Ramipril-induced superficial pemphigus.
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Angiotensin-Converting Enzyme Inhibitors↗
Biomedical subjects
C Paul
Publications and source records attributed to C Paul.
Apoptosis as a mechanism of keratinocyte death in toxic epidermal necrolysis.
Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) are life-threatening diseases characterized by extensive epidermal destruction. The aim of our study was to investigate apoptosis in keratinocytes of patients with TEN and TEN/SJS overlap syndrome. Keratinocytes from TEN patients were found to undergo extensive apoptosis. These results suggest that cell destruction in TEN occurs as a result of apoptosis. Our findings suggest that apoptosis inhibitory agents may play an important part in the therapeutic strategy of TEN.
Adult↗
A novel growth hormone response element unrelated to STAT (signal transducer and activator of transcription)-binding sites is a bifunctional enhancer.
Regulation of gene expression by GH has so far been shown to be mediated by a few cis-acting elements, most of which are signal transducer and activator of transcription (STAT)-binding sites. Here we have characterized a novel GH-response element present in the promoter of rat serine protease inhibitor (spi) genes. It consists of a 13 nucleotide-long GAGA box containing two GAGGAG repeats separated by a G, structurally unrelated to STAT-binding sites. In hepatocytes, the spi GAGA box behaves as a position-dependent bifunctional enhancer controlling basal and GH-dependent transcription. In addition, spi GAGA box oligonucleotides inhibit cell-free transcription driven by GAGA box-containing as well as GAGA box-less promoters, suggesting that the spi GAGA box interacts directly or indirectly with component(s) of the basic transcriptional machinery. Mobility shift assays showed that this GAGA box is specifically recognized by nuclear factors that are unrelated to previously characterized proteins binding to purine-rich elements or to GH-activated STATs. Finally, experiments performed with cells expressing wild type, truncated, or mutated forms of the GH receptor indicate that protein kinase Janus kinase 2 is involved in the GH-dependent activation of the spi GAGA box. These studies reveal the existence of an as yet unidentified Janus kinase-2-dependent, STAT-independent pathway in GH activation of gene expression.
Animals↗
[Traumatic hemipelvectomy. Experiences with 11 cases].
With further improvements of the prehospital rescue systems, an increasing number of patients with extreme injuries such as traumatic hemipelvectomy are admitted to trauma centers alive. The accepted definition of traumatic hemipelvectomy is: unstable ligamentous or osseous hemipelvic injury with rupture of the pelvic neurovascular bundle (open or closed integuments). A review of the literature up to 1995 yielded on 48 surving cases with such an injury. A review of 2002 consecutive patients after pelvic fractures treated from 1972-1994 at the Medical School Hannover, resulted in the identification of 11 traumatic hemipelvectomies with four survivors. The purpose of the study was the analysis of the early clinical course of the patients after traumatic hemipelvectomy and the evaluation of the late outcome of the survivors. All accessible clinical and radiological data were reviewed for the preclinical and primary clinical treatment, concomitant injuries, cause of death and complications. The survivors are under continuous follow-up at our institution and were evaluated on average 5.5 years (range 2-7 years) after trauma. All patients were managed with early and aggressive shock therapy by an emergency physician, hemorrhage control with manual compression of the wound and a short transit time to a trauma center. Immediate surgical hemostasis was attempted in all cases. Despite this, four patients died within the first 4 h secondary to uncontrollable bleeding. Another three died between 2 days and 5 weeks after accident from complications of septic or hemorrhagic shock. In four patients a limb-saving procedure was attempted. Three of these died early, and in the remaining case secondary hemipelvectomy was necessary due to sepsis and paralyses. After primary surgical completion of the hemipelvectomy, three of four patients survived. The late result was good in two children and moderate in one adult (ambulatory and socially reintegrated). A bad result occurred in one male after secondary surgical completion of the hemipelvectomy (social deterioration and drug abuse). A strict protocol has to be set for the primary treatment of a traumatic hemipelvectomy. It includes immediate prehospital hemostasis by local pressure, advanced shock therapy and prompt transfer to a trauma center. In-hospital procedures include immediate surgical hemostasis and debridement. When the criteria or traumatic hemipelvectomy are fulfilled, surgical completion of the hemipelvectomy is mandatory. Limb-saving procedures endanger the patient's life. Early and frequent second-look operations minimize wound healing problems. Early psychological support for the patient and family is advantageous for personal well-being and social reintegration.
Adolescent↗
Epidemiology of pelvic ring injuries.
3260 patients with pelvic and acetabular fractures were assessed using a standardized documentation form by collating the data on 1905 patients treated at the Department of Traumatology of the Hannover Medical School together with those patients treated between 1991 and 1993 in the German Multicentre Study Group (Pelvis) of the German Trauma Society and the German Section of the AO International. 2551 patients had pelvic ring injuries. 61.7% of the patients were multiply injured. 12.2% were suffering a complex pelvic trauma defined as a pelvic injury with concomitant soft tissue injury. The pelvic ring fracture was classified as stable in 54.8% (type A injury), as rotationally unstable in 24.7% (type B injury), and as unstable in translation in 20.5% (type C injury). There were concomitant acetabular fractures in 15.7%. The most frequent single lesions affecting the pelvic girdle were fractures of the ischiopubic bones (transpubic instability), injuries involving the sacroiliac joint (transiliosacral instability), and sacral fractures (transsacral instability). The overall rate of operative stabilizations was 21.6%. Type B injuries were stabilized in 28.9% and type C injuries in 46.7%. The overall mortality rate was 13.4%, depending significantly on the associated extrapelvic trauma. In complex pelvic injuries, the mortality rate was 31.1% whereas for pelvic fractures without concomitant soft tissue injury the rate was only 10.8%.
Accidents, Traffic↗
[The pelvic digital image data bank. Experiences after 18 months in clinical practice].
The simultaneous availability of clinical data and radiographs for orthopedic or traumatology studies is still unsatisfactory. The retrieval of radiological files is especially time-consuming and costly. An existing database holding clinical data for about 2200 consecutive patients after pelvic or acetabular fractures (1972-1995) was supplemented by integration of a commercially available picture database. Data acquisition is performed by a digital photo camera, which is easy to use and provides sufficient resolution (1524 x 1012 pixels). The picture data are optimized but not compressed and, for example, an a.p. pelvic view requires only between 800 KB and 1.5 MB of storage room. Mass storage is performed first on magneto-optical discs and later for permanent storage on CD-ROM. "Clinical" and picture databases are linked by a macro, so the search functions of both databases are available. Thus the clinical data for single patients or group of patients can be analyzed parallel to the corresponding radiographs. By the use of a CD changer, more than 4200 radiographs remain in immediate access. So far more than 3000 radiographs for 350 patients have been acquired. The quality was sufficient for even detailed subclassification and reclassification procedures in over 95% of the cases. Using standard formats and interfaces, the pictures can be either printed in photographic quality or processed as slides for presentation. Using a standard format they have complete access to electronic publishing and mailing. The relatively low price (20,000-30,000 DM) for the complete system and the exclusive use of standard, commercially available hard and software components provide an excellent price/quality relationship and make digital radiograph storage now available for smaller working groups and institutions.
Acetabulum↗
Quantitative determination of polyethylene glycol based upon its salting out and partitioning of a dye into the resulting aqueous two-phase system.
A method is described that allows quantitative determination of polyethylene glycol (PEG) concentrations by spectrophotometric measurement of fluorescein dye absorbance after its partitioning into an aqueous two-phase system containing mPEG (M(r) 5 kDa) in the upper phase and ammonium sulfate in the lower phase. The absorbance decrease of fluorescein in the lower phase is directly proportional to the mPEG concentration, with two proportionality constants equal to 4.42 x 10(5) and 2.84 x 10(5) M-1 cm-1 in the range of 0-0.4 and 0.4-1 microM, respectively. This experimental technique can be extended to PEGs of other molecular weights by means of calibration curves that give for each size of PEG the adequate proportionality constants. The results indicate that the quantitative determination is not affected by the presence of many substances such as proteins, reducing agents, and salts, at the usual concentrations.
Coloring Agents↗
Characterization of an anthracycline-resistant human promyelocyte leukemia (HL-60) cell line with an elevated MDR-1 gene expression.
Multidrug resistance to a variety of cytotoxic drugs is due to decreased drug accumulation at the intracellular site of drug action. When due to increased energy-dependent drug efflux, this transport change is often associated with increased expression of an efflux pump for various lipophilic compounds, for example the P-glycoprotein which is the product of the MDR-1 gene. However, previously described HL-60 human promyelocytic leukemia cell lines resistant to the cytotoxic effect of anthracyclines have been reported not to express P-glycoprotein. We have isolated, by drug selection, an anthracycline-resistant HL-60 cell line that, in comparison to parental drug sensitive cells, exhibits a multidrug resistant phenotype including diminished intracellular drug retention, cross-resistance to multiple cytotoxic drugs, increased expression of a monoclonal antibody C219-reactive 180 kDa P-glycoprotein detected by Western blot analysis as well as increased expression of MDR-1 mRNA as determined by Northern blot and solution hybridization/RNAse protection analyses. Evidence is presented that the anthracycline-resistant HL-60 cells have amplified the MDR-1 gene.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Depot medroxyprogesterone acetate and breast cancer. A pooled analysis of the World Health Organization and New Zealand studies.
BACKGROUND: Although depot medroxyprogesterone acetate (DMPA) (Depo-Provera) has now been approved for marketing as a contraceptive in the United States, there are still unresolved issues about the relation between DMPA and risk of breast cancer. The two substantial case-control studies of this association yielded similar but inconclusive results. Because their designs were compatible, these studies were pooled to obtain more adequate data for analysis. DESIGN: Pooled results from two case-control studies. SETTING: New Zealand (entire country), Thailand (three centers), Mexico (one center), and Kenya (one center). PARTICIPANTS: A total of 1768 women with breast cancer and 13,905 controls, most of whom were younger than 55 years. MAIN OUTCOME MEASURE: Relative risk (RR) of breast cancer in women who had used DMPA. RESULTS: The RR of breast cancer for women who had ever used DMPA was 1.1 (95% confidence interval [CI], 0.97 to 1.4). There was no increase in risk with increasing duration of use of DMPA, but RR estimates were higher in certain subgroups of women. Further analyses suggested that recent (or current) use was the key factor, with women who had started using DMPA within the previous 5 years estimated to have an RR of 2.0 (95% CI, 1.5 to 2.8). CONCLUSIONS: The increased risk of breast cancer observed in recent (or current) users could be due to enhanced detection of breast tumors in women using DMPA or to acceleration of the growth of preexisting tumors. Women who had used DMPA more than 5 years previously had no increase in risk of breast cancer, regardless of their duration of use.
Adolescent↗
Alpha-2a interferon therapy and antibody formation in patients with essential thrombocythemia and polycythemia vera with thrombocytosis.
In ten patients with essential thrombocythemia and polycythemia vera with thrombocytosis we have investigated the therapeutic effect of recombinant alpha-2a interferon (Roceron-A) given subcutaneously in a maintenance dosage of 3 million units three times weekly. The aim was to normalize the platelet count (< or = 400 x 10(9)/L). One of the secondary aims was to study platelet activity measured as beta-thromboglobulin (beta-TG) in urine. All but one patient could administer the injections and in all patients a significant reduction in platelet values was seen. The treatment was discontinued in three patients due to side effects of interferon, two because of hair loss (one with irreversible alopecia), and one because of depression. Three patients developed antibodies to alpha-2a interferon and a concomitant rise in the platelet level; in one patient therapy was switched to leukocyte alpha-interferon with an excellent response. The initial levels of beta-TG were elevated in 9/10 patients and were significantly reduced at 6 months in 4/5 patients not developing antibodies. Six patients are still on alpha-interferon therapy with a long-term follow-up of 3-3.5 years. We conclude that alpha-interferon therapy may be an alternative in patients with thrombocytosis and/or complications necessitating treatment.
Antibody Formation↗
Oral contraceptive use and risk of breast cancer in older women (New Zealand).
The effect of oral contraceptive (OC) use at older ages on the risk of breast cancer was examined in a national population-based case-control study conducted in New Zealand. A total of 891 women aged 25 to 54 years with a first diagnosis of breast cancer, and 1,864 control subjects, randomly selected from the electoral rolls, were interviewed. The relative risk (RR) of breast cancer for women aged 45 to 54 years at diagnosis who had ever used OCs was 1.0 (95 percent confidence interval [CI] = 0.77-1.3). There was no significant increase in risk of breast cancer among recent users of OCs of any age. Analyses according to age at first and last use among women aged 40 years and older at diagnosis showed no group with an elevated risk of breast cancer. Women who had used OCs for 10 years or longer after age 40 had an apparent increase in risk (RR = 2.7, CI = 0.97-7.5), but the trend in risk with duration of use was not significant. These findings suggest that OC use in older women does not affect their risk of breast cancer appreciably, but it is not possible to rule out a modest increase in risk with such use.
Adult↗
Postprandial gallbladder motor function: refilling and turnover of bile in health and in cholelithiasis.
BACKGROUND & AIMS: Impaired gallbladder emptying is implicated in gallstone disease. Ultrasonography and scintigraphy have shown conflicting results because the former is influenced by postprandial refilling, whereas the latter is not influenced by refilling. The aim of this study was to measure postprandial refilling and turnover of bile by combining the two techniques. METHODS: Simultaneous scintigraphy and ultrasonography were used in 14 patients with gallstones and 11 healthy controls. Measurements were performed while the patients were fasting and at 10-minute intervals after a standard meal for 90 minutes, and the measurements were used to calculate postprandial refilling, turnover of bile (in milliliters), and turnover index. RESULTS: Ultrasonography and scintigraphy provided different gallbladder emptying patterns. Compared with controls, patients with gallstones had impaired emptying by both scintigraphy (P < 0.0001) and ultrasonography (P < 0.01). Postprandial refilling and turnover were both reduced between 60 and 90 minutes (P < 0.05), and the turnover index was markedly reduced (1.8 vs. 3.5; P < 0.001). CONCLUSIONS: Simultaneous scintigraphy and ultrasonography provide a new model of gallbladder motor function showing that refilling begins immediately postprandially. In healthy controls, the gallbladder postprandially handles up to six times its basal volume within a period of 90 minutes, but this turnover of bile is markedly reduced in cholelithiasis causing a reduced washout effect of the gallbladder contents, including cholesterol crystals.
Analysis of Variance↗
Pharmacokinetics of mitoxantrone, etoposide and cytosine arabinoside in leukemic cells during treatment of acute myelogenous leukemia--relationship to treatment outcome and bone marrow toxicity.
Twenty-seven patients with acute myelogenous leukemia (AML) were given remission induction treatment with mitoxantrone, etoposide and cytosine arabinoside (ara-C). The pharmacokinetics in leukemic blood cells of mitoxantrone, etoposide and the active metabolite of ara-C, ara-CTP, were determined during the first day of treatment. There was a large interpatient variability of the area under the time versus concentration curve (AUC) for all three drugs. On the individual level, there was no correlation between the AUCs of the different drugs. Neither did the AUC of any individual drug nor the calculated total intracellular drug exposure have any association with the outcome of treatment or hematological toxicity, measured as duration of leukopenia/thrombocytopenia. In conclusion, when combination chemotherapy with mitoxantrone, etoposide and ara-C is given to patients with AML, intracellular drug concentrations, achieved after the first dose of each drug, do not seem to be predictive for treatment response or hematological toxicity.
Adult↗
Hyperkeratotic spicules and monoclonal gammopathy.
Hyperkeratotic spicules are a rare disorder that has been associated with different types of malignancies. An association with multiple myeloma raises the question of a relation between the monoclonal component and skin manifestations. We describe hyperkeratotic spicules in a 61-year-old man with a monoclonal gammopathy of undetermined significance. Immunofluorescence and immunoelectron microscopic findings demonstrated the deposition of the monoclonal immunoglobulin at the dermoepidermal junction. Our findings support previous reports that the association between hyperkeratotic spicules and monoclonal gammopathy is not fortuitous and may be related to particular properties of the monoclonal immunoglobulin.
Humans↗
Inhibition of blood-brain barrier disruption in experimental allergic encephalomyelitis by short-term therapy with dexamethasone or cyclosporin A.
Double radioisotope measurement of neurovascular integrity in Lewis rats inoculated for experimental allergic encephalomyelitis (EAE) showed abnormal elevation of albumin extravasation in the cerebellum, medulla-pons and cervical spinal cord at the time of clinical manifestation. Therapeutically administered dexamethasone (Dex) (0.1-1 mg/kg body weight) or cyclosporin A (CsA) (25-75 mg/kg body weight) dose-dependently reduced albumin movement across the blood-brain barrier (BBB). Dex at a dose of 1 mg/kg completely suppressed abnormal BBB permeability in all tissues (P < or = 0.001), while CsA at the highest dose of 75 mg/kg achieved highly significant (P < or = 0.001), but not complete, suppression of aberrant barrier leakage in the areas studied. The implications of these findings to possible drug action at the immunocompromised cerebrovasculature are discussed.
Animals↗
Immunogenetics of juvenile chronic arthritis. I. HLA interaction between A2, DR5/8-DR/DQ, and DPB1*0201 is a general feature of all subsets of early onset pauciarticular juvenile chronic arthritis II. DPB1 polymorphism plays a role in systemic juvenile chronic arthritis.
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Age of Onset↗
Heterosexual behaviour and HIV risk in New Zealand: data from a national survey.
The pattern of any future major heterosexual epidemic of acquired immunodeficiency syndrome (AIDS) will depend partly on sexual behaviour and condom use among heterosexuals. This survey was designed to provide information on patterns of sexual behaviour in New Zealand. A national sample aged 18 to 54 was selected using a random method and telephone interviews were administered to 2361 people, using a questionnaire based on the protocol developed by the Global Program on AIDS of the World Health Organization. The reported mean lifetime number of partners increased with age up to 25 to 29 years for women and 30 to 34 years for men, and declined at older ages. Fifteen or more lifetime partners were reported by 17 per cent of men and 4 per cent of women. Multiple partnerships in the previous 12 months were commonest in those aged 20 to 24. In this age group, 32 per cent of men and 20 per cent of women reported two or more partners. Recent condom use for contraception was reported by 23 per cent of men and 19 per cent of women. Use was highest amongst those aged 18 to 24, and decreased sharply with age. The true proportion of the population with many sexual partners may be higher than reported. These data will be useful in modelling approaches to estimate the likelihood of future heterosexual spread of AIDS. The data on lifetime numbers of partners suggest that sexual decisions depend not just on age and sex but also on the era, and thus on changing social values about sexual behaviour.
Adolescent↗
Home oxygen therapy. A comparison of 2- vs 6-month patient reevaluation.
STUDY OBJECTIVE: To contrast the effectiveness of 2- vs 6-month reevaluation intervals on both clinical outcome and cost in patients requiring continuous home oxygen therapy (HOT). DESIGN: Prospective, randomized clinical trial. SETTING: The outpatient program of a university-affiliated Veterans Affairs Medical Center (VAMC) Pulmonary Service. PATIENTS: Fifty patients were chosen from among a cohort of 200 patients currently enrolled in our HOT program. All met specific arterial blood gas criteria, were able to give informed consent, had at least 6 months of prior HOT usage, and did not have any illness expected to independently shorten life expectancy. INTERVENTIONS: Baseline resting oxygen flow rates were prescribed based on the results of arterial blood gas measurements so as to attain a PaO2 > 60 mm Hg. Flow rates were adjusted as needed during a 12-min walk to maintain pulse oximetry readings > 90%. No adjustments in baseline flow rates were made during sleep. Identical evaluations were repeated at either 2- or 6-month intervals. MEASUREMENTS AND RESULTS: At 1-year follow-up, there were no significant differences between the 2- and 6-month groups in any of the clinical outcome parameters measured, ie, number of emergency department visits, number of hospitalizations, number of days hospitalized, or mortality. Total costs were not significantly different between the two groups. Evaluation costs were less in the 6-month follow-up group. CONCLUSIONS: After attaining stability following at least 6 months of continuous HOT usage, patients receiving continuous HOT need not be routinely reevaluated more frequently than every 6 months.
Aged↗