'Diagnosing food protein-induced enterocolitis syndrome'.

Food protein-induced enterocolitis syndrome is still a mysterious disease, pathogenically poorly characterized, although the first FPIES case has been described in 1967. Mainly, food protein-induced enterocolitis syndrome diagnosis is based on clinical history. The oral food challenge remains the gold standard to confirm the diagnosis, especially in particular situations. Although there are no diagnostic laboratory or imaging tests which are specific for diagnosis, they could, however, sometimes be helpful to rule out clinical conditions which are similar to food protein-induced enterocolitis syndrome reactions. The purpose of this review is to define the clinical features of FPIES and to summarize the current available tools for the diagnosis of FPIES. This review is intended to be a practical guide for the clinician facing a patient with food protein-induced enterocolitis syndrome avoiding delayed diagnosis with unnecessary laboratory tests and detrimental treatments. Moreover, it highlights the unmet needs in diagnosis that require urgent attention from the scientific community to improve the management of patients with FPIES.

A Metabolic Brain Pattern Associated With Anti-N-Methyl-D-Aspartate Receptor Encephalitis.

BACKGROUND: Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis causes substantial neurological disability. Autoantibodies causing encephalitis directed against the neuronal cell surface or synapse are of diagnostic importance giving the possibility of successful immunotherapy. OBJECTIVE: In this study, we aim to provide supporting evidence that brain 18F-FDG-PET may be helpful in identifying likely patterns of regional brain glucose metabolism. METHODS: Thirty-three patients (18 men and 15 women; age range of 17-55 y) with positive NMDA receptor antibody encephalitis that underwent an 18F-FDG-PET imaging examination were prospectively selected and compared with a reference group of 14 brain 18F-FDG-PET scans from healthy volunteers using voxel-based statistical analysis. Clusters of hyper- and hypo-metabolism were reported for the whole sample of patients (FWE-corrected P < 0.05), and uncorrected at P < 0.005 for a group of relapsed patients. RESULTS: Mixed metabolic patterns (focal/bilateral hypermetabolism in the temporal lobe, insula, and cerebellum; associated with severe bilateral hypometabolism in the occipital and parietal lobes) were found. CONCLUSIONS: Our findings suggest that 18F-FDG-PET should be included as an imaging tool when assessing affected patients in the clinical workup to rule out anti-NMDA encephalitis and help determine the most effective treatment.

Predicting Neonatal Sepsis Using Features of Heart Rate Variability, Respiratory Characteristics, and ECG-Derived Estimates of Infant Motion.

This study in preterm infants was designed to characterize the prognostic potential of several features of heart rate variability (HRV), respiration, and (infant) motion for the predictive monitoring of late-onset sepsis (LOS). In a neonatal intensive care setting, the cardiorespiratory waveforms of infants with blood-culture positive LOS were analyzed to characterize the prognostic potential of 22 features for discriminating control from sepsis-state, using the Naïve Bayes algorithm. Historical data of the subjects acquired from a period sufficiently before the clinical suspicion of LOS was used as control state, whereas data from the 24 h preceding the clinical suspicion of LOS were used as sepsis state (test data). The overall prognostic potential of all features was quantified at three-hourly intervals for the period corresponding to test data by calculating the area under the receiver operating characteristics curve. For the 49 infants studied, features of HRV, respiration, and movement showed characteristic changes in the hours leading up to the clinical suspicion of sepsis, namely, an increased propensity toward pathological heart rate decelerations, increased respiratory instability, and a decrease in spontaneous infant activity, i.e., lethargy. While features characterizing HRV and respiration can be used to probe the state of the autonomic nervous system, those characterizing movement probe the state of the motor system-dysregulation of both reflects an increased likelihood of sepsis. By using readily interpretable features derived from cardiorespiratory monitoring, opportunities for pre-emptively identifying and treating LOS can be developed.

Clinical characteristics and phenotype-genotype review of 25 Omani children with congenital hyperinsulinism in infancy. A one-decade single-center experience.

OBJECTIVES: To report the genotype-phenotype characteristics, demographic features and clinical outcome of Omani patients with congenital hyperinsulinism (CHI). Methods: We retrospectively analyzed the clinical, biochemical, genotypical, phenotypical characteristics and outcomes of  children with CHI who were presented to the pediatric endocrine team in the Royal Hospital, Muscat, Oman between January 2007 and December 2016. Results: Analysis of 25 patients with CHI genetically revealed homozygous mutation in ABCC8 in 23 (92%) patients and 2 patients (8%) with compound heterozygous mutation in ABCC8. Fifteen (60%) patients underwent subtotal pancreatectomy as medical therapy failed and 2 (8%) patients showed response to medical therapy. Three patients expired during the neonatal period, 2 had cardiomyopathy and sepsis, and one had sepsis and severe metabolic acidosis. Out of the 15 patients who underwent pancreatectomy, 6 developed diabetes mellitus, 6 continued to have hypoglycemia and required medical therapy and one had pancreatic exocrine dysfunction post-pancreatectomy, following up with gastroenterology clinic and was placed on pancreatic enzyme supplements, while 2 patients continued to have hypoglycemia and both had abdominal MRI and 18-F-fluoro-L-DOPA positron emission tomography scan (PET-scan), that showed  persistent of the disease and started on medical therapy. Conclusion:  Mutation in ABCC8 is the most common cause of CHI and reflects the early age of presentation. There is a need for early diagnosis and appropriate therapeutic strategy.

Challenging behaviours at early adulthood in autism spectrum disorders: topography, risk factors and evolution.

BACKGROUND: Challenging behaviours are highly prevalent in children and adolescents with autism spectrum disorders (ASD), but little is known about the prevalence and course of these behaviours during adulthood. The aims of this study were to describe the topography of challenging behaviours in a cohort of 106 young adults with ASD and to identify the risk factors for challenging behaviours. Our secondary objective was to study the changes in challenging behaviours from adolescence to early adult years. METHOD: The present study uses data from the EpiTED prospective follow-up study in France. The presence of challenging behaviours was assessed by the Aberrant Behaviour Checklist (ABC) completed by parent informants. Several dimensions of behaviour were studied: irritability, stereotypy, lethargy, hyperactivity and self-injury. Clinical variables were collected on ASD symptom severity, cognitive and language levels, adaptive behaviours and comorbid medical disorders. RESULTS: The presence of challenging behaviours at early adulthood was related to the young adult's cognitive and language level, ASD symptom severity and comorbid gastrointestinal and sleep disorders. The main risk factor for challenging behaviours was ASD symptom severity. The level of language impairment was a significant predictor of self-injury. Gastrointestinal disorders were a significant predictor of stereotypy. The change in behaviour topography from adolescence to early adult years corresponded with decreased parent report of hyperactivity, but no significant decrease in parent reports of irritability, stereotypy, lethargy and self-injurious behaviours. CONCLUSIONS: The challenging behaviours in individuals with ASD persist in early adulthood and are related to core symptom severity, levels of cognitive and language impairments and medical comorbidity. The results emphasise the importance of early interventions for children with ASD to target cognitive and language abilities and to alleviate the severity of ASD symptoms. They also underscore the need to enhance opportunities for individuals with ASD to better communicate discomforts and pain in the context of medical illness.

Propionate enters GABAergic neurons, inhibits GABA transaminase, causes GABA accumulation and lethargy in a model of propionic acidemia.

Propionic acidemia is the accumulation of propionate in blood due to dysfunction of propionyl-CoA carboxylase. The condition causes lethargy and striatal degeneration with motor impairment in humans. How propionate exerts its toxic effect is unclear. Here, we show that intravenous administration of propionate causes dose-dependent propionate accumulation in the brain and transient lethargy in mice. Propionate, an inhibitor of histone deacetylase, entered GABAergic neurons, as could be seen from increased neuronal histone H4 acetylation in the striatum and neocortex. Propionate caused an increase in GABA (γ-amino butyric acid) levels in the brain, suggesting inhibition of GABA breakdown. In vitro propionate inhibited GABA transaminase with a Ki of ∼1 mmol/l. In isolated nerve endings, propionate caused increased release of GABA to the extracellular fluid. In vivo, propionate reduced cerebral glucose metabolism in both striatum and neocortex. We conclude that propionate-induced inhibition of GABA transaminase causes accumulation of GABA in the brain, leading to increased extracellular GABA concentration, which inhibits neuronal activity and causes lethargy. Propionate-mediated inhibition of neuronal GABA transaminase, an enzyme of the inner mitochondrial membrane, indicates entry of propionate into neuronal mitochondria. However, previous work has shown that neurons are unable to metabolize propionate oxidatively, leading us to conclude that propionyl-CoA synthetase is probably absent from neuronal mitochondria. Propionate-induced inhibition of energy metabolism in GABAergic neurons may render the striatum, in which >90% of the neurons are GABAergic, particularly vulnerable to degeneration in propionic acidemia.

Epigenetic mechanisms in the placenta related to infant neurodevelopment.

As the 'third brain' the placenta links the developing fetal brain and the maternal brain enabling study of epigenetic process in placental genes that affect infant neurodevelopment. We described the characteristics and findings of the 17 studies on epigenetic processes in placental genes and human infant neurobehavior. Studies showed consistent findings in the same cohort of term healthy infants across epigenetic processes (DNA methylation, genome wide, gene and miRNA expression) genomic region (single and multiple genes, imprinted genes and miRNAs) using candidate gene and genome wide approaches and across biobehavioral systems (neurobehavior, cry acoustics and neuroendocrine). Despite limitations, studies support future work on molecular processes in placental genes related to neurodevelopmental trajectories including implications for intervention.

Sluggish Cognitive Tempo, Processing Speed, and Internalizing Symptoms: the Moderating Effect of Age.

Sluggish Cognitive Tempo (SCT) has been defined by a constellation of caregiver-reported symptoms that includes daydreaming, difficulty initiating and sustaining effort, lethargy, and physical underactivity. These symptoms have been observed in both typically developing children and in some children with Attention-Deficit/Hyperactivity Disorder (ADHD)-especially those with the predominantly inattentive presentation. Symptoms of SCT (typically identified via rating scales) appear separable from DSM inattentive ADHD symptoms, but have also been associated with internalizing symptoms. To date, however, few studies have examined associations among ratings of SCT and speeded performance-based measures. The present study examined associations among SCT, processing speed, and internalizing symptoms in a sample of 566 clinically referred children (65% male), while also considering how these associations change with age. Findings revealed small but significant age-related differences in the strength of associations between the "Daydreamy" element of SCT and processing speed (as measured by the WISC-IV Processing Speed Index-PSI), with stronger associations observed in younger children. Importantly, this difference in strength of association was not accounted for by the change in WISC-IV test forms for PSI subtests between 6-7 year-olds and 8-16 year-olds. Conversely, the association between SCT and internalizing symptoms remained generally consistent across the age range. Findings contribute to further characterization of the "slowness" of responding seen in SCT and may have implications for behavioral intervention.

Metabolically based liver damage pathophysiology in patients with urea cycle disorders - A new hypothesis.

The underlying pathophysiology of liver dysfunction in urea cycle disorders (UCDs) is still largely elusive. There is some evidence that the accumulation of urea cycle (UC) intermediates are toxic for hepatocyte mitochondria. It is possible that liver injury is directly caused by the toxicity of ammonia. The rarity of UCDs, the lack of checking of iron level in these patients, superficial knowledge of UC and an underestimation of the metabolic role of fumaric acid, are the main reasons that are responsible for the incomprehension of the mechanism of liver injury in patients suffering from UCDs. Owing to our routine clinical practice to screen for iron overload in severely ill neonates, with the focus on the newborns suffering from acute liver failure, we report a case of citrullinemia with neonatal liver failure and high blood parameters of iron overload. We hypothesize that the key is in the decreased-deficient fumaric acid production in the course of UC in UCDs that causes several sequentially intertwined metabolic disturbances with final result of liver iron overload. The presented hypothesis could be easily tested by examining the patients suffering from UCDs, for liver iron overload. This could be easily performed in countries with a high population and comprehensive national register for inborn errors of metabolism. CONCLUSION: Providing the hypothesis is correct, neonatal liver damage in patients having UCD can be prevented by the supplementation of pregnant women with fumaric or succinic acid, prepared in the form of iron supplementation pills. After birth, liver damage in patients having UCDs can be prevented by supplementation of these patients with zinc fumarate or zinc succinylate, as well.

Preclinical Evaluation of the Novel BTK Inhibitor Acalabrutinib in Canine Models of B-Cell Non-Hodgkin Lymphoma.

Acalabrutinib (ACP-196) is a second-generation inhibitor of Bruton agammaglobulinemia tyrosine kinase (BTK) with increased target selectivity and potency compared to ibrutinib. In this study, we evaluated acalabrutinib in spontaneously occurring canine lymphoma, a model of B-cell malignancy similar to human diffuse large B-cell lymphoma (DLBCL). First, we demonstrated that acalabrutinib potently inhibited BTK activity and downstream effectors in CLBL1, a canine B-cell lymphoma cell line, and primary canine lymphoma cells. Acalabrutinib also inhibited proliferation in CLBL1 cells. Twenty dogs were enrolled in the clinical trial and treated with acalabrutinib at dosages of 2.5 to 20mg/kg every 12 or 24 hours. Acalabrutinib was generally well tolerated, with adverse events consisting primarily of grade 1 or 2 anorexia, weight loss, vomiting, diarrhea and lethargy. Overall response rate (ORR) was 25% (5/20) with a median progression free survival (PFS) of 22.5 days. Clinical benefit was observed in 30% (6/20) of dogs. These findings suggest that acalabrutinib is safe and exhibits activity in canine B-cell lymphoma patients and support the use of canine lymphoma as a relevant model for human non-Hodgkin lymphoma (NHL).

Encephalitis Lethargica With Isolated Substantia Nigra Lesions Followed by a Second Encephalitis in a Child With Humoral Immunodeficiency.

BACKGROUND: Encephalitis lethargica is an encephalitic illness with multiple nervous system symptoms. Lesions only involving substantia nigra on magnetic resonance imaging are uncommon, especially in children. A second encephalitis illness after encephalitis lethargica has never been reported before. PATIENT DESCRIPTION: We describe a 7-year-old boy with humoral immunity deficiency who developed encephalitis lethargica associated with bilateral substantia nigra lesions on magnetic resonance imaging. After a nearly complete recovery, he developed encephalitis once again. He was diagnosed with encephalitis lethargica with somnolence, akinetic mutism, and ophthalmoplegia after intermittent fever. Cerebrospinal fluid pleocytosis and positive oligoclonal bands were documented. Symmetrical substantia nigra lesions on high-intensity magnetic resonance imaging gradually evolved into a liquid signal. He had almost recovered when he developed fatigue and hypersomnia and was diagnosed with encephalitis again, supported by mild pleocytosis in cerebrospinal fluid and subcortical white matter lesions in the frontal lobes. His symptoms resolved following administration of corticosteroids and immunoglobulins. CONCLUSION: This is the first report of an immune-deficient child to develop encephalitis lethargica with isolated substantia nigra lesions on magnetic resonance imaging and a second encephalitis illness after recovery from encephalitis lethargica.

Longitudinal trajectories of aberrant behavior in fragile X syndrome.

The Aberrant Behavior Checklist-Community (ABC-C; Aman et al., 1995) has been increasingly adopted as a primary tool for measuring behavioral change in clinical trials for individuals with fragile X syndrome (FXS). To our knowledge, however, no study has documented the longitudinal trajectory of aberrant behaviors in individuals with FXS using the ABC-C. As part of a larger longitudinal study, we examined scores obtained on the ABC-C subscales for 124 children and adolescents (64 males, 60 females) with FXS who had two or more assessments (average interval between assessments was approximately 4 years). Concomitant changes in age-equivalent scores on the Vineland Adaptive Behavior Scales (VABS) were also examined. As expected for an X-linked genetic disorder, males with FXS obtained significantly higher scores on all subscales of the ABC-C and significantly lower age-equivalent scores on the VABS than females with FXS. In both males and females with FXS, scores on the Irritability/Agitation and Hyperactivity/Noncompliance subscales of the ABC-C decreased significantly with age, with little to no change occurring over time on the Lethargy/Social Withdrawal, Stereotypic Behavior, and Inappropriate Speech subscales. The decrease in scores on the Hyperactivity/Noncompliance domain was significantly greater for males than for females. In both males and females, age-equivalent scores on the VABS increased significantly over this developmental period. These results establish a basis upon which to evaluate long-term outcomes from intervention-based research. However, longitudinal direct observational studies are needed to establish whether the severity of problem behavior actually decreases over time in this population.

Fighting insomnia and battling lethargy: the yin and yang of palliative care.

There is an interdependent relationship between insomnia and fatigue in the medical literature, but both remain distinct entities. Insomnia entails problematic sleep initiation, maintenance, or restoration with an accompanying decrease in perceived daytime function. Lethargy is a symptom that has a wide differential diagnosis that heavily overlaps with cancer-related fatigue; however, insomnia may contribute to worsened fatigue and lethargy in cancer patients. Insomnia is a major risk factor for mood disturbances such as depression, which may also contribute to lethargy in this at-risk population. The pathophysiology of fatigue and insomnia is discussed in this review, including their differential diagnoses as well as the emerging understanding of the roles of neurotransmitters, branched-chain amino acids, and inflammatory cytokines. Treatment approaches for insomnia and fatigue are also discussed and reviewed, including the role of hypnotics, psychotropics, hormonal agents, and alternative therapies.

Reduced sleep-like quiescence in both hyperactive and hypoactive mutants of the Galphaq Gene egl-30 during lethargus in Caenorhabditis elegans.

Sleep-like states are characterized by massively reduced behavioral activity. Little is known about genetic control of sleep-like behavior. It is also not clear how general activity levels during wake-like behavior influence activity levels during sleep-like behavior. Mutations that increase wake-like activity are generally believed to also increase activity during sleep-like behavior and mutations that decrease wake-like activity are believed to have decreased activity during sleep-like behavior. We studied sleep-like behavior during lethargus in larvae of Caenorhabditis elegans. We looked through a small set of known mutants with altered activity levels. As expected, mutants with increased activity levels typically showed less sleep-like behavior. Among these hyperactive mutants was a gain-of-function mutant of the conserved heterotrimeric G protein subunit Galphaq gene egl-30. We found, however, that an unusual semidominant hypoactive mutant of egl-30 also had reduced sleep-like behavior. While movement was severely reduced and impaired in the semidominant egl-30 mutant, sleep-like behavior was severely reduced: the semidominant egl-30 mutant lacked prolonged periods of complete immobility, reduced spontaneous neural activity less, and reduced responsiveness to stimulation less. egl-30 is a well-known regulator of behavior. Our results suggest that egl-30 controls not only general activity levels, but also differences between wake-like and sleep-like behavior.

Spectrum of nonconvulsive status epilepticus in patients with cancer.

PURPOSE: Determine incidence, clinical presentation, electrographic correlates, and outcome of nonconvulsive status epilepticus (NCSE) in cancer patients on whom an EEG was performed. METHODS: Retrospective review of 947 EEG reports on 658 patients in whom any type of EEG was performed at Memorial Sloan-Kettering Cancer Center (July 2006 to March 2008). Using the Epilepsy Research Foundation criteria, patients were classified as definite or probable NCSE. Medical records were reviewed for diagnosis, causes of NCSE, response to treatment, and outcome. Mortality was determined for patients with NCSE. RESULTS: Twenty-six episodes of NCSE were identified in 25 patients (25/658, 4%). Eleven patients had primary brain tumor, 12 patients systemic cancer, and two had both. At diagnostic EEG, 18 were awake, 3 were lethargic, and 5 patients were comatose. EEG revealed a seizure in 62% of the patients, periodic lateralized epileptiform discharges in 42%, and periodic epileptiform discharges in 7.7%. Neuroimaging revealed new intracranial pathology in 54% of the patients. Seventy-seven percent of the patients achieved control; 65% required ≥3 antiepileptic drugs, and 33% required intubation. Three patients died from NCSE. DISCUSSION: In our cohort, awake NCSE was more common than comatose NCSE. Treatment was successful in patients with heterogeneous central nervous system disease. EEG evaluation should be considered in patients with cancer because NCSE is treatable despite a high prevalence of structural brain disease. Nonconvulsive status epilepticus control did not always require intubation and burst suppression, but frequently required three or more antiepileptic drugs.

Caenorhabditis-in-drop array for monitoring C. elegans quiescent behavior.

STUDY OBJECTIVES: To develop a method, called Caenorhabditis-in-Drop (CiD), encapsulating single worms in aqueous drops, for parallel analysis of behavioral quiescence in C. elegans nematodes. DESIGN: We designed, constructed, and tested a device that houses an array of aqueous droplets laden with individual worms. The droplets are separated and covered by immiscible, biocompatible oil. We modeled gas exchange across the aqueous/oil interface and tested the viability of the encapsulated animals. We studied the behavior of wild-type animals; of animals with a loss of function mutation in the cGMP-dependent protein kinase gene egl-4; of animals with a loss of function mutation in the gene kin-2, which encodes a cAMP-dependent protein kinase A regulatory subunit; of animals with a gain-of-function mutation in the gene acy-1, which encodes an adenylate cyclase; and of animals that express high levels of the EGF protein encoded by lin-3. MEASUREMENTS AND RESULTS: We used CiD to simultaneously monitor the behavior of 24 worms, a nearly 5-fold improvement over the prior best methodology. In support of our gas exchange models, we found that worms remain viable on the chip for 4 days, past the 12-h period needed for observation, but show reduced longevity to that measured on an agar surface. Measurements of duration of lethargus quiescence and total leth-argus quiescence showed reduced amounts as well as reduced variability relative to prior methods. There was reduced lethargus quiescence in animals that were mutant for kin-2 and for acy-1, supporting a wake-promoting effect of PKA in C. elegans, but no change in lethargus quiescence in egl-4 mutants. There was increased quiescence in animals that expressed kin-2 in the nervous system or over-expressed EGF. CONCLUSIONS: CiD is useful for the analysis of behavioral quiescence during lethargus as well as during the adult stage C. elegans. The method is expandable to parallel simultaneous monitoring of hundreds of animals and for other studies of long-term behavior. Using this method, we were successful in measuring, for the first time, quiescence in kin-2(ce179) and in acy-2(ce2) mutants, which are hyperactive. Our observations also highlight the impact of environmental conditions on quiescent behavior and show that longevity is reduced in CiD in comparison to agar surfaces.

Neurotoxic effects of ivermectin administration in genetically engineered mice with targeted insertion of the mutated canine ABCB1 gene.

OBJECTIVE: To develop in genetically engineered mice an alternative screening method for evaluation of P-glycoprotein substrate toxicosis in ivermectin-sensitive Collies. ANIMALS: 14 wild-type C57BL/6J mice (controls) and 21 genetically engineered mice in which the abcb1a and abcb1b genes were disrupted and the mutated canine ABCB1 gene was inserted. PROCEDURES: Mice were allocated to receive 10 mg of ivermectin/kg via SC injection (n = 30) or a vehicle-only formulation of propylene glycol and glycerol formal (5). Each was observed for clinical signs of toxic effects from 0 to 7 hours following drug administration. RESULTS: After ivermectin administration, considerable differences were observed in drug sensitivity between the 2 types of mice. The genetically engineered mice with the mutated canine ABCB1 gene had signs of severe sensitivity to ivermectin, characterized by progressive lethargy, ataxia, and tremors, whereas the wild-type control mice developed no remarkable effects related to the ivermectin. CONCLUSIONS AND CLINICAL RELEVANCE: The ivermectin sensitivity modeled in the transgenic mice closely resembled the lethargy, stupor, disorientation, and loss of coordination observed in ivermectin-sensitive Collies with the ABCB1-1Δ mutation. As such, the model has the potential to facilitate toxicity assessments of certain drugs for dogs that are P-glycoprotein substrates, and it may serve to reduce the use of dogs in avermectin derivative safety studies that are part of the new animal drug approval process.

Identification of cancer-related symptom clusters: an empirical comparison of exploratory factor analysis methods.

CONTEXT: Symptom clusters, important for symptom management strategies, have been determined empirically by various analytical methods. Guidance to select methods from the options available in standard statistical packages is limited. OBJECTIVES: To compare alternative common factor analysis (FA) extraction methods appropriate to the data, to assess whether or not they determine similar symptom clusters, and to propose analytical approaches that are useful in this clinical context. METHODS: Within one month of commencing chemotherapy, outpatients from oncology and hematology clinics (n = 202) reported their symptom experience on a modified Rotterdam Symptom Checklist. Symptom distress levels in the past week were rated on a scale of one (not at all) to four (very much). In a secondary data analysis of 42 symptoms, the associations between symptoms and factors were determined using alternative common FA methods: principal axis factoring, unweighted least squares, image factor analysis, and alpha factor analysis (AFA). Symptom inclusion in a cluster was based on the interpretation of pattern and structure coefficients, and importantly, clinical relevance of the grouping. RESULTS: Five symptom clusters were commonly identified across methods: musculoskeletal discomforts/lethargy, oral discomforts, upper gastrointestinal discomforts, vasomotor symptoms, and gastrointestinal toxicities. In AFA, three additional clusters were lethargy, somatic symptoms, and treatment-related symptom clusters. CONCLUSION: The most parsimonious solution resulted from principal axis factoring, but for large numbers of symptoms, AFA may be superior by identifying symptom clusters more useful for symptom management. Interpreting complex symptom relationships may lead to the investigation of pathophysiological mechanisms and intervention opportunities. Future studies should include psychological and cognitive symptoms.

Study of clinical and aetiological profile of 100 patients of pancytopenia at a tertiary care centre in India.

Pancytopenia is not a disease but an important clinico-haematological entity encountered in our day-to-day clinical practice with findings that may result from a number of disease processes. A total of 100 patients of pancytopenia admitted in medicine wards of Civil Hospital, Ahmedabad, Gujuarat, India, were studied. The most common cause of pancytopenia was megaloblastic anaemia (45%) followed by infections (20%) and hypersplenism (15%). As compared with other causes, megaloblastic anaemia was statistically significant cause (P < 0.01) of pancytopenia, in our study. The most common clinical presentation of patients with megaloblastic anaemia was lethargy (100%) and pallor (100%). In patients with megaloblastic anaemia, mean haemoglobin (Hb) was 5.6 ± 1.7 g/dl, mean white blood corpuscle (WBC) count was 2735 ± 4152 and mean platelet count was 52,250 ± 24,213. Mean corpuscular volume (MCV) was 101.2 ± 11 in patients of megaloblastic anaemia. Morphology of RBC was marocytic in 95% of patients with megaloblastic anaemia, whereas hypersegmented neutrophils and macrovalocytes were seen in 60-65% patients of megaloblastic anaemia.