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Biomedical subjects

J Groen

Publications and source records attributed to J Groen.

At least 73 records · Page 4Linked to original sources

Treatment of refractory urge urinary incontinence with sacral spinal nerve stimulation in multiple sclerosis patients.

BACKGROUND: Urge urinary incontinence in multiple sclerosis patients is usually due to detrusor hyperreflexia. Patients who do not respond to conservative measures such as anticholinergics, with or without clean intermittent catheterisation, are difficult to manage. METHODS: We applied electrical stimulation to the S3 sacral spinal nerves with the aim of activating afferent somatic nerve fibres. Stimulation of these fibres can inhibit the micturition reflex. An S3 electrode coupled to a subcutaneously placed pulse generator was implanted in four women who had shown a good response during temporary stimulation via a percutaneously placed wire electrode. All patients were followed for at least 2 years. FINDINGS: The number of leakage episodes decreased from a mean of 4 to 0.3 per 24 h. Two patients were completely dry. The hyperreflexia disappeared in one, improved in two, and got worse in one patient. The urodynamic result in the last patient may be explained by clinical progression of the multiple sclerosis. INTERPRETATION: Chronic stimulation of the S3 sacral spinal nerve by an implantable neuroprosthesis is a promising treatment option for selected multiple sclerosis patients with refractory urge incontinence.

Adult↗

Rabies vaccine potency control: comparison of ELISA systems for antigenicity testing.

Potency control of inactivated rabies vaccines for human and veterinary application is usually undertaken by vaccination-challenge tests (e.g. the mouse potency test). For practical and ethical reasons there is an urgent need to replace in vivo potency control procedures, at least in part, by reliable methods of in vitro potency testing. Quantitative ELISA systems for potency control were developed using monoclonal antibodies (MAbs) directed to the glycoprotein (GP) and to the nucleoprotein (NP) of the virus. Although immuno-capture and competition ELISAs for GP measurement had almost equal sensitivity (detection level GP < 0.1 IU), the competition data showed the best correlation with potency values when a panel of rabies vaccines for human use was tested (r = 0.88, n = 10). The NP values for this panel of vaccines in the competition system (detection level NP < 1 IU) also correlated well with potency values (r = 0.90, n = 10). The competition system proved to be best also with liquid adjuvanted veterinary rabies vaccines of LEP, PM, PV and SAD origin. The implementation of ELISA systems for potency control of rabies vaccines is discussed.

Animals↗

The influence of extracellular Ca2+ on the time course of isovolumetric pressure development in the guinea-pig urinary bladder.

Isovolumetric contractions were induced electrically in five guinea-pig bladders in a 1.8 mM Ca2+ buffer solution at two different volumes. The rate of pressure development was studied by analysis of phase-plots, which are plots of the rate of change of intravesical pressure as a function of pressure. At relatively large volumes the rate of pressure development showed a biphasic nature, suggesting that two different processes were involved in different phases of contraction. Extracellular Ca2+ was manipulated to identify these processes. Removal of extracellular Ca2+ led to an 85% reduction of the maximum isovolumetric pressure in subsequent stimulations, but pressure developed faster. The biphasic nature of pressure development at large volumes tended to disappear. It was concluded that at large bladder volumes pressure development in this type of smooth muscle is determined by the release of intracellularly stored Ca2+ in the early phase of contraction. In the final phase the rate of pressure development is limited by the extracellular Ca2+ influx. At small bladder volumes the Ca2+ influx takes place at a higher rate, so that the contribution of intracellular Ca2+ release to pressure development could not be identified at these volumes.

Animals↗

Shortening induced deactivation in the guinea-pig urinary bladder.

Shortening induced deactivation, the depressant effect of active muscle shortening on the subsequently measured isometric force, has been shown in smooth muscle strips and rings. The guinea-pig bladder permits the investigation of this phenomenon in a whole organ preparation. Previous work in our laboratory showed that shortening of the in vitro guinea-pig detrusor muscle had a depressant effect on the isovolumetric pressure that could be generated immediately afterwards. To test the hypothesis that this was caused by deactivation, the effects of active and passive detrusor shortening on the subsequently measured isovolumetric pressure were compared. The isovolumetric pressures measured after 5 min periods of recovery were taken as control values. It was found that the isovolumetric pressure after passive shortening was 7% smaller than the isovolumetric pressure without preceding shortening. This difference was ascribed to viscoelastic relaxation during shortening. Active shortening had an additional 8% depressant effect on isovolumetric pressure compared with passive shortening. The effects of active and passive shortening differed significantly. It was concluded that shortening induced deactivation in the guinea-pig urinary bladder smooth muscle in toto can be considered proven. The fact that deactivation is shown both by striated and smooth muscle preparations is in line with the assumption that it is caused by reduced actin-myosin interaction. The hypothesis that (in striated muscle) the latter is effected by a decrease in troponin-calcium binding, however, needs reconsideration.

Animals↗

Neurogenic modulation of urethral resistance in the guinea pig.

PURPOSE: The resistance offered to urinary flow by the urethra is one of the factors determining the course of micturition. It was the aim of the present work to study the dependence of urethral resistance on the degree of relaxation of the urethra. MATERIALS AND METHODS: Experiments were done in the guinea pig. Ten animals were used. In 5 animals saline was forced through the (unrelaxed) urethra at imposed flow rates in the range of 1.1 to 43.0 ml. per minute while the urethral pressure was measured. Second degree polynomials were fitted to the pressure/flow data. In the other 5 animals micturition contractions were evoked and pressure/flow plots were derived from the measured signals. A straight line was fitted to the lowest pressure values at each flow rate in these plots. These pressure values represent the most relaxed state of the urethra in these voidings. RESULTS: The pressures measured in the unrelaxed urethra were much higher than the pressures measured during voiding in the same flow rate range, but the intercepts of the mathematical equations fitted to the pressure/flow data on the pressure axis were not significantly different in the 2 groups. CONCLUSIONS: The unrelaxed urethra has a much "steeper" pressure/flow characteristic than the relaxed urethra. However, the urethral closing pressure, that is, the intercept of the pressure/flow characteristic on the pressure axis, does not depend on the state of relaxation of the urethra.

Animals↗

Development and evaluation of alternative testing methods for the in vivo NIH potency test used for the quality control of inactivated rabies vaccines.

The potency control of rabies vaccines is routinely performed in a vaccination-challenge test (NIH test), which induces substantial distress and suffering in laboratory mice. Although, according to the recommendations by the WHO, partial replacement of this in vivo potency test by in vitro antigenicity testing is permitted, no internationally accepted alternative testing method is yet available. In the present study, we focussed on the use of monoclonal antibody-based ELISA systems for the quantitative detection of rabies glycoprotein in vaccines for human and veterinary use. Results in the newly developed competitive binding ELISA for glycoprotein quantification showed good correlation with NIH potencies. Also, the applicability for vaccines based on different virus strains was demonstrated. Quantification methods were remodelled to convenient ELISA kits for interlaboratory evaluation of the sensitivity and reproducibility in an internal collaborative study. The relevance of the data generated with these assays is currently assessed by parallel studies evaluating vaccine-induced B and T cell-mediated immunity. We speculate that the assays developed will provide, at least in part, a suitable replacement for the NIH potency test.

Animal Testing Alternatives↗

Hantavirus antigen detection in kidney biopsies from patients with nephropathia epidemica.

Renal biopsies collected from ten patients with serologically confirmed Puumalavirus (PUUV) infection in the acute stage with renal dysfunction who lived in the same PUUV endemic area in The Netherlands, were studied histologically, immuno-histochemically and subsequently examined for the presence of viral antigen by immunoperoxidase staining. Interstitial hemorrhages and deposition of IgM, complement component C3 and fibrin along the basal side of the tubular epithelial cells, were found in PUUV seropositive patients. In six of these patients viral antigen was detected in the cytoplasm of renal tubular epithelial cells with focal distribution in the cortical and medullary areas of the kidneys. Surprisingly, also in two of the ten renal biopsies from PUUV seronegative patients, PUUV antigen was demonstrated, with essentially the same localization. Comparison of severity and extent of the lesions in the seropositive group with those of these two patients showed no significant differences between tubular and interstitial abnormalities. These findings indicate that the demonstration of certain histopathological alterations and the detection of viral antigen by immunoperoxidase techniques in kidney biopsies, may be useful as additional tools for the diagnosis of PUUV infection.

Adult↗

Hantavirus nephropathy in The Netherlands: clinical, histopathological and epidemiological findings.

Until 1995, 39 cases of serologically confirmed hantavirusnephropathy in humans, caused by the Puumala type of Hantavirus, have been documented in the Netherlands. Thirty-two of these occurred in Twente, a small region in the eastern part of the country, in which the presence of Puumala-like Hantavirus in feral rodents has recently been demonstrated. Sixteen of the cases documented in humans occurred in 1993. Here we present an overview of clinical, histopathological and epidemiological findings of hantavirus infections. All the clinical and laboratory findings of the 39 documented cases were similar to those found in infections with the same virus in neighbouring countries. Complete recovery of renal function occurred in all patients. One patient developed a Guillain-Barré syndrome after having recovered from her renal failure. Histopathological examination of kidney biopsies collected from 13 of the patients in the acute stage, confirmed the presence of acute interstitial inflammation of differing severity in these individuals. A serological survey carried out amongst 4232 healthy blood donors in the endemic area showed a seroprevalence of 0.7%. This suggests that less severe or perhaps even subclinical infections occur.

Acute Kidney Injury↗

Hantavirus infections in The Netherlands: epidemiology and disease.

A serological survey for the prevalence of hantavirus infections in The Netherlands was carried out on > 10,000 sera, from selected human populations, and different feral and domestic animal species. Hantavirus-specific antibodies were found in about 1% of patients suspected of acute leptospirosis, 10% of patients with acute nephropathia, and in less than 0.1% haemodialysis and renal transplant patients. Among individuals with a suspected occupational risk, 6% of animal trappers, 4% of forestry workers, 2% of laboratory workers and 0.4% of farmers were seropositive. The majority of the seropositive individuals lived in rural and forested areas. The main animal reservoir of the infection was shown to be the red bank vole (Clethrionomys glareolus). Epidemiological, clinical and laboratory findings seen in serologically confirmed human cases were similar to those associated with nephropathia epidemica.

Adolescent↗

Epidemiology and laboratory diagnosis of hantavirus (HTV) infections.

Hantavirus (HTV) is recently discovered "hemorrhagic fever virus" belonging to the Bunyaviridae family, which is spread throughout the world by wild rodents and/or laboratory rats. During an epidemic in the Belgian-French Ardennes in 1993, more than 200 acute cases were recorded of the milder European form of HTV-illness, otherwise known as Nephropathia epidemica (NE). This variant may be recognized by the sudden onset of fever, acute renal failure, thrombocytopenia and sometimes by ophthalmologic complications. The symptomatology is rather aspecific and diagnosis can only be confirmed by serologic tests, of which the best option nowadays seems to be: screening by IgG EIA, followed by IgM confirmation with a mu-capture EIA test. Some of the tests described allow an evaluation of the causative serotype or even the moment of infection. Next to the "classic" serologic assays for detection of specific viral antibodies, we describe briefly our own experience with newer tests such as "high density particle agglutination" and "line immuno assay". Polymerase chain reaction for viral RNA genome typing and immunohistochemical colouring of the viral antigen in tissues seem to offer promising alternatives for the immediate future.

Belgium↗

A macaque model for hantavirus infection.

Cynomolgus macaques (Macaca fascicularis) were experimentally infected with Puumala virus (strain Hällnäs), which causes nephropathia epidemica in humans in western Europe. During the first week after intratracheal inoculation, the monkeys exhibited signs of lethargy followed by mild proteinuria and microhematuria. Histopathologic changes during the first 7 weeks after infection were largely confined to abnormalities in medullary tubular cells of the kidneys, which coincided with the demonstration of viral antigen and viral RNA. The development of different classes of virus-specific plasma antibodies to the respective viral antigens were similar to those observed in humans with nephropathia epidemica. This first description of a nonhuman primate model for hantavirus infection shows that the cynomolgus macaque provides a suitable model with which to study the pathogenesis of Puumala virus infections and to evaluate new diagnostic methods, immunization strategies, and therapies.

Animals↗

Neurogenic modulation of micturition: the relation between stimulation intensity and the maximum shortening velocity of the guinea pig detrusor muscle.

The course of micturition depends on bladder contractility and urethral resistance. The former is determined by geometrical, muscular and neurogenic factors. The muscular aspects of bladder contractility can be characterized by the parameters Pisv, the isovolumetric detrusor pressure, and vmax, the maximum (unloaded) shortening velocity of the detrusor muscle. The neurogenic control system of the urinary tract modulates bladder contractility, which might effectively change the values of Pisv and vmax. These parameters also depend on the instantaneous bladder volume. In previous work the dependence of Pisv on the intensity of stimulation and bladder volume was measured in guinea pig bladders in vivo and in vitro. In the present work vmax was derived in 5 guinea pig bladder in vitro, using electrical stimulation and the stop-flow technique. This technique implies that pressure values measured at a certain shortening velocity of the bladder circumference and in an isovolumetric contraction at the same volume are used to derive vmax mathematically from the Hill equation. vmax was independent of the bladder volume in the range of 0.6 to 6.1 ml., but it was significantly different for the two intensities of stimulation used. Therefore, it is concluded that the maximum shortening velocity of the guinea pig detrusor muscle depends on the intensity of stimulation. During submaximal stimulation the detrusor not only generates lower pressures, it also contracts more slowly. A possible explanation for this phenomenon is that the bladder is not uniformly stimulated. The isovolumetric pressure measured in the stop-flow test was compared with the isovolumetric pressure measured at the same bladder volume some minutes later. It was observed that shortening had a depressant effect of approximately 33% on the isovolumetric pressure. This implies that the clinically employed stop-flow test might underestimate detrusor contraction strength.

Animals↗

Sacral (S3) segmental nerve stimulation as a treatment for urge incontinence in patients with detrusor instability: results of chronic electrical stimulation using an implantable neural prosthesis.

PURPOSE: We studied the effects of sacral (S3) nerve stimulation in patients with urge incontinence due to detrusor instability. MATERIALS AND METHODS: A permanent S3 foramen electrode was implanted in 18 patients (average age 46 years) who had shown a good response during temporary stimulation via a percutaneously placed wire electrode. Average followup was 29 months. RESULTS: The average voiding frequency and pad use per 24 hours decreased significantly. Improvement in several urodynamic parameters was noted. The correlation between symptomatic and urodynamic improvement was incomplete. CONCLUSIONS: Neuromodulation appears to be a valuable treatment option in these patients.

Adult↗

A comparative study of voiding in rat and guinea pig: simultaneous measurement of flow rate and pressure.

In this study, the voiding phase of the micturition cycle in the anesthetized rat and guinea pig is analyzed. In both animals, voiding is characterized by an increase in intravesical pressure and then a decrease, which is accompanied by flow through the urethra and emission of urine. An ultrasonic flow probe was used in both species to measure the flow rate in relation to the intravesical pressure. In the (male) rat, so-called high-frequency oscillations are superimposed on the decreasing bladder pressure. These oscillations do not occur in the guinea pig. It is concluded that the high-frequency oscillations are caused by intermittent flow and not by variations in the bladder contraction. The intermittent flow most likely is caused by the relaxation and contraction of the external urethral sphincter and may have a function in territory marking. In our view, it is not likely that the oscillations enhance bladder emptying, as has been suggested in the literature.

Animals↗

Class and subclass distribution of Hantavirus-specific serum antibodies at different times after the onset of nephropathia epidemica.

Sera from Dutch and Belgium individuals who suffered from nephropathia epidemica (NE), a mild form of haemorrhagic fever with renal syndrome (HFRS), were tested for the distribution of classes and subclasses of Hantavirus (HV)-specific antibodies at different times after the onset of the disease, with class- and subclass-specific Ig capture enzyme-linked immunosorbent assays (ELISAs). In the acute, early convalescent, and convalescent phases, predominantly specific IgA, IgM, and IgG3 antibodies were detected. Specific IgG2 antibodies were only detected at low levels in the early convalescent and convalescent phases. In the late convalescent phase specific IgG1 and IgG3 antibodies were found, whereas in the late postconvalescent phase only specific IgG1 antibodies proved to be present. Specific IgG4 antibodies were not detected in any of the respective phases. These data show that the simultaneous determination of classes and subclasses of HV specific serum antibodies allows the estimation of the time elapsed after the onset of NE.

Adolescent↗

Contractility of the guinea pig bladder measured in situ and in vitro.

To study the relative importance of neurogenic factors in detrusor contractility and to relate a total bladder in vitro contractility model to a previously described bladder wall strip model, active intravesical pressure values were compared in situ and in vitro in eight male guinea pigs. In situ, the active pressure was measured in spontaneous isometric and non-isometric micturition contractions. In vitro, the active pressure was measured in isometric contractions of the same bladders, developed in response to optimal electrical stimulation. The volume dependence of the active pressure generated by the bladder was measured in vitro in order to relate bladder capacity to the volume where the generated force is maximal and to determine the optimal volume at which to study detrusor contractility. The results indicated that in normal micturition the detrusor muscle was not fully stimulated: active pressure in isometric contractions in vivo was about 60% of the pressure values attained in vitro at the same bladder volume. Most micturitions occurred at a volume where the active pressure generated in vitro was about 80% of the maximal pressure. The active pressure-bladder volume relationship complied with the sliding filament-cross bridge theory. In whole bladder preparations active stress was about twice as high as in strips.

Animals↗

Methods for the purification of equine rabies immunoglobulin: effects on yield and biological activity.

Since rabies is still a major cause of human death in many developing countries and the implementation of recommended post-exposure prophylaxis by vaccination and specific immunoglobulin therapy is largely hampered by its high cost, the development of cheap rabies vaccines and immunoglobulin preparation are a high priority in these countries. In this paper various purification methods of equine rabies immunoglobulin based on different principles are compared with respect to their effect on final yield and biological activity. It is shown that a combination of ammonium sulphate (AS) precipitation and DEAE ion exchange chromatography results in an acceptable recovery rate of biological activity and a product of relatively high purity. Although affinity chromatography with protein G in combination with AS precipitation results in a similar recovery rate and a product of considerably higher purity, the cost of this procedure may be prohibitive for routine use in most developing countries. The effects of pepsin digestion time on the biological activity of the product and on the reduction of intact horse Ig are also studied. The desirability of this digestion procedure with respect to reduction of adverse side effects and efficacy of the product for post-exposure treatment is discussed.

Animals↗