Efectos de la rehabilitación pulmonar en pacientes con EPOC según la clasificación GOLD 2020 en Cali, Colombia / Pulmonary rehabilitation effects in patients with COPD according to GOLD 2020 classification in Cali, Colombia

Introducción: La enfermedad pulmonar obstructiva crónica dispone de una guía encargada de la prevención y tratamiento, denominada Global Initiative for Chronic Lung Disease, la cual anualmente se actualiza y cataloga la rehabilitación pulmonar, dentro de las opciones de tratamiento. Objetivo: Describir los efectos en variables clínicas, de capacidad funcional, de ansiedad/depresión y calidad de vida relacionada con la salud en pacientes con enfermedad pulmonar obstructiva crónica, después de un programa de rehabilitación pulmonar, de acuerdo con la clasificación GOLD 2020 en una clínica de Cali. Materiales y métodos: Estudio descriptivo, longitudinal donde se incluyeron 79 pacientes divididos en 3 grupos (B, C y D). Resultados: La edad media fue de 70 años; el 69% eran hombres. La cantidad de días hospitalizados fue mayor para el grupo C y D, con un promedio de 8 y 13 días, respectivamente (p≤0,000). La capacidad funcional evidenció una mayor distancia en el grupo C (421m) y la menor distancia para el grupo D (328m), p≤0,006. En la ansiedad y depresión, el grupo D logró obtener mejorías al igual que en el cuestionario de calidad de vida. Conclusión: El grupo C presentó mayor capacidad funcional y mejor calidad de vida, el grupo B tuvo mejores resultados en las variables clínicas, y el grupo D tuvo peor condición clínica, capacidad funcional y calidad de vida. Al finalizar la rehabilitación pulmonar el grupo D presentó mayores cambios en la capacidad funcional y calidad de vida.(AU)

Introduction: Chronic obstructive pulmonary disease has a guide in charge of prevention and treatment, called the Global Initiative for Chronic Lung Disease, which is annually updated and catalogs pulmonary rehabilitation, within the treatment options. Objective: To describe the effects on clinical variables, functional capacity, anxiety/depression and health-related quality of life in patients with chronic obstructive pulmonary disease, after a pulmonary rehabilitation program, according to the GOLD 2020 classification in a Cali clinic. Materials and methods: Descriptive, longitudinal study where 79 patients divided into 3 groups were included (B, C and D). Results:The mean age was 70 years, 69% men. The number of hospitalized days was greater for groups C and D with an average of 8 and 13 days, respectively (p≤0.000). The functional capacity showed a greater distance in group C (421m) and the shortest distance for group D (328m), p≤0.006. In anxiety and depression, group D managed to obtain improvements as well as in the quality of life questionnaire. Conclusion: Group C presented greater functional capacity and better quality of life, group B had better results in clinical variables, and group D had worse clinical condition, functional capacity and quality of life. At the end of pulmonary rehabilitation, group D presented greater changes in functional capacity and quality of life.(AU)

[Pulmonary rehabilitation effects in patients with COPD according to GOLD 2020 classification in Cali, Colombia]. / Efectos de la rehabilitación pulmonar en pacientes con EPOC según la clasificación GOLD 2020 en Cali, Colombia.

INTRODUCTION: Chronic obstructive pulmonary disease has a guide in charge of prevention and treatment, called the Global Initiative for Chronic Lung Disease, which is annually updated and catalogs pulmonary rehabilitation, within the treatment options. OBJECTIVE: To describe the effects on clinical variables, functional capacity, anxiety/depression and health-related quality of life in patients with chronic obstructive pulmonary disease, after a pulmonary rehabilitation program, according to the GOLD 2020 classification in a Cali clinic. MATERIALS AND METHODS: Descriptive, longitudinal study where 79 patients divided into 3 groups were included (B, C and D). RESULTS: The mean age was 70 years, 69% men. The number of hospitalized days was greater for groups C and D with an average of 8 and 13 days, respectively (p≤0.000). The functional capacity showed a greater distance in group C (421m) and the shortest distance for group D (328m), p≤0.006. In anxiety and depression, group D managed to obtain improvements as well as in the quality of life questionnaire. CONCLUSION: Group C presented greater functional capacity and better quality of life, group B had better results in clinical variables, and group D had worse clinical condition, functional capacity and quality of life. At the end of pulmonary rehabilitation, group D presented greater changes in functional capacity and quality of life.

Neurosyphilis in a young man having HIV infection, blurring of vision and skin rash.

We report a 22-year-old homosexual man, a known case of HIV-1 infection but non-compliant to medications, who presented with a 5-month history of progressive painless non-pruritic coin-shaped skin lesions and recent gradual bilateral blurring of vision. His history divulged a primary syphilitic event 1 year prior to the present clinical manifestations. Investigation led to the diagnosis of neurosyphilis with ocular involvement with concurrent signs of secondary syphilis. Treatment with aqueous crystalline penicillin G, ophthalmic steroid and tropicamide drops, and topical emollients resulted in significant clinical improvement of ocular symptoms and skin lesions. The diagnosis of neurosyphilis requires a high degree of clinical suspicion and should be included in the differential diagnosis of unexplained ocular symptoms, particularly in men who have sex with men and HIV-infected patients. This is necessary for the early diagnosis, appropriate management, and good outcome of these patients.

Telerrehabilitación en personas con enfermedad cardiovascular durante el periodo de aislamiento preventivo obligatorio por COVID-19 en Colombia / Telerehabilitation in people with cardiovascular disease during the period of compulsory preventive isolation by COVID-19 in Colombia

Introducción: La enfermedad cardiovascular es una de las principales causas de morbimortalidad a nivel mundial. Como resultado de la pandemia de COVID-19, muchos programas de rehabilitación han pasado a modelos de entrega remota. La telerrehabilitación es una forma de realizar rehabilitación cardiaca mientras se reduce el riesgo de transmisión del COVID-19. Objetivo Describir los efectos de un programa de ejercicio terapéutico en personas con enfermedad cardiovascular que realizan telerrehabilitación, en el periodo de aislamiento preventivo obligatorio por COVID-19. Materiales y métodos Estudio cuasiexperimental, de 6 meses, en personas con enfermedad cardiovascular que ingresaron a un programa de ejercicio terapéutico asistido por tecnología virtual en una clínica de Cali (Colombia). Resultados De 31 personas, 21 eran hombres. La edad promedio fue de 60,48±11,21 años. Se encontraron diferencias significativas al inicio y al final del estudio en las variables de fracción de eyección del ventrículo izquierdo, frecuencia cardiaca, presión arterial, frecuencia respiratoria, índice de masa corporal, perímetro de abdomen, porcentaje de grasa, porcentaje de masa muscular, colesterol, estado de depresión, distancia recorrida, consumo de oxígeno e índice metabólico (MET), con p<0,05. Conclusión Un programa de ejercicio terapéutico en personas con enfermedad cardiovascular que realizan telerrehabilitación resulta eficaz, al alcanzar las metas de tratamiento (AU)

Introduction: Cardiovascular disease is one of the leading causes of morbidity and death globally. As a result of the COVID-19 pandemic, many rehabilitation programs have shifted to remote delivery models. Telerehabilitation is a way to perform cardiac rehabilitation while reducing the risk of COVID-19 transmission. Objective This study aimed to describe the effects of a physical exercise program in persons with cardiovascular disease who performed telerehabilitation in the period of mandatory preventive isolation due to the COVID-19 emergency. Materials and methods This was a quasiexperimental 6-month study of persons with cardiovascular disease who entered a virtual technology-assisted physical exercise program in a clinic in Cali, Colombia. Results Significant differences were found at the beginning and end of the study in the variables of left ventricular ejection fraction, heart rate, blood pressure, respiratory rate, body mass index, abdominal perimeter, percentage of fat, percentage of muscle mass, cholesterol, state of depression, distance traveled, oxygen consumption and metabolic equivalent (METs), showing p-value <0.05. Conclusions A physical exercise program in persons with cardiovascular disease performing telerrehabilitation proves effective in achieving treatment goals (AU)

Respuesta a rehabilitación pulmonar en mujeres con EPOC: comparación entre enfermedad asociada a humo de leña y cigarrillo / Response to pulmonary rehabilitation in women with COPD: Comparison between disease associated with wood smoke and cigarette

Introducción: La enfermedad pulmonar obstructiva crónica es una entidad de alta morbimortalidad que principalmente se genera por exposición a consumo de cigarrillo y exposición a humo de leña; estudios previos han demostrado creciente interés entre los 2 tipos de exposición. Objetivo: Comparar el efecto de la rehabilitación pulmonar en pacientes con enfermedad pulmonar obstructiva crónica que han tenido exposición a cigarrillo versus pacientes expuestos a humo de leña por biomasa en una clínica de cuarto nivel en Santiago de Cali (Colombia). Materiales y métodos: Estudio prospectivo y longitudinal, se reclutaron a todos los pacientes que asistieron durante enero de 2016 a diciembre de 2017 y cumplieron con los criterios de inclusión; posteriormente se dividieron en 2 grupos: humo de leña y cigarrillo. Se registraron pruebas de función pulmonar, evaluación de calidad de vida relacionada de la salud, valoración de síntomas y comparación de capacidad aeróbica funcional con test de caminata de 6 minutos y consumo de oxígeno estimado antes y después de rehabilitación. Resultados: Quince pacientes con exposición a leña y 17 a cigarrillo culminaron la rehabilitación. En la comparación intragrupo, se encontraron diferencias significativas (p<0,05) en la distancia recorrida, en la escala modificada de disnea del Medical Research Council (mMRC) y en el consumo de oxígeno estimado, también en el Saint George Respiratory Questionnaire. En la comparación entre grupos no se encontraron diferencias en las variables estudiadas. Conclusión: La rehabilitación pulmonar generó cambios clínicos significativos en las variables estudiadas en los 2 tipos de exposición, al ser estos cambios similares en los 2 grupos estudiados en la presente investigación. (AU)

Introduction: Chronic obstructive pulmonary disease is an entity with high morbidity and mortality that is mainly generated by exposure to cigarette smoking and exposure to wood smoke; previous studies have shown increasing interest between the 2 types of exposure. Objective: To compare the effect of pulmonary rehabilitation in patients with chronic obstructive pulmonary disease who have had exposure to cigarettes versus patients exposed to biomass wood smoke in a fourth level clinic in Santiago de Cali (Colombia). Materials and methods: Prospective and longitudinal study, all patients who attended from January 2016 to December 2017 were recruited and met the inclusion criteria, later they were divided into 2 groups: Wood Smoke and Cigarette. Pulmonary function tests, health-related quality of life assessment, symptom assessment and comparison of functional aerobic capacity were recorded with the six-minute walk test and estimated oxygen consumption before and after rehabilitation. Results: Fifteen patients with exposure to wood smoke and 17 to cigarettes completed the rehabilitation. In the intragroup comparison, significant differences (P<.05) were found in the distance traveled, in modified Medical Research Council dyspnea scale (mMRC) the estimated oxygen consumption, also in the Saint George Respiratory Questionnaire. In the comparison between groups, no differences were found in the variables studied. Conclusion: Pulmonary rehabilitation generated clinics changes significant in the variables studied in the 2 types of exposure; these changes being similar in the 2 groups studied in the present investigation. (AU)

Cambios en la tolerancia al ejercicio, disnea y calidad de vida a las 8 vs. 12 semanas de rehabilitación pulmonar en pacientes con EPOC / Changes in tolerance to exercise, dyspnoea and quality of life at 8 vs. 12 weeks of pulmonary rehabilitation in patients with COPD

Introducción En pacientes con enfermedad pulmonar obstructiva crónica (EPOC), la rehabilitación pulmonar reporta mejorías en la tolerancia al ejercicio, la calidad de vida y la disminución de síntomas; sin embargo, pocos estudios comparan programas de rehabilitación pulmonar de menor y mayor duración. El objetivo fue describir los beneficios de la RP en cuanto a tolerancia al ejercicio, percepción de disnea y de calidad de vida, en pacientes con EPOC que asisten a un programa de rehabilitación pulmonar durante 8 semanas comparados con los que asisten durante 12 semanas en una institución de tercer nivel de la ciudad de Cali-Colombia. Métodos Estudio cuasiexperimental vinculando pacientes con EPOC, 15 pacientes en el programa de rehabilitación pulmonar de 8 semanas y 15 pacientes en el programa de rehabilitación pulmonar de 12 semanas. Se valoró al inicio y final del programa el índice de masa corporal, distancia recorrida en el test de caminata de los 6 minutos (TC6M), la calidad de vida CRQ-SAS. Resultados El índice de masa corporal no presentó cambios estadísticamente significativos en los grupos, la tolerancia al ejercicio presentó mejoría estadísticamente significativa en la rehabilitación pulmonar de 12 semanas (p<0,05), el cuestionario CRQ-SAS evidenció una mejoría en todos los dominios, pero no hubo diferencias entre ambos grupos. Conclusiones Pacientes con EPOC presentaron mejorías estadísticamente significativas después del programa de rehabilitación pulmonar en variables como la disnea y la calidad de vida; sin embargo, solo el grupo de rehabilitación pulmonar de 12 semanas presentó mejorías estadísticamente significativas en la distancia recorrida del TC6M comparado con el grupo de rehabilitación pulmonar de 8 semanas (AU)

Introduction In patients with chronic obstructive pulmonary disease (COPD), pulmonary rehabilitation reports improvements in exercise tolerance, quality of life and decrease in symptoms; however, few studies compare shorter and longer pulmonary rehabilitation programmes. The objective was to describe the benefits of PR in terms of exercise tolerance, perception of dyspnoea and quality of life, in patients with COPD attending a pulmonary rehabilitation programme for 8 weeks compared to those attending for 12 weeks in a third level institution in the city of Cali, Colombia. Methods Quasi-experimental study linking patients with COPD, 15 patients in the 8-week pulmonary rehabilitation programme and 15 patients in the 12-week pulmonary rehabilitation programme. Body mass index (BMI), distance covered in the 6-minute walk test (TC6M), quality of life CRQ-SAS questionnaire were assessed at the beginning and end of the programme. Results BMI did not show statistically significant changes in the groups, exercise tolerance showed statistically significant improvement in 12-week pulmonary rehabilitation programme (p<.05), the CRQ-SAS questionnaire evidences improvement in all domains, but there were no differences between both groups. Conclusions COPD patients, statistically significant improvement after the pulmonary rehabilitation programme in variables such as dyspnoea and quality of life; however, only the 12-week pulmonary rehabilitation programme group presented statistically significant improvements in the distance travelled of the TC6M compared to the 8-week pulmonary rehabilitation programme group (AU)

Effectiveness of 12 week ledipasvir/sofosbuvir and predictors of treatment failure in patients with hepatitis C.

OBJECTIVE: The efficacy of ledipasvir/sofosbuvir (LDV/SOF) have been demonstrated in randomized controlled trials, however,there is an unmet need for real-world effectiveness data. It is important to gather data regarding potential predictors of treatment failure with (LDV/SOF). Predictors of sustained virologic response (SVR) to all-oral HCV regimens can inform nuanced treatment decisions. The objectives of this study were to evaluate the effectiveness of LDV/SOF, SVR12 as main endpoint and SVR24 as second endpoint, and identify predictors of treatment failure. METHODS: Retrospective and observational study carried out from April 2015 to January 2016. Inclusion criteria: patients with HCV infection treated with LDV/SOF for 12 weeks during study period. The patients that were treated during 24 weeks were excluded as well as those treated with peg-interferon. Binary logistic regression was used to predict what variable was associated with treatment failure. RESULTS: A total of 122 patients were analyzed achieving SVR12 91.80% (112/122) of them. The patients with HCV genotype (GT) 1a or GT1b or GT4 achieved SVR12. Only one pre-treated non-cirrhotic HCV GT1 patients relapsed to treatment. The lowest SVR12 were obtained for GT3, 43.75%, (7/16). Everybody that got SVR12 achieved SVR24. None of the variables analyzed significantly influenced the SVR12, except GT (p=0.001). Almost all the relapses occurred in GT3. CONCLUSIONS: LDV/SOF combination has been very effective to treat GT1 and GT4 infected patients, however, has constituted a suboptimal therapeutic option for those patients infected with GT3, regardless of the rest of the variables analyzed.

Direct-acting antiviral agents in patients with hepatitis C genotype 1-4 infections in a tertiary hospital.

OBJECTIVE: Hepatitis C virus (HCV) infection is a major cause of chronic liver disease. Six different genotypes (GT) of HCV (genotypes 1-6) have been identified. The genotype is clinically relevant since the majority of current direct antiviral agents (DAA´s) do not have pangenotypic efficacy. The purpose of this study was to describe the clinical characteristics of real world patients and evaluate the effectiveness of different treatment regimens. METHODS: Retrospective and observational study carried out in a third level hospital. Study period: January 2015-January 2016. Inclusion criteria: HCV patients of any genotype treated with either DAAs ± rivabirin (RBV) or DAAs + RBV + pegilated interferon (Peg-IFN) regimens for 12 weeks. Exclusion criteria: patients without adequate clinical or analytical information available for further analysis. Patients treated for 24 weeks were excluded. The main endpoint was sustained virologic response 12 weeks after the end of treatment (SVR12), and secondary endpoint was SVR24. RESULTS: A total of 515 patients were included (aged 55.52±8.97 years). GT1: patients treated with simeprevir + sofosbuvir (SIM + SOF), ledipavir (LDV)/SOF and paritaprevir/ritonavir/ombitasvir + dasabuvir (PTV/r/OBV + DSV) ± RBV had a SVR12 of 93.59% (190/203), 98.82% (N=84/85), 94.28% (66/70), respectively. Regarding daclatasvir (DCV) + SOF and SIM + DCV, everybody (19/19) and 87.5% (7/8) got SVR12, respectively. GT2: 71.42% (N=10/14) of patients achieved SVR12, concretely, SOF + RBV had a SVR12 75% (N=6/8). GT3: 43.75% (N=7/16), 90% (N=9/10) and 95% (N=19/20) of patients treated with LDV/SOF, LDV/SOF + RBV and SOF + DCV obtained SVR12, respectively. GT4: patients treated with LDV/SOF, SIM + SOF and PTV/r/OBV ± RBV had a SVR12 rate of 100% (21/21), 91.67% (22/24) and 92% (23/25), respectively. All patients that got SVR12 achieved SVR24. CONCLUSIONS: Our study confirmed the efficacy data reported in clinical trials in a cohort of patients with GT1-4 and a wide range of basal characteristics.

Interferon-free treatments in patients with hepatitis C genotype 3 infection in a tertiary hospital.

OBJECTIVE: Hepatitis C virus genotype 3 represents a unique entity within HCV treatment and multiple studies have documented that HCV genotype 3 infection is associated with more rapid disease progression than other genotypes, resulting in increased risk of cirrhosis, hepatocellular carcinoma, and all-cause mortality. In the current study, we further evaluated the real-world effectiveness of 12 weeks of ledipasvir/sofosbuvir ± ribavirin (LDV/SOF ± RBV) and sofosbuvir + daclatasvir (SOF + DCV) for treatment-naive or treatment-experienced patients infected with HCV genotype 3, with or without cirrhosis. METHODS: Retrospective and observational study carried out in a third level hospital. Study period: April 2015 to January 2016. Inclusion criteria: Patients with HCV genotype-3 infection treated either with LDV/SOF ± RBV or with SOF + DCV during study period treated for 12 weeks. The patients that were treated during 24 weeks were excluded and those treated with peg-interferon. The main endpoint measured was the sustained virologic response (SVR) at 12 weeks (SVR12) and the secondary endpoint was SVR at 24 weeks (SVR24). RESULTS: During the study period, 603 patients were treated in our hospital: 71 with genotype 3. We included 46 patients who were treated with LDV/SOF ± RBV or SOF + DCV for 12 weeks. A 43.75% (7/16) of all patients treated with LDV/SOF achieved SVR12, 90% (9/10) of the patients treated with LDV/SOF+RBV achieved SVR12 and 95% (19/20) of the patients treated with SOF+DCV achieved SVR12. There was statistically significant difference (p=0.001) between LDV/SOF respect to SOF+DCV and between LDV/SOF with regard to LDV/SOF +RBV (p=0.018) used to treat HCV genotype 3 infection. CONCLUSIONS: In conclusion, in our cohort of patients, the combination of SOF + DCV followed by LDV/SOF + RBV 12 weeks were the most effective in patients with HCV genotype 3 and with cirrhosis (SVR12 90% and 80%, respectively) and in those without cirrhosis (SVR12 100% in both combinations). All patients who achieved SVR12 also achieved SVR24, regardless of the regimen received.

[Darunavir/cobicistat monotherapy. Experience in a tertiary hospital]. / Monoterapia con darunavir/cobicistat. Experiencia en un hospital de tercer nivel.

OBJECTIVE: Ritonavir-boosted protease inhibitor (IP/r) monotherapy: darunavir/ritonavir (DRV/r) or lopinavir/ritonavir (LPV/r) monotherapy is only provided in the major treatment guidelines in pretreated patients to prevent toxicity associated with nucleoside/nucleotide reverse transcriptase inhibitor (NRTI), reduce costs and simplify antiretroviral treatment. To start IP/r monotherapy, according to GESIDA guidelines 2016, patients need to meet the following criteria: absence of chronic hepatitis B, plasma viral load <50 copies/ mL for at least 6 months and absence of protease inhibitors mutations or previous virologic failures to IP/r. Currently, there are no studies that evaluate the efficacy and safety of darunavir/cobicistat (DRV/COBI) monotherapy. METHODS: This prospective study analyzed pretreated HIV patients with DRV/r monotherapy that were switched to DRV/COBI monotherapy. The aim of the study is to describe the effectiveness and safety of the DRV/COBI monotherapy. RESULTS: Seventy-eight patients were evaluated. Patients had a median of 31.29 months of DRV/r monotherapy before DRV/COBI monotherapy. Nine of the 78 patients developed "blips" (plasma viral load: 50-200 copies/ml) and four patients had plasma viral load ≥200 copies/mL. An 83.3% (65/78) of the patients remained with undetectable plasma viral load. As for safety, there were no significant differences in lipid profile, liver function (transaminases) and renal function between DRV/r and DRV/COBI monotherapy. CONCLUSIONS: DRV/COBI monotherapy seems to be effective and safe (lipid profile, liver and kidney function). However, it will be necessary to design specific studies comparing DRV/r vs DRV/COBI monotherapy to confirm these results.

Oculocutaneous albinism types 1 and 3 are ER retention diseases: mutation of tyrosinase or Tyrp1 can affect the processing of both mutant and wild-type proteins.

Various types of oculocutaneous albinism (OCA) are associated with reduced pigmentation in the skin, hair, and eyes that results from mutations in genes involved in melanin synthesis. Immortal mouse melanocyte lines (melan-a, melan-b, and melan-c) provide opportune models with which to investigate the etiology of two different types of OCA (types I and III), which arise from mutations in Tyr and Tyrp1, respectively. We compared intracellular processing, sorting, and degradation of tyrosinase and Tyrp1, and the effects on their catalytic function and melanin synthesis, in these wild-type and mutant melanocytes. A mutation in either Tyr or Tyrp1 increased the time of association of tyrosinase and Tyrp1 with calnexin and Bip, which in turn resulted in the retention of these mutant products in the ER. A mutation in either gene selectively enhanced the duration and efficiency of chaperone interactions (even with the wild-type protein in the mutant melanocytes) and markedly slowed their transport to melanosomes. These results show that OCA1 and OCA3 are (in some cases, at least) ER retention diseases wherein a mutation in one melanogenic protein affects the maturation and stability of the other in the melanogenic pathway.

Distribution and mRNA expression of insulin-like growth factor system in pulmonary lymphangioleiomyomatosis.

BACKGROUND: Insulin-like growth factors (IGF-1 and IGF-2), the IGF-1 receptor (IGF-1R), and IGF-binding proteins (IGFBPs) are involved in normal pulmonary development and in the pathogenesis of smooth muscle cell tumors. METHODS: To evaluate the role of the IGF system in lymphangioleiomyomatosis (LAM), we used immunohistochemical and in situ hybridization techniques to characterize the expression of IGF-1, IGF-2, IGF-1R, and IGFBP-2, -4, -5, and -6 in lung tissue from 18 LAM patients. RESULTS: IGF-1, ICGF-2, IGF-1R, IGFBP-1, IGFBP-2, IGFBP-4, IGFBP-5, and IGFBP-6 were expressed by LAM cells. Reactivity and mRNA expression for IGF-2 were observed in LAM cells and resembled that found in normal smooth muscle cells during pulmonary development as well as in smooth muscle cell tumors. IGFBP-2, IGFBP-4, and IGFBP-6 were associated with spindle-shaped LAM cells, whereas IGFBP-5 was associated mainly with epithelioid LAM cells. CONCLUSIONS: These findings suggest that the IGFBPs modulate the effects of the IGFs on LAM cells. Thus, the patterns of localization and expression of components of the IGF system in LAM strongly suggest that these agents are involved in the proliferation of LAM cells.

Lymphangioleiomyomatosis (LAM): a review of clinical and morphological features.

A review is presented of the clinical and morphological manifestations of lymphangioleiomyomatosis (LAM), a systemic disorder of unknown etiology that affects women. The clinical features include dyspnea, hemoptysis, recurrent pneumothorax, chylothorax, and chylous ascites. It is characterized by: 1) proliferation of abnormal smooth muscle cells (LAM cells) in pulmonary interstitium and along the axial lymphatics of the thorax and abdomen; 2) thin-walled pulmonary cysts, and 3) a high incidence of angiomyolipomas. The pulmonary cystic lesions have a characteristic appearance on high resolution computed tomography. The most specific method for diagnosing LAM is lung biopsy to demonstrate the presence of LAM cells, either by their characteristic histological appearance or by specific immunostaining with HMB-45 antibody. LAM cells differ in several important respects from the types of smooth muscle cells normally present in lung. Their reactivity with HMB-45 antibody is localized in stage I and stage II melanosomes. LAM cells show additional evidence of incomplete melanogenesis, and the significance of these observations remains to be determined. Two types of LAM cells are recognized: 1) small, spindle-shaped cells that are centrally located in the LAM nodules and are highly immunoreactive for matrix metalloproteinase-2 (MMP-2), its activating enzyme (MT-1-MMP), and proliferating cell nuclear antigen (PCNA), and 2) large, epithelioid cells that are distributed along the periphery of the nodules and show a high degree of immunoreactivity with HMB-45 antibody and with antibodies against estrogen and progesterone receptors. Types of treatment used for LAM include oophorectomy, administration of Lupron or progesterone and in very severe cases, pulmonary transplantation (following the onset of respiratory insufficiency, not relieved by O(2)).