Insuficiencia suprarrenal secundaria: una causa subestimada de hiponatremia euvolemica

RESUMEN Introducción: La hiponatremia por insuficiencia suprarenal secundaria es subestimada tratamiento inapropiados. Objetivos: Describir las características clínicas y bioquímicas de pacientes con hiponatremia por insuficiencia suprarrenal secundaria y sus causas. Materiales y Metodos: Revisión retrospectiva de historias clínicas de pacientes consultantes a un hospital de tercer nivel entre Enero 2015 a Septiembre 2017 con hiponatremia y bioquímica de insuficiencia suprarenal secundaria. Los hallazgos fueron comparados con los reportados por estudios previamente publicados. Resultados: Todos los pacientes con insuficiencia suprarrenal secundaria se presentaron con hiponatremia euvolemica hipotónica. 54.5% eran mujeres, la edad promedio fue 57 años. Solo 1 paciente tuvo hiponatremia leve. La mediana de la concentración de cortisol fue 2.8 mcg/dL (RIQ 1.75-3.25 mcg/dL) y la de ACTH fue de 7.7 pg/nL (RIQ 4.5-9.5 pg/nL). Todos los pacientes tuvieron densidad urinaria alta indistinguible del SSIDH. El hipogonadismo hipogonadotrópico y el hipotiroidismo central fueron las alteraciones de ejes hipofisarios mas comúnmente asociados. La presencia de hipoglicemia, hipotensión e hipercaliemia fue baja. La causa más frecuente fue silla turca vacía. Conclusiones: La hiponatremia hipotonica euvolémica es una presentación común de insuficiencia suprarrenal secundaria y no suele acompañarse de otras manifestaciones de deficiencia de glucocorticoides. Es clínica y bioquímicamente indistinguible del SSIDH. Un bajo umbral de sospecha y la medición de cortisol serico matutino es esencial en estos pacientes para evitar un diagnostico y manejo inapropiados.

ABSTRACT Introduction: Hyponatremia due to secondary adrenal insufficiency is frequently underestimated and underdiagnosed. This paper underscores the importance of an adequate evaluation of euvolemic hyponatremia to avoid an inappropriate treatment and diagnosis. Objectives: To describe the clinical and biochemical characteristics of patients with hyponatremia due to secondary adrenal insufficiency and its causes. Materials and Methods: A retrospective review of the clinical records of patients presenting to a third level hospital between January 2015 to September 2017 with hyponatremia and a biochemical profile of secondary adrenal insufficiency. Findings were compared with previously published reports. Results: All patients with secondary adrenal insufficiency presented with hypotonic euvolemic hyponatremia. 54.5% of patients were females, median age was 57 years. Only 1 patient had mild hyponatremia. Cortisol median concentration was 2.8 mcg/dL (IQR 1.75-3.25 mcg/dL) and median ACTH concentration was 7.7 pg/nL (IQR 4.5-9.5 pg/nL). All the patients had high urinary density and features indistinguishable from SIADH. Hypogonadotropic hypogonadism and central hypothyroidism were the most commonly accompanying hypophyseal axis. Hypoglycemia, hypotension, and hyperkalemia were infrequent findings in these patients. The most frequent etiology identified was empty sella syndrome. Conclusions: Euvolemic hypotonic hyponatremia is a common presentation of secondary adrenal insufficiency and is often not accompanied with other manifestations of glucocorticoid deficiency. This disease is clinical and biochemical indistinguishable from SIADH. A low threshold for suspicion and a serum morning cortisol measurement in these patients is essential to avoid an inappropriate diagnosis and management.

Production and properties of a bioemulsifier obtained from a lactic acid bacterium.

In the present work, the production of bioemulsifier (BE) by a lactic acid bacterium (LAB) grown at 25 °C in lactic whey-based media for 24 h was evaluated. Maximum production was detected in a medium containing yeast extract, peptone and lactic whey (LAPLW medium), with a yield of 270 mg L-1. The BE proved to be more innocuous for Caco-2 cells, used as a toxicological indicator, than the non-ionic surfactant Triton X-100. In addition, the microbial product presented higher stability to changes in temperature (37 °C to 100 °C), pH (2-10), and salt concentration (5% and 20%, w/v) than the synthetic surfactant. Regarding emulsifying capacity tested against different hydrophobic substrates (kerosene, motor oil, diesel, sunflower oil, and grape oil), the BE displayed E24 values similar to or even better than those of Triton X-100. Finally, Triton X-100 caused irreversible modifications on the giant unilamellar vesicles (used as model membrane system), promoting the solubilization of the lipid bilayers. Nevertheless, BE induced temporary modifications of the membrane, which is associated with incorporation of the bioproduct in the outer layer. These results demonstrate the role of BE in biological processes, including reversible changes in microbial membranes to enhance the access to hydrophobic substrates.

Concurrent chemoradiation for locally advanced stage III non-small cell lung cancer with cisplatin, vinorelbine, and thoracic radiotherapy: a phase II study from the Galician Lung Cancer Group.

PURPOSE: The aim of this phase II study was to evaluate the activity and safety of the combination of cisplatin and vinorelbine with thoracic radiotherapy in unresectable locally advanced stage III non-small cell lung cancer (NSCLC). The primary endpoint was the objective response rate (ORR). Secondary objectives included toxicity profile, progression-free survival (PFS), and overall survival (OS). MATERIALS AND METHODS: A total of 48 NSCLC patients were enrolled (median age 60 years, 52% stage IIIA and 48% stage IIIB, 52% adenocarcinoma). Patients received three cycles of chemotherapy every 21 days [intravenous cisplatin 80 mg/m2 and intravenous vinorelbine 25 mg/m2 on day 1 and oral vinorelbine on day 8 (60 mg/m2)] concurrent with radiotherapy (66 Gy, administered at 1.8 Gy per day, five consecutive days per week). RESULTS: ORR was 79.2% (72.9% showing partial response and 6.3% showing complete response). With a median follow-up of 20.7 months, median PFS was 12 months and median OS was 36 months. Grade 3/4 toxicities were: neutropenia (14.5%), anaemia (6.2%), vomiting (2%), and oesophagitis (4.2%). No toxic deaths were reported. CONCLUSION: This combined regimen shows efficacy and a manageable safety profile. PFS and OS outcomes are encouraging and warrant further research.

Divergence in mating signals correlates with genetic distance and behavioural responses to playback.

Animals use acoustic signals to defend resources against rivals and attract breeding partners. As with many biological traits, acoustic signals may reflect ancestry; closely related species often produce more similar signals than do distantly related species. Whether this similarity in acoustic signals is biologically relevant to animals is poorly understood. We conducted a playback experiment to measure the physical and vocal responses of male songbirds to the songs of both conspecific and allopatric-congeneric animals that varied in their acoustic and genetic similarity. Our subjects were territorial males of four species of neotropical Troglodytes wrens: Brown-throated Wrens (Troglodytes brunneicollis), Cozumel Wrens (T. beani), Clarion Wrens (T. tanneri) and Socorro Wrens (T. sissonii). Our results indicate that birds respond to playback of both conspecific and allopatric-congeneric animals; that acoustic differences increase with genetic distance; and that genetic divergence predicts the strength of behavioural responses to playback, after removing the effects of acoustic similarity between subjects' songs and playback stimuli. Collectively, these results demonstrate that the most distantly related species have the most divergent songs; that male wrens perceive divergence in fine structural characteristics of songs; and that perceptual differences between species reflect evolutionary history. This study offers novel insight into the importance of acoustic divergence of learned signals and receiver responses in species recognition.

Adjuvant chemotherapy for elderly patients with stage I non-small-cell lung cancer ≥4 cm in size: an SEER-Medicare analysis.

BACKGROUND: The role of adjuvant chemotherapy for non-small-cell lung cancer (NSCLC) stage I patients with tumors size ≥4 cm is not well established in the elderly. PATIENTS AND METHODS: We identified 3289 patients with stage I NSCLC (T2N0M0 and tumor size ≥4 cm) who underwent lobectomy from the Surveillance, Epidemiology and End Results (SEER)-Medicare linked database diagnosed from 1992 to 2009. Overall survival and rates of serious adverse events (defined as those requiring admission to hospital) were compared between patients treated with resection alone, platinum-based adjuvant chemotherapy, or postoperative radiation (PORT) with or without adjuvant chemotherapy. Propensity scores for receiving each treatment were calculated and survival analyses were conducted using inverse probability weights based on the propensity score. RESULTS: Overall, 84% patients were treated with resection alone, 9% received platinum-based adjuvant chemotherapy, and 7% underwent PORT with or without adjuvant chemotherapy. Adjusted analysis showed that adjuvant chemotherapy [hazard ratio (HR), 0.82; 95% confidence interval (CI) 0.68-0.98] was associated with improved survival compared with resection alone. Conversely, the use of PORT with or without adjuvant chemotherapy (HR 1.91; 95% CI 1.64-2.23) was associated with worse outcomes. Patients receiving adjuvant chemotherapy had more serious adverse events compared with those treated with resection alone, with neutropenia (odds ratio, 21.2; 95% CI 5.8-76.6) being most significant. No significant difference was observed in rates of fever, cytopenias, nausea, and renal dysfunction. CONCLUSIONS: Platinum-based adjuvant chemotherapy is associated with reduced mortality and increased serious adverse events in elderly patients with stage I NSCLC and tumor size ≥4 cm.

Competency frameworks for advanced practice nursing: a literature review.

AIM: This paper describes a literature review that identified common traits in advanced practice nursing that are specific to competency development worldwide. BACKGROUND: There is a lack of international agreement on the definition of advanced practice nursing and its core competencies. Despite the lack of consensus, there is an ongoing process worldwide to establish and outline the standards and competencies for advanced practice nursing roles. INTRODUCTION: International agencies, such as the International Council of Nurses, have provided general definitions for advanced practice nursing. Additionally, a set of competency standards for this aim has been developed. METHODS: A literature review and a directed search of institutional websites were performed to identify specific developments in advanced practice nursing competencies and standards of practice. To determine a competency map specific to international advanced practice nursing, key documents were analysed using a qualitative approach based on content analysis to identify common traits among documents and countries. RESULTS: The review process identified 119 relevant journal articles related to advanced practice nursing competencies. Additionally, 97 documents from grey literature that were related to advanced practice nursing competency mapping were identified. From the text analysis, 17 worldwide transversal competency domains emerged. CONCLUSIONS: Despite the variety of patterns in international advanced practice nursing development, essential competency domains can be found in most national frameworks for the role development of international advanced practice nursing. These 17 core competencies can be used to further develop instruments that assess the perceived competency of advanced practice nurses. IMPLICATIONS FOR NURSING AND HEALTH POLICY: The results of this review can help policy developers and researchers develop instruments to compare advanced practice nursing services in various contexts and to examine their association with related outcomes.

[Preiser's disease. A case study]. / Enfermedad de Preiser. A propósito de un caso.

The idiopathic avascular necrosis of the scaphoid or Preiser's disease is condition about which few cases have been described. In the majority of cases, it is debatable whether it is actually a spontaneous osteonecrosis, or a pathological process secondary to a systematic disease, or a result of chemotherapy treatment, or associated with taking steroids. We present the case of a 20-year old woman, with no previous trauma, with pain in her right wrist, which progressed over a period of four years. It was wrongly diagnosed as a tendinitis, and was treated conservatively without any improvement. A simple X-ray was requested that showed an abnormality of the proximal pole of the scaphoid that was beginning to fragment; a fact which was confirmed later by performing a CT scan. This was followed by nuclear magnetic resonance spectroscopy (NMR), which showed signs of ischaemia, mainly in the proximal pole. There were signs of viability in the distal fragment in the NMR using paramagnetic contrast. After the imaging tests, idiopathic avascular necrosis of the scaphoid was diagnosed. The surgical treatment consisted of the removal of necrotic fragments of the proximal pole and removal of the posterior interosseous-nerve. Two years after the intervention, the patient is asymptomatic and with a complete range of movement in the operated wrist.

Enfermedad de Preiser. A propósito de un caso / Preiser's disease. A case study

La necrosis avascular idiopática del escafoides o enfermedad de Preiser es una entidad de la que se han descrito pocos casos. En algunas ocasiones es discutible si se trata de una osteonecrosis espontánea o representa un proceso patológico secundario a enfermedades sistémicas, tratamiento quimioterápico o está relacionada con el consumo de esteroides. Presentamos el caso de una mujer de 20 años de edad, sin traumatismo previo, con dolor en la muñeca derecha de 4 años de evolución. Había sido erróneamente diagnosticada de una tendinitis y tratada de forma conservadora sin mejoría. Se solicitaron estudios de imagen mediante radiología simple. Los hallazgos radiológicos presentaban una anomalía del polo proximal del escafoides que originaba una fragmentación del mismo, hecho que se confirmó posteriormente con la realización de una TC. A continuación se realizó una RMN en la que se observaron criterios de isquemia, fundamentalmente en polo proximal. En la RMN con contraste paramagnético aparecieron signos de viabilidad en el fragmento distal y de osteonecrosis en el proximal. Tras las pruebas de imagen se diagnosticó de necrosis avascular idiopática del escafoides. El tratamiento quirúrgico consistió en extirpar los fragmentos necróticos del polo proximal y practicar una neurectomía del nervio interóseo posterior. A los 2 años de la intervención, la paciente se encuentra asintomática y con un balance articular completo de la muñeca intervenida (AU)

The idiopathic avascular necrosis of the scaphoid or Preiser's disease is condition about which few cases have been described. In the majority of cases, it is debatable whether it is actually a spontaneous osteonecrosis, or a pathological process secondary to a systematic disease, or a result of chemotherapy treatment, or associated with taking steroids. We present the case of a 20-year old woman, with no previous trauma, with pain in her right wrist, which progressed over a period of four years. It was wrongly diagnosed as a tendinitis, and was treated conservatively without any improvement. A simple X-ray was requested that showed an abnormality of the proximal pole of the scaphoid that was beginning to fragment; a fact which was confirmed later by performing a CT scan. This was followed by nuclear magnetic resonance spectroscopy (NMR), which showed signs of ischaemia, mainly in the proximal pole. There were signs of viability in the distal fragment in the NMR using paramagnetic contrast. After the imaging tests, idiopathic avascular necrosis of the scaphoid was diagnosed. The surgical treatment consisted of the removal of necrotic fragments of the proximal pole and removal of the posterior interosseous-nerve. Two years after the intervention, the patient is asymptomatic and with a complete range of movement in the operated wrist (AU)

Brain metastases from prostate adenocarcinoma.

Brain metastases of prostate adenocarcinoma are rare. We report a case of brain metastases from prostate adenocarcinoma 15 months after the diagnosis of the primary tumour. The patient had headache and one solitary metastasis upon magnetic resonance imaging (MRI). The biopsy performed showed metastatic prostate adenocarcinoma. He was treated with surgery and cranial irradiation.

Brain metastases from prostate adenocarcinoma

Brain metastases of prostate adenocarcinoma are rare. We report a case of brain metastases from prostate adenocarcinoma 15 months after the diagnosis of the primary tumour. The patient had headache and one solitary metastasis upon magnetic resonance imaging (MRI). The biopsy performed showed metastatic prostate adenocarcinoma. He was treated with surgery and cranial irradiation (AU)

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Factors associated with type 1 diabetes in Kuwaiti children.

Type 1 diabetes is a common chronic disease in childhood, and the outcome of environmental, genetic and immunologic interactions. The aim was to study the social and metabolic characteristics (lipids, lipoproteins, apolipoproteins, lipoprotein a (Lpa) and total sialic acid) and predisposing factors in 6-18-year-old Kuwaiti children with type 1 diabetes. This pair-matched case-control study included 348 type 1 diabetic children (131 males, 217 females) matched by age and gender to 348 non-diabetic controls. Diabetic children were identified, according to the WHO and the American Diabetes Association criteria, at 182 randomly selected schools. Social and metabolic characteristics were adversely affected in diabetic children compared to their controls. The logistic regression analysis showed that the predisposing factors: family history of type 1 and type 2 diabetes and thyroid disease, were significant associated factors with type 1 diabetes after adjusting for demographic and social variables. The significant correlations of Lpa and total sialic acid with glycated haemoglobin, lipoproteins and apolipoproteins partially explain reporting them as possible markers for coronary heart disease. There are adverse metabolic changes in children with type 1 diabetes. As these changes are associated with early onset atherogenesis, metabolic markers need to be measured and possibly corrected at an early stage in children with diabetes.

Social and psychological characteristics of Kuwaiti children and adolescents with type 1 diabetes.

Type 1 diabetes mellitus is a chronic disease that may have an impact on children's psychosocial adjustment. This study aimed to investigate the psychosocial characteristics of Kuwaiti children with type 1 diabetes as compared to healthy children without diabetes, and assess the impact of glycaemic control on psychosocial variables. A total of 349 school children aged 6-18 years with type 1 diabetes, and 409 children without diabetes having comparable age, gender, and social class were included in the study. Data were obtained by interviewing children and parents using a questionnaire. Psychological distress was measured by the Hopkins symptoms checklist-25 scale including anxiety and depression. Glycaemic control was assessed by glycosylated haemoglobin, HbA(IC) level. Glycaemic control was considered 'good to excellent' at HbA(IC)<8.0%, 'fair' at HbA(IC) 8.1 to 10.0%, and 'poor' at HbA(IC)>10.0%. Median scores of anxiety, depression, and total distress were significantly higher in children with diabetes indicating worse psychological adjustment. There was also significant difference between children with diabetes and those without diabetes in social aspects and school absence days. There was significant positive correlation between HbA(IC) concentration and scores of the psychological functioning indices. Children with poor glycaemic control had worse psychological adjustment. After controlling the variance accounted by gender and age, stepwise multiple regression analysis showed that girls, older children, children in need of emotional support, and those with higher HbA(IC) were at higher risk for psychological maladjustment. These variables explained 47.9% of the variation in total distress. In conclusion, the study supported our hypotheses. Children with diabetes had worse psychological adjustment, and distress was related to glycaemic control. Since psychological distress increases the risk for future complications due to its relation with glycaemic control, longitudinal studies are recommended to identify children with diabetes having distress at an early stage when preventive interventions are effective.

Typical and atypical presentations of gastroesophageal reflux disease and its management

Gastroesophageal Reflux disease (GERD) has a common clinical presentation of a burning discomfort in the retroesternal area, regurgitation and dysphagia. Yet, an estimated of 20 to 60 percent of patients with GERD have head and neck symptoms without any appreciable heartburn. Careful history and a meticulous physical exam can guide us to have a correct diagnosis and give adequate treatment. Other methods, such as gastroscopy and gastric pH monitoring, as well as other diagnostic studies can help us to confirm the diagnosis. Once we have the correct diagnosis stabilized, life style modification should be the first step in the management of GERD, aided with antacids, H2 receptors antagonists and/or Proton pump inhibitors. Family physicians should be aware that helping patients to understand the cause of their symptoms and reinforcing the life style modifications will bring better control of the disease and patients can have improvement of their symptoms leading to possible cure of the disease. Gastroesophageal Reflux Disease (GERD) is defined as the movement of gastric contents into the esophagus without presence of vomiting. It is frequently associated with heartburn, the sensation of burning discomfort in retrosternal area, that moves upward, toward the throat. GERD is a chronic, relapsing condition with associated morbidity and adverse impact on quality of life. The purpose of this article is to give an overall look at the clinical presentations of GERD with typical and atypical symptoms, the various presentations of this disease in all of the age groups, and to identify all of the aspects that contribute to the progression and solution of this problem

Lipoprotein(a) and other cardiovascular metabolic risk factors in Kuwaiti children with type-1 diabetes.

BACKGROUND/AIMS: Lipoprotein(a) synthesis and catabolism could be influenced by insulin or by diabetes metabolic complications in patients with type-1 diabetes. The aim of the study was to investigate the relation of plasma lipoprotein(a) concentrations with metabolic cardiovascular risk factors in Kuwaiti children with uncomplicated type-1 diabetes. METHODS: This case-control study included 115 (44 males and 71 females) diabetic children aged 6-18 years matched by age and sex to 115 non-diabetic children as controls. RESULTS: There was no significant difference between the mean lipoprotein(a) concentrations in type-1 diabetic children (27.34 mg/dl) and their controls (22.80 mg/dl). Total cholesterol, apolipoprotein A1 and B levels were significantly higher in diabetic children than controls. In diabetic children, significant correlations were found between lipoprotein(a) levels and glycated hemoglobin (r = 0.249, p = 0.011), total cholesterol (r = 0.208, p = 0.025), and apolipoprotein B (r = 0.349, p < 0.001). The proportion of diabetic children with lipoprotein(a) >30 mg/dl was significantly higher in those having poor glycemic control (glycated hemoglobin >9.0%, p = 0.013), raised total cholesterol (p = 0.033), or with a family history of cardiovascular disease (p = 0.006). CONCLUSION: Plasma lipoprotein(a) levels were not elevated in young type-1 diabetic children compared to non-diabetic controls; however, lipoprotein(a) levels were significantly higher in diabetic children with poor glycemic control. Moreover, there were significant correlations between lipoprotein(a) and the metabolic cardiovascular risk factors total cholesterol, atherogenic index, apolipoprotein B and apolipoprotein B/A1 ratio.

Angiotensin-converting enzyme gene polymorphism and lipid profiles in Kuwaiti children with type 1 diabetes.

METHODS: We studied angiotensin-converting enzyme (ACE) gene polymorphism and lipid profiles in Kuwaiti children with uncomplicated type 1 diabetes. A total of 125 children with type 1 diabetes were matched in a case-control study on age and gender to 125 non-diabetic children as controls. Serum lipids (total cholesterol, TC; high-density lipoprotein cholesterol, HDL; low-density lipoprotein cholesterol, LDL-c; triglycerides, TG; apolipoprotein A1 and B, apo A1 and B; lipoprotein(a), Lp(a)); and glycated hemoglobin, HbA1c were evaluated according to ACE genotypes. RESULTS: Genotype distributions were found to be similar in cases [ACE insertion/insertion (II) 9.6%, ACE insertion/deletion (ID) 38.4%, ACE deletion/deletion (DD) 52.0%], and controls (II 8.8%, ID 43.2%, DD 48.0%), and were characterized by higher frequencies of DD, ID, and lower frequencies of II. Diabetic children with DD genotype showed significantly higher levels of TC (p < 0.01), HDL (p < 0.001), and apo A1 (p < 0.001) than controls. There was a higher proportion of diabetic children with family history of cardiovascular disease (CVD) in the DD genotype group (51.9%) than those with II genotype group (11.1%) (p < 0.001). Also, there was a significant increase in the frequency of diabetic children with Lp(a) > 30 mg/dL in children with a family history of CVD (p = 0.008). Lp(a) levels were correlated with HbA1c in the diabetic group (r = 0.239, p = 0.019), but when patients with poor glycemic control (HbA1c > 9%) were excluded, the significant correlation disappeared (r = 0.127, p = 0.381). After adjusting confounding between variables, the logistic regression analysis showed that the two significantly related variables with the rise in Lp(a) were increasing TC level and poor glycemic control. CONCLUSIONS: In children with type 1 diabetes, the role of ACE polymorphism as a probable contributor to CVD seems to be partially mediated through other factors such as poor glycemic control, TC, and Lp(a) level. A longitudinal study is recommended with a larger number of patients in each ACE genotype group in order to assess such associations.

Regulation of tumor necrosis factor alpha and its specific receptors during Toxoplasma gondii infection in human monocytic cells.

The coccidian Toxoplasma gondiiis an obligate intracellular parasite which can infect all cell types. Among the cytokines elicited by the immune response to Toxoplasma, tumor necrosis factor alpha (TNF-alpha) acts synergistically with gamma interferon (IFN-gamma) and plays a major role in host cell resistance. We have previously reported that TNF-alpha production induced by IFN-gamma/LPS decreases after T. gondii infection of human myelomonocytic THP-1 cells. Here, we investigated the regulation of TNF-alpha and its specific receptors during T. gondii infection of THP-1 cells. We found that TNF-alpha production was regulated at a post-transcriptional level and that TNF receptor expression was regulated at a pretranscriptional level. The TNF receptor I shedding and the fall in TNF-alpha levels observed after T. gondii infection would thus be induced by a parasite component with serine protease activity. These findings indicate that T. gondii participates not only in controlling the cytotoxic effects of TNF-alpha during the infection process, but also in signal transduction mediated mainly by TNF receptor I.

Primary motor cortex neuronal discharge during reach-to-grasp: controlling the hand as a unit.

This study has begun to test the hypothesis that aspects of hand/object shape are represented in the discharge of primary motor cortex (M1) neurons. Two monkeys were trained in a visually cued reach-to-grasp task, in which object properties and grasp forces were systematically varied. Behavioral analyses show that the reach and grasp force production were constant across the objects. The discharge of M1 neurons was highly modulated during the reach and grasp. Multiple linear regressions models revealed that the M1 discharge was highly dependent on the object grasped, with object class, volume, orientation and grasp force as significant predictors. These findings are interpreted as evidence that the CNS controls the hand as a unit.

Hand synergies during reach-to-grasp.

An emerging viewpoint is that the CNS uses synergies to simplify the control of the hand. Previous work has shown that static hand postures for mimed grasps can be described by a few principal components in which the higher order components explained only a small fraction of the variance yet provided meaningful information. Extending that earlier work, this study addressed whether the entire act of grasp can be described by a small number of postural synergies and whether these synergies are similar for different grasps. Five right-handed adults performed five types of reach-to-grasps including power grasp, power grasp with a lift, precision grasp, and mimed power grasp and mimed precision grasp of 16 different objects. The object shapes were cones, cylinders, and spindles, systematically varied in size to produce a large range of finger joint angle combinations. Three-dimensional reconstructions of 21 positions on the hand and wrist throughout the reach-to-grasp were obtained using a four-camera video system. Singular value decomposition on the temporal sequence of the marker positions was used to identify the common patterns ("eigenpostures") across the 16 objects for each task and their weightings as a function of time. The first eigenposture explained an average of 97.3 +/- 0.89% (mean +/- SD) of the variance of the hand shape, and the second another 1.9 +/- 0.85%. The first eigenposture was characterized by an open hand configuration that opens and closes during reach. The second eigenposture contributed to the control of the thumb and long fingers, particularly in the opening of the hand during the reach and the closing in preparation for object grasp. The eigenpostures and their temporal evolutions were similar across subjects and grasps. The higher order eigenpostures, although explaining only small amounts of the variance, contributed to the movements of the fingers and thumb. These findings suggest that much of reach-to-grasp is effected using a base posture with refinements in finger and thumb positions added in time to yield unique hand shapes.

Representation of accuracy in the dorsal premotor cortex.

The endpoint accuracy of a reaching movement strongly affects kinematics, particularly during the final phases of movement. However, where and how accuracy is represented in the central nervous system remains unknown. In this study, the discharge of 150 neurons located primarily in the dorsal premotor cortex (PMd), were recorded from monkeys performing an instructed delay, centre-out reaching task in which movement direction and target size were systematically varied. Linear regression analyses were used to assess the dependence of movement kinematics and cell discharge on target direction, size and tangential velocity (i.e. speed). The speed and timing of the movement were dependent on both direction and target size. Initially direction was the dominant predictor whilst target size became more important as the hand reached the target. A temporal multiple linear regression analysis found significant correlations with target size in 99 of 150 cells. The discharge of 134 cells was directionally tuned and 83 cells modulated with mean speed. Significant correlations of discharge with target size occurred throughout the task as did correlations with direction. However, correlations with direction preferentially occurred early in the task, prior to movement onset, whilst correlations with target size tended to occur late, well after movement onset. This temporal dependency of the firing in relationship to target direction and size mirrored that observed for the kinematics. We conclude that the discharge of PMd cells is highly correlated with the accuracy requirement of the movement. The timing of the correlations suggest that accuracy information is available for the planning and for the on-line control of endpoint accuracy.

whmD is an essential mycobacterial gene required for proper septation and cell division.

A study of potential mycobacterial regulatory genes led to the isolation of the Mycobacterium smegmatis whmD gene, which encodes a homologue of WhiB, a Streptomyces coelicolor protein required for sporulation. Unlike its Streptomyces homologue, WhmD is essential in M. smegmatis. The whmD gene could be disrupted only in the presence of a plasmid supplying whmD in trans. A plasmid that allowed chemically regulated expression of the WhmD protein was used to generate a conditional whmD mutant. On withdrawal of the inducer, the conditional whmD mutant exhibited irreversible, filamentous, branched growth with diminished septum formation and aberrant septal placement, whereas WhmD overexpression resulted in growth retardation and hyperseptation. Nucleic acid synthesis and levels of the essential cell division protein FtsZ were unaltered by WhmD deficiency. Together, these phenotypes indicate a role for WhmD in mycobacterial septum formation and cell division.