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Biomedical subjects

W Fett

Publications and source records attributed to W Fett.

At least 19 recordsLinked to original sources

Pyridinium cross-links in multiple myeloma: correlation with clinical parameters and use for monitoring of intravenous clodronate therapy--a pilot study of the German Myeloma Treatment Group (GMTG).

The relevance of quantitative determinations of urinary deoxypyridinolines (DPY) and pyridinolines (PY), and of serum type I collagen carboxyterminal cross-linked telopeptides (ICTP), has been evaluated for patient monitoring in multiple myeloma (MM). In 178 untreated MM patients, a clear correlation was found between ICTP concentrations, bone destructions and serum calcium levels. Furthermore, serum ICTP, urinary DPY and PY concentrations were estimated before and during treatment in a further 33 MM patients randomly allocated to four groups receiving intravenous melphalan/prednisone (MivP) chemotherapy alone, or MivP in combination with three different doses of i.v. clodronate. 1800 mg of i.v. clodronate combined monthly with MivP induced a rapid and sustained reduction in bone resorption parameters to the normal range, a result not obtained with either MivP alone, or with a lower clodronate dose. While confirming the relevance of determining pyridinium cross-links for estimating bone resorption in MM, our data indicate that measurements of these parameters could be useful for dose finding and monitoring of bisphosphonate therapy.

Adult↗

Combined preoperative chemotherapy and radiotherapy in patients with locally advanced esophageal cancer. Interim analysis of a phase II trial.

PURPOSE: The prognosis of patients with locally advanced esophageal cancer (LAEC) remains poor when treated with local modalities. An intensive preoperative program with chemoradiotherapy was used to evaluate the curative resection rate, pathologic response, and survival of patients with LAEC. PATIENTS AND METHODS: Ninety patients with LAEC were treated preoperatively with chemotherapy (three courses of fluorouracil, leucovorin, etoposide, and cisplatin [FLEP]) followed by concurrent chemoradiotherapy (one course of cisplatin plus etoposide in combination with 40 Gy of radiation). Transthoracic esophagectomy was performed 4 weeks after the end of radiation. RESULTS: Seventy-two patients were included in this evaluation. Forty-four (61%) underwent a complete tumor resection, and 16 (22%) had no tumor in the resected specimen (pathologic complete response [PCR]). The operative mortality rate was 15%. At a median follow-up time of 22 months (range, 12 to 41), the median survival duration of all 72 patients was 17 months (range, 1 to 41+). The calculated survival rates at 3 years were 33%, 42%, and 68% for all patients, patients after complete resection, and patients with PCR, respectively. CONCLUSION: This combined treatment modality is active in LAEC, with a PCR in 33% of the patients undergoing surgery. The results appear improved compared with those reported with surgery alone, by approximately doubling the 3-year survival rate. The high efficacy of preoperative chemoradiation warrants evaluation of the role of surgery in LAEC.

Adenocarcinoma↗

Randomized study of the combination of hydroxyurea and interferon alpha versus hydroxyurea monotherapy during the chronic phase of chronic myelogenous leukemia (CML Study II). The German CML Study Group.

It is the long-term goal of the German CML Study Group and of the Süddeutsche Hämoblastosegruppe (SHG) to improve survival of patients with chronic myelogenous leukemia (CML). In a first randomized study (CML Study I) monotherapies with hydroxyurea or interferon alpha (IFN-alpha) were compared with a standard busulfan regimen with regard to duration of the chronic phase and survival. The main results of this study were published, 1-3 and a long-term follow up is planned. In a second randomized study the effect of the combination of IFN-alpha and hydroxyurea versus hydroxyurea monotherapy on survival is being investigated. This paper provides a first preliminary report on the study concept, patient recruitment, state of documentation and initial patients' characteristics 9 months after closure of the study.

Adult↗

A comparison of polychemotherapy and melphalan/prednisone for primary remission induction, and interferon-alpha for maintenance treatment, in multiple myeloma. A prospective trial of the German Myeloma Treatment Group.

406 untreated multiple myeloma patients of stage I (n = 54), II (n = 148) and III (n = 204) were enrolled in the trial. 51/54 stage I and 60/148 stage II patients were asymptomatic and followed without treatment until disease progression (progression free survival: 60% after 4 years for stage I versus 50% after 1 year for stage II). Symptomatic patients of stage I (n = 3/54) and II (n = 88/148) presenting with tumour progression, received melphalan 15 mg/m2 intravenously (i.v.) and prednisone 60 mg/m2 oral days 1-4 (MP). Stage II disease remission rate was 59%, and 50% tumour related survival (TRS) was 59 months. Stage III patients were randomised to receive MP or VBAMDex (vincristine/BCNU/doxorubicin/melphalan/dexamethasone) treatment. 43% of MP treated patients responded compared with 64% of the VBAMDex group. 50% TRS was 36 months in both groups without a detectable difference. 117 responders of stage II and III with stable disease were randomised to receive either IFN-alpha (5 x 10(6) IU, subcutaneous (S.C.) 3 times per week) or no maintenance treatment. The relapse rate in both groups was 50% after 13 months. No survival benefit for IFN alpha treated patients was observed (50% TRS: 45 months).

Aged↗

Low-dose recombinant interleukin-2 therapy in advanced multiple myeloma.

In vitro data have demonstrated autologous T-lymphocytes with anti-tumour activity in multiple myeloma (MM). Therefore a phase I/II trial was conducted to study the feasibility, the effect on several immunological parameters, and the tumour response induction of low-dose recombinant interleukin-2 (rIL-2) in MM patients. 18 MM patients of advanced stages in progress, who had failed on standard chemotherapy received 9 x 10(6) IU/m2 rIL-2 twice daily on days 1 and 2 and 0.9 x 10(6) IU/m2 twice daily for 5 subsequent days per week subcutaneously from days 3 to 56 (repeated every 12 weeks until progression). Patients were treated for between 8 and 1086 + d (mean 241 d) without serious side-effects. 6/17 patients experienced tumour response (2/17 objective tumour mass reduction, 4/17 long-lasting stable disease following tumour progression before initiation of rIL-2 treatment). During therapy the number of eosinophils increased 15-fold, CD4+ T lymphocytes were activated as demonstrated by enhanced CD25 antigen expression, and CD56+ NK cells expanded in the peripheral blood. Furthermore, a diminished pre-treatment ratio of CD4+/CD8+ lymphocytes was normalized during rIL-2 treatment. NK cell activity and lymphokine activated killer (LAK) cell activity was significantly enhanced. Endogenous IL-2 production and elevated soluble IL-2 receptor serum concentrations were induced. Low-dose rIL-2 can stimulate immune enhancement in MM despite the characteristic tumour-induced immunodeficiency. The treatment has proven though limited efficacy in advanced MM. Because most of the responders experienced termination of tumour progression rather than tumour regression, rIL-2 maintenance of chemotherapy-induced remissions should be investigated.

Aged↗

Isovolemic hemodilution alters the ratio of whole-body to large-vessel hematocrit (F-cell ratio). A prospective, randomized study comparing the volume effects of hydroxyethyl starch 200,000/0.62 and albumin.

OBJECTIVE: To evaluate potential changes in the ratio of whole-body/large-vessel hematocrit (f-cell ratio) during isovolemic hemodilution and to compare the volume effects of 2 different plasma exchange solutions (hydroxyethyl starch 200,000/0.62 6% and human albumin 5%). DESIGN: Prospective, randomized, controlled trial. SETTING: Operating theater in a university hospital. PATIENTS: 24 gynecological patients scheduled for elective surgery. INTERVENTIONS: Isovolemic hemodilution was performed using 2 different plasma exchange solutions. Plasma volume was determined using dye dilution technique before and after hemodilution. The volume of withdrawn blood was measured from the change in weight of the blood bags taking into account the specific gravity of blood. RESULTS: The volume of administered plasma exchange solutions exceeded the amount of withdrawn blood by 80 +/- 47 ml (p < 0.001). Plasma volume was 3,067 +/- 327 ml before and 3,517 +/- 458 ml after hemodilution. Using red cell volumes calculated from measured plasma volumes and peripheral hematocrit, a deficit of 249 +/- 133 ml (p < 0.0001) in red cells after hemodilution appeared with the measured withdrawn red cell volumes taken into account. This finding can be explained by a change in the f-cell ratio during isovolemic hemodilution. The volume effect of the exchange solutions was 1.05 for hydroxyethyl starch and 0.95 for albumin. CONCLUSIONS: The results demonstrate that a change in the f-cell ratio occurs during isovolemic hemodilution. The estimation of red cell volume or plasma volume changes by using either the hematocrit or plasma or red cell volume determinations together with the hematocrit may lead to erroneous results.

Adult↗

Mid-latency auditory evoked potentials in humans during anesthesia with S (+) ketamine--a double-blind, randomized comparison with racemic ketamine.

Mid-latency auditory evoked potentials (MLAEP) reflect the primary cortical processing of auditory stimuli. They are suppressed widely during general anesthesia. Under ketamine, in contrast, MLAEP seem to be preserved. Ketamine exists in two optical isomers, S (+) ketamine and R (-) ketamine, which differ in their pharmacodynamic properties. S (+) ketamine has a higher anesthetic-hypnotic and analgesic potency than R (-) ketamine or the racemic mixture of S (+) ketamine and R (-) ketamine. In a blinded, randomized evaluation we compared the effect of induction of general anesthesia with the more potent ketamine compound--S (+) ketamine--to induction with the racemic ketamine on MLAEP in 60 patients scheduled for minor gynecologic procedures. Anesthesia was induced with S (+) ketamine (1 mg/kg Group I, n = 30) or an equi-anesthetic dose of racemic ketamine (2 mg/kg, Group II, n = 30). Auditory evoked potentials (AEP) were recorded before, during, and after induction of general anesthesia. Latencies of the peaks V, Na, Pa, Nb, and P1 and amplitudes Na/Pa, Pa/Nb, and Nb/P1 were measured. A fast-Fourier transform was used to calculate the power spectra of the AEP. The baseline MLAEP peaks of the awake patients were of normal amplitude and demonstrated a characteristic periodic wave form morphology. Power spectra indicated high energy in the 30-40 Hz frequency range. After induction of general anesthesia with S (+) ketamine or racemic ketamine, there was no increase in latencies of peaks V, Na, Pa, Nb, or P1. No decrease in amplitudes Na/Pa, Pa/Nb, or Nb/P1 could be observed. There was no significant change in the power spectra.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Determination of plasma volume with indocyanine green in man.

We investigated the feasibility of using indocyanine green (ICG) for plasma volume (PV) determination in man. Duplicate PV measurements were carried out in 23 healthy subjects to test repeatability. ICG (0.25 mg/kg) was injected intravenously into one arm and venous blood was withdrawn from the opposite arm. Optical density of plasma samples from minute 3 to 9 was measured in a densitometer. ICG concentration at injection time was determined by monoexponential extrapolation. The mean (SD) difference (MD) was -23 ml (183) or -0.6% (5.7%). Linear regression revealed PV2 = 0.92.PV1 + 226 (r = 0.92). The PV values corresponded well with data from other studies. In 26 surgical patients PV was determined using two methods: 1) the same as in healthy subjects and 2) using a modification of this method in whole blood (PVB). For PVB measurement blood was drawn through a cuvette-densitometer from an arterial line. Calculations were the same as in PV determination except for the use of hematocrit to achieve plasma concentrations of ICG from whole blood. In patients MD were -53 ml (144) or -1.3% (4.3) for PV and -19 ml (161) or -0.3% (5.1) for PVB. Comparing PVB and PV revealed MD = -113 ml (149) or -3.3% (4.2). The whole blood method is easier to perform and reduces blood waste to almost zero. In conclusion, ICG is a suitable tracer for PV determination.

Adult↗

Karyotype in multiple myeloma and plasma cell leukaemia.

Between October 1988 and October 1991, 104 patients with multiple myeloma and 6 with plasma cell leukaemia were studied cytogenetically. Abnormal karyotypes were found in bone marrow cells of 33 patients (30%). Most pathological karyotypes were complex with numerous modal and structural anomalies. Numerical anomalies most frequently involved chromosome 11 and structural aberrations occurred most often in chromosomes 1, 11 and 14. The most consistent structural aberration was a 14q+ chromosome (10 patients) resulting from a t(11;14)(q13;q32) in 4 patients and a t(8;14)(q24;q32) in 1 patient. Sequential cytogenetic studies were performed in 15 patients. In 5 of 8 cases with a normal karyotype at diagnosis, chromosomal anomalies were detected when disease progressed. In concomitant cytogenetic/cytological studies it was found that in the majority of patients with normal karyotype the mitoses originated from contaminating normal bone marrow cells. Pathological karyotypes were detected more frequently in pretreated than in untreated patients, in patients with plasma cell leukaemia than in patients with multiple myeloma, in patients with stage III and dense bone marrow infiltration than in patients with stage I. Patients with abnormal karyotype, irrespective if pretreated or not, had a significantly shorter median survival than those with normal karyotype. These findings suggest that karyotype is an independent prognostic factor in multiple myeloma.

Adult↗

[Acoustic evoked potentials of medium latency. Anesthesia induction with S-(+)-ketamine versus ketamine racemate].

Mid-latency auditory evoked potentials (MLAEP) reflect the primary cortical processing of auditory stimuli. They are widely suppressed during general anaesthesia with volatile anaesthetics. Under ketamine, in contrast, they seem to be preserved, which has been interpreted as indicating insufficient suppression of consciousness during ketamine anaesthesia. Ketamine exists in two optical isomeres, S-(+)-ketamine und R-(-)-ketamine, which differ in their pharmacodynamic properties: S-(+)-ketamine has higher anaesthetic-hypnotic and analgesic potency than R-(-)-ketamine. It thus appears obvious to question whether S-(+)-ketamine has a different effect on the primary cortical processing of sensory, i.e., auditory stimuli. We therefore studied the effects of S-(+)-ketamine versus ketamine-racemate on MLAEP. PATIENTS AND METHODS. Institutional approval and informed consent were obtained for 40 patients scheduled for minor gynaecological procedures. The patients were assigned randomly to one of the two experimental groups. All experimental evaluations were conducted under double-blind conditions. Anaesthesia was induced with S-(+)-ketamine 1 mg/kg (group I, n = 20) or ketamine-racemat 2 mg/kg (group II, n = 20). MLAEP were recorded before, during, and after induction of general anaesthesia from the vertex (positive) and mastoids on both sides (negative). Auditory clicks were presented binaurally at 70 dBnHL at a rate of 9.3 Hz. Using the electrodiagnostic system Pathfinder I (Nicolet), 1000 successive stimulus responses were averaged over a 100-ms poststimulus interval and analysed off-line. Latencies of the peak V, Na, Pa, Nb, P1, N1, and amplitudes Na/Pa, Pa/Nb, and Nb/P1 were measured. V belongs to the brainstem-generated potentials, which demonstrates that auditory stimuli were correctly transduced. Na, Pa, Nb, P1, and N1 are generated in the primary auditory cortex of the temporal lobe and are the electrophysiological correlate of the primary cortical processing of the auditory stimuli. A Fast-Fourier transformation calculated powerspectra of the AEP. RESULTS. In the awake state, AEP peak latencies were in the normal range. MLAEP had high amplitudes and a periodic wave form. Powerspectra indicated high energy in the 30-40-Hz frequency range. After induction of general anaesthesia with (S+)-ketamine or ketamine-racemat, there was no increase in the latencies of the peaks V, Na, Pa, Nb, P1, and N1. No decrease in amplitudes Na/Pa, Pa/Nb, or Nb/P1 could be observed. In the power spectra, frequencies in the range of 30-40 Hz retained high energy. CONCLUSIONS. MLAEP do not change in amplitude or latency during induction of general anesthesia with S-(+)-ketamine or ketamine-racemat. Primary cortical processing of auditory stimuli seems to preserved under S-(+)-ketamine and ketamine-racemat. This must be viewed in connection with dreams and hallucinations and could be interpreted as inadequate suppression of auditory information processing during general anaesthesia with S-(+)-ketamine and ketamine-racemat.

Adult↗

Primary squamous cell carcinoma of the stomach.

Primary squamous cell carcinoma of the stomach is a rare lesion. Fewer than 80 such cases are found in the literature. The present case meets strict criteria and, despite direct extension into the liver, an aggressive surgical resection followed by chemotherapy seems to have effected a cure.

Carcinoma, Squamous Cell↗

Association of actinomyces and intrauterine contraceptive devices.

We analyzed the clinicopathologic aspects of 19 cases of actinomycosis associated with intrauterine devices (IUDs) seen and treated at hospitals affiliated with the State University of New York at Buffalo between 1972 and 1982. Clinical manifestations included the following: (1) asymptomatic IUD-associated Actinomyces colonization, (2) endocervicitis, (3) endometritis, (4) endometritis with salpingitis and/or tuboovarian abscesses and (5) abdominopelvic abscesses. No consistent relationship was found between the total peripheral lymphocyte count and/or degree of histologic lymphocytic reaction and the clinical picture. Abnormal uterine bleeding and/or discharge, pain, fever and abdominopelvic masses were among the symptoms and signs encountered. Patients with endocervicitis and/or endometritis responded to removal of the IUD, dilatation and curettage and antibiotic therapy for two to four weeks. Those who developed abscesses were treated successfully with surgical drainage and added antibiotic treatment.

Abscess↗

Microinvasive squamous carcinoma of the vulva.

The clinico-pathologic aspects of 15 cases of microinvasive squamous cell carcinoma of the vulva are analyzed and the literature on this subject is reviewed. Three patients in this group and 12.5% of the 279 reported cases, all with 5 mm or less depth of invasion, have had lymph node metastases and/or recurrences or have ultimately died of their disease. The prognostic value of lymphatic/vascular permeation, the degree of cellular anaplasia, the pattern as well as the depth of invasion, all have been alluded to, and the latter is popularized. It is noted, however, that the arbitrarily chosen 3 or 5 mm depth of invasion alone does not allow for consistent identification of individuals with a negligible risk for groin lymph node metastasis. There is indeed documentation of nodal metastases in 20 of 178 (11%) of the reported cases with 1-3.5 mm invasion. It is suggested that the level of invasion, as determined by Clark's classification, which provides a histologic reference point, may correlate better with the incidence of groin nodal metastasis, and its use may allow for individualized therapy and eventually aid in identifying cases of microinvasive carcinoma of the vulva that could safely be treated without lymphadenectomy.

Adult↗