Search

Feline chronic enteropathies (FCE) are challenging to diagnose and monitor for progression and response to treatment. Fecal calprotectin might be a useful non-invasive marker to evaluate clinical endpoints of therapeutic monitoring in FCE. We evaluated fecal calprotectin concentrations in cats with FCE before and after initiation of treatment comprised of immunomodulation and/or dietary intervention. Included were 17 cats with FCE and 18 healthy controls. Clinical investigation of FCE cases included clinical severity grading (feline chronic enteropathy activity index, FCEAI) in all cats, abdominal ultrasonography in 15 cats, and gastrointestinal biopsies in 6 cats. Fecal calprotectin was measured in samples from 12 cats with FCE before treatment, all 17 FCE cats ≥6weeks after treatment initiation, and all healthy controls. Fecal calprotectin concentrations in FCE cases before treatment (median: 61 µg/g) were significantly higher than after treatment initiation (median: 15 µg/g; p =0.0098) and compared to controls (median: 6 µg/g; p =0.0235) and correlated with the FCEAI scores (ρ =0.54, p =0.0316). Fecal calprotectin concentrations after treatment initiation were higher with more severe duodenal/proximal jejunal pathology (ρ =0.83, p =0.0427) and shorter intervals between sampling time points (ρ = -0.54, p =0.0250). Relevant decreases in initially increased fecal calprotectin concentrations are seen in cats with FCE on varying treatment strategies that significantly improve or have remission of clinical signs. This supports the utility of fecal calprotectin as a surrogate biomarker to assess disease severity in FCE cases. Further studies need to evaluate fecal calprotectin concentrations longitudinally in relation to mucosal healing vs. clinical response. [ABSTRACT FROM AUTHOR]

Chronic diarrhea presents a significant challenge for managing nutritional and electrolyte deficiencies, especially in children, given the higher stakes of impacting growth and developmental consequence. Congenital secretory diarrhea (CSD) compounds this further, particularly in the case of the activating variants of the guanylate‐cyclase 2C (GUCY2C) gene. GUCY2C encodes for the guanylate‐cyclase 2C (GC‐C) receptor that activates the downstream cystic fibrosis transmembrane receptor (CFTR) that primarily drives the severity of diarrhea with an unclear extent of influence on other intestinal channels. Thus far, management for CSD primarily consists of mitigating nutritional, electrolyte, and volume deficiencies with no known pathophysiology‐driven treatments. For activating variants of GUCY2C, experimental compounds have shown efficacy in vitro for direct inhibition of GC‐C but are not currently available for clinical use. However, Crofelemer, a CFTR inhibitory modulator with negligible systemic absorption, can theoretically help to treat this type of CSD. Herein, we describe and characterize the clinical course of a premature male infant with a de novo missense variant of GUCY2C not previously reported and highly consistent with CSD. With multi‐disciplinary family‐directed decision‐making, a treatment for CSD was evaluated for the first time to our knowledge with Crofelemer. [ABSTRACT FROM AUTHOR]

Objective: The identification of effective therapeutics for ALS necessitates valid and responsive outcome measures to track disease progression and therapeutic gain in clinical trial settings. The Amyotrophic Lateral Sclerosis-Health Index (ALS-HI) is a multifaceted, disease-specific patient-reported outcome measure (PRO) designed to measure ALS symptomatic disease burden in adults with ALS. Methods: Through a national cross-sectional study of individuals with ALS, we identified the most important symptoms in ALS. These symptoms were incorporated into the ALS-HI, a measure that quantifies the multifaceted disease burden in ALS. We performed factor analysis, qualitative patient interviews, test-retest reliability assessment, and known groups analysis to evaluate and validate the ALS-HI. Results: The cross-sectional study included 497 participants with ALS who identified the most important symptoms to include in the ALS-HI. Fifteen participants beta tested the ALS-HI and found it to be clear, easy to use, and relevant. Twenty-one participants engaged in a test-retest reliability study, which indicated the reliability of the instrument (intraclass correlation coefficient = 0.952 for full instrument). The final ALS-HI and its subscales demonstrated a high internal consistency (Cronbach's α = 0.981 for full instrument) and an ability to differentiate between groups with dissimilar disease severity. Conclusions: This research supports use of the ALS-HI as a valid, sensitive, reliable, and relevant PRO to assess the multifactorial disease burden faced by adults with ALS. The ALS-HI has potential as a mechanism to track disease progression and treatment efficacy during therapeutic trials. [ABSTRACT FROM AUTHOR]

Background: When developed properly, disease-specific patient reported outcome measures have the potential to measure relevant changes in how a patient feels and functions in the context of a therapeutic trial. The Huntington's Disease Health Index (HD-HI) is a multifaceted disease-specific patient reported outcome measure (PROM) designed specifically to satisfy previously published FDA guidance for developing PROMs for product development and labeling claims. Objective: In preparation for clinical trials, we examine the validity, reliability, clinical relevance, and patient understanding of the Huntington's Disease Health Index (HD-HI). Methods: We partnered with 389 people with Huntington's disease (HD) and caregivers to identify the most relevant questions for the HD-HI. We subsequently utilized two rounds of factor analysis, cognitive interviews with fifteen individuals with HD, and test-retest reliability assessments with 25 individuals with HD to refine, evaluate, and optimize the HD-HI. Lastly, we determined the capability of the HD-HI to differentiate between groups of HD participants with high versus low total functional capacity score, prodromal versus manifest HD, and normal ambulation versus mobility impairment. Results: HD participants identified 13 relevant and unique symptomatic domains to be included as subscales in the HD-HI. All HD-HI subscales had a high level of internal consistency and reliability and were found by participants to have acceptable content, relevance, and usability. The total HD-HI score and each subscale score statistically differentiated between groups of HD participants with high versus low disease burden. Conclusion: Initial evaluation of the HD-HI supports its validity and reliability as a PROM for assessing how individuals with HD feel and function. [ABSTRACT FROM AUTHOR]

Introduction: Sodium selenate increases tau dephosphorylation through protein phosphatase 2 activation. Here we report an open-label Phase 1b study of sodium selenate as a disease-modifying treatment for behavioral variant frontotemporal dementia (bvFTD). Methods: Twelve participants with bvFTD received sodium selenate (15 mg, three times a day) for 52 weeks. Safety assessments were carried out throughout the trial. Primary outcomes were frequency of adverse events (AEs), serious adverse events (SAEs), and discontinuations. Secondary outcomes of potential efficacy included cognitive and behavioral assessments, magnetic resonance imaging (MRI)whole brain volume, and cerebrospinal fluid (CSF) and blood total tau (t-tau), phosphorylated tau (ptau), and neurofilament light (NfL) levels, which were measured at baseline and at week 52. Results: Sodium selenate was safe and well tolerated. All participants completed the study, and the majority (64.7%) of reported AEs were mild. One SAE occurred, which was not treatment related. Small declines in MRI and cognitive and behavioral measures were observed over the treatment period. There was no evidence for change in CSF protein levels (t-tau, p-tau, or NfL). Further analysis showed two distinct groups when measuring disease progression markers over the course of the study--one (n = 4) with substantial brain atrophy (2.5% to 6.5% reduction) and cognitive and behavioral decline over the 12-month treatment period, and the second group (n=7) with no detectable change in cognitive and behavioral measures and less brain atrophy (0.3% to 1.7% reduction). Conclusion: Sodium selenate is safe and well tolerated in patients with bvFTD. Randomized-controlled trials are warranted to investigate potential efficacy. [ABSTRACT FROM AUTHOR]

Background: The Global Initiative for Asthma has only recently added tiotropium bromide as adjunct controller therapy in severe asthma (Step 4 or 5) in adults (2015) and children (2019). Although not yet approved for pediatric use by Health Canada, it has been occasionally offered by asthma specialists as a therapeutic trial in children with troublesome asthma or treatment for adverse effects. The objective of this study was to describe the indications and real-life clinical experience in initiating tiotropium in children with asthma. Methods: We designed a retrospective mixed-method case series study of children aged 1–17 years who initiated tiotropium in our tertiary-care centre between 2013 and 2020. Clinical information was extracted from electronic medical records and tiotropium dispensing, from drug claims. Parents/children and physicians independently completed a questionnaire about treatment goals, perceived efficacy, safety, satisfaction, and lessons learned. Results: The 34 (11 females; 23 males) children had a median (range) age of 9.1 (1.4–17.8) years. Children were primarily on Step 4 (85%) or 5 (6%) prior to tiotropium initiation, yet most (84%) did not increase their treatment step after tiotropium initiation. The physicians' treatment goals were to improve asthma control, alleviate adverse effects of current therapy, and/or improve lung function. The most improved symptoms were coughing/moist cough, difficulty breathing, whistling breath, and bronchial secretions/mucus. Although most parents and physicians reported a significant benefit with tiotropium bromide, physicians particularly remarked, as their "lesson learned', on the improvement in chronic symptoms in asthmatic children, particularly those with prominent moist cough and in lung function, in those with seemingly none (or incompletely) reversible obstruction as well as the ability to decrease the ICS and/or LABA dose to lessen adverse effects. A few physicians raised caution on the risk of lower adherence with an additional inhaler. Conclusion: In children with severe asthma on Step 4 or 5, tiotropium bromide was primarily used as substitute, rather than additional, adjunct therapy to improve asthma control, alleviate adverse effects, and/or to improve lung function. The latter two indications, combined with its perceived effectiveness in children with prominent moist cough, also suggest additional indications of tiotropium to be formally explored. [ABSTRACT FROM AUTHOR]

Introduction: The Spinal Muscular Atrophy Health Index (SMA-HI) is a multifaceted, disease-specific, patient-reported outcome to measure an SMA patient's perception of their disease burden. In preparation for upcoming therapeutic trials, we examine the validity, reliability, and usability of the SMA-HI in adults, teenagers, and children with SMA.Methods: Using data from a cross-sectional study of 359 international adult patients with SMA, we identified the most relevant symptoms to include in the SMA-HI. We utilized factor analysis, patient interviews with adults and minors (age 8-15 years), known-group validity testing, and test-retest reliability assessments to evaluate and refine the SMA-HI.Results: The SMA-HI measures overall disease burden and 15 areas of SMA health. Fifteen adult patients and five patients, age 8 to 15 years, participated in semistructured qualitative interviews and found the SMA-HI to be comprehensive, easily completed, and to have clear meaning. The final SMA-HI and its subscales demonstrated good internal consistency (Cronbach α = 0.77-0.96), high test-retest reliability (intraclass correlation coefficient = 0.60-0.96), and an ability to differentiate between SMA groups with different disease severities affecting areas such as employment and ambulation (P < .0001 for both).Discussion: This research provides evidence that the SMA-HI is a valid, relevant, and reliable outcome measure to assess multifaceted patient-reported disease burden in older children, teenagers, and adults with SMA. The SMA-HI provides an opportunity for researchers and clinicians to measure a SMA patient's perception of their health and determine relevant changes in response to therapeutic intervention or disease progression. [ABSTRACT FROM AUTHOR]

Background: Patients with the heritable disease, Fanconi anemia (FA), have a 500‐fold risk of developing head and neck squamous cell carcinomas (HNSCC). However, the use of conventional cytotoxic agents including radiation therapy and cisplatin‐based chemotherapy is contraindicated in patients with FA due to underlying DNA repair defects. Methods/Results: We present a young FA patient with recurrent HNSCC and high‐risk pathologic features treated with a therapeutic trial of chemoradiation. This novel strategy employs a gentle radiation dose and volume escalation with concurrent pembrolizumab. The patient completed the entire course of therapy with no treatment delays or interruptions. Conclusions: The FA patient population has a clear need for adjuvant treatment regimens given their predilection for HNSCC. A therapeutic trial may allow FA and other radiosensitive patients to trial radiation with the option to terminate treatment before any severe side effects occur and for some to complete a full course of treatment. [ABSTRACT FROM AUTHOR]

Résumé: Les essais cliniques sont fondamentaux pour déterminer si un nouveau médicament conduit réellement à une amélioration de la prise en charge des patients. Pourtant, beaucoup d'incompréhension demeure au sujet de la conception des essais, du choix des critères de jugement et de l'interprétation des résultats. En prenant pour exemple les essais récents dans le lymphome folliculaire, cette revue évoquera le choix du critère de jugement principal, la définition d'un marqueur de substitution, la notion de quantité d'effet et les analyses de sous-groupes. Ces concepts doivent être appréhendés par les cliniciens pour pouvoir questionner tout résultat issu d'un essai clinique. Clinical trials are crucial to address whether a new drug actually leads to a significant improvement in patient care. However, there is often a misunderstanding of how clinical trials are designed, why specific endpoints are chosen and how results should be interpreted. Based on recent trials in the field of follicular lymphoma, this review will deal with primary endpoint choice, surrogate endpoint definition, effect size and subgroups analysis. These statistical concepts need to be clearly understood by clinicians to challenge any result of a clinical trial. [ABSTRACT FROM AUTHOR]

We performed a randomized, double-blind phase I clinical trial for six months on the effects of oral L-serine in patients with ALS. The protocol called for enrollment of patients with a diagnosis of probable or definite ALS, age 18–85 years, disease duration of less than three years and forced vital capacity (FVC) ≥ 60%. Patients were randomly assigned to four different oral twice-daily dose regimens (0.5, 2.5, 7.5, or 15 g/dose). Blood, urine and CSF samples, ALS Functional Rating Scale-Revised (ALSFRS-R) scores and forced vital capacity (FVC) were obtained throughout the trial. Disease progression was compared with matched historical placebo controls from five previous ALS therapeutic trials. Of 20 patients enrolled, one withdrew before receiving study drug and two withdrew with gastro-intestinal problems. Three patients died during the trial. L-serine was generally well tolerated by the patients and L-serine did not appear to accelerate functional decline of patients as measured by slope of their ALSFRS-R scores. Based on this small study, L-serine appears to be generally safe for patients with ALS. [ABSTRACT FROM AUTHOR]

Introduction: The Myotonic Dystrophy Health Index (MDHI) is a disease-specific patient-reported outcome measure. Here, we examine the associations between the MDHI and other measures of disease burden in a cohort of individuals with myotonic dystrophy type-1 (DM1).Methods: We conducted a cross-sectional study of 70 patients with DM1. We examined the associations between MDHI total and subscale scores and scores from other clinical tests. Participants completed assessments of strength, myotonia, motor and respiratory function, ambulation, and body composition. Participants also provided blood samples, underwent physician evaluations, and completed other patient-reported outcome measures.Results: MDHI total and subscale scores were strongly associated with muscle strength, myotonia, motor function, and other clinical measures.Conclusions: Patient-reported health status, as measured by the MDHI, is associated with alternative measures of clinical health. These results support the use of the MDHI as a valid tool to measure disease burden in DM1 patients. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effect of a microkinesitherapy session on pain and the amplitudes of flexion-extension in post-traumatic acute neck pain. Methods: Randomized double blind clinical trial involving two groups of patients. The microkinesitherapy group benefitted from the check-up treatment sequence, the control group from a check-up simulation sequence. The primary outcome measure was evolution of pain, secondary endpoint amplitudes of movement. Results: 29 patients were studied: 15 in the microkinesitherapy group and 14 in the control group. A significant decrease in the visual analog scale (0-10) of pain was noted for the microkinesitherapy group (5,2 ± 2,3 at initial check-up versus 2.5 ± 1.7 in the second check-up, p <0.001), but no decrease in the control group (4,0 ± 2,3 initial check-up versus 3,1 ± 2,4 in the second check-up, ns). The evolution of the amplitude of flexion-extension was significant for the microkinesitherapy group (95° ± 29° ° in the first check-up versus 107° ± 27° in the second check-up, p <0.02) but no improvement in the control group (104° ± 26° initial check-up versus 107° ± 28° in the second check-up, ns). Conclusion: Our study shows that an early microkinesitherapy session is effective on pain and recovery of flexion-extension in the treated group. [ABSTRACT FROM AUTHOR]

Asthma often starts before six years of age. However, there remains uncertainty as to when and how a preschool-age child with symptoms suggestive of asthma can be diagnosed with this condition. This delays treatment and contributes to both short- and long-term morbidity. Members of the Canadian Thoracic Society Asthma Clinical Assembly partnered with the Canadian Paediatric Society to develop a joint working group with the mandate to develop a position paper on the diagnosis and management of asthma in preschoolers. In the absence of lung function tests, the diagnosis of asthma should be considered in children one to five years of age with frequent (≥8 days/month) asthma-like symptoms or recurrent (≥2) exacerbations (episodes with asthma-like signs). The diagnosis requires the objective document of signs or convincing parent-reported symptoms of airflow obstruction (improvement in these signs or symptoms with asthma therapy), and no clinical suspicion of an alternative diagnosis. The characteristic feature of airflow obstruction is wheezing, commonly accompanied by difficulty breathing and cough. Reversibility with asthma medications is defined as direct observation of improvement with short-acting ß2-agonists (SABA) (with or without oral corticosteroids) by a trained health care practitioner during an acute exacerbation (preferred method). However, in children with no wheezing (or other signs of airflow obstruction) on presentation, reversibility may be determined by convincing parental report of a symptomatic response to a three-month therapeutic trial of a medium dose of inhaled corticosteroids with as-needed SABA (alternative method), or as-needed SABA alone (weaker alternative method). The authors provide key messages regarding in whom to consider the diagnosis, terms to be abandoned, when to refer to an asthma specialist and the initial management strategy. Finally, dissemination plans and priority areas for research are identified. [ABSTRACT FROM AUTHOR]

ABSTRACT Introduction: In preparation for clinical trials we examine the validity, reliability, and patient understanding of the Myotonic Dystrophy Health Index (MDHI). Methods: Initially we partnered with 278 myotonic dystrophy type-1 (DM1) patients and identified the most relevant questions for the MDHI. Next, we used factor analysis, patient interviews, and test-retest reliability assessments to refine and evaluate the instrument. Lastly, we determined the capability of the MDHI to differentiate between known groups of DM1 participants. Results: Questions in the final MDHI represent 17 areas of DM1 health. The internal consistency was acceptable in all subscales. The MDHI had a high test-retest reliability (ICC = 0.95) and differentiated between DM1 patient groups with different disease severities. Conclusions: Initial evaluation of the MDHI provides evidence that it is valid and reliable as an outcome measure for assessing patient-reported health. These results suggest that important aspects of DM1 health may be measured effectively using the MDHI. Muscle Nerve 49: 906-914, 2014 [ABSTRACT FROM AUTHOR]

Purpose: Participation in therapeutic clinical trials rarely reflects the race and ethnic composition of the patient population. To meet National Institutes of Health-mandated goals, strategies to increase participation are required. We present a framework for institutional enhancement of minority clinical trial accrual. Methods: We implemented structural changes on four levels to induce and sustain minority accrual to clinical trials: (1) leadership support; (2) center-wide policy change; (3) infrastructural process control, data analysis, and reporting; and (4) follow-up with clinical investigators. A Protocol Review and Monitoring Committee reviews studies and monitors accrual, and the Program for the Elimination Cancer Disparities leads efforts for proportional accrual, supporting the system through data tracking, Web tools, and feedback to investigators. Results: Following implementation in 2005, minority accrual to therapeutic trials increased from 12.0 % in 2005 to 14.0 % in 2010. The 'rolling average' minority cancer incidence at the institution during this timeframe was 17.5 %. In addition to therapeutic trial accrual rates, we note significant increase in the number of minorities participating in all trials (therapeutic and nontherapeutic) from 2005 to 2010 (346-552, 60 % increase, p < 0.05) compared to a 52 % increase for Caucasians. Conclusions: Implementing a system to aid investigators in planning and establishing targets for accrual, while requiring this component as a part of annual protocol review and monitoring of accrual, offers a successful strategy that can be replicated in other cancer centers, an approach that may extend to other clinical and translational research centers. [ABSTRACT FROM AUTHOR]

Abstract: Glutamine synthetase (GS) is ubiquitously expressed in mammalian organisms and is a key enzyme in nitrogen metabolism. It is the only known enzyme capable of synthesising glutamine, an amino acid with many critical roles in the human organism. A defect in GLUL, encoding for GS, leads to congenital systemic glutamine deficiency and has been described in three patients with epileptic encephalopathy. There is no established treatment for this condition. Here, we describe a therapeutic trial consisting of enteral and parenteral glutamine supplementation in a four year old patient with GS deficiency. The patient received increasing doses of glutamine up to 1020 mg/kg/day. The effect of this glutamine supplementation was monitored clinically, biochemically, and by studies of the electroencephalogram (EEG) as well as by brain magnetic resonance imaging and spectroscopy. Treatment was well tolerated and clinical monitoring showed improved alertness. Concentrations of plasma glutamine normalized while levels in cerebrospinal fluid increased but remained below the lower reference range. The EEG showed clear improvement and spectroscopy revealed increasing concentrations of glutamine and glutamate in brain tissue. Concomitantly, there was no worsening of pre-existing chronic hyperammonemia. In conclusion, supplementation of glutamine is a safe therapeutic option for inherited GS deficiency since it corrects the peripheral biochemical phenotype and partially also improves the central biochemical phenotype. There was some clinical improvement but the patient had a long standing severe encephalopathy. Earlier supplementation with glutamine might have prevented some of the neuronal damage. [ABSTRACT FROM AUTHOR]

Copyright of Otorhinolaryngology & Phoniatrics / Otorinolaryngologie a Foniatrie is the property of Czech Medical Association of JE Purkyne and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Although the cyanobacteria/BMAA hypothesis of the cause of ALS and other age-related neurodegenerative diseases remains to be proven, it is not too early to ask whether treatment would be possible if the hypothesis were correct. This paper reviews the possible ways that chronic BMAA neurotoxicity could be prevented or treated. [ABSTRACT FROM AUTHOR]

Aminopterin offers advantages over the related antifolate, methotrexate, including greater potency, complete bioavailability, and more consistent accumulation and metabolism by patients’ blasts. This current trial was done to document the toxicity of the aminopterin within a multiagent therapeutic regimen for children with newly diagnosed ALL. Patients at high risk of relapse were non-randomly assigned to therapy including oral aminopterin 4 mg/m2, in two doses 12 h apart, in place of methotrexate 100 mg/m2 in four divided doses. Thirty-two patients, 22 with pre-B ALL and ten with T-lineage ALL, have been treated with aminopterin, with median follow up of 40 months. Hematologic, mucosal and hepatic toxicity has been tolerable and reversible. There have been no toxic deaths among patients in remission. During weekly AMT therapy, higher mean neutrophil counts were observed among patients who were wild type for polymorphisms in methylene tetrahydrofolate reductase and methionine synthase reductase. Aminopterin can be safely incorporated in multiagent therapy for patients with ALL, in place of systemic methotrexate, without causing excessive toxicity. These results support a larger trial comparing the efficacy and toxicity of aminopterin and methotrexate in therapy for patients with ALL. [ABSTRACT FROM AUTHOR]

Cough and wheeze are common symptoms in childhood, but mostly do not signify a serious illness. On the basis of history and examination, such children should be allocated into one of five diagnostic categories. Very few need additional tests, although there are specific pointers in the initial evaluation which should actively be sought, and result in referral for investigation. In a community setting, isolated cough with no wheeze or breathlessness is most unlikely to be due to asthma. In pre-school children who cannot perform lung function tests, a therapeutic trial of asthma treatment may be indicated, but a three step protocol is mandatory, stopping therapy if there appears to be a response, and only restarting if symptoms recur. In older children, documentation of variable airflow obstruction before giving a diagnosis of asthma is important, to avoid over-diagnosis. Prophylactic therapy on a long term basis with inhaled steroids in preschool children does not reduce the likelihood of progression to asthma in mid-childhood, and the results of treatment in terms of symptoms are disappointing. [ABSTRACT FROM AUTHOR]

Copyright of Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

BACKGROUND: Vascular endothelial growth factor and mitochondrial abnormalities have been described in ALS and its animal models. We have reported that hyperbaric oxygen (HBO) treatment delayed the onset of weakness in the wobbler mouse. OBJECTIVE: To perform a Phase I safety study of HBO in patients with ALS. METHODS: Five patients with ALS were treated for 60 min with 100% oxygen at 2 atmospheres pressure daily for five days a week for four weeks. The patients reported any deterioration in their condition after each treatment, and their neurological condition was measured serially during the four weeks of the treatment, and for four further weeks. RESULTS: Four patients reported decreased fatigue, while one patient dropped out at three weeks because of increased fatigue. Maximum isometric voluntary contraction (MVIC) of all muscle groups except right hand grip improved significantly by up to 97%. Most improvement occurred during the four weeks after treatment. It is possible that the improvement in muscle strength was a placebo or a learning effect, though no such effects have been detected in prior therapeutic trials in ALS using MVIC. No change was detected in other measures of neuromuscular function. CONCLUSIONS: A longer duration, placebo controlled trial in a larger number of patients is needed to determine the safety and efficacy of HBO. Until that is completed, it is not recommended that ALS patients should be treated with HBO. [ABSTRACT FROM AUTHOR]

Copyright of Italian Journal of Neurological Sciences is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Calcitriol and alfacalcidol are useful in suppressing parathyroid hormone (PTH) in haemodialysis patients, but hypercalcaemia and hyperphosphataemia are frequent. The vitamin D analogue, 1α-hydroxy-vitamin D2 (1αD2), has a higher therapeutic index in animal models. Previously, 1αD2, 4 μg/day or 4 μg/haemodialysis, lowered iPTH to the target range in 87.5% of 24 haemodialysis patients with moderate to severe secondary hyperparathyroidism (plasma iPTH, 359-1521 pg/ml). The incidences of hypercalcaemia (serum Ca>2.8 mM) or hyperphosphataemia (serum P>2.23 mM) were low. Later, 10 of these patients were re-treated with 1αD2, initial dose, 10 μg, thrice weekly with haemodialysis. The iPTH was suppressed as readily, and there was no greater incidence of hypercalcaemia and hyperphosphataemia. Based on these data, a large, multicentre study is ongoing in California and Tennessee/Mississippi, using 1αD2 in haemodialysis patients with iPTH >400 pg/ml. In this and the earlier studies, only calcium-based phosphate binders were used to control serum phosphorus. The initial dose, 10 μg thrice weekly with haemodialysis is adjusted to maintain a target iPTH within the range of 150-300 μg/ml; the final dose range is 2.5-20 μg per haemodialysis. The protocol includes 8 weeks of randomized double blinded treatment with either continued 1αD2 or placebo. Forty two patients from California and 38 from Tennessee/Mississippi have completed 16 weeks of open label treatment. In California, iPTH declined from 832±95 pg/ml at baseline to 222±71 pg/ml at the nadir and to 477±117 pg/ml at week 16 of the treatment. In Tennessee/Mississippi, the iPTH declined from 977±65 pg/ml to 286±42 pg/ml at the lowest point and to 493±79 at the end of the treatment. Plasma iPTH reached or fell below the target range in 84% of the 80 patients completing open treatment. Asymptomatic hypercalcaemia (serum Ca >2.8 mM) increased from 0.3 episodes/100 weeks during wash-out to 3.6 episodes/100 treated weeks in California and from 0 to 3.7 episodes in Tennessee/Mississippi. In California and Tennessee, the episodes of hyperphosphataemia (serum P >2.2 mM) increased from 5.0 and 5.0 episodes per 100 patient/week during wash-out to 10.1 and 10.9 episodes/100 treatment weeks, respectively, with 1αD2 treatment. There were no adverse events in association with 1αD2 treatment. Thus, oral 1αD2 is safe and highly effective for the treatment of secondary hyperparathyroidism. [ABSTRACT FROM PUBLISHER]

In order to replace the central venous line necessary for continuous infusion of vincristine and doxorubicin with high-dose dexamethasone (VAD) and to avoid hospitalization, we evaluated the efficacy and toxicity of oral idarubicin, vincristine and dexamethasone (VID) inpatients with multiple myeloma. Vincristine (1.6 mg/m², max 2 mg) was given as a bolus injection on day 1. Idarubicin was given in capsules 10 mg/m²/day for days 1-4 with an intraindividual dose escalation, 40 mg dexamethasone were given on days 1-4, 9-12, 17-20. Treatment cycles were repeated every 28 days. At this interim analysis, 53 patients have been entered into the ongoing trial; 46 patients are evaluable for toxicity. The median age was 60 years (interquartile range, 52-65). 46% were primary or secondary refractory, 20% had previously been treated with VAD and 30% had previously untreated disease, 4% had two or more relapses. Four patients died within 2 months from entry and were considered as early deaths (8.7%). 45% of the 42 patients evaluable for efficacy achieved a partial remission and 26% a minor remission. The median reduction of the M-component was 43% (interquartile range, 25-64%). VID is an effective and convenient alternative to VAD even in relapsed or refractory patients. [ABSTRACT FROM AUTHOR]

Tetrahydroaminoacridine (THA), a centrally acting anticholinesterase, was used in a two-month, double-blind, placebo-controlled crossover trial to treat 10 patients meeting DSM-III-R criteria for dementia of the Alzheimer type. Eight patients continued to take THA for a further three months. Nausea was a frequent side-effect. Five patients developed abnormal liver function tests; liver biopsies showed evidence of liver cell necrosis in three patients, a granulomatous reaction in one, and one recovered after reduction of THA dosage. During the trial, patients as a group showed a significantly better performance on one of 10 memory tests when taking THA as compared to placebo. One patient showed a marked clinical improvement, six showed some improvement, and three patients showed no improvement with the active treatment. The group of eight patients who completed a further three months of THA treatment showed a significant deterioration on two psychological test scores. [ABSTRACT FROM AUTHOR]

The effect of supplements of vitamins B-1, B-2, niacin, B-6 and C has been assessed in a randomized double-blind trial in 15 hospitalized elderly patients suffering from senile dementia. Supplementation did not prevent an increase in either cognitive impairment or behavioural disturbance. However, it did result in weight gain over a six-week period. Hospitalized demented patients generally suffer significant weight loss, which increases with the duration of hospitalization. Vitamin supplementation may therefore protect against physical deterioration and the development of cachexia. [ABSTRACT FROM AUTHOR]

In order to assess the clinical characteristics and survival rate of pulmonary hemorrhage (PH) in systemic lupus erythematosus (SLE), we studied SLE patients who developed this complication. We found 34 patients within a total lupus cohort of 630 patients.A11 the patients had severe respiratory failure. We identified three different treatment regimens: (a) oral prednisone (1 mg/kg); (b) conventional methylprednisolone (3 g total dose) and (c) massive methylprednisolone ( > 4 g).The overall survival rate was 38.2% and it was correlated with the massive regimen and early treatment (within the first 48 h after the onset of the acute event). [ABSTRACT FROM PUBLISHER]

Background Huntington's disease (HD), a neurodegenerative disorder caused by an expanded CAG repeat in the HD gene, remains without a cure. Lithium, a drug widely used for the treatment of bipolar disorder, has been shown to exert neuroprotective effects in a number of models of neurological disease, including Alzheimer's disease, spinocerebellar ataxia type 1 and fragile X syndrome but has various toxic effects at conventional therapeutic doses. Aims To examine whether treatment with NP03, a low dose lithium microemulsion, would improve the phenotype of the YAC128 mouse model of HD. Methods YAC128 mice were treated with 0, 20 or 40 μg Li/kg of lithium carbonate in the form of NP03, a microemulsion of reverse micelles, via a daily deposit on rectal mucosa for 10 months, starting at 2 months of age. The microemulsion preparation allows for an increase in cellular bioavailability of lithium. Low doses of lithium in NP03 form are sufficient to achieve the intended therapeutic levels, while mitigating the toxic side effects associated with conventional lithium preparations. Wild-type (WT) animals were treated with NP03 either at 0 or 40 μg Li/kg. Motor function was assessed using the accelerating rotarod test at 2, 4, 6, 8, 10 and 12 months of age. Striatal pathology was assessed using unbiased stereology at 12 months of age. Results Treatment with NP03 at 40 μg Li/kg resulted in significant improvements in motor function in YAC128 HD mice. Further, the deficits in striatal volume, neuronal counts and DARPP-32 expression observed in YAC128 HD animals treated with vehicle alone were prevented in YAC128 HD animals treated with NP03 at 40 μg Li/kg. The motor function, striatal volume and neuronal counts of WT animals treated with NP03 at 40 μg Li/kg were similar to those of WT animals treated with vehicle alone. Furthermore, treatment with NP03 at 40μg Li/kg resulted in significant rescue of the testicular weight loss observed in YAC128 HD. Finally, treatment with NP03 at 40 μg Li/kg resulted in improved survival in YAC128 mice compared with animals treated with vehicle alone. There were no obvious toxic side effects associated with long term lithium treatment in YAC128 or WT animals. Conclusions Our findings, demonstrating multiple positive effects of low dose lithium in the form of NP03 on behavioural and neuropathological endpoints in an animal model of HD, support its further development as a potential therapeutic agent in HD. [ABSTRACT FROM PUBLISHER]

Background Huntington's Disease (HD) is an inherited neurological disorder characterised by loss of motor coordination, cognitive dysfunction and psychiatric disturbances that remains without a cure. Arimoclomol, a compound reported to enhance cellular stress induced heat shock protein response, has been shown to be neuroprotective in a mouse model of amyotrophic lateral sclerosis (ALS). Aims To examine whether treatment with arimoclomol would (a) protect against quinolinic acid (QA) mediated excitotoxicity and (b) improve the phenotype of the YAC128 mouse model of HD. Methods 3 month old wild-type (WT) mice were pretreated with PBS or arimoclomol (40 mg/kg, intraperitoneally followed by an intrastriatal injection of QA (20 nmol) 30 min later). Striatal lesion volume in arimoclomol and PBS treated animals was assessed 7 days later. YAC128 and WT mice were treated with 80 mg/kg of arimoclomol administered in the drinking water for 10 months, starting at 2 months of age. YAC128 and WT animals receiving water only served as no treatment controls. Motor function was assessed using the accelerating and fixed speed rotarod tests at 2, 4, 6, 8, 10 and 12 months of age. Striatal pathology was assessed using unbiased stereology at 12 months of age. Results In animals that received intrastriatal injections of QA, there was no significant difference in lesion volume between those pretreated with arimoclomol compared with those treated with PBS only. In animals receiving arimoclomol chronically, there was no significant difference between arimoclomol treated and untreated WT animals in motor performance, as assessed by the accelerating and fixed speed rotarod tests. The motor performance of untreated YAC128 HD mice was significantly lower compared with that of untreated WT animals. Treatment with arimoclomol had no effect on motor performance of YAC128 HD animals compared with untreated YAC128 HD animals. Further, brain weight and striatal volume of untreated YAC128 HD animals was significantly lower compared with untreated WT animals. Treatment with arimoclomol had no effect on brain weight or striatal volume of YAC128 HD animals compared with untreated YAC128 HD mice. Conclusions Our findings demonstrate that treatment with arimoclomol does not lead to improvements in motor function or rescue of striatal pathology in YAC128 HD mice. [ABSTRACT FROM PUBLISHER]