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Biomedical subjects

G C Townsend

Publications and source records attributed to G C Townsend.

At least 19 recordsLinked to original sources

The use of corticosteroids in the management of bacterial meningitis in adults.

Despite the introduction of newer antimicrobial agents, bacterial meningitis continues to be associated with significant morbidity and mortality. Evidence from in-vitro studies, experimental animal models, and clinical studies indicate that the host inflammatory response is responsible for much of the deleterious consequences of this disease. Thus, there is much interest in the adjunctive use of antiinflammatory agents in the therapy of bacterial meningitis. Although there is considerable evidence from animal models and from clinical trials in children that adjunctive antiinflammatory therapy with corticosteroids is effective in reducing inflammation and in improving long-term outcomes, similar data involving adults are largely lacking. The rationale for the use of corticosteroids in the management of bacterial meningitis, and the applicability to disease in adults, are discussed, and some recommendations for their use in this setting are made.

Adrenal Cortex Hormones

In vitro models of the blood-brain barrier to study bacterial meningitis.

In vitro models of the blood-brain barrier involving culturing cerebral microvascular endothelial cells may provide information critical to understanding diseases of the central nervous system, such as bacterial meningitis, that would be difficult to obtain from clinical studies or from in vivo models. These models may also identify targets for therapeutic intervention.

Animals

Genetic and environmental influences on facial profile.

Observed variation in facial morphology results from the influences of both genetic and environmental factors. To investigate the role of genetic influences on variation in facial profile, lateral photographs of 23 male and 19 female monozygous (MZ), and 15 male and 22 female dizygous (DZ) twin pairs were selected from the records of the South Australian Twin Study. Soft tissue landmarks and facial profiles were identified, traced and digitized. Linear and angular measures defined by the landmarks were calculated and a series of Fourier functions derived to describe the facial profiles. These Fourier amplitudes were interpreted in terms of the specific regions which they represented. Correlations within MZ pairs were consistently higher than within DZ pairs for both the facial dimensions and the Fourier amplitudes, providing evidence of significant genetic contribution to facial convexity, facial height and facial depth. Variability in nose and lip morphology appeared to be under stronger environmental influence.

Adolescent

Potential role of nitric oxide in the pathophysiology of experimental bacterial meningitis in rats.

We have investigated the possible role of nitric oxide (NO) in the pathophysiology of bacterial meningitis (BM) by using the rat model of experimental BM. The nitrite concentration in cerebrospinal fluid (CSF) was used as a measure of NO production in vivo since NO rapidly degrades to nitrite and nitrate. Rats were inoculated intracisternally with live bacteria (5 x 10(6) CFU of Haemophilus influenzae type b strain DL42 or Rd-/b+/O2), with bacterial endotoxin (20 ng of DL42 lipooligosaccharide [LOS] or 200 ng of Escherichia coli lipopolysaccharide), or with a saline control vehicle. CSF samples were collected preinoculation and at the time of maximal alteration in blood-brain barrier permeability (BBBP). CSF [nitrite] was quantified by measuring A550 after addition of the Greiss reagent and comparison to a standard curve of sodium nitrite. Rats inoculated with either DL42, Rd-/b+/O2, LOS, or lipopolysaccharide demonstrated a significantly elevated mean peak CSF [nitrite] (8.34, 15.62, 10.75, and 10.44 mM, respectively) versus the concentration prior to treatment and/or those in saline-treated animals (5.29 and 5.33 mM, respectively; P < 0.05 for each comparison). We then determined if there was a correlation between CSF [nitrite] and percent BBBP (%BBBP) at various time points postinoculation with Rd-/b+/O2. %BBBP was defined as the concentration of systemically administered 125I-labeled bovine serum albumin in the CSF divided by the level of 125I-labeled bovine serum albumin in serum multiplied by 100. The mean %BBBP increased in tandem with the mean CSF [nitrite] (R = 0.84, P = 0.018), which peaked at 18 h in the absence of a change in the serum [nitrite]. Systemic administration of the NO synthase inhibitor N-nitro-L-arginine methyl ester demonstrated a significant reduction of mean CSF nitrite production (0.95 versus 6.0 mM in controls; P = 0.02) when administered intravenously to animals which had been inoculated intracisternally with 20 ng of LOS. Suppression of mean leukocyte pleocytosis (3,117 versus 11,590 leukocytes per mm3 in control LOS-challenged rats; P = 0.03) and mean alterations of BBBP (2.11 versus 6.49% in control LOS-challenged rats; P = 0.009) was observed concomitantly with decreased CSF [nitrite]. These results support the hypothesis that NO contributes to increased %BBBP in experimental BM.

Animals

Genetic covariance structure of incisor crown size in twins.

Previous studies of tooth size in twins and their families have suggested a high degree of genetic control, although there have been difficulties separating the various genetic and environmental effects. A genetic analysis of variation in crown size of the permanent incisors of South Australian twins was carried out, with structural equation modeling used to determine the relative contributions of genetic and environmental factors. Maximum mesiodistal crown dimensions of maxillary and mandibular permanent incisors were recorded from dental models of 298 pairs of twins, including 149 monozygous (MZ) and 149 dizygous (DZ) pairs. The analysis revealed that: (i) an adequate fit required additive genetic and unique environmental components; (ii) augmenting the model with non-additive genetic variation did not lead to a significant improvement in fit; (iii) there was evidence of shared environmental influences in the upper central incisors of males; (iv) the additive genetic component constituted a general factor loading on all eight teeth, with group factors loading on antimeric pairs of teeth; (v) unique environmental effects were mostly variable-specific; (vi) most factor loadings on antimeric tooth pairs could be constrained to be equal, indicating a symmetry of genetic and environmental influences between left and right sides; and (vii) estimated heritability of the incisor mesiodistal dimensions varied from 0.81 to 0.91.

Adolescent

Platelet-activating factor augments meningeal inflammation elicited by Haemophilus influenzae lipooligosaccharide in an animal model of meningitis.

Research into the pathophysiology of bacterial meningitis has suggested a role for various endogenous inflammatory mediators, such as platelet-activating factor (PAF). In the present study, rats were inoculated intracisternally with various doses of PAF, with Haemophilus influenzae lipooligosaccharide (LOS) in high doses (20 ng) alone, and with a low dose of LOS (200 pg) with or without low doses of PAF (25 ng to 2.5 micrograms). Values for cerebrospinal fluid leukocytosis and percent blood-brain barrier permeability to systemically administered 125I-labeled albumin observed after inoculation of low-dose LOS with PAF were greater (P < 0.05) than those observed after inoculation of low-dose LOS alone and not statistically different from those observed after inoculation of high-dose LOS. PAF alone elicited an inflammatory response only at high doses (25 micrograms). These results support the hypothesis that low cerebrospinal fluid PAF concentrations, such as those observed in children with bacterial meningitis, may augment the inflammatory response to the presence of bacteria in the subarachnoid space.

Animals

The endalveolar crest: anatomic and prosthodontic considerations of an overlooked mandibular landmark.

Surgical and prosthodontic treatment of edentulous patients have confirmed the presence of a seldom-described crest of bone situated above and distal to the mylohyoid ridge of the mandible. This study aimed to establish the frequency of occurrence and range of expression of the feature, which it is suggested should be called the endalveolar crest in humans and other primates. Evidence of the crest was noted in all specimens examined although the expression varied. Dissection of fresh and preserved cadavers indicated that the crest provided attachment for part of the superior constrictor muscle and that it may also afford some protection to the lingual nerve in the retromolar region.

Alveolar Process

Adjunctive therapy for bacterial meningitis: rationale for use, current status, and prospects for the future.

Despite the introduction of numerous therapeutic advances, the morbidity and mortality associated with bacterial meningitis remain significant. Research into the pathophysiology of bacterial meningitis has revealed that the inflammatory response resulting from bacterial invasion of the subarachnoid space is due in large part to the activity of host-derived mediators. This inflammatory response is ultimately responsible for the long-term neurological sequelae and death associated with bacterial meningitis. In vitro and in vivo models of bacterial meningitis have identified several points in the inflammatory cascade that may be amenable to therapeutic intervention. Numerous potential therapeutic agents that may limit inflammation of the subarachnoid space have been and are being developed, and trials in animal models and in humans are under way. The judicious use of safe and effective agents with demonstrated efficacy as adjuncts to bactericidal antimicrobial agents in the therapy for bacterial meningitis in humans may improve the prognosis of this disease.

Adrenal Cortex Hormones

Craniofacial patterning in Klinefelter (47 XXY) adults.

Radiographic cephalometry incorporating a pattern profile analysis was used to compare 26 adult Klinefelter males from Finland with first degree adult relatives, 15 males and 14 females. Compared with female relatives, the 47 XXY males were larger in almost all craniofacial linear dimensions, but were similar in facial shape apart from greater mandibular prognathism. Mandibular dimensions in particular differed between the Klinefelter and unaffected males, the corpus length being larger, the ramus shorter and the gonial angle more obtuse in the 47 XXY group. The prominent facial profile, most marked in the mandible, was a dominant feature of the Klinefelter subjects who also displayed a more acute median cranial base angle than each control group. Generally, Klinefelter morphology was marked by greater variability or patterning of the craniofacial structures compared with relatives, possibly due to decreased developmental canalization. It is proposed that the 47 XXY complex may affect endochondral growth in the cranial base, as well as having a direct influence on jaw growth.

Adolescent

Nature and frequency of dental wear facets in an Australian aboriginal population.

The nature and frequency of dental wear facets were studied in a sample of 18-year-old Aborigines, 28 males and 31 females, living at Yuendumu in the Northern Territory of Australia. Facet frequencies were scored indirectly using dental models for all permanent teeth, except third molars, and evidence of non-masticatory tooth grinding in eccentric jaw positions was also recorded. The interplay between attrition and abrasion in an individual over time was assessed by examining facet appearance on serial dental models obtained at approximately yearly intervals from 7 to 25 years of age. Facetting was found to be a very common feature of the Aboriginal dentitions, with frequencies ranging from around 65% for pre-molars to about 90% for molars. Evidence of extreme mandibular movement was noted in 93% of males and 100% of females. The longitudinal observations indicated that wear facet definition varied over time, apparently due to episodes of tooth grinding superimposed on continually-acting abrasive influences. These results show that facetting on teeth associated with extreme mandibular positions and, by inference, the related behaviour of tooth grinding or bruxism are very common features in dentitions of Australian Aboriginals living an essentially non-industrial way of life.

Adolescent

Brief communication: interproximal tooth wear: a new observation.

Microscopic observations were made of wear on the proximal surfaces of tooth crowns of Australian Aboriginals and whites. Typical wear facets displayed well-defined borders within which vertical or near vertical furrows, ranging from about 0.1 to 0.5 mm in width, were noted. Furrows on the interproximal surface of one tooth seemed to "interdigitate" with those on the proximal surface of the adjacent tooth. These observations are not consistent with the commonly-held view that interproximal tooth wear results from a buccolingual movement of adjacent teeth that maintain contact through mesial migration. Vertical or near vertical movement of teeth, possibly including a tipping action, must be an important factor, although the precise nature of the movement requires further investigation.

Humans

Fitting genetic models to Carabelli trait data in South Australian twins.

This study aimed to clarify genetic and environmental contributions to Carabelli trait variation on permanent first molar teeth in a large sample of South Australian twins. Estimates of polychoric correlations were obtained between pairs of monozygous (MZ) and dizygous (DZ) twins for Carabelli data and various gene-environment models fitted by a weighted least-squares approach. The favored model included additive genetic effects together with both a general environmental component and an environmental effect specific to each side. An estimate of heritability around 90% indicated a very strong genetic contribution to observed variation. The pattern of correlations for MZ and DZ data suggested that further studies involving other types of relatives would be worthwhile for detection of possible non-additive genetic effects of dominance or epistasis.

Adolescent

Abrasion: an evolutionary and clinical view.

Abrasion is the type of wear produced on the tooth by the friction of exogenous material forced over the surface by incisive, masticatory and grasping functions. It is one of the four common processes that have affected the morphology of newly erupted teeth from the time they first evolved millions of years ago. While some observers have regarded tooth reduction as pathological, there is evidence from comparative and palaeontological studies which demonstrates that these processes are an essential part of the normal, continually changing relationship between the form and function of the dentition. To understand these precise mechanisms is important if one is to replicate nature's 'intentions' in clinical dental procedures.

Adaptation, Biological

Tooth crown size in 46, X, i (Xq) human females.

Permanent tooth crown sizes of six Finnish females with a 46, X, i(Xq) chromosome constitution (isochromosome for the long arm of the X chromosome) were measured from dental casts and compared with those of normal women, first-degree female relatives and 45, X females. Crown diameters of the 46, X, i(Xq) females were not only smaller than in the normal women but even smaller than the 45, X females. These findings can be considered indirect evidence that X chromosome gene(s) for tooth crown growth are most probably located on the short arm.

Chromosome Aberrations

Concepts of occlusion: Australian evidence.

Longitudinal studies of aboriginal children over a 20-year period have drawn attention to the wide variation in morphological features of the dentition and the way in which occlusal relationships develop. This paper summarizes some important determinants of optimal occlusal development, namely, tooth size relationships within and between dentitions, the patterns of alveolar growth, and tooth migrations during the transition from primary to permanent teeth and the nature of growth changes in the dental arches. Dental occlusion constantly changes throughout life in response to changing functional requirements. Observations limited to cross-sectional material provide an incomplete, and sometimes misleading, concept of dental occlusion and masticatory function.

Adult

Occlusal variation in Australian aboriginals.

Variation of dental occlusion around established norms has frequently been related to industrialized or modernized life habits. This tendency has been tested among samples (n = 48) of older (originally nomadic) and younger (settled and rationed) Australian Aboriginals. Although significant differences are found in incisor relation traits, tooth malalignment, and relative arch breadth, these are slight compared to some other studies of peoples undergoing one-generation dietary westernization. Reasons for this might relate to concomitantly subtle differences in diet or masticatory habits, genetic buffering, attrition gradient, tooth size, biased sampling according to tooth retention, or fluoride in water supplies.

Adult

Dental arch morphology in south Australian twins.

Fourth-order polynomials were used to represent dental arch morphology in 29 monozygous and 19 dizygous like-sexed twin pairs, and in 45 unrelated individuals. The polynomial coefficients provided an accurate description of dental arch morphology with the quadratic (chi 2) and quartic (chi 4) terms reflecting arch shape and the linear (chi) and cubic (chi 3) terms summarizing asymmetry. There were no significant differences between the groups in either the quadratic or quartic terms. Values of correlations between polynomial terms indicated that there was no consistent relationship between maxillary and mandibular arch shape or asymmetry. Intraclass correlations between twins suggested that genetic factors contributed to variation in maxillary arch shape and to a lesser extent to variation in mandibular arch shape but not to arch asymmetry.

Adolescent

Variability of palatal dimensions in South Australian twins.

Estimates of genetic contributions to variability in three palatal dimensions were obtained from a sample of 70 pairs of South Australian twins aged between 11 and 26 years. Palatal width and length were measured directly from dental models, while palatal height was assessed indirectly from moiré contourographs. For each of the three palatal variables there was evidence of significant genetic variance, with heritability estimates for palatal width and height generally exceeding those for palatal length. Furthermore, palatal height measurements displayed greatest relative variability and strongest correlation between monozygous twins (r = 0.95), suggesting that this dimension could be useful as an additional comparative feature in forensic odontological investigations.

Adolescent