Search PubMed⌕ Search

Biomedical subjects

G Wood

Publications and source records attributed to G Wood.

At least 37 records · Page 2Linked to original sources

Germline mutations in the extracellular domains of the 55 kDa TNF receptor, TNFR1, define a family of dominantly inherited autoinflammatory syndromes.

Autosomal dominant periodic fever syndromes are characterized by unexplained episodes of fever and severe localized inflammation. In seven affected families, we found six different missense mutations of the 55 kDa tumor necrosis factor receptor (TNFR1), five of which disrupt conserved extracellular disulfide bonds. Soluble plasma TNFR1 levels in patients were approximately half normal. Leukocytes bearing a C52F mutation showed increased membrane TNFR1 and reduced receptor cleavage following stimulation. We propose that the autoinflammatory phenotype results from impaired downregulation of membrane TNFR1 and diminished shedding of potentially antagonistic soluble receptor. TNFR1-associated periodic syndromes (TRAPS) establish an important class of mutations in TNF receptors. Detailed analysis of one such mutation suggests impaired cytokine receptor clearance as a novel mechanism of disease.

Amino Acid Sequence↗

Effect of caffeine on the vocal folds: a pilot study.

Caffeine is considered to be a dehydrating agent with detrimental effects on the quality of voice of persons ingesting it. This has led medical personnel dealing with voice disorders, especially in the case of professional voice users, to give advice against the use of caffeine. Yet this is an anecdotal truth as an extensive Medline literature search did not reveal any scientific evidence of caffeine being proven to have adverse effects on the vocal folds. We, therefore, initiated this pilot study to ascertain the connection between caffeine and voice quality on a laboratory basis. Two hundred and fifty mg of caffeine were provided to eight volunteers in tablet form, and blood levels along with laryngograph readings were recorded to document the changes produced. Analysing the irregularities of frequencies in a) free speech b) a reading passage and c) singing 'Happy Birthday', substantial changes were seen to authenticate the fact that caffeine does produce alterations in voice quality but these alterations have considerable intra-subject variability. A full study with wider parameters is to be performed on this subject as we consider it to be of importance in the management of voice disorders.

Adult↗

Underground coal miners' foot and boot problems.

The New South Wales (NSW) Joint Coal Board Health and Safety Trust funded an investigation into foot problems reported by 400 randomly selected underground coal miners from 15 mines in NSW. Miners were interviewed and their responses were entered directly into laptop computers. Digital cameras were also used to take pictures of skin conditions and miners' posture. Observations of the skin results indicate that miners find gumboots to be hot, sweaty and uncomfortable. Skin breakdown and tinea, is frequent and disabling and responsible for absences from the workforce that are costly for both miner and employer. A more comfortable and better designed boot is needed, fabricated in waterproof leather together with socks that 'wick' the moisture away from the foot. Socks worn were of varying components and washed at irregular intervals, indicating a need for regular changes of socks and improved hygiene.

Coal↗

Mutation and haplotype studies of familial Mediterranean fever reveal new ancestral relationships and evidence for a high carrier frequency with reduced penetrance in the Ashkenazi Jewish population.

Familial Mediterranean fever (FMF) is a recessive disorder characterized by episodes of fever with serositis or synovitis. The FMF gene (MEFV) was cloned recently, and four missense mutations were identified. Here we present data from non-Ashkenazi Jewish and Arab patients in whom we had not originally found mutations and from a new, more ethnically diverse panel. Among 90 symptomatic mutation-positive individuals, 11 mutations accounted for 79% of carrier chromosomes. Of the two mutations that are novel, one alters the same residue (680) as a previously known mutation, and the other (P369S) is located in exon 3. Consistent with another recent report, the E148Q mutation was observed in patients of several ethnicities and on multiple microsatellite haplotypes, but haplotype data indicate an ancestral relationships between non-Jewish Italian and Ashkenazi Jewish patients with FMF and other affected populations. Among approximately 200 anonymous Ashkenazi Jewish DNA samples, the MEFV carrier frequency was 21%, with E148Q the most common mutation. Several lines of evidence indicate reduced penetrance among Ashkenazi Jews, especially for E148Q, P369S, and K695R. Nevertheless, E148Q helps account for recessive inheritance in an Ashkenazi family previously reported as an unusual case of dominantly inherited FMF. The presence of three frequent MEFV mutations in multiple Mediterranean populations strongly suggests a heterozygote advantage in this geographic region.

Amino Acid Substitution↗

The effect of acidified enteral feeds on gastric colonization in critically ill patients: results of a multicenter randomized trial. Canadian Critical Care Trials Group.

OBJECTIVE: To evaluate the effect of acidified enteral feeds on gastric colonization in critically ill patients compared with a standard feeding formula. DESIGN: Randomized, double-blind, multicenter trial. SETTING: Eight mixed intensive care units at tertiary care hospitals. PATIENTS: We recruited mechanically ventilated critically ill patients expected to remain ventilated for >48 hrs. We excluded patients with gastrointestinal bleeding, acidemia, and renal failure requiring dialysis. We enrolled 120 patients; 38% were female, age (mean +/- SD) was 57.6+/-19.3 yrs, and Acute Physiology and Chronic Health Evaluation II score (mean +/- SD) was 21.6+/-7.6. INTERVENTIONS: Vital High Nitrogen (Abbott Laboratories, Ross Products Division, Columbus, OH) was used as the standard feeding formula for the control group (pH = 6.5). Hydrochloric acid was added to Vital High Nitrogen to achieve a pH of 3.5 in the experimental group. MEASUREMENTS AND MAIN RESULTS: The main outcome measure was gastric colonization. Secondary outcomes included gastric pH, pneumonia, and mortality. The mean gastric pH in patients receiving acid feeds was lower (pH = 3.3) compared with controls (pH = 4.6; p<.05). One patient (2%) on acid feeds was colonized in the stomach with pathogenic bacteria, compared with 20 patients (43%) in the control group (p<.001). There was no difference in the incidence of pneumonia (6.1% in the acid feeds group vs. 15% in the control group; p = .19). Overall, there were 15 deaths in the acid feeds group and seven in the control group (p = .10); four patients in the acid feeds group and three in the control group died during the study period (p not significant). CONCLUSIONS: Acidified enteral feeds preserve gastric acidity and substantially reduce gastric colonization in critically ill patients. Larger studies are needed to examine its effect on ventilator-associated pneumonia and mortality.

Bacteria↗

Acute stress persistently enhances estrogen levels in the female rat.

Here we tested whether exposure to either tailshock or swim stress alters ovarian hormone levels, estrogen and progesterone, in females and whether the effects are persistent. Adrenal hormone levels were also measured in males and females. Estradiol levels were elevated in unstressed females during proestrus relative to females in other stages of estrous, and exposure to the stressors enhanced estradiol beyond basal levels. For females stressed during diestrus 2, estradiol levels were elevated immediately after stressor cessation and up to 24 hrs. Exposure to tailshock, but not swim-stress, transiently enhanced progesterone in females stressed during the stage of proestrus and estrus. Glucocorticoid levels were elevated in response to both stressors and were supraelevated in females under both basal and stress conditions relative to males, particularly in blood from females exposed to acute swim stress. These results indicate that exposure to a relatively acute stressful event immediately and persistently enhances serum estradiol and are discussed in the context of reports that exposure to the same stressors immediately and persistently impairs associative learning in the female rat.

Acute Disease↗

A comparison of sucralfate and ranitidine for the prevention of upper gastrointestinal bleeding in patients requiring mechanical ventilation. Canadian Critical Care Trials Group.

BACKGROUND: Critically ill patients who require mechanical ventilation are at increased risk for gastrointestinal bleeding from stress ulcers. There are conflicting data on the effect of histamine H2-receptor antagonists and the cytoprotective agent sucralfate on rates of gastrointestinal bleeding, ventilator-associated pneumonia, and mortality. METHODS: In a multicenter, randomized, blinded, placebo-controlled trial, we compared sucralfate with the H2-receptor antagonist ranitidine for the prevention of upper gastrointestinal bleeding in 1200 patients who required mechanical ventilation. Patients received either nasogastric sucralfate suspension (1 g every six hours) and an intravenous placebo or intravenous ranitidine (50 mg every eight hours) and a nasogastric placebo. RESULTS: The patients in the two groups had similar base-line characteristics. Clinically important gastrointestinal bleeding developed in 10 of 596 (1.7 percent) of the patients receiving ranitidine, as compared with 23 of 604 (3.8 percent) of those receiving sucralfate (relative risk, 0.44; 95 percent confidence interval, 0.21 to 0.92; P=0.02). In the ranitidine group, 114 of 596 patients (19.1 percent) had ventilator-associated pneumonia, as compared with 98 of 604 (16.2 percent) in the sucralfate group (relative risk, 1.18; 95 percent confidence interval, 0.92 to 1.51; P=0.19). There was no significant difference between the groups in mortality in the intensive care unit (ICU) (23.5 percent in the ranitidine group and 22.9 percent in the sucralfate group) or the duration of the stay in the ICU (median, nine days in both groups). CONCLUSIONS: Among critically ill patients requiring mechanical ventilation, those receiving ranitidine had a significantly lower rate of clinically important gastrointestinal bleeding than those treated with sucralfate. There were no significant differences in the rates of ventilator-associated pneumonia, the duration of the stay in the ICU, or mortality.

Aged↗

Construction of an approximately 700-kb transcript map around the familial Mediterranean fever locus on human chromosome 16p13.3.

We used a combination of cDNA selection, exon amplification, and computational prediction from genomic sequence to isolate transcribed sequences from genomic DNA surrounding the familial Mediterranean fever (FMF) locus. Eighty-seven kb of genomic DNA around D16S3370, a marker showing a high degree of linkage disequilibrium with FMF, was sequenced to completion, and the sequence annotated. A transcript map reflecting the minimal number of genes encoded within the approximately 700 kb of genomic DNA surrounding the FMF locus was assembled. This map consists of 27 genes with discreet messages detectable on Northerns, in addition to three olfactory-receptor genes, a cluster of 18 tRNA genes, and two putative transcriptional units that have typical intron-exon splice junctions yet do not detect messages on Northerns. Four of the transcripts are identical to genes described previously, seven have been independently identified by the French FMF Consortium, and the others are novel. Six related zinc-finger genes, a cluster of tRNAs, and three olfactory receptors account for the majority of transcribed sequences isolated from a 315-kb FMF central region (between D16S468/D16S3070 and cosmid 377A12). Interspersed among them are several genes that may be important in inflammation. This transcript map not only has permitted the identification of the FMF gene (MEFV), but also has provided us an opportunity to probe the structural and functional features of this region of chromosome 16.

Amino Acid Sequence↗

Pyogenic granuloma-like lesions in a patient using topical tretinoin.

A 16-year-old male developed numerous pyogenic granuloma like-lesions across his neck, chest and back after 6 weeks isotretinoin therapy for cystic acne. The isotretinoin was ceased and he was commenced on oral steroids. After 6 weeks, the lesions were almost completely healed. However, due to worsening comedonal acne, the patient was commenced on topical tretinoin cream 0.05% twice daily to his chest. He was reviewed 2 weeks later and, surprisingly, 2 new pyogenic granuloma-like lesions had developed on his chest. These lesions persisted until the topical tretinoin was ceased 3 months later.

Acne Vulgaris↗

Presence of paraoxonase in human interstitial fluid.

Human serum paraoxonase (PON1) is postulated to have anti-atherosclerotic properties through its ability to prevent lipid peroxide generation on LDL. However, in order to perform this role it must be present in interstitial fluid, to prevent LDL oxidation which takes place in the sub-intimal space of the artery wall. The PON1 activity in interstitial fluid was 15.7 (2.3-183.0) (median (range)) nmol/min/ml compared to 105.3 (74.6-323.9) nmol/min/ml in serum. The PON1 concentration in interstitial fluid was found to be 20.2 (1.1-78.1) microg/ml (median (range)) compared to 109.6 (11.1-485.7) microg/ml in serum. Interstitial fluid PON1 concentration was dependent on the interstitial fluid apo AI concentration (r = 0.690, P < 0.005) indicating PON1 remained associated with HDL. However, the ratio of PON1 concentration to apo AI was lower in interstitial fluid (0.60 +/- 0.20) than in the serum (0.95 +/- 0.18) (P < 0.001) indicating sequestration of PON1 in the sub-intimal space. Therefore, PON1 is present and active in interstitial fluid where it can perform its anti-atherosclerotic function.

Adult↗

A high-resolution genetic map of the familial Mediterranean fever candidate region allows identification of haplotype-sharing among ethnic groups.

Familial Mediterranean fever (FMF) is a recessive disorder of inflammation caused by mutations in a gene (designated MEFV) on chromosome 16p13.3. We have recently constructed a 1-Mb cosmid contig that includes the FMF critical region. Here we show genotype data for 12 markers from our physical map, including 5 newly identified microsatellites, in FMF families. Intrafamilial recombinations placed MEFV in the approximately 285 kb between D16S468/D16S3070 and D16S3376. We observed significant linkage disequilibrium in the North African Jewish population, and historical recombinants in the founder haplotype placed MEFV between D16S3082 and D16S3373 (approximately 200 kb). In smaller panels of Iraqi Jewish, Arab, and Armenian families, there were significant allelic associations only for D16S3370 and D16S2617 among the Armenians. A sizable minority of Iraqi Jewish and Armenian carrier chromosomes appeared to be derived from the North African Jewish ancestral haplotype. We observed a unique FMF haplotype common to Iraqi Jews, Arabs, and Armenians and two other haplotypes restricted to either the Iraqi Jewish or the Armenian population. These data support the view that a few major mutations account for a large percentage of the cases of FMF and suggest that some of these mutations arose before the affected Middle Eastern populations diverged from one another.

Alleles↗

Construction of a 1-Mb restriction-mapped cosmid contig containing the candidate region for the familial Mediterranean fever locus (MEFV) on chromosome 16p 13.3.

In this paper we describe the assembly and restriction map of a 1.05-Mb cosmid contig spanning the candidate region for familial Mediterranean fever (FMF), a recessively inherited disorder of inflammation localized to 16p13.3. Using a combination of cosmid walking and screening for P1, PAC, BAC, and YAC clones, we have generated a contig of genomic clones spanning approximately 1050 kb that contains the FMF critical region. The map consists of 179 cosmid, 15 P1, 10 PAC, 3 BAC, and 17 YAC clones, anchored by 27 STS markers. Eight additional STSs have been developed from the approximately 700 kb immediately centromeric to this genomic region. Five of the 35 STSs are microsatellites that have not been previously reported. NotI and EcoRI mapping of the overlapping cosmids, hybridization of restriction fragments from cosmids to one another, and STS analyses have been used to validate the assembly of the contig. Our contig totally subsumes the 250-kb interval recently reported, by founder haplotype analysis, to contain the FMF gene. Thus, our high-resolution clone map provides an ideal resource for transcriptional mapping toward the eventual identification of this disease gene.

Base Sequence↗

Emergence of further serotypes of multiple drug-resistant Streptococcus pneumoniae in Queensland.

We describe 27 cases of multiple drug-resistant pneumococcal infection in Queensland children (7 cases) and adults (20 cases), between February 1995 and October 1996. Seven patients had invasive disease. Serotypes were those commonly associated with paediatric infections and included types 19F (15 strains), 14 (6), 23F (4), 6A (1) and 19A (1). No rifampicin or vancomycin resistance was encountered. However, pneumococci fully resistant to cotrimoxazole, erythromycin and tetracycline were isolated from 25 of 27 cases (93%). Strains with high level resistance to penicillin and chloramphenicol were also recovered from 16 (59%) and 19 (70%) patients respectively. Twelve of 16 penicillin-resistant isolates showed intermediate resistance to ceftriaxone and two strains were fully resistant to this antibiotic. Clones of types 19F and 14 pneumococci, each with two distinctive resistance patterns, appear to be established in south-east Queensland.

Adult↗

Cytokines (IL-1beta and TNFalpha) in relation to biochemical and immunological effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in rats.

Previous studies in different strains of rats and mice have shown that the inhibition of gluconeogenesis as a result of reduced liver phosphoenolpyruvate carboxykinase (PEPCK) activity together with appetite suppression play critical roles in the acute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Recent immunological studies in rats demonstrated that exposure to low doses of TCDD resulted in an early and enhanced IgG response to immunization with sheep red blood cells (SRBC) and an enhanced delayed-type hypersensitivity (DTH) reaction as well as a positive popliteal lymph node (PLN) response. However, high doses of TCDD suppressed the DTH reaction. This study aimed at examining the involvement of cytokines (IL-1 and TNF) in mediating the above effects. Liver samples from a previous dose-response study on DTH reaction were investigated, in which rats were treated with TCDD (1, 3, 10, 30 and 90 microg/kg) and immunized with an antigen. mRNA levels of IL-1beta were elevated begining at the 1 microg/kg (non-lethal) dosage group with a maximum increase of about 5-fold above controls in the 90 microg/kg (lethal) dosage group. mRNA levels of TNFalpha were also significantly elevated begining at the 30 microg/kg dosage group. These results suggest that at low doses of TCDD, increased IL-1beta could be responsible for immune function stimulation, whereas at high doses of TCDD, greatly elevated TNFalpha and IL-1beta levles may exacerbate or mediate acute toxicity including immune suppression and related biochemical effects. A time course study (60 microg TCDD/kg without immunization) revealed that liver mRNA levels of TNFalpha were significantly elevated starting 24 h, and reaching a maximum 48 h after dosing with TCDD. This change was accompanied by a transient increase of mRNA levels of IL-1beta at day 4 after TCDD dosage. Thus, these data demonstrated that TCDD alone (without immunization) can cause transient increases of mRNA levels of TNFalpha and IL-1beta in liver. Results from these experiments suggest that TCDD-induced cytokine changes may play important roles in various effects of TCDD.

Animals↗

Effect of antihypertensive agents on the arterial partial pressure of oxygen and venous admixture after cardiac surgery.

OBJECTIVE: To determine whether stopping nitroglycerin and sodium nitroprusside (both vasodilators) infusions in hypertensive, postcardiac surgical patients requiring a high FIO2 improves PaO2 and venous admixture. DESIGN: Prospective, clinical trial. SETTING: Intensive care unit in a university-affiliated hospital. PATIENTS: Thirty postcardiac surgical patients who, because of high FIO2 requirements, did not meet the criteria for weaning from mechanical ventilation and who were receiving infusions of nitroglycerin and/or sodium nitroprusside to control blood pressure. INTERVENTIONS: PaO2, venous admixture, and oxygen transport data were determined at baseline using arterial and mixed venous blood gas samples and hemodynamic values from a pulmonary artery catheter. The nitroglycerin and sodium nitroprusside infusions were stopped, and intravenous boluses of labetalol were administered to maintain a target blood pressure. After the vasodilator infusions were stopped, the baseline measurements were repeated to redetermine PaO2, venous admixture, and oxygen transport values. MEASUREMENTS AND MAIN RESULTS: Results included a mean increase in PaO2 from 79.3 +/- 15 torr (10.5 +/- 2.0 kPa) to 118.3 +/- 38 torr (15.7 +/- 5.1 kPa) and a mean decrease in venous admixture from 26.4 +/- 5.8% to 17.6 +/- 5.6% when the vasodilators were stopped. All 30 patients had an increase in PaO2 and a decrease in venous admixture. Because of the improvement in oxygenation, 28 of the 30 patients met the criteria for weaning from mechanical ventilation once nitroglycerin and sodium nitroprusside were stopped or decreased. Labetalol was well tolerated in this group of patients who had preserved ventricular function. CONCLUSIONS: Substituting labetalol for nitroglycerin and sodium nitroprusside improves arterial oxygenation and venous admixture in hypertensive postcardiac surgical patients who require a high FIO2. This change in therapy may allow patients to be weaned from mechanical ventilation sooner.

Aged↗

Clinical improvement with bottom-line impact: custom care planning for patients with acute and chronic illnesses in a managed care setting.

A fully capitated, integrated healthcare delivery system endeavored to improve the care of its sickest members. A computer algorithm severity index that encompassed a 1-year history of hospitalization and adjusted for inclusion of a variety of chronic conditions was calculated on the basis of clinical and administrative claims databases for the entire membership of the healthcare system. Monthly updated lists were produced to find patients with acute and chronic illnesses. These patients accounted for one-fourth of hospital admissions and almost half of inpatient days, but they numbered less than 1% of system membership. Each listed person, regardless of age or diagnosis, had a custom care plan formulated by nurses in consultation with the primary care physician and involved specialists. Plan development featured in-home assessments in most instances and incorporated a variety of ancillary services, telephone and home-care follow-up, and strategies to increase continuity and access to care. Patient-reported functional status was obtained at establishment of the care plan and periodically thereafter in expectation of raising the cross-sectional mean values of the population. Three months after initiation of the program, the expected winter hospitalization peak did not occur, and utilization tended to be lower in subsequent months. Inpatient admissions among members with acute and chronic illnesses decreased 20%, and inpatient days decreased 28% from baseline levels. Among the subset of seniors in the population, inpatient days decreased 37%. Net financial impact was a medical expenditure decrease of more than 5% from 1995 levels. On a population basis, functional status was raised, and the acuity of patients' conditions and need for inpatient hospital care were reduced.

Acute Disease↗

Subcutaneous zygomycosis due to Saksenaea vasiformis: rapid isolate identification using a modified sporulation technique.

Saksenaea vasiformis, a zygomycete belonging to the order Mucorales, is a rare cause of zygomycosis with 17 cases documented world-wide. It usually infects the immunocompromised or traumatized and has a high mortality rate. Because of its failure to sporulate under normal laboratory conditions it may be difficult to identify. We describe here an unusual case report of Saksenaea vasiformis with sporulation and identification within a week using a modified sporulation technique.

Adult↗