RESUMEN
PURPOSE: The purpose of the present study was to prospectively compare the predictive accuracy of static venous pressure (SVP); dynamic venous pressure (DVP) and access blood flow (ABF) in determining subsequent graft thrombosis and/or failure. METHODS: This study included 43 patients with functional arteriovenous grafts (AVG's) who underwent monthly seri-al measurements of SVP, DVP and ABF for 3 consecutive months. Patients were then followed for an additional 6 months. The primary end point was graft thrombosis. RESULTS: Six patients were excluded from the final analysis. Of the 37 patients completing the study, 7 episodes of graft thrombosis occurred within 6 months of follow up. Neither SVP nor DVP exhibited satisfactory sensitivity or specificity for graft thrombosis. Ten patients either began with or developed an ABF < 600 during the 3 months of measurements, but only 5 clotted. delta ABF of >20% provided the best combination of sensitivity (86%) and specificity (90%) for graft thrombosis. In AVG's that have an ABF<600, it is those grafts with falling ABF that appear most likely to clot in the short term. CONCLUSION: The study supports the concept that it is a falling level of access flow rather than the absolute level that is the most potent predictor of graft thrombosis.
Asunto(s)
Velocidad del Flujo Sanguíneo , Oclusión de Injerto Vascular/diagnóstico , Diálisis Renal , Trombosis/diagnóstico , Presión Venosa , Anciano , Derivación Arteriovenosa Quirúrgica/efectos adversos , Implantación de Prótesis Vascular/efectos adversos , Femenino , Oclusión de Injerto Vascular/etiología , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Prospectivos , Diálisis Renal/métodos , Trombosis/etiología , Factores de TiempoRESUMEN
The purpose of this study was to retrospectively review our experience with a consecutive group of 41 renal transplant recipients (R) who received a kidney from a cytomegalovirus (CMV) seropositive donor (D(+)) and had 3 months of prophylaxis with oral ganciclovir. Patients were prospectively monitored clinically and with determinations of CMV antigenemia for at least 6 months. Patients were followed for a mean period of 247+/-16 days. CMV antigenemia developed in 51% of patients (53% D(+)R(-), 47% D(+)R(+)) after the transplant, but in no case was antigenemia seen during the period of oral ganciclovir therapy. Antigenemia developed at a median of 167 days post transplant (range 99-522 days) and peak antigen counts ranged from <1-3940, and tended to be higher in D(+)R(-) recipients. Infection was symptomatic in 67% of the antigenemic patients and symptoms tended to be more marked in the D(+)/R(-) than in the D(+)/R(+) group. All symptomatic patients were treated with intravenous ganciclovir (21 days) followed by 9 weeks of oral ganciclovir and responded with resolution of symptoms and antigenemia. No evidence of tissue-invasive disease was seen. Recurrence of antigenemia was observed exclusively in the D(+)R(-) group, occurred with less severe manifestations of CMV infection, and invariably responded to retreatment with ganciclovir. Our results suggest that oral ganciclovir prophylaxis is effective in preventing CMV infection during the 3-month period of prophylaxis, that a 3-month period of prophylaxis appears to be sufficient for D(+)R(+) recipients, but a longer period of oral ganciclovir prophylaxis may be needed in D(+)R(-) recipients. Clinicians caring for renal transplant recipients should be vigilant to the possibility of late CMV infection, especially in D(+)R(-) recipients.
Asunto(s)
Antivirales/uso terapéutico , Infecciones por Citomegalovirus/diagnóstico , Citomegalovirus/aislamiento & purificación , Ganciclovir/uso terapéutico , Trasplante de Riñón/efectos adversos , Administración Oral , Antígenos Virales/sangre , Antivirales/administración & dosificación , Infecciones por Citomegalovirus/prevención & control , Infecciones por Citomegalovirus/virología , Femenino , Ganciclovir/administración & dosificación , Humanos , Masculino , Estudios RetrospectivosRESUMEN
In an effort to prolong the life of synthetic grafts used for hemodialysis access, current recommendations suggest regular monitoring of vascular access by means of measurements of access blood flows (ABFs) and/or pressures and prompt referral for prophylactic angiography with angioplasty when appropriate. Previous data suggested that angioplasty transiently reduces venous pressure, but repeated angioplasty is often required. Few data exist on the effect of angioplasty on ABF, especially the durability of the response. In this study, we report our experience with 49 consecutive angioplasties of 32 synthetic polytetrafluoroethylene grafts in which ABF was measured serially preangiography and postangiography using the Transonic hemodialysis monitor (Transonic Inc, Ithaca, NY). The primary indication for angiography was a low graft ABF rate (<600 mL/min). Although the most common site for stenosis was the venous anastomosis, the majority of grafts had multiple lesions requiring angioplasty. Mean ABF rate increased from 596 +/- 41 to 922 +/- 48 mL/min postangiography, an increase of almost twofold. This level of blood flow was maintained for the first month, but thereafter ABF began to decrease, reaching 672 +/- 70 mL/min at 3 months and 658 +/- 93 mL/min at 6 months. Two patients were lost to follow-up (one patient died, one patient received a transplant) and 2 grafts were electively ligated. The remaining 28 grafts were followed up for at least 6 months. Four grafts clotted within 3 months of angioplasty and were lost. Nine additional grafts required a second intervention (surgical revision, 2 grafts; repeated angioplasty, 7 grafts) within 6 months, either for a poor initial response to angioplasty or recurrent stenosis. Two of these 9 grafts subsequently clotted and were lost. In all, 22 of the 28 grafts remained patent at 6 months postangioplasty, and 15 grafts were maintaining an ABF greater than 600 mL/min without reintervention at 6 months. In summary, this study indicates that preemptive angioplasty of graft stenoses results in an initial doubling of ABF, but the effect is temporary, with the average ABF decreasing to baseline values by 3 months. Approximately half the grafts required reintervention for either thrombosis or recurrent low flow. However, sustained responses with ABF maintained at greater than 600 mL/min were achieved in the other half.
Asunto(s)
Derivación Arteriovenosa Quirúrgica , Prótesis Vascular , Cateterismo , Oclusión de Injerto Vascular/terapia , Diálisis Renal/instrumentación , Grado de Desobstrucción Vascular , Angiografía , Oclusión de Injerto Vascular/diagnóstico por imagen , Oclusión de Injerto Vascular/fisiopatología , Humanos , Politetrafluoroetileno , Flujo Sanguíneo Regional , Reoperación , Estudios Retrospectivos , Trombosis/terapia , Ultrasonografía , Presión VenosaRESUMEN
Burning mouth syndrome (BMS) is known to have multiple precipitating factors and exists in various clinical subtypes. If salivary gland function was compromised in BMS it could help explain the link with diverse precipitating factors. This study quantified stimulated right and left parotid flow rates (SPFR) in 114 patients with BMS. It also attempted to correlate SPFR with haematinic parameters, oral candidal carriage, concurrent drug therapy and BMS subtype. No relationship was found between haematinic parameters and SPFR nor between SPFR and oral candidal carriage. Patients with Type 2 BMS had a significant reduction in SPFR. Antidepressant medication was associated with reduced SPFR but there was no such association with either tranquillisers or hypnotics. These results provide evidence of reduced parotid gland function in Type 2 BMS and a role for antidepressant medication in reducing SPFR.
Asunto(s)
Síndrome de Boca Ardiente/fisiopatología , Ácido Cítrico/farmacología , Glándula Parótida/efectos de los fármacos , Saliva/efectos de los fármacos , Antidepresivos/uso terapéutico , Análisis Químico de la Sangre , Síndrome de Boca Ardiente/sangre , Síndrome de Boca Ardiente/clasificación , Candidiasis Bucal/diagnóstico , Distribución de Chi-Cuadrado , Diabetes Mellitus Tipo 2/diagnóstico , Femenino , Humanos , Hipnóticos y Sedantes/uso terapéutico , Deficiencias de Hierro , Glándula Parótida/metabolismo , Saliva/metabolismo , Tasa de Secreción/efectos de los fármacos , Tranquilizantes/uso terapéuticoRESUMEN
BACKGROUND: Optimal prophylaxis against cytomegalovirus (CMV) disease for organ transplant patients at risk for primary infection (donor seropositive, recipient seronegative, D+R-) remains to be determined. We hypothesized that prolonged oral ganciclovir therapy following intravenous therapy would provide increased protection. METHODS: A total of 155 evaluable D+R- organ transplant recipients from 13 transplant centers were entered into the study: all received intravenous ganciclovir (5 mg/kg/day) for 5-10 days and then either oral acyclovir (400 mg tid) or oral ganciclovir (1 g tid) for an additional 12 weeks. Patients were assigned to their treatment groups at a central randomization site, with a separate randomization scheme for each of the organs transplanted (kidney, heart, or liver). In the case of kidney transplants, the patients were stratified according to source of the kidney (living related vs. cadaveric donor). The primary endpoint was the incidence of CMV disease in the first six months post-transplant. RESULTS: Treatment with oral ganciclovir was associated with a significant decrease in the incidence of symptomatic disease or viremia when compared with the oral acyclovir group (32% vs. 50%, P<0.05). This difference was most marked in terms of tissue invasive disease: only 3 of 15 symptomatic patients in the ganciclovir group vs. 10 of 21 in the acyclovir group developed tissue-invasive infection (P<0.05). There was a significant difference in the time to CMV disease or viremia in the two groups: mean time 212+/-17 days post-transplant for the acyclovir group vs. 291+/-13 days for the ganciclovir group (P<0.001). The incidence of allograft rejection was 34% in the ganciclovir group and 46% in the acyclovir group (P=NS). Leukopenia was more common in the ganciclovir group (P<0.05), but in no case did it require drug discontinuation. Ganciclovir resistance did not develop in this study. CONCLUSION: Prophylaxis with oral ganciclovir following a brief course of intravenous ganciclovir provides useful protection against primary CMV disease.
Asunto(s)
Aciclovir/uso terapéutico , Antivirales/uso terapéutico , Infecciones por Citomegalovirus/prevención & control , Ganciclovir/uso terapéutico , Trasplante de Corazón , Trasplante de Riñón , Trasplante de Hígado , Complicaciones Posoperatorias/virología , Aciclovir/administración & dosificación , Aciclovir/efectos adversos , Administración Oral , Adolescente , Adulto , Anciano , Antivirales/efectos adversos , Niño , Quimioterapia Combinada , Femenino , Ganciclovir/administración & dosificación , Ganciclovir/efectos adversos , Trasplante de Corazón/inmunología , Humanos , Terapia de Inmunosupresión/métodos , Inyecciones Intravenosas , Trasplante de Riñón/inmunología , Trasplante de Hígado/inmunología , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/prevención & controlRESUMEN
The female kidney tends to be smaller, have a lower glomerular filtration rate, and be less susceptible to glomerulosclerosis than the male kidney. Insulin-like growth factor-I (IGF-I) is a peptide growth factor that appears to be important for normal and adaptive kidney growth. The purpose of this study was to compare the kidney growth response of the male and female rat kidneys to increased dietary protein intake and to see whether differences in IGF-I production or receptor expression might underlie any gender differences seen. Male (M) and female (F) Munich-Wistar rats (6 to 9 weeks of age) were randomized to isocaloric diets containing either 20% (NP) or 50% (HP) protein and studied after 3 and 14 days. In the male rat, wet kidney weight was significantly increased with HP at both day 3 (M-HP 1028+/-21 mg vs M-NP 891+/-19 mg, p < 0.01) and day 14 (M-HP 1499+/-41 mg vs M-NP 1246 +/-37 mg, p < 0.01). In contrast in the female rat, while there was evidence of initial increased growth at day 3 in the kidneys of F rats fed HP (F-HP 788+/-39 mg vs F-NP 650+/-23 mg, p < 0.01), this difference was not sustained at 14 days (F-HP 961+/-67 mg vs F-NP 931+/-71 mg, p = NS). At day 3, kidneys of both male and female rats fed HP exhibited an increase in total protein but not DNA content. The kidneys of male rats showed increased protein/DNA ratios in the medulla and inner cortex, whereas in the kidneys of female rats, the increase in protein/DNA ratio was confined to the cortex. After 14 days of HP ingestion, the kidneys of male rats showed increases in total kidney content of both DNA and protein, and protein/DNA ratios returned to control values in whole kidney, inner cortex, and medulla. In contrast, in the kidneys of female rats, not only was overall growth response reduced, but neither total kidney protein content nor DNA content was increased. Increased protein/DNA ratios were seen in inner cortex and in outer and inner medulla, similar to that seen at day 3 in the kidneys of male rats. Neither baseline plasma (M-NP 793+/-10 ng/ml, F-NP 704+/-32 ng/ml, p = NS) nor kidney IGF-I content (M-NP 520+/-55 ng/gm tissue, F-NP 506+/-54 ng/gm tissue, p = NS) differed between male and female rats fed NP diets. Both male and female rats showed a comparable increase in kidney IGF-I after 3 days of HP ingestion, and kidney IGF-I returned to control values by 14 days. There was no significant difference in the number or affinity of glomerular IGF-I receptors between male and female rats. In conclusion, we have shown that in the adult male rat, an increase in dietary protein ingestion results in a sustained increase in kidney size that is initially consistent with a hypertrophic response but subsequently shows elements of hyperplasia. In contrast, in the female rat, although there was evidence of the initial hypertrophic (and IGF-I) responses to increased dietary protein, the increase in kidney size was not sustained. However, these profound gender-based differences in the growth response to dietary protein did not appear to be due to differences in kidney expression of IGF-I or its receptors.
Asunto(s)
Proteínas en la Dieta/administración & dosificación , Hormona del Crecimiento/fisiología , Factor I del Crecimiento Similar a la Insulina/fisiología , Riñón/crecimiento & desarrollo , Factores Sexuales , Animales , Peso Corporal , ADN/metabolismo , Ingestión de Energía , Femenino , Factor I del Crecimiento Similar a la Insulina/clasificación , Factor I del Crecimiento Similar a la Insulina/metabolismo , Riñón/metabolismo , Masculino , Tamaño de los Órganos , Ratas , Ratas WistarRESUMEN
In this study, the utility of the cytomegalovirus antigen (CMV-AG) and the shell vial (SV) tests in the diagnosis and monitoring of posttransplant CMV infection were compared. Previous retrospective studies from the authors' center suggested that the CMV-AG test, which uses monoclonal antibodies to detect viral antigen in circulating peripheral blood leukocytes (PBL) may be both a more sensitive and specific test. A cohort of 32 renal transplant recipients was followed-up prospectively with serial CMV-AG testing, as well as conventional culture and SV for blood and urine and tests for immunoglobulin M (IgM) antibody. It was discovered that the CMV-AG test was not only more sensitive than the SV test in detecting CMV infection, but that the degree of antigenemia as expressed by the number of positive cells per 50,000 PBL correlated with the likelihood and degree of symptomatic infection. All patients with a count > 10 positive cells/50,000 PBL developed clinical symptoms; therefore, this threshold could be useful in deciding clinically whether fever is related to CMV infection. Alternatively, if antigenemia were monitored serially after transplant, the same threshold could be used as a trigger for instituting antiviral therapy, because it was often reached prior to the onset of symptoms and had a high specificity for subsequent symptomatic infection. Such an approach could obviate unnecessary treatment of patients not destined to become symptomatic. Based upon the findings in this study, the CMV-AG test is superior to the SV assay because the actual count helps determine the likelihood that symptoms are a result of the virus and the processing time is shorter, it can be used to monitor the response to therapy and as a guide to the institution of preemptive therapy.
Asunto(s)
Infecciones por Citomegalovirus/diagnóstico , Infecciones por Citomegalovirus/etiología , Trasplante de Riñón , Complicaciones Posoperatorias , Antígenos Virales/análisis , Citomegalovirus/inmunología , Infecciones por Citomegalovirus/fisiopatología , Femenino , Humanos , Masculino , Prevalencia , Medicina Preventiva , Sensibilidad y EspecificidadRESUMEN
Cytomegalovirus (CMV) infection is ubiquitous and results in a wide spectrum of clinical manifestations ranging from asymptomatic infection to severe life threatening disease. Infection in normal children and adults usually causes no symptoms but in the immunocompromised host, CMV may result in severe opportunistic infections with high morbidity and mortality. Historically, virus detection was dependent on culture of the virus or on a centrifugation culture system referred to as a shell vial assay. The shell vial assay frequently lacked sensitivity and was unable to detect infection in its early phase. Also, as with culture assays, the results were affected by antiviral therapy. The CMV antigenemia assay was developed to provide more rapid results and has gained wide usage. This assay is limited to detection of the virus in white blood cells and is more sensitive than culture or the shell vial assay. Application of the polymerase chain reaction (PCR) to these problems has resulted in the development of assays for CMV which are more sensitive than previously available methods. This method employs liquid hybridization with 32P labeled probes and gel retardation analysis for detection of amplified DNA specific for each virus. A comparison of the detection of CMV by an antigenemia assay or the PCR method in the leukocytes of renal transplant patients revealed that the PCR assay detects cytomegalovirus earlier and more consistently than the antigenemia assay. Finally, the application of a fluorescent dye detection system and image analysis of the acrylamide gel with a laser scanner provides additional sensitivity to the detection of cytomegalovirus, as well as avoiding the use of radioactivity, making the assay more adaptable to the clinical laboratory.
Asunto(s)
Trasplante de Médula Ósea/efectos adversos , Infecciones por Citomegalovirus/diagnóstico , Infecciones por Citomegalovirus/virología , Citomegalovirus/genética , Citomegalovirus/aislamiento & purificación , Trasplante de Órganos/efectos adversos , Reacción en Cadena de la Polimerasa/métodos , Infecciones por Citomegalovirus/genética , HumanosRESUMEN
Post-transplant diabetes among renal transplant recipients is more prevalent in the African-American population. However, it is unknown if methylprednisolone (a commonly prescribed glucocorticoid in transplant patients) pharmacokinetics is altered among African-American renal allograft recipients compared to Caucasian counterparts. Therefore, the objectives of this study were to identify the occurrence of post-transplant diabetes in our clinic population and to characterize the pharmacokinetics of methylprednisolone among our African-American and Caucasian renal transplant recipients. A retrospective chart survey was done on African-American and Caucasian recipients with stable renal function and no history of diabetes pre-transplantation in order to characterize the occurrence of post-transplant diabetes in our clinical population. The survey was conducted from January 1985 to January 1992 in recipients with graft survival of at least 3 months. Post-transplant diabetes was defined as two fasting glucose serum concentrations greater than 140 mg/dl or one random serum glucose concentration greater than 200 mg/dl which was confirmed by a fasting serum glucose value greater than 140 mg/dl and a 2 hour post-prandial greater than 200 mg/dl. A 24-hour pharmacokinetic evaluation was conducted in a sub-group of African-American and Caucasian patients after intravenous administration of methylprednisolone. Over the survey period, 75 renal transplants (30 females; 45 males) were performed and 50 of these transplant recipients (24 females; 26 males) were not diabetic prior to the allograft placement. Of these 50 patients, 22 males and 17 females fulfilled the inclusion criteria established for the retrospective survey.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Población Negra , Diabetes Mellitus/epidemiología , Glucocorticoides/farmacocinética , Trasplante de Riñón , Metilprednisolona/farmacocinética , Población Blanca , Adulto , Glucemia/análisis , Creatinina/sangre , Diabetes Mellitus/sangre , Diabetes Mellitus/tratamiento farmacológico , Femenino , Glucocorticoides/administración & dosificación , Glucocorticoides/sangre , Supervivencia de Injerto , Humanos , Insulina/uso terapéutico , Trasplante de Riñón/fisiología , Masculino , Metilprednisolona/administración & dosificación , Metilprednisolona/sangre , Persona de Mediana Edad , New York/epidemiología , Estudios Retrospectivos , Factores Sexuales , Trasplante HomólogoRESUMEN
The purpose of a staging system is to stage embryos by morphology rather than chronology. This is particularly useful when embryos do not develop exactly synchronously, as in the case of the chick. At present the Hamburger and Hamilton (1951) series is universally used to stage chick embryos. The aim of the present study was to provide a series of morphological descriptions of the normal stages of development of the chick wing bud from stages 19 to 36, and to correct some errors of the original system which may be overlooked by those new to the chick wing bud as an experimental model, and who rely primarily on the Hamburger and Hamilton stage series. In addition, Summerbell's (1976) observations on the appearance of the cartilaginous elements made from alcian green-stained whole mounts have been correlated with the external appearance of the wing bud to provide a more complete understanding of the skeletal development that influences, and to some degree accounts for, the changes in external morphology. Scanning electron microscopy (SEM) has been used to obtain images of much greater resolution and detail than those available from Hamburger and Hamilton, whilst using comparable magnifications to those attainable using conventional dissecting microscopes. The number of somites across which the proximal part of the wing bud extends has been provided as a measure of the limb width at early stages (19-24). At certain stages there were clear differences between the characteristic wing bud features described by Hamburger and Hamilton and those observed in the present study.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Desarrollo Embrionario y Fetal , Alas de Animales/embriología , Alas de Animales/ultraestructura , Animales , Embrión de Pollo , Microscopía Electrónica de RastreoRESUMEN
Cytomegalovirus (CMV) infection continues to be a major cause of morbidity and mortality in transplant recipients, yet prompt diagnosis remains a problem. A new assay has been developed that detects CMV antigens in peripheral blood leukocytes (CMV-AG). A retrospective analysis of the experience with this assay was performed, and its usefulness in the diagnosis of CMV infection in renal transplant recipients with unexplained fever was compared with that of conventional modalities (buffy coat culture, detection of circulating anti-CMV immunoglobulin M). The results suggest that the CMV-AG assay is a more rapid and sensitive test than existing modalities in the early diagnosis of CMV infection. When expressed quantitatively, it can discriminate between CMV infection and CMV disease, and it is useful in monitoring the course of infection and the response to therapy.
Asunto(s)
Antígenos Virales/sangre , Infecciones por Citomegalovirus/diagnóstico , Citomegalovirus/inmunología , Trasplante de Riñón , Complicaciones Posoperatorias/diagnóstico , Citomegalovirus/crecimiento & desarrollo , Infecciones por Citomegalovirus/sangre , Infecciones por Citomegalovirus/tratamiento farmacológico , Infecciones por Citomegalovirus/mortalidad , Infecciones por Citomegalovirus/transmisión , Ganciclovir/uso terapéutico , Humanos , Trasplante de Riñón/efectos adversos , Complicaciones Posoperatorias/sangre , Complicaciones Posoperatorias/microbiología , Estudios Retrospectivos , Activación ViralRESUMEN
Insulin-like growth factor-I (IGF-I) has been implicated as a possible mediator of renal hypertrophy after uninephrectomy and diabetes mellitus. Because renal hypertrophy is also a consequence of high protein intake, we studied the effect of varying concentrations of dietary protein on circulating levels and renal tissue content of IGF-I. Male Sprague-Dawley rats were fed isocaloric diets containing high (50%, HP), normal (20%, NP) or low (6%, LP) dietary protein for up to 14 days before they were killed. As expected, renal size (dry kidney weight) was greater in HP-fed rats and smaller in LP-fed rats when compared with NP-fed animals (HP, 1415 +/- 26 mg [p < 0.01 vs NP]; NP, 1148 +/- 27 mg; LP, 838 +/- 16 mg [p < 0.01 vs NP]), and most of the relative changes in kidney size occurred during the first week of ingestion of the experimental diet. Renal hypertrophy in the HP-fed animals was accompanied at day 3 by a significant rise in kidney tissue IGF-I that remained elevated at day 7 but had fallen to baseline values by day 14. The rise in renal IGF-I content in the HP-fed rat was accompanied by increases in circulating IGF-I on day 3 only. Both circulating and renal tissue IGF-I levels were suppressed in the LP-fed animals at 3, 7, and 14 days. These data confirm that varying dietary protein intake has profound effects on both circulating and renal IGF-I levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Proteínas en la Dieta/administración & dosificación , Factor I del Crecimiento Similar a la Insulina/fisiología , Riñón/crecimiento & desarrollo , Animales , Hipertrofia , Riñón/metabolismo , Riñón/patología , Masculino , Tamaño de los Órganos , Ratas , Ratas Sprague-DawleyRESUMEN
Antihistamines are common over the counter medications which are frequently involved in overdoses. The usual clinical course is dominated by the anticholinergic affects of these agents; it includes significant autonomic and central nervous system effects and direct cardiac toxicity (1). We report a case of a suicide attempt in a young adult male where ingestion of the antihistamines diphenhydramine and doxylamine was complicated by non-traumatic rhabdomyolysis and acute renal failure.
Asunto(s)
Lesión Renal Aguda/complicaciones , Difenhidramina/envenenamiento , Doxilamina/envenenamiento , Rabdomiólisis/complicaciones , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/fisiopatología , Adulto , Nitrógeno de la Urea Sanguínea , Creatinina/sangre , Sobredosis de Droga , Humanos , Masculino , Rabdomiólisis/inducido químicamente , Rabdomiólisis/fisiopatología , Intento de SuicidioRESUMEN
Pharmacomechanical coupling of vascular smooth muscle is believed to be mediated by inositol trisphosphate (IP3). Numerous studies have demonstrated an increase in inositol phosphates following tissue stimulation using either intact aortic strips or cultured cells from aorta. However, little information is available concerning inositol phosphates in vascular tissue other than in the large conduit vessel, the aorta. This present study was designed to examine the role of inositol phosphate metabolism following adrenergic stimulation of the muscular rat tail artery as compared to the aorta. Segments of thoracic aorta and tail artery from male Sprague Dawley rats were labeled with [3H]inositol and stimulated with norepinephrine. The norepinephrine concentration that resulted in a half-maximal stimulation of inositol phosphates was approximately 10(-6) M in both the aorta and tail artery. Although the sensitivity of the two vessels to norepinephrine stimulation were similar, the stimulated levels of IP, IP2, and IP3 were from 1 to 2 orders of magnitude greater in the tail artery than in aorta. IP production in aorta and tail artery was a linear function of time (from 0 to 30 min). Significant levels of IP3 (the 1,4,5-IP3 isomer as determined by HPLC) could only be detected in the tail artery and appeared to be produced optimally after 5 min of stimulation. The several order of magnitude increase in adrenergic stimulated inositol phosphate production in the tail artery was not due to either an increased magnitude of [3H]inositol incorporated into PI, PIP, and PIP2 or to a greater percentage of smooth muscle cells per unit tissue of the rat tail artery. We believe the results of this study demonstrate that the increased inositol phosphate metabolism in the vascular smooth muscle cells of the tail artery is an intrinsic property of the cell. Moreover, due to the significant levels of all inositol phosphates produced in the tail artery, this muscular artery may be a better model, as compared to the aorta, for future studies investigating pharmacomechanical coupling of vascular smooth muscle.
Asunto(s)
Aorta Torácica/metabolismo , Fosfatos de Inositol/metabolismo , Cola (estructura animal)/irrigación sanguínea , Animales , Aorta Torácica/citología , Arterias/citología , Arterias/metabolismo , Células Cultivadas , Cromatografía Líquida de Alta Presión , Masculino , Músculo Liso Vascular/análisis , Músculo Liso Vascular/citología , Músculo Liso Vascular/metabolismo , Norepinefrina/farmacología , Ratas , Ratas EndogámicasRESUMEN
Male Sprague-Dawley rats (200-250 g) were fed low protein (6%) diets (LP rats), high protein (50%) diets (HP rats), or regular rat chow (approximately 16% protein) (control rats) and studied under anesthesia after 2 weeks. Dietary protein intake did not affect mean arterial pressure, but renal blood flow was increased in the HP rats and decreased in the LP rats compared with the control rats. Mesenteric blood flow was not significantly different in the three diet groups. Captopril (10 mg.kg-1 i.v.) had no effect on renal vascular resistance in the HP rat but did reduce the elevated renal vascular resistance seen in the LP rat. Meclofenamate (5 mg.kg-1 i.v.) did not significantly affect renal hemodynamics in either HP or LP rats. Finally, the HP rat exhibited resistance to the systemic pressor, renal, and mesenteric vasoconstrictor effects of angiotensin II. Captopril restored the systemic pressor and the mesenteric vasoconstrictor response but not the renal vasoconstrictor response to angiotensin II. Meclofenamate, on the other hand, restored both the systemic pressor response and the renal vasoconstrictor response. Thus, in the LP rat, the vascular response to angiotensin II remains intact, and renal vasoconstriction appears to be mediated by angiotensin II. In contrast, in the HP rat, the renovascular response to angiotensin II is blunted apparently because of enhanced renal prostaglandin production. However, neither increased renal prostaglandin synthesis nor blunting of the renovascular response to angiotensin II appears to account for the chronic vasodilation seen in the HP rat.
Asunto(s)
Angiotensina II/farmacología , Presión Sanguínea/efectos de los fármacos , Proteínas en la Dieta/farmacología , Circulación Renal/efectos de los fármacos , Resistencia Vascular/efectos de los fármacos , Animales , Aorta Abdominal/fisiología , Peso Corporal/efectos de los fármacos , Captopril/farmacología , Relación Dosis-Respuesta a Droga , Hematócrito , Masculino , Ácido Meclofenámico/farmacología , Músculo Liso Vascular/fisiología , Ratas , Ratas Endogámicas , Flujo Sanguíneo Regional/efectos de los fármacosRESUMEN
Agonist-induced PIP2 breakdown has been demonstrated in permeabilized vascular smooth muscle and shown to depend on a G protein. Segments of rat tail artery were permeabilized with ATP and EGTA after prelabeling with [3H]inositol. Norepinephrine and GTP gamma S were both able to increase levels of IP, IP2 and IP3 in the segments. The effects of both norepinephrine and GTP gamma S on the segments was non-additive. Aluminum fluoride also increased inositol phosphates in intact segments and norepinephrine-stimulated increases in IP, IP2 and IP3 were insensitive to pertussis toxin.
Asunto(s)
Compuestos de Aluminio , Proteínas de Unión al GTP/fisiología , Músculo Liso Vascular/fisiología , Fosfatidilinositoles/metabolismo , Aluminio/farmacología , Animales , Fluoruros/farmacología , Guanosina 5'-O-(3-Tiotrifosfato) , Guanosina Trifosfato/análogos & derivados , Guanosina Trifosfato/farmacología , Fosfatos de Inositol/metabolismo , Norepinefrina/farmacología , Toxina del Pertussis , Fosfatidilinositol 4,5-Difosfato , Ratas , Tionucleótidos/farmacología , Factores de Virulencia de Bordetella/farmacologíaRESUMEN
Acute deterioration of renal function occurred shortly after the angiotensin-converting enzyme (ACE) inhibitor, enalapril, was administered to two renal transplant patients who were also receiving cyclosporine. Renal function recovered completely in both cases upon discontinuation of enalapril. Neither patient had evidence of transplant artery stenosis or chronic rejection, conditions known to predispose to renal failure during ACE inhibitor therapy. The possibility that afferent vasoconstriction induced by cyclosporine may have predisposed these patients to renal failure from enalapril is discussed.
Asunto(s)
Lesión Renal Aguda/inducido químicamente , Ciclosporinas/efectos adversos , Enalapril/efectos adversos , Rechazo de Injerto/efectos de los fármacos , Trasplante de Riñón/fisiología , Adulto , Femenino , Humanos , Masculino , Circulación Renal/efectos de los fármacos , Vasoconstricción/efectos de los fármacosRESUMEN
Autoregulatory ability was evaluated in male Sprague-Dawley rats (200-250 g) fed either low protein (LP, 6%), high protein (HP, 50%), or standard rat chow (CON) for 2 wk. Renal perfusion pressure (RPP) was first raised above normal by bilateral ligation of the carotid arteries. LP rats exhibited normal autoregulatory behavior between 130 and 100 mmHg, whereas autoregulation in HP rats was impaired (autoregulation factor 100-130; HP 0.86 +/- 0.16, LP 0.38 +/- 0.07, and CON 0.39 +/- 0.04). Autoregulation studies were repeated in HP- and LP-fed rats after administration of the cyclooxygenase inhibitors, meclofenamate and piroxicam. Cyclooxygenase inhibition did not significantly affect base-line hemodynamics but did restore the ability of the HP rat to autoregulate renal blood flow (RBF) at high RPP. (Autoregulation factor between 100 and 130 mmHg; HP 0.29 +/- 0.10, LP 0.19 +/- 0.07, P, NS). Thus an HP diet resulted in impaired autoregulation of RBF at high RPP, an effect that appears to be mediated by excessive production of vasodilatory prostaglandins.