Accuracy of Determining Nodal Negativity in Colorectal Cancer on the Basis of the Number of Nodes Retrieved on Resection

Background: Correct determination of nodal status is pivotal to accurate staging and predicting survival.Methods: This is a secondary analysis of INT0089, an intergroup trial of adjuvant chemotherapy for high-risk stage II and III colon cancer. A subset of patients was studied who underwent right or left hemicolectomy and from whom at least 10 lymph nodes were examined. A mathematical model was created to estimate the probability of a true negative result on the basis of the number of nodes examined. The number of nodes needed to predict nodal negativity with 85%, 50%, and 25% probability on the basis of tumor stage was calculated.Results: In this analysis, 1585 patients were studied. The average number of nodes removed at surgery was comparable between treatment groups at 18.5 (median of 16 in all groups). With this model, when 18 nodes are removed at resection, there is a <25% probability of true node negativity in T1/T2 tumors, whereas <10 nodes need to be examined in T3 and T4 tumors to achieve the same probability.Conclusions: Tumor stage and the number of nodes retrieved at resection influence the accuracy of determining nodal status in colon cancer. Most patients are understaged. Underestimating nodal stage may influence decisions regarding adjuvant therapy, as well as overall prognosis.     

Alterations in the intrauterine environment by glucocorticoids modifies the developmental programme of the auditory system

Prenatal exposure to excessive glucocorticoids alters the programming of the metabolic and endocrine balance of various organs, including the nervous system. In the present study, prenatal glucocorticoid treatment was shown to increase the susceptibility of the inner ear to acoustic noise trauma in adult life. Acute auditory brainstem response thresholds were not different between the age-matched groups. However, when measured at 48 h and 4 weeks postexposure, the dexamethasone (DEX)-treated rats showed little or no recovery from the trauma. In contrast, normal rats showed a significant amount of recovery by 48 h postexposure and continued to show further recovery over 4 weeks. In addition, acoustic trauma resulted in a massive outer hair cell loss in the DEX rats compared to minor loss in the normal rats. To determine whether oxidative stress plays a role in the recovery phase of acoustic trauma, the free radical scavenger PBN (100 mg/kg) was administered before, during and several times after noise exposure. PBN treatment significantly reduced the physiological and morphological cochlear differences which were observed between DEX and control rats after acoustic trauma. These data support the hypothesis that alterations in the intrauterine environment may modify the developmental programme of the cochlea, inducing dysfunction later in adult life. Excessive prenatal exposure to dexamethasone decreased the potential for recovery of the cochlea to oxidative stress induced by acoustic trauma; this decreased recovery potential can be counteracted by treatment with antioxidants.     

Anterograde delivery of brain-derived neurotrophic factor to striatum via nigral transduction of recombinant adeno-associated virus increases neuronal death but promotes neurogenic response following stroke

To explore the role of brain-derived neurotrophic factor for survival and generation of striatal neurons after stroke, recombinant adeno-associated viral vectors carrying brain-derived neurotrophic factor or green fluorescent protein genes were injected into right rat substantia nigra 4-5 weeks prior to 30 min ipsilateral of middle cerebral artery occlusion. The brain-derived neurotrophic factor-recombinant adeno-associated viral transduction markedly increased the production of brain-derived neurotrophic factor protein by nigral cells. Brain-derived neurotrophic factor was transported anterogradely to the striatum and released in biologically active form, as revealed by the hypertrophic response of striatal neuropeptide Y-positive interneurons. Animals transduced with brain-derived neurotrophic factor-recombinant adeno-associated virus also exhibited abnormalities in body posture and movements, including tilted body to the right, choreiform movements of left forelimb and head, and spontaneous, so-called 'barrel' rotation along their long axis. The continuous delivery of brain-derived neurotrophic factor had no effect on the survival of striatal projection neurons after stroke, but exaggerated the loss of cholinergic, and parvalbumin- and neuropeptide Y-positive, gamma-aminobutyric acid-ergic interneurons. The high brain-derived neurotrophic factor levels in the animals subjected to stroke also gave rise to an increased number of striatal cells expressing doublecortin, a marker for migrating neuroblasts, and cells double-labelled with the mitotic marker, 5-bromo-2'-deoxyuridine-5'monophosphate, and early neuronal (Hu) or striatal neuronal (Meis2) markers. Our findings indicate that long-term anterograde delivery of high levels of brain-derived neurotrophic factor increases the vulnerability of striatal interneurons to stroke-induced damage. Concomitantly, brain-derived neurotrophic factor potentiates the stroke-induced neurogenic response, at least at early stages.     

Assessment of magnesium status

The adult human body contains approximately 24 g (1 mol) of magnesium--about half in bone and half in soft tissues. Only about 0.3% of the total body magnesium is present in serum, yet the majority of analytical data obtained is from this body fluid. Assessing the magnesium status of an individual is difficult, there being at present no simple, rapid, and accurate test to determine intracellular magnesium, but determination of total and free magnesium in tissues and physiological tests provide some information. Changes in magnesium status have been linked to cardiac arrhythmias, coronary heart disease, hypertension, and premenstrual syndrome. A better understanding of magnesium transport and of factors controlling magnesium metabolism is needed to elucidate the role of magnesium in disease processes.     

Sickness-certification practice in different clinical settings; a survey of all physicians in a country

Background  

How physicians handle sickness-certification is essential in the sickness-absence process. Few studies have focused this task of physicians' daily work. Most previous studies have only included general practitioners. However, a previous study indicated that this is a common task also among other physicians. The aim of this study was to gain detailed knowledge about physicians' work with sickness-certification and of the problems they experience in this work.     

Osteogenesis promoted by bone matrix combined with marrow: Titanium implants studied in rats

We evaluated the bone-forming potential of isogeneic bone marrow combined with antigen-extracted, autolyzed allogeneic bone matrix (AAA bone a.m. Urist). The purpose of the experiment was to evaluate bone-inducing materials for application in orthopaedic devices designed for fixation by bone ingrowth into a porous surface. The bone-forming materials were packed into tubes of porous fiber titanium and placed in the back musculature of rats for 12 or 25 days. At 12 days the combination of bone marrow and AAA bone had produced more bone than marrow only. At 25 days, however, there was no difference. The bone-inducing materials produced substantial amounts of new bone, and may become an adjuvant for achieving fixation by bone ingrowth. In particular, a combination of AAA bone and marrow might enhance fixation at a very early postoperative stage.