Developing a collaborative international partnership for cancer control in Mexico.

In 2014, a partnership was established between the Univer-sity of California and Mexico, which subsequently catalyzed formation of collaborations between cancer researchers at University of California, San Francisco and in Mexico. Over the past two decades cancer burden has dramatically increased in Mexicans on both sides of the California - Mexico border. Together, we face a growing burden of cancer in the context of globalized economies, diverse migration patterns, and dynamic immigration policies. Our partnership aims to: (1) understand the life course impact of cancer risk factors and interactions with changing environments; (2) address cancer disparities within Mexico, in Mexican migrants to the United States, and in naturalized Mexican-Americans; and (3) identify effective cancer screening strategies and cancer control policies that are tailored to existing healthcare systems and social and cultural factors. Herein, we describe the principles of partner-ship and early successes and challenges of this collaboration.

Developing a collaborative international partnership for cancer control in Mexico / Desarrollo de una alianza internacional colaborativa para el control del cáncer en México

Abstract: In 2014, a partnership was established between the University of California and Mexico, which subsequently catalyzed formation of collaborations between cancer researchers at University of California, San Francisco and in Mexico. Over the past two decades cancer burden has dramatically increased in Mexicans on both sides of the California - Mexico border. Together, we face a growing burden of cancer in the context of globalized economies, diverse migration patterns, and dynamic immigration policies. Our partnership aims to: 1) understand the life course impact of cancer risk factors and interactions with changing environments; 2) address cancer disparities within Mexico, in Mexican migrants to the United States, and in naturalized Mexican-Americans; and 3) identify effective cancer screening strategies and cancer control policies that are tailored to existing healthcare systems and social and cultural factors. Herein, we describe the principles of partnership and early successes and challenges of this collaboration.

Resumen: En 2014, se estableció un convenio de colaboración colaboración entre la Universidad de California y México, que posteriormente catalizó colaboraciones específicas entre investigadores en cáncer en la Universidad de California, San Francisco y en México. En las últimas dos décadas, la carga del cáncer ha aumentado drásticamente en mexicanos de ambos lados de la frontera entre California y México. Juntos, enfrentamos una carga creciente de cáncer en un contexto de economías globalizadas y diversos patrones y políticas de migración dinámicas. Nuestra colaboración tiene como objetivo: 1) entender el impacto a lo largo de la vida de factores de riesgo de cáncer y sus interacciones en un entorno cambiante; 2) abordar disparidades del cáncer dentro de México, en os migrantes mexicanos a los Estados Unidos y en los mexicoamericanos naturalizados; y 3) identificar estrategias efectivas de detección del cáncer y políticas de control del cáncer que se adapten a sistemas de salud existentes y a factores sociales y culturales. Aquí describimos los principios de esta colaboración y los primeros éxitos y retos de la misma.

Improvement in treatment abandonment in pediatric patients with cancer in Guatemala.

BACKGROUND: Treatment refusal and abandonment are major causes of treatment failure for children with cancer in low- and middle-income countries (LMICs), like Guatemala. This study identified risk factors for and described the intervention that decreased abandonment. METHODS: This was a retrospective study of Guatemalan children (0-18 years) with cancer treated at the Unidad Nacional de Oncología Pediátrica (UNOP), 2001-2008, using the Pediatric Oncology Network Database. Treatment refusal was a failure to begin treatment and treatment abandonment was a lapse of 4 weeks or longer in treatment. The impact of medicina integral, a multidisciplinary psychosocial intervention team at UNOP was evaluated. Cox proportional hazards analysis identified the effect of demographic and clinical factors on abandonment. Kaplan-Meier analysis estimated the survival. RESULTS: Of 1,789 patients, 21% refused or abandoned treatment. Abandonment decreased from 27% in 2001 to 7% in 2008 following the implementation of medicina integral. Factors associated with increased risk of refusal and abandonment: greater distance to the centre (P < 0.001), younger age (P = 0.017) and earlier year of diagnosis (P < 0.001). Indigenous race/ethnicity (P = 0.002) was associated with increased risk of abandonment alone. Abandonment correlated with decreased overall survival: 0.57 ± 0.02 (survival ± standard error) for those who completed therapy versus 0.06 ± 0.02 for those who abandoned treatment (P < 0.001) at 8.3 years. CONCLUSION: This study identified distance, age, year of diagnosis and indigenous race/ethnicity as risk factors for abandonment. A multidisciplinary intervention reduced abandonment and can be replicated in other LMICs.

In vivo electrical application on titanium implants stimulating bone formation.

BACKGROUND AND OBJECTIVE: The aim of the present in vivo study was to measure the bone implant contact area after electrical stimulation of dental implants. MATERIAL AND METHODS: Ninety titanium dental implants (6 mm × 11.5 mm) with a smooth surface were placed in six male Beagle dogs and then the implant-bone interfaces was assessed by histological analyses after 7 and 15 d. The 12-mo-old dogs, with a weight of 15 kg, were randomly divided into two groups based on the duration of bone healing: 7 and 15 d. Also, implants were divided into three groups based on electrical stimulation: group A, 10 µA; group B, 20 µA; and group C, control group. The electrical current was applied by an electrical device coupled to the implant connection. RESULTS: After 7 d of electrical stimulation, no statistical differences in bone-implant interface contact area were observed. However, a significantly higher bone-implant interface contact area was recorded for group B than for groups A and C (p < 0.01) after 15 d. No statistical difference was observed between groups A and C (p > 0.05). CONCLUSION: The electrical stimulation of dental implants can generate a larger area of bone-implant interface contact as a result of bone formation. Factors such as different electrical current intensity and duration should be studied in further work to clarify the potential of this method.

[Predictive score of success adapted to our environment to improve results of extracorporeal lithotripsy]. / Sistema predictivo de éxito adaptado a nuestro medio para mejorar los resultados de la Litotricia Extracorpórea.

OBJECTIVE: To present a predictive tool of success of ESWL adapted to our environment. METHODS: We performed a retrospective, descriptive and analytical study of patients with renal and upper ureteral stones whom underwent ESWL with DUET MAGNA lithotripter between January 2014 and March 2015. We included 114 patients in whom demographics and CT scan characteristics were studied. Multivariate analysis by logistic regression was performed to establish independent predictors of success in ESWL. A ROC curve was used to determine success cut-off values of ESWL in each significant variable. The score was established based on the numbers of variables under the cut-off value in each patient. In every one of these categories, percentage of stone free was determined. Finally, the area under the curve of our ESWL treatment success score was made. RESULTS: Of 114 patients studied, 58 (51%) were stone free. After multivariate study, independent predictors of success with ESWL were tomographic density of lithiasis (UH), body mass index (BMI) and stone diameter (mm). Ideal cut off points of treatment success in each one of the score parameters were: density of lithiasis 900 UH, BMI 27 and lithiasis diameter 11 mm. Percentage of stone free was 31.8% for score 0, 37.1% for score 1, 57.5% for score 2 and 88.3% for score 3. Area under the curve for the score was 0.723 (p<0.001). CONCLUSIONS: This score could represent a predictive tool in our environment to predict ESWL results. Utilization of this score could limit the use of this therapy only to patients with favorable profile (score2-3) improving in this way cost-effectiveness of this procedure.

HLA-G polymorphism influences the susceptibility to HCV infection in sickle cell disease patients.

Despite its well known monogenic etiopathogenesis, sickle cell disease (SCD) is characterized by a striking variability of clinical presentation. There is growing evidence that genetic factors may be involved in this variability. Human leukocyte antigen (HLA)-G is a non-classical HLA molecule which was shown to be expressed at sites of inflammation and in inflammatory diseases. Besides its large and highly polymorphic promoter region, the 3' UTR region seems also to play an important role on regulating HLA-G expression. We investigated the influence of the 14 pb (rs1704) and the +3142 (rs1063320) HLA-G polymorphisms in 93 SCD patients in order to evaluate its potential role on clinical parameters. Twenty-one patients presented an HCV infection. Among all SCD patients 16 (22.2%) were homozygous for the +3142C genotype, none of them hepatitis C (HCV) positive. Controlling for blood transfusions in the last year, the C allele represented a dose dependent protection effect for HCV infection (PR = 0.41; 95% CI: 0.24-0.71). The +3142C allele was also underrepresented among patients with history of respiratory-tract infections. Our results support a role of the +3142 polymorphism in the susceptibility to infections, in particular to HCV infection, and suggest a possible interference of the HLA-G molecule in the response to infections, among SCD patients.

Association of the HLA-G 14 bp polymorphism with systemic lupus erythematosus.

Human leukocyte antigen-G (HLA-G) is a nonclassical class I major histocompatibility complex molecule which is induced at the course of inflammatory pathologies, and its expression has been suggested as a possible mechanism of tissue protection against autoimmune inflammatory responses, therefore acting as a mechanism of immune surveillance. We investigated the influence of the 14 bp polymorphism of the HLA-G gene on systemic lupus erythematosus (SLE) by analyzing 293 patients with SLE and 460 healthy controls. The patient's group was not in Hardy-Weinberg equilibrium, presenting an excess of heterozygotes (P = 0.014). The heterozygote group exhibited lower systemic lupus erythematosus disease activity indexes than the homozygous deletion group and the homozygous insertion group (mean value = 2.29 against 2.97 and 3.4, respectively, P = 0.035). Photosensitive patients showed a higher frequency of heterozygotes and an equivalent lower frequency of homozygotes for deletion; on the other hand, patients without arthritis presented a higher frequency of heterozygotes than the arthritis group and also a lower frequency of the del/del genotype. Overall, our results support the idea of a role of the HLA-G insertion/deletion polymorphism and therefore a role for the HLA-G molecule, on the pathology of SLE.

A/G Gln20Arg (exon 1) and G/A Val156Met (exon 5) polymorphisms of the human orosomucoid 1 gene in Mexico.

The human orosomucoid 1 gene (ORM1) codes an alpha-1-acid glycoprotein that has been classified as an acute-phase reactive protein, and a major drug-binding serum component, as well as an immunomodulatory protein with genetic polymorphisms. Evaluation of ORM variation through isoelectric focusing and immunobloting has revealed a world-wide distribution of the ORM1 F and ORM1 S alleles. We evaluated and examined the genetic characteristics of two Mexican populations that have different anthropological and cultural antecedents, examining two ORM1 genotypes (exon 1 - A/G (Gln20Arg) and exon 5 G/A (Val156Met)) in 145 individuals, using nested polymerase chain reaction, sequencing, and restricted fragment length polymorphism. Mexican Mestizos had higher frequencies of the exon 1 A allele (P = 0.020) and AA genotype (P = 0.018) and lower frequency of the G allele (P = 0.020) when compared to Teenek Amerindians. When we examined exon 5 G/A (Val156Met) polymorphisms, we found significantly higher frequencies of the G allele (P = 0.0007) and the GG genotype (P = 0.0003) in the Mexican Mestizo population. The Teenek population had a significantly higher frequency of the A allele than has been reported for Chinese and African (P < 0.05) populations, and the G/A genotype was more frequently found in this Mexican population than in Chinese, African and European populations (P < 0.05).

A/G Gln20Arg (exon 1) and G/A Val156Met (exon 5) polymorphisms of the human orosomucoid 1 gene in Mexico

The human orosomucoid 1 gene (ORM1) codes an alpha-1-acid glycoprotein that has been classified as an acute-phase reactive protein, and a major drug-binding serum component, as well as an immunomodulatory protein with genetic polymorphisms. Evaluation of ORM variation through isoelectric focusing and immunobloting has revealed a world-wide distribution of the ORM1 F and ORM1 S alleles. We evaluated and examined the genetic characteristicsof two Mexican populations that have different anthropological and cultural antecedents, examining two ORM1 genotypes (exon 1 - A/G (Gln20Arg) and exon 5 G/A (Val156Met)) in 145 individuals, using nested polymerase chain reaction, sequencing, and restrited fragment length polymorphism. Mexican Mestizos had higher frequencies of the exon 1 A allele (P = 0.020) and AA genotype(P = 0.018) and lower frequency of the G allele (P = 0.020) when compared to Teenek Amerindians. When we examined exon 5 G/A (Val156Met) polymorphisms, we found significantly higher frequencies of the G allele (P = 0.0007) and the GG genotype (P = 0.0003) in the Mexican Mestizo population. The Teenek population had a significantly higher frequency of the A allele than has been reported for Chinese and African (P < 0.05) populations, and the G/A genotype was more frequently found in this Mexican population than in Chinese, African and European populations (P < 0.05).

Alpha-1-acid glycoprotein, its local production and immunopathological participation in experimental pulmonary tuberculosis.

Alpha-1-acid glycoprotein (AGP) is one of the major acute-phase proteins (APPs). Hepatic production and serum concentrations increase in response to systemic injury, inflammation, or infection. We reported previously that expression of the AGP gene is induced in the liver during experimental pulmonary tuberculosis. Since AGP may also be produced at the infection site and has some immunomodulatory properties, we used a model of progressive pulmonary tuberculosis in Balb/c mice to study the kinetics of AGP production in the lung and its influence on immunopathology. We found that AGP was produced in the lung during experimental tuberculosis. Alveolar macrophages and type II pneumocytes were the most important cellular sources during early infection (days 1-14). From day 21 postinfection, during the progressive phase of the infection, foamy macrophages located in pneumonic areas were the most important source of AGP and 10-fold higher concentrations were found on day 60. In a second part of the study, AGP was inactivated during the progressive phase by the administration of specific blocking antibodies. In comparison with control infected animals, tuberculous mice treated with blocking AGP antibodies showed higher expression of interferon gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), and inducible nitric oxide synthase (iNOS) in association with significantly reduced bacillary loads and tissue damage. Thus, AGP is produced in the lung during experimental pulmonary tuberculosis and it has immunomodulatory activities, suppressing cell-mediated immunity and facilitating growth of bacilli and disease progression.

Anti-avian antibodies and rheumatoid factor in pigeon hypersensitivity pneumonitis.

BACKGROUND: Although several immunological abnormalities may be present in pigeon hypersensitivity pneumonitis (HP), few specific hallmarks have been described. OBJECTIVE: To determine whether the presence of rheumatoid factor (RF) could be useful to discriminate pigeon HP from asymptomatic breeders (AB) and other interstitial lung diseases. METHODS: Fifty-three patients with pigeon HP, 47 AB, 31 idiopathic pulmonary fibrosis (IPF) patients and a rheumatoid arthritis (RA) group were studied. IgM RF was determined through enzyme-linked immunosorbent assay (ELISA) and western blot using human IgG and IgG Fc fragment as antigens. IgG and IgA anti-avian antibodies (AA) against pigeon serum antigen were also measured. The use of F(ab')2 fraction of peroxidase-labelled anti-human immunoglobulins prevented endogenous interferences. Possible cross-binding of RF with avian antigens and the reactivity against human IgG by AA were studied. RESULTS: RF tests were frequently positive in HP (52.8%) in comparison to AB (4.2%) and IPF (12.9%; P = 2.6 x 10-10 and 4.1 x 10-5). Therefore, the presence of RF in pigeon HP showed a sensitivity of 52% and was highly specific considering the results of AB and IPF (95 and 87%, respectively). The RA group revealed positive RF but negative AA tests. RF activity was confirmed through western blot using purified IgG Fc fragment. Overlapping levels of IgG and IgA AA were found in HP and AB. The frequency of AA was low in IPF. The cross-reaction of RF with avian antigens was excluded, and no reactivity against human IgG by AA was detected. Other endogenous interferences were ruled out. CONCLUSION: No single immunological test may definitively distinguish pigeon HP from AB and other interstitial lung disorders; however, positive RF, together with high AA levels, seems to be useful in differentiating the diagnosis.

Association of polymyositis with rheumatoid arthritis.

The association of polymyositis (PM) and rheumatoid arthritis (RA) is described in a 40-year-old female Mexican patient who was studied for a long period of time. The characteristic changes of PM that preceded the onset of RA for 7 years included proximal symmetrical muscle weakness, increased creatine kinase activity, and distinctive electromyography and muscle biopsy results. The occurrence of RA during the final 4 years of the 11-year period was characterized by long-lasting deforming and symmetric polyarthritis, high positive rheumatoid factor, subcutaneous nodules, and erosive joint changes. Through observation, myopathic changes other than those from PM were excluded. Joint changes other than from RA were also ruled out. A review of the literature revealed few specific reports of the coexistence of both diseases.

Inflammatory cytokine production by immunological and foreign body multinucleated giant cells.

Multinucleated giant cells (MGC) are a common feature of granulomas. The mechanism of their formation has been studied extensively, but their function has not been completely characterized. A new method for the in vivo production of MGC was developed involving subcutaneous injection of microscopic nitrocellulose particles with adsorbed mycobacterial antigens into the footpads of sensitized BALB/c mice (immune [I]-MGC), or by nitrocellulose administration to non-sensitized mice (foreign body [FB]-MGC). The development of granulomas with a highly enriched MGC population was observed 2 weeks after the nitrocellulose injection. MGC were larger with a greater number of nuclei in I-MGC than in FB-MGC. From days 7-28 after nitrocellulose administration, the production of interleukin-1alpha (IL-1alpha) and tumour necrosis factor-alpha (TNF-alpha) was demonstrated in both MGC types by in situ reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. After 2 months, the MGC had ceased production of IL-1alpha and TNF-alpha, but the expression of transforming growth factor-beta (TGF-beta) was very high, occurring together with extensive fibrosis. These results suggest that MGC are an active source of inflammatory cytokines, which can contribute to the initiation, maintenance and down-regulation of granulomatous inflammation induced by immunological and inert substances.

Anticardiolipin antibodies in serum and cerebrospinal fluid from patients with systemic lupus erythematosus.

Anticardiolipin antibodies were studied in serum and cerebrospinal fluid from 32 consecutive patients with systemic lupus erythematosus, admitted for the assessment of neuropsychiatric disease. Ten of the 16 patients with active neuropsychiatric complaints showed positive anticardiolipin antibodies in cerebrospinal fluid, including eight with the simultaneous presence of antibodies in their sera. By contrast, only 2 of the 16 patients with headaches, lacking further data of neurological disease, revealed anticardiolipin antibodies in their cerebrospinal fluid. The assessment of Q-albumin index showed abnormal values in a subset of patients with active neuropsychiatric changes who showed positive cerebrospinal anticardiolipin antibodies, suggesting that an impairment of the blood brain barrier function may lead to a leakage of intrathecal antiphospholipid antibodies from systemic circulation. Additionally, few patients revealed normal Q-albumin values with high IgG-cerebrospinal fluid index suggesting increased intrathecal synthesis of autoantibodies. The study of anticardiolipin antibodies in cerebrospinal fluid was useful to detect active neuropsychiatric disease in systemic lupus erythematosus.

Evaluation of disease activity by laboratory tests in juvenile rheumatoid arthritis.

We studied 29 juvenile rheumatoid arthritis patients with polyarticular onset in order to detect the presence of disease activity by laboratory tests. Laboratory studies included hemoglobin, hematocrit, erythrocyte sedimentation rate (ESR), white blood cell (WBC) and platelet counts. We also determined the levels of IgG, IgA, IgM, C3, C4 and C reactive protein, as well as the presence of rheumatoid factor and antinuclear antibodies. There were 13 patients in the group with polyarticular disease activity, and 16 in the group with asymptomatic juvenile rheumatoid arthritis. Low hematocrit and hemoglobin values, abnormal ESR and elevated WBC and platelet counts occurred in polyarticular juvenile rheumatoid arthritis patients with active disease. Increased levels of IgA, C3 and C4 were also found in the exacerbation stage, as compared to the asymptomatic control group. No differences were found in rheumatoid factor and antinuclear antibodies between the active and inactive juvenile arthritis patients. Our data agreed with previous studies in that a single laboratory test cannot necessarily confirm juvenile arthritis activity, and they suggest that two or more abnormal parameters would be useful in assessing the flare-up of the disease.

Rheumatoid factor activity in serum and bronchoalveolar lavage fluid from patients with acute hypersensitivity pneumonitis.

The presence of rheumatoid factor was detected in both serum and bronchoalveolar lavage fluid (BALF) from patients with acute pigeon breeder's disease. IgM rheumatoid factor was positive in 14 of 20 serum samples and 6 of 20 BALF samples by ELISA. In contrast, negative results were found in 20 healthy subjects with a history of avian antigen exposure, as well as in the serum and BALF from 10 normal subjects. The simultaneous presence of rheumatoid factor in serum and BALF occurred in five patients, and four of them revealed high levels of rheumatoid factor in BALF in comparison with serum determinations. These abnormalities may play an important role during the acute inflammatory reaction in hypersensitivity pneumonitis.

[Cardiac myxoma. A report of 23 cases]. / Mixoma cardiaco. Presentación de 23 caso.

Twenty-three cases of cardiac myxoma are reviewed during a period of 11 years. Seventeen patients were females and 6 males with an average age of 36 years. All patients were symptomatic for an average period of time of 4 months. Dyspnea was the main symptom (91%), congestive heart failure (52%), murmurs (74%), atypical chest pain (65%), palpitations (52%), constitutional manifestation (48%), congestive heart failure (36%), embolic events (23%) and ventricular tachycardia as a first manifestation of a right ventricular myxoma in one case (4.5). In all patients the diagnosis of cardiac tumor was made during life. Among they, in 83%, by echocardiogram, 14%, by cardiac catheterization, and in one case (4.5%) with both methods. Seventy percent were located in the left atrium, 18% in the right atrium, 9% in the right ventricule and 4.5% to both right cavities. Two patients died while waiting surgery, one due to pulmonary emboli and another due to refractory congestive heart failure. In all 21 patients who were sent to surgery a direct correlation was seen with the echocardiographic findings. All 23 patients had a confirmatory histopathological diagnosis. There were no surgical deaths. Excision of the tumor resulted in marked symptomatic improvement. The follow up by echocardiography showed that surgery has been curative with no recurrence up till now. We consider that this entity, that is capable to simulate multiple cardiovascular diseases must be removed surgically once it has been diagnosed in order to avoid fatal complications.

[Thrombocytopenic purpura and hemolytic anemia in children with generalized lupus erythematosus]. / Púrpura trombocitopénica y anemia hemolítica en niños con lupus eritematoso generalizado.

We studied 30 children with systemic lupus erythematosus in order to detect the clinical, pathological and serological findings associated with the development of thrombocytopenic purpura and hemolytic anemia. A group of 13 of the 30 children revealed hematological manifestations as the most prominent changes of SLE. Thrombocytopenic purpura and hemolytic anemia were the beginning manifestation of SLE in 11 children. Different causes, for these hematological changes such as hypersplenism, renal microangiopathy or drugs reactions were excluded by history and examination. Interestingly, other immunohematological manifestations including splenomegaly and lymphadenopathy were more frequent in children with thrombocytopenic purpura and hemolytic anemia, than in those patients without these hematological complications. Positive antiplatelet antibodies were found in 4/6 children with thrombocytopenia and 2/5 with hemolytic anemia. A relation of antiplatelet with anticardiolipin antibodies occurred in 4 patients; 3 of them in children with thrombocytopenic purpura and one with hemolytic anemia. Anti-dsDNA and anti-Sm antibodies were positive in almost all patients. Four children shown a transition from anti-dsDNA to anti-Sm antibodies or viceversa and all of them revealed a significant variation in the titer of these antibodies by ELISA, in relation with disease activity. The presence of hematological manifestations associated with anti-platelet and anti-cardiolipin antibodies in children with SLE support that different mechanisms triggers autoimmunity in childhood.

[Postangioplasty renal artery thrombosis treated intraluminally with thrombolysis. A case report]. / Trombosis arterial renal postangioplastía intraluminal tratada con trombólisis. Informe de un caso.

The authors present the clinical case of a 31 year female with systemic vascular hypertension secondary to a 65 percent unilateral fibromuscular renal artery stenosis. The centellographic study demonstrated hypoperfusion on the right kidney and serious functional damage; the patient was subject to intraluminal renal angioplasty resulting in right renal arterial thrombosis, which was treated successfully with intra-arterial and intravenous streptokinase infusion. Following the thrombotic therapy, recanalization of the thrombosed artery and normal renal excretion of the contrast substance was observed.

[Generalized sclerosis (scleroderma) in children]. / Esclerosis generalizada (esclerodermia) en pacientes pediátricos.

Five patients with childhood scleroderma, were studied from a total group of 50 cases with the disease, 39 of them with diffuse systemic sclerosis and 11 with the CREST syndrome. The average age for these five patients when the disease onset was 13 (the age ranged from 5.5 to 16 years) with an average follow-up of 3.6 years (ranging from 1 to 6.5 years). Of the five, four girls were classified as having diffuse systemic sclerosis and the remaining boy, as suffering from the CREST syndrome. We found no family history or personal and occupational antecendents related with the appearance of the illness. Also excluded were conditions associated with changes similar to scleroderma as are seen in cases of diabetes mellitus, phenylketonuria, toxic oil syndrome, or graft-host rejection reactions. The clinical manifestations seen at the start of the disease included the Raynaud phenomenon, subcutaneous edema and muscular-skeletal abnormalities as arthralgia and myalgia with objective data of inflammatory myopathy. Proximal scleroderma was seen in all five patients; three of them, in addition, developed rapidly progressive cutaneous changes, causing the loss of elasticity and cutaneous hardening of the face during the first year of the disease. In all of the cases, the skin biopsy showed histopathological changes compatible with the diagnosis already given. The most important changes seen in the organs of these children were oesophageal dysfunction and fibrosis of the lung. The X-rays of three of the patients showed them to suffer from intestinal malfunction. We found no kidney, liver or nervous system disorders.(ABSTRACT TRUNCATED AT 250 WORDS)