Frank Aldenborg

The AST/ALT ratio as an indicator of cirrhosis in patients with PBC

Abstract: Objectives: A non‐invasive, simple and non‐expensive test to predict cirrhosis would be highly desirable. The aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio has been proven to be such an indicator of cirrhosis in alcoholic liver disease, hepatitis C.

RECRUITMENT, DISTRIBUTION AND PHENOTYPES OF MAST CELLS IN INTERSTITIAL CYSTITIS

PURPOSEnInterstitial 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).nnnMATERIALS AND METHODSnMC 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.nnnRESULTSnClassic 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.nnnCONCLUSIONSnRedistribution 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.

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

PURPOSEnTo 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).nnnMETHODSnThe 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.nnnRESULTSnClinical 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.nnnCONCLUSIONnThe local control results and the minimal toxicity after the combined radiotherapy treatment are promising. However, long term results are necessary before general use.

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

PURPOSEnInterstitial 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.nnnMATERIALS AND METHODSnWe 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.nnnRESULTSnIn 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.nnnCONCLUSIONSnOur 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.

Complete transurethral resection of ulcers in classic interstitial cystitis.

Abstract: 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.

Skeletal Metastases in 102 Patients Evaluated Before Surgery for Renal Cell Carcinoma

During a 3-year period a consecutive series of 102 patients were treated for renal cell carcinoma at one urological unit. Thirty-three patients (32.4%) had metastatic spread, but bone metastases were found in six patients only, i.e. 5.9% of the whole series and 18.2% of the patients with metastases preoperatively. The bone metastases had in all six patients given local symptoms first indicating radiography, and thereafter radionuclide scintigraphy of the entire skeleton. Bone scintigraphy performed merely by routine in 70 patients did not reveal one single case of bone metastasis. Only one patient had a solitary bone metastasis, and this metastasis was considered inoperable because of its location and size and the patients age. The decision about nephrectomy was not in any case altered by the finding of bone metastases. Solitary bone metastasis must be diagnosed early since they may be radically removed. Routine scintigraphy of the skeleton in symptomless patients, however, has a low yield. Screening for skeletal metastases may therefore be best performed by careful physical examination and history-taking.

The immunohistochemical demonstration of chymase and tryptase in human intestinal mast cells

SummaryAn immunohistochemical double-labelling technique for the simultaneous identification of mast cells containing tryptase alone (MCT) or chymase together with tryptase (MCTC) was evaluated quantitatively using two monoclonal antibodies, mAb 1222A (antitryptase) and mAb 1254B (antichymase). Saturation conditions were established for the binding of the antibodies to the mast cell enzymes by counting labelled mast cells in consecutive sections of normal human intestine incubated with serial dilutions of the antibodies. When, under such conditions, the antitryptase was applied after saturation with mAb 1254B, the reproducibility of the double-labelling procedure was excellent. MCT were located preferentially in the intestinal mucosa but, in contrast to what has previously been reported, they were not the predominant type of mast cell at this site. The percentage of MCT of the total number of immunopositive mast cells varied considerably in the colonic mucosa (7–67%, average 30%), while this was not the case in the small intestinal mucosa (5–26%, average 10%). Mast cell chymase, unlike tryptase, was not recognized by the antichymase antibody after aldehyde fixation and a higher apparent fraction of MCT therefore occurred after double labelling. These findings suggest that the proteinase composition of human mast cells, unlike that of murine mast cells, should not be taken as evidence of phenotypic heterogeneity. Taken together with previous observations, they suggest instead that the lack of chymase may be related to functional activity or stage of maturation of the mast cells.

Thymus dependence of connective tissue mast cells: a quantitative cytofluorometric study of the growth of peritoneal mast cells in normal and athymic rats.

The normal growth of peritoneal mast cells was studied in athymic and heterozygote rats over the period of 5-29 weeks of age. The total peritoneal mast cell mass and the mass of the granular components was calculated from mast cell numbers and their content of protein, heparin and 5-hydroxytryptamine. The growth process was analyzed by allometric log-log plots of mast cell quantities versus body weight and linear regressions. The mast cell growth in both groups of rats conformed to the allometric principle and was strictly proportional to the growth of the body as a whole. Two major differences between athymic and heterozygote rats were observed. The total peritoneal mast cell mass and the mass of its components was initially higher in the athymic rats, but the growth rate of the mast cells was lower. We suggest that the thymus may regulate the mast cells by an inhibitory factor acting on the bone marrow stem cell or circulating precursor level. The lower growth rate of the athymic rats may be due to the absence of a second, stimulatory thymic factor acting on the tissue precursor level, or to a tissue homeostatic mechanism triggered by the large initial mast cell mass and unrelated to the thymus.

Prolonged postpartum course of intrahepatic cholestasis of pregnancy

Cholestatic jaundice of pregnancy is generally a self-limiting condition that occurs in the last trimester and disappears within 1-2 weeks after delivery. The cases of two women who developed severe intrahepatic cholestasis of pregnancy are presented. After delivery, pruritus and jaundice increased and the maximal level of bilirubin reached 500 and 433 mumol/L, respectively (normal, < 20 mumol/L). A familial aggregation was present in one case. Extensive laboratory, radiological, and histopathological investigation showed no other cause of jaundice. Cholestyramine, ursodeoxycholic acid, S-adenosylmethionine, evening primrose oil, and ultraviolet light were used without evidence of efficacy. On the other hand, after corticosteroids were given pruritus ceased and biochemical alterations became normal 35 and 43 weeks, respectively, after delivery. During follow-up 2 years after delivery in one patient, symptoms have not recurred and liver function tests have remained normal. A therapy-resistant dry cough in the other patient is described as a new clinical symptom of severe cholestasis.

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.