Opportunities for maternal transport for delivery of very low birth weight infants.

OBJECTIVE: To assess frequency of very low birth weight (VLBW) births at non-level III hospitals. STUDY DESIGN: Retrospective cohort study using linked California birth certificate and discharge data of 2008 to 2010 for deliveries of singleton or first-born infant of multiple gestations with birth weight 400 to 1500 g. Delivery rates by neonatal level of care were obtained. Risk of delivery at non-level III centers was estimated in univariable and multivariable models. RESULTS: Of the 1 508 143 births, 13 919 (9.2%) were VLBW; birth rate at non-level III centers was 14.9% (8.4% in level I and 6.5% in level II). Median rate of VLBW births was 0.3% (range 0 to 4.7%) annually at level I and 0.5% (range 0 to 1.6%) at level II hospitals. Antepartum stay for >24 h occurred in 14.0% and 26.9% of VLBW births in level I and level II hospitals, respectively. CONCLUSION: Further improvement is possible in reducing VLBW infant delivery at suboptimal sites, given the window of opportunity for many patients.

Prospective evaluation of low-dose ketoconazole plus hydrocortisone in docetaxel pre-treated castration-resistant prostate cancer patients.

BACKGROUND: Ketoconazole is a well-known CYP17-targeted systemic treatment for castration-resistant prostate cancer (CRPC). However, most of the published data has been in the pre-chemotherapy setting; its efficacy in the post-chemotherapy setting has not been as widely described. Chemotherapy-naïve patients treated with attenuated doses of ketoconazole (200-300 mg three times daily) had PSA response rate (>50% decline) of 21-62%. We hypothesized that low-dose ketoconazole would likewise possess efficacy and tolerability in the CRPC post-chemotherapy state. METHODS: Men with CRPC and performance status 0-3, adequate organ function and who had received prior docetaxel were treated with low-dose ketoconazole (200 mg orally three times daily) and hydrocortisone (20 mg PO qAM and 10 mg PO qPM) until disease progression. Primary endpoint was PSA response rate (>50% reduction from baseline) where a rate of 25% was to be considered promising for further study (versus a null rate of <5%); 25 patients were required. Secondary endpoints included PSA response >30% from baseline, progression-free survival (PFS), duration of stable disease and evaluation of adverse events (AEs). RESULTS: Thirty patients were accrued with median age of 72 years (range 55-86) and median pre-treatment PSA of 73 ng ml(-1) (range 7-11,420). Twenty-nine patients were evaluable for response and toxicity. PSA response (>50% reduction) was seen in 48% of patients; PSA response (>30% reduction) was seen in 59%. Median PFS was 138 days; median duration of stable disease was 123 days. Twelve patients experienced grade 3 or 4 AEs. Of the 17 grade 3 AEs, only 3 were attributed to treatment. None of the two grade 4 AEs were considered related to treatment. CONCLUSIONS: In docetaxel pre-treated CRPC patients, low-dose ketoconazole and hydrocortisone is a well-tolerated, relatively inexpensive and clinically active treatment option. PSA response to low-dose ketoconazole appears historically comparable to that of abiraterone in this patient context. A prospective, randomized study of available post-chemotherapy options is warranted to assess comparative efficacy.

Low fructose and low salt diets increase mitochondrial DNA in white blood cells of overweight subjects.

OBJECTIVE: To evaluate the effect of sodium and fructose restriction on mitochondrial DNA (mtDNA) content and systemic oxidative stress in a sample of overweight and pre hypertensive subjects. MATERIAL/METHODS: Data and blood samples were collected from 36 overweight and pre hypertensive patients randomly assigned to either an isocaloric (with respect to baseline) low sodium-fructose diet or an isocaloric low sodium diet. Patients were followed for 8 weeks. We measured mitochondrial DNA (mtDNA) content from peripheral blood white cells by Real-time PCR and plasma malondialdehyde (MDA) and 2,4-dinitrophenylhydrazine (DNPH) as markers of reactive oxygen species (ROS). RESULTS: Compared to baseline, at week 8 there was a continued and significant increase in mtDNA in both the low sodium diet group [2.4 vs. 13.1 (relative copy number), p<0.05] and the low sodium diet-fructose group (1.9 vs. 147.2, p<0.05). By week 8 there was a continued decrease in plasma DNPH levels in the low sodium diet group (4.6 vs. 2.6, p<0.05) and in the low sodium diet-fructose group (5.8 vs. 2.2, p<0.05). No significant differences were found with MDA. CONCLUSION: Our studies suggest that simple dietary measures such as reducing salt with or without restricting fructose can increase mtDNA and improve markers of oxidative stress.

Hyperhidrosis related to nevirapine therapy.

A 70-year-old white man presented to the internal medicine outpatient clinic with symptoms of significant hyperhidrosis. He had been started on antiretroviral therapy (ART) with tenofovir, lamivudine and nevirapine. The patient complained of excessive sweating following severe asthenia after taking nevirapine. Based on these findings, we suspected that the causative agent was nevirapine and a diagnosis of hyperhidrosis due to nevirapine was made. Nevirapine treatment was stopped and was substituted with efavirenz: the patient continued on therapy with tenofovir and lamivudine. The hyperhidrosis symptoms resolved in 2-3 days. No relapse was observed with the new ART regimen. Drugs that induce hyperhidrosis can cause patient discomfort and embarrassment. In our patient, this adverse drug reaction also caused severe asthenia that decreased the patient's physical and emotional quality of life. There was a temporal relationship between the developments of symptoms and starting nevirapine therapy. Once nevirapine was suspended and switched to efavirenz, excessive sweating resolved. An objective causality assessment revealed that the adverse effect was probable. Until further data are available, clinicians should consider discontinuation of nevirapine therapy in patients who develop severe hyperhidrosis.

Eficacia de sugammadex para la reversión del bloqueo neuromuscular en una paciente con distrofia muscular de Becker / Sugammadex, efficacious in reversing a neuromuscular block in a woman with Becker muscular dystrophy

La distrofia muscular de Becker es una enfermedad que afecta, sobre todo, al músculo esquelético y se caracteriza por necrosis de las fibras musculares y debilidad progresiva. Presentamos el caso de una paciente de 61 años, diagnosticada de esta enfermedad 45 años antes, que iba a ser intervenida de una neoplasia de mama derecha. Se le realizó una anestesia general con propofol, fentanilo y un bloqueante neuromuscular no despolarizante (rocuronio). Se empleó un monitor TOF Watch SX para evaluar continuamente la función neuromuscular por aceleromiografía, y se revirtió el bloqueo neuromuscular con sugammadex. Tras preoxigenación e inducción con fentanilo y propofol, se calibró el acelerómetro y se registró el cociente del tren de cuatro estímulos (TOFr) basal. Se inyectó rocuronio 1 mg/kg, y se evaluaron las respuestas del TOF cada 15 segundos. El máximo descenso del TOF (O) fue de 52 segundos. Se intubó la tráquea sin incidencias. Se mantuvo la anestesia intravenosa y la cirugía duró 74 min. El segundo componente del TOF (T2) reapareció a los 86 min de la dosis inicial. Se administró sugammadex 2 mg/kg. El tiempo desde la inyección de sugammadex hasta TOFr 0,7 fue de 79 seg, hasta TOFr 0,9 de 108 seg y TOFr 1,0 de 152 seg. No se observaron alteraciones electrocardiográficas ni hemodinámicas durante su administración y no hubo signos de bloqueo neuromuscular residual en el despertar ni acontecimientos adversos en las 24 horas posteriores (AU)

Becker muscular dystrophy affects mainly the musculoskeletal system, causing muscle wasting and progressive weakness. A 61-year-old woman with breast cancer, who had been diagnosed with Becker muscular dystrophy 45 years earlier, was scheduled for right mastectomy. We induced general anesthesia with propofol, fentanyl, and a nondepolarizing muscle blocker (rocuronium). Neuromuscular function was monitored continuously by acceleromyographic train-of-four ratio (TOFr) (Watch-SX monitor). The block was reversed with sugammadex. After preoxygenation with fentanyl and propofol, the device was calibrated and the baseline TOFr was recorded. We injected 1 mg/kg of rocuronium and assessed TOF responses every 15 seconds. The maximum decrease in TOF response (to 0 twitches) was at 52 seconds. Tracheal intubation was uneventful. Anesthesia was maintained by intravenous infusion. The operation lasted 74 minutes. The second TOF twitch (T2) reappeared 86 minutes after the initial dose. After we injected 2 mg/kg of sugammadex, a TOFr of 0.7 was reached at 79 seconds; a TOFr of 0.9 was reached at 108 seconds and a TOFr of 1.0 at 152 seconds. No electrocardiographic or hemodynamic abnormalities occurred during sugammadex administration and there were no signs of residual neuromuscular blockade on awakening or adverse events in the following 24 hours (AU)

[Sugammadex, efficacious in reversing a neuromuscular block in a woman with Becker muscular dystrophy]. / Eficacia de sugammadex para la reversión del bloqueo neuromuscular en una paciente con distrofia muscular de Becker.

Becker muscular dystrophy affects mainly the musculoskeletal system, causing muscle wasting and progressive weakness. A 61-year-old woman with breast cancer, who had been diagnosed with Becker muscular dystrophy 45 years earlier, was scheduled for right mastectomy. We induced general anesthesia with propofol, fentanyl, and a nondepolarizing muscle blocker (rocuronium). Neuromuscular function was monitored continuously by acceleromyographic train-of-four ratio (TOFr) (Watch-SX monitor). The block was reversed with sugammadex. After preoxygenation with fentanyl and propofol, the device was calibrated and the baseline TOFr was recorded. We injected 1 mg/kg of rocuronium and assessed TOF responses every 15 seconds. The maximum decrease in TOF response (to 0 twitches) was at 52 seconds. Tracheal intubation was uneventful. Anesthesia was maintained by intravenous infusion. The operation lasted 74 minutes. The second TOF twitch (T2) reappeared 86 minutes after the initial dose. After we injected 2 mg/kg of sugammadex, a TOFr of 0.7 was reached at 79 seconds; a TOFr of 0.9 was reached at 108 seconds and a TOFr of 1.0 at 152 seconds. No electrocardiographic or hemodynamic abnormalities occurred during sugammadex administration and there were no signs of residual neuromuscular blockade on awakening or adverse events in the following 24 hours.

Teenager donation: investigation of 848 high school students.

AIMS: The aims of this study were to quantify donors among the investigated area, quantify arguments and myths about the donation and transplantation process, and fix predetermined donation variables in a logistical model. MATERIALS AND METHODS: We used an analytical, prospective design, using 848 students from 13 high schools in the Velez Sarsfield Hospital area in an open-closed inquiry. RESULTS: Females were 57.74% and average age was 16.64 +/- 0.06 years, including 65.09% Catholics. The 642 potential donors represented 75% of the study population with the fundamental aim being to "give life" (44.85%). The 193 (22.75%) opposed subjects cited as a principal reason fear and distrust (40.41%). There were 40.21% who had discussed the donation subject with their families. In our study 76.41% believed that human organ traffic exists and 36.88% thought that it is due to corruption. Also, 56.01% fear premature extraction of their organs. In addition, 73.23% of teenagers considered that individuals who refused to donate have the right to receive organs (P = not significant between donors and not a donor). The family discussion and the lack of fear about premature extraction were donation signals. About the low level of donation 43.27% blamed the government (lack of campaigns, information, and knowledge) whereas other reasons were fear, lack of clarity and distrust. In our study 49.17% seemed to wish to increase donation if they received more information. CONCLUSIONS: Individuals predispose to donation represented the great majority of the queried teenagers; education and family discussion were remarkable factors favoring the decision.

Foot ischaemia and toe skin necrosis associated with interleukin-2 infusion in an HIV-infected patient.

A 39-year-old white man developed a severe left toe foot ischaemia and toe skin necrosis following his 12 courses of interleukin (IL)-2 (4.5 MIU twice a day, subcutaneously) for five days every two months. He had no known general risk factors for thrombosis other than HIV infection. An arterial Doppler ultrasound examination of the leg confirmed the permeability of the posterior tibial artery and its digital pulse. A diagnosis of foot ischaemia and toe skin necrosis was made. The suspected causative agent was IL-2 since this was the only drug that the patient was taking before the symptoms appeared. The patient was empirically treated with an aspirin and pentoxifylline in order to improve local microcirculation. We observed a satisfactory response with a quick resolve of skin lesions. The most possible cause of foot ischaemia and toe skin necrosis was considered to be IL-2 because of the temporal relationship between the exposure to the drug and onset of symptoms. Based on the Naranjo probability scale, IL-2 could be considered the probable cause of the foot ischaemia and toe skin necrosis. If clinical evaluation leads to the suspicion of ischaemic process, therapy with IL-2 should be discontinued immediately.

Successful desensitization protocol for hypersensitivity reactions caused by oxaliplatin.

OBJECTIVE: To report the successful desensitization of a patient with a hypersensitivity reaction to oxaliplatin. CASE SUMMARY: A 57-year-old woman with metastatic colon cancer was receiving oxaliplatin, fluorouracil and leucovorin every 2 weeks and showed a partial response to therapy. During the fourth cycle, an anaphylactic reaction with palpitations and rash occurred. The patient was hypotensive with mild pulmonary wheezing. Since oxaliplatin was the probable cause of the hypersensitivity reaction, therapy with this drug was discontinued. Therapy in the patient was continued using cetuximab and irinotecan but this resulted in progression of the cancer. In view of the initial satisfactory response to the oxaliplatin-based regimen, it was decided to attempt desensitization to oxaliplatin using a protocol adapted from carboplatin regimens. The desensitization procedure was successful and the patient subsequently tolerated an additional three cycles using this regimen without further symptoms of hypersensitivity. DISCUSSION: In cases with moderate-to-severe reactions to oxaliplatin, reexposure is not usually considered. However, a need to use first-line therapy when there is recurrence of the cancer has encouraged the development of rapid desensitization procedures which allow patients to be treated with medications to which they have previously shown hypersensitivity reactions. A combination of premedication using intravenous dexamethasone and a desensitization regimen was designed which was used successfully to increase concentrations and flow rates of oxaliplatin. CONCLUSIONS: Hypersensitivity reactions to oxaliplatin are not rare and physicians need to be aware of these. When substitution of another antineoplastic drug is not feasible, oxaliplatin desensitization should be considered even when hypersensitivity reactions to oxaliplatin are severe.

Possible delayed onset of osteonecrosis of the jaw in association with zoledronic acid.

OBJECTIVE: To report a case of possible delayed-onset osteonecrosis of the jaw after treatment with zoledronic acid. CASE SUMMARY: A 53-year-old white man with no history of allergic drug reactions had been diagnosed as having bronchial epidermoid carcinoma. He received therapy with docetaxel and zoledronate. Because of metastatic progression of the disease, he started treatment with irinotecan and zoledronate. The patient received 18 monthly cycles of zoledronate. One year after the last cycle of bisphosphonate therapy, the patient had one tooth extracted. Three weeks later, he complained of continuous mandibular pain and swallowing difficulties. A diagnosis of osteonecrosis of the jaw was made. Surgical treatment was chosen, with debridement and a mucosal flap, complemented with antibiotic therapy. Other potential aetiologic risk factors for osteonecrosis were investigated and could not be identified. Accordingly, a diagnosis of possible delayed onset jaw osteonecrosis associated with zoledronate was made. DISCUSSION: Osteonecrosis of the jaws has recently emerged as a potential complication of bisphosphonate therapy in patients with metastatic cancer undergoing dental surgery. This is the first report of possible delayed-onset osteonecrosis of the jaw associated with zoledronate. Patients appear to remain at low risk of developing osteonecrosis even in the absence of zoledronate, especially after a dental extraction or oral surgery. Based on the Naranjo algorithm the adverse reaction was classed as possible.

[Health problems and social vulnerability in immigrants admitted for an infectious disease: a case-control study]. / Problemas de salud y la vulnerabilidad social en pacientes inmigrantes ingresados con patología infecciosa: estudio caso-control.

BACKGROUND: Health resources needed by immigrants have increased steadily in the last few years. Studying health problems and social vulnerability in immigrants would help to improve the health care quality. PATIENTS AND METHODS: A case-control study performed in the Hospital Clinic of Barcelona. Immigrant patients admitted with infectious diseases from October 2002 to September 2003 were included. Controls were paired by age, gender and HIV infection. Clinical (emergency room attendance, days and number of admission to hospital, amount of clinical procedures and drugs used during the admission, etiological and microbiological diagnosis and post-admission control) and social vulnerability variables (social worker consultation, health care card, relatives or friends caregiver, drug use, language barrier and discharge document of the nurse) were analyzed. RESULTS: One hundred and two patients (51 cases and 51 controls, all of them males) were studied. A total of 56% were HIV-1 infected in both groups. The number of diagnostic or therapeutic procedures was higher in the immigrant group (p = 0.02), a lower proportion of patients had a final etiologic diagnosis (82% vs 98%, p = 0.021) and the number of post-discharge controls was lower (55% vs 77%, p = 0.04). Immigrants had a higher social vulnerability index than the Spanish population and 35% could not speak Spanish, French or English. The number of immigrants with health care card was lower (63% vs 94%, p < 0,0001) and a higher number needed to be admitted to a social-health care center after discharge (16% vs 2%, p = 0.01). DISCUSSION: Social vulnerability influences the etiological diagnosis, the number of diagnostic and therapeutic procedures during the admission to the hospital and post-discharge control of immigrant population.

Problemas de salud y la vulnerabilidad social en pacientes inmigrantes ingresados con patología infecciosa: estudio caso-control / Background. Health resources needed by immigrants have increased steadily in the last few years. Studying health problems and social vulnerability in immigrants would help to improve the health care quality

Introducción. La necesidad de recursos sanitarios de la población inmigrante ha aumentado en los últimos años. El estudio de los problemas de salud y la vulnerabilidad social planteados durante el ingreso hospitalario de estos pacientes ayudaría a mejorar su cuidado. Pacientes y métodos. Estudio caso-control realizado en el Hospital Clínic de Barcelona. Se incluyeron pacientes inmigrantes ingresados con patología infecciosa de octubre de 2002 a septiembre de 2003. Los casos fueron apareados por edad, sexo e infección por virus de la inmunodeficiencia humana (VIH). Se evaluaron variables clínicas (visitas a Urgencias, días y número de ingresos, cantidad de procedimientos y fármacos, diagnóstico etiológico y control post alta) y de vulnerabilidad social (utilización de trabajo social, tarjeta sanitaria, cuidador de referencia, consumo de tóxicos, barrera idiomática y alta de enfermería). Resultados. Se estudiaron 102 pacientes (51 casos y 51 controles, todos varones). El 56% estaban infectados por VIH en ambos grupos. El número de procedimientos diagnósticos o terapéuticos fue mayor en el grupo de inmigrantes (p = 0,02), se llegó en menor proporción a un diagnóstico etiológico (el 82% frente al 98%, p = 0,021) y el número de visitas post alta fue inferior (el 55% frente al 77%, p = 0,04). Los pacientes inmigrantes tuvieron unos índices de vulnerabilidad social mayores que la población autóctona y en un 35% de ellos existía una barrera idiomática. Un menor número tenían tarjeta sanitaria (el 63% frente al 94%, p < 0,0001) y un número mayor tuvieron necesidad de traslado a un centro sociosanitario (el 16% frente al 2%, p = 0,01). Discusión. La vulnerabilidad social de los pacientes inmigrantes influye en una menor obtención del diagnóstico etiológico, mayor número de procedimientos durante la hospitalización y un menor seguimiento posterior al alta (AU)

Health problems and social vulnerability in immigrants admitted for an infectious disease: a case-control study Patients and methods. A case-control study performed in the Hospital Clínic of Barcelona. Immigrant patients admitted with infectious diseases from October 2002 to September 2003 were included. Controls were paired by age, gender and HIV infection. Clinical (emergency room attendance, days and number of admission to hospital, amount of clinical procedures and drugs used during the admission, etiological and microbiological diagnosis and post-admission control) and social vulnerability variables (social worker consultation, health care card, relatives or friends caregiver, drug use, language barrier and discharge document of the nurse) were analyzed. Results. One hundred and two patients (51 cases and 51 controls, all of them males) were studied. A total of 56% were HIV-1 infected in both groups. The number of diagnostic or therapeutic procedures was higher in the immigrant group (p = 0.02), a lower proportion of patients had a final etiologic diagnosis (82% vs 98%, p = 0.021) and the number of post-discharge controls was lower (55% vs 77%, p = 0.04). Immigrants had a higher social vulnerability index than the Spanish population and 35% could not speak Spanish, French or English. The number of immigrants with health care card was lower (63% vs 94%, p < 0,0001) and a higher number needed to be admitted to a social-health care center after discharge (16% vs 2%, p = 0.01). Discussion. Social vulnerability influences the etiological diagnosis, the number of diagnostic and therapeutic procedures during the admission to the hospital and post-discharge control of immigrant population (AU)

Possible macular exanthema associated with linezolid therapy.

OBJECTIVE: To report a case of macular exanthema associated with linezolid therapy. CASE SUMMARY: A 54-year-old white man diagnosed as having laryngeal epidermoid carcinoma attended our emergency department because of fatigue, fever, neck pain and a fistulized fixed mass in the right side of the neck with purulent exudation. Treatment with amoxicillin/clavulanic acid 875 mg/125 mg p.o. every 8 hours as empirical therapy was started. Cultures of the exudates from the fistula confirmed the presence of methicillin-resistant Staphylococcus aureus (MRSA). Amoxicillin/clavulanic acid was discontinued and therapy was started with linezolid 600 mg p.o. every 12 hours but 5 days after commencing linezolid the patient came to our emergency room because of generalized erythematous macular eruptions. A diagnosis of severe and generalized macular exanthema induced by linezolid was made. Administration of linezolid was suspended and there was an improvement in the skin lesions and general state of health. The patient was discharged without further symptoms. DISCUSSION: In this case, there was a close temporal correlation between drug exposure and the onset of symptoms. When linezolid was discontinued, the skin lesions resolved quickly and the general condition of the patient improved. Furthermore, linezolid was the only drug added before the cutaneous lesions appeared. It is possible that the adverse reaction was associated with administration of amoxicillin/clavulanic acid. However, the patient had been treated with this antibiotic previously without appearance of any cutaneous reaction. An objective causality assessment revealed that an adverse effect was possible. CONCLUSION: Based on our observations, we conclude that linezolid was the most likely cause of the adverse reaction. Clinicians should be aware of this infrequent but severe reaction.

Osteonecrosis maxilar asociada a zoledronato / No disponible

No disponible

Glucómetros de uso hospitalario: creación de un equipo pluridisciplinar para el proceso de selección y seguimiento Seis años de experiencia / Glucometers for hospital use: creation of a multi-disciplinary team for the selection and monitoring process

This work highlights what the authors consider to be critical aspects for setting up POCT (point-of-care testing) measurements, whether simple ones such as glucometers or critical ones such as those made with blood gas analyser (AU)

No disponible

Epidemiología de la demanda asistencial urgente por insuficiencia cardíaca congestiva / Epidemiology of the demand for acute health care due to congestive heart failure

Objetivo: Estudio de la demanda urgente y su proceso asistencial por insuficiencia cardiaca congestiva (ICC) en un hospital de área de salud de nivel II. Método: Diseño epidemiológico observacional de corte transversal sobre 242 pacientes mayores de 14 años con criterios de ICC, que demandaron asistencia por urgencias del 1 de junio al 20 de septiembre de 2000.Resultados: La edad media fue de 77,9 años ( =11,2). Había 113 (46,5 por ciento) hombres y 129 (53,1 por ciento) mujeres y sus edades medias (75,6 y 80 años, respectivamente) diferían significativamente (p<0,05).Demandan asistencia urgente un promedio de dos veces al año y uno de cada dos termina siendo ingresado. Los episodios se repiten en promedio cada 75 días. Sólo uno de cada tres fueron atendidos antes por su médico de atención primaria y sólo el 5 por ciento reingresan antes de las 72 horas tras el alta. Los principales factores de riesgo son la hipertensión, cardiopatía isquémica, diabetes, EPOC y obesidad (más diabetes en mujeres y más EPOC en hombres).El esquema terapéutico de la ICC sigue basándose en el diurético de asa, el inhibidor de la enzima conversiva de angiotensina y la digoxina. La práctica clínica analizada muestra poco uso de espironolactona (valvulopatía), IECAs (hipertensión y miocardiopatía) y Beta-bloqueantes (hipertensión). Conclusiones: El paciente tipo es un hombre o mujer de edad avanzada que acude a urgencias por iniciativa propia, siendo su primer ingreso. Sólo la mitad saben que tienen ICC. El varón presenta un mayor deterioro clínico en relación a su disfunción sistólica a diferencia de la mujer en la que descompensación se debe a una arritmia cardiaca por fibrilación auricular con función sistólica conservada. El esquema terapeútico sigue siendo el clásico (AU)

Additional association of intra-MHC genes, MICA and D6S273, with Addison's disease.

Intra-MHC sequences including MHC class I chain-related genes (MICAs), D6S273 and D6S2223 are associated with autoimmune diseases in addition to HLA class II. In the current study, we ascertained the haplotypes of 57 Caucasian patients with Addison's disease composed of these genetic markers and compared them either with 72 general population controls or with 105 child controls carrying Addison's disease high-risk DR3-DQ2/DR4-DQ8 genotypes. The MICA-A5.1/A5.1 genotype as well as HLA DR3/4 especially with DRB1*0404 were the main susceptibility markers. The homozygous MICA-A5.1/A5.1 genotype was significantly more frequent in the patients with Addison's disease (61%) than in the healthy controls (6%). The MICA-A5.1 allele was increased on both the DR3 and DR4 haplotypes, independent of DQ and DRB1 subtyping, in the patients with Addison's disease compared with the controls. Furthermore, the D6S273*140 allele on the DR3 haplotype and the D6S273*134 allele on the DR4 haplotype in the DR3/4 heterozygotes influenced susceptibility relative to the DR3/4 controls. The risk for Addison's disease was increased for the DR3-D6S273*140-MICA-A5.1/DRB1*0404-D6S273*134-MICA-A5.1 genotypes compared with that conferred by the DR3/4 controls. Susceptibility to Addison's disease is influenced by the genes around MICA and D6S273 for both the HLA DR3-DQ2 and DR4-DQ8 haplotypes.

Type 1A diabetes induced by infection and immunization.

Type 1A diabetes is an immune mediated disorder that results from progressive destruction of the islet beta-cells in the setting of genetic susceptibility. Both MHC and non-MHC genes contribute to disease with class II HLA molecules major determinants of susceptibility or protection. The presence of multiple anti-islet autoantibodies is associated with a high risk of disease progression, and the first anti-islet autoantibodies may appear as early as the first year of life. Congenital rubella is the only infection clearly associated with the development of type 1A diabetes. With the ability to detect children in the first year of life activating autoimmunity, prospective studies may in the future document additional environmental factors either increasing or decreasing diabetes risk.