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Biomedical subjects

A M Davis

Publications and source records attributed to A M Davis.

At least 91 records · Page 5Linked to original sources
PubMed1997

Excitatory neurotransmission and sexual differentiation of the brain.

During normal development there is a perinatal sensitive period during which the male brain is exposed to high levels of gonadal steroids, resulting in permanent differentiation of neural substrates. The cellular mechanisms mediating hormonally induced sexual differentiation remain largely unknown. In the adult brain, steroids exert profound influences on the amino acid transmitters, GABA, and glutamate. We have found steroid regulation of amino acid neurotransmission during the perinatal sensitive period and propose this may be functionally related to sexual differentiation of the brain. Specifically, the mRNA coding for the rate-limiting enzyme in GABA synthesis, glutamic acid decarboxylase (GAD), is up to twice as high in some steroid-concentrating regions of the neonatal male brain compared to females, including the arcuate nucleus, dorsomedial nucleus, and the CA1 region of hippocampus. Sex differences in GABA tissue concentrations positively correlate with GAD mRNA differences in several brain regions. There are also sex differences in protein levels of GABA(A) receptor subunits. In parallel with these findings are significantly higher levels of binding to the non-NMDA glutamate receptor in steroid-concentrating regions of male brain. Given that GABA is an inhibitory transmitter and glutamate is an excitatory amino acid, these results initially appear paradoxical. However, in contrast to its inhibitory action in the adult brain, early in development GABA is actually excitatory and acts in a manner analogous to glutamate. Therefore, the combination of increased excitatory GABAergic and glutamatergic activity should result in substantially higher levels of neuronal excitation in the male brain. We speculate that an increased level of neuronal excitation is a potential mechanism mediating the permanent masculinization of the brain.

Aging↗
PubMed1997

Drug-phospholipid interactions. 2. Predicting the sites of drug distribution using n-octanol/water and membrane/water distribution coefficients.

The in vivo tissue distribution of seventeen drugs has been modeled by using estimated n-octanol/water and membrane/water distribution coefficients. In this study, the membrane affinities are estimated using the new technique of immobilized artificial membrane (IAM) column chromatography. delta (log D(n-octanol/water-membrane/water)), which measures a hypothetical equilibrium of the drug between of n-octanol and membrane phase, is a better model of in vivo tissue distribution, as measured by Adipose Tissue Storage Index (ASI), than either n-octanol/ water or membrane/water distribution coefficients alone. This demonstrates the importance of membrane distribution coefficients as a complementary descriptor of lipophilicity to n-octanol/water distribution coefficients, in modeling in vivo distribution of drugs. This rapid method for predicting in vivo distribution of drugs, based on n-octanol and membrane/water distribution coefficients, may be a useful tool to aid the selection of drugs with beneficial pharmacokinetic profiles.

Adipose Tissue↗
PubMed1997

Fresh osteochondral allografts for post-traumatic osteochondral defects of the knee.

We used fresh small-fragment osteochondral allografts to reconstruct post-traumatic osteochondral defects in 126 knees of 123 patients with a mean age of 35 years. At a mean follow-up of 7.5 years (2 to 20), 108 knees were rated as successful (85%) and 18 had failed (15%). The factors related to failure included age over 50 years (p = 0.008), bipolar defects (p < 0.05), malaligned knees with overstressing of the grafts, and workers' compensation cases (p < 0.04). Collapse of the graft by more than 3 mm and of the joint space of more than 50% were seen more frequently in radiographs of failed grafts. Our encouraging clinical results for fresh small-fragment osteochondral allografts show that they are indicated for unipolar post-traumatic osteochondral defects of the knee in young active patients.

Adolescent↗
PubMed1997

Allograft reconstruction of the acetabulum after resection of stage-IIB sarcoma. Intermediate-term results.

Seventeen consecutive patients were managed with an allograft reconstruction of the pelvis (including the acetabulum) following resection of a stage-IIB bone sarcoma during a twelve-year period. The initial diagnosis was chondrosarcoma in nine patients, osteosarcoma in six, Ewing sarcoma in one, and leiomyosarcoma in one. All patients who had osteosarcoma or Ewing sarcoma received chemotherapy preoperatively and postoperatively. Fifteen patients were managed with an allograft-total hip prosthesis composite. Two patients initially were managed with an osteoarticular allograft without a prosthesis, but one had a subsequent revision to an allograft-implant composite. Four patients died with an intact allograft reconstruction. Eight patients survived with an intact allograft reconstruction, and they were followed for at least four years (mean, seven years; maximum, fourteen years). All but one was able to walk in the community with one or two canes at the time of the latest follow-up. There was a high rate of local recurrence, which occurred in three of the seventeen patients, and of infection, which developed in two patients. The five patients had a subsequent hindquarter amputation or removal of the allograft. The mean functional score (and standard deviation), according to the rating system of the Musculoskeletal Tumor Society, was 65 +/- 21.16 per cent (median, 70 per cent; range, 13 to 87 per cent) for the thirteen patients who were thus evaluated. Preservation of the limb and reconstruction with an allograft may be considered as an alternative to hindquarter amputation in carefully selected patients who have a bone sarcoma involving the acetabulum. However, patients who have a high-grade bone sarcoma must be warned that there is a substantial risk of local recurrence or infection. In the present series, more than half of the patients either died or had failure of the reconstruction.

Acetabulum↗
PubMed1997

Sarcoma of bone-cement membrane: a case report and review of the literature.

The development of a cancerous tumour at the site of total joint replacement is a rare but virtually always fatal event. The previously unreported scenario of a patient who was found to have a malignant fibrous histocytoma at the bone-cement membrane after revision for a loose total hip prosthesis is reported. Recent biologic information evaluating the response of mesenchymal cells to metallic debris suggests that the environment surrounding a loosened prosthesis may provide conditions appropriate for the development of a sarcoma.

Biopsy, Needle↗
PubMed1996

A silicate inclusion in Puente del Zacate, a IIIA iron meteorite.

The IIIA and IIIB iron meteorites are considered to have formed in the cores of asteroids. A silicate inclusion within the IIIA meteorite Puente del Zacate consisting of olivine (Fa4), low-calcium pyroxene (Fs6Wo1), chromium diopside (Fs3Wo47), plagioclase (An14Or4), graphite, troilite, chromite, daubreelite, and iron metal resembles inclusions in IAB iron meteorites. The oxygen isotopic composition of the Puente del Zacate inclusion is like chromite and phosphate inclusions in other IIIA and IIIB irons. The Puente del Zacate inclusion may have been derived from the lower mantle of the IIIAB parent asteroid.

Meteoroids↗
PubMed1996

Giant cell tumor of the proximal fibula: surgical management.

Five patients with giant cell tumor of the proximal fibula were treated with intralesional excision of the lesion, preservation of the peroneal nerve, and reconstruction of the lateral collateral ligament. At minimum 24-month follow-up there have been no local recurrences. Four patients exhibit normal function of the peroneal nerve and one has grade 4 strength of the muscles innervated by this nerve. No patient demonstrated varus instability. Marginal excision with nerve preservation and reconstruction of the ligament is a worthwhile procedure for treatment of this relatively uncommon lesion.

Adult↗
PubMed1996

Sex differences in glutamic acid decarboxylase mRNA in neonatal rat brain: implications for sexual differentiation.

Sexual differentiation of rodent brain is dependent upon hormonal exposure during a "critical period" beginning in late gestation and ending in early neonatal life. Steroid hormone action at this time results in anatomical and physiological sexual dimorphisms in adult brain, but the mechanism mediating these changes is essentially unknown. The inhibitory neurotransmitter, GABA, is involved in regulation of sexually dimorphic patterns of behavior and gonadotropin secretion in the adult. Recent evidence suggests that during development GABA is excitatory and provides critical neurotrophic and neuromodulatory influences. We hypothesized that steroid-induced changes in GABAergic neurotransmission during this critical period are important mediators of sexual differentiation in brain. Therefore, we quantified levels of mRNA for GAD, the rate-limiting enzyme in GABA synthesis. On Postnatal Day 1, males had significantly higher levels of GAD mRNA in the dorsomedial nucleus, arcuate nucleus, and CA1 region of hippocampus. On Postnatal Day 15, after the critical period for sexual differentiation has ended, these differences were no longer present. We examined the role of gonadal steroids in regulating GAD by removing testes of males and administering testosterone to females at birth. Exposure to testosterone was correlated with increased GAD mRNA in the dorsomedial nucleus. A sex difference in GAD mRNA was also observed in the medial preoptic area, but the influence of testosterone was inconclusive. We conclude that sex differences in the GABAergic system during development are partially hormonally mediated, and that these differences may contribute to the development of sexually dimorphic characteristics in adult brain.

Animals↗
PubMed1996

Evidence for sexual differentiation of glia in rat brain.

It is well established that gonadal steroids mediate sexual differentiation of the brain via direct effects on neurons during a restricted critical period. In addition, estrogen can influence glial morphology in the adult brain, and in vitro studies suggest estrogen induces glial differentiation. However, there is a lack of in vivo evidence for steroid effects on glia during the critical period. We report here a hormone-mediated sexual differentiation of arcuate glia as early as Postnatal Day 1. Using glial fibrillary acidic protein immunoreactivity (GFAP-ir), we compared the responsiveness of astroglia in the rat arcuate nucleus among five hormonally different groups. The results indicate increased GFAP-ir cell surface area 24 hr after hormonal manipulation in castrate males compared to intact males, intact females (ANOVA; P < 0.01), and females injected with testosterone propionate (50 microg; ANOVA; P < 0.05). However, astroglia in intact males extended their processes significantly greater distances from the cell body compared to all other treatment groups (ANOVA; P < 0.01). The GFAP-ir cells were categorized into four distinct classes ranging from a simple bipolar to a fully stellate morphology. The frequency distribution of classes varied between groups with more stellate cells found in intact males. Finally, these sex differences in arcuate glia persisted into adulthood. We hypothesize that during the critical period, testosterone, or its metabolite estrogen, induce sexual differentiation of glia. We further hypothesize that in females glial cells remain partially undifferentiated and this may be important to glial plasticity seen in adult female arcuate.

Animals↗
PubMed1996

Development of a measure of physical function for patients with bone and soft tissue sarcoma.

Patients undergoing limb salvage surgery for bone and soft tissue sarcoma of the extremities experience significant physical disability as a result of life-preserving treatment. The existing health status measures do not adequately evaluate physical function from the patient's perspective. This paper presents the developmental studies (item selection, reduction, reliability, validity and responsiveness) of a new measure, The Toronto Extremity Salvage Score (TESS). Patients with bone and soft tissue sarcoma (76 upper and 83 lower extremity) were randomly selected and mailed the TESS. Patients rated the severity and importance of physical disabilities; the response options included a 'not applicable' category and open-ended questions that allowed patients to suggest additional items for inclusion in the questionnaire. Therefore, patient perceptions were used to determine item content. Difficulty and importance frequencies were calculated and items rated 'totally unimportant' or 'not applicable' by 30% of the sample were eliminated. Extra items identified 30% of the time were added to the questionnaire. Internal consistency was evaluated by Cronbach's alpha. Test-retest reliability and validity were evaluated on subsequent patient samples. The intraclass correlation coefficient (ICC) was calculated for test-retest reliability and correlations with The Musculoskeletal Tumour Society Rating Scale (MSTS) were calculated for construct validity. Standardized effect sizes were calculated as a measure of responsiveness. Fifty upper extremity and sixty-six lower extremity patients responded to the mailed questionnaire. No items were eliminated based on importance or not applicable ratings. Sporting activities were identified as additional items in both the upper and lower extremity questionnaire. High internal consistency was demonstrated: 0.94 for the lower and 0.92 for the upper extremity questionnaires respectively. Test-retest reliability was evaluated at multiple time-points and the intraclass correlation coefficient was greater than 0.87 in all instances. Construct validity was shown by a moderate correlation with the MSTS. The effect sizes were large demonstrating responsiveness. The use of patients' perceptions in determining the content of the TESS has resulted in a reliable and valid measure that is able to detect change over time.

Activities of Daily Living↗
PubMed1996

Clinical spectrum, therapeutic management, and follow-up of ventricular tachycardia in infants and young children.

We reviewed 40 infants and young children with VT. Median maximum VT rate was 214 beats/min (range 152 to 375 beats/min). A cause was defined in 20 (50%), the most common being cardiomyopathy or myocarditis in 8 (20%). There were six deaths (15%) related to VT, three of which occurred at diagnosis and in patients less than 1 week old. In 5 of 6 deaths related to VT, a cause was defined. At follow-up, 31 (91%) of 34 survivors did not have VT. The presence of symptoms was a predictor of death related to VT. The outlook for asymptomatic patients and those who survived more than 6 months after diagnosis and who do not have progressive myocardial disease appears good.

Actuarial Analysis↗
PubMed1996

Spontaneous vesicle formation at lipid bilayer membranes.

Unilamellar vesicles are observed to form spontaneously at planar lipid bilayers agitated by exothermic chemical reactions. The membrane-binding reaction between biotin and streptavidin, two strong transmembrane neutralization reactions, and a weak neutralization reaction involving an "antacid" buffer, all lead to spontaneous vesicle formation. This formation is most dramatic when a viscosity differential exists between the two phases bounding the membrane, in which case vesicles appear exclusively in the more viscous phase. A hydrodynamic analysis explains the phenomenon in terms of a membrane flow driven by liberated reaction energy, leading to vesicle formation. These results suggest that energy liberated by intra- and extracellular chemical reactions near or at cell and internal organelle membranes can play an important role in vesicle formation, membrane agitation, or enhanced transmembrane mass transfer.

Bacterial Proteins↗
PubMed1996

Normal values for the childhood signal-averaged ECG.

To obtain normative data for the childhood signal-averaged ECG (SAECG), we obtained SAECGs in 155 volunteers, aged 5-15 years, using Frank leads and a Fourier transform filter. Unfiltered QRS duration (QRSDU) and filtered QRS duration (QRSDF) were significantly longer in males, and the root mean square of the terminal 40 ms (RMS40) was significantly higher in females. There were no gender differences in the duration of high frequency low amplitude signals < 40 microV (DHFLA). All SAECG variables were significantly related to body surface area (BSA). Regression models were established for SAECG variables. For males, the predicted mean + 1.96 standard deviations (SD) for QRSDF (97.5th centile) ranged from 114 ms at BSA 0.70 m2 to 123 ms at 1.90 m2. For females, the predicted mean + 1.96 SD for QRSDF ranged from 110 ms at BSA 0.70 m2 to 119 ms at 1.90 m2. For males and females, the predicted mean + 1.96 SD for DHFLA ranged from 34 ms at 0.70 m2 to 38 ms at 1.90 m2. For males, the predicted mean - 1.96 SD (2.5th centile) for RMS40 (based on natural logarithm model) ranged from 30 microV at 0.70 m2 to 15 microV at 1.90 m2. For females, the predicted mean -1.96 SD for RMS40 ranged from 42 microV at 0.70 m2 to 20 microV at 1.90 m2. In children 5-15 years of age, both gender and BSA need to be taken into account when interpreting the SAECG.

Adolescent↗
PubMed1996

P2T purinoceptor antagonists. A QSAR study of some 2-substituted ATP analogues.

FPL67085MX represents the first in a class of novel, highly potent and selective P2T purinoceptor antagonists which are inhibitors of adenosine diphosphate (ADP)-induced platelet aggregation in-vitro. In an early series of compounds we studied the effect of variation of the adenine 2-substituent on potency and derived quantitative structure-activity relationships (QSARs) between the properties of the molecules and their biological activity. This work has recently been revisited using comparative molecular-field analysis (CoMFA) and the comparison of the predictions from the two methods is discussed along with their relative merits in terms of compound design. The model suggests that the receptor for these molecules has a narrow lipophilic cleft, which is occupied by the adenine 2-substituent.

Adenosine Triphosphate↗
PubMed1996

Serum osteocalcin, total and bone-specific alkaline phosphatase following isolated tibial shaft fracture.

We report the changes in osteocalcin concentrations and in total and bone specific alkaline phosphatase activity occurring in the twenty week period following tibial shaft fracture in 20 subjects. Bone formation during the healing process is reflected by progressive increases in the concentration of osteocalcin and bone specific alkaline phosphatase after week 5 and the latter correlated with the height and weight of the subject. In the early post injury period, total alkaline phosphatase activity increased whereas that of the bone isoenzyme initially fell, starting to rise again during the second week. After an immediate post injury rise, osteocalcin concentration also decreased, reaching a nadir by week 5. As only three of our subjects demonstrated delayed union, we have not been able to demonstrate that biochemical monitoring of the healing process can provide an indication of prognosis in tibial shaft fracture.

Adolescent↗