Glucokinase gene is genetic marker for NIDDM in American blacks.

Glucokinase (ATP:D-glucose-6-phosphotransferase), expressed exclusively in liver and pancreatic islet beta-cells, catalyzes the first step of glycolysis and acts as glucose sensor and metabolic signal generator in these tissues. The enzyme plays a key role in glucose homeostasis and as such is an excellent candidate for inherited defects predisposing to non-insulin-dependent diabetes mellitus (NIDDM). A compound-imperfect dinucleotide (CA)n repeat element was found approximately 10-kb 3' of the human glucokinase gene on chromosome 7p, which revealed polymorphism with alleles differing in size by 2-15 nucleotides in unrelated individuals. A polymerase chain reaction assay was developed, and genomic DNA from 275 biologically unrelated American black individuals was typed for glucokinase alleles. The differences in allelic frequencies between individuals with NIDDM and nondiabetic individuals were compared. After typing 112 diabetic and 163 nondiabetic subjects, we found five different-sized alleles, with Z defined as the most common allele, Z + 2, Z + 4, Z + 10, and Z - 15. The Z allele was more common in nondiabetic subjects than in diabetic patients (60.4 vs. 49.6%, P = 0.012). The Z + 4 allele was more common in diabetic patients than in nondiabetic subjects (20.1 vs. 12.0%, P = 0.009). After adjusting for age, sex, and body mass index, the Z + 4 allele continued to have a positive association with NIDDM (P = 0.0018), and the Z allele had a negative association with NIDDM (P = 0.0334). The Z + 4 allele, transmitted as an autosomal dominant trait, appeared to be the most significant one at this locus.(ABSTRACT TRUNCATED AT 250 WORDS)     

An effective treatment of comminuted fractures of the distal radius

One hundred cases of comminuted fracture of the distal radius were treated by a simple uniform method consisting of distraction by an external fixator for 3 weeks followed by functional bracing. During the application of the external fixator, autogenous cancellous bone chips were taken from the iliac crest and packed into the fracture site to realign the juxtaarticular fragments and to fill up the bone gap. Complications have been minimal. The results, after an average follow-up period of 20 months, taking into consideration subjective assessment of pain, objective measurement of wrist motion, and radiologic angles, have been excellent.     

Chromosomal screening of mentally retarded school children in Taipei.

The major concern of the national population policy in Taiwan in recent years has been to lower the incidence of hereditary diseases and mental retardation in the general population. It has been estimated that there are around 10,000 mentally retarded school children in Taiwan. If effective chromosomal screening can be extended to these children, some of the family members who are carriers of balanced chromosomal rearrangements may benefit from follow-up studies and genetic counseling. The present report is the result of a pilot study conducted from 1988 to 1991 to explore the possibility of chromosomal screening of mentally retarded school children in Taipei. A total of 871 blood samples were collected from 1,147 children registered in 46 schools or residing in homes for the retarded. Chromosomal analysis was successfully accomplished on 674 out of 871 blood samples. The following chromosomal abnormalities were observed: 28 Down's syndrome, four Klinefelter syndrome, one XYY, one triple X, 11 translocations, seven inversions, four mosaics, three duplications, one deletion and one with an extra marker chromosome. After follow-up cytogenetic analyses of 13 families with probands with structural chromosomal anomalies, three of these families were shown to have one or two carriers of balanced translocated chromosomes. It seems that the present screening system would not be practical or cost-effective if it were applied island-wide in the future.     

Persistent fifth aortic arch associated with 22q11.2 deletion syndrome.

BACKGROUND: Chromosome 22q11.2 deletion is frequently associated with conotruncal malformations and aortic arch anomalies. This study investigated the association of chromosome 22q11.2 deletion with clinical manifestations in four pediatric patients with persistent fifth aortic arch. METHODS: Four patients with persistent fifth aortic arch treated between July 1997 and June 2004 were included in this retrospective study. There were two girls and two boys, aged 2 days to 11.3 years, with persistent fifth aortic arch and cardiac conotruncal malformations. Chart recordings, plain chest films, two-dimensional and Doppler echocardiograms, cardiac catheterization with angiograms, surgical findings, and cytogenetic study were analyzed. RESULTS: Clinically, all four patients had the cardinal phenotypic features of 22q11.2 deletion syndrome, including cardiovascular malformations (conotruncal malformations and aortic arch anomalies), abnormal facies, thymic hypoplasia, canopy anomaly of the palate (high-arched palate, rather than cleft palate), and hypocalcemia (or hypoparathyroidism). All four patients were confirmed to have chromosome 22q11.2 deletion. CONCLUSION: Congenital conotruncal malformations, including tetralogy of Fallot with pulmonary atresia or stenosis, and aortic arch anomalies including a persistent fifth aortic arch or a right aortic arch, should lead to suspicion of chromosome 22q11.2 deletion when manifested together with any one of the other four cardinal phenotypic features.     

Effects of hypothermia on hemodynamic responses to dopamine and dobutamine.

Hemodynamic characteristics, arrhythmogenicity, and dose-related hemodynamic responses to intravenous dopamine (group I) and dobutamine (group II) were examined in 16 swine at three different core body temperatures (38.5 degrees C, 35 degrees C, and 30 degrees C). The animals were anesthetized with isoflurane and mechanically ventilated. Cooling and re-warming were accomplished by a femoral-jugular A-V shunt. The animals were cooled down to 30 degrees C and stabilized for 1 hour before intravenous infusion of dopamine (group I, n = 8) or dobutamine (group II, n = 8) was started at 2, 5, 10, 15, 20, and 30 micrograms/kg/min. Hemodynamic responses to the two inotropes were continuously monitored with a bedside monitor equipped with a PC mode for customized data collection and analysis. Computerized arrhythmia detection was performed. Our findings were: (1) profound hypothermia (30 degrees C) causes significant depression of hemodynamic functions; (2) IV infusion of dopamine and dobutamine can be used safely and effectively for inotropic support during profound hypothermia, and the optimal dosage for improving cardiac output is 10-20 micrograms/kg/min; (3) no risk of inducing arrhythmia was noted with IV infusion of both inotropes up to a maximum dosage of 30 micrograms/kg/min, even though significant sinus tachycardia was consistently seen at 30 micrograms/kg/min.     

Molecular epidemiology and control of nosocomial methicillin-resistant Staphylococcus aureus infection in a teaching hospital.

BACKGROUND AND PURPOSE: Nosocomial methicillin-resistant Staphylococcus aureus (MRSA) infection is difficult to control. Due to a dramatic increase in the nosocomial MRSA infection rate at our hospital from 2000 to 2001, this study was conducted to identify the source of these infections and the effectiveness of control measures. METHODS: 179 healthcare workers (HCWs) were screened for carriage of MRSA. Starting in April 2001, all patients with MRSA infection or colonization were put in strict contact and cohort isolation. The bacterial isolates of HCW carriers and patients with MRSA infection from April 2001 to September 2001 were subjected to antimicrobial susceptibility testing by disk-diffusion method and molecular typing by pulsed-field gel electrophoresis (PFGE). RESULTS: Fifteen HCWs were found to be carriers of MRSA. They were all given topical mupirocin treatment. After these interventions, the nosocomial MRSA infection rate decreased from 1.23 to 0.53 per 1000 patient-days. All 61 MRSA isolates available for antimicrobial susceptibility testing and molecular typing were multidrug resistant. PFGE study revealed 2 predominant types, type C and type Y, comprising 36 and 12 isolates, respectively. CONCLUSIONS: The current study demonstrates the importance of measures to control nosocomial MRSA infections in hospitals that already have a high incidence of endemic MRSA infection. Elimination of carriage by healthcare workers, and strict contact and cohort isolation are the main effective measures.