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Biomedical subjects

T Gutierrez

Publications and source records attributed to T Gutierrez.

16 recordsLinked to original sources

Treatment of pediatric non-Hodgkin lymphomas in a country with limited resources: results of the first national protocol in Nicaragua.

We report the results of a protocol for the diagnosis and treatment of pediatric non-Hodgkin lymphomas (NHL) conducted in Nicaragua in the context of an international collaborative program. Fifty-three children with NHL treated between 1996 and 2003 were retrospectively evaluated. Therapy was designed based on local drug availability and affordability with dose and schedule adaptations for Burkitt and lymphoblastic lymphomas. With a median follow-up of 3 years, the projected 9-year overall survival was 63% and event-free survival 53%. The treatment was efficacious, feasible, and well tolerated in spite of the local socio-economical conditions.

Adolescent↗

Activation of peripheral cannabinoid CB1 and CB2 receptors suppresses the maintenance of inflammatory nociception: a comparative analysis.

BACKGROUND AND PURPOSE: Effects of locally administered agonists and antagonists for cannabinoid CB(1) and CB(2) receptors on mechanical and thermal hypersensitivity were compared after the establishment of chronic inflammation. EXPERIMENTAL APPROACH: Carrageenan was administered unilaterally to the rat hindpaw on day 1. Prophylactic efficacy of locally administered CB(1)- and CB(2)-selective agonists -arachidonyl-2-chloroethylamide (ACEA) and (R,S)-(2-iodo-5-nitro-phenyl)-[l-(l-methyl-piperidin-2-ylmethyl)-lH-ubdik-3-yl]-methanone ((R,S)-AM1241), respectively- on mechanical and thermal hypersensitivity were compared on day 2. Pharmacological specificity was evaluated using locally administered CB(1) and CB(2)-selective antagonists -N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamidehydrochloride (SR141716A) and N-[(1S)-endo-1,3,3-trimethyl bicycle [2.2.1] heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazole-3-carboxamide (SR144528), respectively. KEY RESULTS: Administration of either ACEA or AM1241 to the inflamed but not noninflamed paw suppressed the maintenance of carrageenan-evoked mechanical hyperalgesia and tactile allodynia and attenuated thermal hyperalgesia. The ACEA-induced suppression of mechanical and thermal hypersensitivity was blocked by local injection of SR141716A but not SR144528. AM1241 suppressed mechanical hypersensitivity with the reverse pharmacological specificity. The AM1241-induced suppression of thermal hyperalgesia was blocked by SR144528 and to a lesser extent by SR14176A. Co-administration of ACEA with AM1241 in the inflamed paw increased the magnitude but not the duration of thermal antihyperalgesia compared to intraplantar administration of either agonist alone. CONCLUSIONS AND IMPLICATIONS: Cannabinoids act locally through distinct CB(1) and CB(2) mechanisms to suppress mechanical hypersensitivity after the establishment of chronic inflammation, at doses that produced modest changes in thermal hyperalgesia. Additive antihyperalgesic effects were observed following prophylactic co-administration of the CB(1)- and CB(2)-selective agonists. Our results suggest that peripheral cannabinoid antihyperalgesic actions may be exploited for treatment of inflammatory pain states.

Animals↗

A non-invasive gating device for continuous drug delivery that allows control over the timing and duration of spontaneous opiate withdrawal.

Opiate dependence in laboratory animals is commonly induced by two methods: (1) subcutaneous (s.c.) insertion of morphine pellets, and (2) daily injections of increasing doses of opiates. While both of these methods reliably induce opiate dependence, they do not allow one to discontinue, and subsequently reestablish steady state opiate plasma levels with minimal invasive procedures. We developed an "ON-OFF" gating device for repeatedly and non-invasively turning ON or OFF opiate delivery by standard osmotic minipumps. The reliability of this "device" was tested utilizing naloxone (NAL)-precipitated somatic signs of withdrawal, and body mass index (BMI) as measures of withdrawal. Rats were implanted with osmotic minipumps equipped with the gating device, containing heroin (2.66 mg per day). Three days after surgery, somatic signs of withdrawal were precipitated every 48 h by NAL (0.3mg/kg), with minipumps gated ON or OFF. For BMI, spontaneous withdrawal was repeatedly (three times) induced by turning OFF and ON the gating devices every 48 h. Body weights were measured every 4h from 06:00 to 22:00 h daily. Results show that NAL precipitated intense somatic signs of withdrawal when gating devices were ON. This effect was almost abolished when gating devices were OFF. BMI rapidly decreased after the gating devices were turned OFF with maximum weight loss occuring 12 h post-OFF position, and gradually returning to baseline values after gating devices were turned back ON. These results demonstrate the validity of the "ON-OFF" gating device for non-invasively and repeatedly inducing physical dependence to opiates over a prolonged time.

Analysis of Variance↗

Effects of neurotoxic destruction of descending noradrenergic pathways on cannabinoid antinociception in models of acute and tonic nociception.

The effects of neurotoxic destruction of catecholaminergic projections to the spinal cord on cannabinoid antinociception were examined in models of acute and tonic nociception. High performance liquid chromatography was used to quantify monoamine levels in sham-operated and lesioned rats. Intrathecal administration of the catecholamine neurotoxin 6-hydroxydopamine (6-OHDA) induced a selective depletion of norepinephrine (by approximately 85% of control) in rat lumbar spinal cord without altering levels of dopamine or serotonin. By contrast, brain levels of monoamines did not differ in sham-operated and lesioned rats. Pain behavior was similar in sham-operated and lesioned rats receiving vehicle in models of both acute and tonic nociception. The cannabinoid agonist WIN55,212-2 (5 or 10 mg/kg, i.p.) produced antinociception in the tail-flick test in sham-operated rats. The antinociceptive effect of WIN55,212-2 was attenuated relative to control conditions in rats depleted of spinal norepinephrine. WIN55,212-2 suppressed tonic pain behavior in the formalin test in sham-operated rats during phase 2 (15-60 min post formalin) of nociceptive responding. By contrast, in lesioned rats, WIN55,212-2 suppressed pain behavior during phase 1 (0-9.9 min) and phase 2A (10-39.9 min), but not during phase 2B (40-60 min). The cannabinoid agonist suppressed formalin-evoked Fos protein expression, a marker of neuronal activity, in the lumbar dorsal horn of sham-operated rats, but no suppression was observed in lesioned rats. The number of formalin-evoked Fos-like immunoreactive (FLI) cells was greater in lamina I and II of lesioned rats relative to sham-operated rats. These data indicate that the suppressive effect of the cannabinoid on formalin-evoked Fos protein expression in the superficial dorsal horn was attenuated following destruction of descending noradrenergic pathways. Our data are consistent with the hypothesis that cannabinoids produce antinociception, in part, by modulating descending noradrenergic systems and support a differential involvement of noradrenergic projections to the spinal cord in cannabinoid modulation of acute versus tonic nociception.

Analgesics↗

Treatment of childhood Wilms' tumor without radiotherapy in Nicaragua.

BACKGROUND: Recent trends in therapeutic strategies for Wilms' tumor are based on an attempt to reduce or omit radiotherapy (RT) in a sizable fraction of patients. We report here the clinical and histological features as well as the results obtained in 37 children (23 males, 14 females; median age at diagnosis 3 years, range 0.8-8 years) diagnosed between 1991 and 1996, and treated with chemotherapy (CT) and surgery at La Mascota Hospital, Managua, Nicaragua. PATIENTS AND METHODS: Patients were grouped as follows: those who underwent surgery at diagnosis (group A, n = 4), patients who received preoperative CT because of large tumor size (group B, n = 27), lung metastases (n = 5) or bilateral disease (n = 1) (group C, n = 6). Treatment consisted of vincristine (VCR) and actinomycin-D (ACTD) for 24 weeks in group A, and of VCR, ACTD and adriamycin for 68 weeks in groups B and C. Histology was classified as favorable in 30 patients (81%), unfavorable in six patients (all of group B) and unknown in one. RESULTS: With a median follow-up time of 6.4 years the event-free survival for the whole group was 80.1%+/-6.8 (SE). No event occurred beyond 5 years of diagnosis. CONCLUSIONS: These results suggest that RT does not appear necessary for the majority of patients, and that an excellent surgical approach associated with an intensive CT schedule can control the disease, even in the absence of adequate information on the intra-abdominal tumor extent.

Antineoplastic Combined Chemotherapy Protocols↗

Trypanosoma cruzi genotypes associated with domestic Triatoma sordida in Bolivia.

Triatoma sordida is the second species of Triatominae considered of epidemiological significance in Bolivia. Associated with Triatoma infestans in various regions, it is as yet the only triatomine species established in human dwellings in localities of Velasco province, Department of Santa Cruz. This domestication is considered as primary. Flagellate parasites were detected in 16.2% of domiciliary T. sordida and the kDNA-PCR confirmed the presence of Trypanosoma cruzi. Frequencies of T. cruzi clonets 20 and 39, common clonets in Bolivian domestic cycle (T. infestans), were established by their direct detection in feces using PCR and hybridization. These clonets present low frequencies in T. sordida and synanthropic mammals. Forty-six stocks were isolated and analysed by multilocus enzyme electrophoresis (MLEE). The MLEE showed a higher clonal diversity than in T. infestans domestic cycle and the genotypes were clustered in the two principal lineages of T. cruzi. Within each lineage, a broad variability was observed. Mixture of genotypes was mostly observed in mammals. The large diversity of T. cruzi in this cycle should be related to its sylvatic origin. Moreover, the current limited sample of stocks suggests a lineage association with specific hosts.

Animals↗

Cryptic speciation in Triatoma sordida (Hemiptera:Reduviidae) from the Bolivian Chaco.

Eight natural Bolivian populations of two closely related species of Triatominae, Triatoma sordida and T. guasayana, were analysed by multilocus enzyme electrophoresis at 20 loci. Both species were readily separated and no natural hybrid was observed. Among the silvatic sample of T. sordida, strong departure from panmixia within and between loci was detected in two sites of the Chaco, suggesting two reproductively separate populations easily recognized at Idh2 and Mdh2 loci. Genetic distance between them was in agreement with the hypothesis of distinct species. However, the detection of 3% of putative hybrids suggested a recent evolutionary divergence.

Alleles↗

Treatment of childhood Hodgkin's disease with COPP or COPP-ABV (hybrid) without radiotherapy in Nicaragua.

BACKGROUND: Childhood Hodgkin's disease (HD) in low-income countries has been reported to have distinct presenting features, including a high prevalence of the mixed cellularity subtype, which also seems to be associated with poorer prognosis. Further investigations are needed to evaluate these issues. Another controversial aspect of childhood HD is the use of radiotherapy (RT) in its treatment and the growing concern about its serious adverse side effects. In this paper, data on the diagnosis and outcome of children treated without RT in a low-income country (Nicaragua) are reported. PATIENTS AND METHODS: Forty-eight consecutive children aged 0-15 years, diagnosed at 'La Mascota' Hospital of Managua (Nicaragua) from January 1990 to October 1995. entered this study. Follow-up was updated in May 1996. Clinical and histopathological staging was performed according to Ann Arbor and Rye criteria, respectively. Treatment consisted of COPP (six cycles) for stages I or IIA, or COPP-ABV hybrid): eight cycles for stages IIB or III, and ID cycles for stage IV. Total cumulative doses of adriamycin and bleomycin in this protocol are, respectively, 200 and 80 mg:sqm for stages II B or III and 250 and 100 mg/sqm for stage IV. RESULTS: The median age of the 48 patients at diagnosis was seven years, and the mean age was 7.9 years (range 3-15 years). Clinical stages were IA in 5, IIA in 9, IIB in 6, IIIA in 5, IIIB in 14, and IVB in 9. Histopathologically, 25 cases presented with mixed cellularity, 15 with nodular sclerosis, 5 with lymphocytic predominance and 3 with lymphocytic depletion. Four patients did not proceed with treatment and were lost to follow-up. Two patients (stages IIIB and IVB), who never achieved complete remission (CR) during treatment, presented progressive disease at the end of the scheduled chemotherapy. The remaining 42 patients were in complete remission at the end of chemotherapy. Following discontinuation of therapy, one patient (stage IA) was lost to follow-up and two patients with stage IIIB, who were in CR after the second chemotherapy cycle, relapsed 20 and 9 months following the diagnosis. EFS at three years is 100% for the 25 patients with stages I, II, IIIA and 74.9% for the 23 patients with stages IIIB or IV. CONCLUSION: The presenting features found in these patients are similar to those reported from other low-income countries. In our experience, however, the high prevalence of the mixed cellularity subtype was not associated with poorer prognosis. Satisfactory results have been achieved in patients with stages I, II or IIIA HD using COPP or COPP-ABV (hybrid) regimens without RT. The treatment was also well tolerated and can thus be recommended for these patients in low-income countries, where RT facilities may be scarce or unavailable. The use of more aggressive treatment schedules and/or RT on involved fields in front-line treatment may, however, be needed for the more advanced stages IIIB or IV. Large studies with adequate follow-up are needed to evaluate whether, if RT is omitted, higher cumulative doses of more toxic drugs are required and thus compare the long-term toxic effects of different treatment modalities.

Adolescent↗

Natural ecotopes of Triatoma infestans dark morph and other sylvatic triatomines in the Bolivian Chaco.

A survey of natural ecotopes of Triatoma infestans dark morph and other triatomine sylvatic species was performed in an uninhabited area of the Bolivian Chaco. Among the 321 triatomines collected by light trapping, only 4 T. infestans dark morph specimens were identified. Predominant flying species were T. guasayana and T. sordida group 2 (51.7% and 37.1% of capture, respectively). The same species prevailed in terrestrial and epiphytic bromeliads where scarce T. infestans dark morph nymphal instars were also detected. In parrot nests T. delpontei prevailed broadly over other species (90.2% of the capture) and only 4 T. infestans dark morph adults were collected. In contrast, T. infestans dark morph was the predominant species captured in hollow trees (46.0% of the total collected). The abundance of immature forms (88.2% of the collection) shows that hollow trees constitute a favourable ecotope for this species. Of the 421 trees investigated, 33.7% were positive for triatomines. T. infestans dark morph, found inside 15.0% of them, also had higher apparent density than other species (average number of T. infestans in positive trees, 2.0 +/- 1.6 vs 1.3 +/- 0.6 for other species). Light trapping seems to be an efficient method to sample the T. sordida-T. guasayana complex in that it shows a similar distribution to that observed in natural ecotopes; however, this method is ineffective for the assessment of the local abundance of T. infestans dark morph.

Animals↗

Low probability of transmission of Trypanosoma cruzi to humans by domiciliary Triatoma sordida in Bolivia.

The role of Triatoma sordida in the domestic transmission of Trypanosoma cruzi was assessed in 7 rural localities in Velasco Province, Department of Santa Cruz, Bolivia. Tri. sordida, the only triatomine species identified in these localities, was found inside 58.0% of houses but not in large numbers (3.1 bugs per infested house on average). A total of 220 faecal samples from domiciliary bugs was examined microscopically and by the polymerase chain reaction for the presence of trypanosomes: 21.4% were infected. Analysis of blood meals of domiciliary Tri. sordida showed that humans were the commonest host (70.4%), followed by chickens and dogs. Four of 418 persons tested were seropositive for Tryp. cruzi. Only 2 of a second group of 62 persons living in dwellings infested by Tri. sordida were seropositive. Tryp. cruzi infection was demonstrated in dogs and domestic rats. Three other species of small mammals were found to be infected with trypanosomes. In our study area, domestic Tri. sordida are mainly incriminated in the transmission of Tryp. cruzi to synanthropic animals, whereas transmission to humans is very rare. The presence in houses of small populations of Tri. sordida infected with Tryp. cruzi is therefore currently insufficient for this insect to constitute a major epidemiological risk factor.

Animals↗

Genetic structure of Triatoma sordida (Hemiptera: Reduviidae) domestic populations from Bolivia: application on control interventions.

The genetic population of Triatoma sordida group 1, a secondary vector of Chagas disease in Bolivia, was studied by multi-locus enzyme electrophoresis. A total of 253 nymphal and adult specimens collected from seven neighbouring localities in the Velasco Province, Department of Santa Cruz, were processed. The relatively low genetic variability was confirmed for this species (rate of polymorphism: 0.20). The absence of genetic disequilibrium detected within the seven localities was demonstrated. A geographical structuration appears between localities with distances greater than 20 km apart. Although T. sordida presents a relatively reduced dispersive capacity, its panmictic unit is wider than compared with T. infestans. Genetic distances between T. sordida populations were correlated with geographic distance. Gene flow between geographic populations of T. sordida provides an efficient framework for effective vigilance and control protocols.

Animals↗

Ecogenetics of Triatoma sordida and Triatoma guasayana (Hemiptera: reduviidae) in the Bolivian chaco.

Triatoma guasayana and two putative cryptic species pertaining to T. sordida complex (named groups 1 and 2) occur in sympatry in the Bolivian Chaco. Using multilocus enzyme electrophoresis and subsequent genetic analysis, our work assesses their population distribution and dispersal capacity in domestic, peridomestic, and silvatic environments. Our collections by light trap in the silvatic environment indicated a predominance of T. guasayana and T. sordida group 2 and a lesser abundance of T. sordida group 1 ( pound 10% of the total of captures). Their similar distribution in two silvatic areas 80 km apart supports the hypothesis of their homogeneous dispersal through the Bolivian Chaco. The distribution of T. guasayana and T. sordida groups 1 and 2 was similar between silvatic environment and peridomestic ecotopes where 25% of positive places was occupied by two or three species. Bromeliads were confirmed as favorable shelter for T. guasayana but were free of T. sordida. T. sordida group 1 and to a lesser extent T. guasayana would be more invasive vectors for houses than T. sordida group 2. The spatial partition in the three species sampled in two distant sites suggested a reduced dispersive capacity.

Animals↗