Maternal uniparental disomy of chromosome 4 in a patient with limb-girdle muscular dystrophy 2E confirmed by SNP array technology.

The limb-girdle muscular dystrophies (LGMDs) are a heterogenous group of diseases characterized by shoulder-girdle and pelvic muscle weakness and wasting. LGMD 2E is an autosomal recessively inherited form of the disease caused by mutations in the ß-sarcoglycan (SGCB) gene located at 4q12. In this report, we describe a patient who demonstrates non-Mendelian inheritance of a homozygous missense mutation in SGCB resulting in disease expression. A combination of single-nucleotide polymorphism (SNP) array technology and microsatellite analysis revealed the occurrence of maternal uniparental disomy (UPD) for chromosome 4 in the patient. As a consequence of segmental isodisomy at 4q12, the patient inherited two identical SGCB alleles carrying a missense mutation predicted to result in abnormal protein function. SNP array technology proved to be an elegant means to determine the most probable mechanism of UPD formation in this case, and enabled us to determine the location of recombination events along chromosome 4. In our patient, UPD likely arose from a trisomy rescue event due to maternal meiotic non-disjunction that we speculate may have been caused by abnormal recombination at the pericentromeric region. Maternal UPD 4 is a rare finding, and to our knowledge this is the first reported case of UPD in association with LGMD.

Cardiopulmonary resuscitation: effect of CPAP on gas exchange during chest compressions.

BACKGROUND: Conventional cardiopulmonary resuscitation (CPR) includes 80-100/min precordial compressions with intermittent positive pressure ventilation (IPPV) after every fifth compression. To prevent gastric insufflation, chest compressions are held during IPPV if the patient is not intubated. Elimination of IPPV would simplify CPR and might offer physiologic advantages, but compression-induced ventilation without IPPV has been shown to result in hypercapnia. The authors hypothesized that application of continuous positive airway pressure (CPAP) might increase CO2 elimination during chest compressions. METHODS: After appropriate instrumentation and measurement of baseline data, ventricular fibrillation was induced in 18 pigs. Conventional CPR was performed as a control (CPR(C)) for 5 min. Pauses were then discontinued, and animals were assigned randomly to receive alternate trials of uninterrupted chest compressions at a rate of 80/min without IPPV, either at atmospheric airway pressure (CPR(ATM)) or with CPAP (CPR(CPAP)). CPAP was adjusted to produce a minute ventilation of 75% of the animal's baseline ventilation. Data were summarized as mean +/- SD and compared with Student t test for paired observations. RESULTS: During CPR without IPPV, CPAP decreased PaCO2 (55+/-28 vs. 100+/-16 mmHg) and increased SaO2 (0.86+/-0.19 vs. 0.50+/-0.18%; P < 0.001). CPAP also increased arteriovenous oxygen content difference (10.7+/-3.1 vs. 5.5+/-2.3 ml/dl blood) and CO2 elimination (120+/-20 vs. 12+/-20 ml/min; P < 0.01). Differences between CPR(CPAP) and CPR(ATM) in aortic blood pressure, cardiac output, and stroke volume were not significant. CONCLUSIONS: Mechanical ventilation may not be necessary during CPR as long as CPAP is applied. Discontinuation of IPPV will simplify CPR and may offer physiologic advantage.

Is epinephrine contraindicated during cardiopulmonary resuscitation?

BACKGROUND: Why pulmonary gas exchange deteriorates after administration of epinephrine during cardiopulmonary resuscitation (CPR) is unclear. METHODS AND RESULTS: Forty-four anesthetized swine received an infusion of six inert gases. Animals underwent ventricular fibrillation with CPR and intravenous administration of saline (control), epinephrine (15 microg/kg), or methoxamine (150 microg/kg). Cardiac output, aortic blood pressure, pH, and arterial oxygen saturation were recorded. Distributions of VA and Q were determined by the multiple inert gas elimination technique. Ventricular fibrillation and CPR caused significant decreases in cardiac output, aortic blood pressure, and arterial pH. With epinephrine (versus saline), diastolic blood pressure was significantly higher (23+/-7 versus 8+/-4 mm Hg), but the increase in shunt (from 7+/-4% to 29+/-17%) and the reduction in SaO2 (from 99.7% to 76.8%) were significantly larger. Also, the increase in dead space was greater and elimination of CO2 less. There were no differences between animals given methoxamine or saline, except for increased diastolic blood pressure. CONCLUSIONS: During experimental ventricular fibrillation and CPR, epinephrine increased intrapulmonary shunt approximately 300% more than saline or methoxamine and significantly reduced arterial oxygen saturation. We suspect that the beta-adrenergic receptor activity of epinephrine attenuated hypoxic pulmonary vasoconstriction. Methoxamine is as effective a pressor as epinephrine for CPR and devoid of beta-adrenergic activity. We recommend that such an agent be considered, instead of epinephrine, for CPR.

Does significant arterial hypoxemia alter vital signs?

STUDY OBJECTIVE: To determine the cardiovascular and respiratory effects of arterial hypoxemia in adult volunteers. DESIGN: Prospective, subject-controlled. SETTING: University-affiliated hospital. SUBJECTS: 16 awake, unsedated, unanesthetized adult volunteers. INTERVENTIONS: Inspired oxygen concentration (FIO2) was decreased in decrements to reduce pulse oximeter values to a range of 95% to 90%, 89% to 85%, 84% to 80%, and 79% to 70%. MEASUREMENTS AND MAIN RESULTS: Heart rate (HR), blood pressure (BP), respiratory rate (RR), arterial blood pH, gas tensions, and oxyhemoglobin saturation were determined during normoxia and each level of oxyhemoglobin desaturation. FIO2 was reduced from 21% to 10%. Arterial blood oxyhemoglobin saturation and oxygen tension ranged from 100% to 71% and 103 to 35 mmHg, respectively. There were no significant changes in RR, BP, or HR during the study. CONCLUSIONS: HR, BP, and RR are not reliable indicators of arterial hypoxemia in awake volunteers. If this finding is also true for sedated or anesthetized patients, then continuous monitoring with pulse oximetry should be used whenever patients are at risk for arterial hypoxemia. Stable HR, BP, and RR may not eliminate the possibility of significant arterial hypoxemia and impending catastrophic events.

Young people's representations of others' views of smoking: is there a link with smoking behaviour?

This paper reports a large-scale survey (n = 1985) of 9-12-year-olds' representations of parents' and friend's views about the nature of smoking. Taking the perspective of Social Representations theory, consensual representations of respondents' views of significant others are identified using cluster analysis without reference to smoking behaviour. Resulting clusters of individuals map on to self-reported behavioural groups at above chance level. These relationships indicate young smokers have access to sets of beliefs about others' smoking views that may differ systematically from those available to nonsmokers. This suggests an additional social psychological mechanism that may be implicated in early onset of smoking in adolescence.

Spirometric versus Fick-derived oxygen consumption: which method is better?

OBJECTIVE: Oxygen consumption (VO2) is often measured in critically ill patients using the Fick equation: VO2 = cardiac output x arterial-venous oxygen content difference. To determine if this method is accurate, it was compared with a spirometric technique. DESIGN: Prospective study. SETTING: University laboratory. SUBJECTS: Nineteen large adult pigs. INTERVENTIONS: Cardiac output, measured with bolus thermodilution technique, and arterial and venous oxygen content values, determined with the galvanic fuel cell method, were used to determine VO2 with the Fick equation. The spirometrically determined VO2 was the rate of disappearance of oxygen from a water-sealed spirometer. Dobutamine and labetalol were titrated to vary VO2 (range 204 to 584 mL/min). MEASUREMENTS AND MAIN RESULTS: The bias between the Fick and spirometrically determined VO2 values was 58 mL/min. The precision (SD of the bias) between the Fick and spirometrically determined Vo2 was 35 mL/min. Fick-derived Vo2 was greater than Vo2 measured spirometrically. The correlation coefficient was 0.90. CONCLUSIONS; Despite all attempts to reduce measurement error, there was an unexplained difference in Fick-derived and spirometrically measured Vo2. Therefore, I feel that the two methods are not interchangeable, and that calculations of Vo2 using the Fick method should be used cautiously when therapeutic maneuvers are based on these data.

Cardiopulmonary bypass temperature does not affect postoperative euthyroid sick syndrome?

STUDY OBJECTIVE: To determine if temperature during cardiopulmonary bypass (CPB) has an effect on perioperative and postoperative thyroid function. DESIGN: Prospective study comparing thyroid function during and after hypothermic and normothermic CPB. SETTING: Cardiac surgical unit at a university-affiliated hospital. PATIENTS: Twelve patients scheduled to undergo cardiac operations with normothermic (n = 6) or hypothermic (n = 6) CPB. INTERVENTIONS: Blood was analyzed for serum concentration of total thyroxine (TT4), total triiodothyronine (TT3), free T3 (fT3), reverse T3 (rT3), and thyroid stimulating hormone (TSH) preoperatively, 60 min after CPB was initiated, 30 min after discontinuing CPB, and on postoperative days (POD) 1, 3, and 5. MEASUREMENTS AND RESULTS: Patients who underwent either cold (26 degrees +/- 5 degrees C) or warm (35 degrees +/- 1 degree C) CPB were comparable with regard to age, body weight, duration of CPB, cross-clamp time, use of inotropes, total heparin dose, and length of hospital stay. Incidence of postoperative myocardial infarction, congestive heart failure, and death were similar. In both groups, TT4 and TT3 were reduced below baseline values beginning with CPB and persisting for up to 5 days after CPB (p < 0.05), free T3 was reduced for up to 3 days after CPB (p < 0.05), mean serum rT3 was elevated on POD 1 and POD 3 (p < 0.05), and TSH remained unchanged. CONCLUSION: The results of this study suggest that normothermic CPB does not prevent the development of the "euthyroid sick syndrome" during and after CPB. Despite these changes in thyroid function, most patients in both groups had a normal postoperative recovery.

Cardiac arrest after oxymetazoline nasal spray.

Oxymetazoline nasal spray is a potent alpha 1-adrenergic agonist commonly used to vasoconstrict blood vessels in the nasal mucosa. In this incident, oxymetazoline nasal spray 0.025% was administered to a 2-year-old patient during general anesthesia for nasal endoscopy. Severe hypertension with reflex bradycardia progressed to sinus arrest and was successfully treated with alropine and cardiopulmonary resuscitation. Decreasing the dose of oxymetazoline and pretreatment with an anticholinergic is recommended.

Continuous thermodilution cardiac output: agreement with Fick and bolus thermodilution methods.

OBJECTIVE: Cardiac outputs were determined with continuous thermodilution, bolus thermodilution, and the Fick method during pharmacologically varied hemodynamics. DESIGN: Prospective comparison of techniques. SETTING: University animal laboratory. PARTICIPANTS: Swine. INTERVENTIONS: Swine were anesthetized, tracheally intubated, and instrumented to measure continuous (QTDC) and bolus (QTDB) thermodilution cardiac outputs and sample arterial and mixed venous blood. Continuous thermodilution of blood was facilitated by computer modulation of a thermal filament wrapped around the portion of the pulmonary artery catheter residing in the right atrium and ventricle. QTDC was computed from the thermodilution curve monitored by the thermistor. Bolus thermodilution was performed in triplicate by injecting 10 mL of 5% dextrose in water (0 to 4 degrees C). Oxygen consumption (VO2) was calculated as the averaged minute rate of disappearance of spirometer oxygen over a 6-minute steady state. Cardiac output was determined with the direct Fick method (QF) by dividing VO2 by the difference in arterial and mixed venous oxygen content. Basal QTDC was increased and decreased with an intravenous infusion of dobutamine or labetalol, respectively. Data are summarized as mean +/- SD or 95% confidence interval (CI 95%). Agreement between methods of determining cardiac output was assessed by calculating bias, percent bias, and percent coefficient of determination (100 r2). MEASUREMENTS AND MAIN RESULTS: Eighteen swine (38.9 +/- 1.2 kg) exhibited a range of QTDC from 2.2 to 14.8 L/min. Mean measurement variance of VO2, CaO2, CvO2, and QTDB was 1.5%, 1.5%, 2.0%, and 11.8%, respectively. Mean bias, percent bias, and 100 r2 was 0.004 +/- 1.05 L/min (CI 95%: 0.18 to 0.19 L/min), -0.37 +/- 13.8% (CI 95%: -2.75 to 2.01), and 89% between QTDC and QF, respectively. Bias, percent bias, and 100 r2 was 0.05 +/- 1.09 L/min (CI 95%: -0.14 to 0.23 L/min, 1.21 +/- 13.06% (CI 95%: -1.03 to 3.46%), and 91% between QTDC and QTDB, respectively. Bias, percent bias, and 100 r2 (Fig 6) was -0.04 +/- 0.69 L/min (CI 95%: -0.16 to -.08 L/min), -1.23 +/- 9.17% (CI 95%: -2.8 to 0.35%), and 94% between QTDB and QF, respectively. CONCLUSION: Automatic cardiac output computed with continuous thermodilution appears accurate and reliable. Also, good agreement was confirmed between cardiac output derived by continuous and bolus thermodilution methods and bolus thermodilution and Fick methods.

Progressive neuronal degeneration of childhood with liver disease (Alpers' disease) presenting in young adults.

Two unrelated and previously healthy girls, aged 17 and 18, presented with a subacute encephalopathy, visual and sensory symptoms and signs, and prominent seizures that were difficult to control. Brain MRI showed lesions (high signal on T2 weighted images) in the occipital lobes and thalamus; EEG showed slow wave activity with superimposed polyspikes. Inexorable downhill progression led to death in hepatic failure within eight months of onset. Histopathological findings in both patients ((a) chronic hepatitis with prominent bile duct proliferation, fatty change, and fibrosis; (b) in the brain a patchy destruction of the cerebral cortex, predominantly involving striate cortex) were characteristic of progressive neuronal degeneration of childhood with liver disease--Alpers-Huttenlocher syndrome--a rare autosomal recessive disorder usually seen in infants and young children.

Radial nerve injury after routine peripheral vein cannulation.

The dorso-radial aspect of the wrist and hand is a common location for intravenous (IV) cannulation prior to anesthesia. The sensory branch of the radial nerve lies superficially in this area, and it can be injured during routine insertion of IV catheters. In this case, the nerve was lacerated during insertion and a painful neuroma developed after elective surgery and anesthesia. Knowledge of this complication may help with its recognition and treatment.

Acute ataxic neuropathy with cross-reactive antibodies to GD1b and GD3 gangliosides.

We report a patient with an acute, self-limiting neuropathy consisting of ataxia and areflexia, but without ophthalmoplegia or limb weakness, with transient, high-titer serum IgG antibodies to a single NeuAc(alpha 2-8)NeuAc-linked disialosyl epitope, as found on GD1b and GD3 gangliosides. The serum did not react with GQ1b, GT1a, or GT1b. This atypical case, which most closely represents an incomplete Miller Fisher syndrome, indicates that anti-GD1b/GD3 antibodies may be able to induce sensory ataxia.