Search PubMed⌕ Search

Biomedical subjects

T Lopez

Publications and source records attributed to T Lopez.

At least 19 recordsLinked to original sources
PubMed2006

Molecular vibrational analysis and MAS-NMR spectroscopy study of epilepsy drugs encapsulated in TiO2-sol-gel reservoirs.

A nanostructured matrix, consisting of titania, was designed in such a way that an antiepileptic drug could be encapsulated and released according to a well-defined time release schedule. The titania was synthesized by a sol-gel method in which titanium n-butoxide was used as the precursor for the formation of the sol. The synthesis was optimized to yield a homogeneous particle size with a high porosity and an anatase crystal structure. The antiepilectic drugs, phenytoine or valproic acid, were added during the gelation stage in order to obtain a homogeneous gel phase. The resulting nanostructured matrix including the drug showed only weak attractive forces, such as London forces, dipole-dipole coupling, and in some cases hydrogen bonds. The resulting assembly, referred to as a reservoir, was characterized using conventional FTIR and NMR spectroscopic techniques. Theoretical simulation studies were performed so as to obtain an understanding of the equilibrium electrostatic potential distribution and the relative charges on the titania and the anticonvulsants.

Anticonvulsants↗
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↗
PubMed2003

Validation of a six-graded faces scale for evaluation of postoperative pain in children.

BACKGROUND: The faces pain scales are often used for self-report assessment of paediatric pain. The aim of this study was to evaluate the validity of a six-graded faces pain scale after surgery by comparing the level of agreement between the children's report of faces pain scores and experienced nurses' assessment of pain by observation of behaviour. The faces pain scores before, at and after administration of analgesics were analysed. The study was performed in two South African hospitals, one with a mainly rural population and the other with an urban population. METHODS: A total of 110 children aged 4-12 years, scheduled for inguinal surgery in the two South African hospitals, were included in the study. The anaesthetic technique was standardized. All patients received a caudal block preoperatively. Postoperative pain assessments were made every hour for 8 h after the caudal block was performed. A designated nurse assessed pain by using a four-graded descriptive scale (no, mild, moderate or severe pain) and thereafter the child reported pain by using the six-graded faces pain scale. RESULTS: A high correlation was found between the two methods of assessment (tau = 0.76, P < 0.0001). The correlation between methods was high in both hospital populations and in all age groups. The weakest correlation was found in children aged 8-12 years (tau = 0.56, P < 0.01). Significantly lower faces pain scores were found after administration of analgesics compared with pain rating before analgesics (P < 0.0001). The proportion of patients with pain scores above 2 decreased from 86% to 31% (P < 0.001). CONCLUSIONS: The findings support this six-graded faces pain scale as a useful and valid instrument for measuring pain in the postoperative period in children aged 4-12 years.

Amides↗
PubMed2003

On archimedes.

Explore the source record for details and available documents.

Evidence-Based Medicine↗
PubMed2002

Remifentanil and the tunnelling phase of paediatric ventriculoperitoneal shunt insertion. A double-blind, randomised, prospective study.

Sixty-two children were randomly allocated to receive, during inhalational anaesthesia with isoflurane and nitrous oxide, either 1.0 microg x kg(-1) remifentanil (n = 33) or saline (n = 29) just before the tunnelling phase of ventriculoperitoneal shunt insertion, in a double-blind study. The remifentanil group showed little stress response to tunnelling as indicated by median (interquartile range [range]) change in heart rate -5.2 (-11.4 to 9.8 [-19.4 to 30.4])%, mean arterial pressure -5.0 (-20.8 to 15.5 [-40.9 to 42.9])% or plasma norepinephrine -13.5 (-38.1 to -2.5 [-77.7 to 81.5])% compared with the saline group, in which the changes were 20.1 (11.5-36.1 [2.1-83.1])%, 42.7 (27.1-56.8 [3.2-73.5])% and 13.3 (0.8-70.0 [-45.2 to 337.5])%, respectively (p < 0.001 for all comparisons). These changes were consistent across most different age categories. The cardiovascular response in the saline group lasted for 8 (4-15 [0-39]) min. Tracheal extubation occurred after 3 (2-4 [1-8]) min in the remifentanil group and 3 (2-6 [0-15]) min in the saline group (p = 0.29), with transfer to the recovery area and discharge to the ward, respectively, 4 (4-5 [1-10]) min and 9 (7-13 [2-32]) min in the remifentanil group and 7 (4-8 [2-18]) min and 14 (10-19 [7-44]) min in the saline group (p = 0.06 and 0.01, respectively). Postoperatively there was some evidence of respiratory depression and increased oxygen requirements in all age categories, but this was similar in both groups. Overall, the maximum increase from baseline in transcutaneous carbon dioxide tension was 41.2 (11.3-66.7 [-2.0 to 141.7])% in the remifentanil group compared with 30.7 (20.5-55.1 [1.7-159])% in the saline group (p = 0.8), and the time taken for transcutaneous carbon dioxide tension to decrease to < 6.0 kPa was 4 (0-13 [0-60]) min compared with 7 (0-13 [0-60]) min, respectively (p = 0.75). There was no difference between the two groups in postoperative analgesic requirements or in blood loss and there were no significant side-effects. We conclude that remifentanil is an appropriate and safe analgesic to provide balanced anaesthesia to cover the tunnelling phase of paediatric ventriculoperitoneal shunt insertion.

Age Factors↗
PubMed2002

The efficacy of caudal ropivacaine 1, 2 and 3 mg x l(-1) for postoperative analgesia in children.

BACKGROUND: The aim of this double blind, randomized, comparative study was to assess the analgesic efficacy and incidence of motor block after caudal block using three different concentrations of ropivacaine, 1, 2 and 3 mg x l(-1), in children 4-12-year-old. METHODS: One hundred and ten children ASA I-II, scheduled for inguinal surgery, were included in the study. After induction of a standardized general anaesthetic technique, all patients received 1 ml x kg(-1) of the ropivacaine solution for a caudal block and were assessed for 8 h after the injection. RESULTS: The ropivacaine was well tolerated in all patients. Median time to treatment with analgesics was 3.3, 4.5 and 4.2 h in the 1, 2 and 3 mg x ml(-1) groups, respectively. During the first 4 h, the pain scores for both a 6-graded faces scale and a 4-graded observer scale were higher in the 1 mg x ml(-1) group than the 3 mg x ml(-1) group. The median sensory block reached T12 in all groups 1 h after the caudal block. Thereafter, the speed of regression was correlated with the ropivacaine concentration. In the patients with a sensory block from T12 and above, the median time to treatment with analgesics was longer than in the children with a sensory block below T12. The incidence of motor block was 28% in the 3 mg x ml(-1) group in comparison with 0 and 13% in the 1 and 2 mg x ml(-1) groups. CONCLUSIONS: It was concluded that 1 ml x kg(-1) of ropivacaine 2 mg x ml(-1) for caudal block provided satisfactory postoperative pain relief after inguinal surgery in 4-12-year-old children. Ropivacaine 1 mg x ml(-1) showed less efficacy while the use of ropivacaine 3 mg x ml(-1) was associated with a higher incidence of motor block with minimal improvement in postoperative pain relief.

Amides↗
PubMed2001

Plasma concentrations of ropivacaine following a single-shot caudal block of 1, 2 or 3 mg/kg in children.

BACKGROUND: For documenting the properties of ropivacaine used for regional anaesthesia in children, the relationship between dose and resulting systemic exposure is essential. The aim of this pharmacokinetic part of a randomised, multicentre, double-blind study was to determine the free and total plasma levels of ropivacaine in children aged between 4 and 12 years following a single-shot caudal dose of 1, 2 or 3 mg/kg of ropivacaine for postoperative pain management. METHOD: Following induction of a standardised general anaesthetic (halothane; nitrous oxide: oxygen 60:40), a caudal block using 1 ml/kg ropivacaine in concentrations of 1, 2 or 3 mg/ml was performed in 43 ASA I children (body weight 12-25 kg) scheduled for elective inguinal surgery. Blood samples were collected prior to and 15, 30, 45, 60 and 240 min after placement of the caudal block for determination of total and free ropivacaine plasma concentrations. RESULTS: The peak plasma concentration of total ropivacaine, reached within 15-241 min after the block, increased in proportion to dose, with mean values at 0.27, 0.64 and 0.90 mg/l following 1, 2 and 3 mg/kg respectively. The peak plasma level of free ropivacaine also increased in a dose-proportional manner, with mean levels at 0.014, 0.030 and 0.042 mg/l. The highest individual peak plasma level of free ropivacaine was 0.070 mg/l, well below the threshold levels of CNS toxicity described in adults. No clinical signs of systemic toxicity were observed. CONCLUSION: Following single-shot caudal doses of 1-3 mg/kg in children up to 25 kg and aged between 4 and 12 years, plasma levels of free ropivacaine increase in proportion to dose and all were shown to be within safe limits.

Amides↗
PubMed2001

Only early intervention with gamma-aminobutyric acid cell therapy is able to reverse neuropathic pain after partial nerve injury.

Pharmacological treatment for neuropathic pain, although often effective for brief periods, can result in intractable persistent pain with certain patients. Cell therapy for neuropathic pain is a newly developing technology useful for an examination of enhanced normal sensory function after nerve injury with the placement of cells near the spinal cord, and grafts of immortalized cells bioengineered to chronically supply the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) have been used to reverse the chronic pain behaviors. However, it is not known whether there is a therapeutic window for the use of intervention with cell therapy after partial nerve injury. To investigate whether neuropathic pain is sensitive to the timing of placement of cell grafts, neuronal cells bioengineered to synthesize GABA were transplanted in the lumbar subarachnoid space one to four weeks after unilateral chronic constriction injury (CCI) of the sciatic nerve and sensory behaviors were evaluated before and after CCI and transplants. Both thermal hyperalgesia and tactile allodynia were reversed when transplants were placed either one or two weeks after partial nerve injury, compared to maintenance of these behaviors with the injury alone. However, if GABA cells were placed any later than 2 weeks after nerve injury, such intervention was ineffective to reverse the thermal and tactile hypersensitivities induced by the injury. This suggests that altered spinal GABA levels may contribute to the early development of chronic neuropathic pain and that early intervention with cellular therapy to restore GABA may prevent the development of that pain.

Animals↗
PubMed2001

Successful use of central venous catheter as permanent hemodialysis access: 84-month follow-Up in lucania.

Cuffed tunneled venous access catheters are commonly used for temporary and permanent access in hemodialysis (HD) patients. These catheters serve an essential role in providing permanent access in subjects in whom all other access options have been exhausted. The predominant complications are catheter thrombosis, catheter fibrin sheating and infection. The aim of this study was to evaluate long-term survival and complications of permanent venous catheters (PVC) placed for the purpose of HD during the period from January 1992 to December 1998, at the Dialysis Units of Lucania (a southern Italian region). A total of 98 PVC were placed in 88 patients during this period. The catheters used were of three types: (a) 72 VasCath Soft Cell catheters (Bard Instrument Company, Toronto, Ont., Canada); (b) 22 PermCath catheters (Quinton Instrument Company, Seattle, Wash., USA), and (c) 4 Tesio catheters (Bellco SpA, Mirandola, Italy). Survival curves of catheters were calculated using the Kaplan-Meier product-limit estimator. The patient survival was 60% at the 78th month. Actually, 52 patients (27 males, 25 females) are still alive: 15 (26.9%) of these patients have diabetes mellitus and 1 has been transplanted. The actuarial survival rate of PVC was 89% in the whole population studied and 82% in subjects alive after 84 months. Twenty-five patients (28.4%) had PVC as the first reliable vascular access. Long-term complications occurred 27 times (1 episode every 44.81 month/patient) as: breakage (3.1%); thrombosis (10.2%); displacement (2.0%); subcutaneous tunnel bleeding (3.1%); inadequate blood flow (7.1%), and infection (10.2%). In conclusion, our data confirm that PVC might represent an effective long-term blood access route for HD. Again, PVC are getting the access of choice for selected patients (i.e., older subjects with cardiovascular diseases and cancer patients) and are enjoying a dramatic increase in use for subjects who are terrified of repetitive venopuncture.

Actuarial Analysis↗
PubMed2000

Selection of the most common chromosome abnormalities in oocytes prior to ICSI.

So far, all preimplantation genetic diagnosis (PGD) protocols in use produce results after the eggs have been fertilized. However, these approaches are not acceptable for patients with moral objections to the generation and discard of supernumerary zygotes or embryos. In these circumstances, only those oocytes to be replaced may be inseminated. The purpose of this study was to develop a PGD protocol to diagnose first polar bodies (PBs) prior to Intracytoplasmatic Sperm Injection (ICSI) in order to inseminate only those oocytes found to be chromosomally normal. PB biopsy was performed 1 hour after ovum pick up, and after fixation, the PBs were analysed by FISH and the eggs inseminated by ICSI no later than 7 hours after retrieval. One third (33.3%) of the PBs were aneuploid. Fifty-four normal and 12 non-resolved oocytes were injected by ICSI, of which 65% became 2-PN zygotes. Embryo transfer on day 2 was possible in all 10 patients (average maternal age 35.2+/-3.2, range 29-39 years), of which 6 became pregnant with 8 fetuses (28.6% or 8/28 transferred embryos). The results indicate that PB analysis of some common chromosome abnormalities is feasible within time limits imposed by ICSI insemination (6 hours or less).

Adult↗
PubMed2000

BLC expression in pancreatic islets causes B cell recruitment and lymphotoxin-dependent lymphoid neogenesis.

CXCR5, the receptor for B lymphocyte chemoattractant (BLC), is required for normal development of Peyer's patches, inguinal lymph nodes, and splenic follicles. To test the in vivo activity of BLC in isolation of other lymphoid organizers, transgenic mice were generated expressing BLC in the pancreatic islets. In addition to attracting B cells, BLC expression led to development of lymph node-like structures that contained B and T cell zones, high endothelial venules, stromal cells, and the chemokine SLC. Development of these features was strongly dependent on B lymphocytes and on lymphotoxin alpha1beta2 and could be reversed by blocking lymphotoxin alpha1beta2. These findings establish that BLC is sufficient to activate a pathway of events leading to formation of organized lymphoid tissue.

Animals↗
PubMed2000

Comparison of remifentanil versus regional anaesthesia in children anaesthetised with isoflurane/nitrous oxide. International Remifentanil Paediatric Anaesthesia Study group.

We compared the efficacy and safety of a remifentanil (0.25 microg x kg(-1) x min(-1)-based balanced anaesthetic technique with a bupivacaine-based regional anaesthetic technique in an open label, multicentre study in 271 ASA physical status 1 or 2 children aged 1-12 years. Subjects requiring major intra-abdominal, urological or orthopaedic surgery were randomly allocated to receive either intravenous remifentanil (group R; n = 185) or epidural bupivacaine (group B; n = 86) with isoflurane/nitrous oxide for their anaesthesia. The majority of children in both groups (85% in group R, 78% in group B) showed no defined response to skin incision, and although the mean increase in systolic blood pressure (+11 mm Hg) was significantly greater in group R than in group B, this change did not represent a serious haemodynamic disturbance. More children in group R (31%) required interventions to treat hypotension and/or bradycardia than those in group B (12%), but these were easily managed by administration of fluids or anticholinergic drugs. Adverse events, mainly nausea and/or vomiting, occurred in 45% of group R and 42% of group B (NS). The adverse event profile of remifentanil in this study was typical of a potent mu-opioid receptor agonist. Remifentanil was as effective as epidural or caudal block in providing analgesia and suppressing physiological responses to surgical stimuli in children aged between 1 and 12 years undergoing major abdominal, urological, or orthopaedic surgery under isoflurane/nitrous oxide anaesthesia.

Analgesia, Epidural↗
PubMed2000

Ten years of liver transplantation at Groote Schuur Hospital.

INTRODUCTION: Liver transplantation has evolved from an experimental procedure to being the treatment of choice for many patients with end-stage liver disease, and is performed on a routine basis in most major centres throughout the world. However, certain situations peculiar to developing countries have a major impact on liver transplant programmes in these countries. We present the results of the liver transplant programme in Cape Town. PATIENTS AND METHODS: All patients undergoing orthotopic liver transplantation at Groote Schuur Hospital and Red Cross War Memorial Children's Hospital were included in this report. Standard surgical techniques were used for procuring the donor liver, the recipient hepatectomy and the subsequent implantation of the liver. All patients received standardised peri-operative management; in particular, the immunosuppressive protocol consisted of cyclosporin, steroids and azathioprine. Since October 1988, 83 patients have undergone 89 orthotopic liver transplants. There were 44 adults and 39 children, the age range being from 6 months to 56 years. The commonest indications for hepatic transplantation in adults included cryptogenic cirrhosis, auto-immune hepatitis and primary sclerosing cholangitis. In children biliary atresia was the commonest cause of liver failure. RESULTS: Of the 81 patients transplanted, 50 are alive and well with follow-up ranging from 2 months to 9.5 years. The cumulative graft survival rate was 72% at 1 year and 61% at 5 years. Six patients have undergone re-transplantation and 4 patients have had combined liver/kidney transplants. De novo hepatitis due to hepatitis B virus (HBV) has occurred in 8 patients following transplantation. Subsequent investigation has shown that 5 of the donors of these livers were hepatitis B core antibody (HBcAb)-positive, while information on the remaining 3 was not available. Tuberculosis (TB) has been a significant problem in 4 patients, with 2 deaths precipitated by anti-TB drug-induced hepatitis. Post-transplant lymphoproliferative disorder was also responsible for significant postoperative morbidity. CONCLUSION: Orthotopic liver transplantation has been established at Groote Schuur Hospital as the treatment of choice for selected patients with chronic end-stage liver disease. However, hepatitis B and TB appear to present a problem. The particularly high prevalence of HBV carrier status in our donor population may necessitate the use of living donors in the future.

Adolescent↗
PubMed2000

Liver transplantation in children--the Red Cross War Memorial Children's Hospital experience.

Liver transplantation for infants and children has been available in South Africa for more than a decade. Current concerns have shifted from an initial target of early post-transplant survival to quality of life in the long term. Since 1985, 175 infants and children have been assessed, with 104 accepted for transplantation. Fifty have had orthotopic liver transplants (OLTx), 48 (3 retransplants) in Cape Town and 2 abroad. Biliary atresia was the most frequent diagnosis (52%) followed by acute liver failure (ALF) (16%). Waiting list mortality has remained high (15%), particularly for the ALF group (50%). Thirty-four patients survive 1 month--14 years post-transplant. Early post OLTx mortality was low (7%) but late morbidity and mortality (23%) were mainly due to viral infection: de novo hepatitis B (5 patients, 2 deaths), EBV-related post-transplantation lymphoproliferative disease (PTLPD) (6 patients, 4 deaths) and CMV disease (9 patients, 4 deaths). Tuberculosis prophylaxis, required in 6 cases, resulted in major morbidity in 1. Hypertension requiring medication along with some compromise of renal function has been present in all but 2 patients. However, all those of school-going age (20) attend school normally and remain in good health and only 3 of the survivors have abnormal liver function tests. Successful liver transplantation is possible in a developing country with limited resources. Scarcity of virus-free donors (HBV and HIV) leading to waiting list mortality and infrequent retransplantation along with long-term consequences of immunosuppression (infection, lymphoma and renal toxicity) remain problems.

Child↗