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Biomedical subjects

L Norlén

Publications and source records attributed to L Norlén.

At least 19 recordsLinked to original sources
PubMed2002

Vitamin B12 and folate after 5-12 years of continent ileal urostomy (Kock reservoir) in children and adolescents.

OBJECTIVE: To assess B12 and folate deficiency after continent urinary diversion via a Kock continent urinary reservoir in children and adolescents. METHODS: Ten boys and 10 girls (10.8-18 years old at surgery) were operated with a Kock reservoir and followed for 5-12 years (mean 8.5). The follow-up period was divided into early (3 months-5 years, EFU) and late (5-12 years, LFU) follow-up. Patients were investigated for haemoglobin, serum iron, total iron binding capacity (TIBC), serum Vitamin B12, serum and blood folate, methylmalonic acid (MMA), homocystine and glomerular filtration rate. RESULTS: Two patients developed subnormal B12 values (median 107.5 pmol/l), one at the EFU, and the other at LFW. The B12 value decreased during the LFU compared to the EFU in nine patients, but it was still within the normal range. Two patients with renal impairment had elevated MMA with normal B12 values. Five patients had high values of homocystine with folate deficiency and/or B12 deficiency and renal impairment. Plasma folate mean value was normal during the whole follow-up. Blood folate was below normal in five patients at the EFU. Two of these five patients, in addition to three patients, had low values at the LFU. Three of four patients with remaining short terminal ileum (20-45 cm) had normal B12 values at both the EFU & LFU and one had low values at the LFU. Six patients had subnormal GFR at the LFU. CONCLUSIONS: To a similar degree as in adults, Vitamin B12, folate and iron deficiency can occur in children and adolescents after continent urinary diversion using an ileal segment. Therefore, Vitamin B12 and folate should be monitored regularly in these patients. Serum MMA and homocystine may offer increased detection of Vitamin B12 deficiency, especially in the patients with normal renal function. Vitamin B12 deficiency is neither correlated with the time elapsed since surgery, nor with the ileum length. Patients are usually asymptomatic, so patients with true B12 deficiency should be identified and placed on life-long Vitamin B12 therapy. An adequate synthetic folic acid as supplements or fortified food is recommended for patients with folate deficiency.

Adolescent↗
PubMed2001

Skin barrier structure and function: the single gel phase model.

A new model for the structure and function of the mammalian skin barrier is postulated. It is proposed that the skin barrier, i.e., the intercellular lipid within the stratum corneum, exists as a single and coherent lamellar gel phase. This membrane structure is stabilized by the very particular lipid composition and lipid chain length distributions of the stratum corneum intercellular space and has virtually no phase boundaries. The intact, i.e., unperturbed, single and coherent lamellar gel phase is proposed to be mainly located at the lower half of stratum corneum. Further up, crystalline segregation and phase separation may occur as a result of the desquamation process. The single gel phase model differs significantly from earlier models in that it predicts that no phase separation, neither between liquid crystalline and gel phases nor between different crystalline phases with hexagonal and orthorhombic chain packing, respectively, is present in the unperturbed barrier structure. The new skin barrier model may explain: (i) the measured water permeability of stratum corneum; (ii) the particular lipid composition of the stratum corneum intercellular space; (iii) the absence of swelling of the stratum corneum intercellular lipid matrix upon hydration; and (iv) the simultaneous presence of hexagonal and orthorhombic hydrocarbon chain packing of the stratum corneum intercellular lipid matrix at physiologic temperatures. Further, the new model is consistent with skin barrier formation according to the membrane folding model of Norlén (2001). This new theoretical model could fully account for the extraordinary barrier capacity of mammalian skin and is hereafter referred to as the single gel phase model.

Cholesterol↗
PubMed2001

Skin barrier formation: the membrane folding model.

We propose that skin barrier morphogenesis may take place via a continuous and highly dynamic process of intersection-free membrane unfolding with a concomitant crystallization of the emerging multilamellar lipid structure representing the developing skin barrier. This implies that the trans-Golgi network and lamellar bodies of the uppermost stratum granulosum cells as well as the multilamellar lipid matrix of the intercellular space at the border zone between stratum granulosum and stratum corneum could be representations of one and the same continuous membrane structure. The profound difference between the earlier Landmann model and the membrane folding model presented here is that the Landmann model includes changes in membrane topology, whereas topology is kept constant during skin barrier formation according to the membrane folding model. The main advantages of the membrane folding model with respect to the Landmann model are the following: (i) smaller energy cost (involves no budding or fusion); (ii) conserves membrane continuity (preserves water compartmentalization and allows control hereof; membrane continuity essential for barrier function); (iii) allows meticulous control (the thermodynamics of the unfolding procedure are related to curvature energy); (iv) faster (milliseconds, as membrane unfolding basically represents a phase transition from cubic-like to lamellar morphology; involves no budding or fusion); (v) membrane folding between lamellar and cubic-like morphologies has been identified in numerous biologic systems; (vi) there is experimental evidence for an "extensive intracellular tubulo-reticular cisternal membrane system within the apical cytosol of the outermost stratum granulosum"; and (vii) may explain the reported plethora of forms, numbers, sizes and general appearances of "lamellar bodies" in transmission electron microscopy micrographs.

Animals↗
PubMed2001

Questioning questions about symptoms of benign prostatic hyperplasia.

OBJECTIVES: Our aim was to conduct a survey about urinary symptoms and to find out if questioning patients about symptoms is helpful for the GP to make medical decisions concerning prostate problems among middle-aged men. METHODS: Twelve hundred randomly chosen men aged 55--65 years from the general population in north-west Stockholm, Sweden were sent a questionnaire consisting of symptom questions focusing on prostate problems based on the International Prostate Symptom Score (I-PSS). A subset of 120 respondents were asked to answer the same questions again and to participate in a urological examination including urodynamics and ultrasonography. The main outcome measures were the prevalence of urinary symptoms and the relationship between the symptom score and objective measures. RESULTS: A response rate of 86% was obtained in the questionnaire study. Twenty-one per cent of the respondents stated that they had general problems related to urination. Among individual symptoms, post-void dribbling and a weak stream were most common. Among the men examined at the Urological Department, the average prostatic volume was found to be 40 cm(3). Three out of four were assessed to have infravesical obstruction. No correlation between subjective symptoms and objective measurements of either a statistical or clinical significance was found. CONCLUSIONS: Urinary symptoms are common among middle-aged men. Further, an enlarged prostate and/or infravesical obstruction is often found in the ageing man. Information obtained by asking prostate-specific symptom questions cannot, however, serve as the foundation for the GP to find those men whose problems would be solved by actions directed at the prostate.

Aged↗
PubMed2000

Structure-related aspects on water diffusivity in fatty acid-soap and skin lipid model systems.

Simplified skin barrier models are necessary to get a first hand understanding of the very complex morphology and physical properties of the human skin barrier. In addition, it is of great importance to construct relevant models that will allow for rational testing of barrier perturbing/occlusive effects of a large variety of substances. The primary objective of this work was to study the effect of lipid morphology on water permeation through various lipid mixtures (i.e., partly neutralised free fatty acids, as well as a skin lipid model mixture). In addition, the effects of incorporating Azone((R)) (1-dodecyl-azacycloheptan-2-one) into the skin lipid model mixture was studied. Small- and wide-angle X-ray diffraction was used for structure determinations. It is concluded that: (a) the water flux through a crystalline fatty acid-sodium soap-water mixture (s) is statistically significantly higher than the water flux through the corresponding lamellar (L(alpha)) and reversed hexagonal (H(II)) liquid crystalline phases, which do not differ between themselves; (b) the water flux through mixtures of L(alpha)/s decreases statistically significantly with increasing relative amounts of lamellar (L(alpha)) liquid crystalline phase; (c) the addition of Azone((R)) to a skin lipid model system induces a reduction in water flux. However, further studies are needed to more closely characterise the structural basis for the occlusive effects of Azone((R)) on water flux.

Azepines↗
PubMed2000

Skin island urethroplasty in deep urethral lesions--a long-term follow-up of 25 consecutive patients.

Strictures and ruptures of the bulbomembranous urethra have traditionally been treated by a two-stage scrotal skin inlay technique (Johanson B. Reconstruction of the male urethra in strictures. Acta Chir Scand 1953; Suppl 176). For the last 10 years we have treated the patients instead with a skin-dartos island flap pedicled on intertesticular septal vessels. The skin island has been taken from the scrotum, the penile base, or the penile shaft. Twenty-five consecutive patients were treated until 1993 and followed up for at least 5 years. Five of the patients had had open urethroplasty before. Fifteen of the patients had urethral strictures and 10 had complete ruptures. Of the 25 patients 6 had to have a further operation; in 4 patients this was because of restricture, in 1 patient a urethral pouch had to be reduced, and in the final patient the operation was both for restricture and pouch formation. At final follow-up impaired micturition occurred in three patients: two of them had had a ruptured urethra treated previously, and one had a chronic infectious stricture. Problems related to hirsutism were low. No obvious advantage was detected from using distal penile skin, so a skin-dartos island from the penile base is advocated. In conclusion, a one-stage skin-dartos island flap pedicled on the intertesticular septal vessels may be recommended in the treatment of both strictures and complete ruptures in the bulbomembranous urethra.

Adolescent↗
PubMed1999

Transrectal ultrasound with separate measurement of the transition zone volume predicts the short-term outcome after transurethral resection of the prostate.

OBJECTIVES: To determine whether the volume of prostatic adenomas as assessed by transrectal ultrasound (TRUS) influenced the outcome after transurethral resection of the prostate (TURP). METHODS: TRUS with total prostate and transition zone (TZ) volume determinations was performed preoperatively in 298 consecutive patients undergoing TURP for benign prostatic hyperplasia without prior urodynamic evaluation. Postoperatively, the outcome of surgery was stated as excellent (no or minor remaining symptoms), improved (but with some remaining symptoms), or failure (the same or aggravated symptoms) according to a patient-administered questionnaire. Six possible risk factors were evaluated: TZ volume 20 cc or less, neurologic disorders, previous TURP/transurethral incision of the prostate (TUIP), diabetes, indwelling catheter, and age older than 80 years. RESULTS: Thirty patients (10.1%) had treatment failure, 45 (15.1%) improvement, and 223 (74.8%) had excellent outcome. After subdivision into preoperative TZ volume of 20 cc or less and greater than 20 cc, it was found that the outcomes of 20.9% (n = 19) were failures if the TZ volume was 20 cc or less but only 5.3% (n = 11) if the TZ volume was greater than 20 cc. Additional independent risk factors for failure were neurologic disorders and previous TURP/TUIP. When all patients with risk factors were excluded (TZ volume 20 cc or less, neurologic disorders, previous transurethral surgery, and diabetes), the risk of failure was 3.3%. CONCLUSIONS: Patients with a preoperative TZ volume greater than 20 cc and no history of neurologic disorders, previous TURP/TUIP, or diabetes had a very high chance of favorable outcome after TURP, even though no pressure/flow evaluation had been performed preoperatively.

Aged↗
PubMed1999

Early and late metabolic alterations in children and adolescents with a kock urinary reservoir.

OBJECTIVE: To assess the early and late metabolic effects of urinary diversion in children and adolescents with a Kock urinary reservoir. PATIENTS AND METHODS: Thirteen children (aged 10.8- 16 years) and seven adolescents (aged 16-18 years; 10 girls and 10 boys), underwent surgery for congenital urinary incontinence. They were followed for 3-10 years (mean 6.5), divided into an early (3 months to 2 years) and a late (2-10 years) period, and assessed for renal function and any metabolic effects. RESULTS: At the early and late follow-up, one of 19 and three of 16 patients, respectively, had metabolic acidosis. Hyperchloraemia was present in four of 20 patients at the early and in eight of 18 at the late follow-up. Serum creatinine was increased in four of 20 patients at the early and eight of 18 at the late follow-up. In patients with infrequent reservoir emptying (</=4 times/day), the serum creatinine level was increased in seven of 13 at the early and eight of 10 at the late follow-up (P<0.05). The glomerular filtration rate was below normal in four of 20 patients preoperatively, in six of 19 at the early and in eight of 18 at the late follow-up. CONCLUSIONS: The continent ileal reservoir in children and adolescents produces similar changes to those previously reported in adults. However, almost all patients with metabolic disorders were younger than 16 years at operation. The pre-existing impairment of renal function, together with associated congenital anomalies, mental and/or physical disorders, young age, recurrent urinary tract infections and infrequent reservoir emptying, leads to deterioration in renal function after the Kock operation. Even with this risk, the Kock pouch remains a viable alternative to other forms of continent urinary diversion, because it has a wide calibre stoma, allowing large-bore catheters, and is therefore especially suitable for individuals with weak hand function, e.g. quadriplegic or meningomyelocele patients. However, as shown by these results, the child with a Kock pouch requires continuous medical attention.

Acid-Base Equilibrium↗
PubMed1999

Inter- and intra-individual differences in human stratum corneum lipid content related to physical parameters of skin barrier function in vivo.

For a full understanding of the properties of the human skin barrier, physical macroscopic parameters of barrier function must be correlated to the structural organization of the barrier on a molecular level. This study was undertaken to relate differences in the relative composition of the three main lipid classes of human stratum corneum, i.e., free fatty acids, cholesterol, and ceramides, to differences in transepidermal water loss, stratum corneum electrical impedance, and corneometer value. A new high performance liquid chromatography/light scattering detection-based analysis method recently developed was used for collection of quantitative lipid data in conjunction with gas chromatography/mass spectrometry/flame ionization detection measurements on the free fatty acid fraction. After subtraction of contaminating lipid fractions we have estimated the molar ratio of the human skin barrier lipid composition to be, respectively, 15% cholesterol esters, 16% saturated long chain free fatty acids, 32% cholesterol, and 37% ceramides. The inter-individual difference in the relative amount of free fatty acids, cholesterol, and ceramides, respectively, can be >100% in the individual case. It was found that the relative amount of ceramides to cholesterol is larger in the wrist area, paralleled by a higher transepidermal water loss and corneometer value as well as different skin electrical impedance values as compared with the upper forearm area. We conclude that the site-dependent differences in the stratum corneum lipid composition are small compared with the large inter-individual variation. Interestingly, in the individual case, no correlation was registered between relative ceramide content and barrier properties.

Adolescent↗
PubMed1999

A new computer-based evaporimeter system for rapid and precise measurements of water diffusion through stratum corneum in vitro.

It is important to have reliable methods for evaluation of skin barrier function when questions such as barrier perturbing effects of different agents and occlusive effects of different formulations are to be elucidated. A wealth of clinical work relates to measurements of transepidermal water loss in vivo, a method much affected by ambient air relative humidity, temperature, skin irritation processes, psychologic status of the subject, etc., factors that cause the method to suffer from low precision (i.e., high random error). Relating to these obstacles, we have developed a closed in vitro system for measurements of water diffusion rate through pieces of isolated stratum corneum at steady-state conditions, where the relative humidity and temperature is held constant and data can be collected continuously. Our evaporimeter-based in vitro system has a more than 3-fold higher precision (lower random error) ( approximately 10%) than measurements of transepidermal water loss in vivo ( approximately 35%). The results of our study show that: (i) the corneocyte envelopes contribute to the barrier capacity of stratum corneum; (ii) removal of the lipid intercellular matrix results in approximately a 3-fold increase in the water diffusion rate through the isolated stratum corneum (n = 20; p < 0.05), not a 100-fold as has previously been suggested; (iii) exposure to sodium dodecyl sulfate in water does neither alter the water diffusion rate (n = 10; p > 0.05) nor the water holding capacity (n = 10; p > 0.05) of stratum corneum; (iv) exposure to 1 M CaCl2 in water yields an increased water diffusion rate through stratum corneum (n = 10; p < 0.05); and (v) when applied to the stratum corneum in excess concentrations, the penetration enhancer Azone has occlusive effects on water diffusion through the stratum corneum (n = 6; p < 0.05).

Azepines↗
PubMed1999

Evaluation of Kock urinary reservoir function in children and adolescents at 3-10 years' follow-up.

The aim of this study was to evaluate Kock reservoir function in children and adolescents operated for congenital urinary incontinence and to determine the complication rate. Reservoir function was investigated in 13 children (age range 10.8-16 years) and 7 adolescents (age range 16-18 years) through enterocystometry, enterocystoscopy and patient history. Patients were followed up for 3-10 years. The follow-up was reported as early (3 months-2 years) and late (2-10 years) postoperative periods. At early follow-up reservoir capacity was high in four patients and normal in the remaining patients. A low reservoir pressure was accompanied by high capacity and compliance. On enterocystometry first sensation for emptying was experienced in 82% of patients at early follow-up and 92% at late follow-up. Reservoir contractions were recorded in 60% of patients at early follow-up and 65% at late follow-up. The contractions were recorded at an average reservoir capacity of 270 ml at early follow-up and 340 ml at late follow-up. The complication rate was high in the child group compared with that in adolescents. Of 13 patients with at least one reservoir complication 10 were from the child group. Nipple dysfunction (angled nipple, prolapsed or stenosed stoma) occurred in 35% of patients, stones in 40% and bleeding during catheterization in 15%. Revision was performed in 38% of the child group and 15% of the adolescents. Reservoir perforation was observed in two patients at 6 and 9 years postoperatively. At late follow-up continence was excellent in 17 of 19 patients and good in 2. We conclude that the Kock reservoir is a good modality for urinary diversion, but the complication incidence is high in the child group (<16 years). Stability of the reservoir in terms of volume and low internal pressures was achieved one year after operation, except in the patients with infrequent reservoir emptying. A time-related increase in the reservoir sensitivity and contractility was reported on enterocystometry. Nipple dysfunction is common during the first two years after surgery, particularly in the child group. Stones may form 3-4 years after surgery. Satisfactory continence was achieved in all patients, although a revisional operation was necessary in some patients in order to obtain permanent continence.

Adolescent↗
PubMed1999

Kock urinary reservoir maturation in children and adolescents: consequences for kidney and upper urinary tract.

OBJECTIVE: To study Kock reservoir maturation in children and adolescents and its effects on the kidneys and upper urinary tract. METHODS: Ten boys and 10 girls, aged 10.8-18 years, had Kock reservoir surgery for congenital urinary incontinence. They were followed for 3-10 years, divided into 3 different periods, and assessed with urography and enterocystography, the findings of which were correlated to renal function as measured by (51)Cr EDTA clearance, reservoir endoscopy and patient's history. RESULTS: The reservoir was located in the pelvis and remained in this position throughout the whole follow-up in 75% of patients and in the lower or midabdomen in 25%. Angled efferent nipple seen on enterocystoscopy or enterocystography coincided with nipple dysfunction, reservoir malposition or infrequent reservoir emptying. Upper urinary tract dilatation was detected in 84% of patients 3 months after surgery, 25% at 1 year and 30% at 2-10 years. The dilatation was improved in 56% of patients and unchanged in 25% after 1 year. The situation continued to improve at late follow-up. New focal renal scars were radiologically detected in 1 of 19 at early and in another 1 of 17 patients at late follow-up. Progression of old scars was detected in 1 of 19 at early and in 4 of 17 at late follow-up. Eight of 19 cases had deterioration of renal function with a change in the split renal function. Of these 8 patients, 7 reported infrequent reservoir evacuation. CONCLUSIONS: Kock reservoir is a useful form of urinary diversion in children and adolescents with congenital urinary incontinence. Radiological examinations are good methods of follow-up of the maturation of the pouch and its effects on the urinary tract and for detection of complications. Urinary tract dilatation is a frequent finding early after surgery but it subsides in most cases 3-12 months after surgery. Long-term efferent nipple dysfunction may be the result of angulation, reservoir stones, malposition and/or overdistension. Permanent renal damage may be due to pyelonephritis, stones, infrequent reservoir emptying or urinary obstruction. A strict regime of reservoir evacuation to avoid overdistension and nipple dysfunction and to decrease the possibility of renal function deterioration is strongly advisable in these patients. It is imperative that their own management of the reservoir is continuously supervised.

Adolescent↗
PubMed1998

A new HPLC-based method for the quantitative analysis of inner stratum corneum lipids with special reference to the free fatty acid fraction.

The inner stratum corneum is likely to represent the location of the intact skin barrier, unperturbed by degradation processes. In our studies of the physical skin barrier a new high-performance liquid chromatography (HPLC)-based method was developed for the quantitative analysis of lipids of the inner stratum corneum. All main lipid classes were separated and quantitated by HPLC/light scattering detection (LSD) and the free fatty acid fraction was further analysed by gas-liquid chromatography (GLC). Mass spectrometry (MS) was used for peak identification and flame ionization detection (FID) for quantitation. Special attention was paid to the free fatty acid fraction since unsaturated free fatty acids may exert a key function in the regulation of the skin barrier properties by shifting the physical equilibrium of the multilamellar lipid bilayer system towards a noncrystalline state. Our results indicated that the endogenous free fatty acid fraction of the stratum corneum barrier lipids in essence exclusively consisted of saturated long-chain free fatty acids. This fraction was characterized as a very stable population (low interindividual peak variation) dominated by saturated lignoceric acid (C24:0, 39 molar%) and hexacosanoic acid (C26:0, 23 molar%). In addition, trace amounts of very long-chain (C32-C36) saturated and monounsaturated free fatty acids were detected in human forearm inner stratum corneum. Our analysis method gives highly accurate and precise quantitative information on the relative composition of all major lipid species present in the skin barrier. Such data will eventually permit skin barrier model systems to be created which will allow a more detailed analysis of the physical nature of the human skin barrier.

2-Propanol↗
PubMed1998

Lower urinary tract symptoms. A comparison of micturition symptoms in patients scheduled for transurethral prostatic resection and outpatients of both sexes referred for non-urological complaints.

The presence of ten different micturition symptoms was investigated by means of a patient-administered questionnaire in 355 males and females over 50 years of age referred for non-urological complaints, and compared to those of 131 patients selected for transurethral prostatic resection (TURP) due to symptomatic benign prostatic hypertrophy. Each symptom was evaluated further by a subsequent "bother" question and the questionnaire also contained a global "bother" question. Each of the symptoms was significantly more frequent and pronounced in the TURP group than in the control group. Moderate or severe symptoms were found in 25% of males and 18% of females in the control group as compared to 92% in the TURP group. In the control group most symptoms increased with age regardless of sex, and this was most pronounced for weak stream and hesitancy. Males in the control group had a significantly higher total symptom score than females (5.3 vs 4.3; p < 0.05). This difference was, however, mainly due to higher scores in weak stream, hesitancy and post-micturition dribbling in males. Females tended to have more urgency. The symptom scores and the associated "bother" scores were highly correlated, indicating that each symptom carried the same potential to bother the patient. The single global "bother" question gave an adequate reflection of the combined "bother" scores, and seems sufficient in the evaluation of the individual patient's concern.

Aged↗
PubMed1997

Stratum corneum swelling. Biophysical and computer assisted quantitative assessments.

The aim of this study was to characterize the swelling behaviour of the stratum corneum. Stratum corneum pieces isolated from the breast region of 20 different females were incubated in distilled water at two different temperatures (20 degrees C and 45 degrees C) for 90 min and 24 h, respectively. Half of the stratum corneum pieces were previously extracted with chloroform-methanol (2:1). The area-enlargement was photographically recorded. The thickness enlargement was determined using a confocal laser scanning microscope. The average swelling (99% confidence interval) in the area dimension at 20 degrees C was 8.4% +/- 1.4% (n = 20), which corresponded to an average swelling in the length (lateral) dimension of approximately 4.1%. The swelling in the thickness dimension was 26.3% +/- 16.3% (n = 8). The swelling was most pronounced in the thickness dimension and was complete after 90 min of water immersion (P < 0.01, n = 5). In addition, the removal of the intercellular lipids with chloroform/methanol (2:1) induced a decreased swelling in the samples (P < 0.01, n = 20). An increase in temperature of the water from 20 degrees C to 45 degrees C resulted in an increase in swelling (P < 0.01, n = 20). Taken together our results support the idea that the mechanism of stratum corneum swelling is linked to the intercellular lipid structure and hence to skin barrier function.

Adolescent↗
PubMed1997

A novel approach to the understanding of human skin barrier function.

The basis for externally caused skin disorders is penetration of the skin barrier. A recent model for the skin barrier, the domain mosaic model, based on current knowledge of the physics of lipid bilayer organization gave tentative explanations for several aspects of function. It is demonstrated here that a development of the model explains how the requirements are met for a water-tight structure that will still allow a controlled, minute loss of water, the perspiratio insensibilis, necessary for maintaining plasticity of the keratin. A major advantage of the extended model is that it allows an interpretation of the changes imposed on the structure when in contact with detergents and/or penetration enhancers.

Administration, Cutaneous↗
PubMed1997

Effects of intravesical instillation of 5-fluorouracil and interferon in patients with recurrent superficial urinary bladder carcinoma. A clinical and pharmacodynamic study.

Eleven patients with recurrent superficial bladder tumours were treated with 6 weekly instillations of 10 million IU Introna and 1000 mg 5-fluorouracil for 1 h. Before and immediately after the first treatment biopsies were taken from normal urothelium and tumour for analysis of thymidylate synthase (TS). One papillary tumour was left as a marker. Tumour tissue had 9 times higher TS concentrations than normal urothelium (0.97 versus 0.11 pmol/g, p < 0.005). Despite a large variation in TS concentration in the tumours between different patients (range 0.02-2.24 pmol/g), after instillation the TS concentration decreased significantly in all but one patient. Six patients had complete and 2 had partial tumour regression after treatment. The effect was inversely correlated to the initial TS value. A low TS value seemed to predict a good response. The data suggest that weekly administrations are not sufficient in those with high TS concentrations. New treatment schedules may be beneficial in those with highly proliferating bladder tumours.

Administration, Intravesical↗