Geographic variation in shape and size of anuran tadpoles: Interpopulation comparisons in Scinax fuscovarius (Anura, Hylidae).

Among anuran species with biphasic life cycle, the occurrence of intraspecific larval morphotypes has been related to variations in developmental time, diet, geographical variation, or response to predators. Here, we evaluated the external morphological variation of larvae among three populations, located more than 270 km apart, of the anuran hylid Scinax fuscovarius by linear and geometric methods, to elucidate the presence of geographically different morphs. Comparisons targeted development, growth, and external morphology. Studied populations exhibited differences in reproductive seasonality, growth rate, timing of development, shape, and size. Shape and size comparisons revealed two well-differentiated morphs, one of them shared by the two closest populations. Morphological differences evidenced a smaller and depressed form of the entire body plan in the most distant population, which showed continuous reproduction throughout the rainy season and under more unpredictable conditions. We interpret the occurrence of the two different larval morphs in S. fuscovarius as a by-product of local geographical conditions, and discuss on possible associations with biotic and abiotic factors cues.

Edad al momento del trasplante: ¿Quiénes tienen riesgo de mala evolución ? / Age at transplantation: who are at risk of a poor outcome ?

Introducción: Si bien la sobrevida de paciente e injerto en niños con trasplante renal (TxR) ha mejorado, algunos sugieren que la edad al TxR es predictora de malos resultados, y los mayores tendrían peor evolución. Objetivo: Definir sobrevida de paciente e injerto según edad al TxR, y factores pronósticos de fracaso en aquellos con peor evolución. Material y métodos: Cohorte retrospectivo de todos los pacientes con TxR en el Hospital Garrahan desde el 01-01-2002 hasta el 01-03-2016. Resultados: de 431 pacientes, 44, (10%) tenían < 6a, 179 (42%)> 6 y <12 y 208 (48%) ≥12 años. La sobrevida del paciente a 8 años fue 97%, 99% y 95% (p=0,2), y la del injerto de: 86%, 69% y 30% respectivamente (p=<0,001). En los ≥ de 12 años, con peor evolución, se incluyeron al análisis univariado como factores de riesgo de pérdida de injerto: GSFS como causa de IRC : HR: 9,4; (p<0,001), Rechazo Agudo (RA) temprano: HR: 8,1; (p<0,001), RA tardío: HR: 4,3; (p<0.001), DGF: HR: 4,1; (p<0,001), No adherencia: HR: 2,3; (p=0,02), Edad de DC > 35a: HR: 1,95 (p=0,1), Tiempo en diálisis: HR: 1,1 (p=0,1), Número de incompatibilidades HLAB y HLADR: HR: 0,8 (p=0,3), Tiempo de Isquemia : 0,9 (p=0,5), Sexo del receptor: HR:0,8 (p=0,6), Donante Cadavérico: HR: 1,2; (p=0,6), 2do TxR : HR: 1,2; (p=0,7). En análisis multivariado: RA tardío: HR: 12,9 (p<0,001), GSFS como causa de IRC: HR: 12,5 (p<0,001), RA temprano: HR: 9 (p<0,001), y DGF: HR: 4,9 (p<0,001). Conclusión: la sobrevida del injerto en adolescentes es inferior. Merecen atención, la prevención de la no adherencia asociada a rechazo, el paciente con GSFS y el retardo de la función pos TxR (AU)

Introduction: Although patient and graft survival of children with a kidney transplantation (KTx) has improved, it has been suggested that older age at KTx is a predictive factor of poor outcome. Aim: To evaluate patient and graft survival according to age at KTx and define predictive factors in those with a poor outcome. Material and methods: A retrospective cohort study was conducted in all patients who underwent KTx at Garrahan Hopital between 01-01-2002 and 01-03-2016. Results: Of 431 patients, 44 (10%) were <6yr, 179 (42%) >6yr, and <12yr, and 208 (48%) ≥12yr. Eight-year patient survival was 97%, 99%, and 95% (p=0.2) and graft survival was 86%, 69%, and 30% (p=<0.001), respectively. In children ≥12 yr, with a worse outcome, the following risk factors of graft loss were included in univariate analysis: FSGS-related CFR: HR: 9.4; (p<0.001), early acute rejection (AR): HR: 8.1; (p<0.001), late AR: HR: 4.3; (p<0.001), DGF: HR: 4.1; (p<0.001), non-adherence: HR: 2.3; (p=0.02), age of deceased donor >35yr: HR: 1.95 (p=0.1), time on dialysis: HR: 1.1 (p=0.1), number of HLA-B and HLA-DR mismatches: HR: 0.8 (p=0.3), cold ischemia time: 0.9 (p=0.5), recipient sex: HR:0.8 (p=0.6), deceased donor: HR: 1.2; (p=0.6), second KTx: HR: 1.2; (p=0.7; and in multivariate analysis: late AR: HR: 12.9 (p<0.001), FSGS-related CFR: HR: 12.5 (p<0.001), early AR: HR: 9 (p<0.001), and DGF: HR: 4.9 (p<0.001). Conclusion: Graft survival is lower in adolescents. Prevention of rejection associated with non-adherence, FSGS, and post-KTx DGF should be taken into account (AU)

Glomerulonefritis con semilunas / Glomerulonephritis with crescents

La glomerulonefritis rápidamente progresiva (GNRP) es una entidad caracterizada por una brusca y progresiva declinación de la función renal y por la presencia en la biopsia renal de proliferación celular extra capilar (semilunas) que ocupan el espacio de Bowmans. Nosotros analizamos en forma retrospectiva 37 niños con diagnóstico de GNRP (50% o más de los glomérulos con semilunas) asistidos en esta institución durante los últimos 20 años. El propósito fue evaluar la presentación clínica e histopatológica, etiología, evolución y factores de mal pronóstico. La edad media al diagnóstico fue de 11 ± 3,5 años. Los síntomas de presentación fueron: hematuria 100% de los casos (hematuria macroscópica 56%); hipertensión arterial 92%; proteinuria 88%; síndrome nefrótico 57%. Fue necesaria diálisis al ingreso en el 64,1% de los casos. Las biopsias renales fueron realizadas a 38 ± 26 días desde el comienzo de los síntomas. El porcentaje de glomérulos que presentaron semilunas fue del 81,4%; las mismas fueron epiteliales en el 28,3% de los casos; fibroepiteliales en el 21,8% y fibrosas en el 31,3%. En el 75,8% de las biopsias se encontró fibrosis intersticial y atrofia tubular moderada y/o severa. La inmunofluorescencia no mostro depósitos de complejos inmunes (GN pauci-inmune) en el 40,6% de las biopsias, mostró depósitos granulares de complejos inmunes en el 48,6% y depósitos lineales de anticuerpos anti membrana basal glomerular (Goodpasture´s) en el 10,8%. El tratamiento fue iniciado a 36 ± 32 días desde el comienzo de los síntomas. Todos los pacientes recibieron tratamiento de sostén; en 29 de ellos se indicaron además esteroides y ciclofosfamida, y en 5 solo esteroides. El tiempo medio de seguimiento fue de 4,6 ± 3,9 años. La sobrevida de los pacientes al final del seguimiento fue del 87% (IC95% 55-97%) y la sobrevida del órgano fue del 17% (IC95% 7-38%). Por análisis multivariado encontramos que la fibrosis intersticial y atrofia tubular moderada y/o severa fue el único factor que se relacionó con pérdida del órgano (OR: 14,6 IC95%2,6-80) p= 0,001. Nuestros resultados muestran que la GNRP en niños es una entidad con pobre pronóstico en relación a la función renal. El factor de peor pronóstico que puede llevar a la pérdida del órgano es el compromiso túbulo-intersticial (AU)

Rapidly progressive glomerulonephritis (RPGN) is characterized by a sudden and progressive decrease of kidney function and extra-capillary cell proliferation (crescents) occupying the Bowman's space on the biopsy. We retrospectively analysed 37 children with RPGN (50% or more of glomeruli with crescents) seen at our institution over the past 20 years. The purpose of the study was to evaluate clinical and histopathological presentation, etiology, outcome, and factors of poor prognosis. Mean age at diagnosis was 11 ± 3.5 years. Presenting symptoms were: hematuria in 100% of the cases (macroscopic hematuria 56%); arterial hypertension in 92%; proteinuria in 88%; and nephrotic syndrome in 57%. Dialysis was necessary on admission in 64.1% of the cases. Kidney biopsies were performed at 38 ± 26 days after symptom onset. The percentage of glomeruli that presented crescents was 81.4%; they were epithelial in 28.3% of the cases, fibroepithelial in 21.8%, and fibrous in 31.3%. In 75.8% of the biopsies interstitial fibrosis and moderate and/or severe tubular atrophy was found. Immunofluorescence techniques did not show immune complex deposits (pauci-immune GN) in 40.6% of the biopsies. Granular deposits of immune complexes were found in 48.6% and linear anti-glomerular basement membrane deposits (Goodpasture´s) in 10.8%. Treatment was started 36 ± 32 days after symptom onset. All patients received support treatment; in 29 steroids and cyclophosphamide were also indicated, and in 5 steroids only. Mean time of follow-up was 4.6 ± 3.9 years. Patient survival at the end of follow-up was 87% (95%CI 55-97%) and organ survival was 17% (95%CI 7-38%). On multivariate analysis we found that interstitial fibrosis and moderate and/or severe tubular atrophy was the only factor related to organ loss (OR: 14.6; 95%CI 2.6-80) p= 0.001). Our results show that RPGN in children has a poor prognosis regarding kidney function. Tubulo-interstitial involvement is the factor of poor prognosis that may lead to organ loss (AU)

Results of a prospective allocation policy of expanded criteria donors kidneys based on clinical parameters.

The ideal system to allocate expanded criteria donors (ECD) kidneys has not been fully elucidated. In a previous retrospective study, we reported that donor clinical characteristics were more predictive of transplant outcome than biopsy findings. Subsequently, we decided to use ECD kidneys solely based on a clinical scoring system. To elucidate the value of the pre-transplant biopsy, the patients were divided in two groups according to the suitability of the kidney they received for single or double transplantation as determined by a histological scoring system (HS). All kidneys were transplanted as a single (vs. dual) transplant. We studied whether a HS of the pre-transplant biopsy was predictive of outcome of single transplant ECD kidneys. Recipients (n = 48) were divided into two groups by whether the histologic system suggested single or double transplants be done. There were no differences between groups in two-yr outcomes. We conclude that a clinical scoring system can predict which ECD kidney donors can be safely used as single transplants in a cohort of low immunological risk de novo kidney transplant recipients. Use of the clinical scoring system maximizes organ use.

Sirolimus in chronic allograft nephropathy in pediatric recipients.

CAN is a common cause of late graft loss. Nephrotoxicity due to CNIs is known to contribute to CAN. We retrospectively evaluated the efficacy and safety of SRL in pediatric renal Tx recipients showing CAN in their allograft biopsy. Twenty-one patients aged 10.4 +/- 4.6 yr at Tx time receiving CNIs as primary immunosuppression were converted to SRL at 58.9 +/- 49.1 months after Tx, due to progressive decline of renal function and biopsy proven CAN. Mean follow-up after switch was 19.7 +/- 9.5 months. All patients received CsA as part of the immunosuppressive regimen, at a mean dose 4.4 +/- 1.2 mg/kg/day. Mean daily dose of SRL three month after conversion was 2.6 +/- 0.8 mg/body surface area/day and the mean through levels where 6.9 +/- 2.5 ng/mL. Graft biopsies showed Grade I CAN in 12 children and Grade II CAN in nine. After SRL introduction, there were neither acute rejection episodes nor graft losses. GFR improved at three months and was sustained thereafter only in children with Grade I CAN. Post-Tx time at conversion was the only significant variable between patients who had Grade I CAN and Grade II CAN (33.6 +/- 33.3 vs. 92.7 +/- 47.5 months, p = 0.003). Nine patients had no AEs, six patients had nine SAE: five diarrhea, one herpes zoster, one pancreatic pseudo cyst, one pneumonia, and one Influenza A infection; 11 patients had 13 AEs: six oral aphthous ulcers, three urinary tract infections, two herpes simplex, one lymphedema, and one nephrotic proteinuria. Significant improvement of GFR occurred in Grade I CAN group at three months from conversion and was sustained during follow-up. Those who had Grade II CAN experienced no change in GFR. The incidence of AEs and SAE is of concern and further studies are necessary to assess their relevance.

Comparison between clinical and histopathological scoring in cadaveric kidney transplantation and its correlation with posttransplant evolution.

INTRODUCTION: There are several scoring systems, both clinical (Deceased Donor Score [DDS]) and histopathological (Remuzzi [REM]), that attempt to determine acceptability criteria for deceased donor kidney transplant. A retrospective study was performed among a group of kidney transplant recipients to evaluate posttransplant evolution with clinical and histopathological scores. MATERIALS AND METHODS: Among 107 first deceased donor kidney transplant patients, 95 had undergone a pretransplant biopsy. Donor age was 38.46 +/- 16.9 years; recipient age: 49.2 +/- 16.3 years; DDS was 15.58 +/- 7.29. REM was 2.89 +/- 1.7. Delayed graft function was 64.2%. Induction therapy was administered to 49.5%. Cold ischemia time (CIT) was 1364 +/- 348 minute. Time on dialysis was 2275 +/- 1501 days. Induction therapy, immunosuppressive regimens, CIT, and time on dialysis were not significantly different among the groups. One-year patient and graft survival were 94.5% and 86%, respectively and 2-year values, 92.6% and 81%, respectively. CONCLUSION: DDS showed a significant correlation with serum creatinine values over 1 and 2 years. REM did not show a significant association with any events. The differences were sustained after adjusting for other variables. Graft survival maintained a strong correlation with DDS categories and no association with REM. The clinical characteristics of a deceased donor appeared to be of greater importance than the biopsy findings in terms of posttransplant events.

Open-label, multicenter study on the safety, tolerability, and efficacy of Simulect in pediatric renal transplant recipients receiving triple therapy with cyclosporin, mycophenolate, and corticosteroids.

INTRODUCTION: Basiliximab is a monoclonal antibody directed to the interleukin-2 receptor. Several studies have demonstrated both its efficacy and safety. Even with the use of polyclonal antibodies in renal pediatric transplant recipients, the local incidence of steroid-resistant rejections has been close to 10% of the total incidence of acute rejection episodes (AREs). An open, multicenter prospective study was performed to assess the safety tolerability, and efficacy of induction with basiliximab in renal pediatric transplant patients receiving cyclosporine, mycophenolate, and steroids. MATERIALS AND METHODS: Eighteen patients (8 boys) of mean age 11.9 +/- 4.5 years and body weight 32 +/- 15 kg received cadaveric (n = 7) or living (n = 11) donor grafts. Simulect was administered on days 0 and 4. Efficacy was assessed by the incidence of biopsy-proven acute rejection (BPAR). Safety assessment consisted of a description of the adverse events (AEs). RESULTS: Six BPAR (Banff I and II) occurred in 5, (27.7%) children all of which were steroid responsive. Creatinine levels at day 7 and months 3, 6, and 12 were 1.6 +/- 1.5 mg/dL, 1.0 +/- 0.4 mg/dL, 1.0 +/- 0.5 mg/dL, and 1.0 +/- 0.4 mg/dL, respectively. Schwartz calculation at 12 months was 71 +/- 15 mL/1.73 m2 AEs were hypertension (12), anemia (9), abdominal pain (8), metabolic acidosis (8), nausea (7), diarrhea (2), gingival hypertrophy (2), hirsutism (2), lymphocele (2), and infections (15). No deaths, graft losses, PTLDs, or malignancies were observed. CONCLUSIONS: No steroid-resistant AREs, were observed in this pediatric group using basiliximab. The Schwartz calculation at 12 months was 71 +/- 15 mL/min/1.73 m2.

Sirolimus in pediatric renal transplantation.

Side effects of calcineurin inhibitors (CNIs) include nephrotoxicity and hypertension. Moreover, children have a higher risk of infections and posttransplantation lymphoproliferative disorders. We retrospectively evaluated the efficacy and safety of Sirolimus (SRL) in 18 patients, who were 10.52 +/- 5.03 years at time of transplantation and received a CNI as the core immunosuppression. The most common indications for starting SRL therapy were chronic allograft nephropathy, Epstein-Barr virus-associated neoplasia, and thrombotic microangiopathy. The patients were converted to SRL at 49.14 +/- 45.9 months posttransplantation. Mean follow-up after the switch to SRL was 13.83 +/- 7.24 months. All patients who began SRL therapy remained on that medication. We observed a significant improvement (P < .05) in glomerular filtration rate assessed using the Schwartz formula at 3 months, which was sustained thereafter. There were no changes in proteinuria, plasma lipids, and platelet number. Although the prevalence of hypertensive patients decreased during follow-up, it was not significant. There was one steroid-sensitive, acute rejection episode. Serious adverse events included 1 death due to a relapse of B lymphoma, 1 sepsis, and 1 pancreatic pseudo-cyst. Adverse events were present in 17% of patients: 3 Herpes Simplex infections, and 1 dose-related lymphedema. Further studies are necessary to assess the impact of adverse events in the pediatric transplant population receiving SRL as immunosuppression.

Enfermedad de injerto contra huésped crónica / Chronic graaft versus host disease

La enfermedad de injerto contra huésped crónica (EICHc) es la principal causa de mortalidad tardía relacionada con el transplante alogénico de células progenitoras hematopoyéticas (TACPH) y causa importante de morbilidad. Se analizó la forma de presentación, evolución, respuesta al tratamiento y complicaciones de un grupo de niños y adolescentes que presentaron EICHc luego de recibir un TACPH. La EICHc fue clasificada según su relación con la EICH aguda en progresiva, quiescente o de novo. Según su extensión se clasificó en limitada o extensa. Durante el período estudiado recibieron un TACHP 140 pacientes. Treinta y uno (22%) de ellos presentaron EICHc. La enfermedad fue extensa en 18 casos y limitada en 13. Al diagnóstico 6 ptes. presentaron plaquetopenia. Recibieron tratamiento 28 ptes. 24 con prednosina, 3 con prednisona y ciclosporina, y 1 con PUVA. Respondieron al tratamiento inicial 61% de los tratados por enfermedad extensa y el 86% de aquellos con enfermedad limitada. En los ptes. que no respondieron al tratamiento inicial se agregaron otras drogas como azatioprina, talidomida, tacrolimus y micofenolato. Todos los ptes. recibieron profilaxis para infecciones por bacterias capsuladas y pneumocistis carinii. se registraron 10 infecciones graves (ocho neumonías, una sepsis y una infección del SNC). la mortalidad relaconada con el transplante fue del 16% (4 ptes. por infección y 1 pte. por bronquiolitis obliterante). Se observaron como secuelas cataratas (4), necrosis aséptica de cadera (3) y déficit hormonales (2). Los sobrevivientes presentaron una buena capacidad funcional de acuerdo a los scores de Lansky y/o Karnosfky. palabras clave: enfermedad de injerto contra huésped, transplante alogénico de células progenitoras hematopoyéticas.

Risk factors for Pneumocystis carinii pneumonia in kidney transplant recipients: a case-control study.

OBJECTIVE: To analyze risk factors for Pneumocystis carinii pneumonia (PCP) in kidney transplant recipients. STUDY DESIGN: In a case-control study, 17 PCP cases diagnosed between July 1994 and July 2000 were matched with two controls each (previous and subsequent kidney transplant recipients who did not develop PCP during the same follow-up period). Demographics, organ origin, human leukocyte antigen (HLA) mismatches, use of poly- or monoclonal anti-CD3 antibodies (Po/MoAb) for induction or rejection treatment, rejection episodes, cumulative steroid dose for rejection treatment, immunosuppressive regimens, and other infections were analyzed. RESULTS: No significant differences were seen in gender (male 10 vs. 15), mean age (39.7 vs. 35.4 years), organ origin (cadaver donor 13 vs. 19), HLA mismatches, or Po/MoAb use in induction treatment. Significant differences were observed in PCP cases for rejection history (P=0.02), and median and total number of rejection episodes (P=0.0018). The relative risks for PCP for 1, 2, and > or =3 rejection treatments vs. no such treatment were 1, 1.05, and 6.30, respectively (P=0.021). The relative risk for PCP for steroid-resistant rejection was 4.34 (95% confidence interval [CI], 1.04-18.89) (P=0.019), and that for the use of Po/MoAb for rejection treatment was 7.23 (95% CI, 1.28-49.34) (P=0.006). The relative risk for PCP for 0, 1, and > or =2 previous or concomitant cytomegalovirus (CMV) infection vs. no such infections were 1.0, 2.32, and 13.0, respectively (P=0.012). The relative risks for PCP for tuberculosis (TB) was 18 (95% CI, 1.76-852.03), that for bacterial pneumonia was 14.22 (95% CI, 2.16-150.23), and that for hepatitis C virus infection was 5.25 (95% CI, 1.03-28.91). Immunosuppressive regimens with tacrolimus, mycophenolate mofetil (MMF), steroids (P=0.06), and MMF as a single variable (P=0.05) were more frequently used in cases. Primary trimethoprim-sulfamethoxazole prophylaxis failure was observed in 12 patients in association with heavy immunosuppression and concomitant infections. CONCLUSIONS: The risk of PCP in kidney transplant recipients is related to the number and type of rejection treatments. It is also related to the occurrence of CMV infection, and to other immunomodulating infections such as TB and hepatitis C, and might also be increased with the use of newer and more potent immunosuppressive agents. Primary prophylaxis failure may occur in association with some of these risk factors.

Single-cell gel (comet) assay detects primary DNA damage in nonneoplastic urothelial cells of smokers and ex-smokers.

A protocol for DNA damage assessment by the single-cell gel (SCG)/comet assay in human urinary bladder washing cells was established. Modifications of the standard alkaline protocol included an increase to 2% of sodium sarcosinate in the lysis solution, a reduction in the glass-slide area for comet analysis, and a cutoff value for comet head diameter of at least 30 microm, to exclude contaminating leukocytes. Distinguishing cell populations is crucial, because significant differential migration was demonstrated for transitional and nontransitional cells, phenomena that may confound the results. When applying the modified protocol to urinary bladder cells from smokers without urinary bladder neoplasia, it was possible to detect a significant (P = 0.03) increase in DNA damage as depicted by the tail moment (6.39 +/- 3.23; mean +/- 95% confidence interval; n = 18) when compared with nonsmokers (1.94 +/- 1.41; n = 12). No significant differences were observed between ex-smokers and current smokers regarding comet parameters. Inflammation was not a confounding factor, but DNA migration increased significantly with age in nonsmokers (r = 0.68; P = 0.014). Thus, age matching should be a concern when transitional cells are analyzed in the SCG assay. As it is well known, DNA damage may trigger genomic instability, a crucial step in carcinogenesis. Therefore, the present data directly support the classification of individuals with smoking history as patients at high risk for urinary bladder cancer.

Langerhans cell histiocytosis: retrospective evaluation of 123 patients at a single institution.

The aim of this study was to retrospectively evaluate clinical characteristics at diagnosis and outcome of patients with Langerhans cell histiocytosis (LCH). From October 1987 to March 1996, 133 patients with confirmed LCH were admitted to Hospital JP Garrahan in Buenos Aires (123 evaluable). Median age was 5 years (range 15 days to 18 years). Initial organ involvement included bone 114 patients, ear 34, skin 30, liver 18, lung 14, lymph nodes 14, spleen 12, diabetes insipidus 9, and bone marrow 2. Nineteen patients had organ dysfunction, pulmonary 14, hematological 14, and hepatic 12. Two groups were defined: Group A included patients with single system disease (uni- or multifocal) and group B multisystem (with or without organ dysfunction). In group A (n = 82), 24 patients were treated with chemotherapy (prednisone and vinblastine), 21 with surgery, 15 received radiotherapy, and 22 were only observed. Patients of group B (n = 41) were treated with chemotherapy consisting of prednisone and vinblastine, DALHX 83, or LCH1-based chemotherapy. At a median follow-up of 3 years (range 1 month-8 5/12 years) 93% of patients of group A and 39% of group B survive free of reactivation. In group B, 22% had a reactivation and 39% died of progressive disease. Sequelae were detected in 35 patients (28%), which included diabetes insipidus in 17, hearing loss in 13, bony sequelae in 11, sclerosing cholangitis in 6, and lung fibrosis with bullae in 6. Two patients had a subsequent malignant disease. A total of 17 (14%) patients died and 16 of them belonged to the group B: 13 died of progressive disease, 2 due to sclerosing cholangitis (with sepsis in one case and encephalitis in the other one), 1 with progressive disease and associated myelofibrosis, and 1 patient of group A with active disease and brain stem tumor. Patients who had organ dysfunction had a reactivation free survival of 32%. All these patients survived with sequelae. Logistic regression analysis showed that organ dysfunction and hematological involvement had significant predictive values in relation to death. Patients of group A had an excellent survival rate, whereas in those of group B a high mortality was found, especially in the subgroup of patients with organ dysfunction. Lahey's criteria should be revised. Sequelae were also more common in this group.

The Pseudomonas aeruginosa algC gene product participates in rhamnolipid biosynthesis.

Pseudomonas aeruginosa produces exoproducts correlated with its pathogenicity. One of these virulence-associated traits is the surfactant rhamnolipid. The production of alginate and lipopolysaccharide (LPS) are also of importance for P. aeruginosa virulence. The product of the algC gene (which is involved in alginate production through its phosphomannomutase activity and in LPS synthesis through its phosphoglucomutase activity) participates in rhamnolipid production, presumably catalyzing the first step in the deoxy-thymidine-diphospho-L-rhamnose (dTDP-L-rhamnose) pathway, the conversion of glucose-6-phosphate to glucose-1-phosphate. Other structural alg genes, encoded in the alg operon, are not involved in rhamnolipid nor LPS production. These results show that the AlgC protein plays a central role in the production of the three P. aeruginosa virulence-associated saccharides: alginate, LPS and rhamnolipid.

Adeno-associated virus and development of cervical neoplasia

Evidence from several sources has suggested that adeno-associated virus (AAV) infection might protect against cervical cancer, in part, by interfering with human papillomavirus (HPV)-induced tumorigenesis. Detection of AAV type 2 (AAV-2) DNA in cervical tissues has been reported. However, there have been few in vivo studies of women with cervical HPV infection or neoplasia, and these have reported inconsistent results. Therefore, we used polymerase chain reaction (PCR) assays targeted to the AAV-2 rep and cap genes to test tissue specimens from women in an epidemiological study of cervical neoplasia in Jamaica. We tested 105 women with low-grade cervical intraepithelial neoplasia (CIN-1), 92 women with CIN-3/carcinoma in situ or invasive cancer (CIN-3/CA), and 94 normal subjects. PCR amplification of human beta-globin DNA was found in almost all cervical specimens, indicating that these materials were adequate for PCR testing. The prevalence of HPV DNA, determined by HPV L1 consensus primer PCR was, as expected, strongly associated with presence and grade of neoplasia. Each of the AAV PCR assays detected as few as 10 copies of the virus genome. However, none of the 291 cervical specimens from Jamaican subjects tested positive for AAV DNA. Negative AAV PCR results were also obtained in tests of cervical samples from 79 university students in the United States. Exposure to AAV was assessed further by serology. Using a whole virus AAV-2 sandwich enzyme-linked immunosorbent assay, we found no relationship between AAV antibodies and presence or grade of neoplasia in either the Jamaican study subjects or women enrolled in a U.S. cervical cancer case (n = 74) - control (n = 77) study. Overall, the data provide no evidence that AAV infection plays a role in cervical tumorigenesis or that AAV commonly infects cervical epithelial cells.(Au)

[Doxycycline-induced esophageal ulcers]. / Ulceras esofágicas inducidas por doxiciclina.

UNLABELLED: Tetracycline is known as one of the antibiotics that induce esophageal ulcers. PURPOSE: Understand how these ulcers may behave and respond to treatment with sucralfate. METHOD: During the last two years we studied all patients complaining of dysphagia and odinophagia with an upper GI endoscopy, who were taking doxycycline in the last few days. All of them discontinued the drug once the diagnosis was done and most of them were treated also with sucralfate, 1 g tid. RESULTS: Eleven patients took doxycycline prescribed for: pelvic inflammatory disease, acne, urinary tract and pulmonary infections. Odinophagia was the most common symptom over the next few days of treatment with some risk factors previously documented, such as taking pills just before bedtime and with a small amount of water. The esophageal ulcers were multiple and located mainly in the middle esophageal third. Symptoms disappeared 3.7 days after the medication was stopped, while those taking sucralfate did not change the period of symptoms. CONCLUSIONS: Physicians must be aware of the doxycycline induced esophageal ulcers and discontinuation of the antibiotic as the main treatment, while sucralfate even though has shown to cover these ulcers, does not change the outcome. Therefore, they must encourage then patients to take the pills with enough liquid, in supine position and have special attention to the elderly and those with any kind of esophageal disease.

[Presence of acinar pancreas in reflux esophagitis and Barrett's esophagus]. / Presencia de páncreas acinar en esofagitis por reflujo y esófago de Barrett.

Pancreatic metaplasia in Barrett's esophagus was originally described by Krishnamurthy et al. They found that these focal clusters of cells resemble pancreatic acinar cells by immunohistochemistry and electron microscopy. Wang et al one year later, described these same cell clusters in normal and inflamed gastroesophageal junction. We studied 318 cases diagnosed as Barrett's esophagus (199 cases) and chronic esophagitis (119 cases) in the ABC Medical Center seen in 1996 and the first four months of 1997, to look for pancreatic acinar metaplasia. We found 14 cases of Barrett's esophagus and 11 cases of chronic esophagitis with pancreatic acinar metaplasia. By immunohistochemistry and electron microscopy that these cell clusters are actually acinar pancreatic cells. Our results are in keeping with those found by Krishnamurthy and Wang that the clusters represent pancreatic acinar cells and may be found in Barrett's esophagus and in chronic esophagitis. The significance of these findings remain to be elucidated.

Infantile-onset multisystem inflammatory disease: a differential diagnosis of systemic juvenile rheumatoid arthritis.

We describe four unrelated children with neonatal maculopapular rash, fever, arthritis, hepatosplenomegaly, lymphadenopathy, eye involvement, and neurologic symptoms. Radiographs of the joints were surprisingly similar, showing an abnormal epiphyseal and metaphyseal appearance. These clinical and radiologic findings allowed us to include these children in a very peculiar syndrome described as infantile-onset multisystemic inflammatory disease. A chondrosarcoma developed in one of our patients.