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Biomedical subjects

G A Smith

Publications and source records attributed to G A Smith.

At least 55 records · Page 3Linked to original sources

Hepatitis A outbreaks among illicit drug users and their contacts in Queensland, 1997.

OBJECTIVE: To describe five outbreaks of hepatitis A virus (HAV) infection associated with illicit drug use during a statewide outbreak of HAV infection in Queensland. DESIGN: Risk factor prevalence survey. PATIENTS AND SETTING: All 875 cases of HAV infection notified to Public Health Units in Queensland in the 12 months to 30 November 1997. MAIN OUTCOME MEASURE: Type and prevalence of illicit drug use. RESULTS: Risk factor assessment was completed for 804 cases (91.9%). We identified five outbreaks of HAV infection linked to illicit drug use. These outbreaks accounted for 24.6% (215/875) of all notified cases and 39% (190/482) of notified cases in the 15-34 years age group. The main type of illicit drug use in four of the five outbreaks was injecting drug use (74%; 118/160), while in the other outbreak it was sharing of smoking implements for marijuana (38%; 21/55). CONCLUSION: Illicit drug use may be an under-recognised risk factor for HAV infection, particularly in young people. Faecal-oral transmission through poor personal hygiene, including sharing of implements for smoking marijuana, is the most probable route of transmission in these drug-linked outbreaks. The role of contaminated drug and needle-sharing remains to be clarified.

Adolescent↗

Effects of fluorinated inositols on the phosphoinositide metabolism and the proliferation of Trypanosoma cruzi.

Inositol has been cited as being essential for the growth of micro-organisms and animals. Its action rests mostly in the formation of a set of inositol-containing lipids, including phosphatidylinositol and its phosphorylated derivatives. To evaluate the functional responses coupled to the phosphoinositide metabolism in Trypanosoma cruzi we used myo-inositol and its six fluorinated analogues. Their uptake into epimastigotes was characterised using tritium-labeled myo-inositol and monodeoxyfluoro-myo-inositols. The analogues were tested for their ability to inhibit [3H]-myo-inositol incorporation into phosphoinositides and the proliferation of epimastigotes and amastigotes. The results showed differences between T. cruzi and mammalian systems in the responses to the fluorinated analogues. We found that the 3-, 5- and 6-fluoro analogues did not enter the cells but had an inhibitory effect on the incorporation of the radioactive inositol into lipids and on the amastigotes' and epimastigotes' replication. The most effective inhibitor, 1-D-6-deoxy-6-myo-inositol, had no effect on mammalian cell division.

Animals↗

Analysis of the thymidine kinase genes of macropodid herpesviruses 1 and 2.

The nucleotide sequences of the entire protein coding regions of the thymidine kinase (TK) genes of macropodid herpesvirus type 1 (MaHV-1) and type 2 (MaHV-2) were determined. The coding region of the MaHV-1 TK gene was 984 bp long and was predicted to encode a polypeptide of 327 amino acids. The coding region of the MaHV-2 TK gene was 1020 bp long and encoded a polypeptide of 340 amino acids. Comparisons of their deduced amino acid sequences with those of fifteen other herpesviruses revealed close homology to those of other alphaherpesviruses, particularly to human herpesvirus type 1 (HHV-1) and type 2 (HHV-2).

Alphaherpesvirinae↗

Diagnostic aids in the differentiation of pyloric stenosis from severe gastroesophageal reflux during early infancy: the utility of serum bicarbonate and serum chloride.

This study evaluated whether serum bicarbonate levels, serum chloride levels, and other diagnostic criteria could be used to differentiate pyloric stenosis (PS) from severe gastroesophageal reflux (GER) during early infancy. The investigation was a retrospective, case-control study conducted in the emergency department of a large, academic children's hospital. Cases were 75 consecutive infants with PS confirmed in the operating room. Controls were 75 consecutive infants 12 weeks of age or younger with the diagnosis of GER whose serum electrolytes had been examined. Projectile vomiting was sensitive (0.93) but not specific (0.39) for PS. The mean serum bicarbonate level was 27.2 mmol/L for PS patients and 22.3 mmol/L for GER patients (P < .00001), and the mean serum chloride level was 95.7 mmol/L and 103.6 mmol/L for PS patients and GER patients, respectively (P < .00001). Serum bicarbonate levels of > or =29 mmol/L and serum chloride levels of < or =98 mmol/L had high positive predictive values (0.96 and 0.97, respectively) and were specific (0.99 for both) but not very sensitive (0.36 and 0.50, respectively) in identifying patients with PS. Only one patient would have been misclassified (false positive) as having PS using either of these cutoff values. These laboratory tests can also help discriminate between PS and GER when the history and physical examination fail to do so. For example, of the 20 patients with PS who did not have a pyloric mass palpated, 3 (15%) had serum bicarbonate levels of > or =29 mmol/L, and 6 (30%) had serum chloride levels of < or =98 mmol/L. In conclusion, the serum bicarbonate or serum chloride level offers a useful additional diagnostic tool in the evaluation of children presenting during early infancy with vomiting of uncertain etiology.

Bicarbonates↗

Interrelationships among biological markers of aging, health, activity, acculturation, and cognitive performance in late adulthood.

In this study a structural equation model of predictors of age differences in cognitive performance in late adulthood was developed. Biological markers of aging (vision, hearing, vibration sense, forced expiratory volume, and grip strength) were used as indicators of a latent variable called BioAge. A sample of 180 community-dwelling women aged 60 to 90 years was assessed. Results showed that BioAge explained all of the age-related variance in cognitive test performance. Physical health and physical activity had direct effects on BioAge. Measures of acculturation explained non-age-related variance in cognitive test performance. Some variables used as biomarkers also explained individual differences in measures of crystallized intelligence and perceptual speed. It is concluded that the association between biomarkers and cognition in old age is due to more than a common statistical association with age.

Acculturation↗

Frequency of early colorectal cancer in patients undergoing colonoscopy.

BACKGROUND: Early colorectal cancer is defined as carcinoma limited to the mucosa or submucosa. Up to 20 per cent of all colorectal cancers treated in some Japanese institutions are early cancers. These cancers are sometimes flat or depressed, and may be less than 1 cm in diameter. The aim of this study was to identify the frequency and morphology of early colonic cancers detected at colonoscopy by a surgeon aware of and looking for such lesions. METHODS: A review was made of all colonoscopies performed by or under the supervision of a single endoscopist between 1990 and 1998. Follow-up and outcome of all patients with early colorectal cancer was undertaken. RESULTS: Ninety-five invasive colorectal cancers were identified from 2198 colonoscopies. Eighteen were early colorectal cancers (T1). Macroscopically these were flat (nine tumours), villous (four) and pedunculated (five). Two patients had lymph node metastasis. The median size of flat cancers was 20 (range 9-30) mm. Median follow-up was 3 years. One patient had local recurrence, and another, whose early cancer was metachronous, died from metastatic cancer. CONCLUSION: This study identified early colonic cancer with similar frequency and morphology to that reported by the Japanese. Colonoscopy should be considered as the investigation of choice for patients with large bowel symptoms.

Aged↗

Rapid phenotyping of HPA-1a using either diabody-based hemagglutination or recombinant IgG1-based assays.

BACKGROUND: The HPA-1 system is carried on the beta3 integrin. HPA-1a (Zw(a), Pl(A1)) is immunogenic in an HPA-1b homozygote (HPA-1b1b). In pregnancy, 1 of 365 women forms anti-HPA-1a, which causes severe thrombocytopenia in 1 in 1100 neonates. Identification of women at risk of forming anti-HPA-1a and the screening of donors to obtain HPA-1a-negative platelets for therapy need reliable, low-cost, automated assays. STUDY DESIGN AND METHODS: A diabody with dual specificity for HPA-1a x D and an IgG1 anti-HPA-1a have been constructed by the use of the genes encoding the first anti-HPA-1a fragment. With these reagents, two complementary HPA-1a phenotyping assays have been developed. RESULTS: This diabody was used in a simple hemagglutination technique to perform HPA-1a phenotyping on soluble glycoprotein IIb/IIIa from EDTA plasma samples. Over 1000 unselected donors have been correctly HPA-1a-phenotyped by use of the diabody. The human recombinant IgG1 anti-HPA-1a was produced in a rat myeloma cell line and was fluorescein labeled for use in a whole-blood flow cytometric HPA-1a phenotyping assay. This IgG1 anti-HPA-1a shows a clear differential between HPA-1a-positive and HPA-1a-negative platelets at nM antibody concentrations. CONCLUSIONS: The two recombinant reagents described are highly suitable for screening and confirmatory HPA-1a phenotyping. They permit rapid determination of the HPA-1a phenotype and are amenable to automation.

Antigens, CD↗

Macropodid herpesviruses 1 and 2 occupy unexpected molecular phylogenic positions within the Alphaherpesvirinae.

The molecular phylogeny of macropodid herpesviruses 1 and 2 (MaHV-1 and -2) has been investigated by cloning and sequencing the genes encoding glycoprotein B from both viruses. Phylogenetic reconstructions based on the putative amino acid sequences of glycoprotein B indicate that MaHV-1 and -2 are most closely related to the subfamily Alphaherpesvirinae. Within the Alphaherpesvirinae, MaHV-1 and -2 are closely associated with those herpesviruses that infect primates. This phylogenetic relationship does not fit the constraints of the proposed co-evolution theory described for other members of the Alphaherpesvirinae which have mammalian hosts.

Alphaherpesvirinae↗

Construction and transposon mutagenesis in Escherichia coli of a full-length infectious clone of pseudorabies virus, an alphaherpesvirus.

A full-length clone of the 142-kb pseudorabies virus (PRV) genome was constructed as a stable F plasmid in Escherichia coli. The clone, pBecker1, was colinear with PRV-Becker genomic DNA, lacking detectable rearrangements, deletions, or inversions. The transfection of pBecker1 into susceptible eukaryotic cells resulted in productive viral infection. Virus isolated following transfection was indistinguishable from wild-type virus in a rodent model of infection and spread to retinorecipient regions of the brain following inoculation in the vitreous body of the eye. Mutagenesis of pBecker1 in E. coli with a mini-Tn5-derived transposon enabled the rapid isolation of insertion mutants, identification of essential viral genes, and simplified construction of viral revertants. The serial passage of a viral insertion mutant demonstrated the transposon insertion to be stable. However, the F-plasmid insertion present in the viral gG locus was found to undergo a spontaneous deletion following transfection into eukaryotic cells. The implications of F-plasmid insertion into the viral genome with regard to phenotype and genomic stability are discussed.

Alleles↗

The hospital record of the injured child and the need for external cause-of-injury codes. American Academy of Pediatrics. Committee on Injury and Poison Prevention, 1998-1999.

Proper record-keeping of emergency department visits and hospitalizations of injured children is vital for appropriate patient management. Determination and documentation of the circumstances surrounding the injury event are essential. This information not only is the basis for preventive counseling, but also provides clues about how similar injuries in other youth can be avoided. The hospital records have an important secondary purpose; namely, if sufficient information about the cause and mechanism of injury is documented, it can be subsequently coded, electronically compiled, and retrieved later to provide an epidemiologic profile of the injury, the first step in prevention at the population level. To be of greatest use, hospital records should indicate the "who, what, when, where, why, and how" of the injury occurrence and whether protective equipment (eg, a seat belt) was used. The pediatrician has two important roles in this area: to document fully the injury event and to advocate the use of standardized external cause-of-injury codes, which allow such data to be compiled and analyzed.

Child↗

American Academy of Pediatrics. Committee on Injury and Poison Prevention. Safe transportation of newborns at hospital discharge.

All hospitals should set policies that require the discharge of every newborn in a car safety seat that is appropriate for the infant's maturity and medical condition. Discharge policies for newborns should include a parent education component, regular review of educational materials, and periodic in-service education for responsible staff. Appropriate child restraint systems should become a benefit of coverage by Medicaid, managed care organizations, and other third-party insurers.

Automobiles↗

American Academy of Pediatrics. Committee on Injury and Poison Prevention. Transporting children with special health care needs.

Children with special health care needs should have access to proper resources for safe transportation. This statement reviews important considerations for transporting children with special health care needs and provides current guidelines for the protection of children with specific health care needs, including those with a tracheostomy, a spica cast, challenging behaviors, or muscle tone abnormalities as well as those transported in wheelchairs.

Adolescent↗

Effects of noradrenaline on intracellular pH in acutely dissociated adult rat hippocampal CA1 neurones.

1. We examined the effects of noradrenaline on steady-state intracellular pH (pHi) and the recovery of pHi from internal acid loads imposed by the NH4+ prepulse technique in hippocampal CA1 neurones acutely dissociated from adult rats. 2. Under nominally HCO3--free conditions, acid extrusion was accomplished by a Na+-dependent mechanism, probably the amiloride-insensitive variant of the Na+-H+ exchanger previously characterized in both fetal and adult rat hippocampal neurones. In the presence of external HCO3-, acid extrusion appeared to be supplemented by a Na+-dependent HCO3--Cl- exchanger, the activity of which was dependent upon the absolute level of pHi. 3. Noradrenaline evoked a concentration-dependent and sustained rise in steady-state pHi and increased rates of pHi recovery from imposed intracellular acid loads. The effects of noradrenaline were not dependent upon the presence of external HCO3- but were blocked by substituting external Na+ with N-methyl-D-glucamine, suggesting that noradrenaline acts to increase steady-state pHi by increasing the activity of the Na+-H+ exchanger. 4. The effects of noradrenaline on steady-state pHi and on rates of pHi recovery from imposed acid loads were mimicked by beta1- and beta2-, but not alpha-, adrenoceptor agonists. The beta-adrenoceptor antagonist propranolol blocked the ability of noradrenaline to increase both steady-state pHi and rates of pHi recovery from acid loads. 5. The effects of noradrenaline on steady-state pHi and on pHi recovery rates following acid loads were not dependent on changes in [Ca2+]i. However, the effects of noradrenaline were blocked by pre-treatment with the adenylate cyclase inhibitor 2',5'-dideoxyadenosine and the cAMP-dependent protein kinase inhibitors Rp-adenosine-3',5'-cyclic monophosphorothioate (sodium salt; Rp-cAMPS) and N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulphonamide (H-89). 6. Forskolin, an activator of endogenous adenylate cyclase, and 3-isobutyl-1-methylxanthine, a phosphodiesterase inhibitor, mimicked the ability of noradrenaline to increase both steady-state pHi and rates of pHi recovery from imposed acid loads, as did Sp-cAMPS, a selective activator of cAMP-dependent protein kinase. The effect of forskolin on steady-state pHi was blocked by pre-treatment with Rp-cAMPS whereas the effect of Sp-cAMPS was enhanced by pre-treatment with the protein phosphatase inhibitor, okadaic acid. 7. Noradrenaline also increased steady-state pHi and rates of pHi recovery from imposed acid loads in cultured postnatal rat hippocampal neurones. In this preparation, the effects of noradrenaline were occluded by 18-24 h pre-treatment with cholera toxin. 8. We conclude that noradrenaline increases the activity of the Na+-H+ exchanger in rat hippocampal neurones, probably by inducing an alkaline shift in the pHi dependence of the antiport, thereby raising steady-state pHi. The effects of noradrenaline are mediated by beta-adrenoceptors via a pathway which involves the alpha-subunit of the stimulatory G-protein Gs (Gsalpha), adenylate cyclase, cAMP and the subsequent activation of cAMP-dependent protein kinase which, in turn, may phosphorylate the exchange mechanism.

Adenylyl Cyclases↗

Trampoline-related injuries to children.

OBJECTIVE: To describe the epidemiological features of trampoline-related injuries among children treated in an urban pediatric emergency department. DESIGN: A descriptive study of a consecutive series of patients. SETTING: The emergency department of a large, urban, academic children's hospital. PARTICIPANTS: Children treated for trampoline-related injuries from May 1, 1995, through April 30, 1997. RESULTS: Two hundred fourteen children were treated for trampoline-related injuries during the study period, representing, on average, 1 child treated approximately every 3 days. Children ranged in age from 1 to 16 years (mean [SD], 9.4 [3.6] years). The area of the body most commonly injured was a lower extremity (36.0%), followed by an upper extremity (31.8%), the head (14.5%), the trunk (9.8%), and the neck (7.9%). The most common type of injury was a soft tissue injury (51.9%), followed by fracture (34.6%) and laceration (11.7%). Several patterns of trampoline-related injury were identified. Extremity fractures were more common in the upper extremities (P=.006; relative risk [RR]=1.64; 95% confidence interval [CI], 1.16-2.31); however, soft tissue injuries were more common in the lower extremities (P=.006; RR=1.66; 95% CI, 1.16-2.38). Lacerations were associated with injury to the head region (P<.001; RR=67.9; 95% CI, 16.8-273.6) and were more common among children younger than 6 years (P=.02; RR=2.58; 95% CI, 1.24-5.34). Soft tissue injuries were more common among children 6 years of age and older (P=.01; RR=1.66; 95% CI, 1.08-2.55). Four patients (1.9%) with fractures were admitted to the hospital. The trampoline was located in the backyard in 96% (119/124) of cases. Adult supervision was present at the time of injury for 55.6% (65/117) of children, including 73.3% (22/30) of children younger than 6 years. Parents reported that they had been aware of the potential dangers of trampolines before the injury event (73% [81/111]), that their child had previously attempted a flip on a trampoline (56.9% [66/116]), that this was not the child's first injury on a trampoline (10% [12/120]), and that their child continued to use a trampoline after the current injury event (54.8% [63/115]). CONCLUSIONS: Trampoline-related injuries to children treated in the emergency department are almost exclusively associated with the use of backyard trampolines. The prevention strategies of warning labels, public education, and adult supervision are inadequate to prevent these injuries. Children should not use backyard trampolines, and the sale of trampolines for private recreational use should be halted.

Adolescent↗

Prefrontal cortex involvement in selective letter generation: a functional magnetic resonance imaging study.

Cerebral responses to alternating periods of a control task and a selective letter generation paradigm were investigated with functional Magnetic Resonance Imaging (fMRI). Subjects selectively generated letters from four designated sets of six letters from the English language alphabet, with the instruction that they were not to produce letters in alphabetical order either forward or backward, repeat or alternate letters. Performance during this condition was compared with that of a control condition in which subjects recited the same letters in alphabetical order. Analyses revealed significant and extensive foci of activation in a number of cerebral regions including mid-dorsolateral frontal cortex, inferior frontal gyrus, precuneus, supramarginal gyrus, and cerebellum during the selective letter generation condition. These findings are discussed with respect to recent positron emission tomography (PET) and fMRI studies of verbal working memory and encoding/retrieval in episodic memory.

Adult↗

Prilocaine-phenylephrine and bupivacaine-phenylephrine topical anesthetics compared with tetracaine-adrenaline-cocaine during repair of lacerations.

The effectiveness of two new topical anesthetics that do not contain cocaine (prilocaine-phenylephrine and bupivacaine-phenylephrine) was compared with that of tetracaine-adrenaline-cocaine (TAC) during laceration repair in children. This study was a prospective, randomized, double-blind trial conducted in the emergency department of a large children's hospital. Participants were 180 children 1 year of age or older with a laceration 5 cm or less in length that required suturing. Pain felt during suturing was scored by suture technicians, research assistants, parents, and patients 5 years of age and older using a visual analogue scale (VAS). There was no statistical difference demonstrated between the effectiveness of prilocaine-phenylephrine and that of TAC for any of the observer groups. A statistically significant difference was seen among anesthetics when comparing VAS scores of research assistants (P = .002), suture technicians (P = .006), and parents (P = .03), but not when comparing VAS ratings of patients (P = .07). Based on Tukey's post hoc test, these statistically significant differences were between TAC and bupivacaine-phenylephrine. When power analyses were performed using alpha = 0.05 and beta = 0.20, it was possible to detect a difference of 1.3 VAS units for each rater group. In conclusion, this study demonstrated the effectiveness and safety of prilocaine-phenylephrine and bupivacaine-phenylephrine. Prilocaine-phenylephrine statistically outperformed bupivacaine-phenylephrine and offers an effective alternative to TAC during laceration repair in children.

Adolescent↗