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Biomedical subjects

M T Williams

Publications and source records attributed to M T Williams.

At least 19 recordsLinked to original sources
PubMed2006

[Imaging in adult chronic otitis].

Chronic otitis media (COM) can be divided into two subtypes: COM with cholesteatoma (including precholesteatomatous states) is an aggressive form of otitis. Surgical treatment is mandatory because of the risk for labyrinthine or cerebromeningeal complications. CT is very important in the preoperative work-up (extension of cholesteatoma, anatomic variants). In patients who have undergone middle ear surgery, CT and presently MRI play an increasing role in the detection of recurrent or relapsing cholesteatoma. COM without cholesteatoma does not have an osteolytic potential, but may leave auditive sequelae that in selected cases may warrant surgical treatment to improve hearing. CT is useful in the etiological work-up of patients with severe hypoacusis. CT also plays an important role in cases of surgical failure, to detect a dislocation of the ossiculoplasty or impairment of the middle ear caused by fluid effusion. The objective of this paper is to specify the indications, the results and the limits of pre- and postoperative imaging in COM.

Adult↗
PubMed2006

Phosphodiesterase 1B differentially modulates the effects of methamphetamine on locomotor activity and spatial learning through DARPP32-dependent pathways: evidence from PDE1B-DARPP32 double-knockout mice.

Mice lacking phosphodiesterase 1B (PDE1B) exhibit an exaggerated locomotor response to D-methamphetamine and increased in vitro phosphorylation of DARPP32 (dopamine- and cAMP-regulated phosphoprotein, M r 32 kDa) at Thr34 in striatal brain slices treated with the D1 receptor agonist, SKF81297. These results indicated a possible regulatory role for PDE1B in pathways involving DARPP32. Here, we generated PDE1B x DARPP32 double-knockout (double-KO) mice to test the role of PDE1B in DARPP32-dependent pathways in vivo. Analysis of the response to d-methamphetamine on locomotor activity showed that the hyperactivity experienced by PDE1B mutant mice was blocked in PDE1B-/- x DARPP32-/- double-KO mice, consistent with participation of PDE1B and DARPP32 in the same pathway. Further behavioral testing in the elevated zero-maze revealed that DARPP32-/- mice showed a less anxious phenotype that was nullified in double-mutant mice. In contrast, in the Morris water maze, double-KO mice showed deficits in spatial reversal learning not observed in either single mutant compared with wild-type mice. The data suggest a role for PDE1B in locomotor responses to psychostimulants through modulation of DARPP32-dependent pathways; however, this modulation does not necessarily impact other behaviors, such as anxiety or learning. Instead, the phenotype of double-KOs observed in these latter tasks may be mediated through independent pathways.

Analysis of Variance↗
PubMed2005

Usefulness of delayed postcontrast magnetic resonance imaging in the detection of residual cholesteatoma after canal wall-up tympanoplasty.

OBJECTIVES/HYPOTHESIS: Imaging takes an increasing place in the follow-up of patients who have undergone surgery for cholesteatoma, with computed tomography (CT) as the first line imaging technique. However, in case of complete opacity of the tympanomastoid cavities, CT is not able to differentiate residual cholesteatoma from postoperative scar tissue. The aim of this study was to assess the usefulness of magnetic resonance imaging (MRI) using delayed postcontrast T1-weighted images for the detection of residual cholesteatoma after canal wall-up tympanoplasty (CWU) in cases where CT was not conclusive. STUDY DESIGN: Prospective study. METHODS: MRI, with delayed postcontrast T1-weighted images (30-45 minutes after contrast injection), was performed before revision surgery in 41 consecutive patients who had undergone CWU for cholesteatoma and presenting with a nonspecific complete opacity of the mastoid bowl on CT. In all the cases, imaging results were compared with operative findings at surgical revision. RESULTS: A residual cholesteatoma was found in 19 of 41 patients at revision surgery and was correctly detected on MRI in 17 patients. In the two remaining cases, cholesteatoma pearls smaller than 3 mm were not seen. There was no false-positive case. Statistics were as follows: sensitivity 90%; specificity 100%; positive predictive value 100%; negative predictive value 92%. CONCLUSION: When postoperative CT is not conclusive because of complete opacity of the tympanomastoid cavities, MRI with delayed postcontrast T1-weighted images is a reliable additional technique for the detection of a residual cholesteatoma when its diameter is at least 3 mm.

Adolescent↗
PubMed2005

Transcriptional responses of rat skeletal muscle following hypoxia-reoxygenation and near ischaemia-reperfusion.

AIM: The effect of ischaemia/reperfusion or hypoxia/reoxygenation on gene expression has not been extensively studied. We hypothesized that in skeletal muscle, tissue hypoxia of similar magnitude but induced by different mechanisms would lead to different transcriptional responses. METHODS: Muscle gene transcription was assessed using microarray analysis and reverse transcriptase polymerase chain reaction in 18 rats exposed to regional hind limb near ischaemia/reperfusion (n = 6), hypoxia/reoxygenation (n = 6) or sham operation (n = 6). Hypoxic burden was measured by the area under the PtO(2)-time curve. RESULTS: PtO(2) was reduced in both the near ischaemia/reperfusion and hypoxia/reoxygenation groups. Although the hypoxic burden was similar, the genomic response was different for each condition. Near ischaemia/reperfusion had a greater effect on gene expression than hypoxia/reoxygenation. Using stringent criteria for changes in gene expression (i.e. more than or equal to twofold change vs. control) unique patterns of gene expression could be identified suggesting individualized transcriptional responses to each of these injuries. Several genes, including insulin-like growth factor 1 (IGF-1) and cyclin-dependent kinase inhibitor (p27(Kip1)) were induced by both injury types and these may have potential clinical application as markers of tissue damage. In contrast, no single gene was downregulated by both injury conditions. CONCLUSIONS: The mechanism of skeletal muscle hypoxia has a profound effect on its subsequent transcriptional response. We identified several potential candidates as markers of skeletal muscle ischaemic damage.

Animals↗
PubMed2003

A comparison of the effect of two anaesthetic techniques on surgical conditions during gynaecological laparoscopy.

In a prospective, randomised, controlled trial, we compared the effects of two anaesthetic techniques on surgical conditions during day-case, gynaecological laparoscopic procedures in 40 female patients. Patients were allocated randomly to two groups, either to breathe spontaneously through a laryngeal mask airway or to receive a neuromuscular-blocking agent (NMB) and have the lungs ventilated via a tracheal tube. We then measured the number of attempts of Verres' needle insertion, initial intra-abdominal pressure, time to reach a steady 15 mmHg (1.97 kPa) of intra-abdominal pressure, adequacy of the pneumoperitoneum, operative view and duration of operation. We found that the initial intra-abdominal pressure was higher and the operation time shorter in the laryngeal mask group. The adequacy of the pneumoperitoneum for trocar placement was better in the NMB group. We conclude that the anaesthetic technique of spontaneously breathing through a laryngeal mask airway reduces total operation time. However surgeons should be aware of the different abdominal pressure patterns produced by each anaesthetic technique, and anaesthetists must consider the implications of the anaesthetic technique on surgical safety.

Ambulatory Surgical Procedures↗
PubMed2002

Impaired spatial and sequential learning in rats treated neonatally with D-fenfluramine.

D-Fenfluramine, a serotonin releaser, was administered to neonatal rats on postnatal days 11-20 (a stage of hippocampal development analogous to third trimester human ontogeny). As adults, the D-fenfluramine-treated offspring exhibited dose-related impairments of sequential and spatial learning and reference memory in the absence of sensorimotor impairments. Procedures to minimize stress and to control for other performance effects prior to testing for spatial learning demonstrated that nonspecific factors did not account for the selective effects of D-fenfluramine on learning and memory. Developmental D-fenfluramine-induced spatial and sequential learning deficits are similar to previous findings with developmental MDMA treatment. By contrast, recent findings with developmental D-methamphetamine treatment showed spatial learning deficits while sparing sequential learning. The spatial learning effects common to all three drugs suggest that they may share a common mechanism of action, however, the effects are not related to long-lasting changes in hippocampal 5-HT levels as no differences were found in adulthood. Whether the cognitive deficits are related to the effects of substituted amphetamines on corticosteroids, other aspects of the 5-HT system, or some unidentified neuronal substrates is not known, but the data demonstrate that these drugs are all capable of inducing long-term adverse effects on learning.

Animals↗
PubMed2001

Acute respiratory infection in patients with cystic fibrosis with mild pulmonary impairment: comparison of two physiotherapy regimens.

Chest physiotherapy is an essential part of the management of cystic fibrosis, yet comparatively few studies have investigated the commonly used forms of chest physiotherapy during acute respiratory exacerbations. Fifteen subjects with cystic fibrosis and predominantly mild pulmonary impairment completed a randomised cross-over trial with 24 hours between treatments. The active cycle of breathing techniques (ACBT) assisted by a physiotherapist was compared with the ACBT performed independently by the patient. Measurement outcomes included pulmonary function tests, indirect calorimetry and oximetry parameters. Energy expenditure was not significantly different between the two treatment regimens, though significant improvements in pulmonary function were apparent 24 hours following the therapist-assisted ACBT. In this group of subjects, neither form of treatment proved superior in terms of energy consumption, but a reduction in airways obstruction was observed as a carry-over effect following the therapist-assisted ACBT.

Acute Disease↗
PubMed1999

The associations between adolescent head-on-neck posture, backpack weight, and anthropometric features.

STUDY DESIGN: A Cross-sectional, observational study, examining the effects of backpack weight on adolescent posture. OBJECTIVES: To investigate the response of the craniovertebral angle to backpack load. SUMMARY OF BACKGROUND DATA: There is a widely held belief that repeated carrying of heavy loads, such as school backpacks, places additional stress on rapidly growing adolescent spinal structures, making them prone to postural change. METHODS: Ten volunteer state high schools in metropolitan Adelaide, South Australia, provided 985 students, aged 12 to 18 years and from five different high school years, for this study. Students' posture was measured with and without their school backpack. All data analyses were undertaken per school year level to account for specific load-carrying requirements and spinal development associated with the age group. RESULTS: A significant change in craniovertebral angle was found at every year level, when comparing standing posture with no backpack with posture when carrying a backpack. The change was greatest for the youngest students. Incremental change in craniovertebral angle was not strongly associated with backpack loads. The association became stronger for the oldest girls when controlled for body mass index and for weight. CONCLUSION: The results support a differential postural response per gender and per level of spinal development but also suggest that the craniovertebral angle may not be the most sensitive measure of head-on-neck postural change for adolescents.

Adolescent↗
PubMed1999

Pre-matriculation program at the University of South Florida College of Medicine.

Underrepresented-minority (URM) students at the University of South Florida College of Medicine increased from 4.9% to 10.5% of the total student body from 1991 to 1997. During that period it became clear that some majority and minority students had serious academic difficulties with the first-year curriculum and that a higher proportion of the minority matriculants had difficulties. In response, the college in 1997 created the Summer Pre-matriculation Program to reduce the number of first-year students who had academic difficulty. In the summer before they matriculate in the college, the students complete a six-week program of lectures, small-group discussions, compute-aided instruction, and laboratory instruction in biochemistry, human embryology, and gross anatomy. URM students, non-science majors, and students who have been away from the academic environment (e.g., pursuing medicine as a second career) are given priority for the 20 positions available each year. At the end of the first cohort's first medical school year, the academic performances of program participants and other students were compared, and it was clear that the program participants had performed as well as or slightly better than their counterparts in gross anatomy, biochemistry, and human embryology. Further, the program participants performed at or above the class average in medical school courses for which they had not had targeted instruction during the program. The College of Medicine is committed to diversifying its student body and realizes that diverse students bring varying levels of academic preparation as well as diversity in cultural and academic backgrounds. Concerted efforts such as the pre-matriculation program may be required to normalize the "playing field" at the very outset of medical school and to ensure that every matriculant has an equal opportunity to succeed.

Adult↗
PubMed1999

Short- and long-term consequences of corticotropin-releasing factor in early development.

Corticotropin-releasing factor (CRF) mediates various stress-related responses in adult animals. Little is known about the effects of CRF during early development. Young mammals often vocalize when isolated in novel surroundings. Heightened levels of CRF inhibit vocalizing in isolated rat and guinea pig pups. Still lower levels of CRF may facilitate or permit vocalizing in rat pups. In guinea pigs, CRF appears to move pups from an initial active, to a subsequent passive, stage of behavioral responsiveness. CRF activity prior to birth can also affect the young. Exposing pregnant female rats to stressors during the last trimester of pregnancy alters the morphological and behavioral development of the offspring. Effects of gestational stress can be mimicked by injecting pregnant females with CRF during the last trimester. CRF appears to mediate both short- and long-term responses to stressors during developmental in rodents.

Animals↗
PubMed1998

Vitamin E and lipoic acid, but not vitamin C improve blood oxygenation after high-energy IMPULSE noise (BLAST) exposure.

Exposure to high energy impulse noise (BLAST) caused by explosions, result in structural and functional damage to the hollow organs, especially to the respiratory and auditory systems. Lung damage includes alveolar wall rupture, edema and hemorrhage, and may be fatal. Previous observations at the molecular level using the rat model, suggested that secondary free radical-mediated oxidative stress occurs post exposure resulting in antioxidant depletion and hemoglobin (Hb) oxidation. This study examined whether a short period of pre-exposure supplementation with antioxidants would protect Hb from the effects of BLAST exposure. Six groups of male Sprague-Dawley rats (8/group) were gavaged with 800 IU vitamin E (VE) in 2 ml corn oil, 1000 mg vitamin C (VC) in 2 ml distilled water or 25 mg or (-lipoic acid (LA) in 2 ml corn oil for 3 days. Matched control groups were gavaged with the respective vehicles. On day 4, rats were deeply anesthetized and exposed to a simulated BLAST wave with an average peak pressure of 62 +/- 2 kPa. Rats were euthanized one hour post exposure and blood samples were obtained by cardiac puncture and analyzed using a hemoximeter. Post exposure oxygenation states (HbO2, O2 saturation, and O2 content) were markedly decreased, while reduced-Hb was increased. Supplementation with VE and LA reversed the trend and increased Hb oxygenation, but VC did not. This suggests that a brief dietary loading with pharmacological doses of VE or LA, but not VC shortly before BLAST exposure may be beneficial. Moreover, measurement of blood oxygenation may function as a simple semi-invasive biomarker of BLAST-induced injury applicable to humans.

Animals↗
PubMed1998

Stress during pregnancy alters rat offspring morphology and ultrasonic vocalizations.

Stress during pregnancy, or prenatal stress, is known to alter offspring behavior, morphology and physiology. We found that a heat, light and restraint stressor applied during the third trimester of pregnancy: 1) decreased the weight gain of adult female rats during pregnancy; 2) reduced the weight of pups, as well as the anogenital distance of male offspring, at birth; and 3) increased the number of ultrasonic vocalizations emitted by pups during isolation in a novel environment on Postnatal Day 14. These results closely approximate those we previously observed after peripheral administration of corticotropin-releasing factor to pregnant females during the third trimester. Together, the studies strongly suggest a role for corticotropin-releasing factor and/or other hormones of the hypothalamic-pituitary-adrenal system in mediating some of the effects of gestational stress.

Animals↗
PubMed1997

Plasma cortisol levels of dogs at a county animal shelter.

Plasmacortisol levels were examined to assess the stress of dogs in a county animal shelter. Groups of dogs confined in the shelter for their 1st, 2nd, or 3rd day had higher cortisol levels than did a group maintained in the shelter for more than 9 days. Dogs in the shelter for an intermediate period (Day 4-9) had intermediate levels of cortisol. The cortisol concentrations of dogs during their first day in the shelter were greater than either those of the same dogs on Day 4/5 in the shelter or those of a group of pet dogs sampled in their own homes. There was no overall effect of 20 min of social interaction with a human (e.g., petting) on the plasma cortisol levels of dogs in the shelter on Day 1-3. However, the gender of the petter did affect cortisol levels. Those dogs interacting with a female had lower cortisol concentrations at the end of the session than did dogs interacting with a male. The results suggest that confinement in a public animal shelter produces a prolonged activation of the hypothalamic-pituitary-adrenal axis. Further, it appears that some subtle aspect of interaction with a human may be capable of moderating this response. Possible implications for the welfare of confined dogs, and for the development of behavior problems in dogs obtained from shelters, are discussed.

Animal Welfare↗
PubMed1996

Tuberculosis, AIDS, and death among substance abusers on welfare in New York City.

BACKGROUND: In New York City, the incidence of tuberculosis has more than doubled during the past decade. We examined the incidence of tuberculosis and the acquired immunodeficiency syndrome (AIDS) and the rate of death from all causes in a very-high-risk group--indigent subjects who abuse drugs, alcohol, or both. METHODS: In 1984 we began to study prospectively a cohort of welfare applicants and recipients 18 to 64 years of age who abused drugs or alcohol. The incidence rates of tuberculosis, AIDS, and death for this group were ascertained through vital records and New York City's tuberculosis and AIDS registries. RESULTS: The cohort was followed for eight years. Of the 858 subjects, tuberculosis developed in 47 (5.5 percent), 84 (9.8 percent) were given a diagnosis of AIDS, and 183 (21.3 percent) died. The rates of incidence per 100,000 person-years were 744 for tuberculosis, 1323 for AIDS, and 2842 for death. In this group of welfare clients, the rate of newly diagnosed tuberculosis was 14.8 times that of the age-matched general population of New York City; the rate of AIDS was 10.0 times as high; and the death rate was 5.2 times as high. There was no significant difference in the rate of new cases of tuberculosis between subjects with positive skin tests and those with negative skin tests at examination in 1984. CONCLUSIONS: Among indigent alcohol and drug abusers in New York City, the rates of tuberculosis, AIDS, and death are extremely high. In this population, a single positive or negative skin test does not predict the development of tuberculosis, probably because both anergy and new infections are common. If programs to control tuberculosis and AIDS are to be effective in groups of indigent substance abusers, health services must be integrated into the welfare delivery system.

Acquired Immunodeficiency Syndrome↗
PubMed1995

CRF administered to pregnant rats alters offspring behavior and morphology.

Pregnant rats injected with 20 micrograms of corticotropin-releasing factor (CRF) from day 14 through 21 gained less weight during gestation than did saline-injected controls. The offspring of CRF-injected females differed from the offspring of control females in several ways: males and females weighed less during the first 2 weeks of life, males had shorter anogenital distances at birth, and males and females emitted more ultrasonic vocalizations during isolation in tests at 6 and 14 days of age. These effects are similar to those that have been observed following exposure of pregnant females to stressors, and provide support for the notion that CRF and/or CRF activation of the hypothalamic-pituitary-adrenal axis mediate effects of gestational stress.

Animals↗