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Biomedical subjects

J Perez

Publications and source records attributed to J Perez.

At least 109 records · Page 6Linked to original sources
PubMed1996

p53 and PCNA expression in advanced colorectal cancer: response to chemotherapy and long-term prognosis.

In a series of 71 patients with advanced colorectal cancer treated with biochemically modulated 5-fluorouracil (5-FU) and methotrexate (MTX), we investigated the relationship between the proliferating-cell nuclear antigen (PCNA) (PC10) and p53 (Pab1801) primary-tumor immunohistochemical expression with respect to clinical response and long-term prognosis. Nuclear p53 expression was demonstrated in 44% of samples (any number of positive tumor cells) while all tumors showed a certain degree of PCNA immunostaining. PCNA immunostaining was correlated with histopathologic grade and p53 expression, while p53 was not correlated with any of the parameters considered. The probability of clinical response to biochemically modulated 5-FU was independent of p53 and PCNA expression. p53 expression (all cut-off values) was not associated with short- or long-term clinical prognosis, whereas patients with higher PCNA primary-tumor expression showed longer survival from treatment and survival from diagnosis, according to univariate and multivariate analysis, particularly in the sub-set of colon-cancer patients. We conclude that the clinical response of advanced-colorectal-cancer patients to biochemically modulated 5-FU and MTX cannot be predicted by PCNA and p53 primary-tumor expression, but high PCNA expression appears to be independently related to long-term prognosis.

Adult↗
PubMed1996

Fluvoxamine and lithium in long-term treatment of unipolar subjects with high recurrence rate.

We prolonged from 24 to 36 months a follow-up study of unipolar subjects with a high probability of recurrence treated with fluvoxamine (n = 32) or lithium (n = 32). During the extra observation period, two patients developed mania and were excluded from the study. There were no further recurrences in either the lithium or the fluvoxamine group. In our sample, previous prescriptions of tricyclics seem to predict a worse prognosis.

Adult↗
PubMed1996

Abnormal pattern of platelet APP isoforms in Alzheimer disease and Down syndrome.

OBJECTIVE: To determine if changes in levels of amyloid precursor protein (APP) isoforms in periphery are associated with Alzheimer disease and Down syndrome. DESIGN: After subjects were grouped according to diagnosis, APP isoform levels in platelets were compared. SETTING: University medical center. SUBJECTS: Ten patients who fulfilled diagnostic criteria for probable Alzheimer disease, 22 healthy volunteers, and 7 elderly (mean age, 42.7 years) and 7 young (mean age, 19.0 years) patients with Down syndrome. MAIN OUTCOME MEASURES: The levels of APP isoforms were evaluated by means of Western blot analysis and immunostaining of whole platelets. RESULTS: The ratio between the 130- and the 106- to 110-kd APP isoforms was markedly lower in patients with Alzheimer disease and in elderly patients with Down syndrome than in control subjects. In young patients with Down syndrome, the ratio did not significantly differ from that in control subjects. CONCLUSIONS: A consistent alteration in platelet APP isoforms has been found in Alzheimer disease and Down syndrome. Further studies will determine whether this alteration could provide a peripheral biochemical marker of the disorder and whether it could intervene in the pathogenesis of Alzheimer disease.

Aged↗
PubMed1996

Regulation of interleukin-10 production by beta-adrenergic agonists.

Catecholamines have been shown to inhibit some aspects of macrophage activation through a beta receptor-dependent mechanism. This study was undertaken to analyze the effects of isoproterenol, a specific beta-adrenergic agonist, on the synthesis of interleukin-10 (IL-10), a major macrophage-deactivating factor. Isoproterenol increased IL-10 release from lipopolysaccharide-(LPS)-activated mouse peritoneal macrophages in a dose-dependent manner. A significant effect was already observed with 1 microM isoproterenol, while a 4.5-fold increase was achieved with 10 microM. This increase was observed only if macrophages were exposed to isoproterenol for at least 2 h before LPS challenge. It was apparent within 0.5 h and persisted through 24 h at all the LPS concentrations used. A similar increase was observed at the IL-10 mRNA level, as judged by enzyme-linked immunosorbent assay-polymerase chain reaction. The macrophage response to isoproterenol that led to cyclic AMP accumulation was markedly inhibited by H-89, a potent inhibitor of protein kinase A. These data suggest the involvement of cyclic AMP in the regulation of IL-10 synthesis by isoproterenol. IL-10 was in turn partly responsible for a reduction in tumor necrosis factor-alpha synthesis. In vivo, the administration of oxprenolol, a beta-receptor antagonist, significantly reduced serum IL-10 levels 90 min after LPS challenge. Thus, the present study provides the first evidence that endogenous catecholamines are of critical importance in determining the magnitude of the IL-10 response in experimental endotoxemia.

Adjuvants, Immunologic↗
PubMed1996

Inhibitory effect of lithium on cAMP dependent phosphorylation system.

The aim of the present study was to assess the direct effect of lithium on cAMP dependent phosphorylation. The results show that lithium, but not rubidium, at therapeutic and high concentrations significantly decreases the cAMP stimulated MAP2 endogenous phosphorylation in microtubule fraction. An inhibitory effect of lithium has also been found using purified heat stable microtubule proteins phosphorylated by the catalytic subunit of PKA. These data suggest a direct effect of lithium on the cAMP dependent protein kinase.

1-Methyl-3-isobutylxanthine↗
PubMed1996

Air bag-related fatality in a short, forward-positioned driver.

Air bag-related fatalities are rare. We report the case of a 17-year-old girl-4 feet, 11 inches tall-who sustained a fatal basilar skull fracture when her vehicle's air bag deployed during a lowspeed motor vehicle accident. This case emphasizes the need for seat belt use in air bag-equipped vehicles. Further study is needed to clarify the increased risk to shorter individuals and to those who drive with the seat in the far-forward position.

Accidents, Traffic↗
PubMed1996

Does total hip arthroplasty predispose to chronic venous insufficiency?

One hundred thirty-four limbs (40% retrieval) were reviewed 14 to 21 years after total hip arthroplasty. Each had been screened for deep vein thrombosis following surgery by the fibrinogen uptake test, with proximal thrombi confirmed venographically. The limbs were assessed for chronic venous insufficiency with a standard clinical grade and photoplethysmography. Clinical chronic venous insufficiency was found in 4 of 36 (12%) limbs without and 11 of 98 (11%) with previous thrombosis (chi-square = .09, P = .77). Clinical chronic venous insufficiency was detected in 9% of limbs (6/67) with calf thrombi, 0% of limbs (0/11) with isolated femoral thrombi, and 25% of limbs (5/20) with calf and femoral thrombi. After photoplethysmographic assessment, only 2 of 98 (2%) cases were thought to be attributable to thrombosis after hip arthroplasty (95% confidence interval, 0.2-7.2). Despite a high incidence of deep vein thrombosis diagnosed on the fibrinogen uptake test after total hip arthroplasty, symptomatic deep chronic venous insufficiency was an unusual outcome 14 to 21 years later.

Aged↗
PubMed1996

Ifosfamide and cisplatin as neoadjuvant chemotherapy for advanced cervical carcinoma.

A phase II trial was performed to evaluate the efficacy and toxicity of a combination of cisplatin (CDDP) and ifosfamide (IFX) as neoadjuvant chemotherapy in advanced cervical carcinoma (ACC). Between August 1991 and September 1993, 57 untreated patients with stages IIB to IVA were entered into this study. Median age was 44 years (range, 25 to 74 years). The distribution by stages (International Federation of Gynecology and Obstetrics) was as follows: IIB, 31 patients; IIIB, 21 patients; and IVA, 5 patients. Therapy consisted of IFX 2000 mg/m(2) 1-h i.v. infusion days 1 to 3; mesna 400 mg/m(2) i.v. bolus at hours 0 and 4, and 800 mg p.o. at hour 8; and CDDP 100 mg/m(2) on day 3. Cycles were repeated every 28 days for a total of three courses. Both staging and response assessment were performed by a multidisciplinary team. An objective response was observed in 30 of 56 patients (54%; 95% confidence interval, 41 to 67%). Four patients (7%) had a complete response (CR) and 26(46%) had a partial response (PR). Patients with CR or operable PR underwent surgery, otherwise received definitive radiotherapy. Toxicity was mild to moderate. There were no toxicity related deaths. These results indicate that IFX/CDDP is an active combination for ACC with mild toxicity. The results of phase III studies that evaluate the real impact of neoadjuvant chemotherapy are awaited.

Adult↗
PubMed1996

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↗
PubMed1996

Comparison of five plating media for isolation of Salmonella species from human stools.

A comparative study was carried out to evaluate the performances of different culture media for the recovery of Salmonella spp. from 1,000 routine samples of human stools. By direct plating we tested Salmonella-Shigella agar (SS), Hektoen enteric agar (HE), bismuth sulfite agar (BS), novobiocin-brilliant green-glycerol-lactose agar (NBGL) and SM-ID medium (SM), and after selenite enrichment, we tested all of the media except HE. C8-esterase and oxidase tests were used for the screening of Salmonella spp. on SS and HE. The total number of Salmonella isolates from direct culture was 74, with respective sensitivities and positive predictive values (PPVs) of 78.4 and 61%, 64.9 and 18.7%, 36.5 and 34.2%, 55.4 and 20.7%, and 39.2 and 43.9% for NBGL, SS, HE, BS, and SMID, respectively. After enrichment, the total number of Salmonella isolates was 88. The respective sensitivities and PPVs obtained were 90.9 and 62.5%, 92 and 17%, 90.9 and 32% and 93.2 and 71.3% for NBGL, SS, BS, and SM, respectively. According to our results, NBGL in direct plating was the medium with the highest sensitivity with respect to the sensitivities of the other media, with significant statistical differences (P < 0.05). Likewise, the PPV for NBGL was also the highest (61%). After enrichment in selenite broth, the sensitivities of the four media tested were similar, with the best PPV obtained with SM (71.3%); this was followed by NBGL (62.5%). When C8-esterase was used on SS or HE, the PPVs improved from less than 40% to about 100%.

Culture Media↗
PubMed1996

Double-blind controlled trial of sertraline versus paroxetine in the treatment of delusional depression.

OBJECTIVE: In this study the authors evaluated the efficacy and the tolerability of sertraline and paroxetine in the treatment of delusional depression. METHOD: Under double-blind conditions, 46 hospitalized patients who met the DSM-III-R criteria for major depression with psychotic features were treated with sertraline or paroxetine for 6 weeks. RESULTS: The response rates were 75% and 46% for sertraline and paroxetine, respectively. The dropout rate was substantial (41%) in the paroxetine group and was attributable to side effects. CONCLUSIONS: Selective serotonin reuptake inhibitors administered alone are useful in the treatment of delusional depression.

1-Naphthylamine↗
PubMed1996

Fluvoxamine alone in the treatment of delusional depression.

OBJECTIVE: The aim of this study was to evaluate the efficacy of fluvoxamine in the treatment of delusional depression. METHOD: Fifty-nine inpatients who met the DSM-III-R criteria for major depression with psychotic features were treated with fluvoxamine for 6 weeks. Patients were assessed at baseline and weekly thereafter with the Hamilton Depression Rating Scale and the Dimensions of Delusional Experience rating scale. RESULTS: Of the 57 subjects completed the trial, 84.2% (N=48) recovered. The index episodes of the patients who did not respond to fluvoxamine were of significantly longer duration than those of the responders. CONCLUSIONS: Fluvoxamine has a response rate similar to that of the currently most efficacious treatments for delusional depression, including antidepressants plus antipsychotics and ECT.

Age of Onset↗
PubMed1996

beta PP and Tau interaction. A possible link between amyloid and neurofibrillary tangles in Alzheimer's disease.

Extracellular deposition of amyloid fibrils and intraneuronal accumulation of paired helical filaments (PHFs) are the neuropathological hallmarks of Alzheimer's disease. The major constituent of amyloid fibrils is a 39- to 43-residue peptide (termed A beta), which is derived from a 695- to 770-amino-acid precursor protein (termed beta PP). The main component of PHFs identified so far is the microtubule-associated protein tau. Yet, there is no direct evidence of interconnection between these two pathological states. We report here that antibodies to an epitope located between residues 713 and 723 of beta PP770 (ie, the transmembrane region of beta PP distal to A beta) consistently labeled PHFs in the brain of Alzheimer patients. Solid phase immunoassay showed that a peptide homologous to residues 713 to 730 of beta PP770 bound tau proteins. This beta PP peptide spontaneously formed fibrils in vitro and, in the presence of tau, generated dense fibrillary assemblies containing both molecules. These data suggest that beta PP or beta PP fragments containing the tau binding site are involved in the pathogenesis of PHFs in Alzheimer's disease.

Alzheimer Disease↗
PubMed1996

Transcranial duplex-sonography in intracranial hemorrhage. Evaluation of transcranial duplex-sonography in the diagnosis of spontaneous and traumatic intracranial hemorrhage.

The aim of this prospective clinical study was to evaluate the potential of bedside transcranial color-coded duplex sonography (TDS) in the assessment of patients with acute intracranial hemorrhage and respective complications. 74 patients (35 with spontaneous and 27 with traumatic hemorrhage, 12 excluded due to insufficient insonability) underwent 152 TDS examinations. The results were compared to computer-tomography (CT) as well as conventional transcranial Doppler sonography (TcD). The size and localisation of intracerebral hemorrhages as detected in TDS coincided in 39/42 examinations with CT findings; in cases of traumatic intracranial extracerebral hematoma TDS correlated in all but one case (18/19). The TDS findings for the diameter of third and lateral ventricles (n = 126) as for midline-shift (n = 26) showed a good correlation (p < 0.0005) to CT-measurements. TDS appears to be a useful bedside, non-invasive tool in order to detect and exclude intracranial complications in patients with intracranial hemorrhages.

Cerebral Hemorrhage↗
PubMed1995

The antiinflammatory activity of topically applied novel calcium-channel antagonists.

The antiinflammatory activities of two novel calcium-channel antagonists, AGN 190742 and AGN 190744, were evaluated in murine models of cutaneous inflammation. These 2(5H)-furanone ring compounds block both depolarization-dependent Ca2+ entry and receptor-mediated responses in GH3 cells. Topical application of AGN 190742 or AGN 190744 inhibits neutrophil infiltration and epidermal hyperplasia induced by repeated treatment of mouse skin with phorbol ester. AGN 190744 also is active in an arachidonic acid model of acute inflammation. These data suggest that topical application of calcium-channel antagonists can inhibit cutaneous inflammatory responses and that AGN 190742 and/or AGN 190744 may serve as useful pharmacological probes for examining these responses in vivo.

Administration, Cutaneous↗
PubMed1995

Embryonic and postnatal mRNA distribution of five somatostatin receptor subtypes in the rat brain.

The messenger RNA (mRNA) expression of somatostatin (SRIF) receptors SSTR-1, SSTR-2, SSTR-3, SSTR-4 and SSTR-5 (called sst1-5, now) was studied in rat brain between embryonic day 17 (E17) and post-natal day 5 (P5) by in situ hybridization histochemistry and compared to that of adult rats. sst1 receptor mRNA expression was very low and restricted at E17, spread out at E18, to reach very high levels comparable to that of adult at P5 (e.g. in temia tecta, posteromedial cortical amygdaloid nucleus, subiculum). At E17/E18, sst2 receptor mRNA expression was low and limited (telencephalon); significant levels were present at P5 in allocortex, hippocampus, locus coeruleus, similarly to adult brain. sst3 receptor mRNA was high at E17 in most brain regions, and almost as ubiquitous as in adult brain at P5. sst4 receptor mRNA was apparently absent at E17, with low levels in the hippocampus, amygdala and habenula at E18; a wider distribution, especially in the hippocampus and cerebral cortex was observed at P5, similar to that of adult. sst5 receptor mRNA was not detected at E17 and negligible at E18; low levels were found in the cortex, hippocampus and cerebellum at P5. However, in adult brain, only the cerebellum and hind-brain showed some sst5 receptor mRNA transcripts. The presence and distribution of SRIF receptor mRNAs differs substantially in embryo and adult brain. Some mRNAs are present throughout development, while others proceed only postnatally to the adult form. There are striking differences within and between the different SRIF receptor mRNAs, suggesting a role in neurogenesis for some SRIF receptors (e.g. sst2). However, mRNA and protein levels do not necessarily correlate.

Age Factors↗