Cerebrospinal fluid kappa and lambda free light chains in oligoclonal band-negative patients with suspected multiple sclerosis.

BACKGROUND AND PURPOSE: Cerebrospinal fluid (CSF) kappa free light chains (FLCs) may be a more sensitive marker of intrathecal immunoglobulin (Ig)G synthesis compared with oligoclonal bands (OCBs). Our aim was to retrospectively determine the additional value of the kappa and lambda index (CSF FLC/serum FLC)/(CSF albumin/serum albumin) in predicting a multiple sclerosis (MS) diagnosis in a group of OCB-negative patients with suspected MS. METHODS: The CSF and serum kappa and lambda FLCs were tested using the Freelite kit (serum) and Freelite Mx (CSF) assay (The Binding Site Group, Bimingham, UK) in 391 OCB-negative patients with suspected/possible MS and in 54 OCB-positive patients with MS. RESULTS: The CSF kappa FLC levels were below the detection limit (0.27 mg/L) in 61% of patients. Using quantitative data, we found the best kappa index cut-off value for the prediction of MS to be 5.8. A kappa index ≥5.8 was present in 25% of OCB-negative MS (23/92) and in 98% of OCB-positive patients with MS. Using a qualitative approach and a kappa index cut-off of 5.9, based on literature data, we likewise found that 24% of OCB-negative patients with MS had a kappa index ≥5.9, compared with 5.4% of OCB-negative patients without MS (P < 0.001). No reliable data could be obtained for the lambda index; lambda FLCs were below the detection limit (0.68 mg/L) in 90% of CSF samples. CONCLUSIONS: The kappa index could contribute to the identification of OCB-negative patients with a high probability of an MS diagnosis. Using more sensitive techniques might even improve the diagnostic performance of the kappa index and better define the role of the lambda index.

Trends of maxillofacial trauma: An update from the prospective register of a multicenter study in emergency services of Chile.

BACKGROUND: Determine the behavior of the maxillofacial trauma of adults treated in 3 tertiary care centers in the central zone of Chile. MATERIAL AND METHODS: descriptive, cross-sectional, multicenter study, based on the prospective records of maxillofacial trauma cases attended between May 2016 and April 2017 by dental and maxillofacial clinical teams of Adult Emergency Units of hospitals Dr. Sótero del Río (metropolitan region), Carlos Van Buren and Dr. Gustavo Fricke (region V). Age, sex, date of occurrence, type of trauma according to ICD-10, etiology, legal medical prognosis and associated injuries were recorded, stratifying by sex and age. Chi square and unpaired Wilcoxon tests were used to compare by groups. RESULTS: 2.485 cases and 3.285 injuries were investigated. The male: female ratio was 1.7: 1 with age under 30 predominant, followed by older adults. Variability was observed in the yearly, weekly and daily presentation. The highest frequencies were in January and September, weekends and at night. The main etiologies were violence (42.3%), falls (13.1%) and road traffic crashes (12.9%) with differences by age and sex (p <0.05). 31,9% of the injuries occurred in hard tissue, being fractures in nasal bones predominant (S02.2). CONCLUSIONS: the profile of the maxillofacial trauma in Chile seems to be mixed by age, affecting young people and the elderly. The male sex predominates; the main cause, which varies by age group, is violence. Their surveillance is possible from hospital emergency records.

Ageing and inflammation in patients with HIV infection.

Nowadays, HIV+ patients have an expected lifespan that is only slightly shorter than healthy individuals. For this reason, along with the fact that infection can be acquired at a relatively advanced age, the effects of ageing on HIV+ people have begun to be evident. Successful anti-viral treatment is, on one hand, responsible for the development of side effects related to drug toxicity; on the other hand, it is not able to inhibit the onset of several complications caused by persistent immune activation and chronic inflammation. Therefore, patients with a relatively advanced age, i.e. aged more than 50 years, can experience pathologies that affect much older citizens. HIV+ individuals with non-AIDS-related complications can thus come to the attention of clinicians because of the presence of neurocognitive disorders, cardiovascular diseases, metabolic syndrome, bone abnormalities and non-HIV-associated cancers. Chronic inflammation and immune activation, observed typically in elderly people and defined as 'inflammaging', can be present in HIV+ patients who experience a type of premature ageing, which affects the quality of life significantly. This relatively new condition is extremely complex, and important factors have been identified as well as the traditional behavioural risk factors, e.g. the toxicity of anti-retroviral treatments and the above-mentioned chronic inflammation leading to a functional decline and a vulnerability to injury or pathologies. Here, we discuss the role of inflammation and immune activation on the most important non-AIDS-related complications of chronic HIV infection, and the contribution of aging per se to this scenario.

Prognostic value of extracapsular tumor spread for locoregional control in premenopausal patients with node-positive breast cancer treated with classical cyclophosphamide, methotrexate, and fluorouracil: long-term observations from International Breast Cancer Study Group Trial VI.

PURPOSE: We sought to determine retrospectively whether extracapsular spread (ECS) might identify a subgroup that could benefit from radiotherapy after mastectomy, especially patients with 1 to 3 positive lymph nodes (LN1-3+). PATIENTS AND METHODS: We randomized 1,475 premenopausal women with node-positive breast cancer to three, six, or nine courses of "classical" CMF (cyclophosphamide, methotrexate, and fluorouracil). After a review of all pathology forms, 933 patients (63%) had information on the presence or absence of ECS. ECS was present in 49.5%. The median follow-up was 10 years. RESULTS: In univariate analyses, ECS was associated with worse disease-free survival (DFS) and overall survival (OS). In multivariate analyses adjusting for tumor size, vessel invasion, surgery type, and age group, ECS remained significant (DFS: hazard ratio, 1.61; 95% CI, 1.34 to 1.93; P < .0001; OS: 1.67; 95% CI, 1.34 to 2.08; P < .0001). However, ECS was not significant when the number of positive nodes was added. The locoregional failure rate +/- distant failure (LRF +/- distant failure) within 10 years was estimated at 19% (+/- 2%) without ECS, versus 27% (+/- 2%) with ECS. The difference was statistically significant in univariate analyses, but not after adjusting for the number of positive nodes. No independent effect of ECS on DFS, OS, or LRF could be confirmed within the subgroup of 382 patients with LN1-3+ treated with mastectomy without radiotherapy. CONCLUSION: Our results do not support an independent prognostic value of ECS, nor its use as an indication for irradiation in premenopausal patients with LN1-3+ treated with classical CMF. However, we could not examine whether extensive ECS is of prognostic importance.

Two-stage treatment of a tectal ganglioglioma: endoscopic third ventriculostomy followed by surgical resection.

Tumours of the quadrigeminal plate in adults are usually benign. Nevertheless, obstructive hydrocephalus due to compression of the Sylvian aqueduct is an almost invariable early finding. Whether or not direct excision is undertaken, temporary or permanent treatment of the hydrocephalus is warranted. Endoscopic third ventriculostomy is an alternative to insertion of a shunt and provides both acute and long-term relief of hydrocephalus-related symptoms. We chose a two-stage approach for treating a tectal ganglioglioma in an adult: endoscopic third ventriculostomy followed by surgical excision. The advantages and disadvantages of each therapeutic strategy are discussed.

Modulation of conjugated linoleic acid-induced loss of chicken egg hatchability by dietary soybean oil.

The main objective of the present study was to determine the minimum level of dietary plant oil supplementation that results in full recovery from loss of hatchability induced by conjugated linoleic acid (CLA). Another objective was to define the changes in egg yolk fatty acid composition associated with the loss and recovery of hatchability. Shaver hens were assigned to groups of 8 and were fed a diet containing either no CLA plus 0.5% soybean oil (control) or 0.5% CLA (1:1 mixture of cis-9, trans-11 and trans-10, cis-12 CLA) plus 0, 2, 4, 6, or 8% soybean oil for 15 d. Supplementation with CLA (CLA plus 0% soybean oil) resulted in complete loss of hatchability of fertile eggs. Hatchability was progressively improved by increasing doses of soybean oil, and full recovery of hatchability compared with the control levels was achieved at 6% soybean oil. There was no further improvement in hatchability when 8% soybean oil was added to the CLA-supplemented diet. Loss of hatchability was associated with a 2- to 3-fold decrease in desaturase ratios (cis-9 C16:1/C16:0 and cis-9 C18:1/C18:0) in the egg yolk total lipids, indicating marked inhibition of delta-9 desaturase in the chicken liver. In addition, the concentration of arachidonic acid was observed to decrease. Recovery of hatchability was associated with an increased proportion of linoleic acid and linolenic acid in the egg yolk. However, there was no change in desaturase ratios, suggesting that delta-9 desaturase inhibition persisted. Increased incorporation of dietary linoleic and linolenic acids might have compensated for the reduced levels of palmitoleic and oleic acid, thus allowing for the improvement in hatchability.

Genetic polymorphisms of Fas (CD95) and FasL (CD178) in human longevity: studies on centenarians.

Apoptosis plays a crucial role in immunosenescence, as also evidenced by the increased expression of Fas in lymphocytes from aged people. However, little is known about the genetic regulation of Fas and its ligand, FasL. We have studied their polymorphisms in 50 centenarians and 86 young donors living in Northern Italy. The first Fas polymorphism, at position -670, has in Caucasian a heterozigosity of 51%; the second, at -1377 position, has the wild type allele (G) with a very high frequency (83%) respect to the mutant allele. Genotype and allele distribution for both polymorphisms were similar in controls and centenarians. Similar results were found as far as two FasL polymorphisms (IVS2nt-124 and IVS3nt169) are concerned. On the whole, our data suggest that Fas and FasL polymorphisms, as well as their haplotypes, are unlikely to be associated with successful human longevity.

Apoptosis-resistant phenotype in HL-60-derived cells HCW-2 is related to changes in expression of stress-induced proteins that impact on redox status and mitochondrial metabolism.

The onset of resistance to drug-induced apoptosis of tumour cells is a major problem in cancer therapy. We studied a drug-selected clone of promyelocytic HL-60 cells, called HCW-2, which display a complex resistance to a wide variety of apoptosis-inducing agents and we found that these cells show a dramatic increase in the expression of heat shock proteins (Hsps) 70 and 27, while the parental cell line does not. It is known that stress proteins such as Hsps can confer resistance to a variety of damaging agents other than heat shock, such as TNF-alpha, monocyte-induced cytotoxicity, and also play a role in resistance to chemotherapy. This elevated expression of Hsps is paralleled by an increased activity of mitochondrial metabolism and pentose phosphate pathway, this latter leading to high levels of glucose-6-phosphate dehydrogenase and, consequently, of glutathione. Thus, the apoptotic-deficient phenotype is likely because of the presence of high levels of stress response proteins and GSH, which may confer resistance to apoptotic agents, including chemotherapy drugs. Moreover, the fact that in HCW-2 cells Hsp70 are mainly localised in mitochondria may account for the increased performances of mitochondrial metabolism. These observations could have some implications for the therapy of cancer, and for the design of combined strategies that act on antioxidant defences of the neoplastic cell.

Impairment of recent thymic emigrants in HCV infection.

Hepatitis C Virus (HCV) often has a more favorable course in younger patients. Considering the involution of the thymic function with age, we investigated the output of recent thymic emigrants (RTE) in HCV patients. To evaluate RTE, we used a competitive quantitative PCR in order to determine the percentages of cells with cj-T cell receptor excision circles (TREC). This study was performed in 14 HCV patients at diagnosis and before any anti-HCV treatment. The results obtained in this group were compared to those obtained in a group of age-matched controls. We found that in the 14 HCV patients naive for anti-HCV treatment the mean percentage of cj-TREC was 3%. We could not detect a correlation between the percentages of cj-TREC and age or patients' viremia. In contrast, in the 26 age-matched controls mean percentage of cj-TREC was 5.6% (P=0.01). Our study describes a novel immune defect in HCV patients. Additional studies are needed to get further insight in the possible role of TREC defect in the pathogenesis and prognosis of the disease.

Quantitation of CD95 and CD95L mRNA expression in chronic and acute HIV-1 infection by competitive RT-PCR.

Human immunodeficiency virus-type 1 (HIV-1) infection is characterized by increased immune cell apoptosis. Apoptosis can be triggered by signals that arise from within the cell, or by signals that are elicited by binding of extracellular "death ligands" to their "death receptors," most of which belong to the tumor necrosis factor (TNF)-receptor family, such as CD95 (Fas/Apo-1). In immune cells the oligomerization of CD95, induced by its ligand CD95L, and the recruitment of different intracytoplasmic molecules that in turn activate FLICE/caspase 8 are crucial. To study the role of CD95/CD95L interactions during HIV-1 infection, we developed an original method based upon quantitative-competitive (QC) RT-PCR that allowed us to quantify the amounts of mRNA coding for the total (tCD95) and membrane (mCD95) forms of CD95. We first studied the expression of different forms of CD95 mRNA in a classical model of chronic HIV infection using two infected cell lines of different origin--lymphocytic (ACH-2) or monocytic (U1). We have shown that infected cells of monocytic origin preferentially produce the "protective" (soluble) form of CD95, and no detectable CD95L mRNA, while lymphoid cells produce more mRNA for the membrane form of CD95 (which triggers apoptosis) along with low but detectable amounts of CD95L mRNA. One can hypothesize that a complex balance exists between pro-apoptotic events, perhaps triggered by the host to limit viral production, and anti-apoptotic events likely triggered by the virus to increase its production and survival. In cells of monocytic origin, which act as a reservoir for the virus, the anti-apoptotic molecules are favored; in cells of lymphocytic origin, molecules with an apoptotic meaning are prevalent.

Pituitary apoplexy, bilateral carotid vasospasm, and cerebral infarction in a 15-year-old boy.

The authors report a case of pituitary apoplexy associated with oculomotor defects and focal cerebral signs; the visual pathways were intact. Computed tomography documented a mass of heterogeneous density within an enlarged sella turcica and a right parietal infarct. Angiograms revealed bilateral carotid spasm and occlusion of the right angular artery. Treatment was conservative. Control angiograms showed spontaneous resolution of the vasospasm and recanalization of the cortical artery. The patient made a complete neurological recovery; he needed only treatment with vasopressin due to transient diabetes insipidus. The risk of vasospasm and brain ischemia should be kept in mind when treating pituitary apoplexy. The early occurrence of vasospasm in our case suggests the participation of powerful vasoactive agents liberated from the tumor.

Evolving brain lesions in the first 12 hours after head injury: analysis of 37 comatose patients.

From January 1, 1990, to April 30, 1994, 412 patients were admitted to our intensive care unit in coma after head injuries. Our study group consisted of 37 patients who were retrospectively identified as harboring lesions or developing new lesions within a 12-hour period from the time of admission. We defined the evolution of a lesion as an increase or decrease in the size of an already present hematoma or as the appearance of a totally new lesion. There were 25 male and 12 female patients (mean age, 34.9 yr), and the cause of trauma was road traffic accidents in 32 patients. Nine patients presented with shock, and six had evidence of abnormal coagulation at admission. Patients were divided into two different groups. In Group 1, 15 patients harbored lesions that evolved toward reabsorption. In Group 2, 22 patients harbored hematomas that evolved toward lesions requiring surgical removal. Fifteen of these patients had initial diagnoses of diffuse injury that evolved in this manner, whereas the remaining seven patients had already been operated upon and had developed second, noncontiguous, surgical lesions. Patients with lesions that required surgical evacuation had their computed tomographic (CT) scans obtained earlier and had a higher incidence of clinical deterioration. There was a significant difference in the evolution of the different lesions (P < 0.001), with subdural hematomas being more prone to reabsorption and intracerebral and extradural hematomas being more likely to increase in size or to appear as new lesions. Second CT scans were obtained because of clinical deterioration in 10 patients and because of increase in intracranial pressure in 5 patients. Scheduled CT scans were obtained in 13 patients, whereas in the remaining 9 patients, the diagnosis emerged from a combination of scheduled CT scans and intracranial pressure monitoring. There was a trend toward a poorer result among the patients with clinical deterioration, which, however, was not significant. A significant proportion of post-traumatic patients, particularly those who are unconscious, harbor early evolving intracranial lesions. When the first CT scan is performed within 3 hours after injury, a CT scan should be repeated within 12 hours.

Infratentorial arachnoid cysts.

The infratentorial compartment represents the second most common location of arachnoid malformations. Ten arachnoid cysts of the posterior fossa, operated on between 1970 and 1983, are reviewed. These lesions, although congenital and developmental in nature, may present at any age, and males are more frequently affected. A high rate of birth-related trauma (50% in this series) is conceivably due to fetal macrocranium, and the enlarged head and psychomotor retardation prevail in infancy and childhood. In arachnoid cysts occurring during adulthood, symptoms and signs more clearly indicate a dysfunction of the posterior fossa. Besides computerized tomography, pneumoencephalography and metrizamide techniques are recommended to rule out a Dandy-Walker syndrome in doubtful cases, and to obtain information about the cerebrospinal fluid (CSF) circulation. It is particularly important to establish the presence and type of communication of cysts with the CSF pathways. Although infratentorial cysts often communicate, they can be space-occupying masses because of increasing CSF retention, which may be due to a ball-valve mechanism or to inadequate communication. The frequently associated hydrocephalus (seven of the 10 cases in this series had hydrocephalus) seemed to be dependent mainly upon mechanical factors. The authors discuss the indications for intracranial surgery versus shunting procedures and report the results achieved by direct cyst excision.

Anti-melanoma effects of R24, a monoclonal antibody against GD3 ganglioside.

R24, a mouse monoclonal antibody against GD3 ganglioside, is potent at mediating in vitro effector functions such as human complement-mediated cytotoxicity and antibody-dependent cellular cytotoxicity, and can block melanoma tumor growth in animal models. Because of these properties and the fact that GD3 is abundantly expressed on virtually all melanomas but is found on few normal tissues, R24 has been tested in a series of clinical trials in patients with metastatic melanoma. As a single agent, R24 can induce responses in patients treated with metastatic melanoma. Overall, there have been 10 responders out of 103 patients reported; two responses have been complete responses. Responses have largely occurred in patients treated with intermediate doses of R24 and have included complete responses. Combining R24 with either cytotoxic drugs or cytokines has not increased this response rate, although one trial with R24 and interleukin-2 resulted in a 43% response rate and merits further investigation. Local-regional treatments R24 (intratumor injections, regional limb perfusion, intrathecal administration) have also been attempted in a small number of patients and responses have been described. Taken together, multiple centers have reported responses in patients with metastatic melanoma treated with R24.

Hepatoma HepG2 cells as a model for in vitro studies on mitochondrial toxicity of antiviral drugs: which correlation with the patient?

Currently, drugs have been synthesised that can significantly delay the course of several viral infections, including those provoked by HBV, HCV or HIV, but that display consistent side effects, including toxicity for organelles such as mitochondria. Several in vitro models and techniques have been developed to analyse the effects of such compounds. HepG2 cells (from human hepatoma) are an excellent model to investigate mitochondrial (mt) toxicity because of their high content of organelles and mtDNA, and actually different investigators are indeed using such cells. Studies in vitro on cell lines are relatively easy, but it is necessary to be careful in the interpretation of data, which are usually obtained on continuously growing, tumour cells, quite different from normal, resting, non-neoplastic cells collected from a patient. Direct analysis of drug-induced mt damage in patients is extremely more complex than that performed using in vitro models because of the difficulty to obtain adequate cells or to have discrete amounts of biological material, the status of the patient at the moment of cell collection, the use of an adequate assay and its correct execution, and finally the possibility to find sex- and age-matched healthy controls as source of reference parameters.

Intraneural ganglion of the peroneal nerve: an unusual presentation. Case report.

The authors report an intraneural ganglion of the peroneal nerve at the fibular head, in which the external appearance of the nerve was normal at operation. Only the incision of the epineurium permitted discovery of the lesion.

Management of low-risk head injuries in an entire area: results of an 18-month survey.

All patients admitted following a minor head injury (GCS is without neurological deficits) during an 18 month period in an entire area were submitted to the same diagnostic and therapeutic protocol. Adult patients were x rayed and in the cases with skull fracture (even asymptomatic), a computed tomographic (CT) scan was performed. Children (below the age of 14) did not routinely receive skull X-rays but were admitted to one of the five regional hospitals where a CT scanner was available 24 hours per day. Neuroradiologic investigations (carried out in over 600 patients) showed posttraumatic lesions in 201 cases; 113 of these patients were transferred to the neurosurgical center. There were 49 patients with extradural hematomas, 41 with brain contusions, 17 with depressed skull fractures, and six with subdural hematomas. Of these 113, 40 patients were operated on (mainly extradural hematomas); surgical indications were based on appearance of clinical deterioration, lesion volume, presence of midline shift, and/or compressed third ventricle and basal cisterns. In eight cases there was a clinical deterioration to a GCS of 13 or less; in all of these patients, the CT diagnosis (and transfer to a neurosurgical center, preceded the onset of deterioration. All patients admitted to such a center had a good outcome, but a survey of deaths related to head injury in the area revealed two fatalities following minor head injury. The only avoidable death was a patient with multiple brain contusions who developed sudden brain swelling on day 12 post-trauma. We conclude that, even if management mortality is not zero, our protocol is sufficiently safe for the treatment of minor head injury.

Effect of BROILACT on the physicochemical conditions and nutrient digestibility in the gastrointestinal tract of broilers.

The effect of the competitive exclusion (CE) product BROILACT on Salmonella colonization, nutrient digestibility, and the ME of the feed and the production of volatile fatty acids in the chicken gut was evaluated. The ileal viscosity and the fecal dry matter content were also determined. Newly hatched broiler chicks were given BROILACT orally either once on the day of hatch or five times during a period of 2 wk. Samples were taken at 12 and 31 d of age. In the beginning of the study and 2 wk later, chicks from each treatment group were taken to separate facilities to be challenged with Salmonella. Five and 4 d later, the chicks were killed and their intestines were examined for Salmonella. The results of the present study show that BROILACT protected the chicks against Salmonella, decreased the viscosity of the ileal contents, and increased the fecal dry matter content, and increased the ME value of the feed by 1.6% and the concentration of propionic acid in the cecal contents.

X-ray evaluation of interferential femoral screw positioning in ACL reconstruction.

In a total of 27 patients the authors performed reconstruction of the anterior cruciate ligament using the mid third of the free patellar tendon (bone-tendon-bone), stabilized with two interferential wires, using a mini-arthrotomic half-tunnel in-out method. X-ray examination in two orthogonal views allows for an evaluation of the orientation of the femoral screw in relation to the joint plane and the diaphyseal axis, and its relationship with the bone graft, thus obtaining useful information on its anchoring. The method used is that reported by Lemos et al. (1993). The results obtained agree with those reported by the American author and substantiate the reliability of the method.

T cell homeostasis in centenarians: from the thymus to the periphery.

The immune system undergoes a process of profound remodelling during aging, referred to as immunosenescence, and characterized by complex modifications of several components. In this review, we discuss recent developments and observations regarding the generation of T cells in the thymus during aging and longevity, and the regulation and maintenance of peripheral blood lymphocytes. The generation of new T cells is indeed crucial to maintain a functional immune system, and is a fundamental step to avoid unsuccessful aging, thus reaching longevity in good health. Mechanisms will be described that are related to the production and maintenance of those lymphocytes defined "recent thymic emigrants", and to the detection of the so called "T cell receptor rearrangement excision circles (TREC)", along with the presence in the periphery of naïve and memory T cells, that can be influenced and regulated by several different mechanisms. Several strategies aimed at improving thymic functionality are currently receiving a growing interest, and some of them are based on molecules that are produced by, and/or act on immune cells. Data on the possible use of these molecules, including cytokines like interleukin (IL)-7, IL-15 and keratinocyte growth factor, to restore thymic function are reviewed and discussed.