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C Guzman

Publications and source records attributed to C Guzman.

At least 19 recordsLinked to original sources
PubMed2006

Description of endoscopic ventricular anatomy in myelomeningocele.

OBJECTIVE: The purpose of this work is to present our endoscopic neuroanatomical findings of a series of myelomeningocele and hydrocephalus patients, treated with endoscopic third ventricular cisternostomy (ETVC), in order to describe ventricular configuration abnormalities in this group of patients, in which this neurosurgical procedure has limited performance. METHOD: We checked the videos of 10 endoscopic third ventricular cisternostomies of myelomeningocele patients taken during 24 months as from December 1998. A previous guideline is designed to record anatomic variables in the lateral ventricles, IIIrd ventricle, and basal cisterns. The topic is analyzed in view of the necropsy and imaging background data. RESULTS: The ETVC of lateral ventricles showed: absence of septum (9/10); absence of anteroseptal vein (8/10); absence of choroid plexus and thalamostriate vein (0/10); absence of fornix (1/10): small foramen of Monro (4/10). The ETVC of the IIIrd ventricle showed: impossibility of recognizing any mammillary bodies (4/10); presence of septations (5/10); presence of atypical veins in the floor (6/10); translucent floor (5/10); floor umbilications (5/10); absence of infundibulum (4/10); arachnoid adherences (7/10); and visual contact of basilar artery (4/10). CONCLUSION: There are categorical structural alterations in the ventricular system of myelomeningocele patients that are well correlated with previous necropsy and imaging reports. The ventricular system of dysraphic children presents severe anatomic alterations, which alter the reference points of the classical endoscopic third ventricular cisternostomy.

Cisterna Magna↗
PubMed2005

Ecteinascidin-743 (ET-743) for chemotherapy-naive patients with advanced soft tissue sarcomas: multicenter phase II and pharmacokinetic study.

PURPOSE: To evaluate the response rate, toxicity profile, and pharmacokinetics of ecteinascidin-743 (ET-743) as first-line therapy in patients with unresectable advanced soft tissue sarcoma (STS). PATIENTS AND METHODS: Thirty-six patients with STS were enrolled onto the study between September 1999 and August 2000. Patients were treated with 1.5 mg/m2 of ET-743 given as a 24-hour continuous intravenous (IV) infusion every 21 days. Pharmacokinetic sampling was performed in 23 patients. RESULTS: One complete and five partial responses were achieved in 35 assessable patients for an overall response rate of 17.1% (95% CI, 6.6% to 33.6%). In addition, one patient had a minor response, leading to an overall clinical benefit of 20%. Neutropenia and transaminitis were the main grade 3 to 4 toxicities, which occurred in 33% and 36% of the patients. The estimated 1-year progression-free and overall survival rates were 21% (95% CI, 11% to 41%) and 72% (95% CI, 59% to 88%), respectively. Total body clearance (L/h) was not significantly correlated with body-surface area (r = -0.28; P = .21). Mild hepatic impairment or the extent of prior cytotoxic therapy does not seem to contribute significantly to the high interpatient variability (49%) in the clearance of this drug. Severity of treatment-related toxicity was not correlated with pharmacokinetic variables. CONCLUSION: ET-743 demonstrates clinical activity as first-line therapy against STS with acceptable toxicity. Additional studies to establish empirical dosing guidelines may be necessary to improve the safety of the drug in patients with varying degrees of hepatic dysfunction and definitively establish the role of ET-743 for patients with these malignancies.

Adult↗
PubMed2004

Phase II and pharmacokinetic study of ecteinascidin 743 in patients with progressive sarcomas of soft tissues refractory to chemotherapy.

PURPOSE: To assess the efficacy of the marine-derived alkaloid ecteinascidin 743 (ET-743) in patients with soft tissue sarcomas that progressed despite prior conventional chemotherapy and to characterize the pharmacokinetic profiles of ET-743 in this patient population. PATIENTS AND METHODS: Thirty-six previously treated soft tissue sarcoma patients from three institutions received ET-743 as a 24-hour continuous intravenous (IV) infusion at a dose of 1,500 microg/m(2) every 3 weeks. Pharmacokinetic studies were also performed. Patients were restaged every two cycles for response by objective criteria. RESULTS: Objective responses were observed in three patients, with one complete response and two partial responses, for an overall response rate of 8% (95% CI, 2% to 23%). Responses were durable for up to 20 months. Two minor responses (43% and 47% tumor reduction) were observed, for an overall clinical benefit rate of 14%. The predominant toxicities were neutropenia and self-limited transaminitis of grade 3 to 4 severity in 34% and 26% of patients, respectively. The estimated 1-year time to progression and overall survival rates were 9% (95% CI, 3% to 27%) and 53% (95% CI, 39% to 73%), respectively. The maximum observed plasma concentration and total plasma clearance of ET-743 (mean +/- standard deviation), 1.04 +/- 0.48 ng/mL and 35.6 +/- 16.2 L/h/m(2), respectively, were consistent with previously reported values from phase I studies of the drug given as a 24-hour IV infusion. CONCLUSION: ET-743 is a promising new option for the management of several histologic subtypes of sarcoma. Durable objective responses were obtained in a subset of sarcoma patients with disease progression despite prior chemotherapy. Additionally, the relatively high survival rate noted in this series of previously treated patients further justifies development of this agent.

Adult↗
PubMed2001

Phase I and pharmacokinetic study of ecteinascidin-743, a new marine compound, administered as a 24-hour continuous infusion in patients with solid tumors.

PURPOSE: To define the maximum-tolerated dose (MTD) and the phase II recommended dose (RD) of ecteinascidin-743 (ET-743) given as a 24-hour continuous infusion every 3 weeks to patients with treatment-refractory solid tumors. PATIENTS AND METHODS: Fifty-two patients received a total of 158 cycles of ET-743 at one of nine dose levels (DLs) ranging from 50 to 1,800 microg/m(2). RESULTS: The MTD was defined as 1,800 microg/m(2) (DL 9), and the phase II RD was 1,500 microg/m(2) (DL 8) for moderately pretreated patients with performance status (PS) 0 to 1 and good hepatobiliary function. Neutropenia and thrombocytopenia were the dose-limiting toxicities (DLTs) and were severe at the MTD (1,800 microg/m(2)) in 94% and 25% of cycles, respectively. At the RD (1,500 microg/m(2)), neutropenia and thrombocytopenia were present in 33% and 10% of cycles, respectively. Transient acute elevated transaminase levels occurred in almost all cycles and was severe in 38% of cycles. Severe toxicities and DLTs were observed in patients with poor PS or abnormal liver function or who had received a large number of previous chemotherapy regimens. Antitumor activity was observed at the three highest DLs, including three partial responses (breast cancer, osteosarcoma, and liposarcoma), and four patients (all with progressing soft tissue sarcomas) had stable disease lasting > or = 3 months. Pharmacokinetic studies were performed on all patients for at least the first cycle, giving a linear pharmacokinetic profile; this showed a relationship between area under the curve (AUC) and transaminitis grade and a clear correlation between AUC and severe hematologic toxicity likelihood. CONCLUSION: The RD for a 24-hour continuous intravenous infusion of ET-743 is 1,500 microg/m(2), with the most prevalent DLTs being hematologic. Patients with minor baseline hepatobiliary function abnormalities have a higher likelihood of severe hematologic toxicities and AUC-related DLTs, requiring dose adjustments or delays.

Adult↗
PubMed2001

A comparison of limited sampling strategies for prediction of Ecteinascidin 743 clearance when administered as a 24-h infusion.

PURPOSE: Ecteinascidin 743 (ET-743) is a novel, marine-derived anticancer agent currently under clinical development for the treatment of solid tumors. The aim of this study was to develop and validate limited sampling strategies for the prediction of ET-743 clearance in phase II studies, using two techniques: the stepwise linear regression approach and the Bayesian estimation approach. METHODS: Data from a phase I dose-finding study were used with ET-743 administered as a 24-h infusion. Plasma concentration time data from 34 patients treated with 1200. 1500 or 1800 microg/m2 ET-743 were randomly divided into an index data set, used for the development of the strategies, and a validation data set. With the linear regression approach, clearance (obtained by non-compartmental analysis) was correlated with the ratios of dose to the observed concentrations. For the Bayesian approach a three-compartment population pharmacokinetic model was developed; optimal time-points were selected using the D-optimality algorithm. The strategies were compared by assessment of their predictive performance of CL in the validation data set. RESULTS: The linear regression method yielded a single-point sampling schedule with no significant bias and acceptable precision (-0.03% and 21%, respectively). With the Bayesian approach, a three-sample strategy was selected which resulted in less-accurate, but unbiased, predictions (bias 13%, precision 34%). CONCLUSIONS: Optimal sampling strategies were developed and validated for estimation of ET-743 clearance. Although the linear regression approach showed slightly better predictive performance, the Bayesian approach is preferred for the current phase II studies as it is more robust and flexible and allows the description of the full pharmacokinetic profile.

Adult↗
PubMed2000

Pharmacokinetics and pharmacodynamics of the novel marine-derived anticancer agent ecteinascidin 743 in a phase I dose-finding study.

Ecteinascidin (ET) 743 is an anticancer agent derived from the Caribbean tunicate Ecteinascidia turbinata. Preclinical studies revealed activity of ET-743 against different tumor types. A Phase I clinical trial was designed with ET-743 to identify the maximum tolerated dose and dose-limiting toxicities (DLTs). Furthermore, the pharmacokinetics of ET-743 and relationships with pharmacodynamics were evaluated. Adult patients with solid, resistant tumors received ET-743 as a 24-h i.v. infusion every 21 days. Blood samples were obtained during the first treatment course and in several consecutive courses. Noncompartmental pharmacokinetic analysis was performed. Relationships between pharmacokinetics and hepatic and hematological toxicities were explored. Fifty-two patients were treated at nine dose levels (50-1800 microg/m2). The DLTs, neutropenia and thrombocytopenia, were experienced at 1800 microg/m2. Twenty-five patients were treated at the recommended Phase II dose of 1500 microg/m2. At this dose, the mean value +/- SD for total body clearance was 59 +/- 31 liters/h, and the mean t(1/2) was 89 +/- 41 h. Pharmacokinetics were linear over the dose range tested. Prior exposure to ET-743 did not alter the pharmacokinetics in subsequent courses. The percentage of decrease in WBC count and absolute neutrophil count was correlated to the area under the plasma concentration versus time curve (AUC). Hepatic toxicity, defined as rise in alanine aminotransferase and aspartate aminotransferase, increased with dose and AUC but was reversible and not dose limiting. In conclusion, ET-743 administered as a 24-h i.v. infusion at a dose of 1500 microg/m2 is clinically feasible; severe thrombocytopenia and neutropenia are the DLTs.

Adult↗
PubMed1999

Oral and topical antibiotic therapy of complete, primary acquired nasolacrimal duct obstruction in adults.

PURPOSE: To determine whether patients with complete, acquired nasolacrimal duct obstruction may be treated with broad spectrum oral antibiotics and office lacrimal irrigation. METHODS: In a retrospective review, patients with complete, primary acquired nasolacrimal duct obstruction (NLDO) were divided by predominant symptoms and signs into two main groups: (a) those with tearing and/or mucous discharge and (b) those with previous acute dacryocystitis and/or lacrimal sac mucocele. All patients received a therapeutic trial of oral and topical antibiotics followed by lacrimal irrigation. RESULTS: Five of 55 patients with tearing and/or mucous discharge showed significant improvement after treatment with a mean follow-up of 16.5 months. A sixth patient with mucous and tearing had resolution of the mucous discharge but persistent tearing and blockage of the nasolacrimal system to irrigation. Two of 20 patients with lacrimal sac mucocele or history of acute dacryocystitis avoided surgery while 18 opted for early lacrimal surgical intervention. CONCLUSIONS: Conservative management of complete acquired NLDO consisting of oral and topical antibiotics and appropriately timed office lacrimal drainage system irrigation may be considered in selected patients.

Administration, Oral↗
PubMed1998

Intraduodenal hematoma complicating intestinal biopsy: case reports and review of the literature.

We report two cases of postbiopsy duodenal hematoma and review 14 additional cases. Duodenal hematoma predominantly occurs in children and presents with abdominal pain, vomiting, and pancreatitis. Upper gastrointestinal series, abdominal ultrasound, and CT scan are useful in visualizing the hematoma. No comparative studies of the usefulness of these techniques are available, but a CT is indicated if perforation is suspected. The treatment is conservative if no perforation is detected, and resolution of symptoms generally occurs within 2 wk.

Adolescent↗
PubMed1997

Chronic obstructive pulmonary disease: effects of hypoxia on neurological and neuropsychological measures.

Eighteen patients with chronic obstructive pulmonary disease (COPD) were administered a series of pulmonary, neurological, and neuropsychological measures to test if there was an effect of COPD on neurological and cognitive functioning. Overall, there was no evidence of general dementia in this sample. Measures of immediate and delayed memory, complex attention, and speed of information processing correlated highly with arterial carbon dioxide partial pressure and, to a lesser extent, with oxygen partial pressure. Measures of language abilities, perceptual-motor functioning, and simple attention generally were not related to arterial gas pressures. A similar pattern of findings was obtained when group differences were examined between participants classified as severely hypoxic or mildly hypoxic, although group differences were mitigated by premorbid IQ differences. Hypoxia in COPD results in a relatively focused pattern of impairment in measures of memory function and tasks requiring attention allocation. The memory dysfunction may be related to involvement of limbic memory regions necessary for explicit memory. The attentional deficits were attributed to diffuse brain involvement resulting in reduced resource allocation. Early diagnosis and treatment of the hypoxia is essential.

Aged↗
PubMed1993

Rheumatic manifestations in human immunodeficiency virus positive and negative individuals: a study of 2 populations with similar risk factors.

OBJECTIVE: Assess the impact of human immunodeficiency virus (HIV) infection on the onset of rheumatic manifestations in HIV+ patients, and to compare them with a control HIV- group with similar risk factors. METHODS: We prospectively studied 74 consecutive HIV+ patients, looking for clinical and laboratory findings of rheumatic manifestations and compared them with 72 control subjects with similar risk factors for HIV who tested negative for HIV. RESULTS: Rheumatic manifestations were more frequently observed in the HIV+ group than the HIV-group (p < 0.001): Arthralgias were found in 34 (45%), arthritis in 8 (10%), and Reiter's syndrome in 6 (8%). Laboratory findings revealed rheumatoid factor in 16 (21%) HIV+ vs 2 (2%) in HIV-, antinuclear antibodies in 13 (17%) HIV+ vs 0 in HIV-, IgG anticardiolipin antibodies in 70 (94%) HIV+ vs 7 (9%) in HIV- (p < 0.001). Hyperuricemia was found in 31 HIV+ patients (41%), and hypouricemia in 4 (5%), compared with none in the HIV- group (p < 0.0001). Neoplasia were identified in 13 HIV+ patients, in 7 associated with hyperuricemia and 3 with hypouricemia. Of interest, 2 patients had urate abnormalities before the diagnosis of neoplasia. CONCLUSIONS: Our study suggests that rheumatic manifestations are more prevalent in HIV+ patients. In advanced HIV infection, hypo and hyperuricemia may be considered markers of neoplasia.

Adult↗
PubMed1989

[Actinic cheilitis in Quinta fishing workers: prevalence and associated histopathological aspects].

The purpose of the present investigation was to study the occurrence and degree of severity of the actinic cheilitis in a sample of 566 artisan fishermen of Valparaíso, Chile. The condition was found in 43% of the sample, the degree of severity was an 8% for the acute expression and a 35% for the chronic type of the disease. A direct relationship between the number of years spent on sun exposure and the degree of severity of the vermillion alterations was found, being the patients between 16 and 45 years old the group most severely involved, a finding similar to the data reported in the current literature. The prone complexion was the fair one: those fishermen with blond or red hair, blue or green eyes and fair skin showed both clinical and histopathologically early disturbances of degenerative nature in the collagenous component of the connective tissue and in the epithelial surface.

Adult↗
PubMed1988

Failure of ornithine decarboxylase inhibition to alter small intestinal epithelial repair after transient segmental ischaemia.

To evaluate the roles of ornithine decarboxylase (ODC) and polyamines in the regulation of epithelial repair, rabbit mid-small intestine after transient ischaemic villus injury in the presence and absence of DL-difluoromethylornithine (DFMO), an irreversible inhibitor of ODC was studied. Rabbits received 2% (w/v) DFMO in drinking water for two days before undergoing a sham laparotomy, or a 90 minute mesenteric vascular occlusion of 20 cm of mid-intestine. DFMO fed and control rabbits were studied four, 24, 72, or 120 hours after this ischaemic intestinal injury. In controls, ischaemic injury caused shortened villi at four hours (p less than 0.01), diminished mucosal sucrase and alkaline phosphatase activities at 24 hours (p less than 0.05), but raised ODC (p less than 0.001) and thymidine kinase (p less than 0.01) activities at four hours with recovery by 72 hours. DFMO treatment significantly reduced ODC activity at all stages of the experiment and significantly inhibited the rise in activity observed after injury (p less than 0.01). Mucosal concentrations of the polyamines, spermidine and spermine, were similar in the sham operated groups; four hours and 24 hours after ischaemia, they increased in the DFMO animals (p less than 0.01) but fell (p less than 0.05) in those that did not receive DFMO. After ischaemic injury, DFMO treatment inhibited ODC but failed to influence recovery of villus structure or enzyme activities in the small intestine. We conclude that ODC and the polyamines, spermidine and spermine, are not key regulators of small intestinal repair after transient ischaemia.

Animals↗
PubMed1987

Morbidity after percutaneous liver biopsy.

The safety of percutaneous liver biopsy with a 1.2 mm Menghini needle in infants aged one year or less was investigated. One hundred and eighty four procedures performed from 1975 to 1985 were reviewed. There were no deaths or major complications within 48 hours associated with the procedure. In five instances specific complications occurred: a drop in haemoglobin concentration (three), transient hypotension (one), and haematoma at the biopsy site (one). The result of liver biopsy was diagnostic in 83% of cases, compatible with unspecified metabolic disease in 8%, and normal or not diagnostic in 9%. This study suggests that percutaneous liver biopsy can be performed with relative safety in small infants if coagulation is normal and there are no major contraindications, and the results yield important diagnostic information which cannot be obtained using less invasive procedures.

Biopsy, Needle↗
PubMed1986

Intestinal repair in chronically undernourished rabbits.

To assess the effect of chronic undernutrition on intestinal epithelial repair after injury, we studied 10-wk-old rabbits, nutritionally deprived for 6 wk (body weight 1.95 +/- 0.2 kg versus controls, 2.68 +/- 0.7 kg, p less than 0.001). Intestinal structure and function were assessed 4, 24, 48, 72, or 96 h after a 90-min vascular occlusion of a 20-cm segment of midintestine in undernourished and control-diet animals. Tritiated thymidine autoradiography showed that movement of epithelial cells along the crypt-villus axis was significantly curtailed in undernourished rabbits after sham operation or after ischemic injury. In sham-operated rabbits, no significant differences were observed in mucosal structure, disaccharidase and Na-K-ATPase activities, or Na transport (Ussing chambers) between nutritionally deprived and control diet rabbits. Four and 24 h after ischemic injury, significant but similar structural and functional small intestinal abnormalities occurred in both diet groups; recovery of enzyme function was not significantly delayed but crypt-villus length recovery was minimally delayed in undernourished rabbits. Glucose-stimulated Na absorption diminished in short circuited jejunum from malnourished but not from control diet animals 24 h after injury and was normal in both diet groups at 72 h. After transient small intestinal villus cell injury we observed suppressed epithelial proliferation but no consistent impact on epithelial differentiation in nutritionally deprived rabbits.

Animals↗
PubMed1985

Psychological intervention for adults with cystic fibrosis.

This study assessed the effects of a stress management and life-style modification program on the physical and psychological well-being of young adults with cystic fibrosis. Four fibrocystic patients recently transferred to an adult rehabilitation centre completed this 6-week program. Instruction in stress management consisted of both behavioural (e.g. relaxation training) and cognitive techniques. Discussion on life-style included the topics of drug and alcohol abuse, leisure, and nutrition. Individual assessments were conducted before and after a 6-week non-intervention control period and after a 6-week training program. Assessments included a battery of psychometric inventories as well as electromyographic testing of trapezius muscle tension. At the end of the program, participants reported that they experienced fewer physical and psychological symptoms of stress. Electromyographic measures provided some suggestion of a trend toward greater stability at posttest.

Adult↗