Neuralgic amyotrophy misdiagnosed as diaphragmatic rupture.
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Adult↗
Biomedical subjects
R Rodriguez
Publications and source records attributed to R Rodriguez.
CD28-dependent killing by human YT cells requires phosphatidylinositol 3-kinase activation.
CD28/B7 interactions have been demonstrated to provide a co-stimulatory signal for the generation of CD8+ cytotoxic T lymphocytes in the absence of CD4+ T helper cells. The CD28 signals required for induction of cytotoxicity have yet to be described. To investigate further the biochemical signaling pathways associated with CD28-dependent cytotoxicity, we have studied the human thymic leukemia cell line, YT. YT cells kill B7+ targets in a non-major histocompatibility complex (MHC)-restricted, CD28-dependent manner. CD28 ligation on the surface of YT cells caused a rapid increase in the tyrosine phosphorylation of four major cellular substrates with masses estimated to be 110, 95, 85, and 44 kDa. The 110 and 85 kDa substrates were identified as the catalytic and regulatory subunits, respectively, of phosphatidylinositol 3-kinase (PI3-K). Engagement of CD28 caused the rapid receptor association and activation of PI3-K but did not activate phospholipase C gamma. CD28-induced tyrosine phosphorylation and PI3-K activation was independent of p56lck protein tyrosine kinase (PTK) activity (previously reported to be associated with CD28) and was insensitive to inhibition by the PTK inhibitor herbimycin A. Two structurally and mechanistically dissimilar inhibitors of PI3-K, wortmannin and 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002) also failed to block CD28-dependent tyrosine phosphorylation events or the association of PI3-K with the CD28 receptor. However, both drugs inhibited CD28-dependent cytotoxicity and CD28 receptor associated PI3-K activity with IC50 values similar to the reported IC50 values for PI3-K inhibition. Although herbimycin A did not significantly block the observed CD28-dependent tyrosine phosphorylation or PI3-K activation, herbimycin did block CD28-dependent cytotoxicity in a dose-dependent manner. These data support a role for PI3-K activation in the CD28-dependent initiation of cytotoxic effector function and suggest that a herbimycin sensitive step(s) is either CD28-independent, resides within a PI3-K-independent CD28 signaling pathway, or is downstream of CD28-dependent PI3-K activation.
Amino Acid Sequence↗
Patients with HIV infection and end-stage renal disease.
There has been a steady increase in the number of dialysis patients with human immunodeficiency viral (HIV) infection. HIV-associated nephropathy (HIVAN) is the most common cause of end-stage renal disease in this patient population. Although the major potential category of risk of HIV transmission is from the dialysis patient to staff, there are no data to indicate that this has occurred. Dialysis of patients with HIV infection is challenging and requires effective care to prolong survival.
HIV Infections↗
Severe community-acquired pneumonia in the elderly: epidemiology and prognosis. Study Group for Severe Community-Acquired Pneumonia.
Ninety-five patients with severe community-acquired pneumonia (SCAP) who were > or = 65 years of age were studied prospectively. A definite pathogen was identified in 37 cases (38.9%) and was most commonly Streptococcus pneumoniae, Haemophilus influenzae, or another gram-negative bacillus. The overall death rate was 40%. Eighty-three patients required mechanical ventilation and 40 needed vasoactive drugs. Multivariate analysis showed that the risk of death was higher in cases involving rapid radiological spread (relative risk [RR] = 6.99; 95% confidence interval (95% CI) = 1.54-31.70), shock (RR = 6.70; 95% CI = 2.13-21.02), previous steroid treatment or immunosuppression (RR = 5.50; 95% CI = 0.77-39.10), acute renal failure (RR = 3.88; 95% CI = 1.30-11.59), or an APACHE II score of > 22 on admission (RR = 2.25; 95% CI = 0.73-6.95). We conclude that SCAP in elderly patients is associated with high mortality, but it is inappropriate to withhold intensive care on account of age. The presence of complications and the severity of illness at initial presentation were the major variables affecting outcome. Except for immunosuppression, comorbidities did not seem to influence outcome. Finally, our data reinforce the current American Thoracic Society guidelines concerning therapy for patients with SCAP.
Acute Kidney Injury↗
Ifosfamide and vinorelbine as first-line chemotherapy for advanced non-small cell lung carcinoma.
We evaluated the efficacy and toxicity of the novel combination of ifosfamide (IFX) and vinorelbine (VNB) as first-line chemotherapy in patients with stage IIIB and IV non-small cell lung cancer (NSCLC). Between March 1993 and November 1994, 44 patients (17 stage IIIB; 27 stage IV) received a regimen consisting of IFX, 2 g/m2 in a 1-h infusion, days 1-3; mesna, 400 mg/m2 in an i.v. bolus at hours 0 and 4 and 800 mg orally at hour 8, days 1-3; and VNB, 35 mg/ m2 in a 20-min infusion, days 1 and 15. During the first course only, a half dose of VNB (17.5 mg/m2) was administered on days 8 and 22. Courses were repeated every 28 days. Forty patients were fully evaluable for response, and 44 were assessable for toxicity. Objective regression was recorded in 13 of 40 patients (33%). No patient achieved a complete response. Thirteen patients presented a partial response (33%); 17 (42%) had no change; and progressive disease was observed in 10 (25%). The median duration of response was 10 months, and the median time to treatment failure for the whole group was 4 months. Median survival was 11 months. The dose-limiting toxic effect was myelosuppression. Leukopenia occurred in 25 patients (57%) and was grade 3 or 4 in 8 patients (18%). Twelve patients (27%) developed peripheral neurotoxicity, while five had mild IFX-induced CNS toxicity. Phlebitis was observed in 15 of 30 patients (50%) who did not have central implantable venous systems. The IFX-VNB combination exhibited an activity against NSCLC that was among the highest reported for non-cisplatin-containing regimens, with a toxicity profile that was easily managed.
Adult↗
Statistical properties of stochastic nonlinear dynamical models of single spiking neurons and neural networks.
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Journal Article↗
Further observations on the role of nitric oxide in the feline lateral geniculate nucleus.
We have examined the responses of a population of 77 cells in the dorsal lateral geniculate nucleus (dLGN) of the anaesthetized, paralysed cat. Here the synthetic enzyme for the production of nitric oxide, nitric oxide synthase, is found only in the presynaptic terminals of the cholinergic input from the brainstem. In our hands, iontophoretic application of inhibitors of this enzyme resulted both in significant decreases in visual responses and decreased responses to exogenous application of NMDA, effects which were reversed by coapplication of the natural substrate for nitric oxide synthase, L-arginine, but not the biologically inactive isomer, D-arginine. Nitroprusside and S-nitroso-N-acetylpenicillamine (SNAP), nitric oxide donors, but not L-arginine, were able to increase markedly both spontaneous activity and the responsiveness to NMDA application. Furthermore, SNAP application facilitated visual responses. Responses of cells in animals without retinal, cortical and parabrachial input to the LGN suggest a postsynaptic site of action of nitric oxide. This modulation of the gain of visual signals transmitted to the cortex suggests a completely novel pathway for nitric oxide regulation of function, as yet described only in primary sensory thalamus of the mammalian central nervous system.
Afferent Pathways↗
The influence of nitric oxide on perigeniculate GABAergic cell activity in the anaesthetized cat.
We have tested the effect of iontophoretic application of the nitric oxide synthase inhibitor L-nitroarginine on the activity of a population of 53 perigeniculate (PGN) cells, recorded extracellularly in the anaesthetized paralysed cat. In all cells tested with visual stimulation during L-nitroarginine application (n = 15), the visually elicited responses were markedly reduced, on average by 63 +/- 15%, and there was a reduction in spontaneous activity too. This effect was blocked by co-application of the substrate for nitric oxide synthase, L-arginine, but not by the inactive D-isoform, although application of L-arginine alone was without effect. Pressure application of the nitric oxide donor S-nitroso-N-acetylpenicillamine (SNAP) elevated both visual responses and spontaneous discharge, an effect also seen with a second nitric oxide donor, sodium nitroprusside (n = 12). The nitric oxide synthase inhibitor L-nitroarginine was applied to a sub-population of seven cells and it selectively decreased NMDA mediated excitation (reduction 80 +/- 14%) with little or no effect on the excitation mediated by alpha-amino-3-hydroxy-5-5-methyl-4-isoxazole-propionic acid (AMPA) or quisqualate (effects not statistically significant), and it had no effect (n = 7) on excitation mediated by the metabotropic agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD). Furthermore, application of SNAP also increased the magnitude of excitatory responses mediated by NMDA receptors. On a different population of seven cells, application of the new NO donor diethylamine-nitric oxide (DEA-NO) enhanced the actions of NMDA without an effect on responses to AMPA. These effects are qualitatively and quantitatively similar to those we have previously described for X and Y type cells in the dorsal lateral geniculate nucleus (dLGN), despite the known opposite effects of acetylcholine (ACh) application in the dLGN and PGN (ACh is co-localized with nitric oxide synthase at both sites). We propose that within the PGN nitric oxide acts to enhance transmission utilizing NMDA receptors selectively (thereby interacting with the globally inhibiting effect of ACh at this site) to enhance visual responses, reducing or removing the non-specific inhibitory drive from PGN to dLGN seen in the spindling activity of slow-wave sleep. These effects will act in concert with the facilitatory actions of both ACh and nitric oxide within the dLGN proper, and will thereby enhance the faithful transmission of visual information from retina to cortex.
Animals↗
Treatment of posttransplant lymphocele with povidone-iodine sclerosis: long-term follow-up.
Percutaneous transcatheter sclerosis with iodate-povidone has been proposed as a treatment of posttransplant lymphocele. We treated 19 lymphoceles with iodate-povidone, 10 of them totally resolved and 6 promptly recurred. Three recurrences were treated conservatively and in 3 the treatment was repeated with success. Therefore, we have a low recurrence and retreatment rate. Our total resolution rate was 100%. Complications due to the treatment were rare. In the long term no patient has developed any renal or perirenal complication related to iodine sclerosis. We conclude that iodine sclerosis is a safe and effective treatment of posttransplant lymphocele. We think that surgical procedures must be reserved to collections adjacent to renal hilum or inaccessible for safe puncturing.
Follow-Up Studies↗
Ifosfamide and vinorelbine as first-line chemotherapy for metastatic breast cancer.
PURPOSE: To evaluate the efficacy and toxicity of the combination of ifosfamide (IFX) and vinorelbine (VNB) as first-line chemotherapy in metastatic breast cancer (MBC). PATIENTS AND METHODS: Between August 1993 and August 1995, 45 patients with untreated MBC received a regimen that consisted of IFX 2 g/m2 by 1-hour intravenous (i.v.) infusion on days 1 to 3, mesna 400 mg/m2 by i.v. bolus at hours 0 and 4 and 800 mg/m2 orally at hour 8 on days 1 to 3, and VNB 35 mg/m2 by 20-minute i.v. infusion on days 1 and 15. Courses were repeated every 28 days. During the first course only, half-dose VNB (17.5 mg/m2) was administered on days 8 and 22. The median age was 53 years and 30 patients (67%) were postmenopausal. Dominant sites of disease were soft tissue in nine patients, bone in seven, and visceral in 29. RESULTS: Objective responses (ORs) were recorded in 25 of 43 assessable patients (58%; 95% confidence interval, 43% to 73%). Complete remissions (CRs) occurred in six patients (14%) and partial remissions (PRs) in 19 (44%). No change (NC) was recorded in 10 patients (23%) and progressive disease (PD) in eight patients (19%). The median time to treatment failure was 12 months and the median survival duration 19 months. Myelosuppression was the limiting toxicity, mainly leukopenia in 32 patients (74%). In contrast, anemia and thrombocytopenia were mild. Other significant toxicities included peripheral neuropathy in nine patients (21%), constipation in 15 (35%), and myalgias in 11 (26%). CONCLUSION: IFX/VNB is an active combination against MBC with moderate toxicity and deserves further evaluation.
Adult↗
MR urography using HASTE imaging in the assessment of ureteric obstruction.
OBJECTIVE: The purpose of this study was to evaluate an MR sequence using half-Fourier acquisition single-shot turbo spin-echo (HASTE) imaging in the assessment of ureteric obstruction. SUBJECTS AND METHODS: We prospectively evaluated 111 kidneys in 56 consecutive patients with HASTE MR urography and compared that imaging technique with excretory urography. The HASTE sequence was used to acquire images in the axial, sagittal, and coronal planes while patients held their breath. Level of obstruction and ureteric diameter were assessed, and the time required to determine the level of obstruction by both techniques was noted. RESULTS: With HASTE MR urography, we correctly diagnosed obstruction in 41 (100%) of 41 kidneys. Of the obstructed kidneys in which the ureter was shown by both excretory urography and MR urography, agreement was high (kappa = .642) between the two imaging techniques regarding the level of obstruction. HASTE MR urography showed perirenal fluid in 20 (87%) of 23 acutely obstructed kidneys. HASTE MR urography showed the site of obstruction on the first 13-sec scan in 33 (80%) of 41 kidneys. CONCLUSION: HASTE MR urography accurately and rapidly shows the level and degree of ureteric obstruction. It can be used to differentiate between acute and chronic obstruction on the basis of its ability to show perirenal fluid.
Acute Disease↗
Vascular neurosurgery: aneurysms, arteriovenous malformations, subarachnoid hemorrhage, and intracranial hemorrhage.
Cerebrovascular disease continues to be a major source of morbidity and mortality in our aging population. Endovascular therapy for the treatment of cerebral aneurysms and associated vasospasm is gaining credibility. Some arteriovenous malformations considered inoperable in the past can now be successfully treated using multimodality therapy. Quantitative measurement of cerebral blood flow is helping to identify patients at risk of ischemic events and defining new guidelines for intervention. New noninvasive imaging modalities may replace conventional angiography for surgical disease. Advances in technology continue to improve our ability to treat cerebrovascular disease prior to irreversible ischemic events.
Cerebral Hemorrhage↗
Tumor vascularization, mitotic index, histopathologic grade, and DNA ploidy in the assessment of 114 head and neck squamous cell carcinomas.
BACKGROUND: Quantification of tumor vascularization recently has been shown to a parameter of potential clinical significance. Several basic and clinical studies have demonstrated that tumor growth correlates significantly with angiogenesis. METHODS: To determine the utility of quantification of tumor vascularization and mitotic index for the pathobiologic assessment of head and neck squamous cell carcinoma, a prospective study of 114 consecutively recruited primary neoplasms was performed. Tumors were also studied for differentiation, keratinization, nuclear atypia, growth pattern, inflammation, desmoplasia, vascular tumor emboli, and DNA content. RESULTS: In this cohort, tumor vascularization was correlated with mitotic index (P < 0.001), nuclear grade (P = 0.03), presence of tumor emboli in the peripheral microvessels (P = 0.05), and lymph nodal status (P = 0.03). A strong relationship between poor differentiation and high N classification (P < 0.001), differentiation and keratinization (P < 0.001) and tumor cell emboli and clinically involved lymph nodes (P = 0.01) was also observed. Emboli were more rare in laryngeal and oropharynx/oral cavity tumors than in hypopharynx/epilarynx (P = 0.02). CONCLUSIONS: This study indicates that tumor vascularization, differentiation, and tumor emboli in peripheral microvessel network are important histologic parameters in the assessment of squamous cell carcinoma of the head and neck.
Adult↗
The current status of academic-mental health linkages in Rhode Island.
The purpose of this study is to describe the current status of academic-public mental health linkages in the State of Rhode Island by querying key informants concerning their opinions in the following areas: clinical orientation and preferred clinical interventions, specific approaches to academic-mental health linkages, training and educational opportunities, obstacles to a career working with persons who have persistent and severe mental illness, and recommendations to improve academic-mental health linkages. Forty-eight of sixty key informants, among them academics, mental health administrators, clinical practitioners and consumer advocates, responded to the mailed survey. More than half the respondents rated affective disorders, schizophrenia and substance abuse to be their highest concern as professionals; most subscribed to biological models of mental illness as well as a variety of prevailing treatment strategies employed in the care of persons with severe mental illness; generally they rated the current status of academic-mental health linkages to be low, but recommended a range of remedies to improve and increase collaborative efforts.
Community Mental Health Services↗
Safety of pneumococcal revaccination.
Indications for pneumococcal polysaccharide revaccination include highest-risk patients vaccinated more than six years previously, but there is controversy regarding revaccination of patients with chronic medical conditions and revaccination of the elderly. The object of the study was to investigate whether revaccination with the pneumococcal polysaccharide vaccine would cause significant adverse reactions. 151 patients were revaccinated and completed a questionnaire concerning the 72 hours after the injection. Valid data were obtained from 127 patients. Mild systemic reactions varied from 4% to 8% and local reactions varied from 40% to 60%, which is not different from the reported reaction with the initial vaccination. This profile of adverse reactions after revaccination should minimize concerns about revaccination.
Aged↗
Concealed umbilical stoma: description of a modified technique.
PURPOSE: We describe a technique for creating a concealed umbilical stoma. MATERIALS AND METHODS: The base of the umbilicus is used as a superiorly based skin flap that is incorporated into the spatulated stoma. Six patients have undergone diversion using this technique. The stoma was constructed from appendix in 4 cases, stomach in 1 and tapered ileum in 1. RESULTS: All patients achieved an easily catheterizable hidden umbilical stoma, are dry on clean intermittent catheterization and have had no stomatitis or peristomal hernia. CONCLUSIONS: This technique for creating a concealed umbilical stoma preserves the native appearance of the umbilicus and combines a superior cosmetic result with an easily catheterizable stoma.
Adolescent↗
High-dose cisplatin with dipyridamole in advanced non-small cell lung cancer. A Grupo Oncológico Cooperativo del Sur study.
From March 1991 to October 1992, 41 patients with advanced non-small cell lung cancer (NSCLC) (20 stage IIIB and 21 stage IV) received a regimen consisting of cisplatin (CP) 100 mg/m2 i.v. days 1 and 8, and dipyridamole (DPD) 100 mg p.o. 75 minutes before CP, and then at hours 6, 12, and 18 as first-line chemotherapy. Cycles were repeated every 28 days for a total of 3. Median age was 56 years (range: 40-70). All patients had a performance status 0 to 1 and a weight loss < or = 10%. Squamous-cell carcinoma was diagnosed in 19 patients; adenocarcinoma in 16, and large-cell carcinoma in 6. A total of 37 patients were fully evaluable for response, whereas 39 were assessable for toxicity. No complete responses were observed: 5 patients (14%) achieved partial response; 23 patients (62%) showed no change, and progressive disease was observed in 9 (24%). The median time to treatment failure was 4 months, whereas median survival was 8 months. The average dose intensity received at the end of the third course of therapy was 46 mg/m2/week. There were no drug-related deaths. Toxicity was mild to moderate, with a high incidence of ototoxicity (54%) and emesis (67%). In conclusion, these results failed to demonstrate any significant advantage from a high-dose CP regimen modulated by DPD in patients with advanced NSCLC.
Adult↗
The effect of creatine monohydrate ingestion on anaerobic power indices, muscular strength and body composition.
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Administration, Oral↗