The incidence of hypoxemia in dogs recovering from general anesthesia detected with pulse-oximetry and related risk factors.

The postoperative period is critical for the development of complications, including hypoxemia. To detect hypoxemia early and provide appropriate care, continuous monitoring of saturation is necessary: pulse oximetry is an easily accessible and simple method for this purpose. However, a SpO2 cut-off value to detect hypoxemia in dogs recovering from general anesthesia is lacking in the veterinary literature. The objectives of this clinical study are to validate the room air SpO2 test (SpAT), to identify a cut-off value to discriminate hypoxemia (Phase 1), and to apply the SpAT to study the incidence of transient postoperative hypoxemia (TPH) (Phase 2) in dogs with healthy lungs recovering from general anesthesia. Phase 1: 87 dogs recovering from general anesthesia with an arterial line were included. After extubation, SpAT was performed simultaneously with arterial blood sampling. A PaO2 < 80mmHg was considered hypoxemia. Phase 2: 654 dogs were enrolled. They underwent general anesthesia with different ventilation settings for different procedures. After extubation, dogs were classified as hypoxemic if the SpO2 was lower than the cut-off obtained in phase 1. Phase 1 showed that the SpO2 cut-off is < 95% (sensitivity 100%, specificity 97.4%; area under the curve, AUC = 0.996; 95% Confidence Interval = 0.944-1; P<0.0001). In Phase 2, 169 dogs were hypoxemic. Body Condition Score (BCS) > 3/5, dorsal recumbency, FiO2 1, absence of Positive End-Expiratory Pressure (PEEP) had a significant odds ratio to induce TPH (5.8, 1.9, 3.7, 1.7, respectively). These results showed that SpO2 < 95% indicates PaO2 < 80mmHg in dogs and TPH occurs in up to 28% of cases. Identification of associated risks could be useful to prevent and to increase awareness for monitoring and treatment.

Prognostic dilemmas for SIDS in idiopathic fetal right atrium dilatation: Case report and review literature.

The authors describe a case of fetal isolated right atrial enlargement or IDRA (idiopathic dilatations of the right atrium) evident in third trimester, complicated by arrhythmia in the female infant during the 1° month of life with ECG diagnosis of Wolf-Parkinson-White syndrome (WPW). The eldest sister died at 6 years because of an arrhythmia with the same diagnosis of WPW. The review of the literature on IDRA frequently shows a familial genetic aggregation. The pathogenetic mechanism underlying the dilation of the right atrium could consist of a myopathy or electrical conduction disorder. The exclusive involvement of the right atrium may be due to the increased pressure in the fetal right atrium. On the basis of our case and after review of the literature, we must be careful in defining as physiological the enlargement of the right fetal atrium in the third trimester of pregnancy. The ultrasound sign of IDRA may be a fetal prodrome of SIDS (sudden infant death syndrome).

Observational study of the clinical value of the canine osteoarthritis staging tool.

The aim of this multi-centred, cohort, prospective, observational study was to evaluate the clinical application of the canine osteoarthritis staging tool (COAST), in dogs affected by osteoarthritis (OA). In all dogs, a COAST stage was obtained based on the Liverpool Osteoarthritis in Dogs (LOAD) score and a complete orthopaedic and radiographic examination. The severity of OA (COAST stage) was scored as 1 (preclinical), 2 (mild), 3 (moderate), and 4 (severe). These scores were compared with the overall subjective opinion of experienced orthopaedic surgeons who examined the dogs (Clinical Opinion). Data were analysed with descriptive statistic, multiple regression analysis, chi-square and Bland-Altman tests (P < 0.05). In total, 362 evaluations were performed in 202 dogs. Clinical Opinion had a greater proportion of stage 1 and 2 cases compared to COAST (P < 0.0001). The proportion of stage 4 cases was higher in COAST compared to Clinical Opinion (P < 0.0001). The proportions of Stage 3 cases were similar in the two evaluation systems. COAST had a strong correlation (r = 0.79; P < 0.01) with Clinical Opinion. Overall, the two evaluation systems exhibited strong agreement (mean bias 0.51). Stages 1 and 2 had weaker agreement (mean bias 1.04 and 0.75, respectively), than stage 3 and stage 4 (mean bias 0.46 and 0.0, respectively).

Comparison of CPAP and oxygen therapy for treatment of postoperative hypoxaemia in dogs.

OBJECTIVE: To compare 5 cmH2 O of continuous positive airway pressure with oxygen therapy in dogs recovering from general anaesthesia with low SpO2 values. continuous positive airway pressure is more effective than oxygen therapy in restoring normoxaemia (SpO2 ≥95%). MATERIALS AND METHODS: Prospectively, dogs recovering from anaesthesia, with SpO2 <95% after extubation (T0), were randomised and treated with continuous positive airway pressure (FiO2 0.21) or oxygen (O2 ; FiO2 0.35-0.40) therapy. Dogs were monitored with SpO2 every 15 minutes for 1 hour (T15, T30, T45, T60). Data from normoxaemic dogs (SpO2 >95%) were used as control (CTR). RESULTS: Of the 42 dogs enrolled, 34 completed the study. Eleven dogs were treated with O2 , 10 with continuous positive airway pressure and 13 were CTR. The SpO2 values at T0 were similar in the continuous positive airway pressure and O2 groups and were lower than in the CTR group. At T15, T30, T45 and T60, the SpO2 values in the continuous positive airway pressure group were higher than at T0; these were similar to those of the CTR group at the same time-points. In the O2 group, SpO2 values were significantly higher at T45 and T60 than at T0; 45.5% of dogs became normoxaemic at T45 and the remaining dogs became normoxaemic at T60. The average time to reach normoxaemia in the O2 group (53.1±7.3 minutes) was longer than in the continuous positive airway pressure group (15.0±0.0 minutes). CLINICAL SIGNIFICANCE: In dogs recovering from general anaesthesia with pulmonary gas exchange impairment, normoxaemia is restored more effectively and rapidly by using continuous positive airway pressure than by oxygen therapy.

Efficacy of levetiracetam on upper limb movement in multiple sclerosis patients with cerebellar signs: a multicenter double-blind, placebo-controlled, crossover study.

BACKGROUND AND PURPOSE: The literature provides contrasting results on the efficacy of levetiracetam (LEV) in multiple sclerosis (MS) patients with cerebellar signs. It was sought to evaluate the efficacy of LEV on upper limb movement in MS patients. METHODS: In this multicenter double-blind placebo-controlled crossover study, MS patients with prevalently cerebellar signs were randomly allocated into two groups: LEV followed by placebo (group 1) or placebo followed by LEV (group 2). Clinical assessments were performed by a blinded physician at T0 (day 1), T1 (day 22), T2 (2-week wash-out period, day 35) and T3 (day 56). The primary outcome was dexterity in the arm with greater deficit, assessed by the nine-hole peg test (9HPT). Secondary clinical outcomes included responders on the 9HPT (∆9HPT >20%), tremor activity of the daily living questionnaire and self-defined upper limb impairment, through a numeric rating scale. Kinematic evaluation was performed using a digitizing tablet, providing data on normalized jerk, aiming error and centripetal acceleration. RESULTS: Forty-eight subjects (45.2 ± 10.4 years) were randomly allocated into two groups (n = 24 each). 9HPT significantly improved in the LEV phase in both groups (P < 0.001). The LEV treatment phase led to a significant improvement (P < 0.01) of all clinical outcomes in group 1 and in dexterity in group 2. No significant changes were reported during both placebo phases in the two groups. Considering the kinematic analysis, only normalized jerk significantly improved after treatment with LEV (T0-T1) in group 1. CONCLUSIONS: Levetiracetam treatment seems to be effective in improving upper limb dexterity in MS patients with cerebellar signs.

Sudden hearing loss as an early detector of multiple sclerosis: a systematic review.

OBJECTIVE: To evaluate whether Sudden Sensorineural Hearing Loss (S-SNHL) may be an early symptom of Multiple Sclerosis (MS). MATERIALS AND METHODS: A systematic review was conducted using the following keywords: "Multiple sclerosis, hearing loss, sudden hearing loss, vertigo, tinnitus, magnetic resonance imaging, otoacoustic emission, auditory brainstem responses, white matter lesions, sensorineural hearing loss, symptoms of MS and otolaryngology, nerve disease and MS". Only the articles that included results of at least one auditory test and MRI were considered. We evaluated the prevalence of SNHL in patients with MS, the presence of different forms of SNHL (S-SNHL and Progressive SNHL (P-SNHL)) and their correlation with the stage of MS, the results of electrophysiological tests, and the location (if any) of MS lesions as detected by white matter hyperintensities in the MRI. RESULTS: We reviewed a total of 47 articles, which included 29 case reports, 6 prospective studies, 6 cohort studies, 4 case-control studies, and 2 retrospective studies. 25% of patients suffered from SNHL. S-SNHL typically occurred in the early stage of the disease (92% of patients) and was the only presenting symptom in 43% of female subjects. Instead, P-SNHL occurred in the late stage of MS (88% of patients). Auditory Brainstem Responses (ABR) were abnormal in all MS patients with S-SNHL. When S-SNHL appeared during the early stage of the disease, MS lesions were found in the brain in 60% of patients and in the Internal Auditory Canal in 40% of patients. ABR remained abnormal after recovery. CONCLUSIONS: S-SNHL can be an early manifestation of MS and should always be considered in the differential diagnosis of this condition, especially in women. The pathophysiology can be explained by the involvement of microglia attacking the central and/or peripheral auditory pathways as indicated by WMHs.

Fertility in a i(Xq) Klinefelter patient: importance of XIST expression level determined by qRT-PCR in ruling out Klinefelter cryptic mosaicism as cause of oligozoospermia.

The presence of an isochromosome Xq in Klinefelter syndrome (KS) is an apparently rare condition. In all cases reported so far, patients showed the classic phenotype. We here describe a case of isochromosome Xq [47,X,i(Xq),Y] in a non-mosaic KS patient. The patient exhibited a normal androgenized phenotype, normal testes and normal cognitive abilities. Semen analysis revealed a medium oligozoospermia (5 x 10(6) spermatozoa/ml). After the patient underwent intracytoplasmic sperm injection, he generated two cytogenetically healthy normal females. Fluorescence in situ hybridization analysis showed the presence of a dicentric Xq chromosome that did not show the presence of residual Xp arm up to the 57,820,478 bp position (Xp 1.1) of X chromosome sequence. Preferential inactivation of Xq isochromosome was demonstrated by bromodeoxyuridine replication analysis and transcriptional silencing by DNA methylation at the HUMARA locus. Furthermore, we demonstrated by quantitative RT-PCR an active XIST RNA expression in blood lymphocytes from Klinefelter patients, comparable to that observed in control females and over 30,000-fold greater than in control males. In conclusion, this qRT-PCR approach could be useful for screening of prepuberty males and for diagnosis or exclusion of cryptic Klinefelter mosaics.

Electroclinical evolution in ring chromosome 20 epilepsy syndrome: a case with severe phenotypic features followed for 25 years.

Intractable epilepsy and peculiar EEG patterns characterize ring chromosome 20 syndrome [r(20)], while dysmorphic features, mental retardation and behavioural disturbances are widely variable. The clinical evolution of r(20) over time is not well defined as relatively few cases have been reported. Here we describe a patient with severe clinical features followed for a 25-year period. The patient was subjected to clinical, psychometric and EEG evaluation twice a year from the age of 21 years. Cytogenetic studies, using chromosome analysis and fluorescence in situ hybridization (FISH) and several immunological investigations were performed. Ring chromosome 20 was found in 50% of examined metaphases with the deletion of subtelomeric regions 20p and 20q. Our patient presented with marked dysmorphic features, severe mental retardation, tetraparesis, dysarthria and intractable epilepsy with onset during the first year of life. During follow up, EEG findings and clinical features progressively worsened: a progressive disorganization of background EEG activity occurred and mental and motor impairment evolved. The severity of clinical expression depended on the extent of chromosomal deletion and on the haploinsufficiency of other important related genetic loci due to ring instability. The progressive worsening of both clinical and EEG features over a long period, which has also been reported by other authors, further characterized this syndrome.

Avoiding health insurance crowd-out: evidence from the Medicare as secondary payer legislation.

The cost of expanding health insurance coverage increases when people who would otherwise purchase insurance obtain public coverage. This paper investigates the effects of one of the first efforts to target insurance benefits to the most needy, the 1982 medicare as secondary payer (MSP) provisions. We find strong evidence of low compliance with the MSP both in terms of medical bill payments (payment compliance) and employer-sponsored insurance coverage (coverage compliance). We estimate payer compliance at approximately 33%. Coverage compliance is lower, at under 25%. We find weak evidence that the MSP caused older workers to shift toward MSP-exempt jobs.

Familial infantile myoclonic epilepsy: clinical features in a large kindred with autosomal recessive inheritance.

PURPOSE: To describe the clinical features of a large kindred with familial infantile myoclonic epilepsy (FIME) with autosomal recessive inheritance, and to discuss the nosology of the early infantile myoclonic epilepsies (IMEs). METHODS: The family descends from the intermarriage of two couples of siblings. In a previous study, we mapped the genetic locus to chromosome 16p13. We analyzed results of family records and personal history, psychomotor development, neurologic examination, epilepsy features, and EEG recordings for each subject. RESULTS: FIME has a strong penetrance (eight affected of 14 subjects) and a homogeneous clinical picture. Like the benign form of infantile myoclonic epilepsy (BIME), FIME is a true idiopathic IME with unremarkable history, no neurologic or mental impairment, good response to treatment, and normal interictal EEG pattern. Conversely, onset with generalized epileptic seizures without fever (four patients) or with fever (one patient), frequency and duration of the myoclonic seizures, occurrence of generalized tonic--clonic seizures (GTCSs) in all patients and persistence of seizures into adulthood are characteristics of the severe infantile myoclonic epilepsy (SIME). CONCLUSIONS: Clinical overlap probably exists among the myoclonic epilepsies of infancy. FIME differs from other forms of IME in its phenotypic features. The peculiar mode of inheritance is explained by the genetic background of the family. Genetic studies suggest linkage to chromosome 16 in familial cases of true IME.

Explaining the decline in health insurance coverage among young men.

This article examines the experience of cohorts of young American men to see how and why their employer-provided health insurance coverage has changed over time. It explores changes in the structure of the labor market, changes in the cost of employer-provided health insurance, and changes in the composition of wages and benefits offered to employees. We find that increases in the cost of health insurance rather than changes in the structure of the labor market are the principal cause of the observed decline in employer-provided health insurance coverage across all cohorts.

Should children with suspected obstructive sleep apnea syndrome and normal nap sleep studies have overnight sleep studies?

STUDY OBJECTIVES: Overnight polysomnography (ONP) is the "gold standard" for the diagnosis of sleep-disordered breathing, but it is expensive and time-consuming. Thus, daytime nap studies have been used as screening tests. If the findings of a nap study are normal or mildly abnormal, should ONP be performed? Do specific abnormalities in nap studies predict abnormal findings in ONP? To answer these questions, we conducted this study. DESIGN: Retrospective chart review. SETTING: Children's hospital. PARTICIPANTS: One hundred forty-three children with suspected obstructive sleep apnea syndrome secondary to isolated adenotonsillar hypertrophy, who had normal or mildly abnormal nap studies, and underwent ONP. MEASUREMENTS AND RESULTS: We compared daytime nap and overnight polysomnograms in 143 children (52 girls; mean [+/- SD] age, 5.6 +/- 3.1 years). Total sleep time was 1 h in daytime nap, and 5.1 +/- 1.3 h in ONP. The interval between the two studies was 5.9 +/- 4.8 months. The findings of 59% of the nap studies were mildly abnormal, while 66% of overnight studies were abnormal. No individual nap study parameter (including short obstructive apneas, hypopneas, hypoxemia, hypoventilation, snoring, paradoxical breathing, gasping, retractions) had good sensitivity at predicting abnormal overnight polysomnograms, but most had good specificity and positive predictive value. CONCLUSIONS: We conclude that individual nap study parameters are not very sensitive in predicting abnormal ONP findings. However, when nap study parameters are abnormal, the chance of obstructive sleep apnea syndrome is high.

Mapping of a locus for a familial autosomal recessive idiopathic myoclonic epilepsy of infancy to chromosome 16p13.

Myoclonic epilepsies with onset in infancy and childhood are clinically and etiologically heterogeneous. Although genetic factors are thought to play an important role, to date very little is known about the etiology of these disorders. We ascertained a large Italian pedigree segregating a recessive idiopathic myoclonic epilepsy that starts in early infancy as myoclonic seizures, febrile convulsions, and tonic-clonic seizures. We typed 304 microsatellite markers spanning the 22 autosomes and mapped the locus on chromosome 16p13 by linkage analysis. A maximum LOD score of 4.48 was obtained for marker D16S3027 at recombination fraction 0. Haplotype analysis placed the critical region within a 3.4-cM interval between D16S3024 and D16S423. The present report constitutes the first example of an idiopathic epilepsy that is inherited as an autosomal recessive trait.

Association between changes in adrenal secretion and cerebral morphometric correlates in normal aging and senile dementia.

The circadian organization of adrenal secretion was studied in 23 healthy elderly subjects, 23 elderly demented patients and 10 healthy young subjects, in order to investigate the relationships between the hypothalamic-pituitary-adrenal axis and some cerebral morphometric parameters. The cerebral morphometric analysis was performed in some subjects of the three groups by MRI. A significant increase in cortisol levels during evening and nighttime was found in both groups of the aged subjects. In elderly subjects, particularly if demented, the mean serum dehydroepiandrosterone sulfate (DHEAs) levels throughout the 24-hour cycle were significantly lower than in young controls. A significant reduction of the hippocampal and temporal volume and an enlargement of the lateral ventricles were found in aged subjects, these changes being significantly related to subjects' age. Moreover, the hippocampal volume was positively correlated with the circadian mesor of DHEAs (i.e., the circadian rhythm adjusted mean) and with the cortisol nocturnal increase. Our data may suggest the existence of a link between the selective impairment of cortisol secretion and DHEAs levels, and the progression of hippocampal degeneration.

Serum glucagon concentration and hyperinsulinaemia influence renal haemodynamics and urinary protein loss in normotensive patients with central obesity.

OBJECTIVES: Insulin-resistance syndrome and hyperinsulinaemia are linked with cardiovascular disease (CVD) in the obese population. In particular, cardiovascular risk is more frequent in central obesity and is associated with microalbuminuria (MA). MA and changes of glomerular permeability to proteins in obesity might be related with renal haemodynamic modifications (that is glomerular hyperfiltration). Since glucagon is physiologically involved in renal haemodynamic regulation, the purpose of this study was to examine whether changes of circulating glucagon levels might haemodynamically induce MA and proteinuria in patients with central obesity. SUBJECTS: Forty normotensive obese out-patients, 22 with central (CO group) and 18 with peripheral (PO group) body fat distribution and 11 healthy subjects. MEASUREMENTS: Serum insulin and glucagon concentrations (fasting and after oral glucose tolerance test (OGTT)) by radio immuno assay (RIA); glomerular filtration rate (GFR, isotopic); total clearances and urinary excretion rates of albumin (AER), IgG (IgGER) and alpha1 microglobulin (computerized immunonephelometry). RESULTS: GFR and insulin concentrations (fasting and during OGTT) were higher in the CO than the PO group. Fasting glucagon concentrations were increased, and not physiologically suppressed during OGTT in patients with CO (fasting, P<0.05; OGTT 60 and 120 min, P<0.001 vs PO group). Moreover, glucagon concentrations were significantly correlated with GFR in the CO group (fasting, r=0.49, P<0.05; 60 min after OGTT, r=0.58, P<0.01); whereas no correlations were found in the PO group. Higher AER (P<0.001), IgGER (P<0.001) and alpha1 microglobulin (P<0.05) urinary concentrations were found in patients with CO than in the PO group. CONCLUSIONS: The increase of serum glucagon concentrations may be associated with the enhancement of GFR in patients with central obesity. Glomerular hyperfiltration might influence the development of MA and of proteinuria by means of a haemodynamic mechanism so contributing to increase the risk of renal microvascular complications and of CVD in central obesity.

Understanding and championing the merger process: key leadership roles for successful outcomes.

Mergers can effectively achieve both financial results and enhancements of quality. The nurse executive plays a vital role in the success of merger activities and has the opportunity to emerge as one of the leaders of the process. A systems approach to cost, quality, and service must be captured for successful merger outcomes to occur. But, in order for the nurse executive to be effective, he or she must understand and champion the merger process, critical roles, and challenges during the merger as well as use efficient communication methods to work effectively with physicians, reporting staff, and hired consultants.

Site-directed mutagenesis combined with chemical modification as a strategy for altering the specificity of the S1 and S1' pockets of subtilisin Bacillus lentus.

By combining site-directed mutagenesis with chemical modification, we have altered the S1 and S1' pocket specificity of subtilisin Bacillus lentus (SBL) through the incorporation of unnatural amino acid moieties, in the following manner: WT --> Cysmutant + H3CSO2SR --> Cys-SR, where R may be infinitely variable. A paradigm between extent of activity changes and surface exposure of the modified residue has emerged. Modification of M222C, a buried residue in the S1' pocket of SBL, caused dramatic changes in kcat/KM, of an up to 122-fold decrease, while modification of S166C, which is located at the bottom of the S1 pocket and is partially surface exposed, effected more modest activity changes. Introduction of a positive charge at S166C does not alter kcat/KM, whereas the introduction of a negative charge results in lowered activity, possibly due to electrostatic interference with oxyanion stabilization. Activity is virtually unaltered upon modification of S156C, which is located toward the bottom of the S1 pocket and surface exposed and whose side chain is solvated. An unexpected structure-activity relationship was revealed for S166C-SR enzymes in that the pattern of activity changes observed with increasing steric size of R was not monotonic. Molecular modeling analysis was used to analyze this unprecedented structure-activity relationship and revealed that the position of the beta-carbon of Cys166 modulates binding of the P1 residue of the AAPF product inhibitor.