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Biomedical subjects

J Gonzalez

Publications and source records attributed to J Gonzalez.

At least 73 records · Page 4Linked to original sources
PubMed1999

Development of muscarinic analgesics derived from epibatidine: role of the M4 receptor subtype.

Epibatidine, a neurotoxin isolated from the skin of Epipedobates tricolor, is an efficacious antinociceptive agent with a potency 200 times that of morphine. The toxicity of epibatidine, because of its nonspecificity for both peripheral and central nicotinic receptors, precludes its development as an analgesic. During the synthesis of epibatidine analogs we developed potent antinociceptive agents, typified by CMI-936 and CMI-1145, whose antinociception, unlike that of epibatidine, is mediated via muscarinic receptors. Subsequently, we used specific muscarinic toxins and antagonists to delineate the muscarinic receptor subtype involved in the antinociception evoked by these agents. Thus, the antinociception produced by CMI-936 and CMI-1145 is inhibited substantially by 1) intrathecal injection of the specific muscarinic M4 toxin, muscarinic toxin-3; 2) intrathecally administered pertussis toxin, which inhibits the G proteins coupled to M2 and M4 receptors; and 3) s.c. injection of the M2/M4 muscarinic antagonist himbacine. These results demonstrate that the antinociception elicited by these epibatidine analogs is mediated via muscarinic M4 receptors located in the spinal cord. Compounds that specifically target the M4 receptor therefore may be of substantial value as alternative analgesics to the opiates.

Alkaloids↗
PubMed1999

[Endoesophageal prosthesis as palliative treatment for malignant esophageal stenosis: cooperative study of the Northwest of the Buenos Aires Province].

PURPOSE: To show the experience in rigid prosthesis used as a palliative treatment for malignant++ esophageal stenosis. MATERIAL AND METHOD: From November 1995 to January 1997, 14 patients between 51 and 83 years old, were referred for rigid prosthesis in a prospective way (71.5 = 2.3); 11 of them were men and 3 women. The criteria for including them was: 11 (eleven) patients suffering from esophagus cancer stage IV; 2 (two) patients suffering from stomach cancer with esophageal invasion stage IV and 1 (one) patient with mediastinum metastasis of breast cancer. Wilson-Cook rigid prosthesis was used for all these cases. The insertion technique was "the dilator method". RESULTS: Successful method: 14 (100%). Mortality: Not recorded. Disorders: In 6 (six) patients (42.8%); 3 (three) (21.4%) at an early stage: migrations and 3 (21.4%) at a later stage: 2 (two) tamponade because of food and 1 (one) magration. Time in hospital or clinic: 24 hours (100%). Improvement on Dysphagia: 14 (100%). Following: 13 (92.8%). Survivance: 18-266 days (92 = 83.6). CONCLUSIONS: 1. High percentage of success in prosthesis setting. 2. No mortality. 3. Low percentage of complications and if so, of minor importance. 4. Minimal time in hospital or clinic. 5. Quick and effective dysphagia improvement. 6. Appropriate follow up. 7. Survival similar to other palliative methods, less morbimortality and cost and better life conditions.

Aged↗
PubMed1998

Over-expression of epidermal growth factor receptor and c-erbB2/neu but not of int-2 genes in benign prostatic hyperplasia by means of semi-quantitative PCR.

It is well established that activation of cellular genes may trigger uncontrolled cell growth and cancer development. Previous reports suggest that the epidermal growth factor receptor (EGFr), c-erbB2/neu and int-2, fibroblast growth factor-3, may be implicated in the development of benign prostatic hyperplasia (BPH). Using the polymerase chain reaction technique, we have assessed the amplification and expression of these molecular markers in 30 prostate samples from patients with BPH as well as from 5 normal donors. We detected mRNA over-expression of EGFr and c-erbB2/neu in 36% and 63%, respectively, of the BPH samples, but no gene amplification was found. No amplification or over-expression of int-2 was detected in any of the samples analyzed, suggesting that int-2 is not involved in BPH. Our results thus suggest a role for EGFr and c-erbB2/neu but not for int-2 in the development of BPH.

Aged↗
PubMed1998

Androgen-independent basal cell re-epithelialization, c-erbB-2 mRNA expression and androgen-dependent EGFr mRNA expression in benign prostatic hyperplasia explant cultures treated with finasteride.

We have analyzed the effects of the 5alpha-reductase inhibitor, finasteride (MK906), on the mRNA expression of the epidermal growth factor receptor and c-erbB-2 genes, in benign prostatic hyperplasia explant cultures treated with testosterone and with testosterone plus finasteride. A decrease of the epithelial cell content and an androgen-independent basal cell re-epithelialization was observed during the first 10 days of culture, suggesting a role of basal cells as stem cells involved in androgen-independent epithelial regeneration. Using a semi-quantitative reverse transcription polymerase chain reaction technique, we observed a significant decrease in expression of the epidermal growth factor receptor in the cultures treated with finasteride whereas no effect of finasteride on c-erbB-2 transcription was detected, although the expression of both genes was increased by dihydrotestosterone.

Cholestenone 5 alpha-Reductase↗
PubMed1998

Serum beta-2 microglobulin is a marker of high bone remodelling in elderly women.

Beta-2 microglobulin (beta2m), the water soluble extrinsic light chain of class I MHC, has been recently isolated from the adult bone culture medium. Serum beta2m plays a role as a bone-derived growth factor regulating both osteoblast and osteoclast cell activity. Serum beta2m has been proposed as a bone remodeling biological marker in high bone turnover conditions. The purpose of our study was to determine the relationship between beta2m and vitamin D status in post-menopausal women. We have studied 44 healthy women from 20 to 80 years with normal hepatic and renal function, without diabetes mellitus and/or inflammatory, tumoral or infectious diseases. We measured the serum levels of calcium, phosphorus, parathyroid hormone (PTH), vitamin D binding protein (DBP), 25-OHD3 (calcidiol), 1,25(OH)2D3 (calcitriol) and beta2m. Serum beta2m levels increased with age (r = 0.54, P < 0.001). Post-menopausal women had higher serum levels than pre-menopausal women of beta2m (1.76 +/- 0.22 mg/l vs. 1.35 +/- 0.2 mg/l, P < 0.01); PTH (61.5 +/- 7.5 ng/ml vs. 39 +/- 6 ng/ml, P < 0.001) and lower serum levels of 25-OHD3 (7.5 +/- 2.3 ng/ml vs. 18.2 +/- 2.5 ng/ml, P < 0.001). Moreover, serum levels of beta2m were negatively correlated with 25-OHD3 (r = -0.34, P < 0.05) and with ionized calcium (r = -0.45, P < 0.01) and positively with PTH (r = 0.48, P < 0.01). These results support the role of beta2m as a regulator of bone metabolism and its potential use as a marker of high bone turnover in post-menopausal women, specially in elderly women with vitamin D deficiency and secondary hyperparathyroidism.

Adult↗
PubMed1998

Automated interpretation of high-energy collision-induced dissociation spectra of singly protonated peptides by 'SeqMS', a software aid for de novo sequencing by tandem mass spectrometry.

SeqMS, a software program designed for the automated interpretation of high-energy collision-induced dissociation (CID) mass spectra of singly protonated peptides ionized by fast atom bombardment, has been developed. The software is capable of probing the sequence of an unknown peptide, and even of certain modified peptides. The program, compiled for WINDOWS95 or NT, also permits the retrieval of raw data and the reconstruction of the spectra on a user-friendly graphical interface with the aid of several tools for processing the spectra, which include setting multiple threshold levels and automatic peak detection. SeqMS is capable of generating candidate sequences, based on the detected peaks, and of displaying the resulting assignments for each candidate in a spectrum or in tabular form. The software has the following capabilities: 1) the ions derived from backbone and side-chain fragmentations, internal and immonium ions, and side-chain loss ions can be used for calculation; 2) 18O-labeling of a peptide at the C terminus, a methodology which was developed to differentiate N-terminal from C-terminal ions, is applicable as an optional setting; 3) modified amino acids and N- or C-terminal blocking groups are taken into account for calculation according to the user's setting in a library; 4) amino acid composition and partial or complete amino acid sequence of a peptide can be used as input for calculation; 5) the assignments of signal output in a spectrum can be graphically edited, and then re-calculated based on the edited peaks. The efficacy of the program is demonstrated by testing 74 high-energy CID spectra, obtained using a four-sector instrument, of synthetic, proteolytic, and biologically active peptides, some of which contain modified groups.

Algorithms↗
PubMed1998

Gabapentin bioavailability: effect of dose and frequency of administration in adult patients with epilepsy.

UNLABELLED: Gabapentin (GBP) is a non-metabolized antiepileptic drug that is eliminated by renal excretion and displays saturable, dose dependent absorption. The recommended dosing schedule for GBP is t.i.d. At large daily doses, oral bioavailability (F) may be improved by giving the daily dose more frequently. OBJECTIVE: To evaluate whether switching GBP dosage regimen from t.i.d. to q.i.d. results in increased oral bioavailability. METHODS: This study consisted of two parts; a computer simulated pharmacokinetic model and a clinical pharmacokinetic study in nine adult epileptic patients receiving 3600 mg/day and 11 receiving 4800 mg/day. All patients were evaluated during both t.i.d. and q.i.d. regimens. F were determined by calculation of percent of dose excreted unchanged using steady-state 24-h urine collections and were compared using a paired t-test. RESULTS: At 3600 mg/day, mean F following t.i.d. and q.i.d. dosing were 38.7+/-22.1% and 40.0+/-18.9%, respectively (P=0.738). At 4800 mg/day, mean F following t.i.d. and q.i.d. dosing were 29.2+/-16.2% and 35.6+/-17.6%, respectively (P=0.006). DISCUSSION: Good agreement was observed between values from this study and predicted values based on the pharmacokinetic model. Improved GBP F at doses of 3600 mg/day was not achieved with more frequent drug administration, and thus is not warranted. At 4800 mg/day, a 22% increase in F was observed with more frequent drug dosing. CONCLUSION: GBP F may be significantly increased by q.i.d. versus t.i.d. dosing, depending upon dose level. This increase in F however must be balanced against the inconvenience of more frequent dosing. Therapeutic drug level monitoring may aid in the evaluation of such pharmacokinetic maneuvers.

Acetates↗
PubMed1998

Bronchial microbial patterns in severe exacerbations of chronic obstructive pulmonary disease (COPD) requiring mechanical ventilation.

We carried out a comprehensive microbiological study of the upper and lower airways in patients with severe exacerbations of chronic obstructive pulmonary disease (COPD) requiring mechanical ventilation in order to describe microbial patterns and analyze their clinical significance. Quantitative cultures of tracheobronchial aspirates (TBAs), bronchoscopically retrieved protected specimen brush (PSB) and bronchoalveolar lavage fluid (BALF) at admission to the ICU and after 72 h, as well as serology for bacteria and respiratory viruses were performed. Fifty patients (mean age 68 +/- 8, 46 males) were studied prospectively. Potentially pathogenic microorganisms (PPMs) and/or a positive serology were present in 36 of 50 (72%) patients, including 12 (33%) polymicrobial cases. Only six (12%) had no pathogen in any sample in the absence of antimicrobial pretreatment. Microbial patterns corresponded to community-acquired pathogens (Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis) in 19 of 34 (56%) and to gram-negative enteric bacilli (GNEB), Pseudomonas, and Stenotrophomonas spp. in 15 of 34 (44%) of isolates. Chlamydia pneumoniae and respiratory viruses were found in 18% and 16% of investigations, respectively. Repeated investigation after 72 h in 19 patients with PPMs in the initial investigation revealed eradication of virtually all isolates of community-acquired pathogens and GNEB but persistence of three of five Pseudomonas spp. and both Stenotrophomonas spp. as well as the emergence of new GNEB, Pseudomonas and Stenotrophomonas spp. Clinical parameters neither predicted the presence of PPMs nor of GNEB and Pseudomonas/Stenotrophomonas spp. Nevertheless, severe pneumonia attributable to initially isolated pathogens occurred in two patients with severe COPD exacerbation. We conclude that pathogens were more frequently present than previously reported. The rate of GNEB and Pseudomonas/Stenotrophomonas spp. isolates was high. The presence of pathogens was clinically unpredictable. Thus, in this population of patients with severe exacerbations of COPD, it may be advisable to obtain respiratory samples and to treat according to diagnostic results. Further studies are warranted to clarify this issue.

Aged↗
PubMed1998

Results of screening 1.9 million Texas newborns for 21-hydroxylase-deficient congenital adrenal hyperplasia.

OBJECTIVE: To assess results of newborn screening for 21-hydroxylase-deficient congenital adrenal hyperplasia (CAH) in Texas over 6 years of screening 1.9 million infants. METHODS: In 1989, CAH was incorporated into the ongoing Texas Newborn Screening Program, which requires two screens on each newborn. 17-Hydroxyprogesterone was assayed, without extraction, by radioimmunoassay of blood collected from heel sticks onto filter paper collection cards. Infants with elevated levels of 17-hydroxyprogesterone were referred for evaluation, and those considered to have CAH were studied with respect to disease characteristics. Data were collected by pediatric endocrinologists using standardized forms that included type of CAH, results of laboratory tests, treatment regimen, disease symptoms and signs, and, for girls, degree of genital virilization. RESULTS: The incidence of classic CAH in Texas is 1:16 008, with a ratio of salt-wasting to simple-virilizing of 2.7:1. A majority of infants detected were undiagnosed until screened, despite signs of salt-wasting or ambiguous genitalia. It was difficult to differentiate salt-wasting from simple-virilizing CAH in infants who were identified before the onset of adrenal insufficiency or electrolyte abnormalities. A substantial number of infants with nonclassic (NC) CAH also were detected. Not all infants were detected on the initial screen; 14% of infants with classic CAH and 87% with NC CAH were detected on the second routine screening test. CONCLUSIONS: Our findings confirm the benefits of newborn screening for CAH and the importance of a second screening test, and suggest that programs for newborn CAH screening must consider complex issues in diagnosis and treatment. These results also confirm that CAH is a continuum of disorders, rather than a disorder with discrete subtypes. In addition, the difficulties in differentiating CAH subtypes in newborns, and thus deciding appropriate treatment, and the high incidence of NC CAH suggest that standard diagnostic criteria and treatment regimens for CAH may need modification. Where screening exists, physicians will encounter more cases of CAH than in the past.

17-alpha-Hydroxyprogesterone↗
PubMed1998

Ovarian germ cell tumors.

UNLABELLED: Ovarian germ cell tumors (OGCT) are a special type of ovarian cancers due to their histology, age of presentation, prognosis and treatment. MATERIAL AND METHODS: Eighteen cases of OGCT out of 313 total ovarian cancer diagnosed in Hospital Materno-Infantil Vall d'Hebredn between 1975 and 1994 are present. RESULTS: Mean age of the patients was 36 years. The most frequent symptom at diagnosis was abdominal bloating (44.5%). Echography was the most used diagnostic method (67%). Surgery was conservative in 44% of the cases, radical in 50% of the cases and palliative in one case. The histological types were 6 dysgerminomas and 6 malignant teratomas (33.3%), 3 malignant dermoid cysts (16.7%), 2 yolk sac tumors (11%) and 1 embryonal carcinoma. According to FIGO 1987 staging classification 14 patients were in stage I disease and 4 in stage III disease. Polychemotherapy was performed on 6 patients and postsurgical radiotherapy was performed on 2 patients. Five patients recurred in an average time of 25 months. The five-year survival rate, according to the Kaplan-Meier method, was 80% in stage I and 0% in stage III. Five-year survival rate of patients only surgically treated was 65% and in patients who underwent postsurgical co-adjuvant treatment it was 100%. CONCLUSION: Conservative surgery followed by a BEP regimen may be performed nowadays with efficacy and acceptable toxicity while conserving the fertility of these patients.

Adolescent↗
PubMed1998

Vabra aspirator and pipelle endometrial suction curette. A comparison.

OBJECTIVE: To compare the Pipelle suction curette with the Vabra aspirating catheter in terms of their ability to obtain a sufficient amount of tissue (> or = 1 mm2 of endometrium) in order to make a histologic diagnosis. STUDY DESIGN: A prospective, randomized, double-blind, crossover study at Dartmouth-Hitchcock Medical Center, which serves as the clinical staff of the Dartmouth Medical School. RESULTS: Agreement between the Pipelle and Vabra was high: 74 of 79 (93.7%) samples. The Pipelle obtained adequate samples in 78 of 79 (98.7%) cases as compared with 75 of 79 (94.9%) for the Vabra. The McNemar test comparing these two proportions, adjusting for the fact that the Pipelle and Vabra readings were taken on the same subjects at the same visits, yielded a nonsignificant result (P = .180). CONCLUSION: The Pipelle and Vabra have equal diagnostic accuracy.

Biopsy↗
PubMed1997

Long-term angiographic and clinical outcome after percutaneous transluminal coronary angioplasty and intracoronary radiation therapy in humans.

BACKGROUND: Ionizing radiation has been shown to reduce neointimal formation after balloon angioplasty in experimental models of restenosis. This study was designed to evaluate the feasibility, safety, and effectiveness of intracoronary radiation therapy (ICRT) after percutaneous transluminal coronary angioplasty (PTCA) for preventing restenosis in human coronary arteries. METHODS AND RESULTS: Twenty-one patients (22 arteries) with unstable angina underwent standard balloon angioplasty. ICRT was performed with the use of an 192Ir source wire that was hand delivered to the angioplasty site. Angiographic follow-up was performed at 24 hours, between 30 and 60 days, and at 6 months. Angioplasty was successful in 19 of 22 lesions, and insertion of the radioactive source wire was successful at all treated sites. Angiographic study at 24 hours demonstrated early late loss of the luminal diameter from 1.92+/-0.55 to 1.40+/-0.27 mm. Between 30 and 60 days, repeat angiography demonstrated total occlusion in 2 arteries, a new pseudoaneurysm in 1 artery, and significant dilatation at the treatment site in 2 additional vessels. At > or = 6 months' follow-up, all remaining arteries (n=20) maintained patent, with a mean lumen diameter of 1.65+/-0.8 mm. The calculated late lumen loss was 0.27+/-0.56 mm, and the late loss index was 0.19. Clinical events at 1 year included myocardial infarction in 1 patient, repeat angioplasty to the treated site in 3 patients, and persistent angina in 7 patients. CONCLUSIONS: These preliminary results demonstrate that ICRT after coronary intervention is feasible and is associated with an acceptable degree of complications and lower rates of angiographic restenosis indexes.

Adult↗
PubMed1997

Comparison of aceclofenac with piroxicam in the treatment of osteoarthritis.

A multicentre, double-blind, randomised, parallel group study was undertaken to investigate the efficacy and safety of aceclofenac (123 patients, 100 mg twice daily) in comparison to piroxicam (117 patients, 20 mg once daily and placebo once daily) in patients with osteoarthritis of the knee. The treatment period of two months was preceded by a washout period of one week duration. On completion of the study, patients in both aceclofenac and piroxicam-treated groups exhibited significant improvement in pain intensity and functional capacity of the affected knee, as represented by the Osteoarthritis Severity Index (OSI) (p < 0.0001 and p < 0.001 respectively). This was further substantiated following the patient's assessment of pain intensity using the Visual Analogue Scale (VAS), in which significant improvements were demonstrated at all time points for each treatment group (p < 0.001). Although both treatment groups showed a significant improvement in all investigator's clinical assessments (functional exploration of the knee, knee flexion and extension (EXT)), there were no significant differences between the groups. There was, however, a more rapid improvement in knee flexion in the aceclofenac group after 15 days of treatment. Both aceclofenac and piroxicam were well tolerated by patients, the most commonly reported adverse events being gastrointestinal, although their incidence was low. Only 24 patients on aceclofenac, as opposed to 33 on piroxicam complained of dyspepsia, epigastralgia and pyrosis. While 7 patients in each group were withdrawn because of adverse events, only one patient with piroxicam was withdrawn because of severe upper gastrointestinal bleeding. Twice as many reports of fecal blood loss were made in the piroxicam group in comparison to the aceclofenac group. In summary, this study confirms the therapeutic efficacy of aceclofenac and suggests that it is a well-tolerated alternative NSAID to piroxicam in the treatment of osteoarthritis.

Adult↗
PubMed1997

Performance of selected lightweight wheelchairs on ANSI/RESNA tests. American National Standards Institute-Rehabilitation Engineering and Assistive Technology Society of North America.

OBJECTIVE: This study provides data for clinicians and wheelchair users to compare the durability, stability, and cost effectiveness of three different lightweight wheelchair models: the Everest & Jennings EZ Lite, the Invacare Rolls 2000, and the Quickie Designs Breezy. A second objective was to compare the results from this study to those published for ultralight and institutional depot wheelchairs. DESIGN: Randomized standards testing of three wheelchair models from each manufacturer (nine wheelchairs total). RESULTS: There were no significant differences (p > .05) in fatigue life, life-cycle cost, or static stability between the three models of lightweight wheelchairs (ie, EZ Lite, Rolls 2000, or Breezy). There were, however, significant differences (p < .05) in fatigue life among the lightweight wheelchairs of this study and the published results for ultralight rehabilitation wheelchairs and for depot wheelchairs. The lightweight wheelchairs had an average fatigue life greater than the depot wheelchairs but less than the rehabilitation wheelchairs. A depot-type wheelchair was defined as a manual wheelchair designed for hospital or institutional use. At lightweight wheelchair was defined as a manual wheelchair with minimal adjustments designed for individual or institutional use. An ultralight rehabilitation wheelchair was defined as a manual wheelchair designed for an individual's use as a long-term mobility aid. CONCLUSION: The three models of lightweight wheelchairs tested are substantially similar and their fatigue lives are significantly (p < .05) lower than rehabilitation wheelchairs. Ultralight rehabilitation wheelchairs are the most cost effective over the life of the wheelchair, costing 3.4 times less (dollars per life cycle) than depot wheelchairs, and 2.3 times less (dollars per life cycle) than the lightweight wheelchairs tested in this study.

Cost-Benefit Analysis↗
PubMed1997

Extracorporeal photochemotherapy in progressive systemic sclerosis: a follow-up study.

BACKGROUND: Extracorporeal photochemotherapy (photopheresis), an immune-modulating therapy, has been demonstrated to elicit a therapeutic response in the treatment of several autoimmune disorders. We evaluated the use of photopheresis in the treatment of patients with progressive systemic sclerosis (PSS; scleroderma). METHODS: Five patients with early-onset, diffuse PSS were treated with photopheresis on 2 successive days monthly for an average of 59 months (range 54-89 months). We initially reported the response this group of patients had to photopheresis treatment at an average of 11 months (range 6-21 months). RESULTS: An improvement or stabilization was noted in most patients in skin thickening, joint mobility, pulmonary function studies, oral aperture, functional index, as well as symptoms including Raynaud's phenomenon, dyspnea, fatigue, dysphagia, arthralgias, and cutaneous ulcers. Renal function tests remained within normal range. A total of 296 monthly treatments were administered without significant toxicity. CONCLUSIONS: This study suggests that extended use of extracorporeal photochemotherapy in the management of early-onset, diffuse PSS is well tolerated and may provide an increasingly beneficial clinical outcome.

Female↗
PubMed1997

[Phototoxic maculopathy after arc welding: value of multifocal ERG].

BACKGROUND: Phototoxic maculopathy most likely results from longer exposure to light from sources such as the sun, welding arcs, tungsten halogen lamp filaments or operation microscopes. The value of the multifocal ERG for the evaluation of functional defects in this rare entity has not been described to date. CASES: We describe the case of a 38-year-old male patient who presented to his local ophthalmologist with bilateral loss of vision and acute ocular pain after having worked for two hours at an electric welding arc. A foveal lesion was found in both eyes, resulting in a bilateral reduction of visual acuity. Nine months later, the patient underwent examination and further investigations at the university eye clinic in Tübingen. Visual field defects on both sides could be detected with automatic threshold perimetry. Using the multifocal ERG with a central element of 2 degrees diameter, a central defect was detected only for the right eye. CONCLUSIONS: In rare cases, a photic maculopathy can result from exposure to light during arc welding. It can be masked in the first days by a phototoxic keratitis. Multifocal ERG and automatic perimetry are useful tools for the detection and quantification of the functional defects.

Adult↗