RESUMEN
The effects of two pyrethroids on recombinant wild-type and mutant (pyrethroid-resistant) Na+ channels of Drosophila melanogaster have been studied. Three mutations that confer resistance (kdr/superkdr) to pyrethroids were inserted, either individually or in combination, into the para Na+ channel of D. melanogaster: L1014F in domain IIS6, M918T in the IIS4-S5 linker, and T929I in domain IIS5. Channels were expressed in Xenopus laevis oocytes and the effects of the pyrethroids permethrin (type I) and deltamethrin (type II) on Na+ currents were investigated using voltage clamp. The Na+ channels deactivated slowly after deltamethrin treatment, the resultant "tail" currents being used to quantify the effects of this pyrethroid. The Hill slope of 2 for deltamethrin action on the wild-type channel and the mutant L1014F channel is indicative of cooperative binding at two or more sites on these channels. In contrast, binding to the mutants M918T and T929I is noncooperative. Tail currents for the wild-type channel and L1014F channel decayed biphasically, whereas those for M918T and T929I mutants decayed monophasically. The L1014F mutant was approximately 20-fold less sensitive than the wild-type to deltamethrin. Surprisingly, the sensitivity of the double mutant M918T+L1014F to deltamethrin was similar to that of M918T alone, whereas the sensitivity of T929I+L1014F was >30,000-fold lower than that of T929I. Permethrin was less potent than deltamethrin, and its binding to all channel types was noncooperative. The decays of permethrin-induced tail currents were exclusively monophasic. These findings are discussed in terms of the properties and possible locations of pyrethroid binding sites on the D. melanogaster Na+ channel.
Asunto(s)
Drosophila melanogaster/efectos de los fármacos , Insecticidas/toxicidad , Permetrina/toxicidad , Piretrinas/toxicidad , Canales de Sodio/metabolismo , Sustitución de Aminoácidos , Animales , Relación Dosis-Respuesta a Droga , Isoleucina/genética , Metionina/genética , Mutación , Nitrilos , Canales de Sodio/efectos de los fármacos , Canales de Sodio/genética , Tirosina/genéticaRESUMEN
The voltage-gated sodium channel is the primary target site of pyrethroid insecticides. In some insects, super knockdown resistance (super-kdr) to pyrethroids is caused by point mutations in the linker fragment between transmembrane segments 4 and 5 of the para-type sodium channel protein domain II (IIS4-5). Here, we identify two mutations in the IIS4-5 linker of the para-type sodium channel of the whitefly, BEMISIA TABACI: methionine to valine at position 918 (M918V) and leucine to isoleucine at position 925 (L925I). Although each mutation was isolated independently from strains >100-fold resistant to a pyrethroid (fenpropathrin) plus organophosphate (acephate) mixture, only L925I was associated with resistance in strains derived from the field in 2000 and 2001. The L925I mutation occurred in all individuals from nine different field collections that survived exposure to a discriminating concentration of fenpropathrin plus acephate. Linkage analysis of hemizygous male progeny of unmated heterozygous F1 females (L925Ixwild-type) shows that the observed resistance is tightly linked to the voltage-gated sodium channel locus. The results provide a molecular tool for better understanding, monitoring and managing pyrethroid resistance in B. tabaci.
Asunto(s)
Resistencia a Medicamentos/genética , Hemípteros/genética , Insecticidas/toxicidad , Mutación , Compuestos Organofosforados , Piretrinas/toxicidad , Canales de Sodio/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Bioensayo , Cartilla de ADN , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Alineación de Secuencia , Homología de Secuencia de AminoácidoRESUMEN
We conducted a 10 cM linkage genome scan in a set of 20 American pedigrees (153 subjects), ascertained through probands with panic disorder (PD). Several anxiety disorders segregate in these families; they were diagnosed on the basis of Schedule for Affective Disorders and Schizophrenia interview. In this article, we describe results for panic disorder and agoraphobia, which are closely related, common, heritable anxiety disorders. This is the first complete linkage genome scan for agoraphobia and the third for PD. A total of 407 markers (389 autosomal, 18 X chromosome) were genotyped. Multipoint LOD score and NPL analysis were completed using GENEHUNTER2. For PD, two genomic regions meet criteria for suggestive linkage. One of these regions is on chromosome 1 (LOD score = 2.04). This region coincides with a region that generated a LOD score of 1.1 in a previous genome scan by Crowe et al. [2001: Am J Med Genet (Neuropsychiatr Genet) 105:105-109]. The other (LOD score = 2.01) is located on chromosome 11p and occurs at marker CCKBR, one of eight candidate genes examined. For agoraphobia, the most promising potential linkage was on chromosome 3 (NPL score = 2.75; P = 0.005). This was accounted for primarily by a single family that by itself generated an NPL score of 10.01 (P = 0.0039) and a LOD score of 2.10. These results provide initial evidence for a genetic locus on chromosome 3 that contributes to risk for agoraphobia. They also support suggestive linkage to two risk loci for panic disorder. Additional potential loci were identified with lesser statistical support; several of these were consistent with previously reported panic disorder linkage results. Overall, the results presented here suggest that PD and agoraphobia are complex traits that share some, but not all, of their susceptibility loci. Published 2001 Wiley-Liss, Inc.
Asunto(s)
Agorafobia/genética , Predisposición Genética a la Enfermedad/genética , Genoma Humano , Trastorno de Pánico/genética , Agorafobia/patología , Mapeo Cromosómico , Cromosomas Humanos Par 1/genética , Cromosomas Humanos Par 11/genética , Cromosomas Humanos Par 14/genética , Cromosomas Humanos Par 3/genética , Cromosomas Humanos Par 4/genética , Salud de la Familia , Femenino , Humanos , Escala de Lod , Masculino , Repeticiones de Microsatélite , Trastorno de Pánico/patología , LinajeRESUMEN
BACKGROUND: The healthy regulation of appetite involves a balance between excitatory (drive) and inhibitory (satiety) processes. For many years research has concentrated on the identification of signalling systems that mediate satiety to the relative exclusion of drive-inducing biological events. However, the so-called long-term regulation of body weight has recently been given substance by the identification of a chemical signal believed to link the brain with adipose tissue stores. ANALYSIS: This signal, leptin, is in position to modulate the expression of a drive to eat. Studies on the relationship between leptin and perceived hunger, and on the eating behaviour of leptin-deficient individuals, are consistent with the intervention of leptin in a drive system. The contrast between the roles of leptin and serotonin in appetite regulation reflects the difference between drive-signalling and satiety signalling processes. CONCLUSION: It is proposed that leptin modulates the drive signals arising from the metabolic demand for energy but also shows some properties of a post-prandial satiety signal.
Asunto(s)
Apetito/fisiología , Peso Corporal/fisiología , Leptina/fisiología , Saciedad/fisiología , Animales , Humanos , Leptina/metabolismo , Modelos Biológicos , Obesidad/etiología , Obesidad/metabolismoRESUMEN
kdr and super-kdr are mutations in houseflies and other insects that confer 30- and 500-fold resistance to the pyrethroid deltamethrin. They correspond to single (L1014F) and double (L1014F+M918T) mutations in segment IIS6 and linker II(S4-S5) of Na channels. We expressed Drosophila para Na channels with and without these mutations and characterized their modification by deltamethrin. All wild-type channels can be modified by <10 nM deltamethrin, but high affinity binding requires channel opening: (a) modification is promoted more by trains of brief depolarizations than by a single long depolarization, (b) the voltage dependence of modification parallels that of channel opening, and (c) modification is promoted by toxin II from Anemonia sulcata, which slows inactivation. The mutations reduce channel opening by enhancing closed-state inactivation. In addition, these mutations reduce the affinity for open channels by 20- and 100-fold, respectively. Deltamethrin inhibits channel closing and the mutations reduce the time that channels remain open once drug has bound. The super-kdr mutations effectively reduce the number of deltamethrin binding sites per channel from two to one. Thus, the mutations reduce both the potency and efficacy of insecticide action.
Asunto(s)
Resistencia a los Insecticidas , Insecticidas/farmacología , Activación del Canal Iónico/efectos de los fármacos , Piretrinas/farmacología , Canales de Sodio/genética , Animales , Drosophila melanogaster , Activación del Canal Iónico/genética , Potenciales de la Membrana/efectos de los fármacos , Mutagénesis/efectos de los fármacos , Nitrilos , Oocitos/fisiología , Plásmidos , Xenopus laevisRESUMEN
BACKGROUND: Association studies between marker alleles at the D2 dopamine receptor gene (DRD2) and various psychiatric illnesses have produced conflicting results. Reports of allelic associations were originally made with alcoholism, but were then extended to other psychiatric disorders, including posttraumatic stress disorder (PTSD). METHODS: We studied allele frequency of the DRD2 TaqI "A," "B," and "D" system markers in 52 European-American subjects with diagnoses of PTSD (based on structured interviews). RESULTS: Frequency of the A1 allele in this sample was .15, not significantly different from the .19 allele frequency seen in 87 control subjects. We were thus unable to replicate the previous reports of allelic association between the DRD2 TaqI "A1" allele and PTSD. There were also no significant differences in allele frequency for the "B" or "D" systems. We then computed three marker (TaqI "A," "B," and "D" system) haplotypes for the sample; DRD2 haplotype frequencies also did not differ between control subjects and subjects with PTSD. CONCLUSIONS: We conclude that DRD2 alleles are not associated with PTSD in this sample, and that genetic variation at the DRD2 locus is not likely to be an important contributor to risk for this disorder.
Asunto(s)
Alelos , Haplotipos/genética , Receptores de Dopamina D2/genética , Trastornos por Estrés Postraumático/genética , Adulto , Femenino , Variación Genética/genética , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo Genético/genéticaRESUMEN
This study tested two hypotheses involving the use of sport spectating as an opportunity to spend time with one's family. First, it was hypothesized that scores on Family Motivation would be higher for fans who were married or had children than for unmarried fans without children. Second, it was predicted that among sport fans who were married or had children, those preferring a Nonaggressive sport would report higher scores on Family Motivation than those preferring an Aggressive sport. Analysis confirmed the first hypothesis while refuting the second.
Asunto(s)
Agresión/psicología , Actitud , Relaciones Familiares , Motivación , Deportes/psicología , Adolescente , Adulto , Anciano , Composición Familiar , Femenino , Humanos , Masculino , Estado Civil , Persona de Mediana EdadRESUMEN
We have cloned the gene for the human adenosine A3 receptor and report characterisation of its intron/exon structure and upstream untranslated region. The open reading frame is interrupted by a single intron of approximately 2.2 kb, within the coding sequence for the second cytoplasmic loop. Sequence analysis of the upstream region reveals no TATA box but the transcriptional start site has been mapped to a common nucleotide in three tissues by 5'-RACE and RT-PCR analysis. Northern blotting, 5'-RACE PCR and analysis of upstream sequences, have provided no evidence for the occurrence of further introns in the upstream untranslated sequence or of transcriptional regulation by alternative splicing in this region.
Asunto(s)
Receptores Purinérgicos P1/química , Receptores Purinérgicos P1/genética , Secuencia de Aminoácidos , Secuencia de Bases , Northern Blotting , ADN Complementario/química , Humanos , Intrones , Datos de Secuencia Molecular , Sistemas de Lectura Abierta , Reacción en Cadena de la Polimerasa/métodos , Receptores Purinérgicos P1/aislamiento & purificación , Análisis de Secuencia de ADN , Homología de Secuencia de Aminoácido , Homología de Secuencia de Ácido Nucleico , TATA Box , Distribución Tisular , Transcripción GenéticaRESUMEN
We have developed an improved vector for the stable expression of recombinant protein in mammalian cells. In this vector, designated pCIN, both the recombinant cDNA and the neomycin phosphotransferase selection marker are transcribed from a single promoter element. To facilitate translation of the second open reading frame, the encephalomyocarditis virus internal ribosome entry site has been inserted into the expression cassette immediately before the start codon of this sequence. We report the use of this vector to generate stable cell lines expressing the human 5-HT1Da serotonin receptor and show that following transfection and clonal selection, all ten cell lines characterized express similar and high levels of receptor (1.5-11.9 pmol receptor/mg protein). Use of pCIN should permit the rapid and efficient production of stable mammalian cell lines for the characterization of recombinant protein, as this vector appears to predispose all transfected cells to express such protein.
Asunto(s)
Resistencia a Medicamentos/genética , Genes/genética , Vectores Genéticos , Proteínas Recombinantes/genética , Animales , Secuencia de Bases , Línea Celular , Cartilla de ADN/genética , ADN Complementario/genética , Expresión Génica , Humanos , Kanamicina Quinasa , Datos de Secuencia Molecular , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , Plásmidos/genética , Receptores de Serotonina/genética , TransfecciónAsunto(s)
Encéfalo/metabolismo , Hominidae/genética , Receptores Purinérgicos P1/genética , Animales , Clonación Molecular , Exones , Femenino , Humanos , Intrones , Sistemas de Lectura Abierta , Especificidad de Órganos , Placenta/metabolismo , Reacción en Cadena de la Polimerasa , Embarazo , Receptores Purinérgicos P1/biosíntesis , Proteínas Recombinantes/biosíntesisRESUMEN
The human 5-HT5A serotonin receptor has been cloned. As with the mouse and rat 5-HT5A receptors, the gene consists of two coding exons separated by a large intron. The deduced amino acid sequence of the gene reveals a protein of 357 residues which shares 93% (nucleotide) and 84% (amino acid) identity to the cloned mouse 5-HT5A receptor. We have determined the tissue distribution of the receptor by reverse transcriptase-PCR and found expression in all regions of the brain examined with little or no expression in peripheral tissues. The receptor has been transiently expressed in Cos M6 cells and exhibits a pharmacological profile closely resembling the mouse and rat 5-HT5A receptors with high, specific binding for ergotamine and methiothepin.
Asunto(s)
Química Encefálica , Receptores de Serotonina/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Clonación Molecular , Proteínas de Unión al GTP/metabolismo , Genoma Humano , Humanos , Ratones , Datos de Secuencia Molecular , Ensayo de Unión Radioligante , Receptores de Serotonina/biosíntesis , Receptores de Serotonina/metabolismo , Análisis de Secuencia de ADN , Homología de Secuencia de Aminoácido , Homología de Secuencia de Ácido Nucleico , Serotonina/metabolismo , Distribución Tisular , TransfecciónRESUMEN
Thoracoabdominal aneurysms are the most extensive of aortic aneurysms, and their correction is associated with the greatest number of complications. The introduction of new techniques has reduced the morbidity and mortality of surgery for these formidable lesions. A description of some of these techniques, as applied to 33 patients, is summarized, and the results presented.
Asunto(s)
Aneurisma de la Aorta/cirugía , Procedimientos Quirúrgicos Vasculares/métodos , Adulto , Anciano , Aneurisma de la Aorta Abdominal/cirugía , Aneurisma de la Aorta Torácica/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
We defined interpopulation differences in the frequency of the dopamine D2 receptor DRD2/Taq1 A1 allele, which has previously been associated with alcoholism. Frequencies of the A1 allele in unrelated subjects were 0.18 to 0.20 (se = 0.02 to 0.03) in several Caucasian populations previously assessed, 0.38 (+/- 0.05) in American Blacks (n = 44), 0.63 (+/- 0.07) in Jemez Pueblo Indians (n = 23), and 0.80 (+/- 0.04) in Cheyenne Indians (n = 52). The existence of large interpopulation differences in the frequency of the Taq1 alleles suggests that associations to disease status could readily be generated or masked if disease and control groups were uneven in ethnic composition. To address the possibility that the 4-fold higher frequency of the A1 allele in Cheyenne Indians was related to an increased vulnerability to alcoholism in that population, 47 Cheyenne Indians were psychiatrically interviewed and blind-rated. However, there was no significant difference between interviewed controls (0.73 +/- 0.06, n = 24), subjects with alcoholism and/or drug abuse (0.74 +/- 0.06, n = 23) and noninterviewed population controls (0.87 +/- 0.05, n = 20). Legitimate association of the DRD2/Taq1 allele to alcoholism would presumably require it to be in linkage disequilibrium (nonrandom association) with a functional mutation at DRD2 or elsewhere. The level of disequilibrium would vary between populations and could place an upper bound on the strength of an association.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Alcoholismo/genética , Genotipo , Indígenas Norteamericanos/genética , Desequilibrio de Ligamiento , Receptores de Dopamina D2/genética , Adulto , Alelos , Población Negra , Frecuencia de los Genes , Marcadores Genéticos/genética , Humanos , Modelos GenéticosRESUMEN
This family and small community-based study reports the occurrence of alcoholism and co-occurring substance abuse in Southern Cheyenne Indians living in western Oklahoma. Sociocultural factors complicate operationalization of clinical data into standard (DSM-III-R) psychiatric disorder terminology; understanding sociocultural factors is essential for assessing the high rate of addictive disorders in this group. To obtain reliable and valid clinical diagnoses, data from several sources were utilized within a blind rating system: 1) SADS-L, a clinician-administered research diagnostic instrument; 2) MAST; 3) relatives; 4) medical records; 5) other official documents. The sample consisted of 69 males (45 alcoholics) and 97 females (36 alcoholics). Among clinically significant substance abusers (moderate impairment of function), 22 of 24 were alcoholics. In non-alcoholics, mean MAST scores were 8.8 (males) and 5.1 (females); in alcoholics, 32.0 (males) and 38.7 (females). Mean age of onset on heavy use of alcohol was 20.1 yrs. (males) and 22.8 (females) (p = 0.047); among all alcoholics, 86% (males) and 64% (females) had early onset (< 25 yrs. old). When data from 98 unrelated subjects were analyzed separately, similar findings were observed except that mean age of onset of heavy use of alcohol was more discrepant between males and females, viz. 20.1 versus 22.8 yrs. (p = 0.02). Among those with substance abuse disorders, early age of onset was present in all but one female. In these Cheyenne, alcoholism is usually clinically severe and early in onset; it often co-occurs with substance abuse, also early in onset.
Asunto(s)
Alcoholismo/epidemiología , Comparación Transcultural , Drogas Ilícitas , Indígenas Norteamericanos/estadística & datos numéricos , Psicotrópicos , Trastornos Relacionados con Sustancias/epidemiología , Adolescente , Adulto , Alcoholismo/genética , Alcoholismo/psicología , Comorbilidad , Estudios Transversales , Femenino , Humanos , Incidencia , Indígenas Norteamericanos/psicología , Masculino , Oklahoma/epidemiología , Razón de Masculinidad , Trastornos Relacionados con Sustancias/genética , Trastornos Relacionados con Sustancias/psicologíaRESUMEN
Four patients with the crush syndrome due to prolonged limb compression were treated at Cook County Hospital, Chicago. Limb injury was caused when the obtunded patient fell asleep lying on the involved extremity. Prolonged limb compression may cause an acute compartment syndrome with ischemic muscle injury. Continued muscle ischemia may lead to myonecrosis resulting in shock or renal failure. A history of prolonged limb compression with a swollen limb should suggest the diagnosis of crush syndrome. Prompt therapy, including rapid correction of volume and metabolic derangements, extensive open fasciotomy, and dialysis for severe acute renal failure should provide good functional results in the majority of patients.
Asunto(s)
Brazo/irrigación sanguínea , Síndromes Compartimentales/complicaciones , Síndrome de Aplastamiento/cirugía , Isquemia/complicaciones , Pierna/irrigación sanguínea , Postura , Choque Traumático/cirugía , Trastornos Relacionados con Sustancias/complicaciones , Lesión Renal Aguda/etiología , Adulto , Síndromes Compartimentales/etiología , Síndrome de Aplastamiento/complicaciones , Síndrome de Aplastamiento/etiología , Síndrome de Aplastamiento/fisiopatología , Humanos , Isquemia/etiología , Masculino , Persona de Mediana EdadRESUMEN
Previous reports have suggested that duplex ultrasonography might supplant arteriography as a guide to operative decision making in selected patients with cerebrovascular disease. This study was undertaken to test that tenet in patients with focal carotid territory symptoms. Seventy-two patients having independently interpreted arch and selective carotid arteriography and duplex scanning underwent 78 carotid endarterectomies. Operative specimens were analyzed in all cases and used as the standard in evaluating the accuracy of the preoperative studies. All patients had disease found at the time of operation. The sensitivity of duplex scanning was 99% vs. 91% for arteriography (p = 0.06). In seven cases the scan accurately predicted disease in patients with normal arteriograms and in a single case the scan was read as normal in a patient with a smooth minimally stenotic plaque read as an irregular 30% stenosis on arteriography. The accuracy of duplex scanning was markedly superior to arteriography in detecting intimal surface abnormalities (92% vs. 64%, p less than 0.001) and ulceration (90% vs. 54%, p less than 0.001). There was no difference between duplex scan and arteriography (p = 1.0) in predicting a greater or less than 50% stenosis (accuracy, 94% for arteriogram; 92% for duplex scanning). Of the patients with preoperative potentially reversible symptoms, 97% were free of symptoms at a mean follow-up of 9 months after operation. Eighty-nine percent (17 of 19 patients) of patients with concomitant, ipsilateral, intracranial, or intrathoracic cerebrovascular disease were free of symptoms after carotid endarterectomy.
Asunto(s)
Enfermedades de las Arterias Carótidas/diagnóstico , Angiografía Cerebral , Ultrasonografía , Enfermedades de las Arterias Carótidas/cirugía , Endarterectomía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Cuidados PreoperatoriosRESUMEN
A recent experience with infrainguinal graft infections was reviewed in an effort to identify factors related to limb loss and mortality. The records of 32 patients who had operative treatment of 33 episodes of infrainguinal graft infection between 1978 and 1985 were reviewed to evaluate the effects of 20 factors possibly affecting outcome. The amputation rate was 79%. Of the 20 factors studied, only the presence of overt limb sepsis was associated with the need for amputation, with 100% of patients having limb sepsis requiring amputation vs. 72% of patients without limb sepsis (p = 0.03). The in-hospital mortality rate was 22%. Eighty-six percent of the deaths were due to ongoing sepsis. Again, a single factor was associated with death. Five of the 12 patients (42%) in whom preservation of axial flow was attempted died in contrast to only 2 of 20 patients (10%) who did not have attempted arterial reconstruction (p = 0.04). Limb salvage did not occur in any of the patients in whom preservation of axial flow was attempted and nine required above-knee amputation. Thirteen of the remaining 20 patients had occluded femoral vessels either because of operative ligation (nine) or previous thrombosis (four). Above-knee amputations healed in all but one of these 13 patients. Determined attempts at increasing limb preservation were associated with no improvement in amputation rate or level and were accompanied by an unacceptably high mortality rate. Aggressive control of sepsis through the early amputation of septic limbs after graft removal may improve survival without further detriment to limb preservation.
Asunto(s)
Amputación Quirúrgica , Prótesis Vascular/mortalidad , Pierna/irrigación sanguínea , Infección de la Herida Quirúrgica/mortalidad , Humanos , Tereftalatos Polietilenos , Politetrafluoroetileno , Flujo Sanguíneo Regional , Vena Safena/trasplanteRESUMEN
Evidence in vitro and in humans suggest that Mg2+ can alter systemic and renal vascular tone. However, the mechanism of these effects is not known. The role of vasodilator prostaglandin release and Ca2+ flux in Mg2+-induced changes in blood pressure and renal blood flow was studied in 10 normal subjects maintained on a fixed 80-mEq Na+ and K+ diet. Magnesium sulfate infused at 200 mg/hr for 3 hours reduced systolic and diastolic blood pressure within 1 hour (from 119 +/- 2 [SEM] to 109 +/- 4 mm Hg systolic; from 74 +/- 3 to 64 +/- 4 mm Hg diastolic; p less than 0.02). This hypotensive response was seen in all subjects and persisted for 3 hours. The pulse rate did not change, but renal blood flow (p-aminohippurate clearance) increased (from 902 +/- 78 to 1108 +/- 130 ml/min/1.73 m2; p less than 0.05). The Mg2+ infusion produced a significant increase in the excretion of the stable prostaglandin I2 (PGI2) metabolite 6-keto-PGF1 alpha (from 96 +/- 12 to 154 +/- 16 ng/g creatinine; p less than 0.01). In contrast, urinary PGE2 was not altered (328 +/- 75 vs 399 +/- 145 ng/g creatinine; p greater than 0.6). To evaluate the functional role of PGI2 release, the cyclooxygenase inhibitors indomethacin (75 mg) or ibuprofen (600 mg) were given before the Mg2+ infusion. Both cyclooxygenase blockers, given in doses that inhibited immunoreactive 6-keto-PGF1 alpha release, completely prevented the Mg2+-induced decline in blood pressure and increased renal blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Presión Sanguínea/efectos de los fármacos , Epoprostenol/fisiología , Magnesio/farmacología , Circulación Renal/efectos de los fármacos , Adulto , Calcio/metabolismo , Femenino , Humanos , Canales Iónicos/metabolismo , Masculino , Vasodilatación/efectos de los fármacosRESUMEN
Because infrainguinal bypasses performed on the basis of normal papaverine testing in patients with multilevel arterial occlusive disease are done below arteriographically diseased although hemodynamically normal vessels, there is concern about progression of suprainguinal disease compromising long-term success. This study has been done to assess the long-term results of such bypasses. Between 1979 and 1985, infrainguinal bypasses selected by papaverine testing were done on 92 limbs having hemodynamically normal inflow in the presence of arteriographically demonstrable aortoiliac stenoses of 15% to 70%. Long-term hemodynamic and clinical success rates were determined with criteria based on papaverine and noninvasive vascular testing. There was no significant difference in hemodynamic success at 48 months (by life-table analysis) (p = 0.98) when comparing limbs with less than 50% aortoiliac stenoses to limbs having 50% or greater stenoses. The difference between the mean degree of preoperative inflow stenoses for long-term hemodynamic successes (32.5% +/- 1.5%) and failures (34.6% +/- 3.0%) was not significant (p = 0.57). There was no significant difference (p = 0.98) in the number of subsequent inflow procedures required in limbs with preoperative aortoiliac stenoses of less than 50% (13.5%) vs. aortoiliac stenoses of 50% or greater (13.3%). Long-term results of infrainguinal bypass done below stenotic but hemodynamically normal aortoiliac vessels are not related to the amount of angiographically demonstrable inflow stenosis. Selection of patients for infrainguinal bypass on the basis of papaverine testing, irrespective of angiographic findings, eliminates unnecessary inflow procedures without detriment to long-term success.