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Biomedical subjects

M Knoll

Publications and source records attributed to M Knoll.

At least 37 records · Page 2Linked to original sources

In vitro analysis of oocyte cumulus complex pickup rate in the hamster Mesocricetus auratus.

In mammals, the oocyte and its surrounding cumulus cells constitute on oocyte cumulus complex (OCC). During ovulation, OCCs are extruded into the peritoneal or bursal cavity, depending on the species, and are then rapidly picked up by the fimbria on the outer surface of the oviductal infundibulum and transported to the ampulla, where fertilization occurs. We developed a method to measure OCC pickup rates quantitatively in vitro, and we used this method to evaluate the effects of viscosity and temperature on pickup rates. Hamster infundibula are placed in a holding pipette in a chamber modified to study OCC pickup. Ciliary beat frequencies (CBF) can be measured in the same preparation. Pickup rates vary depending on the pathway on which the OCC travels over the surface of the infundibulum; however, rates for a given pathway are very consistent. The average pickup rate at room temperature calculated from three different pathways/infundibulum was 55.2 +/- 10.6 microns/sec. Both rates between infundibula from the same female and rates among infundibula from different females were in most cases similar. Preparations preincubated in vitro for 2.75 hr produced rates similar to nonpreincubated samples, while longer preincubation resulted in decreased rates. Inclusion of Ficoll in culture medium to increase viscosity caused a concentration-dependent decrease in both OCC pickup rate and in CBF. However, a significant decrease in OCC pickup rate was only observed at viscosities higher than those found in bursal fluid. When trials were run at physiological temperature (36.4 degrees C) rather ambient temperature, rates increased to 136.7 +/- 29.9 (SD) microns/sec. Linear regression analysis demonstrated a strong positive correlation (r = 0.94) between OCC pickup rate and temperature. The OCC pickup rate assay can be used experimentally, and should be valuable in evaluating factors that affect rate and in studies dealing with the mechanism of OCC pickup.

Animals↗

Intravesical electromotive drug administration for the treatment of non-infectious chronic cystitis.

Seventeen patients with non-infectious chronic cystitis (NICC) (9 with interstitial cystitis, 6 patients with radiation cystitis, 1 with chemocystitis and 1 with lupoid cystitis) were treated with electromotive administration of intravesical lidocaine and dexamethasone followed by hydrodistension of the bladder. Complete resolution of symptoms for an average of 7.5 months was observed in 11 patients (65%), partial improvement in 4 (23.5%). In this series no complications occurred. Electromotive drug administration (EMDA) and cystodistension were well tolerated by all patients. The treatment was performed on an outpatient basis, thus reducing therapeutic costs. The results presented demonstrate that the combination of EMDA and bladder hydrodistension is an effective first-line treatment for NICC patients.

Administration, Intravesical↗

Usefulness of color Doppler proximal isovelocity surface area method in quantitating valvular regurgitation.

To define the clinical utility of the color Doppler proximal isovelocity surface area (PISA) method for estimating regurgitant stroke volume (SV), 160 regurgitant lesions were evaluated in 104 patients with mitral (MR), aortic (AR), and tricuspid (TR) regurgitation. Regurgitant SV by PISA was calculated as 2 pi R2 x V x (time-velocity integral/peak flow velocity), where R is the radius corresponding to the first blue-red interface velocity of the maximal PISA during the cardiac cycle. The time-velocity integral and peak flow velocity from the continuous-wave Doppler recording of the regurgitant jet were used to correct PISA for phasic variations in regurgitant flow. Fifteen lesions were excluded because of difficulty in tracing the continuous-wave Doppler regurgitant curve. Among 145 remaining regurgitant lesions, PISA was measurable in 50 (78%) of 64 cases of MR and 24 (69%) of 35 cases of TR but in only 12 (26%) of 46 cases of AR (p < 0.001). Regurgitant SV by PISA correlated modestly well with jet area/atrial area in all atrioventricular valve lesions (MR: r = 0.55; TR: r = 0.65; p < 0.001). However, the correlation improved if only central jets were considered (MR: r = 0.70; TR; r = 0.75; p < 0.001). These findings are not unexpected because jet area/atrial area underestimates the true severity of regurgitation in cases of eccentric (wall-impinging) jets. PISA was detected in all severe cases of regurgitation but in only 64% of cases of mild MR, 45% of cases of mild TR, and 6% of cases of mild AR (p < 0.01). The color Doppler PISA method is clinically useful in estimating regurgitant SV in MR and TR, including mild cases, but is less useful in AR.

Adolescent↗

Analysis of ciliary beat frequencies in hamster oviducal explants.

We have developed a simple direct method, requiring minimal manipulation, to measure beat frequencies of the cilia on the external surface of hamster oviducal infundibula in vitro. Two perfusion chambers (closed and open) were used; both can be hand-made in a few minutes and discarded after use. Ciliary beat frequencies were determined by measuring variations in light intensity with time in a single pixel positioned over a video image of the beating cilia. Data files were collected using Image 1 software and later transferred to PSI Plot or Lotus 123 spreadsheets for analysis by counting the number of brightness peaks recorded per second or by subjecting the data to Fourier transformation with or without smoothing. These methods of analysis gave similar results. To verify that Image 1 data files contain accurate representations of CBF, videotapes of beating cilia were made and subjected to frame-by-frame analysis. Image 1 interfaced with a standard video camera was found to collect reliable data over a beat frequency range of 0-15 cycles/sec. In some Fourier transforms, secondary peaks were observed and were shown to represent cilia beating at more than one frequency in a sampled region. Coefficients of variation for repeated measurements taken on the same region varied from 4.1% to 9.0%. Small but significant differences were found between beat frequencies at different regions of the same oviduct. When chambers were perfused discontinuously and measurements of beat frequency were made at least 5 min after each perfusion, no effect of perfusion on frequencies was observed. However, during continual perfusion of the open chamber, a slight but significant increase in beat frequency was observed after perfusion was initiated. Muscle contraction, which sometimes occurs in the open chamber, did not affect beat frequency measurements. Infundibula could be stored at 4 degrees C overnight without any negative effect on beat frequencies. Cold storage also reduced muscle contraction. Placement of a small coverslip on infundibula in the open chambers was also found to reduce muscle contraction and facilitate beat frequency measurements. Coverslipping did not affect beat frequencies. This method of beat frequency analysis will be valuable for analyzing factors that regulate or influence cilia in mammalian oviducts.

Analysis of Variance↗

Ciliary beat frequency of hamster oviducts is decreased in vitro by exposure to solutions of mainstream and sidestream cigarette smoke.

Epidemiological data support a correlation between smoking and increased incidence of ectopic pregnancy, yet the causal mechanism responsible for this relationship is unknown. The purpose of this study was to examine the effect of solutions containing dissolved mainstream (MS) or sidestream (SS) cigarette smoke on ciliary beat frequencies (CBF) in explants of hamster oviducts. MS smoke is the puff inhaled by an active smoker, while SS smoke leaves the burning end of cigarette. SS smoke is inhaled by both active and passive smokers. Experiments were performed in handmade perfusion chambers using infundibula from hamster oviducts. After a short incubation in Earle's balanced salt solution containing HEPES buffer (EBSS-H), chambers were flushed with one of six types of smoke solution prepared in EBSS-H, and incubation continued 19 min. A second perfusion (washout) was then done using EBSS-H alone to determine whether effects induced by the smoke solutions could be reversed. CBF were determined at three times in both the smoke and washout solutions, and means were compared to values obtained in the initial EBSS-H incubation. All smoke solutions except the SS particulate solution inhibited CBF in a dose-dependent manner. Whole MS and whole SS smoke solution at the highest strength tested caused the greatest inhibition and in some cases completely stopped ciliary beating. Both single-strength and 0.1-strength MS gas phase solutions, which contained concentrations of nicotine in the range found in typical human smokers, produced about 50% inhibition of ciliary beating. Inhibition was generally seen within 2-12 min of adding smoke solutions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Intravesical application of oxybutynine: mode of action in controlling detrusor hyperreflexia. Preliminary results.

Topical oxybutynine (Oxy) has been used successfully in neurogenic bladder patients who remained wet on oral anticholinergics or could not tolerate oral medication. However, little is known about the pharmacokinetics of intravesical Oxy. The aim of this study was to evaluate the resorption rate of intravesically given Oxy in the bladder in comparison with oral intake, and to find out which pharmacological properties of the drug are responsible for its effect when given intravesically. Our results indicate that peak plasma levels of intravesical Oxy appear later, are lower and stay longer compared to oral intake. Cystometries before, 20 min and 2 h after intravesical application of Oxy indicate that the main effect of intravesical Oxy on the detrusor is systemic due to its resorption. Our findings confirm the clinical experience that intravesical Oxy is well tolerated, very efficacious and better than oral medication.

Administration, Intravesical↗

Detection of genotoxic effects in human gastric and nasal mucosa cells isolated from biopsy samples.

To assess genotoxic burdens from chemicals, it is necessary to relate observations in experimental animals to humans. The success of this extrapolation would be increased by including data on chemical activities in human tissues. Therefore, we have developed techniques to assess DNA damage in human gastric and nasal mucosa (GM, NM) cells. Biopsy samples were obtained during gastroscopy from macroscopically healthy tissue of the stomach or from healthy nasal epithelia during surgery. The specimens were incubated for 30-45 min at 37 degrees C with a digestive solution. We obtained 1.5-8 x 10(6) GM cells and 5-10 x 10(5) NM cells per donor, both with viabilities of 80-95%. The cells were incubated in vitro for 1 hr at 37 degrees C with the test compounds added in their appropriate solvents. In GM cells, we studied N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), sodium dichromate (Na2Cr2O7), nickel sulphate (NiSO4), cadmium sulphate (CdSO4), and lindane. In NM cells, lindane was investigated. Each compound was assessed for DNA damaging activity in cells of at least three different human donor samples using the microgel single cell assay. Similar studies were performed with GM and NM cells obtained from Sprague-Dawley rats. We have found human GM cells to be more sensitive to the genotoxic activity of MNNG than rat GM cells (low effective concentration [LEC] = 0.16 and 0.625 micrograms/ml for human and rat, respectively). Human cells were also more sensitive to the cytotoxic/genotoxic activity of NiSO4 (LEC = 5 and 19 mumoles/ml for human and rat, respectively). CdSO4 was genotoxic in human GM cells (LEC = 0.03-0.125 mumoles/ml), whereas no dose-related genotoxicity was observed in rat GM at concentrations up to 0.5 mumoles/ml. In contrast, approximately equal responses regarding genotoxicity and cytotoxicity were observed in rat and human GM for Na2Cr2O7 (0.25-1 mumoles/ml). Lindane, however, was genotoxic in three out of four rat GM but not in human GM cells (0.5-1 mumoles/ml), whereas it was active in both rat and human NM cells. Together with other recently published in vivo findings, our results with lindane can be interpreted according to a parallelogram approach. In view of possible human exposure situations and the sensitivities of the two target tissues from both species, the data imply that lindane will pose a health risk to humans by inhalation but not by ingestion.

Adult↗

Acute cocaine administration induces ventricular regional wall motion and ultrastructural abnormalities in an anesthetized rabbit model.

Whether acute doses of cocaine can induce left ventricular (LV) regional wall motion abnormalities in animals with otherwise normal coronary arteries is unknown. We studied rabbits receiving constant cocaine infusions (group I: 0.025 to 1.5 mg/kg/min, n = 10), multiple cocaine boluses (group II: 3-5 mg/kg each bolus, n = 10), or saline (group III; n = 8). In group I rabbits, short-axis LV area and diameter increased by 15% to 40% at 60 minutes compared to baseline and to controls (p < 0.01), but percentage of global area fractional shortening was unchanged. Eight rabbits in each of groups I and II, but no controls, developed LV regional wall motion abnormalities as detected by echocardiography: 15 (7 hypokinesis and 8 akinesis or dyskinesis) in the anteroseptal and 2 (hypokinesis) in the posterior LV wall. Among rabbits showing LV wall motion abnormalities, anteroseptal fractional shortening and % area reduction averaged > 20% less (p = 0.03 for area reduction) at 30 minutes versus controls. Only 50% of group I or II rabbits with LV anteroseptal wall motion abnormalities had intraventricular conduction disturbances. Radioactive microsphere flow studies (n = 6) 1 minute after a 4 mg/kg cocaine bolus revealed an equivalent decrease (10% to 20%, average) in septal and LV free wall perfusion (p value not significant). Electron microscopy revealed myocardial cell contraction band necrosis in 3 and sarcoplasmic reticular edema in 7 of 10 cocaine rabbits (unrelated to dose). We conclude that acute cocaine administration in rabbits frequently produces LV anteroseptal wall motion abnormalities even in the absence of differentially decreased perfusion or intraventricular conduction disturbances and produces ultrastructural abnormalities of the myocytes. These findings suggest a direct, nonuniform effect of cocaine on the LV myocardium.

Animals↗

Glucose sensor in containment technology.

A new transducer concept for miniaturized immobilized enzyme glucose sensors is presented. The enzyme containing membrane is anchored inside the microcontainment of a silicon chip together with the metal electrode. Containment based sensors are ideally suited for integration into microsystems. The fabrication process is planned as a full wafer process allowing transfer to low-cost mass-production with a narrow variability. The functionality of the containment concept is demonstrated by the fabrication of chips with single GOD-based amperometric glucose sensors which have been tested in glucose solution. The advantages of the containment technology are discussed.

Biosensing Techniques↗

The chances of a spina bifida patient becoming continent/socially dry by conservative therapy.

One hundred and one patients with neurogenic lower urinary tract dysfunction due to myelomeningocele or sacral dysplasia, all older than 10 years of age, with a mean age of 15 years, and under regular urological control for many years were evaluated to discover if they had achieved urinary continence (dry day and night) or the status of socially dry (with dry intervals of more than 3 hours) with conservative means of treatment; or whether they remained incontinent or required operative procedures. The results were correlated with the urodynamic pattern of their detrusor-sphincter dysfunction and with the methods they used for bladder emptying. Special attention was paid to the effects of the various conservative treatment modalities nowadays available. The chances of becoming continent or at least socially dry by conservative therapy are best for patients with sphincter hyperreflexia provided that (1) the detrusor was already hypo- or areflexic, or detrusor hyperreflexia could be successfully controlled, and (2) that regular bladder emptying was achieved by clean intermittent (self) catheterisation. Twenty-four out of 45 patients in this group fulfilled these criteria: 18 are continent, 6 socially dry, a success rate of 54%. In patients with sphincter weakness the outlook is worse: in combination with detrusor hyperreflexia there is only a 16% chance, and in those with detrusor areflexia a 37% chance of becoming continent or socially dry, with the best results in wheelchair patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Antigenotoxic properties of lactic acid bacteria in vivo in the gastrointestinal tract of rats.

In view of the high incidence of dietary-related tumors, one important research goal is to identify the participating genotoxic carcinogens and the nutritional factors that may counteract their activities. We therefore have further developed a method to assess DNA damage in tumor target tissues of the gastrointestinal tract. Subsequently the prevention of this inducible DNA damage by lactic acid bacteria and by milk products fermented with probiotics was studied as well. The microgel electrophoresis technique was applied to cells of the esophageal, gastric, duodenal, and colonic mucosa. Cells were grouped according to their degree of DNA damage, the simplest measure of which is to discriminate between those with damage (comets) and those without damage. When these cells were isolated from animals treated with a genotoxic carcinogen, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), and exposed to MNNG for 1-24 hours, it was possible to follow the course of genotoxicity throughout the gastrointestinal tract. After the animals were treated with the lactic acid bacteria under study, it was possible to detect antigenotoxic properties as well. The gavage of 10(10) viable Lactobacillus casei cells in 10 ml of 0.9% NaCl per kilogram body weight immediately before the oral administration of MNNG (5 mg/kg body wt) resulted in a reduction of induced DNA damage in gastric and colonic mucosa cells. A sequential treatment schedule was even more effective: when the animals were treated orally with lactic acid bacteria or yogurt (10 ml/kg body wt) in the morning followed by MNNG (7.5 mg/kg body wt) eight hours later and the colon cells were isolated 16 hours later, the percentages of cells remaining intact were distinctly higher in the combination groups (68 +/- 10 and 68 +/- 19 for L. casei and a "Bio" yogurt, respectively) than in the group receiving only MNNG (45 +/- 17). The effect of heating L. casei was studied and was found to yield less clear-cut effects in preventing genotoxicity. The method is an efficient tool to elucidate antigenotoxic properties of food components in vivo in those target tissues actually afflicted by dietary-related tumors.

Animals↗

Percutaneous transrenal ureteral occlusion: indication and technique.

Several techniques for achieving palliative ureteral occlusion in cases of underlying malignant diseases are known to exist. We performed nine ureteral occlusions on seven patients, using two different techniques (occlusion by detachable balloon and by "Harzmann Olive"). Initially, complete occlusion of all ureters was attained; in two cases a second occluding intervention had to be carried out after a period of 6 and 14 weeks. Six of seven patients enjoyed a marked improvement of their quality of life after occlusion. Complications were down to a minimum. In comparison with other techniques described in the literature, Harzmann's method seems to be the simplest, as well as the most fully developed one. It may also be recommended for patients in an advanced tumor stage.

Aged↗

Delusional parasitosis as 'folie à trois'.

Delusional parasitosis can apparently run in families. Three out of 9 members of a German family were fully convinced that their skin had been invaded by 'tiny running animals' even though there was no physical evidence of any infestation. Although the family was reluctant to be injected with neuroleptic drugs as this would have been an acknowledgement that their symptoms were in fact of psychological origin, they eventually agreed to be treated. When last contacted, 3 years after diagnosis, they still believed in the existence of the parasites but admitted that some of their symptoms had improved.

Aged↗

Antiarrhythmic efficacy of Ethmozine (moricizine HCl) compared with disopyramide and propranolol.

In the investigation of new antiarrhythmic drugs, comparative trials with clinically available antiarrhythmic agents provide a perspective from which to judge the new investigational agent. Two clinical investigations of moricizine HCl, each using a placebo-controlled, double-blind, crossover design, are summarized. In the first study, 18 patients with greater than or equal to 30 ventricular premature complexes (VPCs) per hour (mean 369 +/- 95) were given propranolol (120 mg daily) compared with moricizine HCl (816 +/- 103 mg daily). Propranolol suppressed 38% of VPCs in the study group, moricizine HCl, 81% of VPCs, and the combination of both drugs, 87%. Moricizine HCl was more effective than propranolol in suppressing VPCs at all individual levels greater than 70% (p less than 0.05, McNemar's test). The combination of moricizine HCl and propranolol was well tolerated. The second investigation used a placebo-controlled, double-blind, crossover design to compare the efficacy of disopyramide (600 mg daily) and moricizine HCl (800 mg daily) in 27 patients. Patients had greater than or equal to 40 VPCs/hr on a 24-hour ambulatory electrocardiogram. During moricizine HCl administration, the mean VPC frequency decreased from 524 to 151 VPCs/hr (71.2% reduction). In contrast, disopyramide reduced VPC frequency from 535 to 253 VPCs/hr (52.8% reduction) and demonstrated significantly greater side effects (p less than 0.05). Moricizine HCl was more effective than disopyramide in suppressing VPCs at all individual percent reduction levels greater than 70% (p less than 0.05, McNemar's test). Moricizine HCl was more effective in suppressing VPCs than either disopyramide or propranolol, with significantly fewer side effects.

Adult↗

Relationship between age, body size, gender, and blood pressure and Doppler flow measurements in the aorta and pulmonary artery.

Previous studies have demonstrated a relationship between both age and body surface area (BSA) and M-mode echocardiographic measurements of left ventricular, left atrial, and aortic root dimensions and left ventricular wall thickness. We evaluated the relationships between age, BSA, gender and blood pressure, and Doppler aortic and pulmonary artery (PA) flow velocity measurements in 97 adults, aged 21 to 78 years, without clinical evidence of cardiac disease. No significant relationship was found between gender or blood pressure and aortic or PA flow velocity measurements. Aortic peak flow velocity, flow velocity integral, and average acceleration decreased with increasing age (all p less than 0.001), whereas ejection time (corrected for heart rate) increased, and acceleration time did not change. In contrast, there was no relationship between age and Doppler PA flow velocity measurements. Although there was no relationship between BSA and Doppler aortic flow measurements, PA peak flow velocity and average acceleration increased, while acceleration time decreased with increasing BSA (all p less than 0.02). Decreases in aortic peak flow velocity and flow velocity integral may be partly related to known increases in aortic root diameter with aging. The relationship between PA flow velocity measurements and BSA is not readily explained.

Adult↗