PubMed Health⌕ Search

Biomedical subjects

K M Ayers

Publications and source records attributed to K M Ayers.

At least 19 recordsLinked to original sources
PubMed2000

Mechanomyographic and electromyographic responses during fatigue in humans: influence of muscle length.

Mechanomyography (MMG) provides a measure of muscle mechanical changes during contractions. The purpose of this study was to quantify alterations in MMG signals during fatigue at two muscle lengths. Comparisons with electromyographic (EMG) recordings were made. A group of 13 subjects performed isometric dorsiflexions (50% of maximum for 60 s) at 40 degrees of plantarflexion (long, l(l)) and 5 degrees of dorsiflexion (short, l(s)). The mean power frequency of the EMG (f(EMG)) and MMG (f(MMG)) signals and the mean rectified MMG (rMMG) and EMG (rEMG) were determined over each 1-s period, normalized to the respective maximal value, regressed against time, and the resulting slopes (units = %max. s(-1)) were analyzed. The slopes were larger (P = 0.007) at l(l) compared to l(s) [mean l(l) 0.50 (SD 0.26), mean l(s) 0.27 (SD 0.16)], however there were no differences (P = 0.24) between mean fMMG slopes [l(l) -0.10 (SD 0.16), l(s) -0.16 (SD 0.11)]. Similarly, slopes were larger (P = 0.001) at l(l) versus l(s) [l(l) 0.26 (SD 0.13), l(s) 0.08 (SD 0.15)] and there were no differences (P=0.89) between mean fEMG slopes [l(l) -0.15 (SD 0.14), l(s) -0.14 (SD 0.12)]. At 5 s following the exercise to fatigue mean MVC (units = %max) were not significantly different between l(l) and l(s) [P = 0.08; l(l) 78.8 (SD 9.1), l(s) 85.2 (SD 6. 0)]. These results showed that during fatiguing contractions, MMG and EMG amplitudes increased while frequency characteristics decreased at both muscle lengths. The change in and was greater at l(l) but no differences in fMMG or fEMG slopes occurred between lengths. These results would suggest that larger increases in motor unit recruitment occur with time during fatigue at l(l) compared to l(s).

Adult↗
PubMed2000

Leukaemia in children. Part I: Orofacial complications and side-effects of treatment.

Significant orofacial complications of leukaemia in children include lymphadenopathy, spontaneous gingival bleeding, labial and lingual ecchymoses and mucosal petechiae, ulceration, gingival swelling, and infections. The dentist may be the first to notice signs of the illness. Treatment of leukaemia can result in serious orofacial problems which include oral mucositis and ulceration, infections, spontaneous gingival bleeding, neuropathy, xerostomia, and gingival hypertrophy. A prompt diagnosis leading to early intervention can decrease the morbidity and mortality of the disease and its treatment.

Antineoplastic Agents↗
PubMed2000

Leukaemia in children. Part II--Dental care of the leukaemic child, including management of oral side effects of cancer treatment.

The treatment of a leukaemic child requires a multidisciplinary approach. The dental team should provide interceptive and preventive measures prior to the commencement of therapy whenever possible. During therapy, preventive and palliative measures are essential. Once remission is achieved, the child continues to have increased dental needs due to the effects of treatment. These needs may include an increased caries rate, dental maldevelopment, and secondary malignancy.

Antineoplastic Agents↗
PubMed2000

Open wide.

Dentists who work with children can appreciate the difficulties encountered when attempting to provide high quality restorative care within a confined space. In this presentation, I will address the issue of how to maximize space available in the mouth whilst minimizing patient discomfort and maintaining a working position that does not cripple the operator! Topics covered include: Instruments which take up less space in the mouth Behavioural techniques and aids to maximize mouth opening Adaptation of dental equipment for use in the child patient Techniques to obtain radiographs with minimal discomfort Methods for administering local anaesthetic with less fuss Novel methods of rubber dam placement. Space within the dental surgery is also limited. A further issue to be addressed is the management of the whanau/family to optimize their presence in supporting the patient, yet minimize distractions within the confines of the surgery.

Anesthesia, Dental↗
PubMed1998

Halitosis: causes, diagnosis, and treatment.

Halitosis is a major concern to the general public and the source of a multimillion-dollar industry world wide. Although the aetiology may be localised to the oral cavity in up to 90 percent of instances, halitosis may indicate a serious underlying medical condition necessitating medical referral. In general, halitosis of an oral cause can be safely and easily diagnosed and treated by the general dental practitioner.

Halitosis↗
PubMed1997

A transplacental carcinogenicity bioassay in CD-1 mice with zidovudine.

In oral carcinogenicity bioassays, zidovudine (ZDV) induced vaginal epithelial cell tumors in mice given 30 or 40 mg/kg/day and rats given 300 mg/kg/day. To determine if lifetime exposure to ZDV, beginning perinatally, would alter this pattern of carcinogenicity, two groups of 60 pregnant CD-1 mice were given 20 or 40 mg/kg/day of ZDV in 0.5% methyl cellulose from Gestation Day 10 through Lactation Day 21. At weaning, 2 pups per sex from each of 35 litters in each group were assigned to the study and given 20 or 40 mg/kg/day of ZDV in the drinking water until 17-35 days of age, followed by daily gavage for 24 months. Two additional groups of 60 pregnant CD-1 mice each were given 40 mg/kg/day of ZDV daily from Gestation Day 10 through Lactation Day 21; in one, ZDV treatment was halted at weaning and in the other, treatment was stopped 90 days after weaning. Two other groups of 60 pregnant CD-1 mice were left untreated (environmental control) or were given 0.5% methyl cellulose beginning on Gestation Day 10 (vehicle control). Vehicle control progeny received plain drinking water for 17-35 days postweaning and then 0.5% methyl cellulose daily by gavage for 24 months. ZDV treatment did not affect survival or body weight in either sex. In females given 20 or 40 mg/kg/day of ZDV for 24 months there was mild macrocytic anemia. Similar, non-dose-related changes were seen in males in these groups. ZDV-related tumor findings were limited to the vagina, where there were 2 and 11 vaginal squamous cell carcinomas in mice given 20 or 40 mg/kg/day of ZDV daily, respectively. This incidence was not remarkably different from that seen in previously reported bioassays. It was concluded that lifetime oral treatment of mice with ZDV, beginning perinatally, did not alter the previously reported pattern of carcinogenicity and that under the conditions tested ZDV was not a transplacental carcinogen.

Animals↗
PubMed1996

Nonclinical toxicology studies with zidovudine: acute, subacute, and chronic toxicity in rodents, dogs, and monkeys.

In single dose acute toxicity studies in CD-1 mice and CD rats, the median lethal dose (MLD) for zidovudine (ZDV) was > 750 mg/kg after iv dosing and > 3000 mg/kg after po administration (recommended human dose is 100 mg every 4 hr while awake). Because of the short half-life in rats (0.8 hr), dogs (1.0 hr), and monkeys (0.8 hr), the daily dose of ZDV in most studies was given in two equal portions approximately 6 hr apart. Intravenous administration of ZDV was well tolerated in beagle dogs at dose levels up to 42.5 mg/kg bid for 2 weeks and in CD rats at dose levels up to 75 mg/kg bid for 4 weeks. In a 2-week dose range-finding study in beagle dogs, cytostatic effects were noted at po dose levels of 62.5 to 250 mg/kg bid in certain tissues with rapid cell replication rates. In contrast, in 3- to 12-month oral toxicity studies in CD rats and cynomolgus monkeys, the principal toxicologic finding was reversible macrocytic normochromic anemia which occurred at 225-250 mg/kg bid in rats and 17.5-150 mg/kg bid in monkeys. In the 12-month rat study, RBC was decreased at 25 and 75 mg/kg bid. In the 12-month monkey study WBC was slightly decreased at 150 mg/kg bid.

Administration, Oral↗
PubMed1996

Nonclinical toxicology studies with zidovudine: reproductive toxicity studies in rats and rabbits.

Zidovudine (ZDV) was evaluated for adverse effects on reproduction and fetal development in animal test species. Standard preclinical tests for reproduction and fertility, developmental toxicity, and postnatal toxicity were conducted in CD (Sprague-Dawley) rats and a developmental toxicity study was conducted in New Zealand white rabbits. In an additional study, reproductive outcome was characterized in female rats given ZDV before, during, or after mating and drug levels in the plasma and milk of lactating rats were determined. Finally, drug exposure data including observed peak plasma concentrations (Cmax) and area under the concentration-time curve (AUC) were evaluated for pregnant rats and rabbits. In a reproduction/fertility study in CD rats, toxicity to the early rat embryo, manifested as an increase in early resorptions and a decrease in litter size, was noted following dosage of the parental animals with 75 or 225 mg ZDV/kg bid. A dose of 25 mg/kg bid was a no-effect level in rats. At the time of mating, male rats had been dosed for 85 days, and females had been dosed for 26 days. To further evaluate the effects of ZDV on reproduction, dosing of male rats was continued to 149 days when they were mated a second time to virgin, untreated females. All reproductive parameters were normal in the untreated females from this second mating, indicating that the embryotoxic effect of the drug was not likely mediated by a genotoxic or other effect in the male. A separate study in female CD rats given 225 mg/kg bid for various periods pre- or postconception suggests that the toxic effect of ZDV is primarily to the early rodent embryo. Early embryo death did not occur in rats or rabbits in standard developmental (teratology) studies; however, pregnant New Zealand white rabbits given 250 mg/kg bid during gestation Days 6-18 showed reduced weight gain, anemia, and an increase in late fetal deaths. No other evidence of developmental toxicity was noted in either species, and ZDV was not teratogenic in rats or rabbits given up to 250 mg/kg bid during the period of major organogenesis. At this dose, Cmax values in rats and rabbits were approximately 234 and 150 times higher, respectively, than the mean steady-state serum concentration in adults following chronic oral administration of 250 mg every 4 hr. In both the reproduction/fertility study and a peri- and postnatal study in rats, liveborn offspring showed no adverse effects on survival, growth, or developmental measurements.

Animals↗
PubMed1996

Nonclinical toxicology studies with zidovudine: genetic toxicity tests and carcinogenicity bioassays in mice and rats.

Zidovudine (ZDV), an antiviral drug active in the treatment of acquired immunodeficiency syndrome (recommended human dose, 100 mg every 4 hr while awake), was evaluated for mutagenic and carcinogenic potential in a battery of short-term in vitro and in vivo assays and in lifetime studies in mice and rats. In L5178Y mouse lymphoma cells (tk+/- locus), a weak positive result was obtained only at the highest concentrations tested (4000 to 5000 micrograms/ml) in the absence of metabolic activation. In the presence of metabolic activation, the drug was weakly mutagenic at concentrations of 1000 micrograms/ml and higher. Following 24 hr treatment in the absence of metabolic activation, ZDV was moderately mutagenic at concentrations up to 600 micrograms/ml; dose-related structural chromosomal alterations were seen at concentrations of 3 micrograms/ml and higher in cultured human lymphocytes. Such effects were not noted at the two lowest concentrations tested, 0.3 and 1 microgram/ml, and BALB/c-3T3 cells were transformed at concentrations of 0.5 microgram/ml and higher. No effects were seen in the Ames Salmonella plate incorporation and preincubation modification assays (possibly due to bacteriocidal activity of ZDV at low concentrations) at concentrations ranging from 0.01 to 10 micrograms/plate or in a single-dose intravenous bone marrow cytogenetic assay in CD rats. In multidose micronucleus studies, increases in micronucleated erythrocytes were seen in mice at doses of 100 to 1000 mg/kg/day. Similar results were seen in rats and mice after 4 or 7 days of dosing at 500 mg/kg/day. In carcinogenicity bioassays, adjusted doses of 20, 30, or 40 mg/kg/day and 80, 220, and 300 mg/kg/day were given to CD-1 mice and CD rats, respectively, for up to 22 months in mice and 24 months in rats. ZDV caused a macrocytic, normochromic anemia in both species. No evidence of carcinogenicity was seen in male mice or rats. In female mice, five malignant and two benign vaginal epithelial neoplasms occurred in animals given 40 mg/kg/day. A single benign vaginal epithelial tumor was seen in a mouse given 30 mg/kg/day. In rats, two malignant vaginal epithelial neoplasms were seen in animals given 300 mg/kg/day. In a 7-day study in mice, ZDV was shown to be devoid of estrogenic activity. In an oral pharmacokinetics study, the AUC was 17 and 140 micrograms/ml.hr in female mice and rats given 40 or 300 mg/kg of ZDV, respectively. In contrast, the average steady-state concentration in humans at the recommended daily dose is 0.62 microgram/ml. Twenty-four hour urine concentrations were 1245 and 4417 micrograms/ml in female mice and rats given 40 or 300 mg/kg of ZDV, respectively. These values were approximately 26- and 136-fold higher than the human urine concentration at the recommended daily dose. In a one- to three-day study with intravenously administered sodium fluoroscein in rats and mice, retrograde flow of urine into the vagina was demonstrated. In a subsequent lifetime carcinogenicity bioassay in mice in which ZDV was given intravaginally at concentrations of 5 or 20 mg ZDV/ml in saline, 13 vaginal squamous cell carcinomas were seen at the highest concentration tested. It was concluded that the vaginal tumors seen in the oral carcinogenicity studies were the result of chronic local exposure of the vaginal epithelium to high urine concentrations of ZDV.

3T3 Cells↗
PubMed1996

Dental disease levels and reasons for emergency clinic attendance in patients seeking relief of pain in Auckland.

This study examined the reasons for attendance, duration of the problem, treatment expectations and oral health of patients seeking relief of pain at Auckland hospital dental departments and a private accident and emergency clinic. One-third of hospital-clinic participants and 15 percent of private-clinic participants had delayed treatment for more than 1 month. Sixty-three percent of hospital-clinic and 30 percent of private-clinic participants expected to receive an extraction. The hospital-clinic group had a mean of 5.0 (SD 3.9) decayed teeth, and the private clinic group a mean of 2.3 (SD 2.8) decayed teeth. Periodontal treatment needs were also significantly higher among participants attending the hospital clinics. Twenty-five percent of hospital-clinic participants had complex periodontal treatment needs. Further research is required to estimate the size of the population these groups represent and to investigate the reasons for these differences.

Adolescent↗
PubMed1994

5-Chloro-2',3'-dideoxy-3'-fluorouridine (935U83), a selective anti-human immunodeficiency virus agent with an improved metabolic and toxicological profile.

5-Chloro-2',3'-dideoxy-3'-fluorouridine (935U83) is a selective anti-human immunodeficiency virus (HIV) agent. When tested in phytohemagglutinin-stimulated normal human peripheral blood lymphocytes against fresh clinical isolates of HIV type 1 (HIV-1) obtained from patients naive to AZT (3'-azido-3'-deoxythymidine [zidovudine]), 935U83 inhibited virus growth with an average 50% inhibitory concentration (IC50) of 1.8 microM; corresponding IC50s were 0.10 microM for FLT (3'-deoxy-3'-fluorothymidine) and 0.23, 0.49, and 0.03 microM for the approved agents AZT, ddI (2',3'-dideoxyinosine), and ddC (2',3'-dideoxycytosine), respectively. Importantly, 935U83 retained activity against HIV strains that were resistant to AZT, ddI, or ddC. Of additional interest, we were unable to generate virus which was resistant to 935U83 by passaging either HXB2 (AZT-sensitive) or RTMC (AZT-resistant) strains in the presence of high concentrations of 935U83. The anabolic profile of 935U83 was similar to that of AZT, and 935U83 triphosphate was a potent inhibitor of HIV-1 reverse transcriptase. Pharmacokinetic evaluation showed good oral bioavailability (86% in mice and 60% in monkeys) and less extensive metabolism to the glucuronide relative to AZT. 935U83 showed low toxicity. In an in vitro assay for toxicity to a human erythrocyte progenitor, erythroid burst-forming unit (BFU-E), the IC50 for 935U83 (> 400 microM) was more than 1,000-fold those of FLT (0.07 microM) and AZT (0.30 microM). Mild reversible reductions in erythrocytes and associated parameters were seen in mice dosed orally with 2,000 mg of 935U83 per kg per day for 1 and 6 months. In monkeys dosed orally with up to 700 mg/kg/day for 1 and 6 months, the only possible treatment-related finding was cataracts in 1 of 12 animals given the intermediate dose of 225 mg/kg/day. At the highest doses in mice and monkeys, maximal concentrations in plasma were more than 100-fold the anti-HIV IC50s against clinical isolates. This safety profile in animals compares very favorably with that of any of the anti-HIV drugs approved to date and has led us to begin evaluation of 935U83 in patients with HIV infection.

Animals↗
PubMed1993

Sodium azide protects against ischemia-induced acute renal failure in rats.

Sodium azide (AZ) is a nitrovasodilator with diverse biochemical properties. We found that low doses of AZ led to a profound protective effect against postischemic, acute renal failure (ARF) in rats. AZ, given at 250 micrograms/kg iv, before 25 min of renal artery occlusion (RAO) and again before reperfusion, conferred almost complete protection against loss of kidney function determined 18 h after RAO. The effect of AZ was evidenced by a higher creatinine clearance (+348%) and lower levels of blood urea nitrogen (-69%) and histological renal damage (-50%) compared with ischemic control animals. Indexes of kidney function in AZ-treated animals subjected to RAO were not significantly different from those of nonischemic control animals. Two other nitrovasodilators, sodium nitroprusside and hydralazine, at doses which produced decreases in blood pressure similar to that of AZ, were ineffective at preventing ARF. The beneficial effect of AZ may be due to its known ability to inhibit one or more enzymes including adenosinetriphosphatase, cytochrome-c oxidase, and myeloperoxidase.

Acute Kidney Injury↗
PubMed1990

Postnatal survival in Wistar rats following oral dosage with zidovudine on gestation day 10.

Groups of 20 female Wistar rats from Charles River Breeding Laboratories (Kingston, NY) were given three oral doses of 100 mg zidovudine/kg at 5-hr intervals on Gestation Day 10 (total dose = 300 mg/kg). Control rats received three oral doses of the vehicle, distilled water. This design approximated that of an earlier study that reported 38% postnatal mortality among the offspring of Wistar rats given zidovudine. In the study reported here, no adverse effects were noted on maternal body weight, food consumption, reproductive capacity, or hematology. Similarly, no effects on growth or survival of the offspring were noted. Hematology and clinical chemistry values were comparable between offspring of treated and control dams, and no treatment-related gross or histopathologic lesions were noted in the weanling rats. The mean concentration of zidovudine in embryonal homogenates, collected 30 min after administration of the third dose to the dam on Gestation Day 10, was 21.1 micrograms/g tissue. This value is approximately one-third of the mean drug plasma concentration (62.6 micrograms/ml) measured in the dams at the same time point. The dramatic difference in results in the two studies may be related to differences in Wistar rats from two different sources or to other unknown factors associated with the design and conduct of the studies. The results of the current study were consistent with other preclinical studies on the reproductive toxicity of zidovudine in rats and rabbits.

Animals↗
PubMed1989

Purification, toxicity, and antiendotoxin activity of polymyxin B nonapeptide.

Polymyxin B, a relatively toxic antibiotic, has potent endotoxin-neutralizing properties that may be beneficial as adjunctive therapy in gram-negative sepsis. Polymyxin B nonapeptide (deacylated polymyxin B) is devoid of antibiotic activity but retains the capacity to disorganize the outer membrane of gram-negative bacteria. To evaluate the potential therapeutic usefulness of this derivative, we produced purified polymyxin B nonapeptide, tested its in vivo toxicity in animals, and evaluated its in vitro antiendotoxin activity. Effectiveness as an antiendotoxin agent was assessed by examining the ability of polymyxin B nonapeptide to block the enhanced release of toxic oxygen radicals induced by lipopolysaccharide in human neutrophils (priming). In vivo, at doses of 1.5 and 3.0 mg/kg, polymyxin B nonapeptide did not exhibit the neuromuscular blocking, neurotoxic, or nephrotoxic effects that were observed with polymyxin B sulfate. Both polymyxin B and polymyxin B nonapeptide inhibited lipopolysaccharide-induced neutrophil priming in a concentration-dependent manner, but the parent compound, polymyxin B, was 63 times more effective on a weight basis. The inhibitory activity of both compounds, however, diminished rapidly when they were added after the start of the lipopolysaccharide-neutrophil incubation. We conclude that polymyxin B nonapeptide is less toxic than polymyxin B and, at the doses tested, lacks the neurotoxicity and nephrotoxicity of the parent compound. Polymyxin B nonapeptide retains the antiendotoxin activity of polymyxin B but is much less potent. The findings suggest that these compounds block an early step in the neutrophil priming process, possibly lipopolysaccharide attachment to or insertion into the neutrophil membrane.

Animals↗
PubMed1988

Preclinical toxicology of zidovudine. An overview.

The toxicologic potential of zidovudine (azidothymidine) has been extensively investigated in several species. In rats and mice, the median lethal dose was greater than 750 mg/kg intravenously and greater than 3,000 mg/kg orally. In subacute intravenous toxicity studies, no significant toxicologic alterations were seen in rats or dogs. In cynomolgus monkeys, which as in humans rapidly and extensively glucuronidate zidovudine, a reversible, dose-related, macrocytic anemia was seen in animals given 35, 100, or 300 mg/kg per day for three or six months. In three-month and six-month oral toxicity studies in rats, treatment-related alterations consisted of a mild increase in glucose level in the blood in female rats in both studies and a reversible, slight-to-mild macrocytic anemia in the six-month study. There was no evidence of teratogenicity in rats or rabbits given the drug during gestation. Results for zidovudine were negative in a bacterial mutagenicity assay, but the drug was weakly mutagenic at concentrations of 1,000 to 5,000 micrograms/ml in mammalian cells. Zidovudine caused chromosomal aberrations in cultured human lymphocytes at concentrations of 3 micrograms/ml and higher and had positive results in a cell transformation assay at concentrations of 0.5 micrograms/ml and higher. No bone marrow chromosomal alterations were noted in a cytogenetics study in rats given zidovudine at several intravenous dose levels up to 300 mg/kg.

Animals↗