Quality Standards for Allergen Immunotherapy Clinics in Spain: Consensus Document.

BACKGROUND AND OBJECTIVE: Allergen immunotherapy clinics (AITCs) in Spain differ widely in terms of structure, organization, resources, and portfolio of services. Therefore, it is essential to unify treatment criteria and define quality standards for the most complex AITCs. Objective: To establish a series of recommendations that make it possible to guarantee quality and safety in the administration of immunotherapy and define quality standards for the most complex AITCs. METHODS: This project began with an online survey of 65 allergy departments/units throughout Spain in 2013. Next, a 2-phase consensus process was carried out. In the first phase, 10 experts defined and agreed on the standards using the RAND/UCLA Appropriateness method; in the second, the agreements were validated by means of a 2-round Delphi consultation with 84 experts. RESULTS: Consensus was reached on minimum safety and quality criteria in the administration of allergen immunotherapy, and 2 levels of highly complex AITCs were defined: accredited AITCs and accredited AITCs with excellence. Consensus was also reached on quality standards and accreditation criteria for both levels. CONCLUSIONS: This project is pioneering in terms of its purpose (the definition of quality standards for AITCs) and of the use of structured participation techniques (combination of the RAND/UCLA and Delphi methods). It enabled the design of minimum standards for quality and safety in administering AIT, as well as quality criteria for accreditation of AITCs supported by a broad panel of experts from the Spanish Society of Allergology and Clinical Immunology.

Perceived efficacy and satisfaction of patients with subcutaneous hypoallergenic high-dose house dust mite extract.

SUMMARY: The efficacy and safety of subcutaneous immunotherapy with modified, high-dose, major allergen house dust mite extract is widely supported by double-blind, placebo-controlled studies. However, little is known regarding patient-perceived efficacy and satisfaction. An observational, retrospective, multicentre study in patients treated with Acaroid® was conducted to assess the efficacy and degree of satisfaction of the patients after the first six months of treatment with it. All the clinical study procedures were performed according to the routine clinical practice. This study demonstrates that Acaroid® is effective and well tolerated. The patients' condition demonstrated a clear and marked improvement in the first 6 months after treatment initiation. Patients treated with Acaroid® were very satisfied, with a correlation to improvement in patient-perceived symptoms and the administration of treatment by a healthcare professional.

Phase II trial of preoperative chemoradiotherapy with oxaliplatin, cisplatin, and 5-FU in locally advanced esophageal and gastric cancer.

BACKGROUND: Based on a phase I study showing the feasibility of combining of oxaliplatin, cisplatin, and 5-fluorouracil (5-FU) (OCF) with radiation therapy (RT) in esophageal cancer, the efficacy of this regimen in esophageal, gastroesophageal (GE), and gastric (G) cancer was assessed in this phase II multicenter study. PATIENTS AND METHODS: Patients with resectable tumors were eligible. Treatment included two cycles of oxaliplatin 85 mg/m(2), cisplatin 55 mg/m(2), and continuously infused 5-FU 3 g/m(2) in 96 h and concurrent RT (45 Gy), followed by surgery after 6-8 weeks. Primary end point was complete pathologic response (pCR). RESULTS: Forty-one patients were enrolled. Tumor location was esophagus 39% (squamous 10/adenocarcinoma 6), GE junction 32%, and stomach 29%. G3-G4 adverse events included asthenia (27%) and neutropenia (14%). One toxic death occurred. Thirty-one patients (75.6%) underwent surgery (R0 in 94%). Pathologic response was achieved in 58% of patients, with pCR in 50% and 16% of esophageal and GE/G cancer, respectively. pCR was achieved in 67% of squamous cell carcinoma. Survival: median follow-up, 50.4 months; median progression-free survival and overall survival were 23.2 and 28.4 months, respectively. CONCLUSION: Preoperative OCF plus RT showed an acceptable toxicity and promising activity especially in squamous cell esophageal cancer.

Quantitative assessments of late radiation-induced skin and soft tissue toxicity and correlation with RTOG scales and biological equivalent dose in breast cancer.

PURPOSE: Radiation-induced toxicity (RIT) is usually assessed by inspection and palpation. Due to their subjective and unquantitative nature, objective methods are required. This study aimed to determine whether a quantitative tool is able to assess RIT and establish an underlying BED-response relationship in breast cancer. METHODS: Patients following seven different breast radiation protocols were recruited to this study for RIT assessment with qualitative and quantitative examination. The biologically equivalent dose (BED) was used to directly compare different radiation regimens. RIT was subjectively evaluated by physicians using the Radiation Therapy Oncology Group (RTOG) late toxicity scores. Simultaneously an objective multiprobe device was also used to quantitatively assess late RIT in terms of erythema, hyperpigmentation, elasticity and skin hydration. RESULTS: In 194 patients, in terms of the objective measurements, treated breasts showed higher erythema and hyperpigmentation and lower elasticity and hydration than untreated breasts (p < 0.001, p < 0.001, p < 0.001, p = 0.019, respectively). As the BED increased, Δerythema and Δpigmentation gradually increased as well (p = 0.006 and p = 0.002, respectively). Regarding the clinical assessment, the increase in BED resulted in a higher RTOG toxicity grade (p < 0.001). Quantitative assessments were consistent with RTOG scores. As the RTOG toxicity grade increased, the erythema and pigmentation values increased, and the elasticity index decreased (p < 0.001, p = 0.016, p = 0.005, respectively). CONCLUSIONS: The multiprobe device can be a sensitive and simple tool for research purpose and quantitatively assessing RIT in patients undergoing radiotherapy for breast cancer. Physician-assessed toxicity scores and objective measurements revealed that the BED was positively associated with the severity of RIT.

Effects of radiation on toxicity, complications, revision surgery and aesthetic outcomes in breast reconstruction: An argument about timing and techniques.

BACKGROUND: Radiotherapy (RT) combined with breast reconstruction can reduce the risk of cancer recurrence and increase the survival rate. However, this approach seems to worsen aesthetic outcomes and increase complication rates. The impact of breast reconstruction timing and techniques on clinical outcomes, however, remains unclear. For this reason, we aimed to perform a more comprehensive analysis of a series of patients undergoing RT and breast reconstruction. METHODS: Patients were divided into 4 groups according to the timing of reconstruction (before RT and after RT) and surgical technique (heterologous reconstruction and autologous reconstruction (AR)). The median time between RT and reconstruction, number of revision surgeries, incidence of complications, toxicity, aesthetics and associated clinical risk factors were used to assess the clinical outcomes. An objective system of skin toxicity evaluation was performed. RESULTS: Ninety-five patients were included in this study. No significant differences in the median time between RT and reconstruction, incidence of complications, toxicity or aesthetics were noted between different timings or techniques of reconstruction. Patients undergoing AR needed more revision surgeries to complete reconstruction. However, the total number of surgical procedures was similar between the groups. In a comparison between the treated and untreated breasts by an objective system, RT produced an increase in erythema and pigmentation and a decrease in elasticity in the treated breast (p<0.05 for all parameters). On multivariate analysis, smoking was a significant predictor associated with complications. CONCLUSIONS: Combined breast reconstruction and RT seem to be successful regardless of the order of treatment or the type of reconstruction.

Long-term results of a randomized partial irradiation trial compared to whole breast irradiation in the early stage and low-risk breast cancer patients after conservative surgery.

PURPOSE: To report long-term results of a randomized trial comparing accelerated partial breast irradiation (APBI) to whole-breast irradiation (WBI) in terms of efficacy, toxicity, and cosmesis. METHODS AND MATERIALS: WBI group was treated with 3D conformal external irradiation, 2 Gy daily/fraction, 5 fractions/week, to a total dose of 50 Gy. APBI group was treated with 3D conformal external irradiation 3.75 Gy/fraction, twice a day, 5 fractions/week, to a total dose of 37.5 Gy in the APBI group. Patients were followed up every 6 months up to 5 years and yearly thereafter. During follow-up visits, the clinician evaluated chronic toxicity and scored cosmetic results with a four-scale system. RESULTS: After a median follow-up of 10.3 years, 43 patients in each group (84%) are alive without disease. One patient died after disease progression in the APBI arm, and there was no death in the WBI arm. The rest of the patients died from another disease different than breast cancer, similarly between groups. There was greater fibrosis in the APBI group (9 patients grade 1 and one grade 2) compared to WBI (3 patients grade 1 and one grade 2); p = 0.18. Regarding cosmesis, in APBI group, 19 and 21 (43.2 and 47%) patients had excellent or good results, similar to the WBI group with 18 patients (40.9%) in each cosmesis outcome. The WBI group did not have any patient with poor cosmesis but the APBI had 3 (6.8%; p = 0.24). CONCLUSION: After a follow-up of 10 years, there were no differences in efficacy between the 2 treatment arms. Despite slight greater toxicity in the APBI group, the cosmesis was similar and satisfactory in both groups.

Weekly radiotherapy in elderly breast cancer patients: a comparison between two hypofractionation schedules.

PURPOSE: Weekly irradiation in breast cancer in elderly patients is a treatment option, whose tolerance may be influenced by the fractionation used. The objective of this study is to compare the tolerance and long-term side effects of two different fractionations. MATERIALS AND METHODS: 47 elderly patients were recruited after conservative or radical treatment that also received irradiation with a dose per fraction of 6.25 Gy or 5 Gy for one session per week, 6 sessions in total. The long-term tolerance results are compared by assessing toxicity using CTCAE version 5.0 scales for dermatitis, telangectasia, fibrosis and pain of the irradiated breast. In addition, objective parameters of skin status (erythema, hyperpigmentation, elasticity and hydration) by a multi-probe MultiSkin Test-Center system were obtained and compared between groups. RESULTS: After an average follow-up of 5 years, all patients were free of disease and with complete local control. A total of 20 patients with 6.25 Gy fractionation and 27 patients with 5 Gy fractionation have been included. Patients treated with lower fractionation had a lower incidence of dermatitis, telangectasia, fibrosis, or local pain. The decrease in elasticity measured by the multi-probe system was smaller with the fractionation of 5 Gy. No differences were observed in the other objective parameters. CONCLUSION: Weekly irradiation with 5 Gy fractionation is better tolerated than with higher fractionation.

Lineage tracing and resulting phenotype of haemopoietic-derived cells in the pancreas during beta cell regeneration.

AIMS: Transplantation of bone marrow-derived haemopoietic stem cells following streptozotocin (STZ) treatment to induce pancreatic beta cell loss in mice causes the partial regeneration of beta cell mass, with many haemopoietic cells demonstrating endothelial cell markers. This study used genetically tagged haemopoietic lineage-derived cells to determine how endogenous cells are mobilised following beta cell loss and subsequent replacement. METHODS: A double transgenic mouse model, Vav-iCre; R26R-enhanced yellow fluorescent protein (YFP), was used where only haemopoietic lineage cells expressed the Vav1 gene promoter allowing expression of the YFP reporter gene. Between postnatal days 2 and 4 mice were injected with STZ or vehicle (control) and body weight and glycaemia were monitored. Mice were killed between days 10 and 130, and the pancreases were examined by immunofluorescence microscopy. RESULTS: YFP-expressing cells infiltrated the pancreas at all ages, being present around newly forming islets at the pancreatic ducts, and within larger islets. Small numbers of YFP-positive cells (<5%) co-stained for the macrophage markers F4/80 or Mac1, for cytokeratin 19, or for the transcription factor pancreatic and duodenal homeobox 1 (PDX-1), but no co-localisation was seen with insulin or other endocrine hormones. Within islets approximately 30% of YFP-positive cells co-stained for the endothelial cell marker CD31, and following STZ the number of haemopoietic-derived cells, and the proportion that were CD31-positive, both significantly increased after 21 and 40 days, coincident with a partial replacement of beta cells. CONCLUSIONS: Our results suggest that following beta cell loss endogenous haemopoietic-lineage cells contribute to intra-islet angiogenesis, which supports a partial recovery of beta cell mass.

Accelerated hypofractionated radiation therapy (AHRT) for non-small-cell lung cancer: can we leave standard fractionation?

PURPOSE: To report interim results from a single-institution study conducted to assess accelerated hypofractionated radiotherapy (AHRT) delivered with 3D conformal radiotherapy in two groups of patients with non-small cell lung cancer: (1) patients with early stage disease unable to tolerate surgery and ineligible for stereotactic body radiation therapy, and (2) patients with locally advanced disease unsuitable for concurrent chemoradiotherapy. METHODS/PATIENTS: A total of 83 patients (51 stage I-II, 32 stage III) were included. Radiotherapy targets included the primary tumor and positive mediastinal areas identified on the pre-treatment PET-CT. Mean age was 77.8 ± 7.8 years. ECOG performance status (PS) was ≥2 in 50.6 % of cases. Radiotherapy was delivered in daily fractions of 2.75 Gy to a total dose of 66 Gy (BED10 84 Gy). Acute and late toxicities were evaluated according to NCI CTC criteria. RESULTS: At a median follow-up of 42 months, median overall survival (OS) and cause-specific survival (CSS) were 23 and 36 months, respectively. On the multivariate analysis, PS [HR 4.14, p = 0.0001)], stage [HR 2.51, p = 0.005)], and maximum standardized uptake values (SUVmax) [HR 1.04, p = 0.04)] were independent risk factors for OS. PS [HR 5.2, p = 0.0001)] and stage [HR 6.3, p = 0.0001)] were also associated with CSS. No cases of severe acute or late treatment-related toxicities were observed. CONCLUSIONS: OS and CSS rates in patients treated with AHRT for stage I-II and stage III NSCLC were good. Treatment was well tolerated with no grade three or higher treatment-related toxicity. PS, stage, and SUV max were predictive for OS and CSS.

Hypofractionated boost after whole breast irradiation in breast carcinoma: chronic toxicity results and cosmesis.

PURPOSE: To evaluate the impact of hypofractionated boost after hypofractionated whole breast irradiation in breast carcinoma. METHODS AND MATERIALS: Patients after breast conservative surgery were treated all time with hypofractionation of 2.67 Gy/day. Whole breast dose was 40.05 Gy followed in case of risk of local relapse by a boost of 16.02 Gy or 8.01 Gy. Acute and chronic toxicity results were evaluated including cosmetic software-assisted assessment and objective evaluation of fibrosis parameters (elasticity and hydration) by means of a skin tester. RESULTS: A total of 362 patients were evaluated. Acute toxicities comprised grade 1 dermatitis in 48.1 %, grade 2 in 44.5 % and grade 3 in 17 patients 4.7 %, respectively. After a median follow-up of 4.5 years, in 308 cases (86.6 %) there was no chronic skin or subcutaneous changes. In the first consecutive 50 patients, measures with skin tester showed no statistical differences in parameters for skin and subcutaneous fibrosis. Cosmetic results were considered excellent and good in 26 and 62 %, respectively. CONCLUSIONS: Boost to tumour bed with hypofractionated doses is well tolerated and acute and chronic toxicities are mild with good cosmetic results. Objective systems are encouraging methods to assess skin quality and cosmesis.

Influence of incidental radiation dose in the subventricular zone on survival in patients with glioblastoma multiforme treated with surgery, radiotherapy, and temozolomide.

PURPOSE: To determine if there is an association between the incidental radiation dose to the subventricular zone and survival in patients with glioblastoma multiforme treated with surgery, radiotherapy and temozolomide. METHODS AND MATERIALS: Sixty-five patients, treated between 2006 and 2015, were included in this retrospective study. The doses (75th percentile; p75) administered to the ipsilateral, contralateral and bilateral subventricular zone were compared to overall survival and progression-free survival using Cox proportional hazards models. Covariates included: age, sex, surgery, tumor location, and concomitant and adjuvant temozolomide. RESULTS: Median progression-free survival and overall survival were 11.5 ± 9.96 and 18.8 ± 18.5 months, respectively. The p75 doses to the ipsilateral, contralateral and bilateral subventrivular zone were, respectively, 57.30, 48.8, and 52.7 Gy. Patients who received a dose ≥48.8 Gy in the contralateral subventricular zone had better progression-free survival than those who received lower doses (HR 0.46; 95% CI 0.23-0.91 P = 0.028). This association was not found for overall survival (HR 0.60; 95% CI 0.30-1.22 P = 0.16). Administration of adjuvant temozolomide was significantly associated with improved progression-free survival (HR 0.19; 95% CI 0.09-0.41 P < 0.0001) and overall survival (HR 0.11; 95% CI 0.05-0.24 P = 0.001). In the subgroup of 46 patients whose O6-methylguanine-DNA methyltransferase gene promoter status was known, the methylation had no effect on either progression-free survival (P = 0.491) or overall survival (P = 0.203). CONCLUSION: High-dose radiation in the contralateral subventricular zone was associated with a significant improvement in progression-free survival but not overall survival in patients treated for glioblastoma multiforme.

Alterations in intracellular messengers mobilized by gonadotropin-releasing hormone in an experimental ovarian tumor.

Cells derived from an experimental luteinized ovarian tumor are more sensitive to GnRH endocrine action than control luteal cells. In an attempt to understand the possible causes of the differential sensibility to GnRH action, we examined the number and affinity of GnRH receptors and the second messenger response to GnRH stimulation in both tissues. For GnRH receptor studies membranes were obtained from 4- to 6-week-old ovarian tumors (luteoma) and ovaries from prepubertal rats treated with 25 IU PMSG and 25 IU hCG (SPO) and were incubated with [125I]Buserelin. The number of GnRH receptors were increased in luteoma compared with that in SPO ovaries; dissociation constants were similar in both tissues. GnRH stimulation of second messenger release was assessed in cells obtained from luteoma and SPO ovaries by collagenase treatment. Buserelin (100 ng/ml) induced a significant 35% calcium increase in SPO cells, as determined by the fura-2 method; in luteoma cells no response was observed after buserelin stimulation, although a calcium transient was induced by thapsigargin (0.5 microM), an inhibitor of Ca2+-adenosine triphosphatase associated with the endoplasmic reticulum. The effect of buserelin on inositol phosphates was evaluated after incubation of luteoma and SPO cells with [3H]myoinositol for 48 h. Buserelin induced a 400% increase in inositol trisphosphate in SPO cells. Again, luteoma cells did not respond to buserelin stimulation, although NaF (10 mM), an activator of G proteins coupled to phospholipase C, induced an 800% increase in inositol trisphosphate. Although the number of GnRH receptors is augmented in luteoma cells, justifying an increased endocrine response, neither inositol phosphates nor intracellular calcium were released by a GnRH analog, indicating the uncoupling of GnRH receptors from phospholipase C. These data provide evidence that the transformation of the ovary into a luteoma implies the acquisition of novel characteristics in the GnRH receptor second messenger-generating system.

Gonadotropins and inhibins along the development of a luteinized rat ovarian tumor.

Luteinized intrasplenic ovarian tumors develop in response to high circulating gonadotropins. The relationship between tumor development, gonadotropins and inhibins was studied. Tumor-bearing animals were sacrificed weekly along the first 6 weeks of development. Inhibins were measured by enzyme-linked immunosorbent assay (ELISA), serum gonadotropins, GH and IGF-1 by RIA. Inhibin subunit mRNAs were determined by Northern blot. Tumor histology was examined. Ovarian grafts grew significantly along development. LH increased ten-fold on week 1; a further significant increment was observed on week 3. FSH peaked on weeks 1 and 2 and fell significantly thereafter. Serum inhibins markedly increased on weeks 3-5. Tumor inhibin A content and mRNA levels for alpha and beta A subunits also increased on week 3. Inverse correlations between inhibins and FSH and direct correlations between inhibins and LH were observed. Tumor inhibin A and IGF-1 contents correlated significantly. Increasing levels of luteinization were observed along tumor development. These luteinized tumors develop mainly in response to LH, since growth continues under FSH inhibition. The active inhibin secretion and the positive correlation between inhibins and LH suggests that LH may be the main driving force behind this production, while growth factors produced by the gonads may also participate in their regulation.

Actions of immunosuppressor drugs on the development of an experimental ovarian tumor.

Immunosuppression has been related to the incidence of tumor apparition, including endocrine tumors. The intrasplenic ovarian tumor (luteoma) is a typical benign endocrine tumor that develops under high gonadotropin stimulation and, from the immunological perspective, is located in a critical organ involved in immune response. To establish if immunosuppression could alter the development of this experimental tumor, the effects of cyclosporin A (CsA) and dexamethasone (Dex) were evaluated. After surgery, tumor-bearing and sham animals were kept without treatment for 4 weeks; thereafter, they were distributed into CsA (25 mg/kg), Dex (0.1 mg/kg), or vehicle (75:25 castor oil:ethanol) groups and were injected on alternate days for 50 days. Body weight was evaluated weekly. Animals were sacrificed after a jugular vein blood sample was obtained. Thymi were weighed. Tumors were measured and placed in formaline for histological studies. Serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin (PRL), and estradiol were measured by radioimmunoassay. Hematological parameters were determined. CsA induced a significant decrease in survival rates both in tumor-bearing and sham animals (P < 0.01). Dex significantly impaired weight increase in both groups of animals. CsA induced a significant weight loss in sham animals, not observed in tumor-bearing animals. Dex induced thymus weight loss in both groups, whereas CsA induced thymus weight loss only in sham animals. Only Dex induced a decrease in lymphocyte number in both groups. CsA induced an increase in monocyte number only in sham animals. Treatments did not alter LH, FSH, or estradiol, whereas PRL was increased by CsA only in sham rats. Neither Dex nor CsA induced any significant variations in tumor volume, nor did they alter tumor histology. In addition, no visible metastases or alterations in other organs were observed. We conclude that, though immunological parameters were altered by the treatments, immunosuppressor drugs did not condition tumor development. In addition, tumors secrete one or more factor/s that counteract CsA effect.

In vivo interaction of baclofen, TRH and serotonin on PRL and TSH secretion in the developing and adult male and female rats.

Gamma-aminobutyric acid (GABA) is involved in the neural control of hypophyseal hormones, including PRL and TSH. In the present work we investigated the ontogeny of the effect of baclofen, a GABA B agonist, on basal PRL and TSH release and in the presence of releasing stimulus which act at two different levels: TRH, at the hypophyseal level, and serotonin, at the central nervous system. Ages studied were 4, 12, 20, 28-29, 37-38 day-old and adult male and female animals. Rats of each age and sex were separated in groups and each group received two intraperitoneally injections, one 45 minutes after the other: saline-saline, saline-TRH, baclofen-saline, baclofen-TRH, saline-serotonin or baclofen-serotonin. Rats were decapitated 15 minutes after the last injection and serum hormones were measured by RIA. Baclofen (7 mg/kg) significantly elevated basal prolactin levels at 4, 12 and 20 days of age and the stimulating effect increased with age. At 28 days of age baclofen significantly inhibited PRL whereas from 38 days of age onwards it had no effect on basal PRL levels. No sex differences were evident. Interaction of TRH (4 microg/kg) and baclofen on PRL secretion resulted in an additive effect on days 4 and 12, this effect was not observed when baclofen was administered with serotonin (10 mg/kg). In 28 day-old and older animals baclofen completely blunted the PRL releasing effect of TRH or serotonin. Again, no sex differences were observed. With regard to TSH, baclofen did not alter either basal or TRH stimulated TSH secretion regardless of sex and age. The present experiments indicate that GABA B receptors are involved in the regulation of basal and stimulated PRL secretion from the first days of life to adulthood. Receptor activation results in stimulation or inhibition of PRL release depending on the age of the animals and the site of action. This GABA B regulation of PRL secretion is sex independent. In contrast, pituitary GABA B receptors do not seem to be involved in the regulation of TSH secretion.

Development of an experimental ovarian tumor over a year in the rat.

Tumor growth, possible malignant transformation or metastatic propagation and hormonal patterns were evaluated over a year in luteoma induced by introducing an ovary into the spleen of ovariectomized 60 day-old rats. Sham castrated animals had a piece of muscle inserted into the spleen. Jugular blood samples were taken monthly. After a year animals were cycled and decapitated. Troncal blood was collected, autopsies were performed and luteoma were measured and fixed in 10% buffered formalin. Serum LH, FSH, PRL, estradiol and progesterone were measured. Serum inhibin content was determined in one month-old tumors-bearing animals and estrous rats as controls. After one year no external changes in tumor-bearing rats were observed, nor differences in body weight or mortality rates compared to Sham animals. Metastatic propagation was absent. Routine histological examination showed two types of tumors according to either granulosa or luteal cell predomination, tumor type did not determine hormonal patterns. However, a clear relationship between gonadotropin levels and tumor size was established. Low gonadotropins: Small tumors, 18.7% of cases and high gonadotropins: Large tumors, 81.3%. In Sham animals gonadotropins attained castrate levels and remained elevated until the end of the experiment. In the Small group no increases in gonadotropins or estradiol were detected, progesterone and PRL fluctuated. In the Large tumor group LH increased to Sham titers until month 7, then fell to initial levels, FSH augmented significantly as from month three and remained high up to month 5. No variations in either estradiol, progesterone or PRL were observed. Serum inhibin of one month-old tumor-bearing rats was significantly elevated, justifying the lack of FSH increase at this time point. We conclude that these luteoma do not suffer malignant transformation or induce metastases. They appear in two histological types. Tumor size depends on hormonal patterns. The delay in the initial increase and the sharp decrease observed in FSH in animals bearing Large tumors suggest a possible role for inhibin in this regulation.

Construction and validation of a specific quality of life instrument for adolescents with spine deformities.

STUDY DESIGN: The development and construction of a specific instrument for measuring quality of life in adolescents with spine deformities was investigated. OBJECTIVES: To assess the validity and reliability of the Quality of Life Profile for Spine Deformities. SUMMARY OF BACKGROUND DATA: An 88-item questionnaire was self-administered to 174 patients ranging in age from 10 to 20 years with spine deformities. Items were rated on a five-point Likert scale. Higher scores means high level of impairment in quality of life. Age, gender, menarche or voice change, salient symptoms in the medical record, ordinary parameters on physical examination, and measurements on standard anteroposterior and lateral radiographs were recorded. The retest was done 10 days after the initial administration in a subsample of 35 patients. METHODS: The test-retest reliability was analyzed calculating the intraclass correlation coefficient. Internal consistency was measured with the Cronbach's alpha method. Factor analysis was used to obtain a reduced number of variables. Construct validity was assessed using the principal components model of factor analysis based on the correlation matrix and using the varimax computer algorithm for orthogonal rotation. Discriminant validity was assessed using the Kruskal-Wallis test. RESULTS: The Quality of Life Profile for Spine Deformities contained 21 items and five factors in conceptual terms labeled psychosocial functioning, sleep disturbances, back pain, body image, and back flexibility. The overall questionnaire score showed an internal consistency of 0.88 and a test-retest correlation of 0.91. Patients with structural curves showed significantly higher scores in all dimensions of the Quality of Life Profile for Spine Deformities except for the subscale of body image than patients with postural curves. When patients were grouped according to the symptom of back pain, those with backache had a significantly higher quality of life overalls score and scores in the dimensions of sleep disturbances and pain. Brace-treated patients showed statistically significant differences in the quality of life overall score and scores in the dimensions of psychosocial functioning and back flexibility. CONCLUSIONS: The instrument developed for measuring quality of life in patients with spine deformities during the period of bone growth has validity, internal consistency, and high test-retest reliability. The conceptualization of quality of life of the Quality of Life Profile for Spine Deformity includes psychosocial dimensions and pain and function.

Massive burns: a study of epidemiology and mortality.

This study describes the epidemiology and mortality of patients with burns involving over 30 per cent of the body surface who were hospitalized between 1 January 1988 and 1 January 1990. During this period 302 patients were hospitalized (8.1 per cent of those treated); of these, 52 (16.7 per cent) had burns affecting more than 30 per cent of the total body surface. There were 38 males and 14 females (mean age, 43 years). The mean burn extent was 55.3 per cent of the total body surface, and the most common cause was fire (75 per cent); 67.3 per cent of accidents occurred at home. Patient mortality in our series was 30.7 per cent with a mean survival of 10.3 days.