Introduction of a national program for HbA1c testing in Guyana South America and initial results.

Diabetes is an increasing challenge for low- and middle-income countries (LMIC) and access to HbA1c testing is limited. HbA1c, a measure of glycaemic control averaged over 3 months, provides both clinicians and policymakers with a tool to identify the risk of long-term diabetes comorbidity. We describe the steps used to implement standardised testing in Guyana South America and the initial results according to a locally developed protocol as part of a country-wide project to improve the care of people with all forms of diabetes The steps identified include: a standardised method traceable to a recognized international reference standard, participation in a quality control cycle with an international reference laboratory, a clinical pathway for testing to reduce inappropriate use and minimize resource wastage, training of technicians in operation and maintenance of equipment, identification of a suitable space with constant power supply, a reliable procurement system, education of healthcare professionals on interpretation and follow-up of results and feedback of programme results to improve clinical practice. Some steps for implementation of the national HbA1c testing program were initiated better than others. Initial unreliability of the service undermined confidence in the system. Failure to follow the testing protocol led to some patients being tested too soon and others too late. Cost of reagents was about 5.60 USD/test. We trained 340 people in diabetes care and knowledge was improved but were unable to assess whether it was appropriately applied. Over one third of people tested in the 30-70 age group had an HbA1c over 9% (75 mmol/mol) and this did not improve over the 5 years of testing. Despite the difficulties we think our unique experience of implementation of a nationwide HbA1c testing programme has important lessons for other LMICs.

The homeobox gene cut interacts genetically with the homeotic genes proboscipedia and Antennapedia.

The cut locus (ct) codes for a homeodomain protein (Cut) and controls the identity of a subset of cells in the peripheral nervous system in Drosophila. During a screen to identify ct-interacting genes, we observed that flies containing a hypomorphic ct mutation and a heterozygous deletion of the Antennapedia complex exhibit a transformation of mouthparts into leg and antennal structures similar to that seen in homozygous proboscipedia (pb) mutants. The same phenotype is produced with all heterozygous pb alleles tested and is fully penetrant in two different ct mutant backgrounds. We show that this phenotype is accompanied by pronounced changes in the expression patterns of both ct and pb in labial discs. Furthermore, a significant proportion of ct mutant flies that are heterozygous for certain Antennapedia (Antp) alleles have thoracic defects that mimic loss-of-function Antp phenotypes, and ectopic expression of Cut in antennal discs results in ectopic Antp expression and a dominant Antp-like phenotype. Our results implicate ct in the regulation of expression and/or function of two homeotic genes and document a new role of ct in the control of segmental identity.

Depressive symptoms in elderly medical-surgical patients hospitalized in community settings.

The authors examined the rates and correlates of depressive symptoms in adults over age 60 admitted to community hospital settings and compared them with patients admitted to a tertiary-care medical center. Rates of depressive symptoms in patients admitted to five different community hospitals in North Carolina were compared with each other and with a sample of 542 elderly medical patients admitted to Duke University Medical Center (DUMC). Compared with patients at DUMC, community-hospital patients were older and had more cognitive impairment, but had less severe medical illness and shorter hospital stays. The proportion of depressed community patients was significantly higher than among patients admitted to DUMC. In four of the five community hospitals, rates of significant depressive symptoms exceeded 50%. Health correlates of depression were admitting diagnoses other than cardiovascular disease, poor cognitive functioning, and severe medical illness.

Targeted disruption of the Dictyostelium RMLC gene produces cells defective in cytokinesis and development.

Conventional myosin has two different light chains bound to the neck region of the molecule. It has been suggested that the light chains contribute to myosin function by providing structural support to the neck region, therefore amplifying the conformational changes in the head following ATP hydrolysis (Rayment et al., 1993). The regulatory light chain is also believed to be important in regulating the actin-activated ATPase and myosin motor function as assayed by an in vitro motility assay (Griffith et al., 1987). Despite extensive in vitro biochemical study, little is known regarding RMLC function and its regulatory role in vivo. To better understand the importance and contribution of RMLC in vivo, we engineered Dictyostelium cell lines with a disrupted RMLC gene. Homologous recombination between the introduced gene disruption vector and the chromosomal RMLC locus (mlcR) resulted in disruption of the RMLC-coding region, leading to cells devoid of both the RMLC transcript and the 18-kD RMLC polypeptide. RMLC-deficient cells failed to divide in suspension, becoming large and multinucleate, and could not complete development following starvation. These results, similar to those from myosin heavy chain mutants (DeLozanne et al., 1987; Manstein et al., 1989), suggest the RMLC subunit is required for normal cytokinesis and cell motility. In contrast to the myosin heavy chain mutants, however, the mlcR cells are able to cap cell surface receptors following concanavilin A treatment. By immunofluorescence microscopy, RMLC null cells exhibited myosin localization patterns different from that of wild-type cells. The myosin localization in RMLC null cells also varied depending upon whether the cells were cultured in suspension or on a solid substrate. In vitro, purified RMLC- myosin assembled to form thick filaments comparable to wild-type myosin, but the filaments then exhibit abnormal disassembly properties. These results indicate that in vivo RMLC is necessary for myosin function.

Expression of a myosin regulatory light chain phosphorylation site mutant complements the cytokinesis and developmental defects of Dictyostelium RMLC null cells.

In a number of systems phosphorylation of the regulatory light chain (RMLC) of myosin regulates the activity of myosin. In smooth muscle and vertebrate nonmuscle systems RMLC phosphorylation is required for contractile activity. In Dictyostelium discoideum phosphorylation of the RMLC regulates both ATPase activity and motor function. We have determined the site of phosphorylation on the Dictyostelium RMLC and used site-directed mutagenesis to replace the phosphorylated serine with an alanine. The mutant light chain was then expressed in RMLC null Dictyostelium cells (mLCR-) from an actin promoter on an integrating vector. The mutant RMLC was expressed at high levels and associated with the myosin heavy chain. RMLC bearing a ser13ala substitution was not phosphorylated in vitro by purified myosin light chain kinase, nor could phosphate be detected on the mutant RMLC in vivo. The mutant myosin had reduced actin-activated ATPase activity, comparable to fully dephosphorylated myosin. Unexpectedly, expression of the mutant RMLC rescued the primary phenotypic defects of the mlcR- cells to the same extent as did expression of wild-type RMLC. These results suggest that while phosphorylation of the Dictyostelium RMLC appears to be tightly regulated in vivo, it is not essential for myosin-dependent cellular functions.

Effect of vest cardiopulmonary resuscitation rate on cardiac output and coronary blood flow.

We studied the effect of CPR rate on the hemodynamic indices of surgically instrumented canine experimental models. Using pneumatic vest CPR, we applied simultaneous rib cage and abdominal compressions at rates of 1 to 12 Hz. CPR with 2-Hz frequency yielded the highest aortic and coronary flows (252 +/- 14 and 6.8 +/- 1.1 ml/min vs. 178 + 12 and 0.96 +/- 0.08 ml/min at 1 Hz, respectively; p less than .005). The validity of the present American Heart Association recommendation for 1-Hz CPR rate would benefit from further studies.

Bleeding small-bowel varices.

A case of bleeding jejunal varices in a 27-year-old man is reported. Portal hypertension resulted from portal vein thrombosis and the varices were not associated with portasystemic shunting. Because mesenteric varices are rare, they are seldom the cause of gastrointestinal hemorrhage. However, they should be suspected in patients with an obscure source of bleeding and portal hypertension. The pathogenesis, roentgenographic criteria and surgical management are discussed.