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Biomedical subjects

K K Nielsen

Publications and source records attributed to K K Nielsen.

At least 19 recordsLinked to original sources
PubMed1995

Morphological, stereological, and biochemical analysis of the mini-pig urinary bladder after chronic outflow obstruction and after recovery from obstruction.

Chronic partial bladder outlet obstruction was created in nine mini-pigs by implanting a 6-7 mm ring around the proximal urethra. After a median obstruction period of 63 days, the ring was removed and after a recovery period of median 60 days the animals were sacrificed. Changes in muscle and connective tissue were assessed by unbiased, modern morphometry and biochemical analysis. After obstruction the results were as follows: (1) a 6-fold increase in bladder weight, (2) a 2.5-fold increase in smooth muscle cell size, (3) a 3-fold increase in smooth muscle cell number, (4) unchanged proportions between muscle and connective tissue, (5) unchanged hydroxyproline concentrations, (6) an 8-fold increase in total collagen content, (7) an increase in the ratio of type I/III collagen, and (8) a 7-8-fold increase in total content of type I and III collagen. All changes were markedly, though incompletely, reversed after recovery, except smooth muscle cell number and the ratio of type I/III collagen.

Animals↗
PubMed1995

Length density and total length of acetylcholinesterase positive nerves related to cystometry and in vitro studies of muscle strips in mini-pig urinary bladder after chronic outflow obstruction and recovery from obstruction.

Chronic partial bladder outlet obstruction was created in mini-pigs by implanting a 6-7 mm ring around the proximal urethra. After a median obstruction period of 63 days, the ring was removed and after a median recovery period of 60 days the animals were sacrificed. At each occasion stepwise cystometry, measurement of residual urine, muscle strips studies with electrical and carbachol stimulation, and stereological estimations of length density and total length of acetylcholinesterase positive nerves were performed. The results can be summarized as follows: (1) unchanged sensitivity of muscle strips to carbachol, but markedly decreased contractility and rate of contraction to carbachol, (2) no evidence of detrusor instability, but severely decompensated bladders in two pigs, (3) a significant increase in residual volume, (4) a pronounced decrease in length density and total length of acetylcholinesterase positive nerves, and (5) at field stimulation strips from some pigs showed increased sensitivity and contractility with high atropine and TTX resistance, while strips from the other pigs revealed decreased sensitivity and markedly decreased contractility to electrical stimulation. In general, most of the changes were markedly, though incompletely, reversed after recovery. Light and electron microscopy of muscle strips showed no histological or ultrastructural changes during the experiments or after storing 1 day at 4 degrees C.

Acetylcholinesterase↗
PubMed1995

The hypoalgesic effect of imipramine in different human experimental pain models.

In a randomized, placebo-controlled, double-blind, cross-over study, the hypoalgesic effect of a single oral dose of 100 mg imipramine was investigated in 12 healthy volunteers. Test procedures performed before, 3, 6, and 9 h after medication included determination of (1) pain detection and tolerance thresholds to heat and pressure; (2) the thresholds of quadriceps femoris muscle withdrawal reflex to single and repeated electric stimulation of the sural nerve; (3) amplitude of the reflex evoked by 1.5 times the premedication reflex threshold; and (4) continuous pain rating during the cold pressor test. Imipramine significantly increased pain tolerance thresholds to heat (P = 0.03) and pressure (P = 0.01), and both the psychophysical pain tolerance threshold and the reflex threshold to single electric stimulation (P = 0.02 and P = 0.03, respectively). On the repeated stimuli, which consisted of 4 pulses given at 3 Hz, imipramine induced a significant increase in the threshold at which the pain summated through the stimulation series (P = 0.03), whereas the increase in the threshold at which the reflex summated was not significant (P = 0.09). Pain detection thresholds to heat and pressure, the amplitude of the reflex to single suprathreshold stimulation, and pain ratings during the cold pressor test were unaltered by imipramine. It is concluded that imipramine has a differential hypoalgesic effect on different human experimental pain tests. This provides new possibilities of assessing the differential effect of different tricyclic antidepressants on different pain modalities and intensities.

Adolescent↗
PubMed1995

Imipramine metabolism in relation to the sparteine and mephenytoin oxidation polymorphisms--a population study.

1. Sparteine and mephenytoin phenotyping tests were carried out in 327 healthy Danish subjects. Two weeks later each subject took 25 mg imipramine followed by urine collection for 24 h. The urinary content of imipramine, desipramine, 2-hydroxy-imipramine and 2-hydroxy-desipramine was assayed by h.p.l.c. 2. The medians of the hydroxylation ratios (i.e. 2-hydroxy-metabolite over parent compound) were 6 to 14 times higher in 300 extensive metabolizers of sparteine (EMs) as compared with 27 poor metabolizers (PMs), but none of the ratios separated the two phenotypes completely. 3. There were 324 EM of mephenytoin (EMM) and three PM (PMM) in the sample. The demethylation ratios between desipramine, 2-hydroxy-desipramine and their corresponding tertiary amines showed statistically significant correlations with the mephenytoin S/R isomer ratio (Spearman's rs: -0.20 and -0.27, P < 0.05). 4. The demethylation ratios were higher in 80 smokers than in 245 non-smokers. This indicates that CYP1A2, which is induced by cigarette smoking, also catalyzes the N-demethylation of imipramine. 5. CYP2D6 genotyping was carried out by PCR in 325 of the subjects, and the D6-wt allele was amplified in 298 EMs, meaning that they were genotyped correctly. One PMs was D6-wt/D6-B, another PMs had the genotype D6-wt/ and hence both were misclassified as EMs. The remaining 25 PMs were D6-A/D6-B (n = 5), D6-B/ (n = 18) or D6-D/D6-D (no PCR amplification, n = 2).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

A comparison between the effects of paraffin and plastic embedding of the normal and obstructed minipig detrusor muscle using the optical dissector.

PURPOSE: The purpose of this study was to estimate the relative shrinkage of the normal, obstructed and recovery minipig urinary bladder by comparing tissues from the same bladders embedded in paraffin or plastic. MATERIALS AND METHODS: Optical dissectors were used to make nucleus numerical density estimates in thick paraffin and plastic sections from the same bladder. The ratio of the 2 numerical densities depends only on differences in tissue shrinkage. In 9 minipigs a partial bladder outlet obstruction was created by implanting a 6 to 7 mm. Teflon ring around the proximal urethra. After an obstruction period (median 63 days) the ring was removed and after a recovery period (median 60 days) the animals were sacrificed. Biopsies were taken prior to obstruction, at removal of obstruction, and after recovery and were processed for paraffin and plastic sections to evaluate relative shrinkage. Two control pigs were sham-operated and biopsies taken at the same 3 time points. RESULTS: The optical dissector method was found to be an easy way to estimate the relative shrinkage of paraffin-embedded bladder tissue in proportion to plastic-embedded tissue. Both in human and minipig bladders, paraffin embedding caused a relative shrinkage of about 30% in proportion to plastic embedding. Both the obstructed and recovery detrusor muscles responded to embedding by either method in a manner indistinguishable from the normal bladder. CONCLUSION: When dealing with stereological evaluation of the detrusor muscle, the relative shrinkage of the embedded normal, obstructed and recovery bladder tissue can be ignored.

Animals↗
PubMed1994

Subjective and objective evaluation of patients with prostatism and infravesical obstruction treated with both intraprostatic spiral and transurethral prostatectomy.

In order to evaluate the effect of intraprostatic spiral and subsequent transurethral prostatectomy (TURP) on obstructive benign prostatic hyperplasia, 9 men were evaluated with symptom scores and urodynamic studies at inclusion after 4 months of spiral treatment and 4 months after TURP. Six patients in a control group were evaluated at inclusion after an observation period of 4 months and 4 months after TURP. After treatment with spiral the symptom score decreased in 7 patients, increased in 1, and was unchanged in 1. After the observation period in the control group the symptom score decreased in 4 patients, increased in 1, and was unchanged in 1. After TURP the symptom score decreased even further in all patients, but one. After spiral treatment the urethral resistance decreased in 8 of 9 patients, but according to Abrams and Griffith's [(1979): Br J Urol 51:129-134] definition, only 2 were unobstructed. Five patients in the control group were unchanged obstructed after the observation period, while one was unobstructed. After TURP, the patients in both groups were all unobstructed. Intraprostatic spirals decrease the severity of symptoms and reduce the urethral resistance, but TURP in the same patient was much more effective.

Follow-Up Studies↗
PubMed1992

Steady-state plasma levels of clomipramine and its metabolites: impact of the sparteine/debrisoquine oxidation polymorphism. Danish University Antidepressant Group.

After an initial placebo week, 37 depressed inpatients were treated with the fixed dose of 75 mg clomipramine b.d. A sparteine test was carried out during the placebo period and again during the second week of active therapy. Blood for drug assay was collected at the end of the inter-dose interval in the (morning) at weekly intervals. Clomipramine and four metabolites (desmethylclomipramine, didesmethylclomipramine, 8-hydroxyclomipramine, and 8-hydroxydesmethylclomipramine) in plasma were assayed by reversed phase HPLC. The clomipramine and desmethylclomipramine steady-state plasma levels varied by factors of 11 and 9, respectively, and the clomipramine/8-hydroxyclomipramine and desmethylclomipramine/8-hydroxydesmethylclomipramine ratios both varied by 7-fold. During the placebo week, 36 patients were phenotyped as extensive metabolizers (EM) (metabolic ratio, MR, 0.1-2.0), and one patient was phenotyped as a poor metabolizer (PM) (MR > 300). During clomipramine treatment, one patient changed phenotype from EM to PM (MR = 140). In the EM, the median of the MR increased from 0.4 to 2.3. There was a statistically significant correlation between the MR before and during clomipramine treatment, even when the PM was excluded. Neither the steady-state plasma clomipramine levels nor the clomipramine/desmethylclomipramine ratios showed a significant correlation with the MR. In contrast, the desmethylclomipramine and didesmethylclomipramine steady-state levels and the desmethylclomipramine/8-hydroxydesmethylclomipramine and clomipramine/8-hydroxyclomipramine ratios showed a significant positive correlation with the MR. The PM had the highest steady-state plasma desmethylclomipramine level and the highest desmethylclomipramine/8-hydroxydesmethylclomipramine ratio. These correlation coefficients (rs) were generally increased when the correlation analyses were based on the MR obtained during clomipramine treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

A simple method for insertion of an intraprostatic coil.

A simplified method of insertion of a urethral coil for treatment of benign prostatic obstruction has been tested in 25 patients. The prostatic urethra is measured either by abdominal/transrectal ultrasound scanning or by rigid or flexible endoscopy. The coil is inserted into the prostatic urethra using simple measurements taken from a Foley catheter; 21 coils were correctly positioned at the first attempt using this new method--a success rate equivalent to that of ultrasound-guided insertion.

Aged↗
PubMed1991

[The intraurethral plug. A new alternative in the treatment of women with stress incontinence].

The intraurethral plug has been developed for treatment of women with stress-incontinence. The plug is made of thermoplastic-elastomeric material and consists of a meatus plate, a soft stalk and one or two beads along the stalk. The individual plug is constructed on the basis of the result of the urethral pressure profile. The plug is removed manually prior to micturition and after micturition a new plug is introduced by the patient. A plug with two beads was employed in period 1 (seven days) and a plug with one bead for period 2 (seven days). Twenty-two patients completed period 1. Eight of these patients did not complete period 2, mainly on account of unchanged incontinence during period 1 or repeated loss of the plug with one bead. In periods 1 and 2, 73% and 79% of the patients, respectively, were both subjectively and objectively continent or considerably improved. This preliminary investigation demonstrates that the intraurethral plug may be an alternative form of treatment of women with stress incontinence.

Adult↗
PubMed1991

Rate of urinary bladder blood flow evaluated by 133Xe washout and radioactive microspheres in pigs.

Urinary bladder blood flow as measured by the washout of locally injected 133Xe and by the simultaneously performed radioactive microsphere reference-sample method was studied in pigs. The washout curves were analyzed according to the initial slope, the corrected initial slope and the total curve. The corrected-initial-slope flow rates were not statistically significantly different from the microsphere whole-wall flow rates. The variability between the methods shown by the test-retest difference revealed only a minor lack of agreement. The bladder blood flow tended to decrease after the intravesical pressure had been increased to 20 cmH2O, but the difference was not statistically significant. Washout of locally injected 133Xe can be used for the evaluation of urinary bladder blood flow in humans and in longitudinal animal studies. The corrected-initial-slope method is recommended for the analysis of washout curves.

Animals↗
PubMed1991

Cavernosometry: methodology and reproducibility with and without pharmacological agents in the evaluation of venous impotence.

Venous impotence can be evaluated by cavernosometry, although this is a controversial issue. We have evaluated various techniques for cavernosometry: with and without intracavernous papaverine, with different dosages and modalities, with different modes of induction flow and at various intracavernous pressures. A standardised technique was tested and retested in 32 impotent men. If pharmacocavernosometry is accepted as the most reliable test and a maintenance flow less than 20 ml/min indicates optimal venous occlusion, plain cavernosometry gave 6% false positive and 16% false negative results. Pharmacocavernosometry was found to be highly reproducible with regard to maintenance flow for patients thought to have optimal venous occlusion and for those with supposed leakage. The induction flow was of no diagnostic value. After injection of papaverine the maintenance flow became a reproducible parameter for quantifying venous outflow and could be measured with an intracavernous pressure equivalent to systolic blood pressure to minimise cavernous arterial inflow and increase reproducibility.

Adult↗
PubMed1991

Intraprostatic spiral during waiting time for transurethral prostatectomy.

When benign prostatic hyperplasia results in voiding problems such as acute or chronic urinary retention, transurethral prostatectomy is often necessary. We have evaluated 24 patients, treated with an intraprostatic spiral, during waiting time for transurethral prostatectomy. The spiral treatment was a success in 21 patients. Three patients had a transurethral prostatectomy before scheduled time due to spiral failure, 2 with urinary retention, 1 with severe local discomfort. We conclude that spiral treatment of symptomatic benign prostatic hyperplasia while waiting for transurethral prostatectomy has a high success rate and is recommended as a favorable alternative to an indwelling urethral catheter.

Adult↗
PubMed1990

Urethral stricture following transurethral prostatectomy.

Urethral stricture is the most common late complication of transurethral prostatectomy. Uroflowmetry is recommended as the routine screening procedure for strictures postoperatively. If maximal urinary flow rate (Qmax) is below 10 mL/second the patients should be investigated further. The etiology of urethral stricture is still unclear. Further studies are necessary to evaluate the possible etiologic role of infected urine pre- and/or postoperatively, urethral catheterization pre- and postoperatively, catheter material, and the type and size of the resectoscope. A narrow urethra is probably a predisposing factor for stricture formation, but this is not definitively clarified. Only few randomized studies have been performed to evaluate the different prophylactic methods against development of strictures postresection. Resection via perineal urethrotomy, perhaps preceded by urethral calibration, seems to be a way to avoid anterior urethral strictures. The effects of internal urethrotomy preoperatively on stricture formation are conflicting. Further randomized studies are necessary.

Humans↗
PubMed1990

Failure of combined supratrigonal cystectomy and Mainz ileocecocystoplasty in intractable interstitial cystitis: is histology and mast cell count a reliable predictor for the outcome of surgery?

Eight women with severe intractable interstitial cystitis were treated with supratrigonal cystectomy and Mainz ileocecocystoplasty. The preoperative evaluation consisted of symptom analysis, cystometry, cystoscopy and bladder pathological findings. Seven patients had increased mast cell density. Median followup was 10 months. The symptoms resolved in 2 patients but recurred in 6 shortly after the operation. Voiding could not be established in 4 patients. Self-catheterization was difficult and painful. Ultimately, cystectomy and urinary diversion were performed in 5 patients and is scheduled in 1. The 2 cured patients had a small contracted bladder preoperatively while they were under anesthesia, while all 6 failed cases had a large bladder capacity. Postoperative biopsies from the trigone showed no difference in the amount of fibrosis, the degree of degenerative changes in the muscle and mast cell density between the 2 cured patients and the 6 who failed to improve. The mast cell density and the histological status of the trigone cannot be used as predictors of the outcome of supratrigonal cystectomy. The role of the mast cells in interstitial cystitis is reviewed. Combination of supratrigonal cystectomy and a Mainz augmentation cystoplasty cannot be recommended in patients with intractable interstitial cystitis and a large bladder capacity.

Cecum↗
PubMed1990

The urethral plug: a new treatment modality for genuine urinary stress incontinence in women.

A new modality, the urethral plug, was used to treat 22 women with genuine urinary stress incontinence. The plug is made of thermoplastic elastomer (Kraton G), and consists of a meatal plate, a soft stalk and 1 or 2 spheres along the stalk. The spheres were located according to the result of the urethral pressure profile. The midpoint of the proximal sphere was placed at the bladder neck and the distal sphere was placed just above the maximum urethral pressure point. At voiding the plug was removed and afterwards a new plug was inserted. The plug with 2 spheres was tested in week 1 (period 1) and the plug with only the distal sphere was tested in week 2 (period 2). A total of 22 patients completed period 1. Eight patients did not complete period 2, mostly due to either unchanged incontinence during period 1 or a repeated loss of the plug with 1 sphere. In periods 1 and 2, 73 and 79% of the patients were subjectively and objectively continent or improved. A total of 14 patients completed both periods. Eight patients preferred the plug with 2 spheres, 1 preferred the other plug and 5 had no preference. The side effects were few. This preliminary study shows that the urethral plug seems to be a promising alternative treatment for female genuine urinary stress incontinence.

Equipment Design↗