Adult starvation and disease-related malnutrition: A proposal for etiology-based diagnosis in the clinical practice setting from the International Consensus Guideline Committee

Background & aims: Multiple definitions for malnutrition syndromes are found in the literature resulting in confusion. Recent evidence suggests that varying degrees of acute or chronic inflammation are key contributing factors in the pathophysiology of malnutrition that is associated with disease or injury. Methods: An International Guideline Committee was constituted to develop a consensus approach to defining malnutrition syndromes for adults in the clinical setting. Consensus was achieved through a series of meetings held at the ASPEN and ESPEN Congresses. Results: It was agreed that an etiology-based approach that incorporates a current understanding of inflammatory response would be most appropriate. The Committee proposes the following nomenclature for nutrition diagnosis in adults in the clinical practice setting. ""Starvation-related malnutrition"", when there is chronic starvation without inflammation, ""chronic disease-related malnutrition"", when inflammation is chronic and of mild to moderate degree, and ""acute disease or injury-related malnutrition"", when inflammation is acute and of severe degree. Conclusions: This commentary is intended to present a simple etiology-based construct for the diagnosis of adult malnutrition in the clinical setting. Development of associated laboratory, functional, food intake, and body weight criteria and their application to routine clinical practice will require validation. (C) 2009 European Society for Clinical Nutrition and Metabolism and ASPEN American Society for Parenteral and Enteral Nutrition. Published by Elsevier Ltd. All rights reserved.

Adult Starvation and Disease-Related Malnutrition: A Proposal for Etiology-Based Diagnosis in the Clinical Practice Setting From the International Consensus Guideline Committee

Background & Aims: Multiple definitions for malnutrition syndromes are found in the literature resulting in confusion. Recent evidence suggests that varying degrees of acute or chronic inflammation are key contributing factors in the pathophysiology of malnutrition that is associated with disease or injury. Methods: An International Guideline Committee was constituted to develop a consensus approach to defining malnutrition syndromes for adults in the clinical setting. Consensus was achieved through a series of meetings held at the ASPEN. and ESPEN Congresses. Results: It was agreed that an etiology-based approach that incorporates a current understanding of inflammatory response would be most appropriate. The Committee proposes the following nomenclature for nutrition diagnosis in adults in the clinical practice setting. ""Starvation-related malnutrition,"" when there is chronic starvation without inflammation, ""chronic disease-related malnutrition"", when inflammation is chronic and of mild to moderate degree, and ""acute disease or injury-related malnutrition"", when inflammation is acute and of severe degree. Conclusions: This commentary is intended to present a simple etiology-based construct for the diagnosis of adult malnutrition in the clinical setting. Development of associated laboratory, functional, food intake, and body weight criteria and their application to routine clinical practice will require validation. (JPEN J Parenter Enteral Mar. 2010;34:156-159)

Different Patterns in a Cohort of Patients with Severe Leptospirosis (Weil Syndrome): Effects of an Educational Program in an Endemic Area

The aim of this study is to investigate the changes in clinical pattern and therapeutic measures in leptospirosis-associated acute kidney injury; a retrospective study with 318 patients in Brazil. Patients were divided according to the time of admission: 1985-1996 (group I) and 1997-2010 (group II). Patients were younger in group I (36 +/- 13 versus 41 +/- 16 years, P = 0.005) and the numbers of oliguria increased (21% versus 41% in group II, P = 0.014). Higher frequency of lung manifestations was observed in group II (P<0.0001). Although increased severity, there was a significant reduction in mortality (20% in group I versus 12% in group II, P = 0.03). Mortality was associated with advanced age, low diastolic blood pressure, oliguria, arrhythmia, and peritoneal dialysis, besides a trend to better mortality with penicillin administration. Leptospirosis is occurring in an older population, with a higher number of oliguria and lung manifestations. However, mortality is decreasing and can be the result of changes in treatment.

Malformations of Cortical Development in Patients With Mid line Facial Defects and Ocular Hypertelorism

Objectives: We studied the neuroimaging and neurophysiological aspects of 17 patients with midline facial defects with ocular hypertelorism (MFDH). Methods: The investigation protocol included a previous semistructured questionnaire about family history; gestational, neonatal, and postnatal development; and dysmorphologic and neurologic evaluation. Recognized monogenic disorders and individuals with other well-known conditions were excluded. All patients had high resolution magnetic resonance imaging (MRI) with multiplanar reconstruction (MPR) and routine electroencephalograms (EEGs). Results: We detected abnormalities in five patients whose MRIs had been previously reported as normal. MRI showed central nervous system (CNS) structural abnormalities in all patients, which included commissural alterations in 16/17 (94%), malformations of cortical development in 10/17 (58%), disturbances of neural tube closure in 7/17(42%), and posterior fossa anomalies in 6/17 (35%). Some patients had more than one type of malformation occurring at different stages of the embryonary process. EEGs showed epileptiform activity in 4/17 (24%) and background abnormalities in 5/17 (29%) of patients. Conclusion: This study clearly demonstrated the presence of structural and functional neurologic alterations related to MFDH. Therefore, the CNS anomalies cannot be considered incidental findings but an intrinsic part of this condition, which could be related to environmental effects and/or genetic mutations. These findings would provide a basis for future investigations on MFDH and should also be considered when planning rehabilitation.

Therapeutic Leukapheresis in Patients with Leukostasis Secondary to Acute Myelogenous Leukemia

Leukostasis is a relatively uncommon but potentially catastrophic complication of acute myelogenous leukemia (AML). Prompt leukoreduction is considered imperative to reduce the high mortality rate in this condition. Leukapheresis, usually associated with chemotherapy, is an established approach to diminish blast cell counts. We report a single center experience in managing leukostasis with leukapheresis. Fifteen patients with leukostasis of 187 patients with AML (8.02%) followed at our institution were treated with leukapheresis associated with chemotherapy. The procedures were scheduled to be performed on a daily basis until clinical improvement was achieved and WBC counts were significantly reduced. Overall and early mortalities, defined as that occurred in the first 7 days from diagnosis, were reported. A high proportion of our patients with leukostasis (46.66%) had a monocytic subtype AML (M4/M5, according to French-American-British classification). The median overall survival was 10 days, despite a significant WBC reduction after the first apheresis procedure (from 200.7 X 10(9)/L to 150.3 X 10(9)/L). Almost half of patients (7/15) had an early death. Therapeutic leukapheresis, associated or not to chemotherapy, is an effective approach to reduce WBC counts in patients with AML and leukostasis; however, this therapeutic procedure does not appear to change significantly the sombre prognosis observed in the majority of patients with this complication. Other forms of treatment must be found to reduce the high mortality rate related to leukostasis. J. Clin. Apheresis 26:181-185, 2011. (C) 2011 Wiley-Liss, Inc.

Screening of autosomal gene deletions in patients with hypogonadotropic hypogonadism using multiplex ligation-dependent probe amplification: detection of a hemizygosis for the fibroblast growth factor receptor 1

P>Objective Congenital hypogonadotropic hypogonadism with anosmia (Kallmann syndrome) or with normal sense of smell is a heterogeneous genetic disorder caused by defects in the synthesis, secretion and action of gonadotrophin-releasing hormone (GnRH). Mutations involving autosomal genes have been identified in approximately 30% of all cases of hypogonadotropic hypogonadism. However, most studies that screened patients with hypogonadotropic hypogonadism for gene mutations did not include gene dosage methodologies. Therefore, it remains to be determined whether patients without detected point mutation carried a heterozygous deletion of one or more exons. Measurements We used the multiplex ligation-dependent probe amplification (MLPA) assay to evaluate the potential contribution of heterozygous deletions of FGFR1, GnRH1, GnRHR, GPR54 and NELF genes in the aetiology of GnRH deficiency. Patients We studied a mutation-negative cohort of 135 patients, 80 with Kallmann syndrome and 55 with normosmic hypogonadotropic hypogonadism. Results One large heterozygous deletion involving all FGFR1 exons was identified in a female patient with sporadic normosmic hypogonadotropic hypogonadism and mild dimorphisms as ogival palate and cavus foot. FGFR1 hemizygosity was confirmed by gene dosage with comparative multiplex and real-time PCRs. Conclusions FGFR1 or other autosomal gene deletion is a possible but very rare event and does not account for a significant number of sporadic or inherited cases of isolated GnRH deficiency.

Evaluation of erythrocyte dysmorphism by light microscopy with lowering of the condenser lens: A simple and efficient method

Aim: To demonstrate that the evaluation of erythrocyte dysmorphism by light microscopy with lowering of the condenser lens (LMLC) is useful to identify patients with a haematuria of glomerular or non-glomerular origin. Methods: A comparative double-blind study between phase contrast microscopy (PCM) and LMLC is reported to evaluate the efficacy of these techniques. Urine samples of 39 patients followed up for 9 months were analyzed, and classified as glomerular and non-glomerular haematuria. The different microscopic techniques were compared using receiver-operator curve (ROC) analysis and area under curve (AUC). Reproducibility was assessed by coefficient of variation (CV). Results: Specific cut-offs were set for each method according to their best rate of specificity and sensitivity as follows: 30% for phase contrast microscopy and 40% for standard LMLC, reaching in the first method the rate of 95% and 100% of sensitivity and specificity, respectively, and in the second method the rate of 90% and 100% of sensitivity and specificity, respectively. In ROC analysis, AUC for PCM was 0.99 and AUC for LMLC was 0.96. The CV was very similar in glomerular haematuria group for PCM (35%) and LMLC (35.3%). Conclusion: LMLC proved to be effective in contributing to the direction of investigation of haematuria, toward the nephrological or urological side. This method can substitute PCM when this equipment is not available.

Secondary PSF/TFE3-associated renal cell carcinoma in a child treated for genitourinary rhabdomyosarcoma

Xp11.2 translocation-associated renal cell carcinoma (RCC) is a rare tumor that accounts for at least one-third of childhood RCC. Different reports have emphasized that previous radio/chemotherapy might be involved in its pathogenesis. We describe a child who developed a t(X;1) (p11.2;p34) associated RCC after previous treatment for genitourinary rhabdomyosarcoma in infancy. The presence of the PSF-TFE3 fusion has only been described in a very limited number of cases. Our report expands the spectrum of tumors in which RCC can arise in the pediatric age group after chemotherapy.

The-202 A Allele of Insulin-Like Growth Factor Binding Protein-3 (IGFBP3) Promoter Polymorphism Is Associated with Higher IGFBP-3 Serum Levels and Better Growth Response to Growth Hormone Treatment in Patients with Severe Growth Hormone Deficiency

Context: Genetic factors that influence the response to recombinant human GH (rhGH) therapy remain mostly unknown. To date, only the GH receptor gene has been investigated. Objective: The aim of the study was to assess the influence of a polymorphism in the IGF-binding protein-3 (IGFBP-3) promoter region (-202 A/C) on circulating IGFBP-3 levels and growth response to rhGH therapy in children with GH deficiency (GHD). Design and Patients: -202 A/C IGFBP3 genotyping (rs2854744) was correlated with data of 71 children with severe GHD who remained prepubertal during the first year of rhGH treatment. Main Outcome Measures: We measured IGFBP-3 levels and first year growth velocity (GV) during rhGH treatment. Results: Clinical and laboratory data at the start of treatment were indistinguishable among patients with different -202 A/C IGFBP3 genotypes. Despite similar rhGH doses, patients homozygous for the A allele presented higher IGFBP-3 SD score levels and higher mean GV in the first year of rhGH treatment than patients with AC or CC genotypes (first year GV, AA = 13.0 +/- 2.1 cm/yr, AC = 11.4 +/- 2.5 cm/yr, and CC = 10.8 +/- 1.9 cm/yr; P = 0.016). Multiple linear regression analyses demonstrated that the influence of -202 A/C IGFBP3 genotype on IGFBP-3 levels and GV during the first year of rhGH treatment was independent of other variables. Conclusion: The -202 A allele of IGFBP3 promoter region is associated with increased IGFBP-3 levels and GV during rhGH treatment in prepubertal GHD children. (J Clin Endocrinol Metab 94: 588-595, 2009)

Long-term treatment of familial male-limited precocious puberty (testotoxicosis) with cyproterone acetate or ketoconazole

Background Familial male-limited precocious puberty (FMPP) or testotoxicosis is a rare gonadotrophin-independent form of sexual precocity caused by constitutively activating mutations of the LH receptor. Several clinical therapeutic approaches have been reported for this disorder, but with a paucity of long-term outcome data. Objective To evaluate the long-term treatment of testotoxicosis with cyproterone acetate or ketoconazole. Design A multicentric retrospective clinical study. Patients Ten boys from eight unrelated Brazilian families who carried known LH-receptor activating mutations were treated with 70 mg/m(2) cyproterone acetate (n = 5) or 10 mg/kg ketoconazole (n = 5) for a mean period of 5 and 8 years, respectively. Measurements Chronological and bone ages, bone age/chronological age ratio, target height (TH) range, adult height, basal and GnRH-stimulated gonadotrophin levels and basal testosterone levels were assessed. Results Growth velocity decreased significantly during treatment with cyproterone acetate or ketoconazole when compared to pretreatment value in each group (P < 0.05). Bone age/chronological age ratio decreased significantly after cyproterone acetate or ketoconazole therapy. Basal testosterone levels were significantly lower in patients undergoing ketoconazole compared to cyproterone acetate treatment [0.6 +/- 0.3 nmol/l (42 +/- 21 ng/dl) vs. 5.6 +/- 4.0 nmol/l (392 +/- 280 ng/dl); P < 0.05], as expected. Secondary gonadotrophin-dependent precocious puberty occurred at a similar frequency (40%) in both groups. Five patients have attained adult height and two patients have already reached 90% of their adult height. Two of them achieved their TH range and one patient, for whom TH was not available, had an adult height of 0.3 SDS. Four boys (two in each group) did not attain their TH range. Conclusion Long-term treatment with cyproterone acetate or ketoconazole resulted in similar outcomes without important side-effects in boys with testotoxicosis. However, both therapies showed limited efficacy in attaining normal adult height.

Septic shock caused by Plesiomonas shigelloides in a patient with sickle beta-zero thalassemia

Invasive infection and extraintestinal complications are rarely caused by Plesiomonas shigelloides, a water-borne bacterium belonging to the Vibrionaceae family. We report a case of a 16-year-old female patient with sickle beta-zero thalassemia who survived septic shock caused by P. shigelloides associated with secondary acute respiratory distress syndrome and disseminated intravascular coagulation. Treatment with a carbapenem was successful, and the patient recovered without any sequelae. The previous reports of P. shigelloides sepsis are cited, and possible pathogenic mechanisms are discussed. (Heart Lung (R) 2010;39:335-339.)

Echocardiographic identification of the oblique vein of the left atrium: its relationship to the persistent left superior caval vein

Thus far, little has been written concerning echocarchographic identification of the oblique of the left atrium, or Marshall`s vein. There is much discussion, nonetheless, on the potential significance of the vein, or its ligamentous remnant, as an arrhythmic substrate. We describe here four patients in whom transthoracic echocardiography revealed a venous structure protruding within the cavity of the left atrium. We discuss the possibility that these structures represent Marshall`s vein, albeit probably as part of a persistent left superior caval vein.

Behavioral effects of acute stimulation of kappa-opioid receptors during lactation

The behavioral effects of the K-opioid receptor agonist U69593 were examined in lactating rats. On day 5 of lactation, animals were treated with 0.1 mg/kg of U69593 to determine whether it influences general activity and maternal latencies toward pups. Because little attention has been given to the possibility that pre-mating treatment with morphine may modulate the response to K-opioid receptor stimulation, another group of animals was submitted to the same acute challenge after abrupt withdrawal from repeated treatment with morphine sulfate during the pre-mating period (5 mg/kg on alternate days for a total of five doses). Acute F;opioid stimulation reduced total locomotion, rearing frequency, and time spent self-grooming and increased immobility duration. These K agonist effects were not observed in animals pretreated with morphine. Similarly, latencies to retrieve pups were longer only in animals pretreated with saline and challenged acutely with U69593. None of these effects were observed in morphine sulfate-pretreated animals. The present results suggest that pre-mating repeated exposure to morphine produces a tolerance-like effect on behavioral responses to low-dose K-opioid receptor stimulation in active reproductive females. (c) 2008 Elsevier Inc. All rights reserved.

Substance P and NK-1R expression in oral precancerous epithelium

The objectives of this study were to investigate the presence and distribution of substance P and neurokinin 1 receptor in oral premalignant epithelium and their relation with the presence of dysplasia, and to analyze whether the expression of substance P can be considered an early oncogenic event in oral carcinogenesis. Substance P and neurokinin I receptor expression was immunohistochemically studied in 83 oral carcinomas and adjacent nontumor epithelia. The presence and degree of epithelial dysplasia was assessed according to WHO criteria. The nuclear, cytoplasmic, and membrane expression of substance P and the cytoplasmic and membrane expression of neurokinin 1 receptor were assessed in tumor and adjacent non-tumor epithelium. Nuclear and cytoplasmic expression of substance P in non-tumor epithelium was significantly associated with the presence of epithelial dysplasia (p<0.001) and carcinoma in. situ (p=0.021). Nuclear, cytoplasmic, and membrane expressions of substance P in non-tumor epithelium were significantly (p<0.001) associated with its expression in the corresponding tumor. These findings suggest that substance P plays a role in early oral carcinogenesis by promoting the proliferation and growth of premalignant fields.

A Role for the Substance P/NK-1 Receptor Complex in Cell Proliferation in Oral Squamous Cell Carcinoma

Objective: To investigate the presence and distribution of substance P (SP) and neurokinin I receptor (NK-IR) in oral squamous cell carcinoma (OSCC) and their relationship with proliferation. Patients and Methods: Ninety OSCCs from 73 patients were immunohistochemically analyzed using monoclonal antibodies against SP, NK-IR and Ki-67 in a case and control study. Results: Seventy-one percent (n=49) of cases expressed SP on tumour cell membrane, 81.3% (n=69) in cytoplasm, 39.4% (n=28) in nucleus, 81.6% (n=71) in infiltrating lymphocytes, and 58.1% (n=43) in peritumoural or intratumoural blood vessels; 14% (n=12) of cases expressed NK-1R on tumour cell membrane, 50% (n=43) in cytoplasm, 48.3% (n=42) in infiltrating lymphocytes and 22.5% (n=18) in tumour blood vessels. All cases expressed Ki-67, which was expressed in >25% of tumour cells in 79.8% of cases (n=63). Direct significant associations were observed in SP expression between different tissue levels (p<0.01), between SP and NK-IR tumour cell membrane expression (p<0.01), and between joint,SP and NK-IR expression in tumour cell cytoplasm and a higher expression of Ki-67 (p<0.05). Conclusion: The ubiquitous presence of SP strongly suggests a role for SP/NK-1R complex in tumour development and progression and possibly for NK-IR antagonists, such as L-773060, in the management of patients with oral cancer.