from each heart. The volume fractions of myocardial fibers (VVMY), interstitial space (VVINT) and connective tissue (VVCT) were determined with a point counting method on these areas. Also the mean fiber diameter was measured. The results were compared with the results from three full thickness samples (mean area 3 cm2) from each heart. The values for fiber diameter estimates were almost identical in endomyocardial samples and full thickness samples. On the other hand, VVCT was significantly higher and VVMY lower in endomyocardial samples. The coefficient of variation (10 endomyocardial areas) was 8.3% for fiber diameter, 17.8% for VVMY and 77.5% for VVCT. When estimates of the regional variation within the heart area are available, it is possible to create a model for the prediction of the number of endomyocardial biopsies needed to reach a given accuracy and probability of measurements. The representativity and clinical value of endomyocardial biopsies are discussed on the basis of this statistical approach.     

Effect of totally absorbable implant volume on wound infection rate: Study of 2500 operated fractures, osteotomies, and ligament injuries

Between November 1984 and January 1994 in our department, a total of 2500 patients were treated with totally absorbable internal fixation devices. We studied these patients and analyzed results with regard to the volume of the absorbable implants and the development of wound infection. Of the 2500 patients 2044 were trauma patients and 456 were operated on for orthopedic disease. In 1466 patients treated with implants made of self-reinforced polyglycolic acid (SR-PGA) only, the patients who developed wound infection had a higher implant volume (P=0.07) than those who did not; this difference was close to statistical significance. In the 446 patients who received only implants made of self-reinforced poly-l-lactic acid (SR-PLLA), the 5 who developed wound infection had a mean implant volume more than three times that of the non-infected patients (P=0.01). We found that in the patients treated with the earlier SR-PGA implants, which contained a green staining material, there was no correlation between implant volume and incidence of wound infections. On the other hand, both the non-stained SR-PGA implants, which have been in clinical use since 1989, and the SR-PLLA implants, seem to be more predictable in terms of wound infections. We believe that this difference, is largely due to the lower level of tissue reactions with these newer implants.     

Effect of Vigabatrin on the Electroencephalogram in Rats

Vigabatrin (gamma-vinyl GABA; GVG) is a new antiepileptic drug (AED) that increases the level of the inhibitory transmitter, gamma-aminobutyric acid (GABA) in the brain. We evaluated the effect of GVG on the EEG of normal rats. GVG was administered intraperitoneally (i.p.) at a dose of 100 mg/kg once a day for 12 days. EEG was recorded at baseline, on the fourth day, at the end of the 12-day GVG period and 10 days after discontinuation of GVG. GVG increased the amplitude of delta (1-4 Hz) and theta (4-8 Hz) frequency bands and resulted in slowing of the peak frequency (Fp) and mean frequency (Fm) in both the frontal and occipital cortex, especially during waking-immobility. EEG changes normalized within 10 days after the last GVG injections. The results suggest that a relationship may exist between the EEG changes and increase in GABA levels with GVG.     

Subtype specificity of γ-aminobutyric acid type A receptor antagonism by clozapine

Clozapine, an atypical neuroleptic, functionally antagonizes the -aminobutyric acid-induced chloride uptake via the main central inhibitory receptor, -aminobutyric acid type A (GABA_A) receptor, in brain vesicles. GABA_A antagonism by micromolar concentrations of clozapine is more efficient in rat cerebrocortical and hippocampal membranes than in cerebellar membranes, as evidenced by clozapine reversal GABA-inhibition of [³⁵S]t-butylbicyclophosphorothionate ([³⁵S]TBPS) binding. A typical neuroleptic, haloperidol, failed to antagonize GABA in any of these brain regions, while the specific GABA_A antagonist 2-(3-carboxy-2,3-propyl)-3-amino-6-p-methoxyphenylpyrazinium bromide (SR 95531) was efficient in all three brain regions. Clozapine action on [³⁵S]TBPS binding was unaffected by the benzodiazepine receptor antagonist flumazenil. Clozapine inhibited the binding of [³H]muscimol and [³H]SR 95531 to the GABA recognition site, but this effect only partially correlated with the regional differences in and the potency of clozapine antagonism of GABA-inhibition of [³⁵S]TBPS binding, suggesting that also other than GABA sites may mediate clozapine actions. Autoradiography of [35S]TBPS binding revealed GABA antagonism by clozapine in most brain regions. Main exceptions were cerebellar granule cell and molecular layers, olfactory bulb external plexiform and glomerular layers and primary olfactory cortex, where clozapine antagonized GABA inhibition less than average, and lateral hypothalamic and preoptic areas where its antagonism was greater than average. Recombinant 622 receptors, the predominant 6 subunit-containing receptor subtype in cerebellar granule cells, failed to show GABA antagonism by clozapine up to 100 M. In contrast, recombinant 122 receptors, forming the predominant receptor subtype in the brain, were clozapine sensitive. Recombinant 622 and 632 receptors resulted in clozapine-insensitive receptors, whereas 612 receptors were clozapine sensitive. The efficacy of clozapine to antagonize GABA in 1x2 receptors decreased in the order of 112>122>132. The results indicate that clozapine antagonizes the function of most GABA_A receptor subtypes, and that the interaction is determined by the interaction of the and subunit variants. GABA antagonism is a unique property of clozapine, not shared by haloperidol, which might be involved in the pharmacological mechanism for the increased seizure susceptibility associated with clozapine treatment.     

Hospital water supply as a source of disseminated Mycobacterium fortuitum infection in a leukemia patient.

Nosocomial acquisition of Mycobacterium fortuitum led to a disseminated infection in a leukemia patient. A linkage to showerhead water was supported by molecular typing of clinical and environmental isolates. Contamination of the hospital water system with microbes that are relatively resistant to common sanitation processes poses an increased risk of infection to neutropenic patients.     

Relationship between Field Strength and Abnormal Development in Chick Embryos Exposed to 50 Hz Magnetic Fields

Summary

Chick embryos were exposed to sinusoidally oscillating 50 Hz magnetic fields during their first 2 days of development. In the first series of experiments magnetic field strengths of 0·1, 0·3, 1 and 10 A/m were used. The percentage of abnormal embryos (%AE) was 16 per cent in the sham-exposed control group. %AE was increased at 1 A/m (29 per cent) and 10 A/m (32 per cent), but not at 0·1 A/m (16 per cent) or 0·3 A/m (14 per cent). In the second series of experiments field strengths of 0·4, 0·6, 0·9 and 1·35 A/m were used. %AE was 17 per cent in the control group, 10 per cent at 0·4 A/m, 19 per cent at 0·6 A/m, 17 per cent at 0·9 A/m and 36 per cent at 1·35 A/m. Only the 1·35 A/m group was significantly different from the controls. The results of this study suggest that exposure of chick embryos to a 50 Hz magnetic field causes abnormal development, and that no abnormalities are induced below a threshold between 0·9 and 1 A/m.     

Successful in vitro graft-versus-tumor effect against an Ia-bearing tumor using cyclosporine-induced syngeneic graft-versus-host disease in the rat

Lethally irradiated LouM rats reconstituted with syngeneic bone marrow and then treated with cyclosporine (CsA) for 40 consecutive days following transplant developed a graft-v-host disease (GVHD)-like syndrome after CsA cessation. This model of GVHD was used to define and characterize a graft-v-tumor (GVT) effect against a syngeneic plasmacytoma CRL1662 cell line which expresses class II major histocompatibility (MHC) antigen (Ia). Nylon wool-nonadherent spleen cells from animals who developed syngeneic GVHD were capable of significant lysis against chromium-labeled tumor target cells in a four-hour chromium released cell mediated lympholysis assay; maximum lysis occurred five days following cessation of CsA when clinical signs first appeared. Cytolytic activity declined to baseline as GVHD symptoms resolved. Fractionation of splenocytes into lymphocyte subsets demonstrated that cytolytic lymphocytes (CTLs) of the OX8 phenotype (non-helper T) were capable of significant lysis against tumor target cells. Lysis of tumor cells was blocked by preincubation with monoclonal antibodies (MoAb) specific for the rat anti-class II MHC antigen but not with MoAb against class I. Incubation of tumor cells with gamma-interferon increased expression of tumor class II MHC antigens and significantly increased their susceptibility to lysis by nylon wool-nonadherent splenocytes from animals with syngeneic GVHD. These studies have demonstrated an in vitro GVT of syngeneic GVHD against an Ia-bearing tumor; the effector cell is a CTL of the OX8 phenotype specific for the class II MHC antigen.     

Low-dose or intermediate-dose cyclophosphamide plus granulocyte colony-stimulating factor for progenitor cell mobilisation in patients with multiple myeloma

Cyclophosphamide (CY) combined with granulocyte colony-stimulating factor (G-CSF) is commonly used to mobilise blood progenitor cells to support high-dose therapy in patients with multiple myeloma (MM). The optimal dose of CY in this setting is unknown. We have retrospectively analysed mobilisation efficiency and need for supportive care in 57 patients with newly diagnosed myeloma previously treated with VAD+/-local radiotherapy. The patients were mobilised either with low-dose CY (LD-CY, 1.2-2 g/m(2)) (n=25) or intermediate-dose CY (ID-CY, 4 g/m(2)) (n=32) plus G-CSF. Both regimens proved to be effective in the progenitor cell mobilisation. At least 2 x 10(6)/kg CD34+ cells were collected from 88% and 84% of the patients with a single apheresis, respectively. Only one patient in the LD-CY group (4%) failed to mobilise vs none in the ID-CY group. Patients mobilised with LD-CY plus G-CSF had less toxicity: fewer hospital days during the mobilisation and apheresis procedures (5 vs 9 days, P<0.001), lower frequency of fever (20 vs 73%, P<0.001) and less need for supportive care including platelet transfusions (0 vs 24%, P=0.004) and days on parenteral antibiotics (0 vs 4 days, P<0.001). While these regimens seem to be equally effective in terms of progenitor cell mobilisation in newly diagnosed patients with MM, LD-CY+G-CSF is preferential because of more optimal resource utilisation and more favourable toxicity profile.