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F Jacobsen

Publications and source records attributed to F Jacobsen.

At least 19 recordsLinked to original sources
PubMed1995

Disseminated intravascular coagulation associated with granulocyte colony-stimulating factor therapy in a child with human immunodeficiency virus infection.

We report a case of disseminated intravascular coagulopathy, apparently caused by exposure to granulocyte colony-stimulating factor (G-CSF). The medical records of patients treated for more than 30 consecutive days with subcutaneously administered G-CSF were reviewed for the occurrence of thrombocytopenia or coagulation abnormalities. New-onset thrombocytopenia with a platelet count less than 100 x 10(9) cells/L (< 100,000 cells/mm3) developed in 9 of 23 patients (39%) after a median of 11 weeks of treatment with G-CSF at dosages between 1 and 10 micrograms/kg per day.

Adolescent↗
PubMed1994

29-week doxazosin treatment in patients with symptomatic benign prostatic hyperplasia. A double-blind placebo-controlled study.

In a placebo-controlled study, the safety and efficacy of the selective alpha 1-adrenoceptor-blocking agent doxazosin 4 mg once daily in the symptomatic treatment of benign prostatic hyperplasia (BPH) were evaluated. One hundred patients were primarily included in a 9-weeks study, and after this 75 patients accepted to continue in the present 20 weeks extension. Of the patients in the doxazosin-group (DG) 61% reported overall improvement against 53% in the placebo-group (PG)--(p = 0.56). In the DG, 49% of obstructive symptoms were improved compared to 27% in the PG (p < 0.01), and a reduction of 60% of irritative symptoms was found in the DG against 36% in the PG (p < 0.01). Daytime frequency was reduced by median 1.5 in the DG and remained unchanged in the PG (p < 0.01). Nocturia was reduced by median 1 and 0.5 respectively (p = 0.06). Maximum urinary flow rate (MFR) was improved by median 1.5 ml/s in the DG, while it deteriorated by median 0.5 ml/s in the PG (p < 0.05), Considering postvoid residual urine volume, cystometry variables (first sensation and bladder capacity), changes in sexual function and adverse events there was no difference between the two groups. In conclusion, doxazosin 4 mg once daily in long-term treatment of patients with BPH reduces both obstructive and irritative symptoms, daytime voiding frequency and although only slightly, significantly augments MFR without interference with sexual function and without other serious adverse effects.

Aged↗
PubMed1992

Role of glycosylation on the secretion and biological activity of erythropoietin.

The erythropoietin (EPO) molecule contains four carbohydrate chains. Three contain N-linkages to asparagines at positions 24, 38, and 83, and one contains an O-linkage to a serine at position 126. We constructed human EPO variants that eliminated the three N-glycosylation sites by replacing the asparagines with glutamines singly or in combination. The O-linked carbohydrate chain was removed by replacing the serine with glutamine, valine, histidine, or alanine. A variant with a double mutation (Gln38,83) and another with a triple mutation (Gln24,38,83) were secreted poorly from COS1 and CHO cells even though RNA encoding these variants was present. All other variants with mutations in N-linked glycosylation sites were secreted normally. Removal of any of the N-glycosylation sites reduced the in vivo but not the in vitro biological activity of the EPO molecule. All the mutations at Ser126, the O-glycosylation site, were secreted normally. In vitro activity was also unaffected except for Ala126 which had a 50-fold decrease. The Val126 variant was tested in vivo, and its specific activity was only slightly less than that of the native EPO, which indicates that the O-linked carbohydrate is not essential for activity.

Animals↗
PubMed1992

Combination treatment with azidothymidine and granulocyte colony-stimulating factor in children with human immunodeficiency virus infection.

Bone marrow suppression is the major dose-limiting toxic effect of zidovudine (azidothymidine; AZT) in children with human immunodeficiency virus infection. We evaluated the effect of subcutaneously administered granulocyte colony-stimulating factor (G-CSF) in pediatric patients whose absolute neutrophil count was less than 0.8 x 10(9)/L during AZT therapy despite dosage reductions to 120 mg/m2 every 6 hours. Nineteen patients between 6 months and 20 years of age were treated with AZT and G-CSF and monitored for 2 to 12 months. All had previously shown improvement while receiving AZT but had required dosage reduction or discontinuation. By using a sliding dosing schedule of G-CSF, we attempted to maintain the absolute neutrophil count between 1.5 and 5.0 x 10(9)/L. Administration of G-CSF resulted in a significant increase in the median leukocyte count (2.0 x 10(9)/L to 4.14 x 10(9)/L; p = 0.004), and the median absolute neutrophil count (1.02 x 10(9)/L to 2.96 x 10(9)/L; p = 0.0006). G-CSF was well tolerated, but mild thrombocytopenia developed in nine children. Administration of G-CSF and AZT was discontinued in two patients because of continuing neutropenia. With doses of G-CSF ranging from 1 to 20 micrograms/kg per day, 17 of 19 patients were able to tolerate AZT at a dose of 120 to 180 mg/m2 every 6 hours. We conclude that G-CSF therapy enables patients who have had AZT-related neutropenia to receive therapeutic doses of AZT.

Adolescent↗
PubMed1992

Clinical pharmacology of 2',3'-dideoxyinosine in human immunodeficiency virus-infected children.

The pharmacokinetics of intravenous and oral 2',3'-dideoxyinosine (ddI) and the relationships between pharmacokinetic parameters and measures of response were studied in 48 human immunodeficiency virus-infected children. Disappearance of ddI from plasma after the intravenous dose was rapid and biexponential, with half-lives of 12 min and 1.0 h and a total clearance of 510 +/- 180 ml/min/m2. After oral administration, ddI absorption was limited and variable (mean bioavailability, 19% +/- 17%). A plasma ddI concentration-response relationship was observed for both decline in viral p24 antigen levels and improvement in intelligence quotient score. A limited sampling model was developed that accurately predicts the area under the ddI plasma concentration-time curve from one to three plasma samples. Although this pharmacokinetic study was done in children, the results also have relevance to adults and suggest that individualization of dose and schedule through therapeutic drug monitoring may be necessary to achieve optimal response.

Absorption↗
PubMed1991

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1985

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↗