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Biomedical subjects

M Wolf

Publications and source records attributed to M Wolf.

At least 73 records · Page 4Linked to original sources
PubMed2002

Laryngo-tracheal anastomosis: post-operative evaluation by helical CT and computerized reformations.

OBJECTIVE: Our purpose was to evaluate the role of post-operative helical computed tomography (CT) and computerized reformations in patients after laryngo-tracheal segmental resection with anastomosis. METHODS: Helical CT and computerized reformations were obtained in 11 consecutive patients who underwent laryngo-tracheal resection with anastomosis for obstruction or stenosis caused by longstanding intubation or tracheostomy. Post-operative computer assisted cross-sectional area, coronal and sagittal diameter measurements at the level of maximal narrowing of the trachea were compared with clinical assessment in all patients. The additive value of various coronal and sagittal computerized reformations over axial images was subjectively evaluated by a consensus of a thoracic radiologist and a neuroradiologist who were blinded to clinical information. RESULTS: Various degrees of restriction in daily activities were reported by patients with cross-sectional area narrowing of more than 50%, by 4/6 patients with cross-sectional area of less than 90mm(2), by 4/5 and 4/6 patients with coronal or sagittal narrowing of more than 25% respectively, and by 4/5 patients with sagittal diameter of less than 12mm. All five patients with cross-sectional area stenosis of less than 50% assessed themselves as 'asymptomatic'. Sagittal multi-planar and volume rendering reformations clarified or added additional information over axial images in all six patients with significant cross-sectional area stenosis (>50%). Volume rendering scores were significantly higher than minimal intensity projection reformations (P=0.01). CONCLUSION: Our preliminary results suggest that CT-based cross-sectional area and diameter measurements of the trachea represent a clinically helpful tool for post-operative evaluation of patients with tracheoplasty. The need for post-operative endoscopy may be obviated in some cases.

Adult↗
PubMed2001

Anisotropy of quasiparticle lifetimes and the role of disorder in graphite from ultrafast time-resolved photoemission spectroscopy.

Femtosecond time-resolved photoemission of photoexcited electrons in highly oriented pyrolytic graphite (HOPG) provides strong evidence for anisotropies of quasiparticle (QP) lifetimes. Indicative of such anisotropies is a pronounced anomaly in the energy dependence of QP lifetimes between 1.1 and 1.5 eV--the vicinity of a saddle point in the graphite band structure. This is supported by recent ab initio calculations and a comparison with experiments on defect-enriched HOPG which reveal that disorder, e.g., defects or phonons, increases electron energy relaxation rates.

Journal Article↗
PubMed2001

Test of low-energy theorems for 1H(--> gamma, pi(0))(H)in the threshold hegion.

The photon asymmetry in the reaction 1H(--> gamma,pi(0))(1)H close to threshold has been measured for the first time with the photon spectrometer TAPS using linearly polarized photons from the tagged-photon facility at the Mainz Microtron MAMI. The total and differential cross sections were also measured simultaneously with the photon asymmetry. This allowed determination of the S-wave and all three P-wave amplitudes. The values obtained at threshold are E(0+) = [-1.33+/-0.08(stat)+/-0.03(syst)] x 10(-3)/m(pi(+)), P(1) = [9.47 +/- 0.08(stat) +/- 0.29(syst)] x 10(-3)q/m(2)(pi(+)), P(2) = [-9.46 +/- 0.1(stat) +/- 0.29(syst)] x 10(-3)q/m(2)(pi(+)), and P(3) = [11.48 +/- 0.06(stat) +/- 0.35(syst)] x 10(-3)q/m(2)(pi(+)).

Journal Article↗
PubMed2001

Spinal neurofibromatosis without café-au-lait macules in two families with null mutations of the NF1 gene.

Spinal neurofibromatosis (SNF) is considered to be an alternative form of neurofibromatosis, showing multiple spinal tumors and café-au-lait macules. Involvement of the neurofibromatosis type 1 (NF1) locus has been demonstrated, by linkage analysis, for three families with SNF. In one of them, a cosegregating frameshift mutation in exon 46 of the NF1 gene was identified. In the present study, we report four individuals from two families who carry NF1 null mutations that would be expected to cause NF1. Three patients have multiple spinal tumors and no café-au-lait macules, and the fourth has no clinical signs of NF1. In the first family, a missense mutation (Leu2067Pro) in NF1 exon 33 was found, and, in the second, a splice-site mutation (IVS31-5A-->G) enlarging exon 32 by 4 bp at the 5' end was found. The latter mutation has also been observed in an unrelated patient with classical NF1. Both NF1 mutations cause a reduction in neurofibromin of approximately 50%, with no truncated protein present in the cells. This demonstrates that typical NF1 null mutations can result in a phenotype that is distinct from classical NF1, showing only a small spectrum of the NF1 symptoms, such as multiple spinal tumors, but not completely fitting the current clinical criteria for SNF. We speculate that this phenotype is caused by an unknown modifying gene that compensates for some, but not all, of the effects caused by neurofibromin deficiency.

Adolescent↗
PubMed2001

Pretreatment prevalence of hypothyroidism in patients with head and neck carcinoma.

BACKGROUND: Hypothyroidism in the normal population age > 60 years is encountered in the range of 0.5-5% clinically, and 5-20% have subclinical hypofunction. Hypothyroidism is recognized as a common complication of treatment in patients with head and neck carcinoma (HNC) and is reported in up to 75% of patients who receive combined treatment. Surprisingly, base-line pretreatment measurements of thyroid function in large series of patients have not been reported. METHODS: Serum thyroid-stimulating hormone, free T4, and total T3 levels were recorded in 110 patients with nonthyroid HNC prior to treatment in a prospective, controlled study. RESULTS: The mean patient age (+/- standard deviation) was 65 years +/- 13.8 years, and 82% of patients had squamous cell carcinoma. A diagnosis of hypothyroidism already was established in 4.5% of patients, and subclinical hypothyroidism was discovered in an additional 6.4% of patients. Sixteen patients had other equivocal anomalies in thyroid function and were referred for further endocrine evaluation. No patients with formerly unrecognized clinical hypothyroidism were found. CONCLUSIONS: Hypothyroidism in patients with head and neck carcinoma in Israel corresponds with the reported incidence in the general population. Hypothyroidism after treatment for head and neck carcinoma stems from the effects of treatment. The need for pretreatment evaluation of thyroid function should be considered.

Adult↗
PubMed2001

Direct observation of a rho decay of the D13(1520) baryon resonance.

The reaction gammap-->pi(+)pi(0)n has been measured at MAMI for photon energies up to 820 MeV. Invariant mass spectra of the particles in the final state (pi(+)n), (pi(0)n), (pi(+)pi(0)) have been determined for several bins of incident photon energy. Differences in pi(+)pi(0) and simultaneously measured pi(0)pi(0) invariant mass distributions are assigned to a rho branch of the D13(1520) nucleon resonance.

Journal Article↗
PubMed2001

Rapid inactivation of stromal cell-derived factor-1 by cathepsin G associated with lymphocytes.

The CXC chemokine stromal cell-derived factor (SDF)-1 is produced constitutively in different tissues. It is the only known ligand for CXCR4, which is widely expressed in leukocytes and in some tissue cells, and acts as coreceptor for X4 HIV strains. Because of the general interest in the mechanisms that regulate the activity of constitutively expressed chemokines, we have studied the inactivation of SDF-1 in cells that bear CXCR4. Here we show that B lymphocytes, NK cells and, to a lesser extent, T lymphocytes inactivate SDF-1 by N-terminal processing. Inactivation is due to cathepsin G which is associated with the membrane of lymphocytes and rapidly cleaves off five N-terminal residues by acting on the Leu(5)-Ser(6) bond yielding SDF-1(6-67). Processing was observed with intact cells, cell membrane preparations and soluble cathepsin G obtained by extraction of the membranes with Triton X-100. Cathepsin G is released by neutrophils and monocytes and binds on the surface of lymphocytes by an apparently saturable process. Analysis of the product obtained, the time course and the sensitivity to inhibitors shows that cathepsin G is the only protease involved. Conversion of SDF-1 to SDF-1(6-67) was complete within minutes to 1-2 h depending on the enzyme source, and was abrogated by inhibitors of serine proteases and chymostatin. Diprotin A, an inhibitor of dipeptidyl peptidase IV, was without effect. Owing to its availability on the surface of SDF-1-responsive cells and its rapid effect, cathepsin G is likely to play a significant role in down-regulating SDF-1 activity.

Amino Acid Sequence↗
PubMed2001

Control of T cell hyperactivation in IL-2-deficient mice by CD4(+)CD25(-) and CD4(+)CD25(+) T cells: evidence for two distinct regulatory mechanisms.

In IL-2-deficient mice, antigen-activated CD4 T cells accumulate and cause lethal immune pathology. Wild-type cells of hematopoietic origin present in the same animal are able to prevent this hyperactivation of T cells, but the mechanisms and cells controlling the IL-2-deficient cells are unknown. Here we show that IL-2(-) CD4 cells with an ovalbumin-specific transgenic TCR (IL-2(-) OVAtg) undergo both clonal expansion and clonal contraction when transferred to euthymic recipients and challenged with antigen, but continuously expand in athymic hosts. Cotransfer of wild-type CD4 T cells prevents the accumulation of IL-2-deficient cells. On the residual IL-2(-) TCRtg cells CD69 and CD25 are up-regulated, suggesting that activation per se is not suppressed and that the cells had received an IL-2 signal. Since IL-2 is able to restore the defective antigen-induced cell death (AICD) of IL-2-deficient T cells in vitro, paracrine IL-2 provided by the wild-type CD4 cells may thus be able to allow clonal contraction of IL-2-deficient cells also in vivo. Interestingly however, regulatory CD4(+)CD25(+) cells also efficiently contain the clone size of antigen-stimulated IL-2-deficient T cells. Since CD4(+)CD25(+) cells do not produce IL-2, this suggests a mechanism of suppression distinct from paracrine IL-2 delivery. In keeping with this, the residual IL-2(-) TCRtg cells recovered after cotransfer of regulatory CD4(+)CD25(+) cells do not show increased CD25 or CD69 expression, suggesting that they had not received paracrine IL-2 and that clonal containment occurred at the level of initial activation rather than clonal contraction by AICD. IL-2 deficiency therefore may upset T cell homeostasis by two distinct mechanisms: the failure to program expanding T cells for apoptosis, and the failure to generate functional CD4(+)CD25(+) regulatory cells.

Adoptive Transfer↗
PubMed2001

Obesity and preeclampsia: the potential role of inflammation.

OBJECTIVE: Systemic inflammation might contribute to the pathogenesis of preeclampsia. In addition, the association between obesity and inflammation in preeclampsia has not been examined in detail. We determined whether first-trimester elevation of serum C-reactive protein, an index of systemic inflammation, was associated with preeclampsia. METHODS: We conducted a prospective, nested case-control study among women enrolled in the Massachusetts General Hospital Obstetrical Maternal Study cohort. High-resolution C-reactive protein assays were performed on first-trimester (11 +/- 2 weeks' gestation) serum samples in 40 women in whom preeclampsia developed (blood pressure [BP] greater than 140/90 mmHg, and proteinuria, either 2+ or more by dipstick or greater than 300 mg per 24 hours), and in 80 matched controls. This sample size had greater than 80% power to detect a difference in C-reactive protein levels between cases and controls. We used nonparametric tests to compare C-reactive protein levels and conditional logistic regression to control for confounding variables. RESULTS: First-trimester C-reactive protein levels were significantly higher among women in whom preeclampsia subsequently developed compared with controls (4.6 compared with 2.3 mg/L, P =.04). When women were subdivided into C-reactive protein quartiles, the odds ratio (OR) of being in the highest quartile of C-reactive protein was 3.2 (95% confidence interval [CI] 1.1, 9.3, P =.02) among cases of preeclampsia compared with controls. When body mass index (BMI) was added to the multivariable model, the highest quartile of C-reactive protein was no longer associated with increased risk of preeclampsia (OR 1.1, 95% CI.3, 4.3, P =.94). In the same model without BMI, the highest quartile of C-reactive protein was associated with increased risk of preeclampsia (OR 3.5, 95% CI 1.3, 9.5, P =.01). CONCLUSION: In women with preeclampsia, there was evidence of increased systemic inflammation in the first trimester. Inflammation might be part of a causal pathway through which obesity predisposes to preeclampsia.

Adult↗
PubMed2001

Granular myringitis in children.

BACKGROUND: Granular myringitis (GM), described mainly in adults, is considered a rare infection of the tympanic membrane (TM) with possible involvement of the external ear canal. The study was aimed to evaluate the clinical characteristics of the disease in children. MATERIAL: A 2-year prospective study on all children with GM in a primary otolaryngology practice affiliated to a tertiary academic medical center. GM was defined by de-epithelization of the TM, granulation-tissue formation and discharge. Children with otitis media were excluded. Treatment included topical application of ear drops, caustic solution in unresponsive cases and mechanical removal of polypoidal granulations. RESULTS: Nine children, five boys and four girls, aged 3--16 (mean=11.5 years) were diagnosed as GM. Mainly plugged ear (6) and aural discharge (5) presented GM. Only a circumscribed area of the pars tensa was involved. GM was expressed either by a tiny shallow lesion (6) or by raised polypoidal masses (3). All children recovered within 2--11 weeks (mean 3.6). Recurrent infection was noted twice in one child. Small dry perforation of the TM was noted in two children. Histopathological studies revealed non specific acute and chronic inflammatory reaction. CONCLUSIONS: Granular myringitis must be recognized in children. GM has a benign course responding to topical treatment. It may be misidentified as persistent chronic suppurative otitis media with polyps protruding through the TM. Although perforation of the TM may develop in the course of the disease, the middle ear remained intact.

Child↗
PubMed2001

Dose intensive chemotherapy in small cell lung cancer.

The rationale for treatment intensification is to overcome the occurrence of drug resistance and to improve the outcome in SCLC. Several different approaches have been tested in the past two decades. Increasing the dose of conventional chemotherapy has failed to improve survival in extensive stage. In limited stage patients one randomized trial demonstrated a significant survival advantage by a 20% increase of the dose of cisplatin and cyclophosphamide given during the first cycle of chemotherapy. Shortening treatment intervals is achievable by weekly chemotherapy or by use of hematopoietic growth factors. Neither weekly chemotherapy, tested in four randomized trials, nor the application of hematopoietic growth factors significantly improved survival. However, two studies described a better survival for patients receiving chemotherapy in shorter treatment intervals. In one trial a 3-week interval was superior to a 4-week interval, and in a second one a 2-week interval superior to a 3-week interval. One smaller study, comparing a 4-week interval with a 2-week interval with stem cell augmentation by whole blood, revealed no difference in survival between both groups. A randomized trial comparing chemotherapy in intervals as short as possible with or without growth factor application showed no difference for the two groups. Thus, growth factor application seems not to be essential for treatment in short intervals and was not associated with superior survival in randomized trials. To achieve a more than two-fold increase in dose intensity some kind of stem cell support is mandatory. Several phase II trials with small patient numbers tested the concept of late intensification with bone marrow support in the 1980s. These trials did not show any convincing benefit. There is one randomized trial available testing the late intensification approach in which a superior progression free survival and a trend for better survival was demonstrated, but this difference was not statistically significant due to a high mortality rate and a substantial number of local relapses in the high dose arm. Newer concepts involving high dose therapy are combining high dose strategies with approaches for better local tumor control, administer high dose regimens earlier in the treatment course, or use multiple sequential high dose cycles. With these approaches 3-year survival rates of up to 40% have been reported. So up to date, the superiority of an intensified treatment strategy has not been demonstrated in a convincing way and further controlled trials will be necessary to clarify the role of dose intense chemotherapy in SCLC.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Patterns of failure with increasing intensification of induction chemotherapy for acute myeloid leukaemia.

Patterns of failure were studied in two consecutive randomized trials of intensified induction therapy carried out by the Australian Leukaemia Study Group (ALSG) between 1984 and 1991 to determine the impact of dose intensification. Patients received standard dose cytarabine and daunorubicin (7-3), 7-3 plus etoposide (7-3-7) or 7-3 plus high-dose cytarabine (HIDAC-3-7) chemotherapy. Patients with FAB M3 morphology were excluded. Time to failure (TTF) was defined as the time from randomization to induction death or removal from study for non-responders, or to relapse or death in complete response (CR) for complete responders. An estimated 86% of 470 de novo patients with acute myeloid leukaemia failed within 10 years of randomization, as a result of death in induction in 17% of the randomized patients, failure to achieve CR in a further 17%, relapse in 44% and death in CR in 8% of patients. An estimated 66% of patients failed as a result of refractory disease or relapse within that period (disease-related failures). Multifactor analysis identified age and peripheral blast count as the most significant pretreatment factors associated with overall TTF. These factors, together with cytogenetics, were significantly associated with disease-related failures. High-dose cytarabine in induction significantly decreased the disease-related failure rate as did allogeneic transplantation in first CR. The impact of high-dose cytarabine did not depend on the cytogenetic risk group.

Acute Disease↗
PubMed2001

High-dose therapy and autologous transplantation for lymphoma: The Peter MacCallum Cancer Institute experience.

BACKGROUND: High-dose therapy (HDT) with autologous bone marrow or blood cell transplantation for the treatment of lymphoma commenced at Peter MacCallum Cancer Institute in 1986. AIM: To examine the patient characteristics and outcomes of patients with non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD) treated with HDT and autologous transplantation at our Institute in the first 10 years of the service (1986-95). METHODS: A retrospective analysis was performed examining patient characteristics, prior chemotherapy regimens, pretransplant disease status, HDT regimen, source of stem cells, time for haematopoietic recovery, complications of transplantation, response rates, overall survival (OS) and progression-free survival (PFS). RESULTS: Sixty-seven patients with NHL were treated with an estimated 5-year OS rate of 44% (95% confidence interval (CI) 32-56%) and PFS rate of 34% (95% CI 21-44%). Factors independently predictive of an unfavourable PFS on multivariate analyses were presence of constitutional symptoms at transplant (P < 0.002) and chemotherapy-resistant disease at transplant (P = 0.02). Twenty-three patients with HD were treated with a 5-year predicted OS rate of 74% (95% CI 56-92%) and PFS rate of 57% (95% CI 36-77%). There was no difference in PFS for HD patients who relapsed either within 12 months of completion of front-line therapy or after this time (P= 0.5). The transplant-related mortality for the entire cohort was 17%, with a progressive decrease over time. CONCLUSION: HDT with autologous transplantation achieves durable PFS and OS in patients with lymphoma. Improved patient selection, therapy modifications according to prognostic factors and ongoing improvements in supportive care should improve outcomes further.

Adolescent↗
PubMed2001

Abnormal von Willebrand factor in bleeding angiodysplasias of the digestive tract.

BACKGROUND & AIMS: Involvement of an abnormal von Willebrand factor in the bleeding expression of gastrointestinal angiodysplasias has been suggested but not assessed by prospective studies. METHODS: To address this issue, 27 patients with either nonbleeding (group A, n = 9) or bleeding (group B, n = 9) digestive angiodysplasias or telangiectasias or diverticular hemorrhage (group C, n = 9) were enrolled. In all patients, an analysis of von Willebrand factor and a screening for the most common disorders associated with an acquired von Willebrand disease were performed. RESULTS: In all patients from groups A and C, von Willebrand factor was normal, and no underlying disease could be found. In contrast, all but 1 patient from group B had a variable selective loss of the largest multimeric forms of von Willebrand factor, associated in 7 cases with a stenosis of the aortic valve. CONCLUSIONS: This study indicates that most patients with bleeding angiodysplasia or telangiectasia have a deficiency of the largest multimers of von Willebrand factor induced by a latent acquired von Willebrand disease. Because these multimers are the most effective in promoting primary hemostasis at the very high shear conditions related to these vascular malformations, we suggest that their deficiency is likely to contribute to the bleeding diathesis.

Adult↗
PubMed2001

Cholestatic hepatitis A complicated by acute renal insufficiency.

31 cases of non-fulminant hepatitis A complicated by acute renal insufficiency are reported in the literature. Two-thirds of those patients needed dialysis, usually when depending on the severity of their hyperbilirubinemia. This report concerns the first published case of non-fulminant cholestatic hepatitis A complicated by acute renal insufficiency in which a spontaneous remission of renal function occurred without need for dialysis despite a very severe hyperbilirubinemia.

Acute Kidney Injury↗