SENSIBILIZACIÓN A AEROALERGENOS EN PACIENTES CON RINITIS Y ASMA

Las enfermedades alérgicas han aumentado en las últimas décadas en todo el mundo. El asma y la rinitis alérgica podrían representar un espectro de la misma enfermedad, cuya patogénesis puede explicarse, entre otros factores, por la sensibilización a aeroalergenos. Los aeroalergenos más frecuentemente involucrados como sensibilizantes se hallan en el polvo del interior del hogar o lugar de trabajo (indoor). Dentro de los aeroalergenos indoor, los dermatophagoides son los más prevalentes. Este estudio demuestra que la prevalencia de sensibilidad a aeroalergenos indoor, en pacientes con rinitis y asma, es coincidente con la bibliografía. Es un área a investigar en el futuro, la prevalencia de sensibilidad a aeroalergenos outdoor

Allergic diseases have increased in recent decades worldwide. Asthma and allergic rhinitis could represent a spectrum of the same disease, whose pathogenesis can be explained, among other factors, by sensitization to aeroallergens. The aeroallergens most frequently involved as sensitizers are found in the dust inside the home or workplace (indoor). Within indoor aeroallergens, dermatophagoides are the most prevalent. This study demonstrates that the prevalence of sensitivity to indoor Aeroallergens, in patients with rhinitis and asthma, is consistent with the literature. It is an area to investigate in the future, the prevalence of sensitivity to outdoor aeroallergens.

Pregnancy in women with a history of Kawasaki disease: management and outcomes.

OBJECTIVE: To characterise the obstetrical management and outcomes in a series of women with a history of Kawasaki disease (KD) in childhood. DESIGN: Retrospective case series. SETTING: Tertiary healthcare setting in the USA. POPULATION: Women with a history of KD in childhood. METHODS: Women completed a detailed health questionnaire and participated in research imaging studies as part of the San Diego Adult KD Collaborative Study. MAIN OUTCOME MEASURES: Obstetrical management, complications during pregnancy and delivery, and infant outcomes. RESULTS: Ten women with a history of KD in childhood carried a total of 21 pregnancies to term. There were no cardiovascular complications during labour and delivery despite important cardiovascular abnormalities in four of the ten subjects. Pregnancy was complicated by pre-eclampsia and the post-partum course was complicated by haemorrhage in one subject each. Two of the 21 progeny subsequently developed KD. CONCLUSIONS: Women with important cardiovascular sequelae from KD in childhood should be managed by a team that includes both a maternal-fetal medicine specialist and a cardiologist. Pre-pregnancy counselling should include delineation of the woman's current functional and structural cardiovascular status and appropriate adjustment of medications, but excellent outcomes are possible with appropriate care. Review of the English and Japanese literature on KD and pregnancy revealed the occurrence of myocardial infarction during pregnancy in women with missed KD and aneurysms that were not diagnosed until their acute event. Our study highlights the need for counselling with regard to the increased genetic risk of KD in offspring born to these mothers.

Herniography: analysis of its role and limitations.

INTRODUCTION: Herniography is a radiographic procedure shown to be valuable in the examination of groin symptoms. It is useful in clinical situations, including the detection of occult hernia, the investigation of groin hernia when physical findings are equivocal, and the assessment of pain after inguinal hernia repair. OBJECTIVE: To systematically review the current literature on the use of herniography and to evaluate its reliability, risk, and limitations. METHOD: The Medline database was searched for publications on herniography. RESULTS: Herniography has a low false-positive rate, ranging from 0 to 18.75%. The sensitivity rate ranges from 81 to 100%, and the specificity rate ranges from 92 to 98.4%. CONCLUSION: Herniography is a safe and effective diagnostic procedure for assessing obscure groin symptoms. It has the potential of reducing the incidence of unnecessary operations. It should be considered in the evaluation of patients where the etiology of inguinal pain is unclear.

Insulin stimulates arterial neointima formation in normal rats after balloon injury.

AIM: Insulin resistance in patients is associated with increased atherosclerosis and arterial restenosis. It is thought that the concomitant hyperinsulinaemia exacerbates vascular disease because resistance to insulin-induced glucose disposal is associated with resistance to certain effects of insulin which inhibit, but with no resistance to other effects which promote, neointimal hyperplasia. We sought to determine the net effect of hyperinsulinaemia on neointimal hyperplasia in normal animals. METHODS: Rats were infused with or without insulin for 16 days and the carotid artery injured by balloon catheter on day 2. RESULTS: Steady-state serum insulin concentrations were 0.56 +/- 0.04 and 1.25 +/- 0.05 nm for control and hyperinsulinaemic rats respectively (p < 0.01). Systolic blood pressures, weights and serum glucose levels were not affected by hyperinsulinaemia. Fourteen days after injury, the neointima-to-media area ratio was 0.72 +/- 0.07 and 1.39 +/- 0.15 for control and hyperinsulinaemic rats respectively (p < 0.05). Media area was unaffected by hyperinsulinaemia. CONCLUSIONS: The effects of hyperinsulinaemia which promote neointimal hyperplasia after balloon injury of rat carotid artery predominate over the effects which inhibit it even in normal animals.

GRbeta expression in nasal polyp inflammatory cells and its relationship to the anti-inflammatory effects of intranasal fluticasone.

BACKGROUND: Nasal polyposis disease is an inflammatory disorder with intense eosinophilic infiltration of respiratory mucosa that is often difficult to control with topical steroids. Recent evidence suggests that overexpression of the glucocorticoid receptor splice variant GRbeta in inflammatory cells might contribute to steroid insensitivity in diseases such as asthma. OBJECTIVE: The purposes of this investigation were to determine whether nasal polyp (NP) inflammatory cells overexpress GRbeta and to examine whether GRbeta overexpression is associated with insensitivity to the potent topical steroid fluticasone propionate (FP). METHODS: Biopsies were obtained from 10 subjects with NPs before and 4 weeks after treatment with intranasal FP. Middle turbinates biopsies from 6 healthy, nonallergic subjects served as normal controls. Biopsies were immunostained for inflammatory cell markers as well as GRbeta and probed for various cytokine mRNA. The anti-inflammatory response to FP was examined in relation to pretreatment levels of GRbeta expression. RESULTS: The total numbers of inflammatory cells were increased in NPs. The percentage of inflammatory cells expressing GRbeta was also increased (40.5% +/- 19.2% vs 16.1% +/- 4.0%, P =.009). GRbeta expression in NPs was almost exclusive to T lymphocytes, eosinophils, and macrophages. An inverse correlation was observed between the baseline inflammatory cell GRbeta expression and the reduction after FP treatment in EG2-positive eosinophils, CD4-positive T lymphocytes, endothelial VCAM-1 expression, and IL-4 mRNA-positive cells. NPs that were "FP-insensitive" in terms of suppression of eosinophil numbers (major basic protein-positive) had a significantly greater percentage of GRbeta-positive inflammatory cells, a higher ratio of GRbeta-positive/GRalpha-positive cells, and increased numbers of GRbeta-positive eosinophils and macrophages in comparison with those that were "FP-sensitive." "FP-insensitive" NPs also demonstrated a higher percentage of IL-5-positive inflammatory cells expressing GRbeta before and after FP treatment. CONCLUSION: GRbeta expression appears to be a marker of steroid insensitivity in NPs. Expression of GRbeta by NP inflammatory cells, particularly T cells and eosinophils, might render them resistant to suppression by topical steroids and thereby contribute to persistent NP inflammation.

Induction, distribution and modulation of upper airway allergic inflammation in mice.

BACKGROUND: To further elucidate mechanisms of human allergic rhinosinusitis, we studied the induction, distribution and modulation of allergen-induced upper airway inflammation in a BALB/c mouse model. METHODS: Allergic inflammation induced with ovalbumin (OVA) by intraperitoneal (IP) injection in alum was compared to repeated intranasal instillation. The type and distribution of inflammatory cells was compared in the respiratory and olfactory epithelial compartments. Eosinophil distribution was assessed using Scarlet Red stain and a polyclonal antibody recognizing eosinophil major basic protein (MBP). The role of interleukin (IL)-5 in upper airway inflammation was tested by administration of polyclonal anti-IL-5 antibody during the sensitization protocol. RESULTS: Unsensitized control mice receiving saline failed to develop upper airway eosinophil infiltration. IP OVA-sensitized mice developed marked upper airway mucosal eosinophil infiltration after aerosol OVA challenge, whereas repeated intranasal instillation of OVA produced qualitatively similar, but less intense eosinophil infiltration. Using either sensitization protocol, eosinophil infiltration was seen in areas of the lower portion of the nasal septum, the floor and the lower lateral walls of the mid-caudal region of the nasal cavity. Immunofluorescence staining for MBP confirmed this distribution of eosinophils but also demonstrated some eosinophils in the maxillary sinuses and in circumscribed regions of the ethmoturbinates. All areas of eosinophil infiltration were lined by respiratory epithelium. The selective infiltration of respiratory but not olfactory epithelium by eosinophils was unassociated with a measurable induction of epithelial ICAM-1 or eotaxin expression. OVA-induced upper airway eosinophil infiltration was found to be IL-5 dependent, since administration of a polyclonal anti-IL-5 antibody (TRFK-5) during OVA sensitization resulted in a marked modulation (80% decrease) in eosinophil infiltration in response to subsequent OVA challenge. CONCLUSION: The mouse upper airway, specifically in areas containing respiratory epithelium, is a target for OVA-induced allergic inflammation. This selective infiltration of respiratory, but not olfactory, epithelium is, in part, dependent upon IL-5. This model is useful for further dissection of the inflammatory response with genetic manipulations and targeted immunological approaches.

Management of burn injuries during pregnancy.

Burns suffered during pregnancy is rare and can be a devastating injury. The presence of a fetus creates many special maternal physiological changes, and the burn wound places additional great stress on systems that are already highly modified. Most of the literature has come from developing countries, and most reports from developed countries have come before 1980 and do not reflect the current standard of care. We have compiled a retrospective review of eight patients burned during pregnancy. The total body surface area (TBSA) burned ranged from 1 to 85% in these patients, and all survived the injury. All patients gave birth to healthy children except the most severely burned patient, whose child suffers from cerebral palsy. Based on our experience as well as a review of the literature, management recommendations are proposed. These include: (1) early pregnancy test for all female patients of childbearing age, (2) prompt and aggressive fluid resuscitation, (3) early supplemental oxygen and low threshold for mechanical ventilatory support, (4) early delivery of the fetus if the pregnancy is in the third trimester, and (5) high suspicion for venous thrombosis and sepsis, with early and aggressive treatment.

Protein kinase C mediates insulin-inhibited Ca2+ transport and contraction of vascular smooth muscle.

Insulin acutely inhibits contraction of primary cultured vascular smooth muscle (VSM) cells from canine femoral artery by inhibiting contractile agonist-induced Ca2+ influx. Insulin also inhibits contraction at step(s) distal to intracellular Ca2+ concentration (Ca2+i) by stimulating cyclic guanosine monophosphate (GMP) production. We wished to see whether these effects of insulin are mediated by protein kinase C (PKC). Ca2+ influx was assessed by measuring the rate of fluorescence quenching of intracellular fura 2 by extracellular Mn2+. We found that 10 micromol/L serotonin (5-HT) stimulated Mn2+ influx 3-fold, and 1 nmol/L insulin inhibited the 5-HT-stimulated component of Mn2+ influx by 63% (P < .05), but insulin had no effect in the presence of 1 micromol/L staurosporine, an inhibitor of PKC. In the absence of insulin, preincubating cells with 0.1 micromol/L phorbol 12-myristate 13-acetate (PMA) for 5 min inhibited the 5-HT-stimulated component of Mn2+ influx by 69% (P < .05). Insulin inhibited cell contraction induced by raising Ca2+i to supraphysiologic levels with ionomycin by 75% (P < .05). We also noted that 10(-6) mol/L calphostin C, another PKC inhibitor, or 16-h preincubation with PMA completely blocked this effect of insulin. Finally, 10-min exposure to insulin or PMA increased cyclic GMP production in ionomycin-treated cells by 50% and 64%, respectively (both P < .05). We conclude that insulin inhibits VSM cell contraction by inhibiting 5-HT-stimulated Ca2+ influx and also at step(s) distal to Ca2+i by a PKC-dependent mechanism.

Insulin increases NO-stimulated guanylate cyclase activity in cultured VSMC while raising redox potential.

Insulin acutely stimulates cyclic guanosine monophosphate (cGMP) production in primary confluent cultured vascular smooth muscle cells (VSMC) from canine femoral artery, but the mechanism is not known. These cells contain the inducible isoform of nitric oxide (NO) synthase (iNOS), and insulin-stimulated cGMP production in confluent cultured cells is blocked by the NOS inhibitor, N(G)-monomethyl-L-arginine (L-NMMA). In the present study, it is shown that iNOS is also present in freshly dispersed VSMC from this artery, indicating that iNOS expression in cultured VSMC is not an artifact of the culture process. Insulin did not stimulate NOS activity in primary confluent cultured cells because it did not affect citrulline or combined NO(-)(3)/NO(-)(2) production. To see whether insulin required the permissive presence of NO to stimulate cGMP production, iNOS and basal cGMP production were inhibited with L-NMMA, and the cells were incubated with or without 1 nM insulin and/or the NO donor, S-nitroso-N-acetyl-D,L-penicillamine (SNAP) at a concentration (0.1 microM) that restored cGMP production to the basal value. In the presence of L-NMMA, insulin no longer affected cGMP production but when insulin was added to L-NMMA plus SNAP, cGMP production was increased by 69% (P < 0.05 vs. L-NMMA plus SNAP). Insulin, which increases glucose uptake by these cells, increased the cell lactate content and the lactate-to-pyruvate ratio (LPR) by 81 and 97%, respectively (both P < 0.05), indicating that the hormone increased aerobic glycolysis and the redox potential. The effects of insulin on LPR and cGMP production were blocked by removing glucose or by adding 2-deoxyglucose to the incubation media and were duplicated by the reducing substrate, beta-hydroxybutyrate. We conclude that insulin does not acutely affect iNOS activity in these VSMC but it does augment cGMP production induced by the NO already present in the cell while increasing aerobic glycolysis and the cell redox potential.

Insulin inhibits migration of vascular smooth muscle cells with inducible nitric oxide synthase.

Vascular smooth muscle cell (VSMC) migration participates in atherosclerosis and arterial restenosis after balloon angioplasty. Because these processes are enhanced in insulin-resistant states, our goal was to determine whether insulin affects VSMC migration and, if so, how. The migration of primary cultured VSMCs from canine femoral artery was measured with the use of a wound migration assay and related to cGMP levels. Insulin (1 nmol/L) did not affect migration or cGMP production in control cells. When inducible nitric oxide synthase (iNOS) was induced by 24-hour preincubation with lipopolysaccharide and interleuken-1beta, basal migration decreased, cGMP production increased, and insulin inhibited migration by >90% and stimulated cGMP production by 3-fold. The nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine blocked the affect of insulin on the migration of VSMCs with iNOS. 8-Bromo-cGMP inhibited VSMC migration in control cells, and 1-H-1[1,2,4]oxadiazolo-[4, 3a]quinoxolin-1-one, a selective inhibitor of guanylate cyclase, blocked the inhibition by insulin of migration of cells with iNOS. We conclude that insulin does not normally affect cGMP production or the migration of these VSMCs. However, after the induction of iNOS, insulin stimulates cGMP production and inhibits migration via an NOS-and a cGMP-dependent mechanism.

Reasons for intracranial hypertension and hemodynamic instability during acute elevations of intra-abdominal pressure: observations in a large animal model.

In previous studies we reported that an acute elevation in intra-abdominal pressure (IAP) is responsible for the elevation in intracranial pressure (ICP) and mean blood pressure (MBP). Thus far, the reasons for the increased ICP during an acute elevation in IAP and the combined effects of increased IAP and ICP on hemodynamics have not been reported. Five large animals (swine) were studied. Each animal served as its own control. A subarachnoid screw was placed for ICP monitoring. The jugular vein, femoral vein, and femoral artery were cannulated. ICP, MBP, central venous pressure above (CVPA) and below (CVPB) the diaphragm, and PaC02 were monitored after a pneumoperitoneum with C02 was established at 5, 15, and 30 mm Hg of IAP. Cavography was performed to evaluate the morphology of the inferior vena cava at different increments of IAP. Measurements were obtained in reverse Trendelenburg (group 1), supine (group 2), and Trendelenburg (group 3) positions. Multiple regression analysis was used to examine the effects of IAP and positioning in separate models with different blood pressures as dependent variables. Increased IAP significantly increased CVPA, CVPB, ICP, and MBP. There were no changes in cerebral perfusion pressure. The change in position (from group 1 to group 3) significantly increased CVPA and decreased the CVPB. Cavograms performed on animals in the supine position with increased IAP showed a narrowing of the IVC at the level of the diaphragm. Increases in IAP will increase ICP and MBP without altering the cerebral perfusion pressure. A mechanical effect mediated by compression of the inferior vena cava at the level of the diaphragm with increased central venous pressure and decreased drainage from the lumbar plexus and central nervous system is responsible for this effect.

Molten metal burns: early treatment improves outcome.

Molten metal burns have received relatively little attention in the surgical literature. We performed a retrospective chart review of 150 patients who sustained molten metal burns between 1972 and 1997. The injuries all occurred in male foundry workers, most commonly from molten aluminum (60%). The typical accident was that of a splatter spill, creating a full-thickness burn. The mean burn size was 2.3 per cent of the body surface area (range, 0.25-25%). The lower extremities were the most commonly injured areas (85%), yet 37 per cent of patients had multiple sites burned. Patients were often initially treated nonoperatively and then referred to a surgeon when the wound failed to heal. Hospitalization was necessary in 89 patients at a mean of 16 days after the injury, and 92 patients required an operation, most commonly excision of the wound with skin grafting. The mean length of hospital stay was 11.2 days, and mean absence from work was 72.6 days. Fifty-one patients treated by the burn surgeon within 2 weeks of injury had a mean length of disability significantly shorter than those referred late (53.5 vs. 83.4 days; P < 0.05). We believe that an underestimation of the severity of these burns often leads to a delay in correct therapy and extends disability.

Herniography: a review of 333 herniograms.

We reviewed 333 consecutive herniographic studies in 306 patients for whom clinical data were available. Symptoms with either a negative or inconclusive physical examination (PE) were the most frequent reasons for requesting a herniogram. The herniogram was found to be more sensitive for the diagnosis of hernia, particularly inguinal, than PE. In 56 of 57 patients who came to operation the herniogram and the PE were concordant. In one patient, an incisional hernia was found at operation that had not been appreciated as such on the herniogram. We believe herniography should be used more frequently when the diagnosis of hernia is uncertain on PE, thereby reducing the incidence of unnecessary operative procedures.

Insulin inhibits vascular smooth muscle contraction at a site distal to intracellular Ca2+ concentration.

Several hypertensive states are associated with resistance to insulin-induced glucose disposal and insulin-induced vasodilation. Insulin can inhibit vascular smooth muscle (VSM) contraction at the level of the VSM cell, and resistance to insulin's inhibition of VSM cell contraction may be of pathophysiological importance. To understand the VSM cellular mechanisms by which insulin resistance leads to increased VSM contraction, we sought to determine how insulin inhibits contraction of normal VSM. It has been shown that insulin lowers the contractile agonist-stimulated intracellular Ca2+ (Ca2+i) transient in VSM cells. In this study, our goal was to see whether insulin inhibits VSM cell contraction at steps distal to Ca2+i and, if so, to determine whether the mechanism is dependent on nitric oxide synthase (NOS) and cGMP. Primary cultured VSM cells from canine femoral artery were bathed in a physiological concentration of extracellular Ca2+ and permeabilized to Ca2+ with a Ca2+ ionophore, either ionomycin or A-23187. The resultant increase in Ca2+i contracted individual cells, as measured by photomicroscopy. Preincubating cells with 1 nM insulin for 30 min did not affect basal Ca2+i or the ionomycin-induced increase in Ca2+i, as determined by fura 2 fluorescence measurements, but it did inhibit ionomycin- and A-23187-induced contractions by 47 and 51%, respectively (both P < 0.05). In the presence of 1.0 microM ionized Ca2+, ionomycin-induced contractions were inhibited by insulin in a dose-dependent manner. In the presence of ionomycin, insulin increased cGMP production by 43% (P < 0.05). 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (10 microM), a selective inhibitor of guanylate cyclase that blocked cGMP production in these cells, completely blocked the inhibition by insulin of ionomycin-induced contraction. It was found that the cells expressed the inducible isoform of NOS. NG-monomethyl-L-arginine or NG-nitro-L-arginine methyl ester (0.1 mM), inhibitors of NOS, did not affect ionomycin-induced contraction but prevented insulin from inhibiting contraction. We conclude that insulin stimulates cGMP production and inhibits VSM contraction in the presence of elevated Ca2+i. This inhibition by insulin of VSM contraction at sites where Ca2+i could not be rate limiting is dependent on NOS and cGMP.

Repigmentation in vitiligo patients. Melanocyte transfer via ultra-thin grafts.

BACKGROUND: Several years ago, a successful surgical technique for treating depigmentation resulting from burn injuries was developed. OBJECTIVE: The purpose of this study was to investigate results of dermabrasion with melanocyte transplantation using new modifications of the technique in patients with vitiligo. METHODS: We performed 17 procedures on 12 patients with stable vitiligo. The epithelium of the vitiliginous areas was removed by dermabrasion. The dermabraded area was then reepithelialized with ultra-thin sheet grafts, which more recently were meshed and partially expanded. RESULTS: Good to excellent repigmentation was observed in 88% of the procedures. Scarring did not develop in the repigmented or donor site regions. The final color match has been good to excellent. CONCLUSIONS: This technique has proven beneficial in 88% of the procedures on our patients. Both our patients and we feel that this provides a valuable treatment option in patients who have failed medical management.

The etiology of the adult indirect inguinal hernia: revisited.

It has generally been historically stated that indirect inguinal hernias develop only in patients who have a patient processus vaginalis that enlarges to become a hernia sac. Occasionally, this theory has been challenged but without any objective evidence. Herniography was performed by placing 50 mL of nonionic contrast material into the peritoneal cavity. The patient was then placed in a prone position with the head of the table elevated. Films of the inguinal fossae were obtained with the patient straining. The herniogram revealed a right indirect inguinal hernia. There was no left inguinal hernia, nor was there a patent processus vaginalis on the left side. Two years later, the patient developed left inguinal discomfort and swelling and was found to have a moderate-sized left inguinal hernia. At the time of operation, an indirect sac of moderate size was present. A mesh plug repair was performed. This case report is the first published objective evidence that, contrary to common thought, a patent processus vaginalis is not a necessary prerequisite to the development of an indirect inguinal hernia.