RESUMEN
BACKGROUND: The outcome for patients with recurrent or progressive Ewing's sarcoma family of tumours (ESFT) is poor. High dose therapy (HDT) has been used for a number of years in an attempt to improve survival; however, evidence for the efficacy of this treatment remains limited. PATIENTS AND METHODS: Between 1992 and 2004, 33 patients with recurrent or progressive ESFT were treated with HDT with bone marrow (n=2), peripheral blood stem cell (n=30), or bone marrow and peripheral blood stem cell support (n=1), at a single institution. HDT was with busulphan and melphalan in 22 patients; melphalan and etoposide in seven patients, three with total body irradiation (TBI); melphalan in three patients (2 with TBI), and busulphan and cyclophosphamide in one patient. RESULTS: The 2 and 5 year event free survival was 42.5% (95% CI, 26-59%) and 38.2% (95% CI, 21-55%) respectively. There was one treatment related death from colitis, and grade 4 infection was observed in two patients. CONCLUSIONS: Long-term survival can be attained in patients with recurrent or refractory ESFT treated with HDT. However, this treatment is associated with severe toxicity. A need remains for prospective randomised clinical trials of HDT in this group of patients.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Óseas/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Sarcoma de Ewing/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Trasplante de Médula Ósea , Neoplasias Óseas/mortalidad , Neoplasias Óseas/terapia , Busulfano/administración & dosificación , Busulfano/efectos adversos , Terapia Combinada , Progresión de la Enfermedad , Etopósido/administración & dosificación , Etopósido/efectos adversos , Femenino , Trasplante de Células Madre Hematopoyéticas , Humanos , Masculino , Melfalán/administración & dosificación , Melfalán/efectos adversos , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/terapia , Sarcoma de Ewing/mortalidad , Sarcoma de Ewing/terapia , Resultado del TratamientoRESUMEN
PURPOSE: To examine the feasibility, tolerability, and toxicity of an intensified induction regimen (vincristine, ifosfamide, doxorubicin, and etoposide [VIDE]) in patients with newly diagnosed Ewing's family of tumors (EFT); to assess ability to maintain dose-intensity, and predictability of peripheral-blood stem cell mobilization. PATIENTS AND METHODS: Thirty patients were treated with vincristine 1.4 mg/m2 (maximum 2 mg) on day 1, doxorubicin 20 mg/m2, ifosfamide 3 g/m2 plus mesna and etoposide 150 mg/m2 on days 1 to 3. Cycles were given every 21 days for up to six cycles. RESULTS: One-hundred and seventy cycles of VIDE were given. The median treatment interval was 21 days (21 to 42) and nadir count: hemoglobin 8.3 (6.3 to 11.9), neutrophils 0.045 (0.0 to 2.1), and platelets 45 (3 to 343). There were 96 episodes of infection requiring hospitalization (56%). Growth factor support reduced infectious complications by 34%. Etoposide dose was reduced, or omitted, in 24% of cycles. Four patients did not complete six cycles due to unacceptable toxicity and one patient progressed on treatment. Twenty patients underwent peripheral-blood stem cell harvesting, 15 after cycle 3, and five after cycle 4. Median CD34+ yield was 4.6 x 106/kg per patient (1.8 to 14.5). Overall response to treatment, measured in 24 patients, was 88%. Seven of 11 patients undergoing surgery achieved greater than 90% necrosis of tumor (64%). CONCLUSION: VIDE is an effective induction regimen with substantial but acceptable toxicity that allows predictable mobilization of stem cells. Maintenance of dose-intensity is feasible in the majority of patients. Growth factors play a role in maintaining dose-intensity and reduce infectious complications.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Movilización de Célula Madre Hematopoyética , Sarcoma de Ewing/tratamiento farmacológico , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Niño , Doxorrubicina/administración & dosificación , Etopósido/administración & dosificación , Estudios de Factibilidad , Femenino , Humanos , Ifosfamida/administración & dosificación , Masculino , Mesna/administración & dosificación , Estadificación de Neoplasias , Resultado del Tratamiento , Vincristina/administración & dosificaciónRESUMEN
BACKGROUND: This pilot study was undertaken to assess the feasibility, toxicity and response to short-course multiagent chemotherapy followed by high-dose chemotherapy (HDC) in patients with poor prognosis osteosarcoma. PATIENTS AND METHODS: A total of 30 patients entered the study. Chemotherapy consisted of four blocks of multiagent chemotherapy administered sequentially over a short period in a dose-intensive manner. This therapy was followed by HDC which consisted of carboplatin at an AUC8 x 3 days, etoposide 400 mg/m(2) x 3 days and cyclophosphamide 60 mg/kg x 2 days. RESULTS: A total of 227 cycles of chemotherapy were administered. The main toxicity (for blocks 1-4) was haematological. There were two treatment-related deaths: one post HDC due to sepsis and one during surgery. High-dose chemotherapy was administered to 11 patients (10 with extremity tumours and only one with a pelvic tumour). Twenty-seven patients underwent surgery to the primary. Histological response was assessed in 23 patients. Seven patients (30%) had >90% necrosis. Eight patients underwent pulmonary metastatectomy. The median survival time for the whole group was 16 months. The 2- and 3-year survival rates were 50% and 21% for those with extremity tumours and 19% and 13% for those with axial skeletal tumours. CONCLUSIONS: Dose-intensive multiagent chemotherapy though feasible in the group of patients with extremity tumours did not significantly improve the treatment outcome compared with conventional relapse therapy. Inferior survival rates in the axial skeletal group are attributed to less intensive treatment and poor local tumour control.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/patología , Dosis Máxima Tolerada , Osteosarcoma/tratamiento farmacológico , Osteosarcoma/patología , Adolescente , Adulto , Biopsia con Aguja , Neoplasias Óseas/mortalidad , Niño , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Humanos , Ifosfamida/administración & dosificación , Ifosfamida/efectos adversos , Infusiones Intravenosas , Neoplasias Pulmonares/secundario , Neoplasias Pulmonares/cirugía , Masculino , Metotrexato/administración & dosificación , Metotrexato/efectos adversos , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Osteosarcoma/mortalidad , Osteosarcoma/secundario , Proyectos Piloto , Pronóstico , Medición de Riesgo , Muestreo , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
We describe a 11-year-old boy with acute myeloid leukaemia who presented with widespread bone disease. Spine X-rays revealed multiple crush fractures and there were multiple hot spots on the bone scan. The bone-mineral density was markedly reduced but there was no hypercalcaemia or hypercalcuria. Bone marrow aspirate revealed 98% blast cells and a balanced translocation between chromosomes 10 and 17 in seven of nine metaphases. Plasma interleukin-6 level before chemotherapy was high at 53 pg/ml. We postulate that the mechanism for bony destruction in this case was similar to that in the adult disease myeloma.
Asunto(s)
Enfermedades Óseas/etiología , Leucemia Mieloide Aguda/complicaciones , Densidad Ósea , Examen de la Médula Ósea , Niño , Humanos , Interleucina-6/sangre , Leucemia Mieloide Aguda/genética , MasculinoRESUMEN
Hepatitis C virus (HCV), a single-stranded ribonucleic acid virus identified in 1989, is estimated to have infected 1%-2% of the United States population. The incidence of HCV in patients requiring orthopedic surgery may be as high as 5%. Surgeons and operating room personnel are at risk for blood-borne diseases transmitted during surgery. The orthopedic surgeon must be aware of viral infection with this pathogen for the safety of the entire operating room team. Further, screening for HCV is routinely done when a patient donates autologous blood prior to elective surgery, and the orthopedic surgeon is often the first or only physician informed of a positive result. The surgeon should know how to interpret the result, advise the patient, and incorporate the diagnosis of HCV into the plan for the proposed surgery. We will review the natural history, transmission, evaluation of, and current treatment for infection with this blood-borne virus.
Asunto(s)
Hepatitis C/complicaciones , Enfermedades Musculoesqueléticas/complicaciones , Procedimientos Ortopédicos , Transfusión de Sangre Autóloga , Hepatitis C/transmisión , Hepatitis C Crónica/terapia , Humanos , Enfermedades Musculoesqueléticas/cirugíaRESUMEN
A 10-year-old girl with Rothmund-Thomson syndrome developed a fibular osteosarcoma. Standard chemotherapy produced intolerable toxicity, necessitating a modification of therapy. Initial DNA repair studies on skin fibroblasts were abnormal, but repeat studies failed to reproduce the defects.
Asunto(s)
Neoplasias Óseas/complicaciones , Peroné , Osteosarcoma/complicaciones , Síndrome Rothmund-Thomson/complicaciones , Neoplasias Óseas/diagnóstico por imagen , Reparación del ADN , Femenino , Peroné/diagnóstico por imagen , Humanos , Lactante , Osteosarcoma/diagnóstico por imagen , Radiografía , Síndrome Rothmund-Thomson/diagnóstico por imagenRESUMEN
Primary sclerosing cholangitis is considered to be an autoimmune disease of the liver in which there is an association with the HLA phenotypes B8 and DR3 and in which circulating autoantibodies occur. Abnormalities of immune regulation may be present but whether or not they are primary or acquired is not known. This report is of a patient with primary sclerosing cholangitis who was homozygous for HLA B8 DR3, had a circulating antinuclear antibody, and a defect in nonspecific suppressor T-cell activity despite glucocorticosteroid treatment. Nevertheless, family studies revealed no evidence of an immunoregulatory defect in first-degree relatives despite the presence of Raynaud's phenomenon and malignancy in two sisters.
Asunto(s)
Anticuerpos Antinucleares/inmunología , Colangitis Esclerosante/inmunología , Linfocitos T Reguladores/inmunología , Adulto , Colangitis Esclerosante/complicaciones , Colangitis Esclerosante/genética , Colitis Ulcerosa/complicaciones , Femenino , Antígeno HLA-B8/genética , Antígeno HLA-DR3/genética , Humanos , Masculino , LinajeRESUMEN
Some patients with autoimmune chronic active hepatitis as well as their disease-free first degree relatives show decreased suppressor cell activity of peripheral blood T lymphocytes. Studies were therefore undertaken in families ascertained by the presence of a single chronic active hepatitis patient to determine if this abnormality of immune regulation represents a genetic phenotype simply controlled by a gene or genes at a putative disease susceptibility locus and, further, if this locus showed linkage to either the HLA or the immunoglobulin constant region loci. In addition to determining circulating autoantibody status and genotyping for HLA and immunoglobulin allotypes, suppressor T cells were evaluated by surface markers and by determining their ability to suppress IgG secretion in vitro. The results suggest that immunoregulatory dysfunction in autoimmune chronic active hepatitis is a familial abnormality, but that this abnormality occurs independent of circulating autoantibody status and of the segregation of genes for HLA or immunoglobulin allotypes.
Asunto(s)
Enfermedades Autoinmunes/inmunología , Hepatitis Crónica/inmunología , Linfocitos T Reguladores/inmunología , Antígenos de Diferenciación , Antígenos de Diferenciación de Linfocitos T/análisis , Enfermedades Autoinmunes/genética , Antígenos HLA/genética , Hepatitis Crónica/genética , Humanos , Inmunoglobulina G/metabolismo , Leucocitos Mononucleares/inmunología , LinajeRESUMEN
The strategy of assigning a surrogate phenotype, defined as the presence of antinuclear and/or antismooth muscle antibodies to disease-free first degree relatives of index cases was used to search for a postulated disease susceptibility gene in autoimmune chronic active hepatitis. In addition to determining circulating autoantibody status, 10 patients, 51 first-degree relatives and 6 spouses of index chronic active hepatitis patients, each ascertained by the single patient, were genotyped for HLA (A, B and DR loci) and immunoglobulin allotype (G1m, G2m, G3m and A2m loci) haplotypes. Among the 10 chronic active hepatitis patients, 6 had HLA haplotypes B8 and DR3, and 3 of these patients had, in addition, the immunoglobulin allotype haplotype Gm a,x;g. Circulating autoantibodies defining the surrogate phenotype was found in 39% of the first-degree relatives. However, segregation analysis offered no support for either single autosomal dominant or recessive inheritance for the autoantibody-positive phenotype. Linkage between the postulated disease susceptibility locus and either the HLA (Chromosome 6) or immunoglobulin (Chromosome 14) locus was excluded by several analyses. Furthermore, logistic regression indicated that neither immunogenetic marker was statistically associated with autoantibody positively in these families. Therefore, despite the occurrence of autoantibody positivity in first-degree relatives of autoimmune chronic active hepatitis patients, we found no evidence that this trait has a simple genetic basis, or that it is an alternative manifestation of a postulated disease susceptibility gene for chronic active hepatitis.
Asunto(s)
Autoanticuerpos/análisis , Enfermedades Autoinmunes/genética , Antígenos HLA/análisis , Hepatitis Crónica/genética , Alotipos de Inmunoglobulinas/análisis , Anticuerpos Antinucleares/análisis , Enfermedades Autoinmunes/inmunología , Antígenos HLA-DR/análisis , Hepatitis Crónica/inmunología , Humanos , Músculo Liso/inmunología , LinajeRESUMEN
The effects upon esophageal motility of water at room temperature and 0 degrees C, taken as repeated small boluses and as 200-ml volumes swallowed as rapidly as possible, were compared before and after pretreatment with isosorbide denitrate 5 mg sublingually, in nine young healthy subjects and two patients with esophageal spasm. Iced water caused reduced strength, increased duration, and reduced velocity of distal esophageal contractions. It also reduced the force of lower esophageal sphincteric contraction, an effect that was more transient than that seen in the esophageal body, but it did not alter the magnitude of sphincteric relaxation. Esophageal responses in normal subjects with water at the two temperatures were not affected by isosorbide denitrate. The responses to iced water in the two patients with esophageal spasm were qualitatively similar to those in normal subjects. These findings indicate that cooling brings about a transient state of relative paralysis in the distal esophagus and lower esophageal sphincter. Taken in conjunction with other observations, they are consistent with the notion that cold-induced chest pain, whether in normal subjects or in patients with esophageal motor disorders, is related to esophageal distension.
Asunto(s)
Unión Esofagogástrica/fisiología , Esófago/fisiología , Hipotermia Inducida , Dinitrato de Isosorbide/farmacología , Adulto , Dolor en el Pecho/etiología , Electrocardiografía , Acalasia del Esófago/fisiopatología , Unión Esofagogástrica/efectos de los fármacos , Femenino , Humanos , Masculino , Peristaltismo/efectos de los fármacos , PresiónRESUMEN
HLA types, serum autoantibodies and serum globulin levels were surveyed in 46 patients with HBsAg-negative chronic active hepatitis. Patients with chronic active hepatitis with viral risk factors were less likely than those without viral risk factors to be HLA type B8 (10% vs 44%) or to have autoantibodies (antinuclear and/or anti-smooth muscle antibodies) (38% vs 84%). Thirty patients (10 with and 20 without viral risk factors) were treated with glucocorticosteroids. Of the 11 patients who were HLA-B8, 100% responded to treatment. Of the 20 patients who were ANA positive, 80% responded. The data suggest that the presence of HLA-B8 may be a useful predictor of response to anti-inflammatory treatment and may define a genetic subset of HBsAg-negative chronic active hepatitis that will benefit from glucocorticosteroid therapy.
Asunto(s)
Autoanticuerpos/análisis , Antígenos HLA/análisis , Antígenos de Superficie de la Hepatitis B/inmunología , Hepatitis/inmunología , Adulto , Enfermedad Crónica/inmunología , Estudios de Evaluación como Asunto , Femenino , Glucocorticoides/uso terapéutico , Antígenos HLA/inmunología , Antígeno HLA-B8 , Hepatitis/tratamiento farmacológico , Prueba de Histocompatibilidad , Humanos , Pruebas Inmunológicas , Masculino , Persona de Mediana EdadRESUMEN
Peripheral blood lymphocytes from patients with primary biliary cirrhosis previously have been reported to demonstrate reduced pokeweed mitogen-stimulated immunoglobulin synthesis and diminished function of suppressor T cells. To determine whether thymic hormone preparations reverse these immunologic defects in vitro, the effects of thymosin fraction 5 and thymosin alpha 1 on immunoglobulin synthesis and concanavalin A-induced suppression of immunoglobulin synthesis were investigated in normal subjects and patients with primary biliary cirrhosis. In normal subjects, no effects of thymosin were observed on unstimulated and pokeweed mitogen-stimulated immunoglobulin synthesis, nor on Con A-induced suppressor cell activity. Lymphocytes from patients with PBC synthesized less IgG and IgM than normals when stimulated by pokeweed mitogen, and this difference was enhanced by both thymosin fraction 5 and thymosin alpha 1. Con A suppression of immunoglobulin synthesis was abnormal in only one PBC subject so that thymosin effects on impaired suppressor T cell activity could not be tested.
Asunto(s)
Inmunoglobulina G/biosíntesis , Inmunoglobulina M/biosíntesis , Cirrosis Hepática Biliar/inmunología , Linfocitos T Reguladores/efectos de los fármacos , Timosina/análogos & derivados , Adulto , Anciano , Células Cultivadas , Concanavalina A/antagonistas & inhibidores , Concanavalina A/inmunología , Femenino , Humanos , Cirrosis Hepática Biliar/metabolismo , Linfocitos/efectos de los fármacos , Masculino , Persona de Mediana Edad , Mitógenos de Phytolacca americana/inmunología , Linfocitos T Reguladores/metabolismo , Timalfasina , Timosina/farmacologíaRESUMEN
Postero-anterior and lateral chest radiographs of patients undergoing endoscopic injection sclerotherapy of esophageal varices were reviewed. Radiographs were obtained prior to and within 48 hours of treatment. Following sclerotherapy, pleural effusions and densities were commonly seen at the azygoesophageal reflection and the posterior wall of the bronchus intermedius; however, on follow-up they had resolved. Most patients were asymptomatic, and morbidity was low. These findings suggest that inflammation developing after endoscopic injection sclerotherapy extends beyond the esophageal wall into the mediastinum and pleural space.
Asunto(s)
Várices Esofágicas y Gástricas/terapia , Mediastinitis/inducido químicamente , Derrame Pleural , Soluciones Esclerosantes/uso terapéutico , Adulto , Anciano , Endoscopía , Femenino , Hemorragia Gastrointestinal/terapia , Humanos , Masculino , Mediastinitis/diagnóstico por imagen , Persona de Mediana Edad , Radiografía , Soluciones Esclerosantes/efectos adversosRESUMEN
In this study a perfusion technique has been used to investigate in vivo jejunal absorption and transmural potential difference evoked by the neutral amino acids phenylalanine (56 or 20 mmol/l) and glycine (20 mmol/l), the dibasic amino acid lysine (56 or 5 mmol/l), and a dipeptide glycyl-l-phenylalanine (20 mmol/l) in 11 children with pancreatic insufficiency due to cystic fibrosis and in three children with other causes of exocrine pancreatic insufficiency. Net absorption and potential difference evoked by phenylalanine in both cystic fibrosis and pancreatic insufficiency, and net absorption of glycine in cystic fibrosis were significantly reduced; but the absorption of lysine and glycyl-l-phenylalanine was normal. Absorption of the constituent amino acids from the dipeptide was normal or increased in cystic fibrosis. Thus, these studies show a defect in active absorption of neutral amino acids in cystic fibrosis with pancreatic insufficiency and exocrine pancreatic insufficiency. We speculate that pancreatic factors participate in neutral amino acid absorption.
Asunto(s)
Aminoácidos/metabolismo , Dipéptidos/metabolismo , Absorción Intestinal , Intestino Delgado/metabolismo , Enfermedades Pancreáticas/metabolismo , Niño , Preescolar , Humanos , Lactante , Lisina/metabolismo , Fenilalanina/metabolismo , Tirosina/metabolismoRESUMEN
Three children aged between 7 and 11 years, after an acute onset of diarrhoea and vomiting, developed protracted diarrhoea and severe loss of weight. None had been abroad. No significant aetiological agent was found. There was evidence of acute inflammatory disease on proximal small intestinal biopsy, and some evidence of more widespread gut involvement--of the rectum in Cases 1 and 2, and the terminal ileum in Cases 2 and 3. The disease resolved spontaneously and without relapse.
Asunto(s)
Enteritis/diagnóstico , Enfermedad Aguda , Peso Corporal , Niño , Diarrea/etiología , Humanos , Masculino , Remisión EspontáneaRESUMEN
Nine children with sucrase-isomaltase deficiency were assessed up to 10 years after diagnosis. All children continued to have episodes of diarrhoea associated with sucrose ingestion. Sucrose tolerance tests showed that malabsorption of sucrose persists into adolescence. Three older patients were unaware of their condition and were eating normal diets with unrestricted amounts of sucrose. They complained of gastrointestinal symptoms which improved after sucrose restriction.
Asunto(s)
Complejos Multienzimáticos/deficiencia , Complejo Sacarasa-Isomaltasa/deficiencia , Preescolar , Diarrea Infantil/etiología , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Sacarosa/metabolismoRESUMEN
Serial small intestinal biopsies related to withdrawal and challenge with cows' milk are described in 5 infants with cows' milk protein intolerenace. On the basis of these serial observations the existence of a cows' milk-sensitive enteropathy in infancy is clearly established. The cows' milk-sensitive mucosal lesion varied in its severity ranging from a partly flat mucosa to a mild degree of partial villous atrophy. Intraepithelial lymphocyte counts rose after a positive milk challenge, but on only one occasion to a level outside the normal range. The technique of serial biopsies related to dietary milk enables a firm diagnosis of cows' milk intolerance to be made upon the basis of a single milk challenge. Clinically this appears to be a temporary condition which disappears by the age of 2 years.
Asunto(s)
Diarrea Infantil/inducido químicamente , Síndromes de Malabsorción/inducido químicamente , Proteínas de la Leche/efectos adversos , Animales , Biopsia , Bovinos , Diarrea Infantil/diagnóstico , Diarrea Infantil/patología , Disacaridasas/metabolismo , Femenino , Humanos , Lactante , Recién Nacido , Mucosa Intestinal/patología , Recuento de Leucocitos , Linfocitos/patología , Síndromes de Malabsorción/diagnóstico , Síndromes de Malabsorción/patología , MasculinoRESUMEN
The aerobic and anaerobic bacterial flora of the duodenum were studied in 10 infants with transient monosaccharide intolerance. 5 infants had protracted diarrhoea after an episode of acute gastroenteritis and 5 had acute gastroenteritis. The duration of monosaccharide intolerance ranged from 1 to 20 days. Serial intubations were performed on 8 infants. In 5 of 8 cases the bacterial flora were of a normal type at the first intubation at 0--4 days after the onset of monosaccharide intolerance. In 4 of those 5 patients there was an increase in bacterial count a few days later and anaerobes appeared. These findings are not consistent with the suggestion that monosaccharide intolerance is caused by abnormal bacteria in the upper small bowel.
Asunto(s)
Duodeno/microbiología , Síndromes de Malabsorción/microbiología , Monosacáridos/metabolismo , Bacterias/aislamiento & purificación , Diarrea/complicaciones , Duodeno/metabolismo , Femenino , Gastroenteritis/complicaciones , Humanos , Lactante , Síndromes de Malabsorción/complicaciones , MasculinoRESUMEN
Twenty-five children with cows' milk protein intolerance were studied. Twenty had presented with an illness clinically indistinguishable from infantile gastroenteritis; an enteropathogenic Escherichia coli was isolated from the stools in two children, and in six another member of the family simultaneously developed acute diarrhoea and vomiting. Twenty-three children had lactose intolerance secondary to cows' milk protein intolerance. Eight out of 20 children were found to be partially IgA deficient. An acute attack of gastroenteritis, in damaging the small mucosa, may act as a triggering mechanism in cows' milk protein intolerance, and a deficiency in IgA may be a predisposing factor in so far as it allows the patient to become sensitised to foreign protein.