RESUMEN
OBJECTIVE: To evaluate the effectiveness of intraoperative and postoperative intermittent pneumatic compression (IPC) as a method used to decrease the incidence of deep venous thrombosis (DVT), in comparison to the standard use of graduated compression stockings, low-molecular weight heparin (LMWH) and physiotherapy during the hospital stay. All patients in this study underwent intracranial surgery for glioblastoma multiforme (GBM) using intraoperative magnetic resonance imaging (MRI) guidance. PATIENTS AND METHODS: We performed a single center retrospective study of a cohort of 153 patients who underwent surgery for GBM aided by intraoperative MRI from October of 2009 to January of 2015 at the International Neuroscience Institute (INI), Hannover, Germany. Out of all patients, 75 in comparison to 78 were operated with and without the additional use of IPC, respectively. Both groups received graduated compression stockings, LMWH and physiotherapy postoperatively as a basic thromboprophylaxis. Postoperatively the patients were screened for DVT by Doppler ultrasonography of the limbs and pulmonary embolism (PE) by CT-scan of the chest. RESULTS: DVTs were found in 6 patients with IPC and in 3 patients without IPC. The incidence of developing DVTs was therefore not significantly increased with the application of IPC from 3.9% to 8% (P-value: 0.33). No statistically significant differences were found in the probability of occurrence of pulmonary embolism (PE) with a reduction from 2.6% to 1.3% (P-value: 0.59). CONCLUSION: Our results demonstrate, that the surgical intervention and the subsequent patient immobilization, as well as the thromboprophylactic techniques used have a relatively low influence on the occurrence of thromboembolic complications than we expected. Our findings might be attributed to the overall low number of these complications in a glioblastoma multiforme patient population expected to be at a high risk for coagulopathy. In other words, in order to produce statistically significant results, we would need to increase the patient cohort. By doing so we may better detect a positive therapeutic effect. Alternatively, because of the multitude of possible complex risk-factors leading to coagulopathy in a glioblastoma patient population it might be the case that IPC has little or no effect and that there is a different underlying mechanism responsible for the observed coagulopathy.
Asunto(s)
Glioblastoma/tratamiento farmacológico , Aparatos de Compresión Neumática Intermitente , Complicaciones Posoperatorias/prevención & control , Embolia Pulmonar/cirugía , Trombosis de la Vena/cirugía , Adulto , Anciano , Femenino , Glioblastoma/complicaciones , Glioblastoma/diagnóstico por imagen , Heparina de Bajo-Peso-Molecular/farmacología , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de RiesgoRESUMEN
A 21-year-old male presented at the emergency room with jaundice, itching, dry cough, malaise and weight loss of 10 kg during the preceding four weeks. Eighteen months earlier, the patient had suffered an automobile accident leading to polytrauma. Serological markers for viral or other causes of hepatitis were absent. For suspected secondary sclerosing cholangitis, ultrasound and ERCP were performed but failed to reveal pathological findings. A liver biopsy showed cholestatic liver disease without signs of portal field-associated hepatitis. Hepato-biliary scintigraphy demonstrated hepatocellular dysfunction. The patient finally mentioned his guinea pig farm with around 50 animals, 20 of which had recently died for unknown reasons. The patient and three of his guinea pigs were subsequently tested for serological evidence of leptospirosis. IgG and IgM antibodies reacting with Leptospira interrogans were detected in the patient's serum, and all 3 guinea pigs were serologically positive for serovar Bratislava. Bacterial culture was not successful, and also PCR tests remained negative. The clinical symptoms quickly resolved after the initiation of antibiotic therapy with amoxicillin.
Asunto(s)
Enfermedades de los Trabajadores Agrícolas/diagnóstico , Crianza de Animales Domésticos , Ictericia Obstructiva/etiología , Leptospira interrogans , Leptospirosis/diagnóstico , Leptospirosis/veterinaria , Enfermedades de los Roedores/diagnóstico , Zoonosis/transmisión , Enfermedades de los Trabajadores Agrícolas/microbiología , Animales , Diagnóstico Diferencial , Cobayas , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Ictericia Obstructiva/diagnóstico , Ictericia Obstructiva/microbiología , Leptospira interrogans/inmunología , Masculino , Microbiología , Enfermedades de los Roedores/microbiología , Enfermedades de los Roedores/transmisión , Adulto Joven , Zoonosis/microbiologíaRESUMEN
Critical illness polyneuropathy (CIP) occurs in association with sepsis and multiple organ failure; however, little is known about the pathomechanisms of CIP and its therapy. In order to determine the parameters which interfere with development of CIP, electrophysiological investigations of peripheral nerves and biochemical measures were correlated to each other. The present study includes 20 consecutive patients in an intensive care unit developing severe sepsis or septic shock. Nerve conduction studies and electromyography were performed with occurring sepsis (day 1, 7, 14) and neurophysiological parameters were correlated with biochemical measures, especially indicators of infection and inflammation. It was found that all patients developed neurophysiological signs of axonal motor polyneuropathy. There was a significant correlation between serum concentrations of endotoxin and interleukin-2 receptors (IL2-R) and reduction of the amplitude of the compound motor action potentials. Other clinical and biochemical parameters showed no significant correlations with neurophysiological data. This finding apparently indicates that endotoxin damages nerve axons directly or indirectly, e.g. by activation of inflammatory cascades (IL2-R). Endotoxin appears to be an essential factor in the pathogenesis of CIP in sepsis, and therapeutic options neutralizing endotoxin may prevent development of CIP.
Asunto(s)
Enfermedad Crítica , Endotoxinas/toxicidad , Polineuropatías/etiología , Sepsis/complicaciones , Axones/patología , Estimulación Eléctrica , Electromiografía , Bacterias Gramnegativas/metabolismo , Humanos , Inflamación/patología , Neuronas Motoras/fisiología , Conducción Nerviosa/fisiología , Examen Neurológico , Neuronas Aferentes/fisiología , Nervios Periféricos/patología , Polineuropatías/patología , Receptores de Interleucina-2/efectos de los fármacos , Receptores de Interleucina-2/metabolismoRESUMEN
Muscle weakness is a common complaint in clinical practice. If this symptom is combined with focal liver lesions there is a broad spectrum of differential diagnoses for the gastroenterologist to consider. Tumors of neuroendocrine origin such as small-cell lung carcinoma (SCLC) produce a wide array of peptide hormones and are common causes of paraneoplastic syndromes. We report on a 68-year-old woman who presented with progressing muscle fatigue and multiple liver lesions on ultrasonography. Hypertension, hyperglycemia, hypokalemia and metabolic alkalosis prompted consideration of underlying hypercortisolism. Further work-up demonstrated an acute ectopic ACTH syndrome as paraneoplastic manifestation of a small cell lung carcinoma. The woman deteriorated rapidly and finally died from intracranial tumor spread and septic complications. This case stresses the diagnostic and therapeutic difficulties of acute ectopic ACTH syndrome in the setting of SCLC.
Asunto(s)
Síndrome de ACTH Ectópico/diagnóstico , Carcinoma de Células Pequeñas/secundario , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/diagnóstico , Debilidad Muscular/etiología , Síndromes Paraneoplásicos/diagnóstico , Tomografía Computarizada por Rayos X , Síndrome de ACTH Ectópico/patología , Anciano , Biopsia , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/terapia , Broncoscopía , Carcinoma de Células Pequeñas/diagnóstico , Carcinoma de Células Pequeñas/patología , Diagnóstico Diferencial , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patología , Pulmón/patología , Neoplasias Pulmonares/patología , Neoplasias Primarias Secundarias/diagnóstico , Neoplasias Primarias Secundarias/patología , Síndromes Paraneoplásicos/patologíaRESUMEN
The past few years have seen the advent of several new antifungal agents. The echinocandin, caspofungin, has greatly expanded the antifungal armamentarium by providing a cell wall-active agent with candidacidal activity as well as demonstrated clinical efficacy in the therapy of aspergillosis refractory to available therapy. In addition, in clinical trials, caspofungin exhibited efficacy comparable to amphotericin B for invasive and/or fluconazole-resistant Candida infections. According to a randomised trial, voriconazole has added a significantly improved therapeutic option for primary therapy of invasive aspergillosis. Additionally, voriconazole may be used successfully as salvage therapy for other fungal infections, i.e. cryptococcosis. Despite the advances offered by each of these drugs, the morbidity and mortality associated with invasive fungal infections remains high. Considering the adverse effects of the available antifungal agents and the considerable costs for their application, meaningful clinical trials for a precise indication in different clinical situations are urgently needed.
Asunto(s)
Antifúngicos/administración & dosificación , Micosis/tratamiento farmacológico , Micosis/mortalidad , Medición de Riesgo/métodos , Ensayos Clínicos como Asunto , Humanos , Guías de Práctica Clínica como Asunto , Pautas de la Práctica en Medicina , Factores de RiesgoRESUMEN
Between 20 and 70 percent of the 50 million people who travel from the industrialized world to the developing world each year report some illness associated with their travel. Approximately 3 percent of people traveling internationally for short periods (<2 weeks) report fever even after travel. Careful assessment of the travel history, likely incubation period, exposure history, associated signs and symptoms, duration of fever, immunization status use or nonuse of antimalarial chemoprophylaxis, and degree of compliance with a chemoprophylactic regimen, if used, helps to establish the diagnosis. Determining an approximate incubation period can be particular helpful in ruling out possible causes of fever. Specific examinations targeting the individual infection, assumed to be responsible for the development of febrile disease may ascertain diagnosis and lead to effective treatment.
Asunto(s)
Enfermedades Transmisibles/diagnóstico , Enfermedades Transmisibles/epidemiología , Transmisión de Enfermedad Infecciosa/prevención & control , Fiebre de Origen Desconocido/diagnóstico , Fiebre de Origen Desconocido/epidemiología , Anamnesis/métodos , Viaje/estadística & datos numéricos , Enfermedades Transmisibles/terapia , Países en Desarrollo/estadística & datos numéricos , Diagnóstico Diferencial , Brotes de Enfermedades/prevención & control , Fiebre de Origen Desconocido/terapia , Humanos , Manejo de Atención al Paciente/métodosRESUMEN
A symptomatic cytomegalovirus (CMV) infection usually occurs in patients with debilitating diseases, immunosuppression, transplantations and acquired immunodeficiency syndrome (AIDS). Gastrointestinal infections with CMV, especially colitis, are usually found in immunocompromised patients and rarely affect immunocompetent subjects. Here we report the case of a young female patient with a history of ulcerative colitis (UC) who presented with an acute attack of colitis caused by CMV infection. This was documented by the presence of CMV early antigen, antibodies and evidence of CMV in the colonic mucosa. After combined anti-inflammatory and antiviral treatment the patient recovered completely. As most attention is given to CMV-pathogeneity in immunocompromised patients, here we discuss the relationship to inflammatory bowel diseases.
Asunto(s)
Colitis Ulcerosa/complicaciones , Colitis/virología , Infecciones por Citomegalovirus/virología , Citomegalovirus/aislamiento & purificación , Enfermedad Aguda , Adulto , Anticuerpos Antivirales/sangre , Antivirales/uso terapéutico , Colitis/diagnóstico , Colitis/tratamiento farmacológico , Colitis Ulcerosa/diagnóstico , Colon/diagnóstico por imagen , Colon/patología , Citomegalovirus/inmunología , Infecciones por Citomegalovirus/diagnóstico , Infecciones por Citomegalovirus/tratamiento farmacológico , Femenino , Ganciclovir/uso terapéutico , Humanos , Inmunocompetencia , Resultado del Tratamiento , UltrasonografíaRESUMEN
A symptomatic cytomegalovirus (CMV) infection usually occurs in patients with debilitating diseases, immunosuppression, transplantations and acquired immunodeficiency syndrome (AIDS). Gastrointestinal infections with CMV, especially colitis, are usually found in immunocompromised patients and rarely affect immunocompetent subjects. Here we report the case of a young female patient with a history of ulcerative colitis (UC) who presented with an acute attack of colitis caused by CMV infection. This was documented by the presence of CMV early antigen, antibodies and evidence of CMV in the colonic mucosa. After combined anti-inflammatory and antiviral treatment the patient recovered completely. As most attention is given to CMV-pathogeneity in immunocompromised patients, here we discuss the relationship to inflammatory bowel diseases.
RESUMEN
Intestinal tuberculosis: Easier overlooked than diagnosed. The medical history of two Asian immigrants suffering from intestinal tuberculosis demonstrates the difficulties in finding the correct diagnosis. Intestinal tuberculosis resembles Crohn's disease with regard to clinical symptoms, macroscopic and microscopic intestinal findings. Sonographic, radiologic, endoscopic, and histological examinations facilitate distinguishing both entities. Diagnosis of intestinal tuberculosis is made by identification of the causative microorganism in tissue specimens. As this may be difficult and time-consuming, a therapeutic trial with anti-tuberculous agents may be warranted.
Asunto(s)
Tuberculosis Gastrointestinal/diagnóstico , Adulto , Antituberculosos/uso terapéutico , Colonoscopía , Terapia Combinada , Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/patología , Enfermedad de Crohn/cirugía , Diagnóstico Diferencial , Emigración e Inmigración , Femenino , Alemania , Humanos , Mucosa Intestinal/patología , Obstrucción Intestinal/diagnóstico , Obstrucción Intestinal/patología , Obstrucción Intestinal/cirugía , Sri Lanka/etnología , Tuberculosis Gastrointestinal/patología , Tuberculosis Gastrointestinal/cirugía , Tuberculosis Pulmonar/diagnóstico , Tuberculosis Pulmonar/patología , Tuberculosis Pulmonar/cirugía , Vietnam/etnologíaAsunto(s)
Infecciones Oportunistas Relacionadas con el SIDA/microbiología , Bacteriemia/microbiología , Infecciones por VIH/complicaciones , Infecciones por Helicobacter/diagnóstico , Helicobacter/aislamiento & purificación , Naranja de Acridina , Adulto , Diarrea/etiología , Diarrea/microbiología , Fiebre/etiología , Fiebre/microbiología , Helicobacter/genética , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/microbiología , Humanos , Masculino , ARN Ribosómico 16S/análisisRESUMEN
BACKGROUND: We conducted a prospective study in patients with multiple injuries investigating the time course of trauma-related changes of systemic immunologic defense mechanisms. METHODS: Patients with multiple injuries with Injury Severity Scores of more than 20 were included if they survived for more than 4 days after injury. Further inclusion criteria were no local or systemic infection (pneumonia, sepsis, soft-tissue infection, acquired immunodeficiency syndrome, tuberculosis, etc.) at the time of injury and no history of liver disease, bowel disease, or abdominal surgery. Serum endotoxin levels were measured from peripheral venous blood, as were the immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies against lipid A and against the core polysaccharide of endotoxin (lipopolysaccharide [LPS]), during the course of intensive care management. Serial central venous levels of interleukin-6 were determined as a marker of the inflammatory response. RESULTS: The patients were grouped according to their survival, with the survivors belonging to group S (48 patients) and the nonsurvivors belonging to group N (16 patients). The time of death for the nonsurvivors was between days 10 and 32 after the initial trauma. Thirteen of these patients (81%) died of multiple organ failure between days 12 and 17, two died of head trauma, and one died of sepsis. In patients who died of multiple organ failure, a significantly lower production of the IgM and IgG antibodies (AB) against lipid A and LPS was found before death (lipid A IgM-AB, day 11: group N, 29 +/- 11 U/mL; group S, 106 +/- 16 U/mL; p = 0.008; lipid A IgG-AB, day 11: group N, 18 +/- 9 U/mL; group S, 57 +/- 18 U/mL; p = 0.007; LPS IgM-AB, day 11: group N, 36 +/- 14 U/mL; group S, 122 +/- 23 U/mL; p = 0.009; LPS IgG-AB, day 11: group N, 17 +/- 12 U/mL; group S, 56 +/- 19 U/mL; p = 0.03). Interleukin-6 levels were significantly increased in the nonsurvivors (day 1: group N, 1,095 +/- 112 pg/mL; group S, 393 +/- 67 U/L; p = 0.008). CONCLUSION: In patients who died of severe trauma and in whom the cause of death was multiple organ failure, a significantly lower production of antiendotoxin antibodies was measured shortly before death. An insufficient immune defense (dysergy) may be involved in the pathomechanisms leading to the development of organ dysfunction.
Asunto(s)
Anticuerpos/sangre , Interleucina-6/sangre , Lipopolisacáridos/inmunología , Insuficiencia Multiorgánica/etiología , Traumatismo Múltiple/inmunología , Adulto , Femenino , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Puntaje de Gravedad del Traumatismo , Lípido A/inmunología , Masculino , Insuficiencia Multiorgánica/inmunología , Insuficiencia Multiorgánica/mortalidad , Traumatismo Múltiple/sangre , Traumatismo Múltiple/complicaciones , Traumatismo Múltiple/mortalidad , Estudios Prospectivos , Tasa de SupervivenciaRESUMEN
A clinical phase II trial of postinfectional idiotype vaccination was performed in early stage HIV + volunteers. The mAb 13B8.2 is directed against the CDR3-homologous CD4/D1 region implicated in HIV-gp120 binding. We have previously shown that this mAb induces HIV-gp120 cross-reactive immunity. In addition, the mAb 13B8.2 was well tolerated in a clinical phase-Ia trial. In this phase-II trial, 158 patients with 350-500 CD4+ cells/microl blood were randomised to receive either 1.2 mg of alum-precipitated mAb 13B8.2 or placebo. The mAb was well tolerated evoking predominantly local side effects. Multivariant analysis of clinical study endpoints demonstrated a significant response in the verum group (intend-to-treat analysis). Titres of HIV-1 neutralisation in vitro were raised along with HIV/gp120 antigen binding titres. Our data indicate that patients treated with the idiotype vaccine will produce an augmented specific anti-viral immune response. The vaccine might thus have a positive impact on the course of HIV disease.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Antígenos CD4/inmunología , Infecciones por VIH/terapia , VIH-1 , Inmunoterapia Activa , Adolescente , Adulto , Anciano , Animales , Anticuerpos Antiidiotipos/efectos adversos , Anticuerpos Antiidiotipos/sangre , Anticuerpos Antiidiotipos/inmunología , Anticuerpos Antiidiotipos/uso terapéutico , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales/inmunología , Femenino , Anticuerpos Anti-VIH/sangre , Anticuerpos Anti-VIH/inmunología , Proteína p24 del Núcleo del VIH/sangre , Proteína gp120 de Envoltorio del VIH/inmunología , Infecciones por VIH/inmunología , Infecciones por VIH/virología , VIH-1/inmunología , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pruebas de Neutralización , Resultado del TratamientoRESUMEN
OBJECTIVES: Wasting is a major feature of advanced HIV infection. Enteral nutrition via percutaneous endoscopic gastrostomy (PEG) is a safe and efficient therapy in malnutrition, but limited experience exists in wasted HIV patients. Here we report on outcome and risk of PEG-feeding in HIV patients compared with HIV-seronegative patients and with HIV patients without PEG. METHODS: In 47 HIV-infected patients, PEG was placed because of wasting (n = 33), neurologic deficits (n = 11), or dysphagia (n = 3). Clinical, immunological, and nutritional data were compared with those of i) 15 HIV patients who refused PEG placement despite an appropriate indication, ii) 76 HIV patients without signs of malnutrition, and iii) 43 miscellaneous PEG patients. RESULTS: PEG was as safe in HIV-infected as in HIV-seronegative patients. PEG feeding resulted in significant increases of body weight (+3.3 +/- 3.6 kg, p < 0.001), serum albumin concentration (+4.5 +/- 7.2 g/L, p < 0.005), and total iron-binding capacity (+9.5 +/- 11.5 mumol/L, p < 0.001). Moreover, our data indicate that PEG feeding may improve survival in wasted AIDS patients. CONCLUSIONS: PEG feeding is safe and effective in the treatment of the AIDS wasting syndrome. Further prospective investigations are necessary to answer the question of whether treatment of wasting improves patient survival.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/terapia , Nutrición Enteral , Gastrostomía , Intubación Gastrointestinal , Trastornos Nutricionales/terapia , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Síndrome de Inmunodeficiencia Adquirida/mortalidad , Adulto , Estudios de Casos y Controles , Femenino , Gastrostomía/efectos adversos , Seronegatividad para VIH , Seropositividad para VIH , Servicios de Atención de Salud a Domicilio , Humanos , Intubación Gastrointestinal/efectos adversos , Masculino , Trastornos Nutricionales/etiología , Estudios Prospectivos , Factores de Riesgo , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
The aim of this study was to assess the efficacy of pentaglobin, a polyclonal polyvalent immunoglobulin containing IgG, IgM, and IgA, in therapy of septicotoxic diseases. Fifty-five patients with sepsis were divided into 2 perspective randomized groups. Group 1 (27 patients) were infused pentaglobin containing specific antibodies to bacterial endotoxin determinant. Immunoglobulin therapy was carried out during the first 3 days after the group was selected for study. In the other group (n = 28) no immunoglobulin therapy was carried out. During 6 weeks from the beginning of the study one patient out of 27 in group 1 (4%) died because of sepsis, whereas in group 2 nine patients died out of 28 (32%) (p < 0.01). A reliably higher titer of circulating endotoxins and a lower titer of antibodies to endotoxin determinant were revealed during the first 48 hours of experiment in the serum or plasma of patients who died in the course of the follow-up period, in comparison with the survivors.
Asunto(s)
Endotoxemia/terapia , Infecciones por Bacterias Gramnegativas/terapia , Inmunoglobulina A/administración & dosificación , Inmunoglobulina M/administración & dosificación , Inmunoglobulinas Intravenosas/administración & dosificación , Adulto , Endotoxemia/sangre , Endotoxemia/etiología , Endotoxemia/mortalidad , Endotoxinas/sangre , Infecciones por Bacterias Gramnegativas/sangre , Infecciones por Bacterias Gramnegativas/etiología , Infecciones por Bacterias Gramnegativas/mortalidad , Humanos , Persona de Mediana Edad , Análisis Multivariante , Selección de Paciente , Estudios Prospectivos , Factores de TiempoAsunto(s)
Infecciones por Actinomycetales/complicaciones , Infecciones por VIH/complicaciones , Neumonía Bacteriana/complicaciones , Rhodococcus equi/aislamiento & purificación , Infecciones por Actinomycetales/diagnóstico , Infecciones por Actinomycetales/tratamiento farmacológico , Infecciones por Actinomycetales/microbiología , Antibacterianos/uso terapéutico , Líquido del Lavado Bronquioalveolar/microbiología , Diagnóstico Diferencial , Humanos , Neumonía Bacteriana/diagnóstico , Neumonía Bacteriana/tratamiento farmacológico , Neumonía Bacteriana/microbiologíaRESUMEN
OBJECTIVE: Tumor necrosis factor alpha (TNF-alpha) is involved in the genesis of HIV-associated malnutrition. We performed an open-label trial on the effects of ketotifen, an in vitro inhibitor of TNF-alpha release from peripheral blood mononuclear cells (PBMCs), on the nutritional status and TNF-alpha release of HIV-infected subjects. PATIENTS: Six HIV-infected subjects received oral ketotifen 4 mg per day for 84 days and were followed up for an additional 70-day period. Body composition was measured by bioelectrical impedance analysis. TNF-alpha plasma levels, TNF-alpha release from PBMCs, and plasma concentration of soluble TNF receptors were measured repeatedly during the study and control period. RESULTS: During ketotifen intake, TNF-alpha release from stimulated PBMCs significantly decreased (68 vs 155 pg ml-1), but not TNF-alpha and soluble TNF receptor plasma concentrations. Subjects gained weight (+ 2.7 kg), whereas weight loss was observed after cessation of treatment (-1.6 kg). CONCLUSION: Ketotifen inhibits TNF-alpha release from stimulated PBMCs and might thus be useful in the management of HIV-associated malnutrition.
Asunto(s)
Síndrome de Emaciación por VIH/tratamiento farmacológico , Cetotifen/farmacología , Cetotifen/uso terapéutico , Leucocitos Mononucleares/efectos de los fármacos , Factor de Necrosis Tumoral alfa/metabolismo , Adulto , Peso Corporal , Femenino , Síndrome de Emaciación por VIH/sangre , Humanos , Leucocitos Mononucleares/metabolismo , Masculino , Persona de Mediana Edad , Mitógenos de Phytolacca americana/farmacología , Receptores del Factor de Necrosis Tumoral/metabolismoRESUMEN
A total of 158 women who either HIV-infected or under iatrogenic immunosuppression were examined regularly during a 4-year period to evaluate if certain vulvar neoplasms and cervical neoplasia have similar associated risk factors. Patients with CIN were matched prospectively with immunocompetent controls with CIN. Forty-eight cervical lesions were detected among patients, including 2 invasive carcinoma and 15 CIN-3 lesions, compared to 11 vulvar lesions, including 2 invasive carcinoma and 7 VIN-3 lesions. Women who have more than five life-time partners were more likely to have HPV-DNA positive cervical swabs and vulvar scrapes as well as cervical and/or vulvar neoplasia. Compared to 2.7% of controls 15.2% of patients with CIN had coexisting high-grade lesions of the vulva. With 1 exception all patients with vulvar neoplasia either suffered from symptomatic immunodeficiency or received immunosuppressive drugs for more than 10 years. Except for 1 VIN-3 lesions, all vulvar neoplasms were associated with HPV-DNA types 16, 31, and/or 33. Six of nine patients as well as the 2 controls with coexisting vulvar and cervical neoplasia had the same HPV-type associated with both lesions. All vulvar lesions were classified as either "warty" or "basaloid". In conclusion cervical and bowenoid/basaloid vulvar neoplasia seem to have a similar HPV-related genesis. Malfunction of the cellular immune response appears to be a cofactor in the genesis of HPV-associated neoplasia at both sites.
Asunto(s)
Condiloma Acuminado/virología , Huésped Inmunocomprometido , Neoplasias Basocelulares/virología , Papillomaviridae/aislamiento & purificación , Enfermedades del Cuello del Útero/virología , Neoplasias del Cuello Uterino/virología , Enfermedades de la Vulva/virología , Neoplasias de la Vulva/virología , Estudios de Casos y Controles , Sondas de ADN de HPV , Femenino , Humanos , Papillomaviridae/genética , Estudios Prospectivos , Displasia del Cuello del Útero/virologíaRESUMEN
Anti-idiotypic vaccination against HIV infection aims at inducing an anti-gp120 immune response through anti-CD4 Abs mimicking epitopes of the gp120 molecule. The mAb IOT4a induces anti-gp120 Abs in rabbits. This study investigates the presence of human serum Abs cross-reacting with anti-CD4 mAbs and gp120 during HIV infection and after parenteral vaccination with IOT4a. Ten HIV-infected volunteers without immunodeficiency were inoculated s.c. with 0.6, 1.2, or 2.4 mg IOT4a. Six booster injections followed until day 35. Sera from study patients, 80 HIV-positive, and 43 seronegative controls were examined by a panel of assays, including an ELISA using competition against biotinylated recombinant CD4, flow cytometry assaying inhibition of anti-CD4 mAbs and biotinylated gp120 binding to CD4-positive lymphocytes, and an IOT4a immunoblot. After vaccination, an increase in competitive binding activity, which was quantitative in ELISA and flow cytometry, was observed. In the ELISA, competition against biotin-CD4 was quantitatively quenched by preincubating sera with r-gp120 or anti-CD4 mAbs such as IOT4a and Leu3a. Naive sera or sera from blood donors had no such effect in the assays employed, while 5/80 HIV sera showed binding qualities similar to vaccinees. These results suggest that 1) CD4 internal-image Abs emerge in a small proportion of HIV-positive individuals, and 2) parenteral vaccination with mAb IOT4a can induce a gp120 cross-reacting immune response that inhibits gp120 binding to CD4.