An unusual cause of abdominal pain in a patient with hepatitis C cirrhosis.
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Biomedical subjects
Publications and source records attributed to A Cárdenas.
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We developed a diabetes management system with a Web interface that allowed patients to transmit their physiological data using either a PC Web browser or a mobile phone capable of working with the WAP protocol. The system could generate automatic responses to input values in accordance with a set of ranges previously defined for each user. User analysis was carried out with personal and online questionnaires. During a nine-month study period on the island of Tenerife, 12 patients were recruited. On average, they used the system every 2.0 days (SD 2.1) and the doctors reviewed their patient data every 4.0 days (SD 3.9). The average number of visits to the Website was 477 per month. Users were satisfied with the continuity and self-efficacy of care, but lack of time was a drawback for 38% of them and 75% expressed a preference for sending their data via the mobile phone short message service (SMS).
We conducted a trial of mobile phone text messaging (short message service; SMS) for diabetes management. In an eight-month period, 23 diabetic patients used the service. Patients used SMS to transmit data such as blood glucose levels and body weight to a server. The server automatically answered with an SMS acknowledgement message. A monthly calculated glycosylated haemoglobin result was also automatically sent to the patient by SMS. During the trial the patients sent an average of 33 messages per month. Although users showed good acceptance of the SMS diabetes system, they expressed various concerns, such as the inability to enter data from previous days. Nonetheless, the trial results suggest that SMS may provide a simple, fast and efficient adjunct to the management of diabetes. It was particularly useful for elderly persons and teenagers, age groups that are known to have difficulty in controlling their diabetes.
The aim of this study was to determine the effect of mood disorders, including psychological distress and depression, on stroke outcome. Male Fischer rats were exposed to immobilisation stress, an animal paradigm of psychological stress, major depression and post-traumatic stress disorder. Either a subacute (1 h for 7 days) or a chronic (6 h for 21 days) exposure to stress was applied 24 h before permanent middle cerebral artery occlusion (MCAO). Stroke outcome was assessed by measurement of infarct size and behavioural characterisation. Serum glutamate and brain ATP levels as well as brain glutamate transporter function and expression were studied in the search for the molecular mechanisms involved. Subacute stress exposure increased infarct size and decreased behavioural scores after stroke. On the contrary, chronic stress exposure decreased infarct size. Peak serum glutamate levels correlated with infarct size after MCAO. Expression of glutamate transporters was decreased by subacute stress, whereas the expression of EAAT1, a glial glutamate carrier, was increased after the chronic stress protocol. Our results indicate that distinct patterns of stress determine different stroke outcomes, and that expressional changes of brain glutamate transporters, able to affect glutamate release after stroke, are involved.
Tumour necrosis factor-alpha (TNF-alpha) is a major immunomodulatory and proinflammatory cytokine which is shed in its soluble form by a membrane-anchored zinc protease, identified as a disintegrin and metalloproteinase (ADAM) called TNF-alpha convertase (TACE; ADAM17). The role of this protease in the adult nervous system remains poorly understood. During cerebral ischemia and subsequent reperfusion, expression and release of TNF-alpha have been shown. We have investigated the expression and activity of TACE in an in vitro model of brain ischemia consisting of rat forebrain slices exposed to oxygen-glucose deprivation (OGD). OGD caused the release of TNF-alpha, an effect which was inhibited by a hydroxamate-based metalloprotease inhibitor, BB-3103, with an IC(50) of 0.1 microM, suggesting that TNF-alpha release results selectively from TACE activity. Assay of TACE enzymatic activity on a fluorescein-labelled peptide spanning the cleavage site in pro-TNF-alpha, as well as Western blot and RT-PCR analyses showed that TACE is present in control forebrain and, more interestingly, that TACE expression is increased in OGD-exposed tissue. TACE enzymatic activity from OGD-exposed slices was significantly inhibited by cycloheximide, suggesting that de novo synthesis of TACE contributes to TNF-alpha release after ischaemia. Moreover, it was also inhibited by bisindolylmaleimide I, indicating that TACE activity is regulated by PKC. These findings posed the question of what was its function therein. Among other actions, TNF-alpha has been described to be involved in the expression of inducible nitric oxide synthase (iNOS), a high-output NOS isoform associated to cellular damage, but the link between TNF-alpha release after brain ischaemia and iNOS expression in this condition has not been shown. We have now found that iNOS expression in OGD-subjected brain slices is inhibited by BB-3103 at concentrations below 1 microM, indicating that shedding of TNF-alpha by TACE plays a necessary part in the induction of this NOS isoenzyme after OGD. Taken together, these data demonstrate that (1) TACE/ADAM17 activity accounts for the majority of TNF-alpha shedding after OGD in rat forebrain slices, (2) an increase in TACE expression contributes, at least in part, to the rise in TNF-alpha after OGD and (3) iNOS expression in OGD-subjected brain slices results from TACE activity and subsequent increase in TNF-alpha levels.
BACKGROUND/AIMS: Parameters evaluating renal function and systemic hemodynamics are of prognostic significance in cirrhosis with ascites but are rarely used in the evaluation of survival of these patients. The aim of the current study was to develop a prognostic model to estimate survival of patients with cirrhosis and ascites. METHODS: 216 Cirrhotic patients admitted to hospital for the treatment of ascites were evaluated. Thirty-two demographic, clinical and laboratory variables, including parameters assessing liver and renal function and systemic hemodynamics, were analyzed as predictive factors of survival by using a Cox regression model. RESULTS: Four variables had independent prognostic value: renal water excretion, as assessed by measuring diuresis after water load, mean arterial pressure, Child-Pugh class, and serum creatinine. According to these features a prognostic index was calculated that allows to estimate survival in patients with cirrhosis and ascites. The model accurately predicted survival in an independent series of 84 patients with cirrhosis and ascites. CONCLUSION: A prognostic model that uses four easily available variables and predicts prognosis in cirrhotic patients with ascites has been developed. This model may be useful in the evaluation of patients with ascites for liver transplantation.
To assess the incidence, clinical course, predictive factors, and prognosis of renal failure in patients with cirrhosis and gastrointestinal bleeding, 175 consecutive episodes of gastrointestinal bleeding in 161 patients were analyzed. Renal failure occurred in 20 (11%) episodes and was transient in 8 episodes and nontransient in 12. Renal failure was more common in patients with cirrhosis than in a control population of bleeding patients without cirrhosis matched by age and severity of the bleeding episode. Among 39 clinical and laboratory variables obtained at admission or during hospitalization related with the bleeding episode or with liver and renal function, the presence of hypovolemic shock, number of packed red blood cells transfused, Child-Pugh class at admission, and baseline platelet count were independent predictors of renal failure. The development of renal failure and hypovolemic shock was the only independent predictors of in-hospital mortality. Mortality rate among the 20 episodes with renal failure was 55% (11 deaths) as compared with only 3% (5 deaths) in the 155 episodes without renal failure (P <.01). The development of nontransient renal failure entailed a much greater mortality as compared with transient renal failure (10 of 12 [83%] vs. 1 of 8 [12%]; P <.01). In conclusion, renal failure is a common event in patients with cirrhosis and gastrointestinal bleeding, the occurrence of which is mainly related to the severity of bleeding and baseline liver function. Renal failure is a strong predictor of mortality in patients with cirrhosis and gastrointestinal bleeding.
Patients with cirrhosis have significant abnormalities in their fluid and electrolyte balance, this is manifested mainly by the development of ascites and edema. Ascites is the most common complication of patients with cirrhosis and its development constitutes the first and most important manifestation of the disease. Patients with advanced cirrhosis and portal hypertension often show an abnormal extracellular fluid volume regulation, which results in accumulation of fluid as ascites, pleural effusion, or edema. This abnormality in volume regulation is associated with significant changes in the splanchnic circulation and renal circulation that induce sodium and water retention. During the last decade significant advances have been accomplished in regard to the pathogenesis and the treatment ascites. The description of a new hypothesis, the identification of new vasoactive factors involved in the pathogenesis of arterial vasodilation and the introduction of different therapeutic modalities such as therapeutic paracentesis, transjugular intrahepatic portosystemic shunt, aquaretics agents, and liver transplantation are all proof of this. Likewise, the description of predictive factors for the survival of patients with cirrhosis has been of major importance for the identification of patients candidates for liver transplantation.
Multiple subjective evaluations and valuations in clinical studies have suggested that the use of external ultrasound in liposuction favors the degree of tissue retraction. However, studies do not exist that evaluate with objective parameters the degree of tissue retraction after liposuction assisted with external ultrasound. It is for this reason that a comparative clinical trial was carried out in 13 female patients to establish clinically and histopathologically the degree of tissue retraction that is produced after tumescent liposuction assisted by external ultrasound compared with the classic tumescent technique. All patients were tattooed in each hemiabdomen with reference points that formed a 7 x 7-cm square. Abdominal tumescent liposuction was carried out in all patients, with external ultrasound applied to the right hemiabdomen only, and without specifying to the patient the side on which the ultrasound was applied. The areas were measured and biopsies were acquired in each hemiabdomen 72 hours, 1 week, 2 weeks, 3 months, and 6 months postoperatively. The samples were evaluated by the same pathologist in a double-blind study. A survey of the patients was carried out regarding their appreciation of the results at the end of 3 months. On physical evaluation of the tattooed square, none of the thirteen patients presented significant differences in skin retraction (95% dependability by means of Student's t-test). The histological results showed that external ultrasound increased the degree of edema, vascular congestion, and inflammatory infiltration in the dermis during the first 3 months postoperatively. However, after 6 months no differences existed. Clinically, no patient observed a marked difference between the two hemiabdominal areas; an equal aesthetic result was obtained on both sides. In this clinical comparative trial, external ultrasound as a complementary method to tumescent liposuction did not increase the degree of tissue retraction after the liposuction, nor did it prove to be a determining factor in the immediate postoperative evolution.
UNLABELLED: Gastrointestinal intraluminal PCO2 (PiCO2) information is used to assess the adequacy of trauma patient resuscitation and to assist in choosing resuscitative interventions. Therefore, determining the limitations and potential caveats of different PiCO2 monitoring systems is clinically important. This study compared two PCO2 monitoring systems. The airflow device adds and then removes air samples to quantitate PCO2, whereas the fiber-optic device does not. METHODS: Airflow (TRIP Tonometer/Tonocap) and fiber-optic (Neotrend) systems were used. In vitro they were compared with each other and to two end-tidal CO2 monitors measuring the PCO2 of humidified air containing 5% and then 10% CO2. In vivo the two systems' catheters were surgically juxtaposed in 15 dogs' stomachs; paired PiCO2 readings were taken throughout hemorrhage and resuscitation. RESULTS: In vitro, paired PCO2 values from the airflow and fiber-optic devices correlated with each other (r = 0.99) and with end-tidal values (r = 0.99 with airflow, r = 0.95 with fiber-optic). In vivo, paired values differed significantly (P < 0.0001), correlating poorly for two devices simultaneously measuring the same variable (r = 0.61). Fiber-optic PiCO2 values were higher than airflow values (mmHg +/- SEM): 69.3 +/- 4.8 vs. 61.3 +/- 5.6 at the start of hemorrhage, 141.3 +/- 12.9 vs. 87.7 +/- 7.9 by end of hemorrhage, and 104.3 +/- 9.6 vs. 82.8 +/- 7.0 by end of resuscitation for fiber-optic and airflow, respectively. CONCLUSIONS: Despite agreement in vitro, airflow methods can influence PiCO2 values obtained in vivo. Passive sensing methods used to monitor PiCO2, such as fiber-optic methods, are preferable because they neither deliver O2 to, nor remove CO2 from the local microenvironment.
Acetylsalicylic acid (ASA, Aspirin) is an anti-inflammatory drug with a wide spectrum of pharmacological activities and multiple sites of action. Apart from its preventive actions against stroke due to its antithrombotic properties, recent data in the literature suggest that high concentrations of ASA also exert direct neuroprotective effects. We have used an in vitro model of brain ischaemia using rat forebrain slices deprived of oxygen and glucose to test ASA neuroprotective properties. We have found that ASA inhibits neuronal damage at concentrations lower than those previously reported (0.1-0.5 mM), and that these effects correlate with the inhibition of excitatory amino acid release, of NF-kappaB translocation to the nucleus and iNOS expression caused by ASA. All of these three mechanisms may mediate the neuroprotective effects of this drug. Our results also show that the effects of ASA are independent of COX inhibition. Taken together, our present findings show that ASA is neuroprotective in an in vitro model of brain ischaemia at doses close to those recommended for its antithrombotic effects.
Fructose-1,6-bisphosphate (FBP) is a glycolytic pathway intermediate with a neuroprotective action in animal models of brain ischaemia. We addressed the question of whether FBP acts through inhibiting inducible nitric oxide synthase (iNOS) expression via reduction of glutamate release, since we have recently demonstrated that glutamate is involved in the expression of iNOS. FBP (5 mM) added to the incubation solution of rat forebrain slices subjected to oxygen-glucose deprivation (OGD) inhibited glutamate release significantly (around 40%). FBP also inhibited the induction of the calcium-independent NOS activity and reduced the levels of iNOS protein in rat forebrain slices subjected to OGD. We conclude that the action of FBP by reducing glutamate release and iNOS expression, both of which have been implicated in cell damage, is a reason for further evaluation of FBP as a neuroprotectant.
BACKGROUND/AIM: Ornipressin, a vasopressin analog with potent splanchnic vasoconstrictor action, has been shown to reverse hepatorenal syndrome. However, its usefulness in clinical practice is limited by frequent ischemic complications. The aim of this study was to assess the efficacy of terlipressin, an analog of vasopressin with a low profile of side effects, plus albumin in this condition. METHODS: Nine consecutive patients with cirrhosis and hepatorenal syndrome were included in a pilot study of terlipressin (0.5-2 mg/4 h i.v.) therapy associated with iv albumin. RESULTS: Treatment (9 days, range 5-15) was associated with a marked reduction of serum creatinine (3.9+/-0.7 to 1.3+/-0.1 mg/dl, p<0.001, mean+/-SE). Reversal of hepatorenal syndrome (reduction of creatinine below 1.5 mg/dl) was observed in seven of the nine patients. There was a remarkable improvement in circulatory function, with an increase in mean arterial pressure (68+/-2 to 80+/-4 mmHg, p<0.05) and suppression of vasoconstrictor systems activity (plasma renin activity and plasma norepinephrine decreased from 23+/-12 ng/ml x h and 1549+/-373 pg/ml to 3.5+/-2 ng/ml x h and 373+/-98 pg/ml, respectively, p<0.01 for both). No patient developed signs of intestinal, myocardial or distal ischemia. CONCLUSIONS: Terlipressin associated with albumin appears to be a safe and effective treatment of hepatorenal syndrome.
Ascites is the most common complication of cirrhosis. It is associated with profound changes in the splanchnic and systemic circulation and with renal abnormalities. The development of ascites is related to the existence of severe sinusoidal portal hypertension that causes marked splanchnic arterial vasodilation and a forward increase in the splanchnic production of lymph. Splanchnic arterial vasodilation also produces arterial vascular underfilling, arterial hypotension, compensatory activation of the RAAS, SNS, and AVP, and a continuous sodium and water retention, leading to ascites formation. Now, therefore, the splanchnic arterial circulation, rather than the venous portal system, is believed to be involved in the pathogenesis of ascites formation.
Nitric oxide synthesis by inducible nitric oxide synthase (iNOS) has been postulated to contribute to ischemia-reperfusion neurotoxicity. The expression of this enzyme has been demonstrated in cells present in the postischemic brain. The mechanisms of iNOS expression after cerebral ischemia are a subject of current research. We therefore decided to investigate whether glutamate, which is released in ischemia and is implicated in neurotoxicity, might be involved in the mechanisms by which oxygen and glucose deprivation (OGD) leads to the expression of iNOS in rat forebrain slices. In this model, we have shown previously that 20 min of OGD causes the expression of iNOS. We have now found that the NMDA receptor antagonist MK-801 blocks the expression of iNOS, suggesting that the activation of the NMDA subtype of glutamate receptor is implicated in the mechanisms that lead to the expression of this isoform. Moreover, we have found that glutamate alone could trigger the induction process, as shown by the appearance of a Ca(2+)-independent NOS activity and by the detection of iNOS mRNA and protein in slices exposed to glutamate. Glutamate-dependent iNOS expression was concentration-dependent and was blocked by EGTA and by the inhibitors of nuclear factor kappaB (NF-kappaB) activation pyrrolidine dithiocarbamate and MG132. In addition, glutamate induced NF-kappaB translocation to the nucleus, an effect that was inhibited by MG132. Taken together, our data suggest that activation of NMDA receptors by glutamate released in ischemia is involved in the expression of iNOS in rat forebrain slices via a Ca(2+)-dependent activation of the transcription factor NF-kappaB. To our knowledge, this is the first report showing an implication of excitatory amino acids in the expression of iNOS caused by ischemia.
Ascites is the most common complication of patients with cirrhosis; its development constitutes the first and most important manifestation of the disease and is an indication for liver transplantation. During the last decade significant advances have been made in regard to the pathogenesis and treatment of ascites. The description of a new hypothesis, the identification of new vasoactive factors involved in the pathogenesis of arterial vasodilation and the introduction of different therapeutic modalities (therapeutic paracentesis, transjugular intrahepatic portosystemic shunt, aquaretics drugs and liver transplantation) are all proof of this. Similarly, the description of predictive factors for the survival of patients with cirrhosis has been of major importance for the identification of candidates for liver transplantation. This chapter reviews current knowledge on the pathophysiology, diagnosis and treatment of ascites in patients with cirrhosis.
We have recently demonstrated that inducible nitric oxide synthase (iNOS) is expressed in rat forebrain slices exposed to oxygen and glucose deprivation (OGD). Now, we have found that the expression of iNOS after OGD is time-dependent since 20 min of OGD produces the appearance of iNOS at earlier times than 10 min of OGD. OGD also causes neurotoxicity in this model, as revealed by the increase in excitatory amino acid, neuron specific enolase and lactate dehydrogenase (LDH) efflux to the incubation solution. Finally, the administration of the NMDA receptor antagonist MK-801 (100 nM) inhibits both the expression of iNOS and the release of LDH. Our findings demonstrate that this method may be considered an useful in vitro model of ischemia-reperfusion to determine the therapeutic role of neuroprotective tools.