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Biomedical subjects

M Wolf

Publications and source records attributed to M Wolf.

At least 235 records · Page 13Linked to original sources

Generation of antibodies to heparin-PF4 complexes without thrombocytopenia in patients treated with unfractionated or low-molecular-weight heparin.

The incidence of antibodies to heparin-PF4 complexes (H-PF4) has been evaluated in patients who were under heparin therapy for more than 7 days: 109 patients treated with unfractionated heparin (UH) and 100 patients with low-molecular-weight heparin (LMWH). The presence of antibodies was identified in 17% of the former group and 8% of the latter. In both the UH and the LMWH groups, IgM antibodies were found in all but four patients who showed IgA antibodies. IgG isotypes were only detected in five patients and were consistently associated to either IgM or IgA antibodies. The follow-up of H-PF4 antibodies in 76 patients treated with UH from 1 to > or = 12 days showed a relationship between the incidence of antibodies and the duration of therapy. Despite the presence of anti-H-PF4 antibodies there was no thrombocytopenia (<150 10(9)/L) in the patients. A significant drop of platelets requiring the discontinuation of heparin was observed, however, in three patients, but their platelet count consistently remained >150 10(9)/L. Our study demonstrates that the induction of antibodies to H-PF4 is a frequent phenomenon in patients treated with UH or with LMWH. The absence of thrombocytopenia and of clinical complications in these patients demonstrates that other conditions must be associated with H-PF4 antibodies for inducing type II HIT: optimal concentrations of heparin and PF4 in the blood circulation to allow the formation of macromolecular H-PF4 complexes, presence of activated platelets that present an increased binding of H-PF4 complexes, increased expression of FcgammaRIIA receptors, or presence of their H 131 phenotype. We conclude that the measurement of antibodies to H-PF4 complexes allows the detection of heparin-treated patients at risk of developing type II HIT.

Autoimmune Diseases↗

Optimising the methodology of calculating the cerebral blood flow of newborn infants from near infra-red spectrophotometry data.

Cerebral blood flow can be measured in neonates by near infra-red spectrophotometry. The tracer is oxyhaemoglobin. The purpose of the study is to compare the test-retest variability of two previously proposed methods (UCH and COP) of analysis, and to investigate the influence of sampling rates, smoothing and integration periods. Under clinical conditions good measurements are often difficult to obtain. Therefore, a second goal is to find ways of determining the quality of individual measurements. 380 cerebral blood flow measurements from 69 infants are analysed. The data set is optimised statistically for the lowest test-retest variability and the following results are obtained. The test-retest variability of measurements at 2 s sampling time data is considerably worse than at 0.5 s sampling time. Smoothing does not change the test retest variability. A 6 s integration period gives higher values and higher test-retest variability than an 8 s integration period. By applying the suggested criteria, a test-retest variability of 17% is achieved, if 50% of the measurements are rejected. The mean cerebral blood flow is 12.2 ml (100 g)-1 min-1 for the UCH method and 9.7 ml [corrected] (100 g)-1 min-1 for the COP method. The test-retest variability of both methods is comparable for 0.5 s sampling time. For 2 s sampling time the method proposed by Skov et al. is significantly better. These test retest variabilities represent maximum values, part of the observed variability may be due to physiological changes of unknown magnitude.

Cerebrovascular Circulation↗

Polycyclic musk fragrances in human adipose tissue and human milk.

Polycyclic musk fragrances-substituted indane and tetraline derivatives-which are intensively utilized in cosmetics and detergents were determined in a total of 14 human adipose tissue samples and 5 human milk samples by GC/EI/MS in the SIM mode. The residue levels ranged from 16 to 189 micrograms/kg fat for HHCB and from 8 to 58 micrograms/kg fat for AHTN, respectively. In a few samples also ADBI, AHDI and ATII were detected at lower levels. In analogy to the nitro musks, the dermal sorption of these lipophilic compounds from cosmetics and detergents is discussed as a possible contamination route.

Adipose Tissue↗

Missing front teeth in exile Tamils--an unresolved phenomenon.

In the period from 1986 to 1995, the Department of Public Health in Wuppertal conducted an examination of 263 patients who had come from Sri Lanka as refugees and applied for political asylum in the Federal Republic of Germany. Isolated front tooth gaps were observed in more than 60% of the patients, an incidence significantly higher than in a control group of asylum seekers from countries other than Sri Lanka, and much higher than the incidence of traumatic tooth loss reported in the literature. The aetiology of this tooth loss remains largely unresolved. The bulk of the medical histories given by the patients did not correspond with the clinical and X-ray evidence gathered. Since medical and dental causes for the loss of the teeth can be excluded, one must ask whether social, cultural or religious causes are responsible.

Adolescent↗

Combination transurethral resection, systemic chemotherapy, and pelvic radiotherapy for invasive (T2-T4) bladder cancer unsuitable for cystectomy: a phase I/II Southwestern Oncology Group study.

OBJECTIVES: Primarily to evaluate the toxicity and, secondarily, the tumor response and patient survival associated with a three-phase combined modality treatment plan for patients with invasive transitional cell carcinoma (TCC) of the bladder (T2-T4,NX-N2, MO) who are medically unsuitable for or who refuse cystectomy. METHODS: Eligible patients initially underwent extensive transurethral resection (TUR) of the primary tumor with the attempt to resect disease totally. Subsequently, they received systemic combination chemotherapy consisting of two cycles of methotrexate, cisplatin, and vinblastine (MCV), followed by cystoscopic re-evaluation of the bladder tumor. Patients then received 6480 cGy radiotherapy to the bladder with concurrent systemic cisplatin. Toxicity, primary tumor response, and overall survival were evaluated. RESULTS: Of 34 eligible patients, 27 patients completed the treatment series. Twenty-two received 80% to 100% of the prescribed doses of MCV and only 2 patients experienced grade 4 hematologic toxicities. The most common toxicities were gastrointestinal (23), hematologic (21), and renal (8). The complete response (CR) rate after all treatment phases was 56% (19 of 34), 10 patients achieving a complete tumor resection of visible tumor at the initial TUR of the bladder (TURB); 3, a CR after MCV; and 6, after radiotherapy and concomitant cisplatin. The median overall survival was 21 months with 6 of 34 (18%) alive at 57 months (range, 36 to 75). Complete resection of tumor by TURB was associated with prolonged overall survival. The bladder was the initial site of recurrence in 85% of patients who had achieved a CR status. CONCLUSIONS: This older age patient group tolerated this combined modality therapy with acceptable toxicities, but the overall survival rate was not improved compared with those reported with radiotherapy alone.

Aged↗

Pathogenicity of IgA and/or IgM antibodies to heparin-PF4 complexes in patients with heparin-induced thrombocytopenia.

Antibodies to heparin-PF4 (H-PF4) complexes have been tested and isotyped in 38 patients who developed severe heparin-induced thrombocytopenia (type II HIT). All patients had a platelet count <120x10(9)/1 or a reduction of > 30% of the initial value, occurring at least 5d after the onset of heparin. Thrombocytopenia, which rapidly reversed following the withdrawal of heparin, was associated with thrombosis in nine patients. Although IgG isotypes were found in most cases (n=26), the presence of only IgM and/or IgA was observed in 12 patients, including three cases showing a thrombotic complication. Our results indicate that type II HIT may be induced by IgA and /or IgM anti-H-PF4 antibodies even in the absence of IgG isotypes. This finding demonstrates that platelet Fc receptors (FcgammaRII) are not necessarily involved in the pathogenicity of heparin-dependent antibodies and emphasizes the major role of platelet PF4 receptors. The increased expression of the latter following a slight activation by thrombin, and the subsequent binding of IgM and IgA antibodies to H-PF4 on the platelet surface, may directly trigger platelet activation aggregation and thrombosis. Alternatively, thrombocytopenia could be indirectly induced through the mediation of neutrophils, monocytes and lymphocytes which expose receptors for IgA (FcalphaR) or IgM FcmuR). IgM-platelet complexes may also bind and activate complement, leading to platelet activation or destruction. Moreover, the reactivity of the antibodies with glycosaminoglycans-PF4 complexes present on the endothelial surface could also induce endothelial lesions and promote procoagulant activity and predisposition to thrombosis.

Adult↗

[History and definition of sepsis--do we need new terminology?].

The history of sepsis demonstrates that despite current knowledge about its pathogenesis the definition of sepsis is more contested than ever. However, a definite terminology is necessary to define the entrance criteria for future clinical studies concerning patients with sepsis or septic shock. For this purpose, in 1991 a consensus conference was held in the US, but its recommendations have not found unequivocal acceptance. These recommendations and their historical background are presented and their consequences discussed.

Diagnosis, Differential↗

Treatment of stage D2 hormone refractory carcinoma of the prostate with 5-fluorouracil and Roferon-A: a Southwest Oncology Group study.

Based upon prior data suggesting that alpha-interferon possesses chemomodulatory activity, the Southwest Oncology Group conducted a study in which patients with hormone refractory, metastatic (stage D2) adenocarcinoma of the prostate were treated with 5-fluorouracil (5-FU) and Roferon-A. All patients had bidimensionally measurable disease. Treatment consisted of 5-FU 750 mg/m2/day by continuous i.v. infusion for 5 days with Roferon-A 9 million units subcutaneously ono days 1, 3 and 5. Roferon-A was continued three times weekly throughout treatment. Following a one week hiatus from 5-FU (week 2), 5-FU was continued at a dose of 750 mg/m2 i.v. bolus weekly. Nineteen patients were evaluable for toxicity. The most common toxicities were gastrointestinal and mucosal, hematologic and a flu-like syndrome. There were no deaths related to treatment. Among the 14 patients evaluable for response, the response rate was 0% (95% confidence interval, 0-18%). Thirteen of the 19 evaluable patients have died with a median survival of 9 months. The combination of 5-FU and Roferon-A does not have sufficient activity against advanced, hormone refractory prostate cancer to warrant further investigation.

Adenocarcinoma↗

A safety study of Albumex 5, a human albumin solution produced by ion exchange chromatography.

Human serum albumin solutions have been used as plasma replacement fluids for many years and adverse events associated with their use are rare. Albumex 5 is a new albumin solution manufactured by a combination of the Cohn fractionation process and a chromatographic technique. A multicentre, randomised study was conducted to compare the safety of Albumex 5 and 5% normal serum albumin (5% NSA) in patients undergoing large volume therapeutic plasmapheresis for a variety of disorders. Up to six exchanges were performed on each patient. A total of 208 evaluable exchanges were performed on 40 patients, 109 5% NSA and 99 Albumex 5. There were 9 adverse events (reaction rate of 8.3%) in 6 patients with 5% NSA and 12 events (reaction rate 12.1%) in 8 patients with Albumex 5. The difference is not statistically significant (p = 0.37, Fisher's exact test). None of the adverse events were considered serious. Only six reactions were thought to be possibly related to the product and three exchanges were modified as a result of an adverse event; one with Albumex 5 was interrupted and two with 5% NSA were slowed. Albumex 5 can be considered to be a safe product with a low adverse event rate.

Adult↗

Impact of central, obstructive and mixed apnea on cerebral hemodynamics in preterm infants.

The objective of this study was to evaluate the effect of central, obstructive and mixed apnea on cerebral total hemoglobin concentration (tHb), which is analogous to cerebral blood volume, and to investigate whether tHb alterations correlate with bradycardia and arterial desaturation. Measurements were carried out on 17 preterm infants (gestational age 26-30 weeks) with frequent apneic events. Near infrared spectrophotometry (NIRS) was used to quantify changes in tHb. Respiration was monitored by chest movements using impedance pneumography and by nasal airflow using a thermistor. In addition, heart rate, arterial oxygen saturation, in each infant and esophageal pressure in 3 babies were continuously recorded. 130 apneic episodes of > 10 s duration showed four different patterns of tHb alterations: (1) no change in tHb (28%); (2) isolated decrease (35%); (3) isolated increase (12%), or (4) both combined, an initial decrease followed by an increase over the previous baseline level (25%). Obstructive apneic episodes were associated with a significantly greater maximum fall in tHb (median 11.5; 5th percentile 0 and 95th percentile 30.5 mumol/l) compared to mixed (4.9, 0 and 26.4 mumol/l) and central events (3.0, 0 and 14.0 mumol/l). Changes in tHb correlated with heart rate only in purely central apnea and were not reflected in arterial oxygen saturation in any type of apnea. Obstructive apnea was observed to have the strongest impact on tHb. As these tHb alterations may exacerbate or cause intraventricular hemorrhage, efforts must be made to prevent obstruction of upper airways and to focus monitoring on cerebral perfusion.

Apnea↗

Postintubation arytenoid subluxation.

Arytenoid subluxation (AS), ie, malpositioning of the arytenoid cartilage with abnormal but existent contact between the joint surfaces, is an uncommon entity, and fewer than 70 cases have been reported, 26 of which were in a recently published series. Usually, AS is the result of upper airway instrumentation, and only a few cases were reported to occur with external trauma to the neck. Some predisposing factors and possible mechanisms have been suggested, but the reason for its occurrence remains obscure. Hoarseness and, to a lesser degree, dysphagia, odynophagia, cough, and sore throat may be indicative of AS. Diagnosis is established by the clinical course, laryngoscopy, and computed tomography. Electromyography and strobovideolaryngoscopy are additional diagnostic measures described. We report 7 cases of postintubation AS of long standing. Three of these patients had prior unilateral vocal cord paralysis, formerly undescribed as a possible contributing factor for AS. The pertinent literature is reviewed and treatment options are discussed.

Adult↗

Severe lymphocytopenia and interstitial pneumonia in patients treated with paclitaxel and simultaneous radiotherapy for non-small-cell lung cancer.

PURPOSE: In a phase II trial with paclitaxel and simultaneous radiotherapy in non-small-cell lung cancer (NSCLC) patients, an unexpected high incidence of interstitial pneumonias was observed. The type of immunodeficiency associated with this treatment approach is characterized. PATIENTS AND METHODS: Fifteen patients with inoperable stage IIIA/B NSCLC were treated with paclitaxel as a 3-hour infusion on day 1 in weeks 1 to 3 and 6 to 8 at dose levels between 50 mg/m2 and 86 mg/m2 and with simultaneous radiotherapy in daily doses of 2 Gy, 5 days per week, in weeks 1 to 3 and 6 to 8 up to a total dose of 56 Gy. Hematologic parameters and lymphocyte subsets were monitored. RESULTS: Fourteen patients are assessable for response. The overall response rate was 78%, with four major responses, six partial remissions, and four minor responses. The major toxic effect observed was a moderate to severe protracted lymphocytopenia (380 +/- 310/microL) in all patients. Seven patients developed moderate to severe interstitial pneumonia; one had an additional herpes zoster infection, while an eighth patient had a cytomegalovirus infection. During treatment, all lymphocyte subsets were reduced, as follows (n = 9, mean +/- SD): CD4+ T cells (100 +/- 90/microL), CD8+ T cells (130 +/- 160/microL), natural killer (NK) cells (70 +/- 80/microL), and B cells (20 +/- 10/microL). Thus, the most pronounced toxicity was seen in CD4+ T and B cells. There was no recovery of lymphocyte subsets during a 3-month follow-up period. CONCLUSION: Paclitaxel with simultaneous radiation induces lymphocytopenia and promotes opportunistic infections. Long-term antibiotic and antimycotic prophylaxis is recommended. Whether the lymphocytopenia is an additive effect of paclitaxel and radiation or whether it can be induced by low-dose weekly paclitaxel alone remains to be determined.

Adult↗

Body composition and energy expenditure in thyroidectomized patients during short-term hypothyroidism and thyrotropin-suppressive thyroxine therapy.

Thyroid hormone levels are a major determinant of energy balance and are thought to modify body composition by their effects on metabolism of lipids, carbohydrate and protein. The present study evaluates changes of body composition and basal energy expenditure (BEE) in thyroidectomized patients studied during short-term profound hypothyroidism while off all thyroid hormone before diagnostic whole-body (131)I-imaging and while on thyrotropin-suppressive thyroxine therapy. Basal energy expenditure was assessed by indirect calorimetry, and four-point body impedance analysis was used to estimate body composition. Patients were compared with healthy controls matched with respect to sex, age, height and weight. Compared to healthy controls the percentages of body water and body cell mass were significantly lower while the percentage of fat was significantly higher in patients during short-term hypothyroidism. Weight did not change significantly when patients were put on thyroxine treatment, but body fat (-0.95 +/- 2.25 kg, p < 0.01) decreased while body water (+0.94 +/- 1.31 kg, p < 0.01) and body cell mass (+0.9 +/- 2.5 kg, p < 0.05) increased. With thyroxine replacement, body composition was not significantly different between patients and controls. Compared to healthy controls, BEE was significantly lower in patients without thyroxine replacement (5265 +/- 766 kJ/24h vs 6362 +/- 992 kJ/24h; p < 0.001). With thyroxine treatment, BEE increased (6492 +/- 967 kJ/24h) but was not significantly different from the controls (p > 0.05). Neither body composition nor BEE was significantly different in a subgroup of thyroxine-treated patients with free triiodothyronine or thyroxine values above the normal range. In conclusion, both body composition and energy expenditure showed significant changes when patients were deprived of thyroid hormone. However, no evidence of excess metabolic effects of thyroid hormone during thyrotropin-suppressive thyroxine therapy was found.

Adult↗

Proinflammatory cytokines interleukin 1 beta and tumor necrosis factor alpha inhibit growth hormone stimulation of insulin-like growth factor I synthesis and growth hormone receptor mRNA levels in cultured rat liver cells.

Low levels of insulin-like growth factor I (IGF-I) in critical illness are observed despite increased or normal levels of growth hormone (GH). The mechanisms for this apparent GH resistance have not been elucidated. As many of the acute inflammatory responses in critical illness are mediated by the proinflammatory cytokines interleukin 1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF-alpha), the present studies evaluated IL-1 beta and TNF-alpha effects on steady-state and GH-stimulated IGF-I synthesis and GH receptor mRNA levels. In rat hepatocytes in primary culture, IGF-I released into culture medium was determined by radioimmunoassay, and quantitative competitive polymerase chain reaction was used to measure IGF-I mRNA and GH receptor mRNA concentrations. Growth hormone increased GH receptor mRNA, IGF-I mRNA and IGF-I protein secreted into the culture medium. In cells not stimulated with GH, modest inhibitory effects of IL-1 beta on GH receptor mRNA, IGF-I mRNA and IGF-I protein levels were seen. However, the stimulatory effects of GH were inhibited in a dose-dependent manner both by IL-1 beta and TNF-alpha, and at higher cytokine concentrations no stimulatory effects of GH were observed. Both IL-1 beta and TNF-alpha in submaximal dose had additive inhibitory effects on IGF-I protein concentrations but these effects did not result in irreversible damage to cells, as indicated by restoration of IGF-I and GH receptor mRNA levels to normal after withdrawal of cytokines. In conclusion, we demonstrated that in rat hepatocytes in primary culture IL-1 beta and TNF-alpha inhibited GH-stimulated IGF-I synthesis. Diminished GH receptor mRNA concentrations in response to IL-1 beta and TNF-alpha indicate that low IGF-I levels during severe illness, despite high circulating GH levels, may at least partially be a consequence of suppression of hepatic GH receptor synthesis by IL-1 beta and TNF-alpha.

Animals↗