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Biomedical subjects

A Rubin

Publications and source records attributed to A Rubin.

At least 37 records · Page 2Linked to original sources

Linear EUS for bile duct stones.

BACKGROUND: Radial scanning endoscopic ultrasonography (EUS) has been shown, in experienced hands, to be a safe and accurate means of detecting bile duct stones. We compared linear array EUS with endoscopic retrograde cholangiopancreatography (ERCP), in our first 50 cases, to evaluate efficacy of this examination as well as the learning curve for this indication. METHODS: A retrospective study was conducted on 50 patients with suspected choledocholithiasis. We compared results of EUS with those of ERCP as a reference. First a linear EUS examination was performed followed by ERCP, at a median interval of 31 days (range 3 to 162 days). RESULTS: The average age of patients was 56 years (range 26 to 76); 48% were women. Fifteen (30%) had undergone cholecystectomy, a mean of 8.5 years (range 1 to 22) before the EUS. EUS compared with ERCP had a 97% sensitivity, 77% specificity, and 90% accuracy. In 14% of patients EUS provided an additional or alternative diagnosis: chronic pancreatitis (n = 3), duodenitis (2), bile duct stricture (1), chronic gastritis (1). No complications were encountered due to EUS. CONCLUSIONS: We found in this early experience that linear array EUS is a reasonably safe and accurate means of detecting choledocholithiasis. Linear array EUS, despite the learning curve, seems to be about equivalent to radial EUS in accuracy. Appropriate use of this less invasive technique may possibly replace the use of diagnostic ERCP.

Cholangiopancreatography, Endoscopic Retrograde↗

Autologous stem cell transplantation for acute myeloid leukemia in first remission.

We studied the feasibility, toxicity, and efficacy of a 2-step approach to autologous stem cell transplantation for patients with acute myeloid leukemia in first remission. Step 1 consisted of consolidation chemotherapy including cytarabine 2000 mg/m2 twice daily for 4 days concurrent with etoposide 40 mg/kg by continuous infusion over 4 days. During the recovery from this chemotherapy, peripheral blood stem cells were collected under granulocyte colony-stimulating factor stimulation. Step 2, autologous stem cell transplantation, involved the preparative regimen of busulfan 16 mg/kg followed by etoposide 60 mg/kg and reinfusion of unpurged peripheral blood stem cells. A total of 128 patients were treated. During step 1, there was 1 treatment-related death. A median CD34+ cell dose of 14 (x10(6)/kg) was collected in 3 aphereses. Ten patients suffered relapse before transplantation, and 117 patients (91%) proceeded to transplantation. During step 2, there were 2 treatment-related deaths, and 35 patients subsequently suffered relapse. With median follow-up of 30 months, 5-year disease-free survival for all patients entered in the study is projected to be 55%. By cytogenetic risk group, 5-year disease-free survival is 73% for favorable-risk patients, 51% for intermediate-risk patients, and 0% for poor-risk patients. We conclude that this 2-step approach to autologous transplantation produces excellent stem cell yields and allows a high percentage of patients to receive the intended therapy. Preliminary efficacy analysis is very encouraging, with outcomes that appear superior to those of conventional chemotherapy.

Acute Disease↗

Outcomes of critically ill patients denied consideration for liver transplantation.

Patients with advanced liver disease (ALD) leading to admission to the ICU are often evaluated for possible orthotopic liver transplantation (OLT). Those deemed ineligible for listing for OLT must be managed by medical therapy. The number of patients not eligible for OLT listing will likely increase given the current organ transplant shortage. We performed a retrospective multivariate analysis of mortality predictors for patients denied listing for OLT. One hundred and eighty-three patients denied OLT listing were evaluated over a 3(1)/(2)-yr period, beginning in 1994. Overall mortality was 56% for those not listed versus 12% for those listed for OLT (p < 0.001). Independent predictors of increased mortality among those not listed were APACHE II score (p = 0.001; OR 1.11), sepsis (p = 0.04; OR 2.41), and the need for mechanical ventilation (p = 0.001; OR 3.71). Gastrointestinal (GI) bleeding was associated with decreased mortality (p = 0.02; OR 0.44). We conclude that critically ill patients with ALD denied OLT listing have substantially higher mortality than those listed for OLT. APACHE II score, sepsis, and the need for mechanical ventilation predict increased mortality in this group. Conversely, GI bleeding predicts decreased mortality; therefore, aggressive resuscitative measures seem merited in these patients.

APACHE↗

Hypoxic induction of vascular endothelial growth factor is markedly decreased in diabetic individuals who do not develop retinopathy.

OBJECTIVE: A small percentage of patients do not develop any evidence of diabetic retinopathy (DR) even after many years of diabetes. Vascular endothelial growth factor (VEGF) has been implicated in the development of DR. Therefore, we sought to determine if the regulation of VEGF differs in those patients who develop DR after many years of diabetes compared with those who do not develop DR. RESEARCH DESIGN AND METHODS: We performed standard 7-field stereoscopic fundus photography on 95 consecutive patients with type 1 and type 2 diabetes. Patients were categorized into 3 groups according to the presence or absence of DR and the duration of diabetes: group 1 was defined by presence of DR, group 2 was defined by absence of DR after >10 years duration of diabetes, and group 3 was defined by absence of DR with long-standing diabetes (> or =20 years for type 1 diabetes and > or =15 years for type 2 diabetes). Monocytes from 40 ml peripheral blood were isolated from all patients, and the hypoxic induction of VEGF was determined in vitro. RESULTS: We found no significant difference in the basal level of VEGF in patients with and without DR. However, we did find a markedly significant difference in the hypoxic induction of VEGF between patients from group 1 and group 3 (4.35+/-0.55 vs. 1.87+/-0.3, P<0.00013). CONCLUSIONS: This study suggests that 1 mechanism for the absence of DR in patients with long-standing diabetes is a decreased hypoxic induction of VEGF.

Cell Hypoxia↗

Human eosinophils regulate human lung- and skin-derived fibroblast properties in vitro: a role for transforming growth factor beta (TGF-beta).

Eosinophils have been associated with fibrosis. To investigate their direct role in fibrosis, human peripheral blood eosinophil sonicate was added to human lung or dermal fibroblasts, and proliferation ([(3)H]thymidine) and collagen synthesis ([(3)H]proline) were evaluated. Proliferation was enhanced significantly in the monolayers in a dose-dependent manner. The activity of the eosinophil fibrogenic factor(s) remained unaltered when heated (56 degrees C, 30 min). Supernatants of cultured eosinophils (20 min or 18 hr) also enhanced lung fibroblast proliferation, indicating that the preformed mitogenic factor(s) can be released both promptly and with a long kinetic. Eosinophils significantly decreased collagen production in lung fibroblasts while increasing it in dermal fibroblasts. However, eosinophils containing matrix metalloproteinase 9 (zymography) in latent form and tissue inhibitors of metalloproteinases 1 and 2 (reverse zymography) did not influence either fibroblast matrix metalloproteinases or tissue inhibitors of metalloproteinases. Eosinophil sonicate added to skin and lung fibroblasts in tridimensional collagen lattices significantly enhanced lattice contraction. Transforming growth factor beta (TGF-beta) is a major fibrogenic cytokine produced by eosinophils. Therefore, to assess its role, eosinophil sonicate was preincubated with anti-TGF-beta neutralizing antibodies. This treatment partially inhibited proliferation of lung and collagen synthesis of dermal fibroblasts and suppressed the stimulation of lattice contraction, indicating the fibrogenic role of eosinophil-associated TGF-beta. In conclusion, we have shown that eosinophils act as direct modulatory cells in fibroblast proliferation, collagen synthesis, and lattice contraction, in part, through TGF-beta. These data corroborate the importance of eosinophils in skin and lung fibrosis.

Cell Division↗

Calcium influx and activation of calpain I mediate acute reactive gliosis in injured spinal cord.

Buffering extracellular pH at the site of a spinal cord crush-injury may stimulate axonal regeneration in rats (1; Guth et al., Exp. Neurol. 88: 44-55, 1985). We demonstrated in cultured astrocytes that acidic pH initiates a rapid increase in immunoreactivity for GFAP (GFAP-IR), a hallmark of reactive gliosis (2; Oh et al., Glia 13: 319-322, 1995). We extended these studies by investigating the effects of certain treatments on reactive gliosis developing in situ in a rat spinal cord injury model. A significant reactive gliosis was observed within 2 days of cord lesion in untreated crush or vehicle-treated, crush control animals as evidenced by increased GFAP-IR and hypertrophy of astrocytes. By contrast, infusion of Pipes buffer (pH 7.4) into the lesion site significantly reduced this increase. The increased GFAP-IR appeared to be linked to Ca2+ influx since infusion of a blocker of L-type calcium channels, nifedipine, reduced the ensuing reactive gliosis significantly. While Ca2+ modulates many signaling pathways within cells, its effect on reactive gliosis appeared to result from an activation of calpain I. Calpain inhibitor I, a selective inhibitor of mu-calpain, also significantly reduced reactive gliosis. However, calpain inhibitor II, a close structural analog which blocks m-calpain, had no salutary effect. We suggest, therefore, that the initial reactive gliosis seen in vivo may result from the activation of a neutral, Ca2+-dependent protease, calpain I, through calcium influx.

Acute Disease↗

Epithelial mucin-1 (MUC1) expression and MA5 anti-MUC1 monoclonal antibody targeting in multiple myeloma.

Multiple myeloma (MM) is the second most common hematological cancer in the United States. It is typically incurable, even with myeloablative chemotherapy and stem-cell transplantation. The epithelial mucin-1 (MUC1) glycoprotein is expressed by normal and malignant epithelial cells but has also been shown to be expressed by MM cells. MUC1 is a useful antigenic target in solid tumors for clinical diagnostic and therapeutic monoclonal antibody (mAb)-based approaches. The MA5 mAb, as well as other anti-MUC1 mAbs reactive with the MUC1 variable number tandem repeat domain, exhibited moderate to strong reactivity with both MM cell lines and clinical samples. To explore the biochemical nature and potential of MUC1 as an antigenic target in MM, studies were performed to: (a) compare the mRNA and the MUC1 glycoprotein species between epithelial cancer and MM cell lines; and (b) develop and use a human MM tumor xenograft model system to study the biodistribution of the MA5 mAb. MA5 mAb was strongly reactive with six of eight human MM cell lines by flow cytometry. In seven of eight MM patient samples (bone marrow and/or peripheral blood) reactivity was found in 10-90% of the cells, whereas normal control (n = 5) and leukemia and lymphoma (n = 5) cells showed only 0-6% reactivity. 125I-labeled MA5 whole-cell binding studies showed quantitatively similar amounts of binding between strongly positive MM lines and high-MUC1-expressing breast carcinoma lines. mRNA expression was assessed by Northern blotting and reverse transcription-PCR. MM cell lines were positive by both methods, with strong similarity in the sizes of the mRNAs and cDNAs that were obtained. Finally, biodistribution experiments were carried out with 131I-labeled MA5 versus a nonbinding control 125I-labeled mAb in a s.c. MM xenograft model. Selective MM tumor uptake of the MA5 mAb was demonstrated, with a potential for delivering a tumor radiation absorbed dose of 8540 cGy/mCi of injected dose compared with 3099 cGy/mCi of tumor-absorbed dose delivered by nonspecific antibody.

Animals↗

Optional introns in mitochondrial DNA of Podospora anserina are the primary source of observed size polymorphisms.

The significant differences in mitochondrial genome size among seven races (B, E, M, T, U, W, and Y) of Podospora anserina have been found to be primarily due to the presence and/or absence of introns, including four introns not previously known to be optional. Information from physical mapping of races M and T, and sequence data from races A and s, was used to identify regions likely to contain insertions or deletions, which were then characterized using PCR and sequence analysis. Newly confirmed optional introns are the first intron of the large ribosomal RNA (LSUr1), the single intron of NADH dehydrogenase subunit 3 (ND3i1), the single intron in ATPase subunit 6 (ATPase6), and the fifth intron of cytochrome oxidase subunit I (COIi5). We have also found that race M exists in two forms as determined by mitochondrial DNA. These results bring to nine (including races A and s) the number of races characterized by mitochondrial intron content with a total of six known optional introns and one optional insertion. Eight of the nine races contain a distinct set of introns, providing a more reliable means for identification and comparison. The identification of optional mitochondrial introns in P. anserina may have evolutionary implications regarding the transfer and/or mobility of these introns.

Ascomycota↗

Rapid rescreening.

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False Negative Reactions↗

Social workers' knowledge of and experience with sexual exploitation by psychotherapists.

A survey of licensed social workers in Texas using self-administered questionnaires revealed that, during the previous 12 months, 17 percent had worked with at least one victim of sexual exploitation by a psychotherapist. Social workers licensed as advanced clinical practitioners, licensed social workers with master's degrees, and those working in private practice were most likely to have worked with a victim of such sexual exploitation. Most respondents were not familiar with the provisions of new Texas legislation concerning sexual exploitation by psychotherapists, including definitions and reporting requirements. The majority indicated they would be interested in additional training.

Crime Victims↗

Outdated practitioner views about family culpability and severe mental disorders.

Current theories and research about the etiology and treatment of psychotic disorders increasingly point to the importance of biological factors. Accompanying this shift in the etiological literature has been an accumulation of evidence indicating the need to move away from treatment modalities that make families of people with psychotic disorders feel culpable in the causation or perpetuation of their relatives' disorders. The current study reports the development of a reliable and valid scale to assess the extent to which practitioners have made this shift. It also reports two surveys, the findings of which imply grounds for concern about what many practitioners do when working with clients with severe and persistent mental illness and their families.

Attitude to Health↗

Variability of the refractive state: meridional profiles and uniform variation.

Variation of the refractive state as measured with autorefraction is the result of many factors which need to be considered if optometry is to develop a more complete understanding of the behavior of the visual process. Various methods can be applied to develop such an understanding including scatter plots, meridional profiles of variance-covariance, and graphs of uniform variation. These methods are used, in this paper, to investigate some results for autorefraction from a sample of 106 university students studying optometry. Some of the eyes in the sample display variation, some or all of whose characteristics are the same in all meridians of the eye. Such eyes are said to exhibit refractive variation that is partially or completely uniform across the meridians of the eye. Most eyes, however, show variation which appears to depart from uniformity. The typical eye in the sample appears to exhibit variation that is mainly spherical in character and of a small magnitude in keeping with the view that the accommodative system mostly is responsible for this variation. Nevertheless, there is an astigmatic component to the variation. The mean variance-covariance matrices for the right and left eyes are presented.

Accommodation, Ocular↗

A multicenter, randomized study comparing the efficacy and safety of intravenous and/or oral levofloxacin versus ceftriaxone and/or cefuroxime axetil in treatment of adults with community-acquired pneumonia.

Five hundred ninety patients were enrolled in a prospective, multicenter, randomized trial comparing the efficacy and safety of 7 to 14 days of levofloxacin treatment with that of ceftriaxone and/or cefuroxime axetil in the management of community-acquired pneumonia in adults. Patients received either intravenous and/or oral levofloxacin (500 mg once daily) or the comparative agents, parenteral ceftriaxone (1 to 2 g once to twice daily) and/or oral cefuroxime axetil (500 mg twice daily). Erythromycin or doxycycline could be added to the comparator arm at the investigator's discretion. The decision to use an intravenous or oral antimicrobial agent for initial therapy was made by the investigator. Clinical and microbiological evaluations were completed at the baseline, during treatment, 5 to 7 days posttherapy, and 3 to 4 weeks posttherapy. Four hundred fifty-six patients (226 given levofloxacin and 230 administered ceftriaxone and/or cefuroxime axetil) were evaluable for clinical efficacy. Streptococcus pneumoniae and Haemophilus influenzae were isolated in 15 and 12%, respectively, of clinically evaluable patients. One hundred fifty atypical pathogens were identified: 101 were Chlamydia pneumoniae, 41 were Mycoplasma pneumoniae, and 8 were Legionella pneumophila. Clinical success at 5 to 7 days posttherapy was superior for the levofloxacin group (96%) compared with the ceftriaxone and/or cefuroxime axetil group (90%) (95% confidence interval [CI] of -10.7 to -1.3). Among patients with typical respiratory pathogens who were evaluable for microbiological efficacy, the overall bacteriologic eradication rates were superior for levofloxacin (98%) compared with the ceftriaxone and/or cefuroxime axetil group (85%) (95% CI of -21.6 to -4.8). Levofloxacin eradicated 100% of the most frequently reported respiratory pathogens (i.e., H. influenzae and S. pneumoniae) and provided a >98% clinical success rate in patients with atypical pathogens. Both levofloxacin and ceftriaxone-cefuroxime axetil eradicated 100% of the S. pneumoniae cells detected in blood culture. Drug-related adverse events were reported in 5.8% of patients receiving levofloxacin and in 8.5% of patients administered ceftriaxone and/or cefuroxime axetil. Gastrointestinal and central and peripheral nervous system adverse events were the most common events reported in each treatment group. In conclusion, these results demonstrate that treatment with levofloxacin is superior to ceftriaxone and/or cefuroxime axetil therapy in the management of community-acquired pneumonia in adults.

Administration, Oral↗

Variation during autorefraction: influence of two different target types.

An investigation was performed on seven subjects of varying ages in order to determine the influence of two different target types on autorefractor results. A single autorefractor capable of presenting two different targets was used. Multivariate statistical methods which only recently have become available in optometry are used to illustrate graphically the results obtained and formal hypothesis tests further demonstrate that most of the eyes in the sample display similar variation or behaviour with both targets. The mean refractive state likewise is not significantly different for both targets for five of the seven eyes at a 99% confidence level. Departures from multivariate normality (such as resulting from outliers) are shown to be of great importance in order to reach appropriate decisions with respect to target influence on autorefractor measurements and an example is provided to illustrate this point. In the absence of departures from normality it is believed that this study exhibits only weak evidence for differences in variation or mean refractive state with the different target types.

Adolescent↗