Predictors of Tumor Response to Cetuximab and Panitumumab in 116 Patients and a Review of Approaches to Managing Skin Toxicity.

INTRODUCTION AND OBJECTIVES: Cetuximab and panitumumab are monoclonal antibodies that target the epidermal growth factor receptor (EGFR) in the treatment of metastatic colorectal cancer. Most patients develop a papulopustular rash, which may predict tumor response. We studied whether the other adverse cutaneous effects associated with these monoclonal antibodies are also clinical predictors of response. We also reviewed publications describing approaches to treating the papulopustular rash since no evidence-based guidelines have yet been published. MATERIAL AND METHODS: We performed a retrospective study of 116 patients with metastatic colorectal cancer receiving anti-EGRF therapy with cetuximab or panitumumab at Hospital Universitario Donostia. RESULTS: In total, 81.9% of the patients developed a papulopustular rash. Patients who received the most cycles of treatment with the EGFR inhibitor were at the highest risk of developing the rash, and these patients also had the most severe rash reactions (P=.03). All of the patients who exhibited a complete tumor response had the rash, and the incidence of rash was lower in patients with poor tumor response (P=.03). We also observed an association between tumor response and xerosis (53.4% of the patients who developed xerosis also exhibited tumor response, P=.002). The papulopustular rash was managed according to an algorithm developed by our department. CONCLUSIONS: Severe papulopustular rash and xerosis may be clinical predictors of good response to anti-EGFR therapy. Patients who develop a papulopustular rash should be treated promptly because suboptimal treatment of this and other adverse effects can lead to delays in taking the prescribed anti-EGFR dose or to interruption of therapy.

Effect of prophylactic CPAP in very low birth weight infants in South America.

OBJECTIVE: The objective of this study was to examine the effect of prophylactic continuous positive airway pressure (CPAP) on infants born in 25 South American neonatal intensive care units affiliated with the Neocosur Neonatal Network using novel multivariate matching methods. STUDY DESIGN: A prospective cohort was constructed of infants with a birth weight 500 to 1500 g born between 2005 and 2011 who clinically were eligible for prophylactic CPAP. Patients who received prophylactic CPAP were matched to those who did not on 23 clinical and sociodemographic variables (N=1268). Outcomes were analyzed using the McNemar's test. RESULTS: Infants not receiving prophylactic CPAP had higher mortality rates (odds ratio (OR)=1.69, 95% confidence interval (CI) 1.17, 2.46), need for any mechanical ventilation (OR=1.68, 95% CI 1.33, 2.14) and death or bronchopulmonary dysplasia (BPD) (OR=1.47, 95% CI 1.09, 1.98). The benefit of prophylactic CPAP varied by birth weight and gender. CONCLUSIONS: The implementation of this process was associated with a significant improvement in survival and survival free of BPD.

[Infants aged 3-24 months with fever without source in the emergency room: characteristics, management and outcome]. / Lactante de 3-24 meses con fiebre sin foco en urgencias: características, tratamiento y evolución posterior.

OBJECTIVE: To determine the characteristics of infants aged 3-24 months admitted to a Hospital Pediatric Emergency Room with fever without source, the management of these infants and their subsequent outcome. PATIENTS AND METHOD: We performed a retrospective survey of 733 children aged 3-24 months with fever without source admitted to our Emergency Room between September 1, 2003 and December 31, 2003. Subsequently, the parents of all infants diagnosed with fever without source who were managed as outpatients were telephoned to ascertain their outcome and changes in the final diagnosis. RESULTS: Onset of fever occurred less than 6 hours before arrival at the hospital in 237 episodes (32.2%). The family reported a temperature of > or = 39 degrees C in 436 episodes. Diagnoses in the Emergency Room were the following: fever without source in 677 (92.3%), urinary tract infection in 53 (7.2%) and bacterial meningitis in three (0.4 %). Fifty-five infants with an altered dipstick were excluded and complete blood count (CBC) and blood culture were performed in 66 infants (9.7%). There was a significant negative association between the probability of a request for CBC and blood culture and higher age [6-11 months vs. 3-6 months OR 0.24 (95 % CI: 0.11-0.49); > or = 12 months vs. 3-6 months, OR 0.15 (0.07-0.3)] and a significant positive association with onset more than 12 hours previously [vs. less than 6 hours OR 2.3 (1.2-4.43)] and highest temperature registered at home > 40 degrees C [vs. less than 39 degrees C OR 4.22 (1.5-11.84)]. Follow-up was completed (by telephone or readmission to the Emergency Room) in 574 infants diagnosed with fever without source and managed as outpatients. The final diagnosis differed from that made in the Emergency Room in 158 infants (27.5%), and 70 received antibiotics (12.1%). CONCLUSIONS: A considerable percentage of infants aged 3-24 months with fever without source visits the Emergency Room with very short-term processes. Patient observation is very useful in the management of these infants, since the final diagnosis differed from that made in the emergency room in nearly 30% and 12% were treated with antibiotics.

Evaluation of the precision obtained with a fixed surgical template in the placement of implants for rehabilitation of the completely edentulous maxilla: a clinical report.

The fabrication of a complete maxillary implant-supported prosthesis in a patient with slight resorption of the alveolar ridge and a high lip line presents a professional challenge. The implants must be placed with high precision to achieve good esthetics, phonetics, and function. A fixed surgical template using microimplants has been developed for this purpose. The objective of this investigation was to compare a fixed surgical template (FST) to a conventional movable surgical template (MST) for the precise placement of implants in the slightly resorbed edentulous maxilla. Three patients (28 implants), edentulous in the maxilla, with slight ridge resorption, in whom the implants were placed with an FST, were compared with 5 controls having the same characteristics and implants placed with an MST (35 implants). After completion of the prosthesis, occlusal photographs (1:1) were taken, and these images were scanned and transferred to a drawing program in which the contours of the teeth, the ideal emergence position of the occlusal hole of the abutment screw, and its real position were drawn. A blind evaluation was made using the following variables: frequency of location of the abutment screw hole outside of the tooth contour, and the relative measurements of the area of coincidence between the circle that represents the ideal position and real position. A significantly smaller frequency of implants outside the tooth contour was seen with the FST (7%) than with the MST (46%) (P < .0008). Also, a significantly higher relative area of coincidence was observed between ideal position and real position in the FST (0.61) than in the MST (0.38) (P < .003). This study revealed that considerably higher precision was associated with the use of an FST.

[The effect of peroperative transfusion on survival in resected lung carcinomas]. / Influencia de la transfusión perioperatoria en la supervivencia de los carcinomas de pulmón resecados.

This paper analyzes the influence of perioperative transfusion on survival after lung cancer surgery. Between January 1991 and December 1995, we enrolled 405 patients, 196 of whom received transfusions and 209 of whom did not. Follow-up extended to December 1997. Excluded were patients undergoing exploratory thoracotomy (n = 92), those who died during the postoperative period (n = 19) and those lost to follow-up (n = 13). The final number of patients in the study was 281 (136 who received transfusions and 145 who did not). We analyzed age, sex, general clinical status measured on the Eastern Cooperative Oncology Group (ECOG) scale, histological type and TNM staging. Single and multiple variable analyses were performed. At the end of the study 158 patients were alive and 123 had died. Transfusions were used more often in pneumonectomies (p < 0.001) and in patients with an ECOG score of 2 (p < 0.01). Survival at 36 and 60 months, calculated using the Kaplan-Meier method was 52% and 30%, respectively, for those who had received transfusions, and 53% and 49%, respectively, for those who had not. The differences were not statistically significant (p > 0.1). Multivariant analysis failed to demonstrate an influence of transfusion on survival (relative risk of 1.08; 95% confidence interval 0.72-1.61; p > 0.1). We conclude that there is no negative prognostic effect of perioperative transfusion.

[Population reference ranges and determinants of plasma homocysteine levels]. / Intervalos de referencia poblacional y determinantes de la homocisteína plasmática.

BACKGROUND: There is a well-known relationship between plasma homocysteine levels and the risk of cardiovascular events. Determination of homocysteine levels may also be of potential diagnostic aid in several clinical situations. The construction of reference ranges should take age and sex variations into account. SUBJECTS AND METHODS: 396 healthy subjects were recruited (172 males and 224 females). Fasting plasma homocysteine levels were measured using the fluorescein polarization immunoassay technique (FPIA). Plasma levels of creatinine, folates, vitamin B12 and TSH were measured. 90% reference ranges were estimated by fractional polynomial regression methods. RESULTS: Homocysteine plasma levels ranged from 4.35 micromol/l to 17,71 micromol/l (median 8.62 micromol/l). These concentrations increased with age and were higher in males (median 9.53 micromol/l [range: 5.45-17.5]) than in females (median 7.79 micromol/l[range: 4.35-17.71]). Sex differences decreased in the elderly. Creatinine plasma levels (with a positive association) and folate levels (with a negative association) had a statistically significant effect on the specific distribution of homocysteine levels according to age and sex. CONCLUSIONS: Age-and sex-specific reference ranges of plasma homocysteine have been defined. Renal function along with folate plasma levels have to be accounted for when assessing these distribution ranges.

Teaching portfolios: an effective strategy for faculty development in occupational therapy.

The special challenge of the occupational therapy practitioner embracing the role of faculty member is discovering a formative process of continual improvement that will also serve as an authentic assessment of teaching and learning within the particular disciplinary boundaries of occupational therapy. Although other means achieve such complex aims, the teaching portfolio is a powerful tool for fostering reflective practice and for creating an ongoing record of substantial evidence. A teaching portfolio is an evidence-based written document in which a faculty member, working in collaboration with a mentor, concisely organizes selective details of teaching accomplishment and effort and uses such information to document his or her teaching enterprise. More importantly, the faculty member uses the information for reflective analysis, leading to improvement of teaching and student learning. The emphasis on reflection, analysis, evidence, and mentoring suggests that the teaching portfolio can set the stage for meaningful collaboration in a system of evaluation that is based appropriately on recorded evidence of improvement and demonstrated positive outcomes of student learning.

[Lyell syndrome associated with lamotrigine]. / Síndrome de Lyell asociado a lamotrigina.

INTRODUCTION: Lamotrigine (LTG) is a new antiepileptic of habitual use in monotherapy as much in partial epileptic as in generalised, which presents among other adverse effects: slight rashes and less frequently severe rashes such as Stevens-Johnson syndrome and Lyell syndrome or toxic epidermal necrolysis, above all in combination with valproate (VPA). CLINICAL CASE: A 44-yr-old woman in toxico-alcoholic epileptic treatment with VPA, showed a neutropenia possibly of secondary type which it was intended to change to LTG, following an ascending dose of LTG joined to a descending dose of VPA. In the sixth treatment week, the patient developed an erythematous rash which after a week of solar exposure, presented temperature, general discomfort, and in the head, on the front and back part of the thoracic and upper and lower limbs, erythematous lesions with scabbed areas, loosening epidermis areas with a positive Nikolsky sign and severe mucous membrane involvement, being diagnostic of Lyell syndrome. The lesions got slowly better with serum therapy, antibiotherapy, parenteral corticoids and topical treatments. CONCLUSIONS: There is a probability of severe rash associated with lamotrigine which has to be taken into account, and we advise patients to suppress the medication when they present a minimum rash.

[Familial eosinophilic fascitis induced by toxic oil]. / Fascitis eosinofílica familiar inducida por aceite tóxico.

Three of four family members in husband, wife and one of two daughters developed in a short time interval (eleven months) eosinophilic fasciitis. The clinical, analytical and histopathological changes were characteristic of this disease. Familial cases of eosinophilic fasciitis have not been previously published. The process of these patients was probably caused by the ingestion of denatured oil (toxic oil syndrome), although the clinical picture begun two and a half years after the epidemic phase of the toxic oil syndrome declined.

[Bowenoid papulosis in a patient with AIDS]. / Papulosis bowenoide en paciente de SIDA.

A patient with a acquired immunodeficiency syndrome (AIDS) and Kaposi's angiosarcoma developed bowenoid papulosis of the genitalia (BP). The clinical and histopathological criteria were both characteristic of BP. With vinblastine treatment a moderate improvement of Kaposi's lesions was observed, but no significant changes of the BP lesions were noted during this treatment.

Vasoactive intestinal polypeptide (VIP)-like immunoreactivity in intraprostatic neurons and major pelvic ganglia in the rat.

VIP-like immunoreactive neurons have been found within the prostate and major pelvic ganglia of the male rats; they are of two different sizes. Moreover many VIP-like nerve fibers were found around the perikarya. On the basis of present data it is suggested that VIP-like prostatic nerves arise from both pelvic ganglia and intraprostatic neurons.

[Recent changes in emergency room visits and hospitalization for asthma in childhood]. / Cambios recientes en la frecuentación a urgencias y hospitalización por asma en la infancia.

OBJECTIVE: The purpose of this study was to investigate recent changes in the emergency room visits and hospital admission rates between 1993 and 1997 in our hospital. PATIENTS AND METHODS: From January 1, 1993 until December 31, 1997, the 12,848 patients between 0 and 14 years of age whose discharge diagnosis was coded as asthma (ICD9) and who were managed in the emergency room of our hospital were included in the study. RESULTS: During the study period, the number of emergency room visits for asthma (EA) remained unchanged. However, in children between 0 and 5 years of age the number of EA showed a significant increase from 1305 in 1993 (53.5% of all EA) to 1849 in 1997 (68.9% of EA), with an increase of the repeat visits in this age group from 46 (35.8% of all EA in this age group) in 1993 to 791 (42.8%) in 1997 (p < 0.01). In the same period of time, the admission rates for asthma decrease from 7.2% to 2.9% (p < 0.01). There was a trend towards more intense treatment of asthma in the emergency observation unit. CONCLUSIONS: There has been an upward trend in the number of acute asthma episodes between 1993 and 1997 in children between 0 and 5 years of age. It was associated with an increase in the number of repeat visits per patient. The use of a more intense treatment in the emergency observation unit was associated with a reduction in the hospitalization rate for asthma.

[Intellectual development in the second year of life in healthy breast-fed children compared with formula-fed children]. / Desarrollo intelectual en el segundo año de vida en niños sanos lactados de forma natural frente a los lactados artificialmente.

BACKGROUND: The role of breast milk with regard to W3 long-chain polyunsaturated fatty acids and infant intellectual development remains controversial. PATIENTS AND METHODS: Thirty-nine children born at term and from homogeneous sociocultural status were enrolled in a blind-prospective trial. Children were divided in two non-randomized groups: a breast-fed group and a standard formula-fed group. Red blood cell phospholipid fatty acids were analyzed at 7 and 60 days of life. Cognitive development was evaluated at the end of the second year of life through Bailey s test. RESULTS: Concentrations of phosphatidylethanolamine and phosphatidylcholine docosahexaenoic acid were significantly lower in the formula-fed group. No statistically significant differences between groups were found in cognitive function. Brain development index was significantly correlated with infant head circumference and educational status of the mother. CONCLUSIONS: Maternal nutrition provides higher red blood cell docosahexaenoic acid, but is not related to a higher developmental quotient at the age of 2 years. However, infant head circumference and maternal educational status were correlated with developmental cognition.

[Microscopic innervation of the spermatic ducts and testis. II. Ductus epididymis]. / Inervación microscópica de las vías espermáticas y testículo. II. Ductus epididymis.

The microscopic innervation of the ductus epididymis in the rat has been studied both in light and electron microscope. The nerve fibres form perivascular, intramuscular and subepithelial plexuses. Occasionally sensory formations were observed in the adventitia of the cauda epididymis. The innervation is more abundant in the cauda epididymis than in the other segments (caput and corpus). The varicosities and endings of nerve fibres have synaptic vesicles of different sizes and electron characteristics. Some of the varicosities were close to the muscle cells and without glial sheath. The epithelial cells were not directly innervated.

Immunohistochemical study of cat Pacinian corpuscles: co-localization of vimentin- and S-100 protein-like in the inner core.

The presence of vimentin and S-100 protein in cat Pacinian corpuscles of cat mesentery has been investigated immunohistochemically (streptavidin-biotin method) using monoclonal antibodies. A positive reaction for both vimentin- and S-100 protein-like was found only in the lamellae of the inner core. The presence of vimentin and the co-expression of vimentin/S-100 protein-like in sensory corpuscles is reported for the first time. The authors discuss the origin of the inner core and capsule of sensory corpuscles on the basis of their immunohistochemical characteristics.

[The influence of human milk and various artificial formulae commercially available in Spain on the fatty acid status of infants in the first two months of life]. / Perfil de ácidos grasos a los dos meses de vida en niños alimentados con lactancia materna frente a varias fórmulas artificiales disponibles comercialmente en España.

OBJECTIVE: To evaluate changes in the fatty acid composition of red blood cell phospholipids in breast-fed infants compared with those in infants fed with different formulas (conventional, omega -6-enriched formula, omega -6- and omega -3-enriched formula and nucleotide-enriched formula). METHODS: Thirty-seven healthy term infants were randomly assigned to one of five different feeding groups. Weight, length, head circumference, and arm circumference were assessed at 7 and 60 days of age. The fatty acid composition of the infants' red blood cell phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were analyzed at these ages. RESULTS: The anthropometric variables studied showed no changes among the different groups. At 60 days old, arachidonic acid concentration (20:4 omega -6) was lower in non-omega -6 enriched formula-fed groups compared with that in the breast-milk fed group (4.03, 3.68 and 5.15 vs 7.20 g/100 g of fatty acids). Docosahexaenoic acid concentration (22:6omega -3) in both PC and PE clearly decreased in the non-omega -3 formula-fed groups compared with that in the breast-milk fed group (PC: 0.72 vs 2.82 g/100 g of fatty acids and PE: 5.15 vs 7.73 g/100 g of fatty acids). CONCLUSIONS: This study demonstrates differences in the fatty acid composition of red blood cell phospholipids between breast-milk fed infants and those fed with any of the artificial formulas available on the Spanish market. These data provide evidence of the influence of diet on certain essential fatty acids in the body.

Expression of glial fibrillary acidic protein-like and S-100 protein like immunoreactivities on cartilages of the rat vestibulum nasi. Post-natal development changes.

The cartilages of vestibulum nasi in rats of different ages (newborns, 1 week, 1 month and 12 months old) were studied immunohistochemically using monoclonal antibodies against glial fibrillary acidic protein (GFAP) and S-100 protein. The immunoreaction for both GFAP and S-100 protein results positive in a variable number of chondrocytes. The number of chondrocytes displaying GFAP-like immunoreaction does not change during development and maturation, whereas those showing S-100 protein-like immunoreactivity increase from birth to the adult state. The formation of cartilaginous tissue from neuroectodermic cells of neural crest has been postulated by several authors and our results strongly support these opinions; moreover, according to present findings S-100 protein could be involved in chondroid tissue formation.