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Biomedical subjects

M Lopez

Publications and source records attributed to M Lopez.

At least 217 records · Page 12Linked to original sources

Physiologic responses to hyperthermia during epidural anesthesia and combined epidural/enflurane anesthesia in women.

BACKGROUND: During combined epidural/isoflurane anesthesia, the core temperature triggering finger-tip vasoconstriction is approximately 1 degree C less than that triggering redilation. This hysteresis suggests that thermoregulatory responses are not dependent entirely on current thermal status (state-dependence), but may be influenced also by the system's recent thermal history (direction-dependence). Once triggered, the gain and maximum response intensity of many thermoregulatory responses is nearly normal during isoflurane anesthesia. However, it remains unknown whether preserved gain and maximum response intensities are a characteristic paradigm describing thermoregulatory responses to general anesthetics. Also unknown is whether the sweating and pre-capillary vasodilation thresholds are comparably impaired by different volatile anesthetics. Accordingly, the authors tested the hypotheses that, during one minimum alveolar concentration of enflurane anesthesia: (1) there is a direction-dependent hysteresis for sweating; (2) the sweating and active vasodilation thresholds increase approximately 1.2 degrees C, as they do during one minimum alveolar concentration of isoflurane; and (3) the gain and maximum intensity of sweating are well preserved. METHODS: Six female volunteers each were studied on 2 days, once during epidural anesthesia alone and once with combined enflurane (1.7%)/epidural anesthesia. On each study day, core hyperthermia was induced by cutaneous warming restricted to the legs. Warming continued until chest sweating reached maximal values; the volunteers then were cooled gradually until sweating stopped. The core temperature at which the sweating rate departed from baseline values was considered the activation threshold. Gain was expressed as the slope of the sweating rate versus core temperature curve within the range 25-75% of the maximum sweating rate. Hysteresis was evaluated by subtracting the tympanic membrane temperature at which the sweating rate suddenly increased during warming (approximately 25% above baseline values) from that at which sweating precipitously decreased during cooling (approximately 75% of maximum values). RESULTS: The sweating threshold was 1.4 +/- 0.7 degrees C higher during combined enflurane/epidural anesthesia than during epidural anesthesia alone. Maximum intensity was approximately 700 g.m-2.h-1, and the gain approximately 1,300 g.m-2.h-1.degrees C-1 during each treatment. No hysteresis was detected on either study day. CONCLUSIONS: One minimum alveolar concentration of enflurane increased the sweating threshold only slightly more than previously reported for isoflurane. As in previous studies of sweating and vasoconstriction during isoflurane anesthesia, gain and maximum response intensity were well preserved during enflurane anesthesia. An increase in the interthreshold range (temperatures not triggering thermoregulatory responses), with little change in gain and maximum response intensities, appears to be the typical effect of volatile anesthetics. Sweating during enflurane anesthesia appears to be state-dependent and little influenced by the direction of core temperature perturbations.

Adult↗

The effects of a multimodal intervention with attention-deficit hyperactivity disorder children: a 9-month follow-up.

Using a double-blind, placebo design, we evaluated 96 attention-deficit hyperactivity disordered children for the effects of methylphenidate alone and in combination with behavioral parent training plus child self-control instruction. Seventy one of the children completed the treatment protocol. As reported previously, main effects were found for medication at posttest; however, there was no evidence of additive effects. Nine months after the termination of the behavioral interventions and the withdrawal of the stimulant medication, we found limited support for the hypothesis that the combined conditions would produce greater maintenance of treatment gains than would medication alone.

Achievement↗

Somatostatin receptor imaging in small cell lung cancer using 111In-DTPA-octreotide: a preliminary study.

Small cell lung cancer is a common and aggressive disease. Combined multiagent chemotherapy and radiotherapy can improve short-term prognosis, but long-term prognosis remains dim. Somatostatin receptors have been identified on the cellular surface of subsets of this cancer and may be associated with less aggressive evolution. Moreover, medical therapy with somatostatin analogues holds promise for neoplastic growth control. Planar scintigraphy has been performed in 15 patients with histologically proven small cell lung cancer at 4 and 24 h after the intravenous (i.v.) injection of 185 MBq 111In-octreotide (Octreoscan, BYK-Gulden). No short-term adverse effects were recorded; tumour uptake of the radiopharmaceutical was observed in 13 patients at 4 h and in 12 patients at 24 h suggesting more extensive disease than apparent by computed tomography (CT). It is highly likely that the 24 h uptake reflects the presence of somatostatin receptors on the tumour. Previous chemotherapy does not seem to play a key role in tumour visualization. 111In-octreotide is a suitable radiopharmaceutical for in vivo evaluation of somatostatin receptor status of small cell lung cancer. Quantitative scintigraphic methods are needed to investigate nonspecific binding and receptor kinetics.

Aged↗

Modifications of PC20 and maximal degree of airway narrowing to methacholine after pollen season in pollen sensitive asthmatic patients.

We examined the effect of cessation of exposure to pollen on non-specific airway responsiveness in 10 grass and/or parietaria pollen sensitive asthmatics. Three methacholine inhalation challenges were performed, the first during pollen season (seasonal period), the second 2 months after the end of season (short time after seasonal period), and the third 5 months after the end of season (long time after seasonal period). The dose-response curves to methacholine were characterized by the PC20 (provocative concentration of methacholine required to produce a 20% fall in FEV1) and maximal response plateau, if possible. A maximal response plateau on the dose-response curve was considered to be present if three or more data points for FEV1 fell within a 5% response range. The challenge was stopped when FEV1 dropped more than 50% or the highest concentration of methacholine (200 mg/ml) was reached. The geometric mean (range) methacholine PC20 increased from 1.08 (0.18-37.22) in the seasonal period to 4.67 (0.71-200) mg/ml during the long time after seasonal period (P < 0.01). On the other hand, in six subjects in whom it was possible to obtain a plateau on at least one challenge, the level of the maximal response decreased from (mean +/- s.e.m.) 44.1 +/- 4.9 in the seasonal period to 30 +/- 4.4 during the long time after seasonal period (P < 0.05). These results suggest that in pollen sensitive asthmatic patients, the cessation of exposure to pollen is associated with a reduction of non-specific bronchial responsiveness (PC20 and maximal degree of airway narrowing to methacholine).

Adolescent↗

Amoxicillin and clavulanic acid in the treatment of actinomycetoma.

BACKGROUND: Mycetoma is a relatively frequent disease in tropical countries. Drugs commonly used need a long period of treatment, and some cases are resistant to these drugs, especially those with bone or visceral involvement. The combination of amoxicillin-clavulanic acid has shown effectiveness against strains of Nocardia brasiliensis in vitro. METHODS: We have used this combination in two cases of mycetoma caused by N. brasiliensis, both with bone involvement and resistance to the drugs usually used. A dose of three tablets a day for 5 to 6 months was given (each tablet contains 500 mg of amoxicillin and 125 mg of clavulanic acid). RESULTS: Clinical and mycologic amelioration was observed in the two cases after completing the treatment. There were no side effects or relapses after 3 to 6 months of follow-up after treatment. CONCLUSIONS: We propose this antibiotic as a new option for the treatment of some special cases of actinomycetoma with bone or visceral involvement or resistance to the drugs commonly used in this disease.

Amoxicillin↗

Diet and ethanol modulate immune responses in young C57BL/6 mice.

Chronic ethanol (ETOH) ingestion adversely affects the immunocompetence of alcohol abusers. ETOH directly impairs host defense mechanisms and indirectly modulates immunocompetence by interfering with the nutritional status of the alcoholic. It is not clear from the current literature, however, to what extent ETOH, nutritional status, or the combination of the two factors modulates immune mechanisms in chronic alcoholics. To date, most animal studies investigating the immunotoxicity of ETOH have neglected the dietary factors, which may have masked additional immunotoxic effects of ETOH. To examine these dietary factors, we fed mice three liquid ETOH diets with different dietary sufficiencies for 7 weeks and investigated various immune responses. Spleen cell number and secretions of immunoreactive interleukin-2 and tumor necrosis factor were totally independent of the diet, being affected only by ETOH. Body, spleen, and thymus weights, interferon-gamma secretion, and natural killer cell and phagocytic activities were modulated by ETOH as well as by diet. Natural killer cell and phagocytic activities were also directly affected by the nutritional quality of the diet. These results suggest that animal diets used in experimental studies of ETOH-induced immunomodulation must be planned and controlled carefully in order to single out the direct effects that ETOH has on the host defense system.

Alcoholism↗

An improved, non-isotopic method of screening cells from patients with abnormalities of sexual differentiation for Y chromosomal DNA content.

The detection of 45,X/46,XY mosaicism in patients with abnormalities of sexual differentiation is of crucial diagnostic importance. Here we present application of a PCR based method of detection of alphoid repeats of Y chromosomal origin. The method detects 0.01% of male DNA on a female DNA background. Out of 28 patients studied, in all cases where the Y chromosome or a part of it containing centromeric sequences was present, a positive amplification signal of Y chromosomal alphoid repeats was detected. In five cases the Y origin of marker chromosomes was diagnosed. The pattern of amplification signal distribution of the SRY gene was identical to that of Y specific alphoid primers, which confirms applicability of this method in the molecular diagnostic laboratory. The other diagnostic advantage is the ability to use dried blood specimens as an easy to handle and efficient source of DNA.

DNA↗

Diagnosis of Leishmania using the polymerase chain reaction: a simplified procedure for field work.

Oligonucleotide primers directed to the minicircle kinetoplast DNA of Leishmania strains supported enzymatic amplification of this DNA by the polymerase chain reaction (PCR). A single product of 70 basepairs was obtained from parasites belonging exclusively to the L. braziliensis complex. Direct sequencing of the amplified product confirmed its minicircle origin. Skin biopsy specimens from human patients were used directly for the PCR. A pulse incubation of such specimens with deoxyribonuclease I prior to the PCR increased the reliability of the assay. Nuclease disruption of the kinetoplast network was expected to make more copies of the minicircle accessible to amplification. Comparative results between the PCR and conventional parasitologic detection procedures indicate that the DNA detection approach presented is by far more sensitive for diagnostic purposes. Innovations in the PCR protocol are presented that adapt the diagnosis of leishmaniasis to settings with minimal equipment and that are distant from central laboratories.

Animals↗

New developments in stem cell detection and stem cell selection in the context of autologous transplantations.

The concept of bone marrow transplantation is now enlarged to hemopoietic stem cell transplantation. Basic research on hemopoiesis, its regulation and markers, allowed concrete progress in the field of autologous transplantation. We report two applications: 1) the improvement of methods for detection of stem cells, which ensure engraftment, using recombinant growth factors, allowed a more sensitive determination of chemotherapeutic in vitro treatments toxicity upon normal progenitor cells; 2) large scale selection of hemopoietic progenitor/stem cell using the CD 34 immunological marker: its application to autologous transplantation.

Bone Marrow Purging↗

Autologous bone marrow transplantation with marrow purged by mafosfamide in seven patients with myelodysplastic syndromes in transformation (AML-MDS): a pilot study.

Seven patients with acute myeloblastic leukemia (AML) occurring on myelodysplastic syndromes (MDS) were consolidated while in complete remission (CR) by autologous bone marrow transplantation (ABMT) with a marrow purged in vitro by mafosfamide. The median age of population was 44 years (range 39-55). MDS FAB diagnosis was established before progression to AML in five patients: refractory anaemia with excess of blast (RAEB) in three patients, RAEB in transformation (RAEB-t) in one patient, and chronic myelomonocytic leukemia (CMML) in one patient. In the remaining two patients, the diagnosis of MDS (as a secondary malignancy in one) was made retrospectively at time of overt AML. Three out the seven patients had karyotypic abnormalities. The median interval between the obtention of CR and ABMT was 7 months (range 6-18). One patient died from transplant related toxicity. Engraftment occurred at a median of 41 days (range 27-60), for white blood cells (> 10(9)/l) and 120 days (range 60-180) for platelets (> 50 x 10(9)/l). Four patients relapsed at 2.5, 6.8, and 25 months post-ABMT. Two patients are alive and well at 10 and 28 months, respectively. ABMT with marrow purged by mafosfamide is feasible in patients with AML following MDS with a prospect of cure. However, further studies are needed to assess the real value of this approach.

Adult↗

In vitro purging of bone marrow with mafosfamide synergizes with in vivo chemotherapy to delay the hematological recovery in a murine model of autologous bone marrow transplantation.

Very long-lasting leukopenias and thrombocytopenias have been observed in patients submitted to transplantation of autologous bone marrow incubated in vitro with cyclophosphamide derivatives. With the aim of evaluating the contribution of in vitro exposure of bone marrow to mafosfamide (Asta-Z) and of in vivo chemotherapy given before bone marrow collection in these cytopenias, we designed a murine model of syngeneic bone marrow transplantation including treatment of donor and recipient mice with high doses of cyclophosphamide and in vitro exposure of the bone marrow transplant to Asta-Z. Blood platelets and leukocytes, medullary splenic colony forming unit (CFU-S), committed megacaryocytic (CFU-Meg) and granulomacrophagic (CFU-GM) precursor cell recovery was followed up to 56 days posttransplant. The data indicate that in vitro exposure of bone marrow to Asta-Z before reinfusion increases the delay in platelet recovery already induced by the chemotherapy given to donor mice and is specifically responsible for the prolongation of leukopenia. In recipient bone marrow, a synergy between the ablative effect of the in vitro treatment of bone marrow graft and the chemotherapy given to donors and recipients on CFU-S, CFU-Meg and CFU-GM was found.

Animals↗

Multiple chromosome abnormalities in patients with acute leukemia after autologous bone marrow transplantation using total body irradiation and marrow purged with mafosfamide.

Cytogenetic follow-up studies such as those reported after allogeneic bone marrow transplantation are not available in patients submitted to an autologous bone marrow transplantation (ABMT). Of 114 patients with acute leukemia (69 acute myelocytic AML, 43 acute lymphocytic ALL, 2 undifferentiated) who underwent an ABMT in our institution in the period from February 1983 to December 1989, 66 had evaluable cytogenetic data post-transplant. They all received a pretransplant regimen consisting of cyclophosphamide (CY) and total body irradiation (TBI) followed by reinfusion of marrow purged with mafosfamide. Twenty patients showed chromosomal damage at some time; of these, six relapsed early post-ABMT, one died while in persisting remission at 81 months post-ABMT from overwhelming pneumococcal sepsis related to a previous splenectomy, and 13 are still alive and well at 13 to 88 months post-transplant. The bone marrow cytogenetic abnormalities were complex: they included various numbers of clonal aberrations or variations or combination of those; they affected all but the Y chromosome, with a predominance however for chromosomes 1, 3, 6, and 7; they were often transitory and in some instances became modified with time. None of these chromosomal abnormalities was connected with the initial leukemia, even in the 6 patients who relapsed early. In the other 14 patients, these abnormalities have so far had no detectable unfavourable implication. The origin of these abnormalities is unknown: both the pretransplant regimen (CY and/or TBI) and/or marrow purging with mafosfamide can be incriminated. Additional studies in patients autografted with pretransplant regimen not containing TBI and/or with unpurged marrow are necessary to discriminate between these two possibilities.

Antineoplastic Agents↗

Reactivity of carrot-specific IgE antibodies with celery, apiaceous spices, and birch pollen.

Although carrot allergy is not well recognized in North America, the celery-carrot-mugwort-spice syndrome is well known in Europe. In the current study, cross reactivity of carrot, stalk celery, and spices, all members of the Apiaceae and birch pollen was assessed with serum from a patient reporting raw carrot-induced, raw stalk celery-induced, or spice-induced laryngeal edema and bronchospasm. By RAST inhibition, some cross-reactivity was demonstrated between raw carrot and stalk celery and other members of the Apiaceae. Immunoprint inhibition revealed common allergic epitopes on a 17-kD band shared by carrot, celery, and birch pollen. The results suggest that subjects sensitized to carrot may also have allergic reaction to other vegetables of spices of the Apiaceous family. Furthermore, carrot hypersensitivity can be associated with birch pollen allergy.

Allergens↗

Carboplatin, methotrexate, and vinblastine in patients with bladder cancer who were ineligible for cisplatin-based chemotherapy.

BACKGROUND: A Phase II trial with a new regimen of methotrexate, carboplatin, and vinblastine (M-CAVI) was conducted for patients with bladder cancer who could not receive cisplatin-based chemotherapy. METHODS: Treatment consisted of methotrexate (30 mg/m2) on days 1, 15, and 22; carboplatin (300 mg/m2) on day 2; and vinblastine (3 mg/m2) on days 2, 15, and 22, scheduled at 28-day intervals. The dosage of carboplatin was adjusted for creatinine clearance. Twenty-five patients with metastatic (n = 9) or locally advanced or locoregional bladder cancer with a poor prognosis (n = 16) were treated with M-CAVI. Fifteen patients had abnormal serum creatinine levels, 4 had a low performance status, 3 had cardiac disease, and 3 were older than 70 years old. RESULTS: Among 23 patients assessable for clinical response, the response rate was 48%. The median duration of response for metastatic disease was 7 months. Among nine patients assessable for pathologic response, there were two complete responses and three partial responses. The toxic effects have been moderate. CONCLUSIONS: M-CAVI is an active and well-tolerated regimen that can be used in patients with bladder cancer who are ineligible to receive cisplatin-based chemotherapy.

Adult↗

Multiple Rh messenger RNA isoforms are produced by alternative splicing.

Three Rh-related cDNAs have been isolated from a human bone marrow cDNA library and by polymerase chain reaction (PCR) amplification of human bone marrow and erythroblast mRNAs. They potentially encode a family of Rh protein isoforms that exhibit several unexpected structural properties as compared with the Rh polypeptide encoded by the cDNA clone identified previously. These modifications include several peptide deletions, the predicted alteration of Rh protein topology within the cell membrane, variations in the number and surface exposition of cysteine residues, and the generation of new C-terminal polypeptide segments caused by frameshift mutations. The four Rh mRNAs now described correspond to different splicing isoforms transcribed from the same Rh gene, and all exist in the same cell lineage (erythroid). Moreover, PCR experiments indicated that at least three of these RNA species exist in reticulocytes from donors with different commonly expressed Rh phenotypes. Although the translated proteins have not yet been characterized, these results suggest that the two genes at the RH locus may direct the synthesis of several protein species possibly corresponding to different Rh antigenic variants.

Amino Acid Sequence↗