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Biomedical subjects

G Rodriguez

Publications and source records attributed to G Rodriguez.

At least 55 records · Page 3Linked to original sources
PubMed1998

Feasibility in the clinical setting of perfusion brain SPECT imaging employing a brain-dedicated gamma camera and the conjugate gradients with modified matrix reconstruction method.

In the present study, we compared Tc-99m HMPAO single photon emission computed tomography (SPECT) brain images obtained using the conventional filtered backprojection (FBP) reconstruction method with the new reconstruction method of conjugate gradients with modified matrix (CGMM). The two methods were employed to generate SPECT images of a brain perfusion study in a 41-year-old patient who had suffered from multiple embolisation of the right hemisphere. Marked improvement in spatial resolution was achieved by CGMM reconstruction as compared to FBP reconstruction; this considerably helped in defining grey matter structures and low-uptake white-matter areas, both in the normal cerebral areas and in the hemisphere that had been affected by stroke. Although the relatively long time still required by the CGMM procedure might be considered as a significant drawback to date, with the increasing diffusion of the new computer facilities the CGMM method can be proposed as a valuable alternative to the standard FBP technique in order to better recognise cerebral areas with different tracer uptake.

Adult↗
PubMed1998

Bowel management for fecal incontinence in patients with anorectal malformations.

BACKGROUND/PURPOSE: Fecal incontinence is common in patients operated on for anorectal malformations. Treatment with enemas, laxatives, and medications are often given by clinicians in an indiscriminate manner and without a demonstrated benefit. A systematic diagnostic approach and bowel management program was developed for patients suffering from fecal incontinence, and a retrospective analysis of the results is presented. METHODS: Three hundred forty-eight patients were seen in consultation for fecal incontinence after repair of imperforate anus at other institutions. Clinical and radiological evaluation helped determine different types of patients. Group I consisted of 147 patients who were considered candidates for reoperation and forms the basis of a future report. Group II included 172 patients who had no potential for bowel control and were therefore candidates for bowel management. These patients fell into two categories; group IIA included 44 patients with incontinence and constipation. The bowel management involved the use of daily large enemas only. Group IIB included 128 patients with incontinence and a tendency to diarrhea. Group III consisted of 29 patients who had pseudoincontinence. They had an original defect with good prognosis, good sphincters, good sacrum, and a well-located rectum. They suffered from severe constipation, megasigmoid, chronic fecal impaction, and overflow pseudoincontinence and were treated with laxatives or sigmoid resection. RESULTS: Bowel management was successful in 93% of patients in the constipation group (IIA) and 88% in the diarrhea group (IIB). Ninety-seven percent of patients in group III became fecally continent. CONCLUSION: Bowel management consisting of enemas, laxatives, and medications is successful when administered in an organized manner. It is vital to determine the type of fecal incontinence from which the patients suffer and to target their treatment accordingly.

Anus, Imperforate↗
PubMed1998

Anorectal malformations and Down's syndrome.

BACKGROUND/PURPOSE: Down's syndrome is a common association in patients with anorectal malformations. The purpose of this study was to determine whether the anorectal defect in patients with Down's syndrome had specific characteristics and whether the presence of Down's syndrome represented a serious detriment to the patient's functional prognosis. METHODS: Nine hundred eighty-seven patients with anorectal malformations were studied retrospectively. Twenty patients (2%) had Down's syndrome. Nineteen of these (95%) had the same specific type of anorectal defect: imperforate anus with no fistula. This defect has a good prognosis, the rectum is located about 2 cm above the perineal skin, the sacrum is normal, and the sphincter mechanism is good. For comparison, a group of 34 patients with the same defect but without Down's syndrome was also studied. All patients were operated on via posterior sagittal approach by the same surgeon. RESULTS: Imperforate anus without fistula occurs in 5% of all patients with anorectal malformations and in 95% of those patients who also suffer from Down's syndrome. The characteristics of the defect were the same in both groups of patients, and surprisingly, the prognosis was good in both groups (80% to 96% of patients had voluntary bowel movement, 100% had urinary continence). CONCLUSIONS: The association of Down's syndrome with imperforate anus without fistula is not coincidental. This particular benign defect can be predicted to occur in most patients with Down's syndrome. The presence of Down's syndrome in cases of anorectal malformations should not be a contraindication to repairing the imperforate anus and to closing the colostomy.

Anus, Imperforate↗
PubMed1998

Tirapazamine-cisplatin: the synergy.

Tirapazamine is a novel bioreductive agent with selective cytotoxicity against hypoxic tumour cells. Synergy with cisplatin and other chemotherapeutic agents has been shown in preclinical trials. Pharmacokinetic studies of tirapazamine have revealed that exposure increases with dose over the range of 18-450 mg m(-2) for a single dose and of 9-390 mg m(-2) for multiple doses. Plasma clearance is high. Tirapazamine has been clinically tested in combination with cisplatin at escalating doses in a phase I trial and at therapeutic doses in three separate phase II trials in patients with advanced non-small-cell lung cancer (NSCLC) in 11 study centres. Limiting toxicity for tirapazamine at an intravenous dose of 390 mg m(-2) was acute, reversible hearing loss. Other frequently observed side-effects included muscle cramping and gastrointestinal symptoms. Tirapazamine did not cause myelosuppression, and no toxic deaths were reported in these trials. The anti-tumour efficacy against previously untreated, advanced NSCLC was evaluated by cumulative intent-to-treat analysis of 132 patients. The objective response rate (confirmed by two independent measurements) was 25% [confidence interval (CI) 17.8-33.33], with a median survival of 38.9 weeks (CI 29.4-49.9). The efficacy of tirapazamine plus cisplatin shown in these trials was better than that of historical controls with cisplatin monotherapy. Two large-scale international trials have been conducted, involving more than 70 centres, to confirm these results. The CATAPULT I trial compares tirapazamine plus cisplatin with cisplatin and has finished accrual with 446 patients. The CATAPULT II trial, which is comparing tirapazamine plus cisplatin with etoposide plus cisplatin, had enrolled 550 patients by June 1997. Follow-up is ongoing. Tirapazamine is the promising first drug from a new class of cytotoxic agents with a novel mechanism of action. It can be effectively combined with cisplatin, and possibly with other agents, because of its safety profile and lack of overlapping dose-limiting toxicity, such as myelosuppression. The combination of tirapazamine and cisplatin appears to be safe and effective in the treatment of NSCLC.

Antineoplastic Agents↗
PubMed1998

Cerebral hemodynamic response to CO2 after severe head injury: clinical and prognostic implications.

OBJECTIVE: To study the cerebrovascular reactivity to CO2 after severe head injury to establish the clinical and prognostic relevance of CO2 reactivity. METHODS: Cerebrovascular reactivity to CO2 was studied in 20 patients with severe head injuries at 3.0+/-1.8 days after trauma onset. Two cerebral blood flow studies were performed to measure CO2 reactivity: the first study in a condition of normocapnia and the second study in a condition of relative hypocapnia. RESULTS: Global reactivity was superimposable to that found in awake, normocapnic subjects and did not correlate with age and Glasgow Coma Scale score but was dependent on the type of brain lesion. Moreover, reactivity correlated with outcome in patients studied after the first 3 days after trauma. CONCLUSIONS: Our data suggest that cerebrovascular reactivity is (a) almost preserved after a severe head injury; (b) significantly influenced by type of brain lesion; (c) prognostically relevant only in patients studied after the first 3 days after trauma.

Acute Disease↗
PubMed1998

Microbiology of acute otitis media in Costa Rican children.

BACKGROUND: Because of the increasing number of resistant middle ear pathogens reported from different centers worldwide, an active surveillance of the microbiology and susceptibility pattern of middle ear pathogens is required for proper antimicrobial recommendations among different regions of the world. OBJECTIVE: To study the microbiology and susceptibility pattern of middle ear pathogens obtained from Costa Rican children with acute otitis media. METHODS: Between 1992 and 1997 a diagnostic tympanocentesis was performed in 398 Costa Rican patients with acute otitis media. Middle ear fluid was obtained for culture and minimal inhibitory concentrations were determined by the E-test technique in those isolates obtained between October, 1995, and January, 1997. RESULTS: The most common pathogens cultured were Streptococcus pneumoniae (30%), Haemophilus influenzae (14%), Staphylococcus aureus (4%) and Streptococcus pyogenes (4%). Moraxella catarrhalis was uncommon. Beta-lactamase production was low (3.7%) among the H. influenzae isolates but frequent among the Staphylococcus aureus (57.1%) and M. catarrhalis (100%) strains. Overall 9 of 46 S. pneumoniae isolates (19.6%) exhibited decreased susceptibility to penicillin of which 8 isolates (17.4%) showed intermediate and one strain (2.2%) high level resistance. Among the penicillin-susceptible S. pneumoniae isolates, susceptibility to the following antimicrobials was: 81%, azithromycin; 89%, clarithromycin; and 100%, ceftriaxone and trimethoprim-sulfamethoxazole (TMP-SMX). Among the penicillin-resistant S. pneumoniae isolates the percentage of susceptible strains was 89% for azithromycin, clarithromycin and ceftriaxone and 67% for TMP-SMX. CONCLUSIONS: Based on this microbiologic information the agents considered first line drugs in the treatment of acute otitis media in Costa Rica remain amoxicillin or TMP-SMX.

Acute Disease↗
PubMed1998

Phase I and pharmacokinetic study of GI147211, a water-soluble camptothecin analogue, administered for five consecutive days every three weeks.

GI1147211 is a 7-substituted 10,11-ethylenedioxy-20(S)-camptothecin analogue that inhibits the nuclear enzyme topoisomerase I. In this Phase I and pharmacological study, 24 patients with advanced solid malignancies received a total of 72 courses of GI147211 as a 30-min infusion daily for 5 consecutive days, at doses ranging from 0.3 to 1.75 mg/m2/day. Severe neutropenia precluded dose escalation above 1.5 mg/m2/day in minimally pretreated patients, and both severe neutropenia and thrombocytopenia were dose limiting in heavily pretreated patients at doses above 1.0 mg/m2/day. These doses are, therefore, recommended for subsequent Phase II evaluations of GI147211 in patients with comparable prior therapy. Nonhematological toxicities, including nausea, vomiting, fatigue, and anorexia, were mild to moderate. The disposition of GI147211 in blood was described by a linear three-compartment model, with renal elimination accounting for only 11% of drug distribution. No relationship was observed between the pharmacological exposure to GI147211 and effects on neutrophils; however, patients who developed dose-limiting myelosuppression did experience greater exposure to both the lactone and total forms of the drug. The hydrolysis kinetics of GI147211 revealed not only a shift of the drug to the inactive carboxylate form in human serum albumin but also stabilization of the lactone in erythrocytes, perhaps accounting for the observed lactone:total area under the concentration-time curve ratio of 0.27. These results indicate that GI147211 exhibits predictable toxicities and that further studies are warranted to determine the distinct role of this compound among currently available camptothecin analogues.

Adult↗
PubMed1998

A Phase I and pharmacological study of the glutamine antagonist acivicin with the amino acid solution aminosyn in patients with advanced solid malignancies.

Acivicin is a glutamine analogue antimetabolite that inhibits several glutamate-dependent synthetic enzymes. Previous studies of this agent administered on a 72-h continuous i.v. infusion schedule every 3 weeks demonstrated a high rate of severe, albeit reversible, central nervous system (CNS) toxicity at the 30 mg/m2/day dose level. Animal studies have shown that the CNS toxicity of acivicin can be prevented by a concomitant infusion of amino acids postulated to block drug uptake in the CNS by a saturable transport system that is common to endogenous amino acids. This study evaluated the feasibility of escalating acivicin doses in cancer patients by administering acivicin with a concomitant 96-h i.v. infusion of a mixture of 16 amino acids (Aminosyn, 10%). Twenty-three patients with advanced malignancies were treated with acivicin on a 72-h continuous infusion schedule at doses ranging from 25 to 60 mg/m2/day every 3 weeks. Reversible, dose-limiting CNS toxicity, characterized by lethargy, confusion, and decreased mental status, occurred in the two patients enrolled at the 60 mg/m2/day dose level, precluding further dose escalation. The maximum tolerated dose (MTD) and recommended dose for additional evaluation of acivicin on this schedule is 50 mg/m2/day. Other toxicities observed were dose-related neutropenia that was grade 4 in four patients (four courses), complicated with fever in three of those patients, and grade 3-4 thrombocytopenia in three patients (three courses). Pharmacokinetics studies performed in 15 patients revealed that the acivicin plasma Css increased from 0.44 microg/ml (range, 0.28-0.59 microg/ml) at the 25 mg/m2/day to 1.06 microg/ml (0.64-1.5 microg/ml) at the 50 mg/m2/dose level. Acivicin Css at the MTD was not significantly higher than previously reported values with single-agent acivicin on the same schedule of administration at the MTD of 25 mg/m2/day dose level (0.60 microg/ml; range, 0.43-0.81 microg/ml). Neurotoxicity did not correlate with acivicin Css, but relationships between exposure to acivicin and the occurrence of both neutropenia and thrombocytopenia were well described by a sigmoidal Emax model. This trial demonstrated that concomitant infusions of amino acid can prevent acivicin-induced CNS toxicity, which allows the dose of acivicin to be escalated 2-fold above previously tolerable doses; however, this effect did not translate in a significant increment in acivicin Css.

Adult↗
PubMed1997

Impaired quantitative cerebral blood flow in scleroderma patients.

Systemic Sclerosis (SSc) is a multisystem disease characterised by proliferation of vascular tissue, obliterative microvascular lesions and diffuse organ fibrosis. Despite widespread vascular disease, Central Nervous System complaints are only infrequently reported and it is uncertain whether they merely derive from systemic complications or whether they may be also caused by a primary vascular process within the brain. Regional cerebral blood flow (rCBF) was quantitatively measured by the 133Xenon clearance technique in twenty-seven consecutive SSc patients without relevant systemic complications and with different severity of vascular involvement, as staged by nailfold capillary videomicroscopy (NCV). Absolute, percent, and asymmetry rCBF values were compared (z-statistics) with age- and sex-matched healthy controls. Cerebral MRI and Mini-Mental State Examination (MMSE) were also performed. Doppler sonography of neck vessels and Transcranial Doppler sonography (TCD) were performed in patients presenting rCBF reduction. Cerebral hypoperfusion was found in the 52% of patients, i.e.: in 33% of patients with the 'early' NCV pattern, in 56% of patients with the 'active' pattern, and in 67% of patients with the 'late' NCV pattern. Thirty percent were the MRIs showing focal and/or diffuse signal abnormalities in the white matter of both hemispheres with the highest rate (44%) in the 'late' NCV pattern. MMSE disclosed mild dementia in one patient in the 'late' NCV group and some mistakes in 6 more patients, in the 'active' or 'late' NCV groups, whereas TCD failed to find significant stenosis of Willis' arteries. Cerebral hypoperfusion is shown for the first time in a substantial part of SSc patients without either neurological symptoms or relevant systemic complications. It is suggested that the rCBF reduction might be related to the systemic scleroderma microangiopathy although, probably due to the paucity of connective tissue in cerebral vessels, the vast majority of patients remains in a subclinical phase.

Adult↗
PubMed1997

Neuropsychological study during video-EEG recording of successive partial seizures of right temporo-central origin.

A 15-year-old, right-handed boy underwent video-EEG study as a first step in presurgical evaluation for a severe drug-resistant right temporo-central epilepsy. He was monitored while performing neuropsychological tests over a 67-minute period during which 23 brief seizures were recorded. Despite his right-handedness, both inter-ictal and ictal verbal performances were impaired. Analysis of the relationships between the characteristics of the EEG and the neuropsychological results revealed that a worsening in cognitive performances correlated with an increase in inter-ictal abnormalities, particularly when subclinical paroxysms were present; that the cognitive tasks executed peri-ictally were correctly performed in almost 50% of the cases; and that the error rate was higher when a task was presented during or immediately after a seizure rather than before its onset. A Wada test, performed on the basis of the cognitive results, demonstrated right hemisphere dominance for language. Our observations underline the importance of neuropsychological testing in presurgical procedures, and suggest that it should be performed peri-ictally whenever possible.

Adolescent↗
PubMed1997

The tethered spinal cord in patients with anorectal malformations.

The aims of this study were to find the prevalence of tethered cord in patients with anorectal malformations; to determine if the presence of tethered cord relates to the severity of the anorectal defect, and to certain symptoms, signs, radiologic findings, and associated anomalies; and finally to determine whether tethered cord impacted on a patient's functional prognosis and whether surgical untethering improved the patient. The authors studied 934 patients with anorectal malformations, 111 of whom had magnetic resonance imaging (MRI) of the spine. We compared patients with and without tethered cord by using parametric and nonparametric statistical tests. Tethered cord occurred in 24% of the patients. The prevalence varied according to the type of anorectal defect from 43% in the complex group to 11% in patients with rectovestibular fistula. Patients with tethered cord had a lateral sacral ratio lower than that of patients without tethered cord (0.410 versus 0.702). Tethered cord was present in 90% of patients with myelodysplasia, 60% of patients with a presacral mass, 57% of patients with sacral hemivertebrae, and 56% of patients with a single kidney. The greater number of associated anomalies a patient had, the greater the risk of having tethered cord (P < .05 for all differences). The authors noted differences between patients with and without tethered cord in the presence of voluntary bowel movements (46% versus 70%), fecal soiling (91% versus 63%), constipation (21% versus 43%), and urinary incontinence (86% versus 42%). The data indicate that patients with tethered cord have a worse functional prognosis than patients without tethered cord. However, the incontinence in our patients was also predictable based on the type of anorectal defect and the character of the sacrum irrespective of the presence of tethered cord. Eighteen patients underwent surgical untethering of the cord, and none had any significant change in bowel or urinary function postoperatively. No patient with tethered cord experienced incontinence that could be attributed to the cord defect alone. This study suggests that tethered cord occurs more frequently in patients with severe anorectal defects, sacral hypodevelopment, myelodysplasia, presacral mass, sacral hemivertebrae, or a single kidney, or in those with an anorectal defect with poor functional prognosis. At present no solid evidence supports the concept that tethered cord by itself affects the functional prognosis of patients with anorectal malformations. Also, there is no good evidence demonstrating that surgical untethering improves the prognosis.

Abnormalities, Multiple↗
PubMed1997

Phase I study of daily times five topotecan and single injection of cisplatin in patients with previously untreated non-small-cell lung carcinoma.

BACKGROUND: The objectives were to determine the dose-limiting toxicity of topotecan in combination with cisplatin, to describe the principal toxicities, and to define the maximally-tolerated doses of the drugs in previously untreated patients with advanced non-small-cell lung carcinoma. PATIENTS AND METHODS: The study was designed to evaluate escalated doses of topotecan (starting at 0.75 mg/m2/day) as a 30-minute infusion daily for five consecutive days with a fixed clinically-relevant dose of 75 mg/m2 cisplatin given on day 1, every three weeks. RESULTS: Fifteen chemotherapy-naive patients entered the study and 14 were evaluable for toxicity. All 11 patients treated at the first topotecan/cisplatin dose level of 0.75/75 mg/m2, experienced at least one episode of grade 4 neutropenia. For six patients, absolute neutrophil counts were below 500/ml for more than five days, and two of them developed a grade 4 thrombocytopenia. At the next higher topotecan/cisplatin dose level (1.0/75 mg/m2), grade 4 neutropenia lasting longer than five days occurred in all three evaluable patients, including one patient who expired due to a severe neutropenia associated with sepsis. Non-hematologic toxicities, predominantly nausea and vomiting, were mild to moderate in severity and manageable. Four patients had partial responses (30.7%; 95% confidence interval (9%-61%) of relatively short duration. CONCLUSION: Both severe neutropenia and thrombocytopenia precluded dose escalation of topotecan and cisplatin administered on this schedule. In previously untreated patients, the first topotecan/cisplatin dose level (0.75/75 mg/m2), was associated with intolerable myelosuppression, and, therefore, the dose levels evaluated in this study cannot be recommended for subsequent phase II investigations. The high toxicity of this schedule and the recent understanding of the pharmacokinetic interaction between those drugs may encourage the investigation of the alternate sequence of cisplatin after TPT in phase II studies.

Aged↗
PubMed1997

Robots in space into the 21st century.

Describes the technological developments which are establishing the foundation for an exciting era of in situ exploration missions to planets, comets and asteroids with advanced robotic systems. Also outlines important concurrent terrestrial applications and spinoffs of the space robotics technology. These include high-precision robotic manipulators for microsurgical operations and dexterous arm control systems.

Electronics↗
PubMed1997

Docetaxel in combination with fluorouracil: study design and preliminary results.

The relatively recent introduction of a new class of chemotherapeutic agents--the taxoids--has raised hope of improved survival for patients with advanced or metastatic cancer. Following encouraging preclinical results of taxoid combinations, this phase I, nonrandomized trial was designed to evaluate a 1-hour intravenous infusion of docetaxel (Taxotere) on day 1 combined with fluorouracil (5-FU) as a daily intravenous bolus for 5 consecutive days. To date, 27 patients with advanced solid neoplasms have received 86 courses of docetaxel/5-FU at the following dose levels: 25/100, 35/150, 50/200, 60/200, and 60/300 mg/m2. Preliminary results showed no unexpected toxicities, and the principal toxicity was neutropenia of short duration. A treatment regimen of 60 mg/m2 docetaxel on day 1 and 300 mg/m2 of 5-FU given for 5 days, with a single course length of 28 days, is projected as the maximum tolerated dose.

Adult↗