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Biomedical subjects

R Blum

Publications and source records attributed to R Blum.

At least 19 recordsLinked to original sources
PubMed2004

Distinct roles of Galpha(q) and Galpha11 for Purkinje cell signaling and motor behavior.

G-protein-coupled metabotropic glutamate group I receptors (mGluR1s) mediate synaptic transmission and plasticity in Purkinje cells and, therefore, critically determine cerebellar motor control and learning. Purkinje cells express two members of the G-protein G(q) family, namely G(q) and G11. Although in vitro coexpression of mGluR1 with either Galpha11 or Galpha(q) produces equally well functioning signaling cascades, Galpha(q)- and Galpha11-deficient mice exhibit distinct alterations in motor coordination. By using whole-cell recordings and Ca2+ imaging in Purkinje cells, we show that Galpha(q) is required for mGluR-dependent synaptic transmission and for long-term depression (LTD). Galpha11 has no detectable contribution for synaptic transmission but also contributes to LTD. Quantitative single-cell RT-PCR analyses in Purkinje cells demonstrate a more than 10-fold stronger expression of Galpha(q) versus Galpha11. Our findings suggest an expression level-dependent action of Galpha(q) and Galpha11 for Purkinje cell signaling and assign specific roles of these two G(q) isoforms for motor coordination.

Animals↗
PubMed2004

A comparison of fluorine-18 fluoro-deoxyglucose PET and technetium-99m sestamibi in assessing patients with multiple myeloma.

OBJECTIVE: The extent of disease in patients with multiple myeloma or related conditions may be difficult to assess. In previous small studies, both FDG-PET (PET) and Tc-99m sestamibi scans (MIBI) have identified sites of occult disease in myeloma. METHODS: We reviewed the results for patients at our institution who have undergone PET and/or MIBI scans to assess myeloma. Concordance between the scans, ability to identify otherwise occult disease and impact on patient management was assessed. RESULTS: Thirty-six patients had > or =1 PET scan, 56 had > or =1 MIBI scan and 23 had concurrent PET and MIBI scans. MIBI detected additional sites to skeletal survey in 38 of 56 (68%) cases. PET detected additional sites to skeletal survey in 18 of 36 (50%) cases. MIBI generally detected more disease sites than PET. PET and MIBI were concordant in eight of 23 (35%) cases. The percentage plasma cell infiltrate within the marrow correlated with the number of sites detected by MIBI, but not by PET. In 23 of 69 cases (33%), scan results impacted on management, particularly by upstaging disease at diagnosis and by recognising subsequent disease progression. The results were also helpful for evaluating the presence of ongoing disease activity in previously irradiated sites remaining abnormal on skeletal survey following treatment. CONCLUSIONS: MIBI and PET are useful additional diagnostic tools for detecting otherwise occult sites of myeloma. The use of MIBI PET should particularly be considered in the evaluation of a patient with an early-stage plasma cell dyscrasia to exclude the presence of more extensive disease.

Adult↗
PubMed2003

[Sarcoidal allergic contact dermatitis due to palladium following ear piercing].

Granulomatous tissue reactions due to jewelry made of gold, silver, nickel and palladium are rare but nevertheless have been known for a long time. A female patient developed nodular infiltrates after having been pierced with ear stickers containing palladium. A contact allergic reaction could be demonstrated as the underlying cause by inducing similar histological changes following patch testing with palladium.

Adult↗
PubMed2003

Primary cutaneous B-cell lymphomas.

B-cell lymphomas comprise up to 25% of primary cutaneous non-Hodgkin lymphoma (NHL). Two main classification systems are used, namely the European Organization for Research and Treatment of Cancer (EORTC) and the World Health Organization (WHO) classification of tumours. Indeed, there is much controversy surrounding which classification system to use, which in turn influences the interpretation of existing data and subsequently how we manage patients with these conditions.

Humans↗
PubMed2002

Significant impairment of high-dose methotrexate clearance following vancomycin administration in the absence of overt renal impairment.

BACKGROUND: Methotrexate is an antimetabolite cytotoxic drug which is predominantly renally excreted. Vancomycin, a glycopeptide antibiotic that is used in the febrile neutropaenic patient, can be nephrotoxic. There are no previous reports of any interactions between these two drugs. PATIENTS AND METHODS: We describe two patients with osteosarcoma treated with high-dose methotrexate-containing chemotherapy who had significantly delayed methotrexate clearance several weeks following exposure to vancomycin. RESULTS: These patients were treated with alternating chemotherapy consisting of 12 g/m2 methotrexate, 60 mg/m2 cisplatin, 75 mg/m2 adriamycin and 15 g/m2 ifosfamide. In both patients, serum methotrexate levels fell to below 0.2 micromol/l within 48-96 h during initial treatment cycles. However, following recent exposure to therapeutic vancomycin in the preceding 10 days and in the absence of overt renal impairment, both patients manifested markedly prolonged methotrexate clearance, requiring 170-231 h to reach serum levels of less than 0.2 microM. Subclinical renal impairment was documented by impaired glomerular filtration rates in both cases by technetium 99 m diethylene triamine penta-acetic acid scanning. Subsequent methotrexate cycles using an unmodified schedule were cleared within 72 h. Both cases had their glomerular filtration rate re-assessed, which showed marked improvement. CONCLUSIONS: Recent exposure to vancomycin, even in the absence of overt renal impairment, may adversely affect methotrexate excretion, which can subsequently lead to increased toxicity of the antimetabolite. The glomerular filtration rate should be measured in such cases so that appropriate dose modification of methotrexate can be made.

Adult↗
PubMed2001

Toxicity and response evaluation of the interferon inducer poly ICLC administered at low dose in advanced renal carcinoma and relapsed or refractory lymphoma: a report of two clinical trials of the Eastern Cooperative Oncology Group.

PURPOSE: Phase II studies were conducted to evaluate the safety and efficacy of the interferon inducer Poly ICLC at low doses in advanced renal cancer and relapsed or refractory lymphoma. PATIENTS AND METHODS: Twenty-nine patients with advanced renal carcinoma and eleven patients with lymphoma were treated with poly ICLC. Patients received 0.25 mg/m2 of poly ICLC intravenously twice weekly three days apart until progression or unacceptable toxicity. RESULTS: There were no objective responses. Six patients with renal carcinoma had stable disease as best response with one patient receiving 62 weeks of therapy. Toxicity included grade 3 anemia in 8 patients and grade 4 anemia in one patient. All patients were anemic prior to entry with a median grade 2 anemia at baseline. Grade 4 neutropenia, thrombocytopenia and injection site pain occurred in one patient each. Grade 3 fever, chills or fatigue occurred in four, three, and three patients respectively. Any grade fever occurred in 10 patients (25.6%) and any grade chills occurred in 9 patients (23.1%). CONCLUSION: Poly ICLC at this dose and schedule is well tolerated in both patient populations and is inactive in renal carcinoma.

Adult↗
PubMed2001

A randomized multicenter study of remifentanil compared with halothane in neonates and infants undergoing pyloromyotomy. II. Perioperative breathing patterns in neonates and infants with pyloric stenosis.

UNLABELLED: Although former preterm birth infants are at risk for postoperative apnea after surgery, it is unclear whether the same is true of full-term birth infants. We evaluated the incidence of apnea in 60 full-term neonates and infants undergoing pyloromyotomy both before and after anesthesia. All subjects were randomized to a remifentanil- or halothane-based anesthetic. Apnea was defined by the presence of prolonged apnea (>15 s) or frequent brief apnea, as observed on the pneumocardiogram. Apnea occurred before surgery in 27% of subjects and after surgery in 16% of subjects, with no significant difference between subjects randomized to remifentanil or halothane anesthesia. This apnea was primarily central in origin, occurred throughout the recording epochs, and was associated with severe desaturation in some instances. Of the subjects with normal preoperative pneumocardiograms, new onset postoperative apnea occurred in 3 (23%) of 13 subjects who received halothane-based anesthetics versus 0 (0%) of 22 subjects who received remifentanil-based anesthetics (P = 0.04). Thus, postoperative apnea can follow anesthesia in otherwise healthy full-term infants after pyloromyotomy and is occasionally severe with desaturation. New-onset postoperative apnea was not seen with a remifentanil-based anesthetic. IMPLICATIONS: Abnormal breathing patterns can follow anesthesia in infants after surgical repair of pyloric stenosis. Occasionally, these patterns can be associated with desaturation. New-onset postoperative apnea was not seen with a remifentanil-based anesthetic.

Anesthetics, Inhalation↗
PubMed2001

Agminated atypical (dysplastic) nevi: case report and review of the literature.

BACKGROUND: Patients with the atypical mole syndrome have multiple dysplastic nevi that appear to be randomly distributed on certain preferred anatomical sites such as the upper back. These dysplastic nevi are thought to be acquired melanocytic nevi that begin appearing at puberty. To our knowledge, the presence of agminated atypical (dysplastic) nevi has not been reported. OBSERVATION: We describe a patient with the atypical mole syndrome who has more than 100 melanocytic nevi, many of which are clinically atypical and one of which proved to be a melanoma. Among his many melanocytic nevi is a cluster of approximately 50 nevi that are distributed in an area measuring 5 x 3 cm. The histopathologic features of these nevi are consistent with the diagnosis of "dysplastic nevus." CONCLUSIONS: To our knowledge, agminated atypical (dysplastic) nevi have not been described previously. The presence of agminated atypical (dysplastic) nevi in a patient with the atypical mole syndrome can be theorized to arise because of loss of heterozygosity.

Adult↗
PubMed2000

Similar outcome of elderly patients in intergroup trial 0096: Cisplatin, etoposide, and thoracic radiotherapy administered once or twice daily in limited stage small cell lung carcinoma.

BACKGROUND: Elderly patients comprise a significant portion of patients with limited stage small cell lung carcinoma. However, the prognostic importance of age has been controversial, and concern for toxicity often hinders enthusiasm for offering full dose therapy. METHODS: In this retrospective analysis of Intergroup Trial 0096, the authors compared the outcome of patients 70 years or older to those younger than 70 years. Patients received cisplatin 60 mg/m(2), Day 1 and etoposide 120 mg/m(2), Days 1-3 for 4 cycles and either once or twice daily concurrent thoracic radiotherapy to 45 grays. RESULTS: Of 381 patients, 50 (13%) were age 70 years or older. The elderly group did not differ significantly from those younger than 70 years with respect to gender distribution, performance status, or weight loss. Severe hematologic toxicity (Grade 4-5: 61% vs. 84%; P < 0.01) and fatal toxicity (1% vs. 10%; P = 0.01) occurred more often among older patients. There were no differences in the frequency of nonhematologic toxicities. Response rate (88% vs. 80%; P = 0.11), event free survival rate (5 year, 19% vs. 16%; P = 0.18), time to local failure, and duration of response did not differ between groups. Overall survival rates (5 year, 22% vs. 16%; P = 0.05) favored those younger than 70 years. Much of the difference in overall survival rates between age groups occurred within the first 6 months on study. CONCLUSIONS: Elderly patients had similar response and survival rates compared with those younger than 70 years. However, toxicity, particularly hematologic, was greater among the elderly. Selected older patients, such as those with a good performance status, should be considered for optimum treatment approaches.

Age Factors↗
PubMed2000

Abdominal haemorrhage--a preventable cause of death after field stabilization?

The causes of preventable death vary in different operational settings, and the topic has not previously been explored in a fully developed central European rescue system. The factors associated with potentially preventable death were studied in a retrospective study of 430 fatal traffic accident victims (1980-96) in Lörrach County, Germany. Mission protocols could be retrieved for detailed analysis in 239 of the cases. These were studied in order to identify factors associated with preventable death. At the scene of the accident, 38% of the patients died without cardiopulmonary resuscitation (CPR) and 18% after CPR. Four patients died after a certain delay without CPR before reaching hospital. A total of 43% of the victims were admitted to hospital, 5% had received prehospital CPR and the remaining 38% had not. In a subgroup representing the experience of a single emergency physician 60 fatalities were studied. Of these, 27 (45%) patients died within the hospital; almost half of these cases (13/27) had been conscious at some time after the accident and of these, seven (7/13) died from intra-abdominal bleeding within 4 h after admission. The same cause of death was found in 3 of the 14 comatose patients. Pleural drainage was carried out in four patients and unrecognized pneumothoraces or spinal injuries did not occur. Tracheal intubation was employed in 24/27. Medical antishock trousers (MAST) were not available. The data indicate that intra-abdominal haemorrhage is an underestimated cause of death in a comprehensive rescue system, possibly as a consequence of field stabilization. The use of MAST may be a relevant therapeutic option to prevent these fatalities. The method offers the possibility of intra-abdominal compression and haemostasis after tracheal intubation has been performed. Previous controlled studies on MAST may have been biased by faulty methodology (e.g. absence of tracheal intubation) and inappropriate indications (e.g. other causes of shock). The value of MAST in comprehensive rescue systems should therefore be reassessed. The difficulties in identifying factors leading to preventable death in a retrospective analysis, are discussed and it is recommended that a permanent prospective quality control be performed in all cases of fatal accidents in order to ensure the continued improvement of prehospital emergency medical systems.

Abdominal Injuries↗
PubMed2000

Video teleconferencing with realistic simulation for medical education.

This report describes how realistic patient simulation can be used with video teleconferencing to conduct long-distance clinical case discussions with realistic re-enactments of critical events. By observing what appears to be a real procedure unfolding in real time, it is intended that audience members will better learn and appreciate the lessons from conferences. A commercially available mannequin simulator and video teleconferencing technology were used in nine sessions between a free-standing simulation center and different conference sites throughout the U.S. Transmission was via high-speed telephone lines. In each conference, a clinical scenario was simulated on a screen. Audience members asked questions of a live simulated "patient" and family and later advised the care team on routine treatments and management of urgent clinical problems that arose during management of the mannequin simulator in a highly realistic clinical setting. Ninety-eight percent of respondents from one audience of 150 (response rate 60%) judged the quality of the presentation as "very good or excellent." In response to the statement that "the educational value of the presentation was much greater than that of a standard case conference," 95% scored 4 or 5 on a five-point Likert scale (where 5 is highest agreement). While all conferences were conducted successfully, there were instances of technical challenge in using teleconferencing technology. Technical information about the teleconferencing system and scenario preparation, contingency planning for failures, and other details of using this new teaching modality are described. Although audiences were enthusiastic in their response to this approach to clinical case conferences, further study is needed to assess the added value of interactive simulation for education compared to standard conference formats.

Education, Medical↗
PubMed2000

Adolescents with learning disabilities: risk and protective factors associated with emotional well-being: findings from the National Longitudinal Study of Adolescent Health.

PURPOSE: To identify differences in emotional well-being among adolescents with and without learning disabilities and to identify risk and protective factors associated with emotional distress. METHODS: Cross-sectional analysis of adolescent in-home interview data of the National Longitudinal Study of Adolescent Health. A total of 20,780 adolescents were included in this study of whom 1,301 were identified as having a learning disability. Initially, emotional distress, suicidal behaviors, and violence involvement were compared among those adolescents with and without learning disabilities using Student's t-test for the continuous or semicontinuous variables and Chi-square for the dichotomous variables. Subsequently, logistic regression analyses were conducted to identify which variables were most strongly associated with risk and protective factors for emotional distress. RESULTS: Adolescents with learning disabilities had twice the risk of emotional distress, and females were at twice the risk of attempting suicide and for violence involvement than their peers. While educational achievement is below that of peers, connectedness to school is comparable. So, too, is connectedness to parents. Connectedness to parents and school was identified as most strongly associated with diminished emotional distress, suicide attempts, and violence involvement among adolescents with learning disabilities. CONCLUSIONS: Given the increased association with emotional distress, suicidal attempts, and violence involvement, clinicians need to assess social and emotional as well as educational and physical functioning of these young people. We also need to be aware of the role protective factors play in the lives of young people with learning disabilities.

Adaptation, Psychological↗
PubMed2000

Influences on adolescents' decision to postpone onset of sexual intercourse: a survival analysis of virginity among youths aged 13 to 18 years.

BACKGROUND: Previous research has focused on risk factors associated with early onset of sexual intercourse among adolescents. This study hypothesizes that protective factors identified for other health compromising behaviors are also protective against early onset of sexual intercourse. The study sample included 26,023 students in grades 7-12 (87.5% white, 52.5% male) who did not report a history of sexual abuse in a statewide survey of adolescent health in 1988. METHODS: Bivariate analyses were stratified into early (13-14 years), middle (15-16 years) and late (17-18 years) adolescence and by gender. Cox proportional hazards survival analysis, stratified by gender, was used to determine risk and protective factors associated with delayed onset of sexual intercourse. RESULTS: Variables showing a significant bivariate association with lower levels of sexual activity across all age groups and genders were: dual-parent families, higher socioeconomic status (SES), better school performance, greater religiosity, absence of suicidal thoughts, feeling adults or parents cared, and high parental expectations. High levels of body pride were associated with higher levels of sexual activity for all age and gender groups. In the multivariate survival analyses, variables significantly associated with delayed onset of sexual activity for both males and females included: dual-parent families, higher SES, residing in rural areas, higher school performance, concerns about the community, and higher religiosity. High parental expectations were a significant protective factor for males but not for females. CONCLUSION: While many protective factors are not subject to intervention, the present analyses indicate that teen pregnancy prevention may be enhanced by addressing family and educational factors.

Adolescent↗
PubMed2000

Hormone-stimulated calcium release is inhibited by cytoskeleton-disrupting toxins in AR4-2J cells.

We have studied the role of the actin cytoskeleton in bombesin-induced inositol 1,4,5-trisphosphate (IP(3))-production and Ca(2+)release in the pancreatic acinar tumour cell line AR4-2J. Intracellular and extracellular free Ca(2+)concentrations were measured in cell suspensions, using Fura-2. Disruption of the actin cytoskeleton by pretreatment of the cells with latrunculin B (10 microM), cytochalasin D (10 microM) or toxin B from Clostridium difficile (20 ng/ml) for 5-29 h led to inhibition of both, bombesin-stimulated IP(3)-production and Ca(2+)release. The toxins had no effect on binding of bombesin to its receptor, on Ca(2+)uptake into intracellular stores and on resting Ca(2+)levels. Ca(2+)mobilization from intracellular stores, induced by thapsigargin (100 nM) or IP(3)(1 microM) was not impaired by latrunculin B. In latrunculin B-pretreated cells inhibition of both, bombesin-stimulated IP(3)- production and Ca(2+)release was partly suspended in the presence of aluminum fluoride, an activator of G-proteins. Aluminum fluoride had no effect on basal IP(3)and Ca(2+)levels of control and toxin-pretreated cells. We conclude that disruption of the actin cytoskeleton impairs coupling of the bombesin receptor to its G-protein, resulting in inhibition of phospholipase C-activity with subsequent decreases in IP(3)-production and Ca(2+)release.

Aluminum Compounds↗
PubMed2000

Lumenal targeted GFP, used as a marker of soluble cargo, visualises rapid ERGIC to Golgi traffic by a tubulo-vesicular network.

The mechanism by which soluble proteins without sorting motifs are transported to the cell surface is not clear. Here we show that soluble green fluorescent protein (GFP) targeted to the lumen of the endoplasmic reticulum but lacking any known retrieval, retention or targeting motifs, was accumulated in the lumen of the ERGIC if cells were kept at reduced temperature. Upon activation of anterograde transport by rewarming of cells, lumenal GFP stained a microtubule-dependent, pre-Golgi tubulo-vesicular network that served as transport structure between peripheral ERGIC-elements and the perinuclear Golgi complex. Individual examples of these tubular elements up to 20 microm in length were observed. Time lapse imaging indicated rapid anterograde flow of soluble lumenal GFP through this network. Transport tubules, stained by lumenal GFP, segregated rapidly from COPI-positive membranes after transport activation. A transmembrane cargo marker, the temperature sensitive glycoprotein of the vesicular stomatitis virus, ts-045 G, is also not present in tubules which contained the soluble cargo marker lum-GFP. These results suggest a role for pre-Golgi vesicular tubular membranes in long distance anterograde transport of soluble cargo. http://www. biologists.com/JCS/movies/jcs1334.html

Animals↗
PubMed2000

Intracardiac mass complicating Malassezia furfur fungemia.

Malassezia furfur is a lipophilic yeast known to colonize indwelling catheters. Although progression to vasculitis and sepsis has been described, it has rarely caused fungemia in adults receiving nutrition via an indwelling catheter. Difficulty in diagnosis occurs as M furfur does not grow on routine culture media unless it is supplemented with fatty acids. We present the first case of M furfur fungemia in an adult, complicated by a pedunculated septic thrombus arising from the superior vena cava and extending into the right atrium. Removal of the catheter, amphotericin-B therapy, and surgical debridement were required for cure.

Catheterization, Central Venous↗
PubMed1999

Inhibition of amylase secretion from differentiated AR4-2J pancreatic acinar cells by an actin cytoskeleton controlled protein tyrosine phosphatase activity.

Disruption of the actin cytoskeleton in AR4-2J pancreatic acinar cells led to an increase in cytosolic protein tyrosine phosphatase activity, abolished bombesin-induced tyrosine phosphorylation and reduced bombesin-induced amylase secretion by about 45%. Furthermore, both tyrosine phosphorylation and amylase secretion induced by phorbol ester-induced activation of protein kinase C were abolished. An increase in the cytosolic free Ca2+ concentration by the Ca2+ ionophore A23187 had no effect on tyrosine phosphorylation but induced amylase release. Only when added together with phorbol ester, the same level of amylase secretion as with bombesin was reached. This amylase secretion was inhibited by about 40%, by actin cytoskeleton disruption similar to that induced by bombesin. We conclude that actin cytoskeleton-controlled protein tyrosine phosphatase activity downstream of protein kinase C activity regulates tyrosine phosphorylation which in part is involved in bombesin-stimulated amylase secretion.

Actins↗