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Biomedical subjects

D Weber

Publications and source records attributed to D Weber.

At least 109 records · Page 6Linked to original sources
PubMed1995

Treatment of Waldenstrom's macroglobulinemia resistant to standard therapy with 2-chlorodeoxyadenosine: identification of prognostic factors.

BACKGROUND: Few effective treatments are available for patients with Waldenstrom's macroglobulinemia that is resistant to standard therapies. We assessed the activity of 2-chlorodeoxyadenosine (2CdA) in patients with resistant macroglobulinemia in order to identify those most likely to benefit. PATIENTS AND METHODS: 2-chlorodeoxyadenosine was given to 46 consecutive patients with Waldenstrom's macroglobulinemia resistant to a combination of an alkylating agent and a glucocorticoid. Two courses were administered to outpatients at a dose of 0.1 mg/kg body weight per day for a 7-day continuous infusion using a portable pump through a central venous catheter. Responding patients were followed without further therapy. RESULTS: Twenty of 46 patients responded to 2CdA therapy (43%; 95 CI; 29 to 60%) with a significantly higher frequency of benefit among patients with disease relapsing off therapy (78%) or with primary resistant disease within the first year (57%) than in those with later phases of disease (22%). The median survival after treatment was 28 months and the median progression-free survival of responding patients was 12 months. The longest survival was measured in patients with primary refractory disease (projected median 36 months) and the shortest in those with disease in refractory relapse (median 13 months). CONCLUSION: 2-Chlorodeoxyadenosine is active against macroglobulinemic lymphoma resistant to standard regimens and most effective in patients with disease relapsing off treatment or during the first year of primary refractory disease. Little benefit was observed among patients with later phases of resistant disease who should receive alternative treatments.

Adult↗
PubMed1995

VAD-cyclosporine therapy for VAD-resistant multiple myeloma.

Few effective treatments are available for patients with multiple myeloma that is resistant to vincristine-doxorubicin by continuous infusion with high dose dexamethasone (VAD). In order to modulate p-glycoprotein, the multidrug resistance gene product, we administered a VAD-cyclosporine combination to patients with confirmed resistance to VAD. Twenty-five patients with multiple myeloma resistant to VAD received cyclosporine 4 mg/kg infused over 2 hours followed by a continuous infusion of 10 mg/kg/24 hrs for a total of 108 hours. VAD was given concurrently as a continuous infusion of vincristine 0.3 mg and doxorubicin 9 mg/m2 daily for 4 days with oral dexamethasone 20 mg/m2/day for 4 days beginning on days 1, 9 and 17. Clinical response and toxicity were correlated with MDR expression in plasma cells and the effects of cyclosporine on liver function. Six of 25 patients responded (24%; 95% CI 9-45%) with a median remission time of 7 months. Clinical response did not correlate with either the measured or the calculated MDR expression in plasma cells. Responses occurred more frequently in patients who developed high cyclosporine blood levels and paralytic ileus. The occasional benefit from VAD-cyclosporine for resistant multiple myeloma appeared to be due to a higher bioeffective dose of VAD rather than successful modulation of MDR.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Incidence and clinical importance of perioperative histamine release: randomised study of volume loading and antihistamines after induction of anaesthesia. Trial Group Mainz/Marburg.

Although histamine release is recognised as a common event during anaesthesia and surgery, few clinicians judge the resultant cardiorespiratory disturbances serious enough to warrant prophylaxis with antihistamines. We have assessed the incidence and importance of histamine release in a randomised 2 x 2 factorial study. 240 patients representing a routine throughput of major general surgery were studied during a standardised induction of anaesthesia and preoperative loading of the circulation with either Ringer solution or Haemaccel-35, with or without antihistamine prophylaxis with dimetindene (H1) plus cimetidine (H2). Cardiorespiratory disturbances were graded as detectable, clinically relevant, or life-threatening from observers' records of the anaesthesia and the actions taken by the anaesthetists. Disturbances that were accompanied by significant rises in plasma histamine were further designated histamine-related, and those that were not were designated histamine-unrelated. Anaesthetists, observers, and designators were blinded to whether or not the patients had received antihistamines and to which solution was used for circulatory volume loading. Clinically relevant or life-threatening histamine-related disturbances occurred in 8% of the patients who after induction of anaesthesia received Ringer without antihistamines, in 26% of those who received Haemaccel without antihistamines, and in 2% or less of those who received antihistamines (p < or = 0.0001). There were 4 life-threatening histamine-related disturbances, all in patients who received Haemaccel without antihistamines (p < 0.01). Histamine-unrelated disturbances occurred in 16% overall, with no obvious effect of Haemaccel or antihistamines. The histamine-related disturbances under anaesthesia were remarkable for their severity (even with small rises in histamine concentrations), for the prevalence of bradycardia, and for the absence of skin signs. Their likelihood and severity were increased in patients with tumours. The results of the trial make a case for routine prophylaxis with antihistamines as part of anaesthetic management.

Adolescent↗
PubMed1994

Outcome of polyarteritis nodosa and Churg-Strauss syndrome. An analysis of twenty-five patients.

OBJECTIVE: To compare outcome in patients with polyarteritis nodosa (PAN) and patients with Churg-Strauss syndrome (CSS) followed up at a single center. METHODS: A retrospective data review of 13 patients with PAN and 12 patients with CSS who were followed up at a vasculitis clinic. Outcome measures included a global damage index, disability and pain dimensions of the Health Assessment Questionnaire, and mortality rate. RESULTS: Compared with patients with CSS, patients with PAN had a significantly higher mean damage index score (5.15 versus 2.42; P = 0.011), a higher disability score (1.09 versus 0.16; P = 0.007), and a higher pain score (1.04 versus 0.01; P = 0.017). Patients with PAN had more relapses (relative risk = 5.07; P < 0.000) and a higher mortality rate (31%) compared with patients with CSS (8%). CONCLUSION: PAN and CSS differ in their morbidity and mortality; therefore, they should be considered as distinct clinical entities.

Adult↗
PubMed1994

Occurrence of 5c,8c,11c,15t-eicosatetraenoic acid and other unusual polyunsaturated fatty acids in rats fed partially hydrogenated canola oil.

Uncommon cis and trans fatty acids can be desaturated and elongated to produce unusual C18 and C20 polyunsaturated fatty acids in animal tissues. In the present study we examined the formation of such metabolites derived from cis and trans isomers of oleic and linoleic acids of partially hydrogenated vegetable oil origin in rats. For two months, adult male rats were fed a partially hydrogenated canola oil diet containing moderately high levels of trans fatty acids (9.6 energy%) and an adequate level of linoleic acid (1.46 energy%). Analysis of the phospholipid (PL) fatty acids of liver, heart, serum and brain showed no new C18 polyunsaturated fatty acids, except for those uncommon 18:2 isomers originating from the diet. However, minor levels (each < 0.3% PL fatty acids) of six unusual C20 polyunsaturated fatty acids were detected in the tissues examined, except in brain PL. Identification of their structures indicated that the dietary 9c,13t-18:2 isomer, which is the major trans polyunsaturated fatty acid in partially hydrogenated vegetable oils, was desaturated and elongated to 5c,8c,11c,15t-20:4, possibly by the same pathway that is operative for linoleic acid. Furthermore, dietary 12c-18:1 was converted to 8c,14c-20:2 and 5c,8c,14c-20:3; dietary 9c,12t-18:2 metabolized to 11c,14t-20:2 and 5c,8c,11c14t-20:4, and dietary 9t,12c to 11t,14c-20:2. These results suggested that of all the possible isomers of oleic and linoleic acids in partially hydrogenated vegetable oils, 12c-18:1, 9c,13t-18:2, 9c,12t-18:2 and 9t,12c-18:2 are the preferred substrates for desaturation and elongation in rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Primary therapy of multiple myeloma with paclitaxel (taxol).

BACKGROUND: The treatment of multiple myeloma remains unsatisfactory and new active agents are needed. Paclitaxel is effective against a variety of solid tumors and we assessed the utility against multiple myeloma. PATIENTS AND METHODS: From March 1993 to May 1994, we treated 33 patients with newly diagnosed multiple myeloma with paclitaxel given intravenously at a dose of 125 mg/m2 over 24 hours (13 patients) or at a dose of 135 mg/m2 over 3 hours (20 patients). RESULTS: Five of 33 patients responded (15%; 95% CI: 5 to 32%) with an unmaintained remission of 3-11+ months. Severe but reversible neutropenia was the major dose limiting toxicity, but myalgias and alopecia were also common. CONCLUSION: Paclitaxel was slightly active against multiple myeloma. Whether higher doses or new analogues of this agent can produce superior results requires further study.

Adult↗
PubMed1994

Hospital-acquired infections in pediatric burn patients.

To determine the epidemiologic characteristics of hospital-acquired infections (HAI) in pediatric burn patients, we retrospectively reviewed hospital charts of pediatric burn patients from two similar burn units. All patients less than 18 years of age admitted to the burn unit from January 1, 1980 to July 10, 1988, were enrolled. Charts were analyzed for age, sex, burn injury (type, depth, burn surface area), and hospital course (burn wound therapy, use of indwelling catheters or tubes, infectious complications, antibiotic use, cause of death if patient died). Statistical analysis was done using a logistic regression model. Of the 224 children admitted, 32 (14%) had 58 infections during their stay in the burn unit. There was no significant difference in age, sex, race, burn type or use of wound excision between patients with or without infection. Patients who acquired an infection were more likely to have sustained a > or = 20% full-thickness burn (14/32 vs 3/192 without infection), a smoke inhalation injury (10/32 vs 8/192), or have an indwelling device (29/32 vs 77/192). Thirteen (22%) of the 58 infections were burn wound infections due to Staphylococcus aureus or Pseudomonas aeruginosa, 12 (21%) were urinary tract infections due to Enterobacteriaceae, 11 (19%) were pneumonias caused by S aureus, Streptococcus pneumoniae or Pseudomonas sp, and 10 (17%) were bacteremias caused by S aureus or coagulase-negative staphylococci. The infection rate in pediatric patients hospitalized for burn injury in our study was significantly lower than the infection rate described for adult burn patients. As in adult patients, burn wound infections, pulmonary infections, and catheter-associated bacteremias are the most common infections in burned children. However, urinary tract infections are more frequent in the pediatric population. Risk factors (> or = 20% full-thickness burns, indwelling devices) and causative organisms are similar in both age groups.

Adolescent↗
PubMed1994

Primary therapy of Waldenström's macroglobulinemia with 2-chlorodeoxyadenosine.

PURPOSE: To assess the activity of 2-chlorodeoxyadenosine (2CdA) as primary therapy for patients with Waldenström's macroglobulinemia. PATIENTS AND METHODS: 2CdA was given to 26 consecutive, previously untreated and symptomatic patients with Waldenström's macroglobulinemia. Two courses were administered to outpatients at a dose of 0.1 mg/kg body weight per day for a 7-day continuous infusion using a portable pump through a central venous catheter. Responding patients were followed up without further therapy and were scheduled to receive two additional treatments with 2CdA on disease relapse. RESULTS: Twenty-two of 26 patients responded to the 2CdA therapy (85%; 95% confidence interval [CI], 65% to 96%), including three patients who achieved a complete response and 19 patients who had a partial response. Treatment was well tolerated, with no acute hematologic toxicity. A marked and sustained reduction of CD4+ lymphocytes occurred in all patients and may have contributed to a fatal infection with disseminated herpes simplex in one patient. With a median follow-up of 13 months, five patients have relapsed and all re-treated patients have responded again to 2CdA. CONCLUSION: 2CdA is highly active in previously untreated patients with Waldenström's macroglobulinemia. A limited program of treatment induced responses of good quality and long duration in more than 80% of patients.

Adult↗
PubMed1993

Combination therapy with interferon-dexamethasone for newly diagnosed patients with multiple myeloma.

BACKGROUND: Alpha-interferon and dexamethasone are each effective in patients with multiple myeloma and have a combined inhibitory effect on the in vitro growth of myeloma colonies. The effect of combined therapy in newly diagnosed patients is unknown. METHODS: Fifty-one consecutive patients with previously untreated multiple myeloma of low tumor mass received primary therapy with 3 million units (mu)/m2/day of interferon administered subcutaneously for 20 days and 20 mg/m2 of dexamethasone given orally each morning for 4 days beginning on days 1, 9, and 17. Courses were repeated after a rest period of 14 days. Results were compared with those of similar patients who received primary treatment with dexamethasone alone in the same dose regimen. RESULTS: The response rate was similar: 57% for patients treated with interferon-dexamethasone and 48% for those treated with dexamethasone alone. Remission and survival times of both groups were identical. Twenty-nine percent of patients resistant to interferon-dexamethasone and 19% of patients resistant to dexamethasone responded subsequently to either standard melphalan-prednisone or to a cyclophosphamide-vincristine-doxorubicin-dexamethasone combination. These regimens were also effective in one third of patients with disease relapse despite interferon. CONCLUSION: In this nonrandomized study of previously untreated patients with multiple myeloma, the addition of interferon in a dose of 3 mu/m2/day to dexamethasone achieved results similar to those with dexamethasone alone.

Adult↗
PubMed1993

Enhancement of experimental metastasis by tumor necrosis factor.

The influence of endogenous and exogenous tumor necrosis factor (TNF) on metastasis was investigated in an experimental fibrosarcoma metastasis model. A single intraperitoneal injection of recombinant human (rh) TNF or recombinant mouse (rm) TNF into mice 5 h before intravenous inoculation of methylcholanthrene-induced fibrosarcoma cells (CFS1) induced a significant enhancement of the number of metastases in the lung. Dose responses of rmTNF and rhTNF demonstrated a stronger metastasis-augmenting effect by rmTNF compared with rhTNF. This effect was time dependent, as administration of rmTNF 5 h before or 1 h but not 24 h after tumor cell inoculation caused an increase of tumor cell colony formation on the lung surface, suggesting an influence of TNF on the vascular adhesion and diapedesis of tumor cells. Since tumor-bearing mice showed an enhanced ability to produce TNF after endotoxin injection compared to control mice, tumor-bearing mice were treated with anti-mTNF antibodies. Neutralization of endogenous tumor-induced TNF led to a significant decrease of the number of pulmonary metastases. Histological analysis of micrometastases in the lung on day 5 by silver staining of proteins associated with nucleolar organizer regions revealed more metastatic foci and augmented proliferative activity of the tumor cells after rmTNF pretreatment of mice. However, no direct effect of rmTNF on the proliferation rate of tumor cells was seen in vitro. These findings suggest that low doses of endogenous TNF or administered TNF during cytokine therapy might enhance the metastatic potential of circulating tumor cells.

Animals↗
PubMed1993

Close linkage with the RET protooncogene and boundaries of deletion mutations in autosomal dominant Hirschsprung disease.

Tight linkage with the RET proto-oncogene (Zmax = 3.41 at theta = 0.00), analysis of recombinants and detection of a familial microdeletion in a large pedigree restrict the mapping of the Hirschsprung (HSCR) gene previously localized on proximal 10q. The molecular characterization of the familial microdeletion and of 3 additional cytogenetically visible de novo deletions, isolated in somatic cell hybrids, identify a smallest region of overlap of 250 Kb. This contains the RET proto-oncogene where missense mutations causing multiple endocrine neoplasia type 2A (MEN 2A) phenotype were recently found. The pentagastrin test (which detects preclinical forms of MEN 2A or B) is negative in adult HSCR patients with deletions of the RET gene. This represents a good candidate for the search of mutations causing HSCR.

Cell Line↗
PubMed1993

Magnetic resonance imaging in the staging of solitary plasmacytoma of bone.

PURPOSE: To assess prospectively the role of magnetic resonance (MR) imaging in the staging of patients with a solitary bone plasmacytoma (SBP). PATIENTS AND METHODS: Twelve consecutive patients with an apparent SBP underwent MR imaging of both the primary tumor and the thoracic and lumbosacral spine to seek additional foci of marrow involvement that might have been undetected by standard skeletal survey. All patients received megavoltage irradiation (total dose, 40 Gy) to the primary lesion. RESULTS: MR imaging of the thoracic and lumbosacral spine showed additional foci of marrow replacement in four of 12 patients, with signal characteristics identical to those of the primary tumor. In all four patients, the abnormal protein persisted at greater than 50% of the pretreatment value following radiation treatment. In contrast, the myeloma protein disappeared or was reduced by greater than 50% in five of the six patients with secretory disease and without additional marrow abnormalities. One of four patients progressed to multiple myeloma 10 months after diagnosis with new lesions on conventional radiographs in the same areas as detected previously by MR imaging. CONCLUSION: Four of 12 patients considered to have a SBP by standard criteria may have been understaged, because MR imaging showed additional marrow abnormalities consistent with myeloma. MR imaging of the spine may contribute to the initial staging of SBP, especially since some patients may be cured with radiotherapy.

Adult↗
PubMed1993

Haematological and plasma biochemical values for healthy Yucatan micropigs.

Blood samples (n = 135) were collected from 36 male and 35 female 20 +/- 4-week-old Yucatan micropigs and were analysed for 19 haematological and 18 plasma biochemical parameters at weeks 20, 24, 33, 46, 59, 71 and 80. For each parameter, the total number of analyses per sex, mean values, standard deviation, lowest and highest values, and 95% confidence intervals are presented as reference values for this breed. Age- and sex-related differences in these parameters are also discussed.

Animals↗