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Biomedical subjects

A Davis

Publications and source records attributed to A Davis.

At least 91 records · Page 5Linked to original sources

A retrospective case-controlled study of 1490 consecutive patients presenting to a neuro-otology clinic to examine the relationship between blood lipid levels and sensorineural hearing loss.

This study set out to test the null hypothesis that the distribution of blood lipid levels is the same in a population with a sensorineural hearing loss (SNHL) as in a control population. Hyperlipidaemia has been implicated as an aetiological factor in SNHL; however, the majority of reports are retrospective, lack adequate controls, or are based on a series of cases which may represent incidental findings and not a true causal relationship. In all, 1490 consecutive patients who presented to a neuro-otology clinic were studied retrospectively. This group is exceptional in that all patients had had fasting lipid profiles done regardless of their presenting problem. Those with a mean SNHL > 25 dB (0.5, 1, 2 and 4 kHz) were compared with those with hearing thresholds < or = 25 dB. An analysis of variance was also done. The study group was also compared with the National Study of Hearing data set to add external validity. Simple correlations were found between hearing thresholds and many parameters such as blood pressure, fasting glucose, triglyceride or fasting cholesterol. Analysis of variance of the neuro-otology group, controlling for variables such as age and sex, showed no significant association between hearing and blood pressure, packed cell volume, mean corpuscular volume, fasting glucose, triglyceride or fasting cholesterol. However, when general linear interactive modelling was used to analyse hearing thresholds, raised total fasting cholesterol was associated with significantly better hearing threshold levels. This study leads to a rejection of the Null hypothesis that the distribution of lipid levels is the same in a population with a hearing loss as in a control population, as hearing thresholds were found to be significantly better in those with raised cholesterol levels.

Adolescent↗

Clinical, biochemical, and genetic characterization of a novel estrogen-dependent inherited form of angioedema.

BACKGROUND: Two genetic forms of hereditary angioedema (HAE) are currently recognized. Both are transmitted in an autosomal dominant manner and are characterized by recurrent episodes of localized angioedema. Involvement of the gut leads to episodes of severe abdominal pain, and laryngeal involvement can lead to airway obstruction and even death. One type results from heterozygosity for a nonexpressed C1 inhibitor allele, and the other results from heterozygosity for a nonfunctional C1 inhibitor allele. OBJECTIVE: This report identifies a third type of HAE, with a unique estrogen-dependent phenotype. METHODS: Detailed medical histories were obtained from family members, and a pedigree was constructed to ascertain the mode of inheritance. Determination of serum complement factors, C1 inhibitor protein, C1 inhibitor function, coagulation factor XII, plasma prekallikrein, high molecular weight kininogen, and selected DNA sequences were performed in affected members by using standard assays. RESULTS: Episodes of angioedema were clinically indistinguishable from those associated with previously described forms of HAE; however, these occurred only during pregnancy or the use of exogenous estrogens. Patients were otherwise asymptomatic, except for one patient who had acetyl salicylic acid/nonsteroidal anti-inflammatory drug-related angioedema later in life. History was available for members spanning 4 generations, and affected individuals were identified in 3 generations. Of 46 family members, phenotype could be determined in 13 members. Seven were affected, and 6 were not. One male of undetermined phenotype was an obligate carrier. The unique estrogen-dependent nature of the phenotype means that the status of several members in the third and fourth generation remains unknown. The disorder appears to be transmitted in an autosomal dominant fashion, although other modes of inheritance cannot be excluded entirely. C1 inhibitor protein, C1 inhibitor function, C2, C4, C1q, coagulation factor XII, prekallikrein, and high molecular kininogen were normal in 3 affected family members during asymptomatic periods. DNA sequencing revealed no abnormality in 3 patients in the coding region of the gene encoding C1 inhibitor or in the 5' flanking regions of the genes encoding C1 inhibitor and factor XII. CONCLUSIONS: This family appears to have a novel form of inherited angioedema that does not result from C1 inhibitor deficiency or dysfunction. The phenotype is uniquely estrogen dependent. Implications for diagnosis and treatment are discussed. Further studies are required to define the exact nature of the genetic abnormality involved.

Adult↗

Births of kittens produced by intracytoplasmic sperm injection of domestic cat oocytes matured in vitro.

In Experiment 1, cleavage frequency and in vitro development of domestic cat embryos produced after in vitro maturation of oocytes obtained from ovaries after ovariohysterectomy (in vitro) with that of oocytes retrieved from follicle-stimulating hormone-treated donors at 24 h after administration of luteinizing hormone (in vivo) and fertilization by intracytoplasmic sperm injection (ICSI) or IVF were compared. In each group presumptive zygotes were assessed for cleavage on IVC Days 1 and 4 and for development to blastocysts on IVC Day 7. In vitro matured oocytes had lower frequencies of meiotic maturation (59.2% v. 66.5%), cleavage at Day 1 (41.4% v. 64.9%) and development to the morula stage at Day 4 (65.8% v. 87.9%) than did in vivo matured oocytes, after ICSI and IVF. Development to the blastocyst stage was lower in in vitro matured oocytes (19.0%) than in vivo matured oocytes (29.5%) after ICSI. In Experiment 2, we evaluated the capacity of sperm injected oocytes without a visible polar body to undergo cleavage and in vitro development. More in vivo matured than in vitro matured oocytes underwent cleavage at Day 1 (46.6% v. 12.6%) and developed to the morula stage by Day 4 (66.7% v. 46.1%), but no blastocysts were obtained at Day 7 in either group. In Experiment 3, we evaluated the in vivo viability of domestic cat embryos derived from ICSI of in vitro matured oocytes. Morula stage embryos were transferred to 18 domestic cat recipients either on Day 4 or 5 after oocyte recovery. A total of 3 domestic cat recipients were pregnant after transfer to recipients on Day 5. Two pregnant cats delivered two normal and healthy live male kittens on Day 68 of gestation and the remaining cat delivered a male kitten on Day 62 that died during the last two days of gestation. These results demonstrate that: (1) inadequate cytoplasmic maturation of in vitro matured domestic cat oocytes is the main cause of deficient oocyte activation; (2) the injection of oocytes without a visible polar body is a useful technique to evaluate oocyte cytoplasmic maturation; and (3) blastocysts obtained after ICSI of in vitro matured oocytes are viable and not a result of parthenogenesis.

Animals↗

Comparison between selective and nonselective nitric oxide synthase inhibition and phenylephrine in normal and endotoxic swine.

OBJECTIVE: To compare the cardiopulmonary and peripheral circulatory effects of the nonselective nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME) to the more selective inducible NOS inhibitor S-methylisothiourea (SMT) and to phenylephrine (PE) in endotoxic and normal swine. DESIGN: Prospective, randomized, unblinded study. SETTING: Research laboratory of academic medical center. SUBJECTS: Nonanesthetized, sedated, mechanically ventilated, minimally invasive swine model. INTERVENTIONS: Animals received either lipopolysaccharide (LPS, LPS groups) or equivalent volume of saline (normal groups). LPS animals were further randomized into four groups when mean arterial pressure (MAP) had dropped to <60 mm Hg: the LPS/saline group received saline only; the other groups received either L-NAME, SMT, or PE. These were titrated to elevate MAP by 20-25 mm Hg, and animals were followed for another 3 hrs. Pulmonary artery occlusion pressure was maintained at one to two times baseline with the infusion of saline. Normal groups received the same agents 1 hr after baseline measurements, and drugs were titrated to achieve similar increases in MAP. We measured gastric-arterial PCO2 gradient by tonometry as an index of gastric mucosal perfusion. Left ventricular volumes were determined echocardiographically; right ventricular volumes were determined by a pulmonary arterial catheter equipped with a rapid thermistor. Plasma nitrite/nitrate (NOx) concentrations were measured hourly. MEASUREMENTS AND MAIN RESULTS: In the LPS groups, all agents elevated MAP and systemic vascular resistance similarly. By hr 4, cardiac output had decreased in all groups, but the decrease with L-NAME (35% +/- 16%) occurred earlier (at hr 3) and was larger than the decrease with SMT at hrs 3 and 5 and larger than the decrease with saline at hrs 3 to 5. L-NAME resulted in a larger increase in mean pulmonary arterial pressure (MPAP) when compared with saline (130% +/- 44% vs. 61% +/- 25%; p < .001) and SMT groups (130% vs. 97% +/- 80%; p < .007). Only L-NAME had detrimental effects on right ventricular function as indicated by an increase in right ventricular end-systolic volume (54 +/- 10 to 87 +/-6 mL; p < .05) and right ventricular end-diastolic volume (90 +/-11 to 128 +/- 18 mL; p < .05). SMT decreased both left ventricular end-systolic volume (10.4 +/- 2 to 7.7 +/- 4 mL; p < .05) and left ventricular end-diastolic volume (18.5 +/- 3 to 14.2 +/- 5 mL; p < .05), indicating improved left ventricular function, whereas L-NAME did not affect left ventricular volumes. Both SMT and PE corrected LPS-induced gastric mucosal acidosis, but L-NAME did not. We did not detect changes in plasma NOx concentrations in any of LPS groups. In the normal groups, all agents increased MAP without changes in plasma NOx concentrations. L-NAME caused a larger decrease in cardiac output, but the increase in MPAP was higher with SMT. Both NOS inhibitors led to left ventricular dilation, but PE did not. Only L-NAME caused right ventricular dilation. There were no changes in gastric-arterial PCO2 gradient. CONCLUSIONS: In LPS animals, we failed to detect changes in plasma NOx concentrations. Furthermore, for similar increases in MAP, SMT improved gastric mucosal acidosis, had less adverse effects on right ventricular function and MPAP, and may have improved left ventricular function. However, apart from its bene-ficial effects on left ventricular function, SMT was not superior to PE. The results from normal animals indicate that both NOS inhibitors have adverse effects on cardiac function beyond those attributed to increased MAP.

Animals↗

The 1.30 A resolution structure of the Bacillus subtilis chorismate mutase catalytic homotrimer.

The crystal structure of the Bacillus subtilis chorismate mutase, an enzyme of the aromatic amino acids biosynthetic pathway, was determined to 1.30 A resolution. The structure of the homotrimer was determined by molecular replacement using orthorhombic crystals of space group P2(1)2(1)2(1) with unit-cell parameters a = 52.2, b = 83. 8, c = 86.0 A. The ABC trimer of the monoclinic crystal structure [Chook et al. (1994), J. Mol. Biol. 240, 476-500] was used as the starting model. The final coordinates are composed of three complete polypeptide chains of 127 amino-acid residues. In addition, there are nine sulfate ions, five glycerol molecules and 424 water molecules clearly visible in the structure. This structure was refined with aniosotropic temperature factors, has excellent geometry and a crystallographic R factor of 0.169 with an R(free) of 0.236. The three active sites of the macromolecule are at the subunit interfaces, with residues from two subunits contributing to each site. This orthorhombic crystal form was grown using ammonium sulfate as the precipitant; glycerol was used as a cryoprotectant during data collection. A glycerol molecule and sulfate ion in each of the active sites was found mimicking a transition-state analog. In this structure, the C-terminal tails of the subunits of the trimer are hydrogen bonded to residues of the active site of neighboring trimers in the crystal and thus cross-link the molecules in the crystal lattice.

Bacillus subtilis↗

GO GIRLS!: results from a nutrition and physical activity program for low-income, overweight African American adolescent females.

This article describes the development, implementation, and results of an intervention designed for inner-city, overweight African American adolescent women. Fifty-seven participants were recruited from four public housing developments. Participants were administered physiologic, dietary, and cognitive assessments at baseline and immediately postintervention. Each session comprised three elements: (1) an educational/behavioral activity, (2) 30 to 60 minutes of physical activity, and (3) preparation and tasting of low-fat meals. In the absence of a control group, results were compared for high and low attenders, the former defined as attending at least 50% of the sessions. High attenders (n = 26) showed more favorable 6-month posttest values for most outcomes compared with low attenders (n = 31). These effects achieved statistical significance for nutrition knowledge, low-fat practices, perceived changes in low-fat practices, and social support.

Adolescent↗

A benign parathyroid cyst presenting with hoarse voice.

Parathyroid tumours and cysts are rare and, when presenting as neck masses, can be clinically misdiagnosed as thyroid lesions. Symptoms may be caused by compression of the surrounding structures or hormonal overactivity. This paper describes a patient with recurrent hoarseness owing to the pressure effects of a parathyroid cyst on the recurrent laryngeal nerve.

Adult↗

Improving the endoscopic view of the hypopharynx with anterior neck traction during the trumpet manoeuvre.

The postcricoid subsite is difficult to visualize on flexible laryngopharyngoscopy. The view can be improved with either auto-insufflation manoeuvres or anterior neck skin traction. In this study, the view of the hypopharynx was graded whilst anterior neck skin traction was applied during the trumpet manoeuvre; the latter involves the patient blowing on his finger as if blowing up a balloon. On auto-insufflation alone, the postcricoid site was demonstrated in 22/25 (88 per cent) of cases and the upper oesophageal sphincter (UOS) in two out of 25 (eight per cent). Of the 22 cases in whom only the postcricoid site was demonstrated, subsequent neck skin traction revealed the UOS in eight. Overall, the use of auto-insufflation solely or in combination with traction resulted in UOS visualization in 40 per cent (10/25) of cases. The application of skin traction during trumpeting is easy to perform and should be used routinely.

Female↗

Effect of pinitol treatment on insulin action in subjects with insulin resistance.

OBJECTIVE: Endogenous low-molecular-weight glycans containing pinitol (3-O-methyl-D-chiro-inositol) and D-chiro-inositol are thought to mediate certain actions of insulin. We tested the hypothesis that oral administration of soybean-derived pinitol would improve insulin sensitivity in obese subjects (BMI = 36.6 kg/m2) with diet-treated type 2 diabetes or glucose intolerance (HbA1c = 6.8%). RESEARCH DESIGN AND METHODS: There were 22 subjects randomized to receive either pinitol 20 mg x kg(-1) x day(-1) (n = 12) or placebo (n = 10) in a 28-day double-blinded trial. RESULTS: No toxicity due to the pinitol was observed during the study The sensitivity of glucose and lipid metabolism to insulin were assessed by measurement of whole-body glucose, palmitate, and glycerol kinetics during basal conditions and a hyperinsulinemic-euglycemic clamp. Metabolic measurements were made at baseline and again at the end of the study Final plasma levels of pinitol were 48-fold (1.06 +/- 0.15 vs. 0.02 +/- 0.01 micromol/l, P < 0.0001) and D-chiro-inositol levels 14-fold (0.56 +/- 0.08 vs. 0.04 +/- 0.02 micromol/l, P < 0.0001) greater in the pinitol group compared with placebo. CONCLUSIONS: Four weeks of pinitol treatment did not alter baseline glucose production, insulin-mediated glucose disposal, or rates of appearance of free fatty acids and glycerol in plasma. We conclude that plasma levels of both pinitol and D-chiro-inositol are very responsive to pinitol ingestion, but insulin sensitivity does not increase after pinitol treatment in individuals with obesity and mild type 2 diabetes.

Blood Glucose↗

Deletion of Dad1 in mice induces an apoptosis-associated embryonic death.

Dad1 is a putative anti-apoptosis gene identified in several distantly related organisms. Expression of Dad1 in transfected cells inhibits apoptosis in vitro. To determine whether Dad1 has a similar function in vivo, we used gene targeting to delete Dad1. Heterozygous adult mice (+/-) show no obvious phenotype or abnormalities, but genotype analysis of over 100 offspring from heterozygous matings detected no weanling, homozygous Dad1 null (-/-) mice. Subsequent analysis of embryos from heterozygous matings detected Dad1 null (-/-) embryos at E3.5 but no later, suggesting Dad1 is required for development beyond the late blastocyst stage. Increased levels of apoptosis were observed in cultured embryos lacking a functional copy of the gene, consistent with an anti-apoptotic role for Dad1.

Animals↗

Bleeding patterns after early abortion with mifepristone and misoprostol or manual vacuum aspiration.

OBJECTIVE: To prospectively determine patterns and predictors of bleeding after early abortion with mifepristone and misoprostol or manual vacuum aspiration (MVA). METHODS: Women fewer than 63 days from the last menstrual period and desiring termination of pregnancy were offered medical abortion with 200 mg oral mifepristone and 800 micrograms oral misoprostol or MVA under local anesthesia. Women completed a bleeding diary during the six weeks after abortion. Telephone calls were used to encourage diary completion and determine contraception use. RESULTS: 212 women were enrolled, 80% of whom completed diaries. Mean days of bleeding was higher in the medical (14 days) than MVA (9 days) group, but days of spotting (about 10) was similar in both groups. Increasing gestational age predicted more bleeding or spotting days after medical, but not MVA, abortion. Prolonged bleeding was not rare and was more common in the medical than the surgical abortion group. Combined oral contraceptive (COC) users and non-COC users had similar bleeding patterns after medical or surgical abortion. CONCLUSION: Bleeding after early medical abortion persists longer than after MVA and continues longer than previously appreciated regardless of method. Oral contraceptive use does not decrease bleeding after early medical or surgical abortion.

Abortion, Induced↗

Effect of early exposure on the integration of dental implants in the baboon: Part 1--Clinical findings at uncovering.

There has been increased discussion on the advantages of a one- versus a two-stage surgical approach in the placement of dental endosseous implants. This study evaluated the influence of early implant exposure on crestal bone height adjacent to the implant surface and Periotest values at uncovering in the baboon. Forty-eight implants (24 commercially pure titanium, 24 titanium alloy) were placed in maxillary and mandibular posterior sites in 6 baboons. Implant exposure was evaluated weekly for 3 weeks after implant placement. The level of bone adjacent to the dental implants was measured at placement from the top of the implant collar to the crest of the bone at the mesial, distal, buccal, and lingual surfaces. The maxillary sites were measured again at a 6-month uncovering, while the mandibular sites were measured at a 3-month uncovering. Periotest readings were also recorded at uncovering. Early implant exposure was more common in the mandible, with the majority occurring by the second week postplacement. There were no significant differences in the crestal bone height changes at uncovering between the pure titanium and alloy implants in either arch. In the maxilla, the changes in crestal bone height were not statistically different between exposed and nonexposed implants at any aspect. In the mandible, the difference in 3-month changes between exposed and nonexposed implants was significant for the distal, buccal, and lingual aspects. The overall percentage of implants with a Periotest reading in the "good" category was greater for the nonexposed sites as compared to exposed sites. The results of this study suggest that the two-stage surgical approach results in a better clinical outcome as compared to the one-stage approach in the baboon model.

Alveolar Process↗

Adenoviral RB2/p130 gene transfer inhibits smooth muscle cell proliferation and prevents restenosis after angioplasty.

Smooth muscle cell (SMC) proliferation that results in neointima formation is implicated in the pathogenesis of atherosclerotic plaques and accounts for the high rates of restenosis that occur after percutaneous transluminal coronary angioplasty, a widespread treatment for coronary artery disease. Endothelial lesions trigger intense proliferative signals to the SMCs of the subintima, stimulating their reentry into the cell cycle from a resting G(0) state, resulting in neointima formation and vascular occlusion. Cellular proliferation is negatively controlled by growth-regulatory or tumor-suppressor genes, or both, such as the retinoblastoma gene family members (RB/p105, p107, RB2/p130). In the present study, we show that RB2/p130 inhibited SMC proliferation in vitro and in vivo. We used the rat carotid artery model of restenosis to demonstrate that adenovirus-mediated localized arterial transduction of RB2/p130 at the time of angioplasty significantly reduced neointimal hyperplasia and prevented restenosis. Furthermore, the ability of pRb2/p130 to block proliferation correlated with its ability to bind and sequester the E2F family of transcription factors, which are important mediators of cell cycle progression. These results imply that RB2/p130 could be an important target for vascular gene therapy.

Adenoviridae↗

Congenital non-syndromal sensorineural hearing impairment due to connexin 26 gene mutations--molecular and audiological findings.

We screened DNA from 72 sibships and 138 sporadically affected individuals with congenital non-syndromal sensorineural hearing impairment (NSSNHI) for mutations in the 26 (CX26) gene. A total of 20 (27.8%) of the sibships and 11 (7.9%) of the sporadically affected individuals were homozygous or compound heterozygotes for CX26 mutations. A total of 11 (17.2%) of 64 individuals with severe and 30 (30%) of 100 with profound NSSNHI compared to eight (8.7%) of 92 persons with moderate and none (0%) of 19 individuals with mild hearing impairment were homozygous or compound heterozygotes for CX26 mutations (chi2 test, 3 df, P = 0.000). CX26 mutation status bad no effect on the symmetry of the hearing impairment or configuration of the audiogram. In addition, serial audiograms showed no evidence of progression of the hearing impairment or differences in the severity of the hearing impairment in affected siblings in persons whether or not due to CX26 mutations. Sporadically affected individuals with congenital NSSNHI should be routinely tested for mutations in CX26, especially if the hearing impairment is severe or profound in severity, since identification of a mutation in CX26 allows use of Mendelian recurrence risks.

Audiometry, Pure-Tone↗

The impact of hearing impairment: a global health problem.

Hearing impairment is a substantial worldwide problem mainly affecting the adult population. The prevalence of permanent childhood hearing impairment (PCHI) is relatively small (1 in 752) but the effects of PCHI are substantial. Children with PCHI (aged 4-12 years; n = 100) who use spoken English as their first language were assessed for cognitive and behaviour performance (controls included hearing children and children with otitis media with effusion). There was a trend in performance across severity for all assessments, with about a 2 SD difference for IQ between hearing controls and PCHI, causing concern for the pervasiveness and impact of even moderate PCHI.

Adolescent↗