A new case of sodium-dependent multivitamin transporter defect occurring as a life-threatening condition responsive to early vitamin supplementation and literature review.

BACKGROUND: Biallelic pathogenic variants in SLC5A6 resulting in sodium-dependent multivitamin transporter (SMVT) defect have recently been described as a vitamin-responsive inborn error of metabolism mimicking biotinidase deficiency. To our knowledge, only 16 patients have been reported so far with various clinical phenotypes such as neuropathy and other neurologic impairments, gastro-intestinal dysfunction and failure to thrive, osteopenia, immunodeficiency, metabolic acidosis, hypoglycemia, and recently severe cardiac symptoms. METHODS: We describe a case report of a 5-month-old girl presenting two recurrent episodes of metabolic decompensation and massive cardiac failure in the course of an infectious disease. We compare clinical, biological, and genetic findings of this patient to previous literature collected from Pubmed database (keywords: Sodium-dependent multivitamin transporter (SMVT), SMVT defect/disorder/deficiency, SLC5A6 gene/mutation). RESULTS: We highlight the life-threatening presentation of this disease, the stagnation of psychomotor development, the severe and persistent hypogammaglobulinemia, and additionally, the successful clinical response on early vitamin supplementation (biotin 15 mg a day and pantothenic acid 100 mg a day). Metabolic assessment showed a persistent increase of urinary 3-hydroxyisovaleric acid (3-HIA) as previously reported in this disease in literature. CONCLUSION: SMVT deficiency is a vitamin-responsive inborn error of metabolism that can lead to a wide range of symptoms. Increased and isolated excretion of urinary 3-hydroxyisovaleric acid may suggest, in the absence of markedly reduced biotinidase activity, a SMVT deficiency. Prompt supplementation with high doses of biotin and pantothenic acid should be initiated while awaiting results of SLC5A6 sequencing as this condition may be life-threatening.

Cost-effectiveness of mifepristone and misoprostol versus misoprostol alone for the management of missed miscarriage: an economic evaluation based on the MifeMiso trial.

OBJECTIVE: To assess the cost-effectiveness of mifepristone and misoprostol (MifeMiso) compared with misoprostol only for the medical management of a missed miscarriage. DESIGN: Within-trial economic evaluation and model-based analysis to set the findings in the context of the wider economic evidence for a range of comparators. Incremental costs and outcomes were calculated using nonparametric bootstrapping and reported using cost-effectiveness acceptability curves. Analyses were performed from the perspective of the UK's National Health Service (NHS). SETTING: Twenty-eight UK NHS early pregnancy units. SAMPLE: A cohort of 711 women aged 16-39 years with ultrasound evidence of a missed miscarriage. METHODS: Treatment with mifepristone and misoprostol or with matched placebo and misoprostol tablets. MAIN OUTCOME MEASURES: Cost per additional successfully managed miscarriage and quality-adjusted life years (QALYs). RESULTS: For the within-trial analysis, MifeMiso intervention resulted in an absolute effect difference of 6.6% (95% CI 0.7-12.5%) per successfully managed miscarriage and a QALYs difference of 0.04% (95% CI -0.01 to 0.1%). The average cost per successfully managed miscarriage was lower in the MifeMiso arm than in the placebo and misoprostol arm, with a cost saving of £182 (95% CI £26-£338). Hence, the MifeMiso intervention dominated the use of misoprostol alone. The model-based analysis showed that the MifeMiso intervention is preferable, compared with expectant management, and this is the current medical management strategy. However, the model-based evidence suggests that the intervention is a less effective but less costly strategy than surgical management. CONCLUSIONS: The within-trial analysis found that based on cost-effectiveness grounds, the MifeMiso intervention is likely to be recommended by decision makers for the medical management of women presenting with a missed miscarriage. TWEETABLE ABSTRACT: The combination of mifepristone and misoprostol is more effective and less costly than misoprostol alone for the management of missed miscarriages.

An automated pressure-swing absorption system to administer low oxygen therapy for persons with spinal cord injury.

Mild episodes of breathing low oxygen (O2) (i.e., acute intermittent hypoxia, AIH) elicits rapid mechanisms of neural plasticity that enhance respiratory and non-respiratory motor function after spinal cord injury (SCI). Despite promising outcomes in humans and rodents with SCI, the translational potential of AIH as a clinical therapy remains dependent on a safer and more reliable air delivery system. The purpose of this study is to investigate the performance of a novel AIH delivery system to overcome inconsistencies in human AIH protocols using a hand-operated (manual) delivery system. Specifically, we characterized system performance of AIH delivery in terms of flow rate, O2 concentration, dose timing, and air temperature. Our data show that a novel 'automated' delivery system: i) produces reliable AIH with a goodness-of-fit at 98.1% of 'ideal'; ii) eliminates dose timing errors via programmable solenoid switches; iii) reduces fluctuations in O2 to less than 0.01%; and iv) delivers 62.7% more air flow than the 'manual' delivery method. Automated physiological recordings, threshold detection, and visual feedback of the participant's blood O2 saturation, heart rate, and blood pressure ensures real-time user safety. In summary, the 'automated' system outperformed the 'manual' delivery method in terms of accuracy, reliability, and safety. The 'automated' system offers several design features that move the technology closer to a medically approved treatment for clinical and home use.

Potential consequences of high-dose infusion of ketamine for refractory status epilepticus: case reports and systematic literature review.

Our goal was to provide comprehensive data on the effectiveness of ketamine in refractory status epilepticus (RSE) and to describe the potential consequences of long-term ketamine infusion. Ketamine, an N-methyl D-aspartate (NMDA) receptor antagonist, blocks excitatory pathways contributing to ongoing seizure. While ketamine use is standard in anaesthetic induction, no definitive protocol exists for its use in RSE, and little is known about its adverse effects in long-term, high-dose administration. We present two cases of RSE that responded rapidly to ketamine infusion, both with fatal outcomes secondary to metabolic acidosis and cardiovascular collapse. We performed a systematic review of the application and consequences of ketamine use in RSE. PubMed, Ovid, MEDLINE and PMC were searched for articles describing ketamine treatment for RSE according to a predetermined search strategy and inclusion criteria. The systematic review revealed wide discrepancies in ketamine dosing (infusion maintenance dose range 0.0075-10.5 mg/kg/hour), but good outcomes in medically managed RSE (75% of studies reported moderate or complete seizure control in adults, 62.5% in paediatrics). Additionally, literature review elucidated a potentially causal relationship between prolonged ketamine infusion and both cardiovascular and metabolic dysregulation. Ketamine is effective in RSE by antagonising excitotoxic NMDA receptors. However, there is high variability in ketamine dosing and scarce data on its safety in long-term infusion. Metabolic acidosis and haemodynamic instability associated with the use of long-term, high-dose ketamine infusions must be of concern to clinicians administering ketamine to critically ill patients.

[A 2-month-old child with complex tracheal hypoplasia]. / Hypoplasie trachéale complexe chez un enfant de 2 mois.

We describe the case of a 2-month-old child with complex tracheal hypoplasia with bilateral bronchial hypoplasia and left pulmonary hypoplasia. Tracheal hypoplasia is complex when it is associated with critical stenosis, cricoid stenosis, bronchial hypoplasia, tracheal bronchus, or esophageal atresia with severe tracheomalacia. Slide tracheoplasty is the gold standard treatment for the complex tracheal hypoplasia.

Surgical-site infection surveillance in general surgery: a critical issue.

This prospective study assessed the Surgical Site Infection (SSI) rates in General Surgery and the microorganisms isolated. From January 2000 to October 2000, 898 patients were enrolled and electively operated in a General Surgery Clinic in Athens, Greece. Pre-coded questionnaires were used. The diagnosis and surveillance of SSIs was made by the surgeon-investigator who interviewed the patients. Patients were monitored during hospitalization and post-discharge for 30 days. Overall, 402 patients underwent a clean and 496 patients underwent a clean-contaminated operation. A total of 17 SSIs (4.2%) were observed in clean and 64 SSIs (12.9%) in clean-contaminated operations. Microorganisms were isolated in 36 of 65 (55%) of cases that microbiological evaluation was performed. Staphylococcus aureus was the commonest microorganism isolated, followed by Escherichia coli and Pseudomonas aeruginosa. SSI rates were higher than expected and most SSIs, 43 of 81 (53.1%), were diagnosed post-operatively. Post-discharge surveillance of SSIs remains a critical issue. Health care professionals, especially surgeons, should participate in surveillance networks and be aware of the results so to take appropriate action.

Adherence to guidelines for antibiotic prophylaxis in general surgery: a critical appraisal.

OBJECTIVES: To evaluate the adherence of general surgeons to guidelines for antimicrobial prophylaxis. This study was held from January 2000 until October 2000 in a General Surgery Clinic in a hospital in Athens, Greece. METHODS: Eight hundred and ninety-eight patients were enrolled and operated on electively. Questionnaires concerning demographic data, health status, type of surgery (clean and clean-contaminated) and parameters of antibiotic prophylaxis (antibiotic choice, route, dose, timing of first dose, timing of operative redosing and duration of prophylaxis) were completed. RESULTS: Of the patients, 44.8% underwent a clean surgical operation and 55.2% underwent a clean-contaminated surgical operation. Inguinal hernia repair and laparoscopic cholecystectomy were the commonest operations in each category. Second-generation cephalosporins were the most frequently prescribed antibiotics, in 67%. Although, only 78.5% of procedures required prophylaxis, it was administered in 97.5%, so it was not justified and inappropriately administered in 19%. It was revealed that 100% of patients received antibiotic prophylaxis on time. The choice of antimicrobial agent was appropriate in 70% and the duration of prophylaxis was optimal in 36.3%. The overall compliance rate of surgeons with guidelines for antibiotic prophylaxis was 36.3%. CONCLUSIONS: Adherence to separate aspects of guidelines for surgical prophylaxis has to be improved. The duration of antibiotic prophylaxis was the main parameter of interest. Interventions have to be made about the development, distribution and adoption of adequate guidelines in collaboration with surgeons.

The significance of circulating levels of both cardiac troponin I and high-sensitivity C reactive protein for the prediction of intravenous thrombolysis outcome in patients with ST-segment elevation myocardial infarction.

OBJECTIVES: To evaluate, using continuous 12-lead ECG ST-segment monitoring, the role of circulating levels of both cardiac troponin I (cTnI) and high-sensitivity C reactive protein (hs-CRP), on presentation, in the prediction of intravenous thrombolysis outcome in patients with ST-segment elevation myocardial infarction (STEMI). DESIGN AND SETTING: Prospective observational study in a tertiary referral centre. PATIENTS: 786 consecutive patients with STEMI, who received intravenous thrombolysis in the first 6 h from index pain. MAIN OUTCOME MEASURES: The incidence of failed thrombolysis and of cardiac death by 30 days. Failed thrombolysis was defined as the absence of abrupt and sustained > or =50% ST-segment recovery in the first 90 min after the initiation of intravenous thrombolysis. RESULTS: The incidence of failed thrombolysis and 30-day cardiac death was 57.4% and 11.8%, respectively. By multivariate logistic regression analysis according to tertiles of both cTnI (RR, 1.5; 95% CI 1.1 to 1.8, p = 0.004 for highest vs middle third; 2.2, 1.9 to 3.5, p<0.001 for highest vs lowest third; 1.5, 1.2 to 1.8, p = 0.001 for middle vs lowest third) and hs-CRP (RR, 2.0, 95% CI, 1.6 to 2.2; p<0.001 for highest vs middle third; 2.6, 2.1 to 3.5, p<0.001 for highest vs lowest third; 1.3, 1.2 to 1.7, p = 0.02 for middle vs lowest third), were independently associated with failed thrombolysis. Moreover, by multivariate Cox regression analysis according to tertiles of both cTnI (HR 1.2, 95% CI 1.1 to 1.8, p = 0.03 for highest vs middle third; 1.5, 1.2 to 2.2, p = 0.004 for highest vs lowest third; 1.1, 0.6 to 1.4, p = 0.6 for middle vs lowest third) and hs-CRP (HR1.2, 95% CI 1.1 to 1.6, p = 0.04 for highest vs middle third; 1.7, 1.3 to 2.6, p = 0.001 for highest vs lowest third; 1.1, 0.9 to 2.1, p = 0.1 for middle vs lowest third), were independently related with an increased risk of 30-day cardiac death. CONCLUSIONS: High circulating levels of both cTnI and hs-CRP are related with an independent increased risk of intravenous thrombolysis failure and 30-day cardiac death in patients who received intravenous thrombolysis in the first 6 h of STEMI.

Utilization of a glucagon infusion in the management of a massive nifedipine overdose.

This case report describes a continuous i.v. infusion of glucagon used to reverse the cardiovascular manifestations of a nifedipine overdose in a patient who presented after a massive nifedipine extended-release tablet ingestion. In this patient, glucagon appeared to be effective in the management of this toxicologic emergency.

Effect of low-dose methylprednisolone on calcium balance and bone composition in rats.

Glucocorticoid induced osteoporosis has been associated with high doses and it has been partially attributed to decreased absorption and to increased calcium excretion. The present study examined the effect of low but effective doses of methylprednisolone (MP) on calcium balance and on skeleton in rats. Total duration of the experiment 29 days. Thirty-one male Wistar rats (MP group) were injected with 4mg/kg body weight MP s.c. at the 1st, 11th and 20th day of the experiment and 28 rats (C group) were used as matched controls. The 1st, 11th and 20th day of the experiment rats were placed in individual metabolic cages for three days. Food and water consumption were measured at the 2nd and 3rd days after each injection; urine and faeces were collected at the same days for calcium estimation. Calcium intake and excretion after each injection was significantly lower in the MP group as compared to controls. A statistically significant positive correlation between calcium consumption and calcium excretion was found in both groups resulting in a negative final balance. Rats were killed the 29th day. Adrenal weight was statistically significant lower in MP group (p<0.001). Morphometric properties were evaluated for the right femur. No significant difference was found between the two groups. Mineral and calcium content was slightly increased in the MP group. According to these results, it seems that methylprednisolone while effective on HPA axis did not have any effect on calcium absorption and on bone calcium deposition in rats.

High-affinity binding of short peptides to major histocompatibility complex class II molecules by anchor combinations.

We have previously identified four anchor positions in HLA-DRB1*0101-binding peptides, and three anchors involved in peptide binding to DRB1*0401 and DRB1*1101 molecules, by screening of an M13 peptide display library (approximately 20 million independent nonapeptides) for DR-binding activity. In this study, high stringency screening of the M13 library for DRB1*0401 binding has resulted in identification of three further anchor positions. Taken together, a peptide-binding motif has been obtained, in which six of seven positions show enrichment of certain residues. We have demonstrated an additive effect of anchors in two different ways: (i) the addition of more anchors is shown to compensate for progressive truncation of designer peptides; (ii) the incorporation of an increasing number of anchors into 6- or 7-residue-long designer peptides is shown to result in a gradual increase of binding affinity to the level of 13-residue-long high-affinity epitopes. The anchor at relative position 1 seems to be obligatory, in that its substitution abrogates binding completely, whereas the elimination of other anchors results only in partial loss of binding affinity. The spacing between anchors is critical, since their effect is lost by shifting them one position toward the N or C terminus. The information born out of this study has been successfully used to identify DR-binding sequences from natural proteins.

[Antibiotic levels in blood serum and mandibular bone in rats with and without phenylbutazone administration]. / Epipeda antibiotikon ston oro tou aimatos kai sto ostoun tes kato gnathou epimyon me kai choris chroegese phainylboutazones.

Antibiotics' level was estimated in mandible and serum of wistar albino rats with and without co-administration of phenylbutazone, 5 groups of animals were used. The animals of group A were injected with 1 g/kg ampicillin and these of group B 1g/kg ampicillin and 100 mg/kg phenylbutazone im. To the animals of group C cephapirin was given 1 g/kg and these of group D 1g/kg cephapirin with 100 mg/kg phenylbutazone. The animals of group E were injected only with phenylbutazone. All the drugs, were given at a single dose. The level of antibiotics was estimated in serum and in mandible with the method of minimal inhibitory concentration (MIC). An increase of the levels of antibiotics (ampicillin, cephapirin) was observed in those groups (B, D) to the animals of which phenylbutazone was given (together with antibiotics), compared with the groups (A, C) which had received antibiotics alone.

Concentration of metronidazole in rat serum and mandible.

The levels of metronidazole in rat serum and mandibular bones was measured 2, 5 and 8 h after oral administration of three doses of 200 mg/kg. Effective levels of the drug in serum and mandible were found at all time intervals as well as a higher concentration in mandible than in serum.

[Anatomo-pathologic lesions of kidneys in mice subjected to chronic stress]. / Lésions anatomo-pathologiques des reins de souris soumises à un stress chronique.

Three groups of white mice were used. The experiment took place over 138 days. The first Group was used as a control group. The second group was exposed to continuous stress (Population Stress). The third Group was exposed to chronic Stress by electroshock with 22-45 volts for a duration of 4 seconds each minute for one hour each day. The blood vessels are the first to be affected quickly followed by degenerative changes of the glomeruli, which are possible due to hemodynamic disturbances, results in progressive destruction of the kidneys. The following pathanatomical changes were found in the stressed kidneys. (1) Spasm of the arterioles and dilation of the veins. (2) Excavation of hemolysed RBC into Bowmans Capsule. (3) Retraction of the glomerula apparatus with degenerative changes of the cells which to a great extent reached total necrosis or even total destruction of the whole glomerulus. (4) Injury to the renal tubules : the cells of the renal tubules were found edematous with unclear borders between cells in the renal cortex and protoplasmic atrophy medullary cells. The observations derived from this work clearly show that stress causes functional disturbances and histologic changes in the kidneys of white mice.