Aerosolized spread of bacteria and reduction of bacterial wound contamination with three different methods of surgical wound debridement: a pilot study.

BACKGROUND: Debridement is essential in wound treatment to remove necrotic tissue and wound bacteria, but may lead to the transmission of bacteria by aerosolization. AIM: To investigate bacterial transmission and wound bacterial reduction induced by debridement using a cold steel curette, plasma-mediated bipolar radiofrequency ablation (Coblation(®)) or hydrodebridement (Versajet(®)) using a wound model inoculated with Staphylococcus aureus. METHODS: A full-thickness dermal wound was created in fresh porcine joint specimens, inoculated with S. aureus and incubated at 37°C for 24h. The specimens were surgically debrided with a curette, Coblation or Versajet, or were left untreated. During and after each debridement, aerosolized bacteria were measured by active and passive sampling. To assess the bacterial load of the wound, three quantitative swabs and one cylinder scrub sample were taken from each wound at baseline, post incubation and post debridement. FINDINGS: Versajet debridement resulted in significant bacterial aerosolization, but this was not the case when using a curette or Coblation. Only Coblation was able to reduce the bacterial load of the wound significantly. CONCLUSION: Extra protective means should be implemented when using Versajet debridement for infected and colonized wounds. The same precautions may be less essential when using a curette or Coblation.

High prevalence of metabolic complications in patients with non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is considered to be the liver component of the metabolic syndrome and is frequently associated with obesity, dyslipidemia and type II diabetes mellitus (NIDDM). We aimed to determine the development of liver function tests (LFTs) and metabolic complications in patients previously diagnosed with NAFLD. METHODS: One-hundred-and-two patients with NAFLD diagnosed in the period 1994-2001 were identified. Eighty were brought in for new investigations, including LFTs, blood pressure, BMI, lipid profile, blood glucose and insulin. Original liver biopsy was re-evaluated. RESULTS: Sixty-two patients (77%) were males (median age 46 years; mean follow-up time 2.8 +/- 1.2 years). Fifty-four patients (68%) were light to moderately overweight with body mass index (BMI) 25-30 kg/m. Mean BMI (28.2) was the same at diagnosis and at follow-up (28.3). At the new examination, 18 patients (23%) had developed diabetes mellitus type II (n = 6) or had impaired fasting glucose (IFG) (n = 12), compared to only 2 patients at diagnosis. Hyperinsulinemia was observed in 19 patients (24%). Dyslipidemia, with elevated triglycerides and/or hypercholesterolemia, was now present in 65 patients (81%). Twenty-two patients (27%) had hypertension compared to 9 (11%) at diagnosis. Liver biopsy was performed in 24%, and 89% of those fulfilled the criteria for NASH. However, mild inflammation and fibrosis was observed, grade 1-2 (n = 17), stage I-II (n = 13) and none had cirrhosis. CONCLUSION: A significant proportion of patients with both clinical and histological diagnosis of NAFLD develop metabolic problems soon after diagnosis. These patients should be screened regularly for metabolic disorders.

Cytopathological expression of different types of urothelial carcinoma in situ in urinary bladder washings.

OBJECTIVE: To evaluate and compare the cytopathological expression of the five major histological types of carcinoma in situ (CIS) in urinary bladder washings from patients with flat urothelial lesions. MATERIALS AND METHODS: Seventy-five cases of primary and secondary urothelial CIS with no concomitant tumours, and having tissue and cytological samples, were identified. Biopsies were evaluated based on the consensus classification as: large-cell pleomorphic; large-cell non-pleomorphic; small-cell; clinging; and cancerization of the urothelium. In the cytological classification the 'clinging' category was excluded, as its definition depends on the histological appearance. kappa statistics were used to evaluate the correlation between histopathology and cytology. RESULTS: More than one subtype of CIS could often be identified in both the histological and cytological specimens. Cytology often showed more subtypes than did histopathology. Statistically, there was only a moderate correlation between histopathology and cytology for recognising different patterns. CONCLUSION: Different patterns of CIS can be identified by cytology; it is important for cytologists to be aware of the cytological spectrum of CIS and not to under-diagnose monomorphic, pagetoid (cancerization) and small-cell forms. Studies on treatments for CIS and of the clinical significance of different subtypes of CIS should include both cytopathology and histopathology.

Functional effects of dextran sulphate sodium (DSS) treatment on the longitudinal muscle of rat distal colon.

1. The current study addressed how acute colitis, induced in male Sprague-Dawley rats by the administration of dextran sulphate sodium (DSS) in their drinking water, may affect some functional properties of the longitudinal muscle layer of the distal colon. 2. Dextran sulphate sodium was provided at a concentration of 3% for 3 or 7 days, or 5% for 7 days, and the rats were thereafter killed. Specimens of the distal colon were taken for histology or for organ bath experiments. 3. The colitis score increased significantly with increasing dose of DSS administered. At 5% concentration, there was sometimes even transmural inflammation. Functionally, there was a progressive increase in optimal preload (P(o)) for the contractile response to carbachol (1 microM), in relation to the severity of the colitis. At 5% DSS, the magnitude of the response to carbachol at P(o) was significantly increased compared with control rats. Such an effect could not be verified when, instead, K+ (60 mM) was used as a spasmogen. 4. It is concluded, that the colitis score increased in severity progressively with increasing amounts of DSS administered. The longitudinal muscle layer was functionally affected by the inflammation. Thus, there was a progressive increase in optimal preload for muscle contraction. Moreover, severe colitis resulted in an increase of the contractile response to carbachol, while a significant increase in the response to depolarization with K+ could not be found.

Complete transurethral resection of ulcers in classic interstitial cystitis.

Interstitial cystitis (IC) is a chronic disease of obscure etiology. It commonly affects females, who present with symptoms of pain on bladder filling and urinary frequency. There are two types of IC: classic and non-ulcer disease, which differ in many respects, including response to different therapies. In this retrospective study we evaluated the hitherto largest series of patients with classic IC treated by transurethral resection (TUR) of visible ulcers. Altogether 259 TURs of Hunner ulcers were performed on 103 patients: 92 experienced amelioration, and in 40% symptom relief lasted more than 3 years. In the remaining patients, although symptom recurrence was common, the majority responded well to subsequent TUR. In conclusion, TUR has a good outcome in patients with classic interstitial cystitis, and we suggest it as first-line treatment in this patient group.

Stage T1 adenocarcinoma of the urinary bladder--complete response after transurethral resection and intravesical bacillus Calmette-Guerin.

OBJECTIVE: To report the results of treatment of adenocarcinoma of the urinary bladder with transurethral resection and intravesical bacillus Calmette-Guerin (BCG). METHODS: Out of 183 patients in our department treated with BCG between 1992 and 1996, three patients had adenocarcinoma, stage T1. RESULTS: All three patients had normal cystoscopy and negative cytology 53-82 months after the start of treatment. CONCLUSIONS: BCG appears to be effective not only in the treatment of transitional cell carcinoma, but also in adenocarcinoma of the bladder.

Increased tyrosine hydroxylase immunoreactivity in bladder tissue from patients with classic and nonulcer interstitial cystitis.

PURPOSE: Interstitial cystitis is a chronic debilitating condition which mainly affects women. Accumulated evidence indicates that interstitial cystitis is a heterogeneous syndrome. The nonulcer subtype appears different than classic interstitial cystitis in regard to symptoms, and endoscopic and histological findings as well as response to various treatments. We further explore the neurogenic nature of this disease using indirect immunofluorescence to evaluate the presence and density of various autonomic and sensory nerve fibers. MATERIALS AND METHODS: Specimens from the bladder wall of 6 patients with classic interstitial cystitis, 7 with nonulcer interstitial cystitis and 6 controls were evaluated to determine the presence and density of nerve fibers containing tyrosine hydroxylase, calcitonin gene-related peptide, neuropeptide Y and substance P using specific antibodies, and the general presence of nerve fibers using a mixture of antibodies against nerve filament, neuron specific enolase and S-100 protein. RESULTS: Increased density and number of nerve fibers immunoreactive for tyrosine hydroxylase were noted in interstitial cystitis cases compared to controls. Furthermore, there was a difference between classic and nonulcer disease in the overall density of nerves using the antibody mixture. CONCLUSIONS: Our findings indicate an altered peripheral sympathetic innervation in interstitial cystitis cases, which may be an indication of primary neurogenic etiology. The difference in nerve density observed after incubation with the antibody mixture between classic and nonulcer interstitial cystitis supports the hypothesis that the 2 forms represent separate entities.

Recruitment, distribution and phenotypes of mast cells in interstitial cystitis.

PURPOSE: Interstitial cystitis (IC) is a chronic disabling condition of unknown etiology. One of its major characteristics is an increase in mast cells (MC) showing signs of activation. It has been suggested that the proteinase content defines two MC types: MC(TC), containing chymase and tryptase, and MC(T), which contains tryptase but lacks chymase. Here, we investigated the MC distribution and the MC proteinase expression in IC together with the tissue expression of the major MC growth factors, stem cell factor (SCF) and interleukin-6 (IL-6). MATERIALS AND METHODS: MC were enumerated in bladder specimens from patients with classic IC, nonulcer IC and controls. MC were visualized in terms of metachromasia, reflecting glycosaminoglycan content, and immunohistochemically, visualizing tryptase, chymase and IL-6 as well as the surface markers CD117 and SCF. RESULTS: Classic IC displayed a 6 to 10-fold increase of MC identified by proteinase content while in nonulcer IC there were twice as many MC as in controls. In contrast to nonulcer IC and controls, classic IC displayed an abundance of epithelial MC. Fewer CD117+ than proteinase+ MC were detected in IC but not in controls. Classic IC coexpressed SCF and IL-6 in the epithelium and displayed numerous SCF and IL-6+ cells in the mucosa and detrusor muscle, many of which were MC. CONCLUSIONS: Redistribution of MC into the epithelium and a high bladder wall MC density distinguish classic IC from nonulcer IC. Our findings suggest an SCF/IL-6-driven MC response in IC. They also indicate a downregulation of the SCF receptor in IC.

S-phase fraction related to prognosis in localised prostate cancer. No specific significance of chromosome 7 gain or deletion of 7q31.1.

A flow-cytometric (FCM) and fluorescence in situ hybridization (FISH) study was performed in 153 patients with clinically localised prostate cancer (PC) to evaluate retrospectively the prognostic significance of DNA ploidy, S-phase fraction (SPF) and chromosome 7 copy number. Deletions in 7q31.1 were analysed in a subset of 26 tumours. The mean follow-up time was 6 years (range 4-16 years). Twelve cases of benign prostatic hyperplasia (BPH) were studied as a control. Chromosome 7 enumeration and deletion studies were conducted using the alpha-satellite D7Z1 probe and a cosmid probe specific for the marker D7S522 on 7q31.1. Higher SPF was associated with shorter overall survival and shorter time to local progression and metastasis. Near diploid (DNA index 1.05-1.20) cases had a lower frequency of metastases and lower Gleason scores than aneuploid cases. Increased absolute chromosome 7 copy number (centromere count) was associated with higher Gleason score, higher SPF and shorter local progression-free and prostate cancer survival. Absolute chromosome 7 copy number was concordant with FCM DNA ploidy in the majority (75%) of cases. Relative gain or loss of chromosome 7 (centromere counts compared to ploidy) was infrequent, and no correlation was found with clinical parameters. Deletions in 7q31.1 were infrequent. Our results indicate that in localised PC (i) SPF is a prognostic factor, (ii) absolute chromosome 7 copy number is concordant with the ploidy status of the tumour (relative gain or loss of chromosome 7 is infrequent and has no independent prognostic value) and (iii) the frequency of deletions in 7q31.1 is low and not correlated with clinical outcome.

Metaplastic transformation of urinary bladder epithelium: effect on mast cell recruitment, distribution, and phenotype expression.

Mucosal mast cells (MCs) are normally found in the connective tissue stroma but are redistributed into the epithelium in conditions associated with immunoglobulin E responses, such as allergic inflammation and nematode infections, as well as in interstitial cystitis, a condition of unknown etiology. The potential role of epithelium-derived factors in this response prompted this inquiry into growth and differentiation signaling in normal tissue as well as in tissues from five different metaplastic conditions of the urothelium (cystitic cystica, cystitis glandularis, colonic metaplasia, squamous cell metaplasia, and nephrogenic metaplasia). Expression of the two major human MC growth factors, stem cell factor (or kit ligand) and interleukin 6, was detected using immunohistochemistry. In the case of interleukin 6, its mRNA expression was also detected using in situ reverse transcription-polymerase chain reaction. Among the different metaplastic lesions, nephrogenic metaplasia was the only one associated with an abundance of MCs, which were distributed within or in close relationship to the epithelium. Unlike in the other types of metaplasia, the epithelium strongly co-expressed interleukin 6 and stem cell factor. The MCs expressed the stem cell factor receptor CD117 and exhibited a variable tryptase immunoreactivity, but lacked chymase. They also displayed a relative deficiency of granular glycosaminoglycan, as indicated by a lack of metachromasia, and were sensitive to strong aldehyde fixation. The findings suggest that the MC response in nephrogenic metaplasia may be the result of local epithelial stem cell factor/interleukin 6 expression.

Gastrointestinal pacemaker cell tumor (GIPACT): gastrointestinal stromal tumors show phenotypic characteristics of the interstitial cells of Cajal.

The interstitial cells of Cajal (ICC) form a complex cell network within the gastrointestinal tract wall where they function as a pacemaker system. Expression of the kit proto-oncogene is essential for the development of this system. The aim of our study was to examine the hypothesis that gastrointestinal stromal tumors differentiate toward cells with an ICC phenotype. Ultrastructurally, 58 stromal tumors were characterized and found to share many features with ICC. Seventy-eight stromal tumors were immunophenotyped, particularly with regard to the kit receptor. All 78 tumors revealed strong, homogeneous immunoreactivity for the kit receptor as did ICC of adjacent and control gastrointestinal walls. Focal hyperplasia and hypertrophy of kit receptor positive cells were also observed in the gastrointestinal wall adjacent to the tumors. CD34 immunoreactivity observed in interstitial cells surrounding Auerbach's ganglia suggests that a subpopulation of ICC is CD34 positive and may explain why 56 of 78 stromal tumors were CD34 positive. Thirty control tumors, including gastrointestinal leiomyomas and leiomyosarcomas, were all negative for the kit receptor. We conclude that gastrointestinal stromal tumors show striking morphological and immunophenotypic similarities with ICC and that they may originate from stem cells that differentiate toward a pacemaker cell phenotype. We propose that the noncommittal name "gastrointestinal stromal tumor" be replaced by gastrointestinal pacemaker cell tumor.

Fulminant hepatic failure associated with dicoumarol therapy.

Coumarins have been associated with non-predictable hepatic injury. In the case of dicoumarol, there is no hard evidence in the literature of a causal connection with liver damage. We report the case of a 73-year-old woman who developed a fatal liver disease of a mixed hepatocellular-cholestatic type after 3 months of treatment with dicoumarol. A thorough diagnostic work-up did not reveal any other possible cause of the liver disease.

The treatment of interstitial cystitis with supratrigonal cystectomy and ileocystoplasty: difference in outcome between classic and nonulcer disease.

PURPOSE: Interstitial cystitis is a chronic debilitating condition that mainly affects women. Accumulated evidence indicates that interstitial cystitis is a heterogeneous syndrome. The nonulcer type seems to respond less favorably to various conservative treatments than the classic type. Supratrigonal cystectomy with ileocystoplasty is established treatment for interstitial cystitis refractory to conservative treatment. We evaluate whether classic interstitial cystitis responds differently than nonulcer disease to subtotal bladder resection and ileocystoplasty. MATERIALS AND METHODS: We evaluated 13 patients 27 to 79 years old with interstitial cystitis who underwent supratrigonal cystectomy and ileocystoplasty due to failure to respond to conservative treatment. RESULTS: In all 10 patients with classic interstitial cystitis symptoms were relieved after ileocystoplasty. In the 3 patients with nonulcer interstitial cystitis pain remained, while the frequency of voiding somewhat decreased. In these patients trigonal resection and urinary diversion with a Kock pouch resolved the symptoms. CONCLUSIONS: Our study confirms that supratrigonal cystectomy with ileocystoplasty results in a good outcome in classic interstitial cystitis. However, this method seems to be unsuitable for nonulcer disease. Identification of the relevant subtype of interstitial cystitis is of crucial importance for selecting the appropriate method of lower urinary tract reconstruction.

Decreased levels of S-100 protein in non-ulcer interstitial cystitis.

Interstitial cystitis (IC) is a chronic debilitating condition which mainly affects women. Accumulated evidence indicates that IC is a heterogeneous syndrome. As compared to classic IC, the non-ulcer type of IC appears to be different concerning symptomatic, endoscopical and histological findings, as well as in response to various forms of treatment. S-100 is a neural protein considered to be located primarily in the axons. To explore further the neurogenic nature of the disease, we compared bladder wall S-100 content in controls and in patients with classic and non-ulcer IC. We noticed a decrease in S-100 content in non-ulcer IC as compared to controls. This may be an expression of altered peripheral innervation in non-ulcer IC, which, in turn, may be an indication of primary neurogenic etiology. The difference in S-100 content between classic and non-ulcer IC supports the hypothesis that they represent separate entities, which may explain differences in response to various treatments.

Nephrogenic adenoma--a study with special reference to clinical presentation.

OBJECTIVE: To obtain information on the presenting symptoms, location, sex distribution, age, endoscopic appearance, histopathology, suitable treatment and recurrence of nephrogenic adenoma, a rare, benign lesion of the urinary tract mucosa. PATIENTS AND METHODS: The records of 31 patients with nephrogenic adenoma diagnosed at the Sahlgrenska University Hospital between 1980 and 1996 were reviewed to determine the symptomatology, imaging investigations, endoscopic presentation, clinical outcome after resection and the frequency of recurrence. RESULTS: The lesions were found in the urinary bladder, bulbar urethra, urethral diverticula and the prostatic urethra. Eight patients presented with haematuria, 13 complained of urinary frequency and bladder pain and in 12 patients without subjective symptoms from the urinary tract, the lesion was found accidentally. Twenty-seven of the patients had a history of previous urothelial trauma, either by instrumentation or inflammation. Seventeen of the lesions were polypoid at endoscopy, the remainder being flat except for two cases, in which they were not noted because they were concealed in another lesion to be resected. Seven patients had one or more recurrences. All patients with symptoms responded well to transurethral resection. CONCLUSION: Nephrogenic adenoma mimics tumour or chronic cystitis and it is rarely suspected on clinical grounds; instead, the diagnosis is almost always histological. This study supports the view that nephrogenic adenoma may represent a metaplastic response to trauma of the urothelium and that transurethral resection provides a good method of relieving the symptoms in symptomatic nephrogenic adenoma.

Combined treatment with temporary short-term high dose rate iridium-192 brachytherapy and external beam radiotherapy for irradiation of localized prostatic carcinoma.

PURPOSE: To evaluate the treatment outcome after radical radiotherapy of localized prostate cancer in 50 patients (38 patients with stage T1-2 and 12 patients with stage T3) after a median follow-up time of 45 months (range 18-92 months). METHODS: The treatment was given by combination of external beam radiotherapy (50 Gy) and brachytherapy (2 x 10 Gy). The brachytherapy was given using TRUS-guided percutaneously inserted temporary needles with a high dose rate remote afterloading technique with Ir-192 as the radionuclide source. Three target definitions and dose levels inside the prostate gland were used. Local control was evaluated by digital rectal examination, TRUS-guided biopsies and serum PSA evaluations. RESULTS: Clinical and biopsy verified local control was achieved in 48 of the 50 (96%) patients; for stage T1-2 in 37 of 38 (97%) patients and for stage T3 in 11 of 12 (92%) patients. A posttreatment serum PSA level < or =1.0 ng/ml was seen in 42 (84%) patients, values from >1.0 to < or =2.0 ng/ml were seen in four (8%) patients and values exceeding 2.0 were seen in four (8%) patients. The late toxicity was minimal. CONCLUSION: The local control results and the minimal toxicity after the combined radiotherapy treatment are promising. However, long term results are necessary before general use.

Analysis of the local control in lymph-node staged localized prostate cancer treated by external beam radiotherapy, assessed by digital rectal examination, serum prostate-specific antigen and biopsy.

OBJECTIVE: To describe local disease control after radical external beam radiotherapy of prostatic carcinoma, as judged by digital rectal examination (DRE), transrectal ultrasonography (TRUS)-guided biopsies and estimates of serum prostate-specific antigen (PSA). PATIENTS AND METHODS: The study comprised 175 patients (mean age 67.5 years, range 49-82; > 90% aged > or = 60 years) with localized prostatic carcinoma (T1-T3C, N0, M0) who underwent external beam radiation therapy (70 Gy), and were then regularly followed with a DRE, measurements of serum PSA and TRUS-guided biopsies to determine the outcome. RESULTS: The DRE revealed four patients with evidence of residual cancer in the prostate and biopsies showed no evidence of residual cancer in 131 (75%) of the patients. There was no correlation of residual cancer with tumour stage or grade but tumour size, as estimated by TRUS, correlated with the results of the biopsy. The nadir serum PSA level was < or = 1.0 ng/mL in 116 (66%) of the patients, of whom 76 (43%) had a nadir serum PSA level of < or = 0.5 ng/mL. The median time to the nadir level was 11 months. Serum PSA progression (> 4.0 ng/mL) at the latest PSA measurement after reaching the nadir occurred in 13% of the patients with a nadir PSA of < or = 0.5 ng/mL and in 25 of the 29 (86%) patients with a nadir serum PSA > 2.0 ng/mL. Cox regression analysis showed that tumour size and rectal irradiation dose were the most important factors for local control. CONCLUSIONS: Radiotherapy is effective in achieving local control in small prostate cancer tumours but less effective in large tumours. Tumour size and dorsal extension of the irradiated target, the rectal dose, were the two important factors for local control. A serum PSA level of < or = 1.0 ng/mL was associated with a higher chance of prolonged disease control.

Paracetamol-induced cholestatic and granulomatous liver injuries.

OBJECTIVE: To describe uncommon (previously unreported) types of adverse liver reactions to paracetamol. DESIGN: In addition to describing patients, with uncommon types of liver reactions to paracetamol, admitted to our hospitals, we surveyed all the liver reactions to paracetamol reported to the Swedish Adverse Drug Reactions Advisory Committee from 1973 to 1993. SETTING: The Swedish population of 8 million inhabitants. MEASUREMENT: Extensive medical evaluation. RESULTS: We found one case with a cholestatic liver reaction and one with granulomatous hepatitis. The reactions were probably idiosyncratic and took several months to disappear. CONCLUSION: In addition to the well-known dose-related toxic liver damage paracetamol may rarely cause non-dose-related severe, prolonged cholestasis or granulomatous hepatitis with cirrhosis.