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Biomedical subjects

R Kraft

Publications and source records attributed to R Kraft.

At least 91 records · Page 5Linked to original sources
PubMed1994

Invasion depth is the most important prognostic factor for transitional-cell carcinoma in a prospective trial of radical cystectomy and adjuvant chemotherapy.

The aim of this prospective study was to examine the prognostic pathomorphological factors in urothelial cancer of the urinary bladder. Clinical and morphological variables were evaluated by univariate and multivariate analysis in 70 patients with invasive transitional-cell carcinoma of the bladder (pTI-pT4a). The patients were treated according to a prospective program consisting of radical cystectomy and pelvic-node dissection, either alone or followed by adjuvant cisplatinum chemotherapy. Nodal status was pN0 in 89% of the patients. The median follow-up time was 5.75 years and the 5-year survival was 58%. Among the morphologic variables, deep invasion of the bladder wall and squamous differentiation indicated a poorer prognosis. Differentiation grade, pattern of growth (infiltrating versus expanding), angioinvasive growth, glandular differentiation and concomitant prostate carcinoma (pT1) were not significative factors for survival. By contrast, a significant reduction in mortality rate was found in patients with concomitant carcinoma in situ. Multivariate analysis confirmed that depth of invasion is an independent prognostic factor of outcome. The results confirm the primary importance of tumor stage in the prediction of survival after radical cystectomy.

Adult↗
PubMed1994

Selective chemical modification of Cys264 with diiodofluorescein iodacetamide as a tool to study the membrane topology of cytochrome P450scc (CYP11A1).

Cys264 of cytochrome P450scc (CYP11A1) was selectively labelled with diiodofluorescein iodacetamide in solution and in proteoliposomes. The labelling affected the interaction of P450scc with adrenodoxin and significantly inhibited the side-chain cleavage activity of the soluble and membrane-bound hemeprotein in the reconstituted system. In proteoliposomes both the labelled and unlabelled hemeproteins were susceptible to trypsin and split into F1 and F2, two fragments corresponding to the two main domains of P450scc. These results suggest that the hinge connecting the two domains in the region Arg250-Asn257 is exposed to the surface of the membrane and involved in the interaction of P450scc with adrenodoxin.

Adrenodoxin↗
PubMed1994

Adjuvant cisplatin chemotherapy following cystectomy for bladder cancer: results of a prospective randomized trial.

Between April 1984 and May 1989, 77 eligible patients with invasive, nonmetastatic (stage M0) transitional cell carcinoma of the bladder were stratified after radical cystectomy and pelvic lymph node dissection on the basis of nodal status (stage pN0 versus pN1-2) and were randomly assigned to either observation or postoperative cisplatin chemotherapy (3 courses of 90 mg./m.2 cisplatin given for 3 consecutive days at monthly intervals). Patient eligibility included a creatinine clearance of greater than 60 ml. per minute. There were 40 eligible patients in the control group (median age 61 years) and 37 in the cisplatin group (median age 64 years). In regard to postoperative tumor stage and nodal status, there was no statistical difference between the 2 patient groups. In the cisplatin group 21 patients received the full dose, 9 required dose reduction and 7 refused treatment. Median followup was 5 years 9 months (range 3 to 8 years). Survival analysis showed no significant difference (log rank p = 0.65) between the 40 patients in the control group and the 37 in the cisplatin group. The survival rate at 5 years was 54% (95% confidence interval 39 to 69%) in the control group and 57% (95% confidence interval 40 to 74%) in the treatment group. Patients with cancer confined to the bladder wall (stage pT3a or less) had a 5-year overall survival rate of 70% and those with tumor growth in the perivesical fat or into the prostate (stages pT3b plus pT4a) had a 5-year overall survival rate of 40%. This difference in survival between the low stage subgroup (stages pT3a or less) and the high stage subgroup (pT3b plus pT4a) is highly significant (p = 0.0043). However, no difference between the controls and the cisplatin group was found within either the low or high stage subgroups. The reasons for failing to show a survival benefit from adjuvant high dose cisplatin monotherapy after radical cystectomy are discussed.

Carcinoma, Transitional Cell↗
PubMed1994

[Urogenital malformation complex including the Mullerian system].

Symptomatic cystic epididymis in a 21-year-old man led to the detection of several genital malformations, including a partially obstructing pelvic cyst, prostatic and bilateral testicular atrophy and penoscrotal hypospadias. These malformations are probably due to a deficiency of either testosterone or müllerian inhibiting hormone (MIH). Development of the male genitalia is influenced by testosterone secreted in the Leydig cells during weeks 8-16 of gestation, while regression of the müllerian ducts is induced by MIH secreted in the Sertoli cells from weeks 9-12 of gestation.

Abnormalities, Multiple↗
PubMed1994

[Morphological diagnosis and classification of lung tumors].

Morphologic examination is mandatory for distinction between benign and malignant pulmonary lesions and separation of primary tumors from metastatic disease. Tumors are classified as to their type and grade by histology and/or cytology. Differences in behavior and response to treatment make the distinction between small cell carcinoma [SCLC] and non-small cell carcinoma [NSCLS] the single most important decision the pathologist must make when examining a lung tumor. The considerable cellular heterogeneity of bronchogenic carcinoma may be the source of problems and pitfalls in morphologic classification of these tumors, discussed in this review together with the concept of neuroendocrine neoplasms.

Carcinoma↗
PubMed1993

Epstein-Barr virus subtype distribution in angioimmunoblastic lymphadenopathy.

The tissues of 16 patients bearing a T-cell lymphoma of angioimmunoblastic lymphadenopathy type (AILD-TCL) were investigated for the distribution of Epstein-Barr virus (EBV) subtypes 1 and 2. EBV-association had been proven in these cases by polymerase chain reaction (PCR) for EBV-DNA, in situ hybridization (ISH) for EBV-encoded small nuclear RNAs (EBER) and immunohistology for EBV-encoded latent membrane protein (LMP). PCR and EBER-ISH produced mostly identical results, but some cases were positive with only one of the 2 methods employed. LMP was detected in a few large cells of 8/13 cases. Twelve cases were investigated for the distribution of EBV subtypes. One case contained EBV genome of subtype 2, 3 cases contained subtype 1 and 4 cases contained both subtypes. Four cases could not be typed. These findings suggest that in AILD, as in AIDS-associated lymphomas and lymphomas of the lethal midline granuloma type, subtype 2 of EBV may occur, perhaps in relation to an immunodysfunction developing progressively in these patients.

Antigens, Viral↗
PubMed1993

Association of the subtype 2 of the Epstein-Barr virus with T-cell non-Hodgkin's lymphoma of the midline granuloma type.

Lethal midline granuloma (LMG) is associated with Epstein-Barr virus (EBV). The latter has at least two subtypes with different biological properties. The subtypes can be identified by their genomic configuration. Using EBV-RNA (EBER) in situ hybridization and EBV polymerase chain reaction (PCR), we have looked for the presence of EBV in six LMGs and six non-Hodgkin's lymphomas (NHLs) located in the nasopharyngeal region, and determined the subtype of EBV. Six of six LMGs were positive by PCR and EBER in situ hybridization, whereas NHLs were either negative or, in three of six cases, showed few EBER-positive cells considered to be nonneoplastic lymphocytes. The subtype 2 was found in LMG lesions of three of six patients; the remaining three of six patients with LMG had the generally occurring subtype 1. The results indicate that the association of EBV with NHL may depend more on tumor type than on its localization. The occurrence of the rare subtype 2 in LMG may relate to a covert immune defect.

Aged↗
PubMed1993

A tetrameric complex of membrane proteins in the endoplasmic reticulum.

The translocation site (translocon), at which nascent polypeptides pass through the endoplasmic reticulum membrane, contains a component previously called 'signal sequence receptor' that is now renamed as 'translocon-associated protein' (TRAP). Two glycosylated subunits of the TRAP complex have been identified before (alpha and beta subunits). We now show that TRAP complex is actually comprised of four membrane proteins (alpha, beta, gamma, delta), present in a stoichiometric relation, which are genuine neighbours in intact microsomes. The amino acid sequences of the additional, non-glycosylated subunits were deduced from cloning of the corresponding cDNAs. The delta subunit spans the membrane only once and has its major portion, containing a disulfide bridge, at the lumenal side. The gamma subunit is predicted to span the membrane four times.

Amino Acid Sequence↗
PubMed1993

Late results in patients treated with pi-mesons for bladder cancer.

BACKGROUND: The treatment of bladder cancer with 60 converging pion beams was expected to have certain dose-distribution advantages with possibly fewer side effects than other high linear-energy-transfer (LET) radiation therapies, such as neutrons. RESULTS: Early results were promising: 20 of 24 (83%) evaluable patients with sessile invasive bladder carcinomas had clinically complete responses. However, only 3 of 10 (30%) evaluable patients with superficial bladder tumors had clinically complete responses. This article reports the long-term follow-up (6-8 years) of these patients with emphasis on the late side effects of pion radiation therapy. Thirty-eight of the 41 (93%) patients treated died after a median survival time of 17 months (range, 4-98 months). Seventeen (45%) died of metastatic disease (in two instances, this was combined with a local recurrence) 5-27 months after radiation therapy. Four (10%) died of locally progressive disease, and eight (21%) died of late side effects of radiation therapy 9-98 months after treatment. All these patients were treated with more than 33 pion Gy and had generally a symptom-free interval of 9-18 months. The observed side effects were severe, consisting of chronic inflammation and vascular damage in the pelvic region often followed by ulceration, fistulas, and perforations throughout the intestines. In 11 patients, cystectomy and urinary diversion was necessary because of excessive fibrosis and bladder shrinkage. In eight patients, a colostomy was required for stenotic inflammatory disease, necrosis, and perforations of the intestines. The remaining nine patients (24%) died of causes unrelated to the primary disease 4-60 months after radiation therapy. CONCLUSIONS: The results of the first Phase I/II trial using the Swiss piotron showed a high complete response rate in patients with sessile bladder cancers but also a high incidence of local recurrences and severe, in some instances lethal side effects. Although it is expected that these results will be the basis for future improvements, particularly regarding dosing and fractionation, this experience emphasizes the need for a sufficiently long observation period before reaching conclusions about any high LET treatment, such as neutron, pion, or heavy ion radiation therapy.

Adult↗
PubMed1993

Metastatic disease of the ureter: patterns of tumoral spread and radiologic findings.

The radiographic and sectional imaging features (ultrasound [US], computed tomography [CT], and magnetic resonance imaging [MRI]) of ureteral obstruction due to metastatic disease are reviewed. The radiologic findings depend on the pattern of the tumoral spread: hematogenous submucosal/mucosal metastasis, hematogenous adventitia metastases spreading along periureteral vessels, scirrhous metastatic spread along periureteral vessels, or metastatic spread into lymph nodes with perinodal desmoplastic reaction. Solitary or multiple extraluminal obstructions without substantial displacement of the ureter are characteristic. CT is the examination of choice for morphological analysis. Together with the patient's history and clinical data, a presumptive diagnosis of ureteral obstruction caused by metastatic disease can be made.

Adult↗
PubMed1993

Invasive infection with Mycobacterium genavense in three children with the acquired immunodeficiency syndrome.

Three children with human immunodeficiency virus infection and invasive infection with Mycobacterium genavense are reported. Fever spikes, abdominal cramps and distension, diarrhea or ileus, and anemia were the predominant symptoms in the severely immunodeficient patients (CD4 lymphocytes < 0.04 x 10(9)/l). Numerous acid-fast bacilli were readily detectable by microscopy in stool samples and in lymph node biopsies, but cultures for mycobacteria remained negative. Mycobacterium genavense should be sought when invasive non-tuberculous mycobacteriosis is suspected and mycobacterial cultures from blood or other sites show limited growth. Multiple-drug regimens including amikacin, ethambutol, rifampin, and clarithromycin may be of benefit in controlling the infection, as observed in two patients.

AIDS-Related Opportunistic Infections↗
PubMed1993

Distinction between diffuse cutaneous malignant follicular center cell lymphoma and lymphoid hyperplasia by computerized nuclear image analysis.

The difficult differential diagnosis between the diffuse variants of cutaneous lymphoid hyperplasia (CLH; synonym; pseudolymphoma) and malignant follicular center cell lymphomas (FCCL) often requires a multidisciplinary approach. Eighteen CLH and 11 FCCL, diagnosed by conventional histology and immunophenotyping and subsequently examined with a polymerase chain reaction to show clonal immunoglobulin heavy-chain gene rearrangements, were subjected to a novel type of automated nuclear image analysis. Of all nuclear parameters tested in azure A-stained semithin sections, the mean nuclear profile area (TN) of lymphoid cells was the best criterion to distinguish between CLH and FCCL (p = 9 x 10(-6)). Additional distinctive features, in the order of decreasing significance, were the SD of TN; all chromatin textural parameters combined; and the light and the dark fractions of the central nuclear profile areas. Parameters related to the chromatin pattern were independent of nuclear profile size in FCCL, but not in CLH. Two lesions registered as CLH displayed the nuclear characteristics favoring this diagnosis, but showed B-cell monoclonality at the DNA level. In conclusion, computerized nuclear image analysis is a helpful additional diagnostic tool in the evaluation of diffuse CLH and cutaneous FCCL.

Adolescent↗
PubMed1993

Adjuvant chemotherapy after orchiectomy in high-risk patients with clinical stage I non-seminomatous testicular cancer.

In patients with clinical stage I non-seminomatous germ cell tumor the relapse rate seen after orchiectomy alone is approximately 30%. If retroperitoneal lymph node dissection is adopted the relapse rate in patients with histologically negative retroperitoneal nodes is reduced to approximately 10%. Nevertheless, follow-up is still mandatory and 70-80% of clinical stage I patients undergo unnecessary surgery. Metastases and relapses are mostly seen in patients with histological evidence of vascular invasion, growth beyond the testicular capsule and/or embryonal carcinoma in the primary tumor. We conducted a prospective trial of two cycles of cisplatin-based adjuvant chemotherapy for 43 patients with clinical stage I non-seminomatous germ cell tumors and at least one of these risk factors (vascular invasion n = 5, pT > 1 n = 21, embryonal carcinoma n = 42). After a median follow-up of 42 months (12-82 months) 40/41 patients (97.5%) who received the planned chemotherapy remain relapse-free. One patient had surgical excision of a mature teratoma in the ipsilateral iliac region 26 months after orchiectomy and is now disease-free without further treatment after 25+ months. No life-threatening toxicity from chemotherapy was encountered. Two patients who refused the chemotherapy relapsed. In patients with high-risk clinical stage I non-seminomatous testicular cancer two cycles of adjuvant chemotherapy are highly effective in preventing relapses and may be used as an alternative to a 'wait and watch' program or retroperitoneal lymph node dissection, particularly in patients with a compromised follow-up.

Adult↗
PubMed1993

Correlations between apoptotic and proliferative indices in malignant non-Hodgkin's lymphomas.

Cell production versus cell loss rates were estimated, across the boundaries of histological classification, in 50 cases of malignant non-Hodgkin's lymphomas by use of mitotic indices, percentage of Ki-67+ cells and percentage of PC10+ cells as proliferative indices, and the relative number of apoptotic bodies (apoptotic indices, AIs) as parameters. Regression analysis revealed significant (P < 0.01) positive correlations between the AIs and the proliferative indices; among the immunohistochemically assessed proliferative indices; and between these, the mitotic indices and the AIs on the one hand and histological malignancy grades on the other hand. The cellular protein BCL-2, which counteracts apoptosis, was significantly (P < 0.01) more often expressed in lymphomas with low than in those with high AIs. Multivariate analysis of data showed that of all parameters tested in this series, only the AIs correlated significantly (P < 0.05) with overall lethality. The correlation between BCL-2 positivity of lymphoma cells and overall survival did not quite attain significance (P = 0.08). Results of the present study suggest that high AIs and lack of BCL-2 expression may be adverse prognostic factors, independent of histological grade.

Apoptosis↗
PubMed1993

[Vitrectomy in oculocerebral non-Hodgkin's lymphoma].

Ocular non-Hodgkin lymphoma (NHL) is thought to be a rare intraocular tumor; the clinical diagnosis, however, is difficult, and ocular NHL might occur more frequently than we thought. Vitrectomy is essential for establishing the diagnosis. During the last 6 years, we performed vitrectomies for ocular NHL in seven eyes of four patients. We report on the visual outcome and cytological findings. In three patients, we suspected the oculocerebral form of the disease; one patient suffered from a systemic lymphoma. The mean observation time was 19 months (5-30 months). In one patient, we failed to examine the vitreous fluid; this patient has since died. The other three patients underwent radiation treatment and/or chemotherapy; they are alive, and no recurrence of the NHL has since occurred. In all five cases in which cytological examination of the vitreous fluid was performed, we were able to establish the diagnosis of NHL on the first attempt. This accuracy is due to rapid and careful processing by the cytologist. Vision improved considerably in most cases. In only one eye with heavy retinal infiltration could vision not be restored. Secondary cataract extraction was necessary in five cases; otherwise, vision remained stable. We conclude that vitrectomy has to be done early in atypical vitreous "inflammations". Immediate processing and cytological examination of the vitreous fluid establishes the diagnosis of NHL and permits accurate radiation or chemotherapy. Early vitrectomy is greatly beneficial not only for visual rehabilitation but maybe even for a longer life expectancy.

Aged↗
PubMed1992

Phenotypic overlaps between pleomorphic malignant T-cell lymphomas and mixed-cellularity Hodgkin's disease.

Histologically diagnosed, or in part questionable, malignant pleomorphic peripheral T-cell lymphomas (pPTCLs, n = 16) and mixed-cellularity Hodgkin's disease (MCHD, n = 12) were objectively compared by the use of combined immunohistochemistry on paraffin sections, test-point analysis of tissue components, and semi-automated nuclear morphometry on semi-thin resin sections. Classical, qualitative histomorphological distinction of these sub-types of lymphomas proved to be valid and is probably still the best method. Quantitative discriminant features, in order of decreasing significance, were: (i) expression by large atypical cells (LACs) of CD45R0, CD43 and CD45 in pPTCLs, and of CD30 and CD15 in MCHD; (ii) means and standard deviations (SDs) of LAC nuclear-profile areas (greater in MCHD than in pPTCLs); (iii) expression of CD3 by LACs in pPTCLs; (iv) prominence of small lymphoid cells in MCHD; (v) higher percentage of medium-sized lymphoid cells in pPTCLs; and (vi) higher SDs of nuclear-profile circularity factor of small lymphoid cells in MCHD. The medians of the largest nucleolar profile areas in LACs per field did not differ in pPTCLs and MCHD, but dispersion of individual values towards higher levels was significantly greater in the latter. Stepwise discriminant analysis of test point and nucleometric variables that best distinguished pPTCLs from MCHD revealed considerable overlaps, and questionable cases tended to be intermediate between the two. In conclusion, our results confirm and expand the notion of intra-group heterogeneity, with indistinct borders and the existence of intermediate phenotypes between these two taxonomic categories of malignant lymphomas.

Adolescent↗