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Biomedical subjects

F Jacobsen

Publications and source records attributed to F Jacobsen.

At least 37 records · Page 2Linked to original sources

Stereological estimates of nuclear volume in the prognostic evaluation of primary flat carcinoma in situ of the urinary bladder.

Primary, flat carcinoma in situ of the urinary bladder is rare and its behaviour is unpredictable. The aim of this retrospective study was to obtain base-line data and investigate the prognostic value of unbiased, stereological estimates of the volume-weighted mean nuclear volume, nuclear vv, in 78 bladder biopsies from 22 patients with primary flat carcinoma in situ (Bergkvist grades III-IV). On average, nuclear vv was 77 microns 3 in nine biopsies with morphologically normal urothelium, 292 microns 3 in 56 isolated primary lesions and 266 microns 3 in lesions of luminal urothelium in 13 biopsies with co-existing invasive carcinoma. No recognizable developmental pattern of nuclear vv in relation to the time course of disease was found. Nuclear volume in the first biopsy was of the same magnitude in lesions with and without co-existing invasive carcinoma (2P = 0.55), and in lesions with short and long duration of invasion-free period (2P greater than 0.20). Nuclear vv in the first biopsy did not differ between patients who survived and those who died from their primary flat carcinoma in situ (2P = 0.07). Dividing the patients on the basis of the group median of the first biopsy showing flat carcinoma in situ (nuclear vv = 261 microns 3), the survival was the same in patients with nuclear vv above and below the cut-off point (2P = 0.16). However, the survival curves showed a tendency to differ in the first 2-8 years of observation. Stereological estimates of nuclear vv provide objective, quantitative information, but their prognostic value in patients with primary flat carcinoma in situ of the bladder needs further clarification in larger data bases.

Aged↗

Germline transmission of exogenous genes in the chicken.

Difficulties associated with in vitro manipulation and culture of the early chicken embryo have restricted generation of transgenic chickens to approaches that use replication-competent retroviruses. The need to produce transgenic chickens in the absence of replicating virus prompted development of a new method of gene transfer into the chicken. Microinjection of the replication-defective reticuloendotheliosis virus (REV) vector ME111 beneath unincubated chicken embryo blastoderms results in infection of germline stem cells. This vector contains genetic information exogenous to the chicken genome, including both the herpes simplex virus type 1 thymidine kinase gene and the Tn5 neomycin phosphotransferase gene. About 8 percent of male birds hatched from injected embryos contained vector DNA in their semen. All four positive males tested passed vector sequences onto their progeny. Analysis of G1 offspring showed that gonads of G0 male birds were mosaic with respect to insertion of vector provirus. Thus, primordial germ cells present in the unincubated chicken embryo blastoderm are susceptible to infection by defective REV vectors.

Animals↗

Impact of the category of early tumor recurrence on tumor progression in bladder tumors treated by transurethral resection.

Forty-six newly diagnosed patients with T1 and T2 bladder tumors were treated with transurethral resection. During a 6-months period more than 50% of the tumors recurred. Subsequent progression of tumors was seen within 24 months in 35 and 28% of the patients with T1 and T2 tumors, respectively. Prognosis with regard to progression was significantly better in patients with Ta recurrence at first control than in patients with invasive recurrent tumors, irrespective of category of tumor at a later recurrence. It is concluded that the continued transurethral treatment of patients with early recurrent invasive tumors may have to be reconsidered.

Humans↗

Painful bladder disease: clinical and pathoanatomical differences in 115 patients.

The diagnostic criteria for interstitial cystitis considered as a subgroup of painful bladder disease (that is sensory bladder disease and chronic abacterial cystitis) are not well established. Some urologists rely on symptoms, while others rely on cystoscopic appearance or pathological findings. Among 115 patients with painful bladder disease we compared symptoms, and cystoscopic and urodynamic findings in those with and without detrusor mastocytosis (28 or more mast cells per mm.2) and attempted to elucidate possible differences between the groups. We chose the pathological anatomical criterion of detrusor mastocytosis to be diagnostic for interstitial cystitis. A total of 43 patients had detrusor mastocytosis and other pathological anatomical signs of interstitial cystitis, and 72 had no mastocytosis but the pathological diagnoses of chronic unspecific cystitis, fibrosis of the bladder, detrusor myopathy, intestinal metaplasia and normal findings. When the 2 groups of patients were compared we found no differences in regard to symptoms (pain, dysuria, frequency, nocturia and urgency), frequency of allergy and hysterectomy, duration of symptoms, petechial bleeding during cystoscopy with bladder distension and cystometric findings. The patients with mastocytosis differed from those without mastocytosis in that they were older, and had a higher frequency of hematuria, a higher frequency of a red, scarred and richly vascularized bladder at cystoscopy before distension, and a smaller cystoscopic bladder capacity. We conclude that by dividing patients with painful bladder into 2 groups according to the mast cell counts in the detrusor, certain differences in the clinical findings in the groups can be ruled out. However, in individual patients one cannot note with certainty to which pathological anatomical group the patient belongs, since great overlapping between the groups exists. Whether only patients with detrusor mastocytosis have interstitial cystitis depends on definitions and still remains an open question.

Adult↗

A prospective double-blind clinically controlled multicenter trial of sodium pentosanpolysulfate in the treatment of interstitial cystitis and related painful bladder disease.

Painful bladder disease, sensory bladder disease, chronic abacterial cystitis and interstitial cystitis are ill-defined conditions of unknown etiology and pathogenesis, and, therefore, they are without any rational therapy. Pathogenetic theories concerning defects in the epithelium and/or mucous surface coat (including glycosaminoglycans) of the bladder, and theories concerning immunological disturbances predominate. Sodium pentosanpolysulfate (Elmiron) acts by substituting a defective glycosaminoglycan layer and inhibits complement reactions in inflammatory processes. We compared sodium pentosanpolysulfate versus placebo in a prospective double-blind, clinically controlled multicenter trial of 115 patients with painful bladder disease. Two protocols were used. Protocol A included 43 patients with clinically and pathologically anatomically verified interstitial cystitis (28 or more mast cells per mm.2), and protocol B included 72 patients with a painful bladder and unspecific histological findings. The patients were randomized to receive either sodium pentosanpolysulfate (200 mg. twice daily) or placebo capsules for 4 months. Before and after the trial the patients were evaluated with symptom grading, urodynamics and cystoscopy with distension and deep bladder biopsies. The results showed no difference between the pre-trial and post-trial values in the sodium pentosanpolysulfate and placebo groups in both protocols in regard to symptoms, urodynamic parameters, cystoscopic appearance and mast cell counts. A significant increase in the cystoscopically determined bladder capacity in the sodium pentosanpolysulfate group in protocol A was found. We conclude that no statistically or clinically significant effect of sodium pentosanpolysulfate was found compared to placebo in patients with painful bladder disease.

Adult↗

Urine eosinophil cationic protein in painful bladder disease.

Urine eosinophil cationic protein (U-ECP), blood eosinophils and eosinophils in bladder biopsy specimens were studied in 30 patients with painful bladder disease (15 with detrusor mastocytosis, i.e. interstitial cystitis (IC) (greater than or equal to 28 mast cells/mm2 in the detrusor muscle) and 15 patients without detrusor mastocytosis). In patients with IC the median concentration of U-ECP was 140 arbitrary u/l versus 14 arb. u/l in the remaining patients (P less than 0.001). The mean peripheral leukocyte count was significantly lower in the IC group (P less than 0.05). Tissue infiltration with eosinophils was found in 43% of the bladder biopsies from patients with IC compared with 4% of the biopsies in the remaining patients (P less than 0.05). A negative correlation between peripheral eosinophils and U-ECP was found in the patients with IC (r = 0.52, P less than 0.05). These results suggest that eosinophils are attracted to the inflammatory site in the bladder wall where ECP is released. Eosinophils thus seem to participate actively in the inflammatory process. U-ECP seems to provide valuable diagnostic information when diagnosing IC in patients with painful bladder disease. It is suggested that ECP might be involved in the process of tissue destruction in IC.

Adult↗

Nephroid metaplasia of the urinary tract. A survey of the literature, with the contribution of 5 new immunohistochemically studied cases, including one case examined by electron microscopy.

Nephroid metaplasia is an unusual lesion confined to the lamina propria of the lower urinary tract. It is defined by a characteristic histologic picture of tubular structures, formed by a single layer of cuboidal cells, surrounded by a thick basement membrane. Two main theories concerning the histogenesis of the condition have been proposed: embryonic origin, or metaplasia. Five cases of nephroid metaplasia were studied light-microscopically and by immunohistochemistry for the content of Tamm Horsfall's uromucoprotein. In addition, one case was examined by electron microscopy. The results were compared to current knowledge of the lesion obtained from a survey of the literature, with special reference to histogenesis. Morphologically, one case of nephroid metaplasia was associated with mesonephroid adenocarcinoma. It is concluded that nephroid metaplasia arises as a metaplastic lesion, nearly always in previously traumatized urothelial mucosa. The natural history of the typical nephroid metaplasia is benign, but a possible relationship to mesonephroid adenocarcinoma, representing the malignant counterpart of the lesion, is discussed in relation to the histological findings, suggesting a rare but possible malignant potential of nephroid metaplasia. The diverse nomenclature used for this histologic entity needs re-evaluation and should be changed to: nephroid metaplasia.

Adenocarcinoma↗

Transurethral treatment of invasive tumours of the urinary bladder (T1, T2): recurrence and progression.

Forty-six newly diagnosed patients with T1 and T2 bladder tumours were treated with radical transurethral resection. During a six-month period more than 50% of the tumours recurred. Subsequently progression of tumours was seen within 24 months in 30 and 50% of the patients with T1 and T2 tumours, respectively. Prognosis with regard to the progression was significantly better in patients with Ta recurrence at first TUR control than in patients with invasive recurrent tumours.

Aged↗

Flat intra-epithelial carcinoma in situ of the urinary bladder.

A follow-up investigation of 19 patients with carcinoma in situ per se of the urinary bladder (Tis) has been performed. Ten patients developed invasive cancer during a mean observation period of about 4 years. The natural history is unpredictable and therapeutic management of this potentially malignant neoplasm should be individualised. Early radical cystectomy is advocated in selected cases of Tis.

Aged↗

Vascular graft infection: an analysis of sixty-two graft infections in 2411 consecutively implanted synthetic vascular grafts.

Among 2411 consecutive arterial reconstructions performed with synthetic prosthetic material in Denmark during a 4-year period, 62 patients (2.6%) developed graft infection. Graft infection occurred only when the groin had been incised. The incidence of infection and the spread of infection along the graft did not relate to the graft material used (Dacron velour, Dacron woven, polytetrafluoroethylene, and umbilical vein). Retrospective analysis disclosed predisposing or precipitating factors in 50 of the 62 cases; the most important seemed to be unsatisfactory surgical technique. Fifty-three percent of the graft infections occurred within 30 days. Gram-positive cocci were the most common pathogen. The 62 patients had been in the hospital for a mean of 90 days and had undergone an average of 1.4 operations for graft infections. Of the patients, 25.8% died and 30.6% underwent amputations. Vascular graft infection is still one of the major problems in vascular surgery; greater care should be taken to improve antiseptics, improve surgical technique, and establish a rational prophylactic antibiotic regimen. A prophylactic antibiotic regimen of a combination of cephalosporin and ampicillin is recommended.

Anti-Bacterial Agents↗

Use of Trypanosoma equiperdum infected rabbits as a source of splenic mRNA; construction of cDNA clones and identification of a rabbit mu heavy chain clone.

Rabbits were infected by Trypanosoma equiperdum and the splenic mRNA was isolated. In vitro translation of this RNA and immunoprecipitation with anti-light chain, anti-heavy chain, anti-mu and anti-VH antibodies demonstrated that T. equiperdum infection elicits large quantities of splenic mRNA encoding mu and kappa chains. The mu and gamma heavy chains and the kappa light chains synthesized in the cell-free translation system were specifically immunoprecipitated by antisera to heavy chain VHa and light chain kappa b allotypes. In vitro labeling of spleen cells from trypanosome-infected animals demonstrated that the biosynthetically labeled IgM has a mu chain of higher molecular weight than the mu chain synthesized by in vitro translation, a difference that is largely abolished when cellular glycosylation is blocked with the antibiotic tunicamycin. Enrichment for heavy chain or light chain mRNA was achieved by fractionating mRNA from trypanosome-infected animals on a sucrose gradient. cDNA clones carrying mu heavy chain sequences were produced using a 'one tube' protocol and identified by cross species hybridization and hybridization selection. Infection of rabbits with T. equiperdum followed by sucrose gradient enrichment of splenic mRNA has provided sufficient quantities of mRNA encoding mu heavy chain suitable for cDNA cloning.

Animals↗

Analyses of the splenic mRNA expressed by rabbits of different immunoglobulin kappa-light chain allotypes: conserved sequences in the 3' untranslated region and allotype-specific probes.

The allelism of the structural genes for the complex rabbit b allotypes of immunoglobulin kappa-light chains has been questioned because of observations of unexpected phenotypic expression of "latent" allotypes. We find that the coding sequences of the b4 and b5 "alleles" are only 80% homologous for the last 60 nucleotides but there is a high degree of homology (96%) in the 3' untranslated region (3'DT). The high conservation of 3' DT region sequences enabled us to detect kappa-light chain mRNAs from rabbits of different genetic types (b4, b5, b9 and bbas) on northern blots and dot blots. We can distinguish mRNA encoding b9 and b5 allotypes on dot blots with b5 fragment-probes of known sequence and detect mRNA produced by unstimulated cultured splenic lymphocytes. Analyses of mRNA from cultured cells manipulated to enhance mRNA synthesis and production of unexpected or "latent" b allotypes can now be conducted.

Animals↗

The influence of prednisone on serum angiotensin-converting enzyme activity in patients with and without sarcoidosis.

The influence of prednisone on S-angiotensin-converting enzyme (SACE) activity was examined by serial measurements in 20 non-sarcoidosis patients and 8 sarcoidosis patients on prednisone, compared with 26 patients and healthy controls not under treatment. All but the sarcoidosis patients had SACE within normal limits (12.0-36.8 kU/l). In the three groups initial or pretreatment SACE levels (mean +/- SD) were 20.1 +/- 5.7, 66.9 +/- 27.4 and 26.4 +/- 4.1 kU/l, respectively. Non-sarcoidosis patients on prednisone had a lower pretreatment SACE than untreated control persons, presumably due to the different diseases represented in the groups. During the observation period SACE was rather stable in untreated patients and also in the treated group as a whole. But in 12 patients with SACE greater than 18.2 kU/l (mean of reference series minus 1 SD) a significantly decreasing SACE was observed after 1 week of treatment, whereas SACE was unchanged in patients with lower pretreatment levels, suggesting that in these patients prednisone could not decrease any further a level which was already low. In sarcoidosis the elevated SACE declined, reaching a normal level after 4 weeks on prednisone. In the assay ACE was markedly inhibited by SQ 14,255 (Captopril), moderately by methylprednisolone in concentrations exceeding those generally used clinically, while no inhibition was seen using acetylsalicylic acid.

Adolescent↗