Arteriovenous carbon dioxide and pH gradients during cardiac arrest

In a porcine preparation of cardiac arrest, we demonstrated that there is a marked paradox of venous acidemia and arterial alkalemia. This paradox is related to decreased clearance of CO2 from the lungs when pulmonary blood flow is critically reduced. Accordingly, increased venous PCO2 rather than metabolic acidosis due to lactic acidosis predominates during the initial 8 min of cardiopulmonary resuscitation. Arterial blood gases fail as indicators of systemic acid-base status and therefore as indicators of tissue acidosis.     

Intracellular beta-blockade: overexpression of Galpha(i2) depresses the beta-adrenergic response in intact myocardium

OBJECTIVE: Increased levels of inhibitory G proteins have been observed in heart failure, but their physiological relevance in mediating the reduced beta-adrenergic response is largely unknown. METHODS: To evaluate the functional consequences of Galpha(i2) overexpression, we studied myocardial contraction in intact isometric contracting cardiac rabbit trabeculae and isolated myocytes after adenovirus-mediated gene transfer of Galpha(i2). RESULTS: Neither Galpha(i2) nor lacZ (control) overexpression altered baseline contractile force. After 72 h of continuous contractions, developed force (F(dev)) increased after addition of 1 microM isoproterenol by 28.5+/-9.7 mN/mm(2) in the control group, which was unchanged from the initial response at t=0 h (23.7+/-3.8 mN/mm(2)). In sharp contrast, in preparations transfected with AdGalpha(i2), the response to isoproterenol was significantly attenuated (5.9+/-2.0 vs. 27.6+/-4.2 mN/mm(2), t=72 vs. 0 h, respectively, P<0.01). In a primary culture of transfected isolated myocytes from a nearly identical baseline, isoproterenol increased cell shortening by 3.1+/-0.6% in the lacZ transfected myocytes, but only by 1.3+/-0.5% in Galpha(i2) transfected myocytes (t=72 h, P<0.01). In Galpha(i2) transfected myocytes, pertussis toxin restored beta-adrenergic responsiveness, indicating specificity of attenuation by the transgene. CONCLUSIONS: Overexpression of Galpha(i2) attenuates the positive inotropic effects of beta-adrenergic stimulation in myocardium. In addition, the method we developed allows investigation of a causal link between altered protein expression and subsequent alterations in contractile function in a physiological relevant in vitro manner.     

Detection of circulating parasite antigen in bancroftian filariasis by counterimmunoelectrophoresis

We used counterimmunoelectrophoresis (CIEP) with rabbit antibodies to Dirofilaria immitis and Brugia malayi to detect soluble filarial antigen in sera collected in a Wuchereria bancrofti-endemic area in South India. Filarial antigen was detected in 38 of 38 sera from microfilaremic patients, 3 of 48 sera from amicrofilaremic patients with lymphatic pathology, and 3 of 5 sera from former microfilaria carriers with negative blood examinations 6 months or more after diethylcarbamazine therapy. One of 32 endemic control sera, 0 of 35 nonendemic sera, and 0 of 20 B. malayi sera were positive. Antigenemia was equally detectable in sera collected at night or during the day (when microfilariae are absent from the blood). Parasite antigen was also detected in the urine of patients with positive serum tests. Antibodies to circulating filarial antigen (also detected by CIEP) were absent in all but 2 antigen-positive sera but present in 22 of 45 antigen-negative sera from clinical filariasis patients and in 9 of 31 antigen-negative sera from endemic controls. Parasite antigen detection by CIEP appears to be a sensitive, specific, and practical diagnostic test for active W. bancrofti infection.     

Outcome of delayed primary internal fixation of distal radius fractures: A comparative study

Introduction and aim

Operative fixation of distal radius fractures using fixed-angle devices has become increasingly common. Although good to excellent results have been reported in acute fractures, little is currently known regarding the fixation of healing displaced distal radius fractures that were presented late. The aim of this study was to evaluate the results of internal fixation of distal radius fractures presented late (>21 days) as compared with an acute-care control group.

Methods

Forty patients operated on for displaced distal radius fractures, presenting more than 21 days after injury (delayed treatment (DT) group), were compared with 75 age-matched controls with acute fracture repair (≤21 days). The same surgical approach was used in both groups, together with dorsal soft-tissue and brachioradialis release. No osteotomy was required. Direct and indirect reduction aids were used. A fixed-angle device (DVR; Biomet Inc., Warsaw, IN, USA) was used in both groups. Mean follow-up was 3.4 years. Quick DASH (Disabilities of the Arm, Shoulder and Hand) and Short Form 12 scores were used to evaluate outcome, as well as radiographic analysis for Arbeitsgemeinschaft für Osteosynthesefragen(AO)/Orthopaedic Trauma Association(OTA) classification, volar tilt, radial inclination and radial length.

Results

Average age was 53 years in both groups and male to female (M/F) ratio was similar in the study groups. Mean time to surgery was 30 days in the DT group and 8 days in the control group. There were significantly more type C (91.5% vs. 67.5%) fractures in the control group. The average quick DASH score was 27.1 in the DT group as compared with 6.3 in the control group (p < 0.03); however, when controlling for two outlier cases with complications (hardware irritation and a sensory neuropathy) there was no significant difference. Volar tilt, radial inclination and length were similar in both groups and were within normal anatomical values.

Conclusions

Delayed primary operative fixation of displaced unstable distal radial fractures is a viable option for cases that were presented late, with predictable, favourable results. Neither extensile approaches nor formal osteotomies are required.     

Global estimates of undiagnosed diabetes in adults

Aims

The prevalence of diabetes is rapidly increasing worldwide. Type 2 diabetes may remain undetected for many years, leading to severe complications and healthcare costs. This paper provides estimates of the prevalence of undiagnosed diabetes mellitus (UDM), using available data from high quality representative population-based sources.

Methods

Data sources reporting both diagnosed and previously undiagnosed diabetes were identified and selected according to previously described IDF methodology for diabetes in adults (aged 20–79). Countries were divided into 15 data regions based on their geographic IDF Region and World Bank income classification. The median UDM proportion was calculated from selected data sources for each of data region. The number of UDM cases in 2013 was calculated from country, age and sex-specific estimates of known diabetes cases and data region-specific UDM proportion.

Results

Of 744 reviewed data sources, 88 sources representing 74 countries had sufficient information and were selected for generation of estimates of UDM. Globally, 45.8%, or 174.8 million of all diabetes cases in adults are estimated to be undiagnosed, ranging from 24.1% to 75.1% across data regions. An estimated 83.8% of all cases of UDM are in low- and middle-income countries. At a country level, Pacific Island nations have the highest prevalence of UDM.

Conclusions

There is a high proportion of UDM globally, and especially in developing countries. Further high-quality studies of UDM are needed to strengthen future estimates.     

Whole-Genome Analysis of Exserohilum rostratum from an Outbreak of Fungal Meningitis and Other Infections

Exserohilum rostratum was the cause of most cases of fungal meningitis and other infections associated with the injection of contaminated methylprednisolone acetate produced by the New England Compounding Center (NECC). Until this outbreak, very few human cases of Exserohilum infection had been reported, and very little was known about this dematiaceous fungus, which usually infects plants. Here, we report using whole-genome sequencing (WGS) for the detection of single nucleotide polymorphisms (SNPs) and phylogenetic analysis to investigate the molecular origin of the outbreak using 22 isolates of E. rostratum retrieved from 19 case patients with meningitis or epidural/spinal abscesses, 6 isolates from contaminated NECC vials, and 7 isolates unrelated to the outbreak. Our analysis indicates that all 28 isolates associated with the outbreak had nearly identical genomes of 33.8 Mb. A total of 8 SNPs were detected among the outbreak genomes, with no more than 2 SNPs separating any 2 of the 28 genomes. The outbreak genomes were separated from the next most closely related control strain by ∼136,000 SNPs. We also observed significant genomic variability among strains unrelated to the outbreak, which may suggest the possibility of cryptic speciation in E. rostratum.