Granulocyte-macrophage colony-stimulating factor in the management of severe ecthyma gangrenosum related to myelodysplastic syndrome.
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Aged↗
Biomedical subjects
E Berger
Publications and source records attributed to E Berger.
Residential radon exposure and lung cancer among nonsmoking women.
BACKGROUND: Radon at sufficiently high concentrations is known to cause lung cancer among underground miners and in experimental laboratory animals. PURPOSE: Our aim was to determine whether indoor levels of radon are associated with a detectable increase in lung cancer. Nonsmoking women were selected because they offer the best opportunity to detect radon-related risk while minimizing the potentially confounding influences of cigarette smoking and occupation. METHODS: A population-based, case-control study of incident lung cancer was conducted in Missouri. A total of 538 non-smoking white women diagnosed with lung cancer between 1986 and 1992 and 1183 age-matched control subjects were identified from the Missouri Cancer Registry and from driver's license and Medicare listings, respectively. Information on lung cancer risk factors was obtained by telephone interview. Year-long radon measurements were sought in every dwelling occupied for the previous 5-30 years. RESULTS: Radon measurements covered 78% of the relevant residential period, and women reported being indoors for 84% of this time. The time-weighted average radon concentrations were exactly the same for case subjects and control subjects (1.82 pCi/L of air [pCi L-1]). Radon levels greater than 4 pCi L-1 were experienced by 6.5% of the case subjects and 6.8% of the control subjects. For all data combined, there was little evidence for a trend of lung cancer with increasing radon concentrations (two-tailed trend test, P = .99 continuous data analysis; P = .19 categorical data analysis). A positive dose-response trend was suggested for the adenocarcinoma cell type and among directly interviewed women (two-tailed trend test; P = .31 continuous data analysis; P = .04 categorical data analysis), but not for other histologies or among those who had surrogate interviews. CONCLUSIONS: The possibility of detecting a risk from indoor radon in this study was maximized by (a) including a large number of nonsmoking women with high indoor occupancy, (b) conducting a large number of radon measurements near the time of the diagnosis of cancer, and (c) controlling for known causes of lung cancer. However, an association between lung cancer and the exposure to domestic levels of radon was not convincingly demonstrated. IMPLICATIONS: The magnitude of the lung cancer risk from radon levels commonly found in U.S. dwellings appears low.
Adenocarcinoma↗
Synthesis and structure-activity relationships of novel retinoid X receptor-selective retinoids.
Two series of potent retinoid X receptor (RXR)-selective compounds were designed and synthesized based upon recent observation that (E)-4-[2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthalenyl)-1- propenyl]benzoic acid (TTNBP) binds and transactivates only the retinoic acid receptor (RAR) subtypes whereas (E)-4-[2-(3,5,5,8,8-pentamethyl-5,6,7,8- tetrahydro-2-naphthalenyl)-1-propenyl]benzoic acid (3-methyl TTNPB) binds and transactivates both the RAR and RXR subfamilies. Addition of functional groups such as methyl, chloro, bromo, or ethyl to the 3 position of the tetrahydronaphthalene moiety of 4-[(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)carbonyl]benzoic acid (5a) and 4-[1-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2- naphthyl)ethenyl]benzoic acid (6a) results in compounds which elicit potent and selective activation of the RXR class. Such RXR-selective compounds offer pharmacological tools for elucidating the biological role of the individual retinoid receptors with which they interact. Activation profiles in cotransfection and competitive binding assays as well as molecular modeling calculations demonstrate critical structural determinants that confer selectivity for members of the RXR subfamily. The most potent compound of these series, 4-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)ethenyl]ben zoi c acid (6b), is the first RXR-selective retinoid (designated as LGD1069) to enter clinical trials for cancer indications.
Benzoates↗
The transjugular intrahepatic portosystemic stent-shunt procedure for variceal bleeding.
BACKGROUND: Transjugular placement of an intrahepatic stent is a new technique to establish a portosystemic shunt for treatment of portal hypertension. A puncture needle is advanced in a catheter through the inferior vena cava into a hepatic vein; then an intrahepatic branch of the portal vein is punctured and an expandable stent of metallic mesh is implanted to establish the shunt. METHODS: We attempted the stent-shunt procedure in 100 of 112 consecutive patients with variceal bleeding due to cirrhosis, who were then followed for a mean (+/- SD) of 12 +/- 6 months. Of the 100 patients, 22 had Child-Pugh class C cirrhosis, 10 were treated on an emergency basis, and 68 had alcoholic cirrhosis. The shunt was established with use of Palmaz stents expanded to 8 to 12 mm in diameter. RESULTS: Technical success was achieved in 93 percent of the patients. The mean (+/- SD) time for the procedure was 1.2 +/- 0.3 hours. The shunt reduced the portal venous pressure gradient by 57 percent. Major complications were hemorrhage (intraabdominal bleeding in six patients, biliary bleeding in four, and bleeding in the liver capsule in three) and migration of the stent into the pulmonary artery (in two patients). At follow-up, stenosis of the shunt was evident in 21 patients and occlusion in 10 patients; 10 of these 31 patients had variceal rebleeding. Stenoses and occlusions of the shunt were all treated successfully by redilation, thrombolysis, or implantation of an additional stent. Hepatic encephalopathy (stages I to III) developed in 25 percent of the patients. The proportion of patients with shunts who remained free of variceal rebleeding was 92 percent at six months and 82 percent at one year. The 30-day mortality was 3 percent. The cumulative one-year survival was 85 percent. CONCLUSIONS: These results suggest that the transjugular placement of an intrahepatic portosystemic stent is an effective and safe treatment for variceal hemorrhage in patients with portal hypertension due to cirrhosis.
Esophageal and Gastric Varices↗
Influence of acridine tracer dyes on neutrophil function.
A study was performed to elucidate the effect of two commonly used fluorescent dyes in in vivo microscopic studies, acridine orange (AO) and acridine red (AR), on the ability of phorbol myristate acetate (PMA)- or formyl peptide (fMLP)-stimulated human neutrophils to adhere to a bovine serum albumin matrix and to generate superoxide anions (SOX). Unlabeled stimulated human neutrophils showed 36 +/- 9% (PMA, 10(-7) M) and 11 +/- 7% (fMLP, 10(-7) M) adherence to the matrix. This adhesion was CD18 dependent as evidence by 98% and 92% reduction, respectively, when the anti-CD18 antibody IB4 was included. A dose-dependent inhibition of stimulated human neutrophil adhesion was evident after 30 min of in vitro dye labeling and the EC50 was approximately 70 micrograms/ml (AR) and 145 micrograms/ml (AO). SOX generation by PMA-stimulated neutrophils was unaffected up to 100 micrograms/ml AR and AO but was reduced by 40-60% at higher doses. Rabbit neutrophils labeled in vivo or in vitro with 100 micrograms/ml AR exhibited 41% and 61% lower SOX generation, respectively. The study indicate that neutrophil function, in terms of ability to adhere to a BSA matrix using CD11/CD18 integrins and to generate SOX upon stimulation, is reduced depending on the dose and choice of fluorescent dye. Caution should be exercised when using these compounds at high concentrations in studies of PMN function.
Acridine Orange↗
[Cerebrovascular complications of non-bacterial thrombotic endocarditis: value of transesophageal echocardiography].
Non bacterial thrombotic endocarditis is a frequent cause of cerebrovascular complications in patients with cancer. Clinical features are often misleading and symptoms are hardly linked to valvular thrombosis in the absence of systemic embolism. We describe here a case mainly illustrating two aspects: clinical and neuroradiological manifestations of multiple distal brain infarcts and the value of transoesophageal echocardiography for the diagnosis.
Cerebral Infarction↗
[Hemodynamics, liver function and clinical follow-up after TIPS].
In 126 patients with liver cirrhosis treated electively with transjugular intrahepatic portosystemic stent shunt (TIPS) to prevent variceal rebleeding, the portosystemic pressure gradient decreased by 60%. In spite of this incomplete effect the risk for variceal rebleeding was still under 20% after 2 years. Only 1 patient died of variceal rebleeding. Shunt insufficiency occurred in 50%, mainly during the first year, but shunt function was restored in nearly all cases by radiologic intervention, i.e., redilatation or implantation of an additional stent. During the follow-up of 16 +/- 9 months, 21 patients (17%) died, one-third of them from progressive liver failure aggravated in 4 cases by severe drinking. De novo hepatic encephalopathy was observed in 10%, especially in older patients and patients with impaired liver function before TIPS. In such patients it is recommended that the shunt be dilated to 0.8 cm at most, and the TIPS procedure can be combined with transjugular embolization of the varices. The advantages of TIPS over both endoscopic sclerotherapy and drug treatment must be clarified in randomized studies, which have already been initiated in several centers.
Catheterization↗
Treatment with very low-dose GM-CSF in myelodysplastic syndromes with neutropenia. A report on 28 cases.
We treated 28 cases of myelodysplastic syndrome (MDS) with neutropenia by very low-dose GM-CSF (0.25 or 0.5 micrograms/kg/day). Median age was 69 years. Nine patients had RA, 18 had RAEB, and one had RARS. Eighteen patients had absolute neutrophil counts (ANC) < or = 0.5 x 10(9)/l, and ten had ANC between 0.5 and 1.0 x 10(9)/l. Ten patients had experienced > or = WHO grade II infection(s) during the preceding 3 months. Eighteen patients (64%) had a response (i.e. ANC at least doubled and > or = 1 x 10(9)/l after 1 month), including 4/8 patients treated at 0.25 mu/kg/day, and 14/20 treated at 0.5 microgram/kg/day (difference not significant). Two of the non-responders obtained a response after dose escalation to 0.5 and 1 microgram/kg/day, respectively. The only prognostic factor of response was FAB subtype (10/11 responses in patients with RA or RARS, vs. 8/17 in RAEB, p = 0.04). Patients with ANC < or = 0.5 x 10(9)/l had a 55% (10/18) response rate, which was not significantly lower than the 80% (8/10) response rate observed in patients with ANC > 0.5 x 10(9)/l. Side-effects were generally moderate, except in three patients where the drug had to be discontinued, including the only patient who progressed to AML. In responders, GM-CSF was continued during 2 to 14 months (median 6), and the response persisted in all but one case, who relapsed after 60 days of treatment. During follow-up, only one responder had > or = WHO grade II infections, as compared to five of the non-responders (of whom two had fatal infectious episodes). In conclusion, very low-dose GM-CSF can durably increase ANC in about two thirds of MDS with neutropenia. Although it remains to be shown in randomized trials that it can reduce the incidence of infections and improve survival in MDS, very low-dose GM-CSF may be an interesting approach in MDS, associated to reasonable cost.
Aged↗
High mannose type N-linked oligosaccharides on endothelial cells may influence beta 2 integrin mediated neutrophil adherence in vitro.
We report herein on the role of N-linked oligosaccharide processing of endothelial cell surface proteins on the adhesion of neutrophils. Monolayers of human umbilical vein endothelial cells were treated for 24 h with deoxymannojirimycin (DMJ), an inhibitor of golgi mannosidase I, which results in changes in glycoprotein processing, and then incubated with neutrophils to examine their ability to adhere to the treated endothelial cells. Treatment with DMJ, which leads to accumulation of high mannose type oligosaccharides, resulted in a twofold increase in adherence of phorbol ester (PMA) activated neutrophils compared to attachment to untreated endothelial cells. This adherence was likely mediated by the beta 2 integrin, Mac-1, and could be specifically inhibited with monoclonal antibodies to ICAM-1 and to the integrin beta 2 subunit. Similarly, IL-1 treatment resulted in a beta 2 integrin mediated increase in neutrophil adherence to the DMJ treated endothelial cells in a dose dependent manner. However, the IL-1 induced adherence was not significantly inhibited by the anti-ICM-1 antibody, thus, suggesting the presence of other inducible components on the endothelial cell surface. Our results demonstrate that alterations in glycosylation of N-linked oligosaccharides, resulting in the synthesis of high mannose type sugars on molecules that may interact with the beta 2 integrins, leads to an increased adherence of PMA activated neutrophils to endothelial cells.
Asparagine↗
CD11b/CD18-dependent polymorphonuclear leucocyte interaction with matrix proteins in adhesion and migration.
Adhesion of human polymorphonuclear leucocytes (PMN) stimulated with phorbol myristate acetate (PMA) to plastic dishes coated with the matrix proteins laminin (LM), fibronectin (FN), collagen type I (CI) or collagen type IV (CIV) was inhibited by the monoclonal antibody 60.3 (MoAb 60.3; anti-CD18). The highest inhibitory effect was seen on adhesion to CI. PMN adhesion to CI was also effectively inhibited by Mo1 (anti-CD11b) but this antibody had only a minor effect on attachment of PMN to the other matrix proteins. In other experiments MoAb 60.3 inhibited LTB4-induced migration of PMN through polycarbonate filters (3 microns pores) coated with LM, FN, CI or CIV, with the most pronounced effect on migration through those filters coated with CI. By contrast, the antibody Mo1 had no effect on migration through any of the protein-coated filters tested. The results in this study suggest that the CD18 epitope, recognized by 60.3, mediates both adhesion and migration of PMN while the epitope on CD11b recognized by the antibody Mo1 is restricted to adhesion. The results also indicate that CD11b/CD18 is the major receptor on human PMN for CI while interaction with LM, FN and CIV may in addition involve other mechanisms.
Antibodies, Monoclonal↗
Levator ani muscle morphology and recurrent genuine stress incontinence.
OBJECTIVE: To assess the impact of levator ani muscle morphology on the outcome of patients with genuine stress incontinence undergoing reconstructive surgery of the pelvic floor. METHODS: A follow-up investigation was performed on 30 patients from a previous study, who had undergone hysterectomy with combined anteroposterior vaginal repair for pelvic floor relaxation and genuine stress incontinence. Biopsy specimens of the pubococcygeal muscle had been obtained during posterior colporrhaphy and subsequently evaluated for evidence of striated muscle tissue. Eleven patients had striated muscle tissue in the biopsy specimens (group A), whereas 19 subjects did not (group B). Before operation and at 41 months (range 37-44) after operation, the patients underwent urodynamics, perineal sonography, and perineometry. RESULTS: At follow-up, all patients in group A were continent, whereas ten of 19 patients (53%) in group B showed recurrent genuine stress incontinence (P < .01). Compared with group B (48.5 +/- 21.9%), group A patients (71.8 +/- 16.5%) had a significantly higher abdominal pressure transmission ratio at follow-up (P = .02). At postoperative perineal sonography, group A patients (107.7 +/- 14.0 degrees) showed a significantly smaller retrovesical angle during straining than did group B patients (134.6 +/- 25.9 degrees) (P < .01). CONCLUSION: The levator ani muscle morphology has prognostic importance for the outcome of patients with genuine stress incontinence undergoing anteroposterior vaginal repair.
Female↗
Effect of divalent cations on adhesion of polymorphonuclear leukocytes to matrix molecules in vitro.
Adhesion of N-formyl-methionyl-leucylphenylalanine-stimulated human polymorphonuclear leukocytes (PMNs) to dishes coated with laminin, fibronectin, or collagen types I and IV was dependent on the presence of magnesium (Mg2+) but not calcium (Ca2+). Addition of manganese (Mn2+) in combination with Ca2+ and Mg2+ further increased the number of PMNs adhering to the matrix proteins. Monoclonal antibody 60.3 (mAb 60.3) was equally effective at inhibiting adhesion of PMNs to all the matrix proteins. The presence of Mn2+ (50 microM), in addition to 1 mM Ca2+ and Mg2+, required higher concentrations of mAb 60.3 to inhibit adhesion of PMNs to collagens type I or IV, suggesting increased affinity of PMNs for these substrates. These findings suggest that the PMNs may regulate the affinity of CD11/CD18 for multiple ligands by binding different divalent cations to the receptor.
Antigens, CD↗
[The value of the urethral depression quotient in diagnosis of female stress incontinence using the Brown-Wickham method].
Various parameters of the urethral pressure profile have been developed to improve diagnosis of genuine stress incontinence. By application of micro-tip transducers, a positive correlation between "depression ratio" and degree of incontinence as had been observed by Eberhard. The aim of this study was to examine Eberhard's observations by the use of Brown-Wickham's method. Significant differences in the parameters of the urethral pressure profile during stress, such as the urethral closure pressure, depression pressure, depression ratio, transmission ratio, and the area of continence, were found between continent and incontinent patients. Although pressure transmission and transmission ratio revealed significant differences, depression pressure and depression ratio were found to be similar in patients with mild and severe degree of incontinence. According to the results of this study, depression ratio does not reflect the degree of urinary loss, when open catheters are used.
Female↗
Influence of age on outcome of mechanically ventilated patients in an intensive care unit.
OBJECTIVE: To assess the influence of age on the outcome of patients receiving prolonged mechanical ventilation. DESIGN: Retrospective study. SETTING: Intensive care unit. PATIENTS: A total of 1,141 patients in our ICU during a 32-month period. A total of 536 patients required mechanical ventilation. After exclusion of 171 patients ventilated for less than 24 hrs after surgery, 365 patients were investigated. MEASUREMENTS AND MAIN RESULTS: Two hundred sixty-six (73%) patients were aged less than 70 yrs; 99 (27%) patients were greater than or equal to 70 yrs. There was no significant difference in mortality rate between the younger and the older age groups. There was no significant influence of other important factors, such as severity of illness, duration of mechanical ventilation, or length of ICU stay. The only factor showing a significant influence on patient outcome was the reason for mechanical ventilation. There were more survivors in the group being ventilated because of ventilatory insufficiency than in the group with oxygenation impairment (57.8% vs. 23.9%, p less than .001). CONCLUSION: An influence of age on the outcome of mechanically ventilated patients in the ICU could not be ascertained in this study.
Adolescent↗
[Cervix dysplasia and HPV infections in females treated with immunosuppressive therapy].
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Adolescent↗
[Case report of primary irradiated melanoma of the cervix uteri].
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Aged↗
Granulocyte adhesion, deformability, and superoxide formation in acute stroke.
BACKGROUND AND PURPOSE: Impaired rheological properties of as well as cytotoxic substances produced by granulocytes may contribute to tissue damage in acute ischemic stroke. To assess changes in the properties of circulating granulocytes, we measured their adhesion, deformability, and superoxide generation in the first 3 days after ischemic stroke. METHODS: Granulocytes from 18 male patients and 20 age- and risk-matched controls were investigated. Adhesion to murine laminin-, human fibronectin-, and bovine serum albumin-coated surfaces was measured with and without the stimulus phorbol myristate acetate and the antiadhesion antibody IB4. Superoxide anion formation was assessed by the reduction of ferricytochrome C. In a subgroup of 10 patients and 11 controls, granulocyte deformability was determined using the micropipette aspiration technique. RESULTS: The patients had significantly greater granulocyte adhesion to laminin (p less than 0.005) and fibronectin (p less than 0.05) but not bovine serum albumin. Cell stimulation enhanced the differences between the groups, whereas the antiadhesion antibody inhibited adhesion in both patients and controls. There were no significant differences in granulocyte deformability. Superoxide production by granulocytes was significantly lower in the patients without the stimulus (p less than 0.05) and with 10 nM phorbol myristate acetate (p less than 0.005). CONCLUSIONS: These findings suggest that circulating granulocytes in ischemic stroke exhibit increased adhesive properties, a feature that represents one of the risk factors for granulocyte entrapment, impairment of microvascular flow, and tissue injury.
Acute Disease↗
Complications of vaginal hysterectomy under "difficult" circumstances.
Vaginal hysterectomy is less invasive than hysterectomy performed via the abdominal approach. The vaginal approach may be made difficult by prior conisation, a need to remove the adnexae or marked uterine enlargement requiring morcellement. In this retrospective study we have investigated the impact of these factors on the incidence of complications in 1912 patients subject to vaginal hysterectomy. We have studied the incidence of intraoperative hemorrhage, bladder damage, hemorrhage up to 48 h after surgery, hemorrhage up to 14 days after surgery, vault abscesses or collections and pelvic peritonitis. In patients with prior morcellement, intraoperative hemorrhage was significantly more frequent. All other complications were not significantly increased by the intraoperative difficulties specified above. Thus even "difficult" vaginal hysterectomy would seem to carry low morbidity.
Female↗