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Biomedical subjects

G White

Publications and source records attributed to G White.

At least 55 records · Page 3Linked to original sources

A three dimensional clinical approach for anterior crossbite treatment in early mixed dentition using an Ultrablock appliance: case report.

An 8-year-old girl patient presented to Pediatric Dentistry Department at Tufts University School of Dental Medicine for orthodontic consultation. The patient was in early mixed dentition with anterior crossbite and underdeveloped posterior occlusal vertical. Anterior crossbite correction and proper posterior occlusal vertical were established in 6 months of treatment by using an Ultrablock appliance (a removable Ultrablock appliance followed by fixed Ultrablock appliance) which was designed in three dimensions (horizontal, vertical and transverse) on Denar Witzig articulator. An increase of 5 mm in the posterior occlusal vertical is reported.

Child↗

Clinical evaluation of recombinant factor IX.

The pharmacokinetics, safety, and efficacy of recombinant factor IX (rFIX) have been evaluated in previously treated and untreated patients with hemophilia B. In a study of 56 previously treated patients, there was a total of 1,070 hemorrhages, which required 1,514 infusions of rFIX. Of the 1,070 episodes, 80% resolved after a single rFIX infusion. The majority of the remaining episodes requiring more than 1 infusion were either major or complicated hemorrhages. Eighty-seven percent of the 1,514 infusions were rated by the physicians or patients as providing an excellent or good response. These results are consistent with the efficacy data from other hemophilia product clinical trials. rFIX has also been administered as bolus doses or by continuous infusion in conjunction with 13 surgical procedures. Estimated blood loss during and after surgery was as expected when compared with blood loss for similar procedures in patients without hemophilia, and 97% of the clinical responses during and after surgery were rated by physicians or patients as excellent or good. Pharmacokinetic comparison of rFIX with one plasma-derived product showed a statistically significant lower recovery (28% less) of rFIX. The half-lives between the two products were comparable. Common adverse events associated with rFIX treatment have been comparable to other factor IX products. As expected, there has been no evidence of viral transmission by rFIX.

Drug Evaluation↗

Factor VIII inhibitors in mild and moderate-severity haemophilia A. UK Haemophilia Centre Directors Organisation.

Twenty six patients with mild or moderate haemophilia A and inhibitors are described. The inhibitor was detected at a median age of 33 years, after a median of 5.5 bleeding episodes. This usually following intensive replacement therapy. The median presenting inhibitor titre was antihuman 11.6 BU/ml, antiporcine 1.45 BU/ml. Plasma basal factor VIII level declined from a median of 0.08 IU/ml to 0.01 IU/ml following the inhibitor development. This caused spontaneous bleeding in 22 and a bleeding pattern similar to acquired haemophilia in 17. Bleeding was often severe and caused two deaths. The inhibitor disappeared spontaneously, or following immune tolerance induction, in 16 cases after a median of 9 months (range 0.5-46), with a return to the original baseline VIIIC level and bleeding pattern accompanied inhibitor loss. The inhibitor persisted in the remainder of the cases over a median period of 99 months (range 17-433 months) of follow-up. Inhibitors are an uncommon complication of mild haemophilia which frequently persist and may be associated with severe, life-threatening, haemorrhage. Forty-one percent of treated haemophilic family members had a history of factor VIII inhibitors, suggesting a familial predisposition to develop inhibitors in these kindreds. Sixteen patients from 11 families were genotyped. Seven different missense mutations affecting the light chain were detected and two in the A2 domain. Five patients from three families had a mutation causing a substitution of Trp2229 by Cys in the C2 domain which appears to predispose to inhibitor formation since 7 of the 18 affected individuals have a history of inhibitor development.

Adolescent↗

Sexual behavior changes with vulvar vestibulitis syndrome.

OBJECTIVE: To study the changes in normal sexual behavior that accompany the vulvar vestibulitis syndrome and to gauge an appropriate classification for the resulting sexual dysfunction. STUDY DESIGN: Following full medical screening, questionnaires were administered to assess sexual history, illness behavior and vulvar discomfort. Forty patients who met the criteria of vestibulitis syndrome composed the study cohort. RESULTS: The average duration of reported vulvar pain was 33 months (range, 3-240). The cohort showed no significant differences when compared with normative data on the sexual history form in their level of sexual desire, duration of intercourse or chance of female orgasm with intercourse or masturbation. Patients were: (1) highly likely to experience vulvar pain with intercourse (P < .001), (2) highly likely to have significantly reduced arousal potential (P < .001), (3) highly likely to complain of vulvar symptoms preventing intercourse from occurring (P < .001), (4) highly likely to have a reduced interest in intercourse and to have negative feelings toward it (P < .001); and (5) highly likely to refuse a partner's sexual advances (P < .001). CONCLUSION: In the case of vulvar vestibulitis, the most appropriate Diagnostic and Statistical Manual of Mental Disorders, fourth edition, classification appears to be sexual dysfunction due to a general medical condition.

Adolescent↗

A role for the Ras signalling pathway in synaptic transmission and long-term memory.

Members of the Ras subfamily of small guanine-nucleotide-binding proteins are essential for controlling normal and malignant cell proliferation as well as cell differentiation. The neuronal-specific guanine-nucleotide-exchange factor, Ras-GRF/CDC25Mm, induces Ras signalling in response to Ca2+ influx and activation of G-protein-coupled receptors in vitro, suggesting that it plays a role in neurotransmission and plasticity in vivo. Here we report that mice lacking Ras-GRF are impaired in the process of memory consolidation, as revealed by emotional conditioning tasks that require the function of the amygdala; learning and short-term memory are intact. Electrophysiological measurements in the basolateral amygdala reveal that long-term plasticity is abnormal in mutant mice. In contrast, Ras-GRF mutants do not reveal major deficits in spatial learning tasks such as the Morris water maze, a test that requires hippocampal function. Consistent with apparently normal hippocampal functions, Ras-GRF mutants show normal NMDA (N-methyl-D-aspartate) receptor-dependent long-term potentiation in this structure. These results implicate Ras-GRF signalling via the Ras/MAP kinase pathway in synaptic events leading to formation of long-term memories.

3T3 Cells↗

A cohort study (with re-sampled comparator groups) to measure the association between new NSAID prescribing and upper gastrointestinal hemorrhage and perforation.

This cohort study examined the relationship between newly prescribed NSAIDs (none in the previous six months) and upper gastrointestinal hemorrhage and perforation in Tayside, Scotland. Exposure was classified by prescription duration. The study population consisted of the population of Tayside. A Comparator Group was chosen at random (within age and sex strata). Two hundred re-sampled comparator groups were created. Statistical analyses were carried out by Poisson regression (repeated for each of the re-samples). The analyses controlled for age, sex, prior hospitalization for upper gastrointestinal events, prior endoscopy, and the use of ulcer healing drugs. There were 78,191 subjects in the NSAID group, and 78,207 in each of the comparator groups. The increased risk with NSAIDs was only apparent for subjects without a history of upper gastrointestinal events; univariate rate ratio = 2.76 (1.90, 4.01). The final, re-sampled estimate of NSAID risk was rate ratio = 2.48 (1.87, 3.29).

Adult↗

Bifurcated stent-graft for abdominal aortic aneurysm.

The purpose of this study was to examine bifurcated stent-graft implantation for abdominal aortic aneurysm. Fifty-seven patients were treated and followed with serial computed tomography scans for up to 3 years. Patients were allocated to three groups (first 20, second 20, last 17) according to when the repair was performed. Successful treatment is defined as exclusion of the aneurysm from the circulation, based on contrast computed tomography. Success rates in the three groups were 55%, 70% and 100%. Perigraft leak (endoleak) was present on initial assessment in 4/20, 2/20 and 1/17. Two of these aneurysms ruptured early in the postoperative period. Thereafter, leaks were sought and treated aggressively. Kinking and thrombosis occurred in six of the first 20 patients, but did not occur in any of the last 37 patients, in whom the graft limbs were routinely stent-supported throughout. Infrarenal implantation in very a short neck (< 10 mm), or a thrombus-lined neck was associated with proximal stent migration. In conclusion, changes in patient selection and technique have led to a steady rise in the short-term success rate of the stent-grafted implantation.

Aneurysm, Ruptured↗

Ethanol inhibition of N-methyl-D-aspartate-activated current in mouse hippocampal neurones: whole-cell patch-clamp analysis.

1. The action of ethanol on N-methyl-D-aspartate (NMDA)-activated ion current was studied in mouse hippocampal neurones in culture using whole-cell patch-clamp recording. 2. Ethanol inhibited NMDA-activated current in a voltage-independent manner, and did not alter the reversal potential of NMDA-activated current. 3. Concentration-response analysis of NMDA- and glycine-activated current revealed that ethanol decreased the maximal response to both agonists without affecting their EC50 values. 4. The polyamine spermine (1 microM) increased amplitude of NMDA-activated current but did not alter the percentage inhibition of ethanol. 5. Compared to an extracellular pH of 7.0, pH 6.0 decreased and pH 8.0 increased the amplitude of NMDA-activated current, but these changes in pH did not significantly alter the percentage inhibition by ethanol. 6. The sulphydryl reducing agent dithiothreitol (2 mM) increased the amplitude of NMDA-activated current, but did not affect the percentage inhibition by ethanol. 7. Mg2+ (10, 100, 500 microM), (5, 20 microM) or ketamine (2, 10 microM) decreased the amplitude of NMDA-activated current, but did not affect the percentage inhibition by ethanol. 8. The observations are consistent with ethanol inhibiting the function of NMDA receptors by a non-competitive mechanism that does not involve several modulatory sites on the NMDA receptor-ionophore complex.

Animals↗

Establishing a programme for continuous ambulatory infusion chemotherapy.

BACKGROUND: The development of venous access devices (VADs) and portable infusion pumps has enabled chemotherapy to be administered continuously within the home environment. AIM: The objective of this study was to describe the experience of establishing an ambulatory chemotherapy programme for patients receiving protracted infusions (PVIs) of 5-fluorouracil (5-FU). METHODS: The files of all patients receiving PVI 5-FU as a component of their treatment for gastrointestinal malignancy were reviewed. The types of VADs, infusion pump systems and their management were documented. Information packages and education programmes were developed for patients. RESULTS: Seventy-four patients with gastrointestinal cancer were studies. At the end of the period the Portacath was the preferred VAD, while both pumps used were found to have advantages and disadvantages. The choice of pump was decided more by patient preference than systematic differences in performance of the pumps. CONCLUSIONS: The findings in this review confirm that, with close attention to the potential pitfalls of ambulatory chemotherapy, an acceptable service can be provided.

Adult↗

Lactone modulation of the gamma-aminobutyric acid A receptor: evidence for a positive modulatory site.

The gamma-aminobutyric acid-A (GABA(A)) receptor complex is allosterically modulated by a variety of substances, some of clinical importance. Barbiturates and neurosteroids augment GABA-currents and also directly gate the channel. A variety of gamma-butyrolactone analogues also modulate GABA-induced currents, with some potentiating and others inhibiting. Because several gamma-thiobutyrolactone analogues have biphasic effects on GABA currents, experiments with wild-type and picrotoxinin-insensitive GABA(A) receptors were performed to analyze whether some gamma-thiobutyrolactones interact with two distinguishable sites on the GABA(A) receptor. beta-Ethyl-beta-methyl-gamma-thiobutyrolactone inhibited GABA-induced currents at low concentrations (0.001-1 mM), but potentiated GABA-induced currents at higher concentrations (3-10 mM) in wild-type alpha1beta2gamma2-subunit containing ionophores. The related alpha-ethyl-alpha-methyl-gamma-thiobutyrolactone potentiated submaximal GABA currents in wild-type receptors at both low and high concentrations (0.1-10 mM). Mutations in the second transmembrane domain of alpha1, beta2, or gamma2 conferred picrotoxinin-insensitivity onto GABA(A) receptor complexes. When these mutated alpha1, beta2, or gamma2 subunits were incorporated into the receptor complex, beta-ethyl-beta-methyl-gamma-thiobutyrolactone potentiated GABA currents over the entire concentration range (0.1-10 mM). Neither the potentiating activity nor the EC50 of alpha-ethyl-alpha-methyl-gamma-thiobutyrolactone changed in the mutant receptors. Further studies demonstrated that the mutations did not affect the EC50 of chlordiazepoxide or phenobarbital. These and our earlier results identify a modulatory site on the GABA(A) receptor distinct from that interacting with barbiturates, benzodiazepines, and steroids. Additionally, they show that the gamma-butyrolactones probably interact at two different sites on the ionophore to produce opposite effects on GABA-mediated current.

4-Butyrolactone↗

Evaluation of endovascular abdominal aortic aneurysm repair: anatomical classification, procedural success, clinical assessment, and data collection.

PURPOSE: To detail a methodology for evaluation of endovascular abdominal aortic aneurysm (AAA) repair that has been achieved through consensus of an international multidisciplinary team of investigators. METHODS: This schema features an anatomical classification for AAAs, a definition of procedural success, and a procedure for clinical assessment, as well as the necessary data collection forms. Patient data include demographics, procedural and clinical success, complications, and follow-up. Procedural details can be related to anatomic situations, comorbid processes, devices, and effective aneurysmal exclusion. RESULTS: These data would allow assessment of the procedures, physician learning curves, procedural indications, techniques, methodologies, the relationship of indications to success and complications, devices and subsequent graft patency, and aneurysmal exclusion. CONCLUSIONS: The use of this standardized data collection system could enable physicians and industry to better understand endovascular AAA repair and ultimately improve patient care.

Aortic Aneurysm, Abdominal↗

The vestibulitis syndrome. Medical and psychosexual assessment of a cohort of patients.

OBJECTIVE: To study medical, psychosexual, personality and relationship parameters and the resulting illness behavior and psychopathology in patients with the vestibulitis syndrome. STUDY DESIGN: Following full medical screening, questionnaires were administered that included assessment of vulvar pain, sexual history, personality, depression and illness behavior. The 50 patients who met the diagnostic criteria of vestibulitis syndrome formed the cohort of this study. RESULTS: Medical and psychological conditions most frequently reported included vulvovaginal candidiasis (96%), premenstrual syndrome (85%), dysmenorrhea (85%), urologic symptoms (67%), depression (60%), change in body image (63%) and suicidal ideation (57%). The mean duration of dyspareunia-associated vulvar pain was 85 months (range, 2-480), with an associated decrease in sexual interest, desire and activity (91%). Although patients satisfied a number of somatization disorder criteria related to age, course of the condition, gastrointestinal symptoms, sexual problems and multiple pain sites, there was insufficient evidence for such a diagnosis. Patients scored high on personality scales, including organization, concern about mistakes and personal standards. CONCLUSION: Common medical profiles, personality traits and psychosexual problems highlight the parallelism between the vestibulitis syndrome and somatization disorders, but subtle variations allow differentiation on clinical assessment.

Adult↗

Establishing the diagnosis of vulvar vestibulitis.

OBJECTIVE: To study the pelvic floor electromyographic (EMG) responses of a cohort of patients diagnosed with vulvar vestibulitis. STUDY DESIGN: Following full medical and laboratory workup, patients with vestibulitis were given pelvic floor EMG. Results were compared with the collated data, termed the "nonmorbid EMG pelvic floor response," derived from a study control group of 50 symptomless subjects. Six aspects of the EMG response were examined: resting baseline, contractile potential, resting standard deviation, recruitment, recruitment recovery and power spectral analysis. RESULTS: As compared to the study control group, the cohort demonstrated elevated resting baseline above 2.0 microV) in 23 (71%); poor contractile potential, < 17 microV, in 20 (65%); elevated resting standard deviation, > 0.20, in 30 (93%); slow to poor recruitment recovery after contraction, > or = 0.2 seconds in 27 (86%) and low frequency, < 115 Hz in 22 (69%). CONCLUSION: The study confirmed that of vestibulitis patients, 88% will show at least three of the above altered criteria and that the diagnosis can be confirmed by: (1) the instability of muscle, (2) poor muscle recovery after contraction, and (3) elevated resting baseline plus one other optional criterion, either (4) reduced frequency or (5) reduced muscle contraction strength.

Adult↗

Clinical morphology of the mesial fossa of the maxillary first permanent molar in relation to operative dentistry.

The purpose of this in vivo study was to identify a previously unreported occlusal enamel ridges in the mesial fossa of the maxillary first permanent molars by using caries detector dye. Seventy two maxillary right and left first permanent molars of thirty-six patients were examined in this study. Horizontal linear measurements in millimeters, location, and shape of the occlusal ridge in the mesial fossa were examined clinically and were compared to the transverse ridge in a percentage form. Five occlusal enamel ridges with different locations, and pathways were detected in addition to the transverse ridge, two major ridges (> 33.33% of the transverse ridge) and three minor ridges (< 33.33%) of the transverse ridge). There were symmetrical patterns of the ridges between right and left maxillary first permanent molars (80.5%).

Contraindications↗

Exposure to passive smoking and other predictors of reduced nasal volume in children 7 to 12 years old.

The purpose of this study was to assess the nasal volume and the cross-sectional areas of the nose in 7 to 12 year old children, and to identify factors that may influence those parameters. Specifically we investigated the effect of passive smoking at home, body mass, presence of allergies, and history of removal of the tonsils, controlling for the age, gender and race of the child. Fifty-four children participated in the study. Five consecutive nasal measurements were taken from each nostril in one visit, using the acoustic reflection technique (acoustic rhinometry). The nasal volume and the cross-sectional area were computed from the nasal readings. We observed that the minimal cross sectional area is located at the laminal valve, which has been considered one of the main anatomical structures that affect the regulation of breathing in the anterior part of the nose. We also concluded that body mass and exposure to environmental tobacco by-products play a significant role in determining reductions in a child's nasal volume. The clinical significance of such a finding and its effect to the normal craniofacial development of a growing child may force parents to reconsider smoking while at home.

Airway Obstruction↗

Different types of Na+ and A-type K+ currents in dorsal root ganglion neurones innervating the rat urinary bladder.

1. Whole-cell patch-clamp recording in combination with axonal tracing techniques was used to examine the electrical properties of afferent neurones innervating the urinary bladder of the adult rat. Individual bladder afferent cells were labelled by Fast Blue (FB), injected into the bladder wall. 2. Passive and active electrical parameters at room temperature (20-22 degrees C) in FB-labelled bladder afferent neurones were comparable with those in unlabelled neurones. Unselected dorsal root ganglion (DRG) neurones as well as bladder afferent neurones exhibited two different types of action potential: high-threshold humped spikes in small-sized neurones and low-threshold narrow spikes in large-sized neurones. 3. The majority (70%) of bladder neurones which were small in size expressed high-threshold tetrodotoxin (TTX)-resistant Na+ channels and slow-inactivating A-type K+ channels (KA), which were available at the resting membrane potential, whereas large-sized DRG neurones had low-threshold TTX-sensitive Na+ channels and fast-inactivating KA channels, which were almost completely inactivated at the resting membrane potential. 4. Half-maximal conductances of activation of TTX-resistant and TTX-sensitive Na+ currents were obtained at -10.3 and -25.3 mV, respectively. The TTX-resistant and TTX-sensitive Na+ currents were half-inactivated at -25.3 and -56 mV, respectively. 5. In the TTX-resistant neurones, the transient outward K+ current (A-type current, IA) with half-maximal conductance at -40.8 mV was half-inactivated at -77.5 mV, and exhibited slower decaying kinetics (mean decay constant (tau), 240 ms) than the IA current recorded from the large-sized TTX-sensitive neurones (mean tau, 20 ms). 6. These results suggest that the majority of bladder afferent neurones have high electrical thresholds for spike activation due to the TTX-resistant Na+ current and the slow-inactivating IA current, which reflect the large population of unmyelinated high-threshold C fibre afferents that innervate the urinary bladder.

Action Potentials↗