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Biomedical subjects

T Ferrer

Publications and source records attributed to T Ferrer.

At least 19 recordsLinked to original sources
PubMed2001

Characterization of two Bunodosoma granulifera toxins active on cardiac sodium channels.

1. Two sodium channel toxins, BgII and BgIII, have been isolated and purified from the sea anemone Bunodosoma granulifera. Combining different techniques, we have investigated the electrophysiological properties of these toxins. 2. We examined the effect of BgII and BgIII on rat ventricular strips. These toxins prolong action potentials with EC50 values of 60 and 660 nM and modify the resting potentials. 3. The effect on Na+ currents in rat cardiomyocytes was studied using the patch-clamp technique. BgII and BgIII slow the rapid inactivation process and increase the current density with EC50 values of 58 and 78 nM, respectively. 4. On the cloned hH1 cardiac Na+ channel expressed in Xenopus laevis oocytes, BgII and BgIII slow the inactivation process of Na+ currents (respective EC50 values of 0.38 and 7.8 microM), shift the steady-state activation and inactivation parameters to more positive potentials and the reversal potential to more negative potentials. 5. The amino acid sequences of these toxins are almost identical except for an asparagine at position 16 in BgII which is replaced by an aspartic acid in BgIII. In all experiments, BgII was more potent than BgIII suggesting that this conservative residue is important for the toxicity of sea anemone toxins. 6. We conclude that BgII and BgIII, generally known as neurotoxins, are also cardiotoxic and combine the classical effects of sea anemone Na+ channels toxins (slowing of inactivation kinetics, shift of steady-state activation and inactivation parameters) with a striking decrease on the ionic selectivity of Na+ channels.

Action Potentials↗
PubMed2001

Cardiac cellular actions of hydrochlorothiazide.

In long term treatment, thiazide diuretics such as hydrochlorothiazide (HCTZ) lower blood pressure by decreasing peripheral resistance rather than by their diuretic effect. This action has been attributed to the opening of Ca2+-activated K+ channels in vascular smooth muscle cells. However, little is known about their cardiac cellular actions. Here we investigated the possible actions of HCTZ on action potential and contraction of rat ventricular muscle strips and on the ionic currents of isolated rat ventricular cardiomyocytes. HCTZ depressed ventricular contraction with an IC30 of 1.85 microM (60% decrease at 100 microM). Action potential duration at -60 mV and maximal rate of depolarization were, however, only slightly decreased by 12% and 22%, respectively, at 100 microM. At the single cell level, HCTZ (100 microM) depressed the fast Na+ current (INa) and the L-type Ca2+ current (ICaL) by 30% and 20%, respectively. The effects on ICaL were not voltage-or frequency-dependent. In cells intracellularly perfused with 50 microM cyclic adenosine, monophosphate HCTZ reduced ICaL by 33%. The transient (Ito), the delayed rectifier and the inward rectifier potassium currents were decreased by 20% at 100 microM HCTZ. The effects on Ito were voltage-dependent. In conclusion, HCTZ at high concentrations possesses a negative inotropic action that could be in part due to its blocking action on INa and ICaL. The actions of HCTZ on multiple cardiac ionic currents could explain its weak effect on action potential duration.

Action Potentials↗
PubMed2001

Hypohidrosis related to the administration of topiramate to children.

PURPOSE: Topiramate (TPM) is an antiepileptic agent, first licensed in the United Kingdom in 1994, that is used in the treatment of patients with refractory seizure disorders. TPM is a monosaccharide d-fructose derivate, with sulfamate function, and so far, few adverse side effects have been reported. METHODS: We describe three patients with epilepsy who were treated with TPM and developed hypohidrosis, heat and exercise intolerance, as well as fever. The sudomotor function was assessed after peripheral stimulation with pilocarpine iontophoresis. RESULTS: Sweat response was reduced in all three patients. Signs and symptoms ceased after drug suppression. CONCLUSIONS: This side effect associated with TPM, which has not been described previously, can be clinically significant during heat stress and exercise challenge.

Adolescent↗
PubMed2001

Flutamide-induced hepatotoxicity: report of a case series.

OBJECTIVE: To evaluate the characteristics of flutamide induced hepatotoxicity. MATERIAL AND METHODS: In this retrospective study we have analyzed all cases of flutamide hepatotoxicity submitted to the Andalucian Registry of drug-induced liver disease. Data were collected using a structured reporting form. Causality assessment was performed using two clinical scales: the standard CIOMS scale and the recently developed María and Victorino scale. RESULTS: Nine of 185 patients (4.9%) were identified. In 8 male patients, mean age 75 years (range 65-83), flutamide was indicated for palliative therapy of disseminated prostatic carcinoma, and in one young female (14 years) was given for the treatment of facial hirsutism. The mean duration of the flutamide therapy was 151 days (range 4-443). All patients presented with overt liver injury, the most frequent features being asthenia, anorexia, weight loss, nausea, vomiting and jaundice. No patient showed hypersensitivity features. In two patients (22%) the hepatic damage evolved to fulminant liver failure, one of them undergoing a liver transplantation and the other subsequently died. An additional patient died of a non-hepatic related cause when his liver function was improving. Causality assessment by the two clinical scales did not exclude any case, but the two patients who died where classified as unlikely by the María and Victorino scale. CONCLUSIONS: Flutamide can induce severe acute hepatitis, probably due to an idiosyncratic metabolic mechanism. Liver tests monitoring should probably be mandatory during the first months of flutamide therapy and the drug withdrawn if transaminases began to increase.

Adolescent↗
PubMed2000

Neurophysiological studies of thin myelinated (A delta) and unmyelinated (C) fibers: application to peripheral neuropathies.

Dysfunction of small fibers may appear in isolation or associated with large fiber lesions. In some acute neuropathies, such as pandysautonomia, small-fiber impairment is relatively pure but it may also appear in disorders with prominent somatic damage, such as Guillain-Barré syndrome, in which autonomic failure worsens the prognosis. At the present time, chronic idiopathic distal small-fiber neuropathy is diagnosed more frequently, and in some prevalent disorders, such as diabetic or amyloidotic polyneuropathies, small-fiber dysfunction is very noticeable. In pure autonomic failure, a peripheral autonomic failure exists, distinguishing it from multiple-system atrophy. Complex regional pain syndrome is a severe condition in which small fibers are responsible for disabling signs and symptoms, and only instrumental recordings lead to the proper treatment. Standard neurophysiological techniques evaluate large myelinated fibers exclusively. Small-fiber polyneuropathy has been considered as a type of somatic neuropathy, but thin myelinated and unmyelinated fibers are responsible not only for temperature and pain perception but also autonomic function. For instance, full autonomic evaluation is needed in some clinical situations such as autonomic failure in the elderly or orthostatic intolerance syndrome. To evaluate small-fiber impairment we need a battery of sensitive, reproducible, specific and noninvasive tests covering somatic and autonomic systems. In this review, we describe and analyze a number of neurophysiological techniques used to diagnose and characterize small-fiber dysfunction in humans. These include cardiovascular monitoring, sudomotor testing, pupillary responses and quantitative sensory tests, and also to some extent thermography and laser evoked potentials. The use of such techniques has proven useful not only for diagnosis, but also to guide adequate therapy and optimize follow-up.

Electrophysiology↗
PubMed2000

Systemic inflammatory response syndrome score at admission independently predicts mortality and length of stay in trauma patients.

BACKGROUND: Recent studies have documented that the systemic inflammatory response syndrome (SIRS) score is a useful predictor of outcome in critical surgical illness. The duration and severity of SIRS are associated with posttrauma multiple organ dysfunction and mortality. We sought to determine whether the severity of SIRS at admission is an accurate predictor of mortality and length of stay (LOS) in trauma patients. METHODS: Prospective data of 4,887 trauma admissions to a Level I trauma center over a 18-month period (January 1997 to July 1998) were analyzed. Patients were stratified by age and Injury Severity Score (ISS), and a SIRS severity score (1 to 4) was calculated at admission (1 point for each component present: fever or hypothermia, tachypnea, tachycardia, and leukocytosis). The SIRS score was evaluated as an independent predictor of mortality and LOS by chi2 and multivariate logistic regression. RESULTS: Trauma patients (n = 4,887, 83% blunt injuries, 72% male) had the following characteristics: 73.1% were age 18 to 45 years, 17.5% were age 46 to 65 years, and 9.4% were age > or =66 years; 77.7% had ISS less than 15, 18.8% had ISS 16 to 29, and 3.5% had ISS greater than 29. Analysis of variance adjusting for age and ISS determined that SIRS score of 2 was a significant predictor of LOS. Furthermore, the relative risk of death increased significantly with SIRS score of 2 when age and ISS were held constant. CONCLUSION: Logistic regression analysis confirmed that a SIRS score of 2 was a significant independent predictor of increased mortality and LOS in trauma patients. These data suggest that admission SIRS scoring in trauma patients is a simple tool that may be used as a predictor of outcome and resource utilization.

Adolescent↗
PubMed1998

Complex regional pain syndrome I (CRPS I): prospective study and laboratory evaluation.

OBJECTIVE: To relate clinical features to autonomic laboratory indices used in the diagnosis of Complex Regional Pain Syndrome type I (CRPS I) (reflex sympathetic dystrophy) to generate improved diagnostic criteria. DESCRIPTION: CRPS I is a chronic pain syndrome, characterized by diffuse limb pain with allodynia and prominent vasomotor and sudomotor dysfunction. METHODS: We conducted a prospective study on 102 patients referred for possible CRPS I. These patients completed a structured questionnaire and underwent neurologic examination, with special attention to the evaluation of clinical features of vasomotor, sudomotor, motor, and sensory, including pain, dysfunction. All patients were tested using a standard autonomic protocol that compared side-to-side skin temperature, resting sweat output, and quantitative sudomotor axon reflex test (QSART) measurements. Composite autonomic clinical (CRPS-Sx) and laboratory (CRPS-LAB) scores were defined. The clinical (subjective and objective) and the laboratory data were analyzed using Pearson's correlation analysis and Bonferroni's probability value to assess concordance and their value in correctly diagnosing CRPS I. RESULTS: All cases occurred after limb injury. One-third of cases did not fulfill our criteria of CRPS I. Highly significant correlations (p<.001) were found among certain clusters of symptoms and signs that shared unifying pathophysiologies. CRPS-Sx correlated with CRPS-LAB (p = .035). The indices that correlated most reliably with clinical data and with each other were RSO, QSART, and skin temperature reductions. CONCLUSION: Clinical and autonomic laboratory probability scores correlate in an internally consistent manner. Both CRPS-Sx and CRPS-LAB are sensitive and reliable tools to formulate a correct diagnosis of CRPS I and can be combined to provide an improved set of diagnostic criteria for CRPS I.

Adult↗
PubMed1998

[Postural hypotension with non-neurogenic triggers in the elderly].

INTRODUCTION: Orthostatic hypotension (OH) symptoms are the most frequent reason for patients to undergo an autonomic examination. The incidence of these symptoms is greater in two groups: young people with neurally mediated syncope, and adults older than 60 years, all who have normal results in the EKG and EEG test. The baroreflex afferents induce a continuous blood pressure adjustment through the heart rate variation. There are functional changes with aging which reduce this baroreflex sensitivity and therefore the accommodation to the haemodynamic requirements is frequently impaired. A number of no neurogenic triggers can be implicated in the development of OH symptoms such as electrolytic disorders, arrhythmia with low stroke volume and drugs side effects. MATERIAL AND METHODS: To study the influence of these factors in the elderly suffering from OH, we reviewed patients older than 60 years sent to our laboratory during the last three years. In 40 out of 207 cases we found the existence of some of the above mentioned factors as possible trigger of the symptoms, since no autonomic abnormality was present. After arrhythmia correction, in two cases, and the pharmacologic agent suppression, in four more patients, symptoms disappeared and no OH was found in a second tilting test. OH is a frequent problem in the elderly and requires a careful review of the numerous causes that could contribute to develop the symptoms. CONCLUSIONS: To take the proper therapeutic decision, a long term monitoring seems to be necessary for the main parameters: blood pressure and EKG.

Aged↗
PubMed1996

Autonomic profile of subjects prone to fainting.

Syncope is the most common form of fainting that may occur at least once during a life-time in up to one-third of the general population. In 50% of patients the cause remains unknown. In an attempt to identify subtle disturbances of the autonomic nervous system, we examined 70 subjects, aged from 14 to 39 years, who suffered from recurrent neurally mediated syncope. We performed a battery of non-invasive tests assessing cardiovagal, sympathetic cholinergic and sympathetic adrenergic function. We compared the results with a group of 30 healthy, non-fainting subjects matched for age and sex. Basal records were similar in both groups. Patients had preserved cardiovagal function. The multivariate cluster analysis allowed us to find a homogeneous group of cases (46%) that simultaneously presented: greater fall in systolic and diastolic blood pressure after standing, increased 15:30 ratio, exaggerated absolute heart rate rise in response to standing and subclinical reduced sudomotor function in the foot. The results suggest the existence of a subclinical autonomic profile, with subtle sympathetic postganglionic impairment, evident in lower limbs. These findings may contribute to proving the existence of different types of neurally mediated syncope, all different in their onset and mechanism but with a common final manifestation: syncopal loss of consciousness.

Adolescent↗
PubMed1996

Evaluation of congenital dysautonomia other than Riley-Day syndrome.

We report on four children, from different families, who suffer from a congenital autonomic disorder, presumably inherited. Three of them have a sensory neuropathy but do not fit any described hereditary sensory and autonomic neuropathy. All four were examined along with some of their immediate family members. We assessed the cardiovagal, sympathetic adrenergic and sympathetic cholinergic functions with a battery of non-invasive tests. Results demonstrated that sudomotor and cardiovascular orthostatic regulation exhibited the greatest abnormalities, pointing to a predominant impairment of sympathetic components, both cholinergic and adrenergic. The overall examination showed a heterogeneous group of congenital dysautonomia, exclusive of Riley-Day or other recognized hereditary sensory and autonomic neuropathies. We emphasize the importance of studying whole family groups to diagnose subclinical impairment and to provide correct genetic counselling.

Adolescent↗
PubMed1995

Sympathetic sudomotor function and aging.

Many studies have reported the influence of aging on different portions of the autonomic nervous system components but only partially for the sympathetic cholinergic system. We evaluated postganglionic sudomotor function in 196 healthy subjects, 104 women and 92 men, by determining sweat gland density (SGD) per square centimeter of skin, on the dorsum of the hand and foot, with the impression mold technique. The age range was from 5 to 84 years. A significant decrease of SGD was observed in both hand and foot in relation to age (P < 0.001). The ANOVA analysis of foot data shows that age is the only significant factor for SGD reduction. In the hand, both sex and body surface area are significant covariates with age. The dorsum of the foot is the most appropriate place to examine sweating in studies of aging. The lower normal limits for SGD in the foot are 213/cm2 for subjects younger than 30 years, 199/cm2 for those from 30 to 59 years, and 123/cm2 for subjects over 59 years old.

Adolescent↗
PubMed1995

Sympathetic skin response: correlation with autonomic and somatic involvement in multiple sclerosis.

The sympathetic skin response (SSR) was studied in 63 multiple sclerosis (MS) patients, 54 with clinical definite and 9 with clinical probable form. The test was recorded from palms and soles and induced by electric stimulus. SSR was abnormal, absent or mildly delayed, in 26 patients (41%). The average score in the Kurtzke Expanded Disability Status Scale was higher in patients with abnormal SSR, showing a positive correlation with the latencies (p < 0.05). When compared to other evoked responses (somatosensory, brainstem auditory and visual evoked potentials), only visual evoked potentials showed a positive correlation (p < 0.05). Among the signs of autonomic dysfunction, bladder impairment was the most frequently associated with altered SSR (p < 0.05). These results could be probably due to the higher incidence of these abnormalities during the course of the disease. It is concluded that SSR is a simple test for a dynamic evaluation of MS, well correlated with the degree of disability, able to detect subclinical lesions in the sympathetic tracts, but with slight localizing value. It has also a low sensitivity for autonomic impairment related only with the bladder dysfunction. These facts exclude the SSR as a primary diagnostic tool in MS.

Adolescent↗
PubMed1994

[S. pneumoniae sternoclavicular arthritis in a patient with HIV infection].

HIV infection is a predisposing factor for pneumococcic infection. While pneumonia is the most frequent location, other locations (articular, meningeal, endocardiac, etc) have been less frequently described. Among the articular infections described in patients with HIV infection, the sternoclavicular affection is extremely rare and it usually develops in association with parenterally drug addiction, being Staphylococcus aureus and Pseudomonas aeruginosa the most frequently germs involved. We describe the first case of sternoclavicular arthritis by Streptococcus pneumoniae in a patient with HIV infection. In our case, the chronic hepatopathy associated to alcohol consumption is a predisposing factor related to the pneumococcic infection. Our case suggests the need to formally investigate the HIV infection in young patients with invasive pneumococcic infection.

Adult↗
PubMed1989

[Inflammatory pseudotumor of the liver].

Certain rare, reactive, non-neoplastic processes are defined under the term inflammatory pseudotumor, which is constituted by the proliferation of connective tissue and chronic inflammatory infiltrate of circumscribed location. Its etiopathogenesis ins unknown, although it is thought to have a possible infectious nature. It has been described various organs, but location in the liver is exceptional. We present a new case of inflammatory pseudotumor of hepatic location, related to an "hour-glass" abscess adhered to diaphragm, this being the first case of this relation. We reviewed the literature concerning etiopathogenic, histopathologic, clinical and diagnostic aspects, and our findings are discussed.

Adult↗