The impact of skin diseases on quality of life: a multicenter study / El impacto de las enfermedades cutáneas en la calidad de vida: un estudio multicéntrico

INTRODUCTION: To date, no formal study has been published regarding how Colombian patients with skin disorders could be affected according to their perception of disease. OBJECTIVE: To determine the impact in quality of life of skin diseases in a Colombian population. METHODS: This multicenter study included patients with skin disease from almost the whole country. Individuals >18 years old; of any gender; with any skin disease and who signed informed consent, were included. We applied the Colombian validated version of the Skindex-29 instrument. RESULTS: A total of 1896 questionnaires had sufficient information for the analyses. No significant differences in sociodemographic characteristics of patients who returned the questionnaire incomplete vs. complete, were found. Participants mean age was 41.5 years. There were no statistical differences in men vs. women regarding the global (p = 0.37), symptoms (p = 0.71) and emotions (p = 0.32) domains, whereas statistical differences were found in the function domain (p = 0.04; Mann-Whitney U test). Psoriasis, contact dermatitis, atopic dermatitis, urticaria, hair disorders, Hansen's disease, scars, hyperhidrosis and genital human papillomavirus disease scored the highest. Limitations. Skindex-29 score variability as a result of differences in the location of the skin lesions, their inflammatory or non-inflammatory nature, and the start of therapy. CONCLUSIONS: Even the most localized or asymptomatic skin lesion in our population leads to a disruption at some level of patient's wellness. This study adds well supported scientific data of the burden of skin diseases worldwide

INTRODUCCIÓN: En Colombia se carece de estudios que hayan evaluado formalmente el impacto de las enfermedades dermatológicas en la calidad de vida de los pacientes que las padecen. OBJETIVO: Determinar el impacto en la calidad de vida de las enfermedades cutáneas en una población colombiana. MÉTODOS: Estudio multicéntrico que incluyó a individuos>18 años de edad; de cualquier sexo, con cualquier trastorno cutáneo y que firmaron el consentimiento informado. Se aplicó la versión validada en Colombia del instrumento Skindex-29. RESULTADOS: Un total de 1.896 cuestionarios se incluyeron en el análisis. No se observaron diferencias significativas en las características sociodemográficas entre los que devolvieron el cuestionario incompleto vs. completo. La edad promedio fue de 41,5 años. No hubo diferencias significativas entre hombres y mujeres con respecto al puntaje global del instrumento, ni de los dominios sintomático o emocional, mientras que sí las hubo en el dominio funcional. Entre las enfermedades que más afectaron la calidad de vida se incluyen: psoriasis, dermatitis de contacto, dermatitis atópica, urticaria, trastornos capilares, lepra, cicatrices, hiperhidrosis y las verrugas genitales. Limitaciones. Las puntuaciones del Skindex-29 mostraron una gran variabilidad explicable por diferencias en la localización de las lesiones de la piel, su naturaleza inflamatoria/no inflamatoria, y la iniciación o no del tratamiento. CONCLUSIONES: Cualquier lesión dermatológica por más localizada o asintomática que sea, condujo a una alteración en algún grado de la calidad de vida dermatológica. Este estudio añade soporte científico a la carga de enfermedad que generan los trastornos cutáneos en el mundo

Inhibición de PCSK9: una nueva alternativa para reducir el colesterol y prevenir la enfermedad cardiovascular aterosclerosa / Inhibition of PCSK9: a new alternative for cholesterol reduction and prevention of atherosclerotic cardiovascular disease

Resumen La enfermedad cardiovascular aterosclerosa ocupa el primer lugar mundial en morbilidad y mortalidad. El principal factor de riesgo de enfermedad es el colesterol unido a lipoproteínas de baja densidad (C-LDL). El tratamiento farmacológico de elección para reducir el C-LDL son las estatinas; sin embargo, han sido insuficientes para eliminar el riesgo cardiovascular, especialmente en pacientes con formas primarias de hipercolesterolemia relacionadas con mutaciones genéticas, o intolerantes a estatinas. Es de gran importancia el desarrollo de nuevos fármacos para abatir el riesgo que persiste a pesar de la administración de estatinas. La proconvertasa subtilisina-kexina 9 (PCSK9) es un regulador primordial de la cantidad de receptores de LDL, ya que su función es dirigir dichos receptores a su destrucción lisosomal. El advenimiento de anticuerpos monoclonales para bloquear la PCSK9 ha permitido mejorar la cantidad y eficiencia de los receptores de LDL, de esto resulta la disminución notable del colesterol circulante. Hasta el momento, la eficacia e inocuidad de estos anticuerpos resultan aceptables, y los datos preliminares en cuanto a su efecto en la reducción de la morbilidad y mortalidad cardiovasculares son alentadores.

Abstract Atherosclerotic cardiovascular disease represents the leading cause of morbidity and mortality in most countries. The main risk factor for developing this disease is low density lipoprotein cholesterol (LDL-C). The pharmacological treatment of choice for reducing LDL-C is statins; however, in spite of the widespread use of statins, these drugs have been insufficient to eliminate cardiovascular risk. This residual risk is most relevant in patients with primary forms of hypercholes-terolemia associated with genetic mutations, or in those who are intolerant to statins. The development of new drugs to reduce residual cardiovascular risk is of vital importance. Proprotein convertase subtilisin-kexin 9 (PCSK9) is an important regulator of the amount of LDL receptors since its function is to direct these receptors to their lysosomal destruction. The development of monoclonal antibodies to block extracellular PCSK9 has allowed us to improve the quantity and efficiency of LDL receptors, resulting in a significant decrease in plasma cholesterol. Efficacy and safety of these antibodies is currently considered acceptable and preliminary data are encouraging but still insufficient to assess the favorable impact of these antibodies in reducing cardiovascular morbidity and mortality.

The impact of skin diseases on quality of life: A multicenter study.

INTRODUCTION: To date, no formal study has been published regarding how Colombian patients with skin disorders could be affected according to their perception of disease. OBJECTIVE: To determine the impact in quality of life of skin diseases in a Colombian population. METHODS: This multicenter study included patients with skin disease from almost the whole country. Individuals >18 years old; of any gender; with any skin disease and who signed informed consent, were included. We applied the Colombian validated version of the Skindex-29 instrument. RESULTS: A total of 1896 questionnaires had sufficient information for the analyses. No significant differences in sociodemographic characteristics of patients who returned the questionnaire incomplete vs. complete, were found. Participants mean age was 41.5 years. There were no statistical differences in men vs. women regarding the global (p=0.37), symptoms (p=0.71) and emotions (p=0.32) domains, whereas statistical differences were found in the function domain (p=0.04; Mann-Whitney U test). Psoriasis, contact dermatitis, atopic dermatitis, urticaria, hair disorders, Hansen's disease, scars, hyperhidrosis and genital human papillomavirus disease scored the highest. LIMITATIONS: Skindex-29 score variability as a result of differences in the location of the skin lesions, their inflammatory or non-inflammatory nature, and the start of therapy. CONCLUSIONS: Even the most localized or asymptomatic skin lesion in our population leads to a disruption at some level of patient's wellness. This study adds well supported scientific data of the burden of skin diseases worldwide.

CBP/catenin antagonist safely eliminates drug-resistant leukemia-initiating cells.

CREB-binding protein (CBP) and p300 are highly homologous transcriptional coactivators with unique, non-redundant roles that bind a wide array of proteins, including catenins-ß and γ. ICG-001 is a small-molecule inhibitor that specifically inhibits the CBP/catenin interaction. Importantly, ICG-001 does not inhibit the p300/catenin interaction. We demonstrate that specifically inhibiting the interaction between CBP and catenin with ICG-001 results in the differentiation of quiescent drug-resistant chronic myelogenous leukemia-initiating cells (CML LICs), thereby sensitizing them to BCR-ABL tyrosine kinase inhibitors, for example, Imatinib. Using ICG-001 in a NOD/SCID/IL2Rγ(-/-) mouse model of engrafted human chronic myelogenous leukemia, we now demonstrate the complete elimination of engrafted leukemia after only one course of combined chemotherapy. Combination-treated animals live as long as their non-engrafted littermates. Results from these studies demonstrate that specifically antagonizing the CBP/catenin interaction with ICG-001 can eliminate drug-resistant CML LICs without deleterious effects to the normal endogenous hematopoietic stem cell population.

Modelling phenolic and technological maturities of grapes by means of the multivariate relation between organoleptic and physicochemical properties.

The ripeness of grapes at the harvest time is one of the most important parameters for obtaining high quality red wines. Traditionally the decision of harvesting is to be taken only after analysing sugar concentration, titratable acidity and pH of the grape juice (technological maturity). However, these parameters only provide information about the pulp ripeness and overlook the real degree of skins and seeds maturities (phenolic maturity). Both maturities, technological and phenolic, are not simultaneously reached, on the contrary they tend to separate depending on several factors: grape variety, cultivar, adverse weather conditions, soil, water availability and cultural practices. Besides, this divergence is increasing as a consequence of the climate change (larger quantities of CO(2), less rain, and higher temperatures). 247 samples collected in vineyards representative of the qualified designation of origin Rioja from 2007 to 2011 have been analysed. Samples contain the four grape varieties usual in the elaboration of Rioja wines ('tempranillo', 'garnacha', 'mazuelo' and 'graciano'). The present study is the first systematic investigation on the maturity of grapes that includes the organoleptic evaluation of the degree of grapes maturity (sugars/acidity maturity, aromatic maturity of the pulp, aromatic maturity of the skins and tannins maturity) together with the values of the physicochemical parameters (probable alcohol degree, total acidity, pH, malic acid, K, total index polyphenolics, anthocyans, absorbances at 420, 520 and 620 nm, colour index and tartaric acid) determined over the same samples. A varimax rotation of the latent variables of a PLS model between the physicochemical variables and the mean of four sensory variables allows identifying both maturities. Besides, the position of the samples in the first plane defines the effect that the different factors exert on both phenolic and technological maturities.

New evidence of a dihydropyridine-activated cationic channel in the MDCK cell line.

Newborn rat distal cells express an apical Ca2+ channel activated by dihydropyridine drugs. Similarly, in Madin-Darby canine kidney (MDCK) cells, nifedipine increased Ca2+i in a concentration-dependent manner (IC50=4 µM) in fura-2-loaded cells. Response to nifedipine was abolished by EGTA, suggesting that it depends on extracellular calcium. Ca2+ channel antagonist isradipine and agonist BayK8644 increased Ca2+i indicating that this effect is related to the dihydropyridine group. Diltiazem (20 µM) and gadolinium (200 µM) decreased the nifedipine effect (62 and 43%, respectively). Lanthanum (100 µM) did not change the response. Valinomycin clamping of the membrane potential did not modify nifedipine-induced increment, indicating that it was unrelated to potassium fluxes. We performed whole cell clamp experiments in MDCK cells maintained at -50 mV with perfusion solution containing 10 mM CaCl2. Nifedipine (20 µM) induced an increase in current (1.2±0.3 nA), which was partially inhibited by Gd3+. No significant current was induced by nifedipine in the presence of 0.5 mM EGTA. To determine the effects of nifedipine on the membrane potential, we performed oxonol fluorescence experiments. The addition of nifedipine or Bay K8644 induced depolarization, highly dependent on external sodium. Nifedipine (20 µM) induced depolarization of 6.9±0.8 mV (n=21). EC50 to nifedipine was in the 10 µM range. We conclude that MDCK cells exhibit a dihydropyridine-activated cationic channel.

Nifedipine-activated Ca(2+) permeability in newborn rat cortical collecting duct cells in primary culture.

To characterize Ca(2+) transport in newborn rat cortical collecting duct (CCD) cells, we used nifedipine, which in adult rat distal tubules inhibits the intracellular Ca(2+) concentration ([Ca(2+)](i)) increase in response to hormonal activation. We found that the dihydropyridine (DHP) nifedipine (20 microM) produced an increase in [Ca(2+)](i) from 87.6 +/- 3.3 nM to 389.9 +/- 29.0 nM in 65% of the cells. Similar effects of other DHP (BAY K 8644, isradipine) were also observed. Conversely, DHPs did not induce any increase in [Ca(2+)](i) in cells obtained from proximal convoluted tubule. In CCD cells, neither verapamil nor diltiazem induced any rise in [Ca(2+)](i). Experiments in the presence of EGTA showed that external Ca(2+) was required for the nifedipine effect, while lanthanum (20 microM), gadolinium (100 microM), and diltiazem (20 microM) inhibited the effect. Experiments done in the presence of valinomycin resulted in the same nifedipine effect, showing that K(+) channels were not involved in the nifedipine-induced [Ca(2+)](i) rise. H(2)O(2) also triggered [Ca(2+)](i) rise. However, nifedipine-induced [Ca(2+)](i) increase was not affected by protamine. In conclusion, the present results indicate that 1) primary cultures of cells from terminal nephron of newborn rats are a useful tool for investigating Ca(2+) transport mechanisms during growth, and 2) newborn rat CCD cells in primary culture exhibit a new apical nifedipine-activated Ca(2+) channel of capacitive type (either transient receptor potential or leak channel).

Effects of thrombin on intracellular calcium and pH in human and murine platelets.

The aim of this study was to compare the effect of thrombin (Thr) on cytosolic calcium [Ca2]+i and intracellular pH [pH]i in human and murine platelets. Rich-platelet suspensions from both species were loaded with Fura-2 (2 microM) or BCECF (0.75 microM) by incubation with their respective acetoxymethyl esters to measure cytosolic calcium [Ca2+]i or intracellular pH [pH]i, respectively. Suspensions were challenged with increasing concentrations of Thr, from 0.1 to 10 IU/ml. Basal [Ca2+]i in human platelets was 98 +/- 6 and 99.1 +/- 9 nM in rat platelets (n = 20). Thr increased [Ca2+]i, EC50 was 1.1 +/- 0.04 in human and 0.97 +/- 0.06 IU/ml in rat platelets (n = 7). Extracellular Mg2+ (4 or 8 mM) abolished Thr response on [Ca2+]i. [pH]i in human was 7.09 +/- 0.08 and 7.11 +/- 0.04 in rat platelets. Thr induced alkalinization of platelets in both species. Our results indicate that the potency of Thr to change [Ca2+]i and [pH]i was similar in both species, allowing for comparisons between human and murine platelets and to extrapolate results from an animal model to human pathology.

Bis(acetylacetonato-O,O')(eta 4-trans-2,4-hexadiene)ruthenium(II) 1/6-ethanol solvate.

The title compound, [Ru(C5H7O2)2(C6H10)].1/6C2H6O, has a pseudo-octahedrally coordinated RuII center, where two coordination sites are occupied by a diene ligand. The diene ligand exhibits a eta 4-trans-diene coordination mode. The compound crystallizes in space group R3, incorporating disordered ethanol in cylindrical voids.

Influence of sex differences on the renal secretion of organic anions.

The kidney's responsiveness to male sexual hormones has been often neglected. Renal secretion of organic anions is higher in male than in female individuals; as a consequence, most of the xenobiotics that are excreted from the organism through this pathway are eliminated more rapidly by males than by female animals. To gain further insight into this issue, we studied in vitro and in vivo characteristics of the transport of p-aminohippurate (PAH), a suitable marker for this system, in male and female rats, under different hormonal conditions. Kinetics of PAH showed a shorter elimination half-time in male than in female rats (t(1/2el): male = 16.2 +/- 2.1 min, female = 25.7 +/- 4.5 min, P < 0.05). Castration of male rats increased t(1/2el) to a value similar to that of female rats (t(1/2el): orchiectomized rat = 28.1 +/- 7.1 min). Testosterone treatment of female rats increased the elimination rate to a value similar to that of male rats. In vitro PAH uptake by renal cortical slices from intact male rats was higher than that by slices from orchiectomized rats. Kinetic analyses of PAH uptake suggest that the difference was caused by a lower number of transporting molecules in orchiectomized than in intact animals, whereas the transporting capacity for each carrier was similar in male and in orchiectomized rats. Our results suggest that testosterone increases the number of functional carriers for PAH in the kidney.

Opening-wedge osteotomy, bone graft, and external fixation for correction of radius malunion.

A technique of radius opening-wedge osteotomy, bone graft, and external fixation for the treatment of symptomatic radius malunion is presented. It provides direct rigid fixation to the osteotomy components, thus maintaining the correction while allowing early wrist exercises. This technique has been effective for 7 patients in correcting deformities that averaged--20 degrees palmar tilt with radial shortening of 3.4 mm to a postoperative average palmar tilt of 5.3 degrees and -0.4 mm radial shortening. It is an alternative technique for the hand surgeon treating radius malunion and can be easily combined with adjunctive procedures.

Membrane permeability transition as induced by dysfunction of the electron transport chain.

The results in this paper indicate that mitochondrial permeability transition is activated by dysfunction of the respiratory chain caused by anaerobiosis, exhaustion of the oxidative substrate, and antimycin A, in the presence of 100 microM Ca2+. Membrane damage coincides with the collapse of the electric gradient. The opening of the non-selective pore is prevented by cyclosporin A.

Disseminated American cutaneous leishmaniasis.

BACKGROUND: While studying cutaneous leishmaniasis in the central part of western Venezuela, we found four cases of disseminated American cutaneous leishmaniasis, three from the Lara State and one from Portuguesa State. METHODS: A clinical history was taken for each of these patients, followed by microscopic examination of the Giemsastained smears from their cutaneous lesions and by a Montenegro skin test. Serum from a skin lesion were grown in Novy-MacNeal-Nicolle medium (NNN). Hamsters were inoculated with suspension of tissues taken from the patient's lesions. Biopsies were taken for histopathologic examination. Isolates from cultures on NNN medium and from hamsters were subcultured in Schneider's medium for parasite identification, using molecular techniques. Treatment with injections of N-methyl glucamine antimonate, 25 mg/kg/day was prescribed for each patient for 20 consecutive days and, after a week of rest, a second course of injections was administered. RESULTS: Patients had disseminated papular, ulcerous, nodular, and ulceronodular lesions on the skin. Smears of the skin lesions from all of the patients showed abundant amastigotes within histiocytes or free in the tissues. The skin test was negative in two patients. On histopathologic examination of skin lesions, mainly numerous vacuolated histiocytes filled with amastigotes were observed. Isolates from all the patients were identified as Leishmania venezuelensis. One of the patients healed after treatment with N-methyl glucamine antimonate. The others were resistant to this therapy. CONCLUSIONS: Diffuse cutaneous leishmaniasis can be caused also by Leishmania venezuelensis. Patients with nodular lesions who presented a negative Montenegro skin test were more resistant to treatment with specific pentavalent antimonials.

Trombolisis en infarto agudo del miocardio de origen embólico / Thrombolysis in embolic myocardial infarction

El infarto agudo del miocardio de origen embólico presenta una incidencia del 5-13 por ciento; se asocia a factores de riesgo de embolia sistémica. El mecanismo del infarto tiene similitud con el infarto de origen aterosclerótico, por lo que es suceptible de tratamiento con trombolisis. Se reportan 3 casos de pacientes con cardiopatía reumática inactiva, coartación de aorta y prótesis valvular mecánica, como probables causas de infarto embólico, de localización posteroinferior con estensión dorsal y a quienes se les administró estreptoquinasa intravenosa. Los pacientes presentaron criterios de reperfusión miocárdica; presentándose en dos, angor post-infarto. El primero presentó reoclusión de la coronaria derecha, llevandolo a colocación de hemoducto venoso. En el segundo se observó la persistencia de trombo en la arteria circunfleja, dejándole con anticoagulación por tres meses y en el tercer caso no se observó lesiones coronarias. Se concluye que la terapia trombolíca con estreptoquinasa en el infarto agudo del miocardio embólico previene la progresión del daño isquémico y favorece la evolución clínica del paciente. Además, debe sospecharse tal enfermedad en pacientes que presentan factores de risgo para embolia sistémica y arterias coronarias normales con obstrucción de un solo vaso

Specificity of circulating and tissue-bound autoantibodies in Goodpasture syndrome.

Goodpasture syndrome is an often fatal autoimmune disease associated with glomerulonephritis and/or pulmonary hemorrhage. The clinical manifestations of this disease correlate well with the presence of circulating antiglomerular basement membrane (GBM) autoantibodies. The primary target antigen in glomerular and alveolar basement membranes is thought to be the alpha 3 chain of type IV collagen. Nearly all that is known about anti-GBM antibodies in humans comes from work on unbound circulating antibody. We recently had the unique and rare opportunity to obtain early postmortem antibody and tissues from a patient who died with catastrophic Goodpasture syndrome. The specificity of circulating, kidney-bound and lung-bound autoantibodies from this patient was evaluated against a variety of purified basement membrane constituents. The results indicate that the primary target for the circulating and tissue-bound autoantibodies is the NC1 domain of the alpha 3(IV) chain of type IV collagen. Additionally, all the antibodies recognize a cryptic epitope/s on the alpha 3(IV)NC1 hexamer. Furthermore, tissue-bound and circulating antibodies compete with one another for overlapping epitopes on the antigen. These findings demonstrate that circulating autoantibodies in Goodpasture syndrome are highly representative of those bound to organ tissues, strengthening the notion that pathogenic autoantibodies are targeted to the alpha 3(IV)NC1 collagen, and that previous reports of findings in the circulation may be applicable to tissue injury.

Endocytosis inhibition protects the isolated guinea pig heart against ouabain toxicity.

We have tested whether toxicity and uptake of ouabain are linked phenomena in isolated guinea-pig heart. We perfused toxic dose of either ouabain, dihydroouabain (hydrophilic cardiac steroids), ouabagenin or digitoxin (hydrophobic steroids) in conditions of endocytosis inhibited. We used two schemes of inhibition of endocytosis. First, we cooled the heart at 0-4 degrees C and exposed it 60 min to either 1 X 10(-6) M ouabain or 3 X 10(-7)M digitoxin. Upon rewarming, the heart exposed to ouabain relaxed with a shorter time constant than those exposed to digitoxin. Second, we perfused four receptor mediated endocytosis (RME) inhibitors at the same time that the cardiac glycosides. RME inhibitors significantly delayed the cardiac arrest caused by ouabain and dihydroouabain but they did not modify the toxicity of 3 X 10(-7)M digitoxin or 5 X 10(-6)M ouabagenin. None of RME inhibitors modified the toxicity of 0.5 mM K+ or zero Na+ saline solution. We suggest that the protection against ouabain toxicity brought by endocytosis inhibition, is related to the Na-pump recycling. We infer that besides the sarcolemmal exposed Na-pumps, the intracellular Na-pumps pool may be of importance for the pharmacological effects of digitalis steroids.

AIDS in the elderly: New York City vital statistics.

The HIV infection primarily affects young adults, but older adults are also susceptible. The number of AIDS cases among persons aged 50 or greater is growing and is of major concern. As our awareness of the prevalence of HIV-related illnesses presenting to the emergency department improves in the younger population, we must not ignore the disease in older patients. Early recognition of HIV infection will ensure the greatest opportunity for treatment and prevention of many of the consequences of opportunistic infections. We present a case of HIV in an elderly patient in order to heighten awareness of the possibility of HIV infection in older patients presenting to the emergency department. We also review the epidemiological, diagnostic, and therapeutic aspects of AIDS in older adults.

Age-related differences in the glomerular and renal tubular effects of amikacin in the rat.

Several biological responses to drugs are dependent on the age of the individual. Renal excretion of amikacin occurs mainly through glomerular filtration and this function is diminished in the young animal. We evaluated the renal response to amikacin in the unanesthetized infant rat (21-day-old) and we compared it with that of the adult rat. Either amikacin (7.5 and 75.0 mg/kg body weight, i.m.) or vehicle were administered to infant rats and the effects on sodium, potassium and water balance were assessed. Creatinine clearance (Ccr) was calculated. Amikacin induced an increment in sodium absolute excretion, whereas the Ccr decreased. In the infant rat the effects were more marked. Changes in FENa were more marked than those in Ccr, suggesting a direct effect of amikacin on the tubular reabsorption of electrolytes in addition to deleterious effects on glomerular dynamics. Our results suggest that amikacin induces more changes in renal function in the infant than in the adult rat and therefore it might be convenient to carefully evaluate the renal condition in the patients that receive this drug.

Etiology and outcome of non-estrogen associated hyperthyroxinemia in euthyroid patients at the San Juan City Hospital.

INTRODUCTION: Hyperthyroxinemia does not always equate to hyperthyroidism. Laboratory tests should always be correlated with the clinical picture. A mismatch should make one doubt true hyperthyroidism. The purpose of our study was to assess the etiology of euthyroid hyperthyroxinemia not associated with estrogen use or pregnancy and to review the outcome of those erroneously treated. METHODS: The medical records of thirteen euthyroid patients with non estrogen associated hyperthyroxinemia were reviewed. They had a complete set of thyroid function tests including free T3 and free T4 by membrane dialysis, TRH stimulation test and thyroid hormone binding panel. RESULTS: Two diagnostic groups were identified: Hyperthyroxinemia secondary to binding abnormalities (7/13), better known as familial dysalbuminemic hyperthyroxinemia (FDH) and hyperthyroxinemia secondary to Thyroid Hormone Resistance (THR) (6/13). The FDH group had an elevated T4 and FTI, with normal T3RU, TSH, TRH stimulation test but an abnormal thyroid hormone binding panel which was used to confirm the diagnosis. The THR group had two laboratory presentations: Four patients presented with all the thyroid hormone tests elevated (T4, T3, T3RU, FTI) including a free T3 and free T4 by membrane dialysis with a normal TSH and TRH stimulation test and a normal T4 binding panel. This presentation is typical for a TRH patient with a nuclear receptor defect where all the precursos to the defect accumulate. Two patients with THR presented elevated T4 and free T4 but normal T3 and free T3, localizing the defect at the level of the active T4 transport mechanism across the cellular membrane. These two patients had a normal TSH, TRH stimulation test and T4 binding panel. Two patients were treated erroneously with radioactive iodine and became extremely hypothyroid in spite of normal TFTs. Very high dose of thyroid hormone replacement were required to restore euthyroidism. CONCLUSION: One must suspect these two entities in patients clinically euthyroid who have elevated T4 but non-suppressed TSH. A normal TSH and TRH test confirm euthyroidism. A thyroid hormone binding panel differentiates FDH from THR. Neither group require treatment. If treated erroneously and T4 drops to normal values, one must again induce hyperthyroxinemia to restore euthyroidism in these patients.

Modulation of the release of adenosine by glucose and chemical hypoxia in cultured renal cells (MDCK line).

The effect of changes in the external concentrations of glucose on the release of adenosine of cultured renal cells (MDCK line) was studied. Adenosine release was markedly increased by the addition of glucose (5.5 mM) to monolayers of MDCK cells deprived of glucose for 24 hours. Addition of glucose to either the apical or basolateral side of the monolayer elicited a marked release of adenosine at the contralateral compartment. Removal of sodium in the external media blunted the response to glucose. Methylglucose that is transported into the cell but not metabolized also markedly increased adenosine release. Deoxyglucose that induces chemical hypoxia stimulated the release of adenosine. These results suggest that variations in extracellular glucose might be a physiological modulator of the cell regulation of adenosine.