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Biomedical subjects

D A Richardson

Publications and source records attributed to D A Richardson.

At least 19 recordsLinked to original sources

Prevalence of hypotensive disorders in older patients with a pacemaker in situ who attend the Accident and Emergency Department because of falls or syncope.

AIMS: To ascertain the proportion of adults with a pacemaker in situ attending the Accident and Emergency Department because of syncope or unexplained falls and the cause of index symptoms in these patients, including the prevalence of hypotensive syndromes. METHODS AND RESULTS: Patients presenting to the Accident and Emergency Department with unexplained syncope or non-accidental falls, who had a pacemaker in situ, were studied. Eligible patients had cardiovascular assessment (morning orthostatic blood pressure measurement, heart rate and BP measurements during carotid sinus stimulation (supine and upright), head-up tilt at 70 degrees for 40 min), assessment of haemodynamics during fixed mode pacing and gait and balance assessment. Of 5863 patients screened, 13.5% had unexplained syncope or a non-accidental fall; of these only 3% (26 patients) had pacemakers in situ. Of 18 study patients (82 +/- 8 years), 10 were female. Sixteen had a hypotensive diagnosis. Seven had more than one attributable hypotensive diagnosis. Five of 13 with vasodepressor carotid sinus syndrome had no previous diagnosis of carotid sinus hypersensitivity. No patients had vasovagal syncope induced during passive head-up tilt testing. CONCLUSION: It is rare for patients who attend the Accident and Emergency Department because of syncope or unexplained falls to have a pacemaker in situ. In those who do, hypotensive disorders are a common finding.

Accidental Falls↗

How reproducible is the cardioinhibitory response to carotid sinus massage in fallers?

AIMS: To ascertain the reproducibility of the cardioinhibitory subtype of carotid sinus hypersensitivity (CICSH) in fallers. METHODS AND RESULTS: One hundred and seventy-five subjects with CICSH and unexplained or recurrent falls were randomized to pacemaker implantation or control. Sixty-four control subjects (61% female, mean age 71.8 years, median 2 falls in the previous year) completed one-year follow-up and had carotid sinus massage (CSM) performed on 4 occasions (twice before randomization, at 6 months and 1 year following randomization). CSM was performed sequentially on the right and then left sides, initially supine and then upright at 70 degrees head-up tilt by the same investigator. On each occasion CSM was discontinued once CICSH was demonstrated. CICSH was demonstrated on 82% of occasions, 75% on right CSM and 77% whilst the subject was supine. Before randomization, and at 6 months and 1 year, 91%, 67%, and 70% of subjects had reproducible CICSH respectively. Half had CICSH on all 4 occasions. Only 17% had a consistent response on the same side in the same position. CONCLUSIONS: In the majority of subjects CICSH is reproducible and this is more likely shortly after the initial response. However the cardioinhibitory response to CSM is inconsistent both in side elicited and subject position.

Accidental Falls↗

Carotid sinus syndrome: a modifiable risk factor for nonaccidental falls in older adults (SAFE PACE).

OBJECTIVES: The aim of the study was to determine whether cardiac pacing reduces falls in older adults with cardioinhibitory carotid sinus hypersensitivity (CSH). BACKGROUND: Cardioinhibitory carotid sinus syndrome causes syncope, and symptoms respond to cardiac pacing. There is circumstantial evidence for an association between falls and the syndrome. METHODS: A randomized controlled trial was done of consecutive older patients (>50 years) attending an accident and emergency facility because of a non-accidental fall. Patients were randomized to dual-chamber pacemaker implant (paced patients) or standard treatment (controls). The primary outcome was the number of falls during one year of follow-up. RESULTS: One hundred seventy-five eligible patients (mean age 73 +/- 10 years; 60% women) were randomized to the trial: pacemaker 87; controls 88. Falls (without loss of consciousness) were reduced by two-thirds: controls reported 669 falls (mean 9.3; range 0 to 89), and paced patients 216 falls (mean 4.1; range 0 to 29). Thus, paced patients were significantly less likely to fall (odds ratio 0.42; 95% confidence interval: 0.23, 0.75) than were controls. Syncopal events were also reduced during the follow-up period, but there were much fewer syncopal events than falls-28 episodes in paced patients and 47 in controls. Injurious events were reduced by 70% (202 in controls compared to 61 in paced patients). CONCLUSIONS: There is a strong association between non-accidental falls and cardioinhibitory CSH. These patients would not usually be referred for cardiovascular assessment. Carotid sinus hypersensitivity should be considered in all older adults who have non-accidental falls.

Accidental Falls↗

ATR/ATM-mediated phosphorylation of human Rad17 is required for genotoxic stress responses.

Genotoxic stress triggers the activation of checkpoints that delay cell-cycle progression to allow for DNA repair. Studies in fission yeast implicate members of the Rad family of checkpoint proteins, which includes Rad17, Rad1, Rad9 and Hus1, as key early-response elements during the activation of both the DNA damage and replication checkpoints. Here we demonstrate a direct regulatory linkage between the human Rad17 homologue (hRad17) and the checkpoint kinases, ATM and ATR. Treatment of human cells with genotoxic agents induced ATM/ATR-dependent phosphorylation of hRad17 at Ser 635 and Ser 645. Overexpression of a hRad17 mutant (hRad17AA) bearing Ala substitutions at both phosphorylation sites abrogated the DNA-damage-induced G2 checkpoint, and sensitized human fibroblasts to genotoxic stress. In contrast to wild-type hRad17, the hRad17AA mutant showed no ionizing-radiation-inducible association with hRad1, a component of the hRad1-hRad9-hHus1 checkpoint complex. These findings demonstrate that ATR/ATM-dependent phosphorylation of hRad17 is a critical early event during checkpoint signalling in DNA-damaged cells.

Animals↗

A collapsed non-native RNA folding state.

At physiological Mg2+ concentrations, the catalytic core of the bI5 group I intron does not fold into its native structure. In contrast, as judged by the global size, this RNA undergoes structural collapse at Mg 2+ concentrations much lower than required to drive folding of the RNA completely to the native state. The bI5 RNA therefore exists in equilibrium between expanded and collapsed non-native states. The activation energy of RNA folding from the collapsed state to the native state is negligible and the reaction is not accelerated by the addition of urea. This collapsed state is thus distinct from the kinetic traps observed during folding of other large RNAs. The collapsed non-native state forms readily in the case of bI5 RNA and may exist generically prior to assembly of other ribonucleoprotein holoenzymes, such as the ribosome.

Base Sequence↗

Complications of carotid sinus massage--a prospective series of older patients.

BACKGROUND: there is a causal association between carotid sinus hypersensitivity, falls and syncope in elderly subjects. Neurological complications during carotid sinus massage have been reported in case studies and two retrospective series. Our aim was prospectively to ascertain the incidence of complications occurring after carotid sinus massage performed for diagnostic purposes in a consecutive series of patients. METHODS: 1000 consecutive subjects aged 50 years or over who attended the accident and emergency department with syncope or 'unexplained' falls had carotid sinus massage. Carotid sinus massage was performed for 5 s on the right and then left sides both supine and upright (70 degrees head-up tilt) with continuous heart rate and phasic blood pressure recording. Contraindications to carotid sinus massage were the presence of a carotid bruit, recent history of stroke or myocardial infarction or previous ventricular tachyarrhythmia. RESULTS: complications occurred in nine patients immediately after cessation of carotid sinus massage. Eight had transient neurological complications possibly attributable to carotid sinus massage: visual disturbance, 'pins and needles' and sensation of finger numbness in two cases each, leg weakness in one and sensation of 'being drunk' in one. All transient complications resolved within 24 h. In one patient mild weakness of the right hand persisted. CONCLUSIONS: no subjects had cardiac complications and 1% had possible neurological symptoms, which resolved in most cases. Persistent neurological complications are uncommon, occurring in 1:1000 patients (0.1%) or 1: 3805 episodes of carotid sinus massage (0.03%).

Accidental Falls↗

Diagnosis of carotid sinus hypersensitivity in older adults: carotid sinus massage in the upright position is essential.

OBJECTIVE: To assess the diagnostic value of supine and upright carotid sinus massage in elderly patients. DESIGN: Prospective controlled cohort study. SETTING: Three inner city accident and emergency departments and a dedicated syncope facility. PATIENTS: 1375 consecutive patients aged > 55 years presenting with unexplained syncope and drop attacks; 25 healthy controls. INTERVENTIONS: Bilateral supine carotid sinus massage, repeated in the 70 degrees head up tilt position if the initial supine test was not diagnostic of cardioinhibitory and mixed carotid sinus hypersensitivity. MAIN OUTCOME MEASURES: Diagnosis of cardioinhibitory or mixed carotid sinus hypersensitivity; clinical characteristics of supine v upright positive groups. RESULTS: 226 patients were excluded for contraindications to carotid sinus massage. Of 1149 patients undergoing massage, 223 (19%) had cardioinhibitory or mixed carotid sinus hypersensitivity; 70 (31%) of these had a positive response to massage with head up tilt following negative supine massage (95% confidence interval, 25.3% to 37.5%). None of the healthy controls showed carotid sinus hypersensitivity on erect or supine massage. The initially positive supine test had 74% specificity and 100% sensitivity; these were both 100% for the upright positive test. The clinical characteristics of the supine v upright positive subgroups were similar. CONCLUSIONS: The diagnosis of carotid sinus hypersensitivity amenable to treatment by pacing may be missed in one third of cases if only supine massage is performed. Massage should be done routinely in the head up tilt position if the initial supine test is negative.

Aged↗

Pelvic floor electrical stimulation for genuine stress incontinence: who will benefit and when?

This study sought to determine the characteristics of women in whom pelvic floor electrical stimulation will reduce stress urinary incontinence. It also evaluates how long electrical stimulation should be used before significant improvements are seen in clinical outcomes. Subjects with genuine stress incontinence were enrolled into a multicenter non-randomized trial. They used electrical stimulation for 15 minutes twice daily or every other day for 20 weeks. At the end of 20 weeks, those with a 50% reduction in leakage episodes on voiding diary ('responders') were compared with those who did not show a 50% reduction ('non-responders'). Thirty-one subjects were enrolled and 28 completed the study. After the treatment period, 19 subjects were defined as responders and 9 as non-responders. There were no significant differences between the two groups in baseline demographics (e.g. age, parity, largest birth weight etc.) other than body mass index (greater in nonresponders). Significant subjective and objective improvements were noted among responders by 10 and 14 weeks, respectively. Compliance was higher in responders during weeks 12-15 of the study (P=0.05). It was concluded that a minimum of 14 weeks of pelvic floor stimulation was necessary before significant objective improvements were seen. Body mass index and patient compliance may affect success.

Electric Stimulation Therapy↗

Pelvic floor electrical stimulation for the treatment of urge and mixed urinary incontinence in women.

OBJECTIVES: To determine the efficacy of daily or every-other-day electrical stimulation in treating detrusor instability (urge) or urge plus genuine stress (mixed) urinary incontinence in women. METHODS: A multicenter, prospective, nonrandomized study enrolled subjects with urge and mixed urinary incontinence assigned to daily or every-other-day treatments (15 minutes twice daily) using pelvic floor stimulation. Outcome measures assessed were (1) leakage episodes, nocturnal episodes, voiding frequency, total voids, and pad count, and (2) patient subjective assessment and quality of life. RESULTS: Seventy-two subjects were enrolled. Sixty-eight subjects completed the 20-week protocol: 33 treated daily and 35 treated every other day. The entire study group (n = 68) experienced a significant decrease in total leaks (P < 0.001), nocturnal episodes (P = 0.001), pad count (P = 0.002), and total voids (P = 0.003) and on visual analog scales. Sixty-nine percent (n = 46) of subjects with urge or mixed incontinence were cured or improved by at least 50%, with 28% (n = 19) being cured. There were no significant differences between daily and every-other-day users. Nonresponse was correlated with number of previous therapies (P < 0.001) and number of vaginal deliveries (P = 0.007). Overall, subjects were 93% compliant with device use, and 72% (n = 47) were satisfied with the therapy. CONCLUSIONS: Twenty weeks of pelvic floor electrical stimulation therapy is effective in treating urge and mixed urinary incontinence, regardless of daily or every-other-day treatments.

Adult↗

Assessing medical students' perceptions of mistreatment in their second and third years.

PURPOSE: To study medical students' perceptions of mistreatment in their second and third years of training. METHOD: A questionnaire was distributed at Wayne State University School of Medicine to the class of 1993 at the end of its third year and to the class of 1994 at the end of its second and third years. The students were asked if they had been subjected to various forms of mistreatment; the third-year students were asked to rate their perceptions of each clinical department's response to them on the basis of gender and race-ethnicity, as well as their overall treatment. The students also completed demographic information about age, gender, and marital status, number of children, and race-ethnicity. Results were analyzed using chi-square statistics, multivariate statistical analyses, analyses of variance, and Duncan's post-hoc comparisons. RESULTS: The response rate for the class of 1993 was 71.5%; response for the class of 1994 were 66.9% in their second year and 75.2% in their third year; 41.7% were women, and the racial-ethnic breakdown was 71.2% white/Caucasian, 11.7% black/African American and 16.8% other. There was a significant difference between the percentages of second-year and third-year students reporting any experience of mistreatment (37.2% vs 75.8%, p < .001). Canonical correlation analysis revealed bias in the third year based on gender (p < .0001) and race-ethnicity (p < .0002); both variates were related to sexual humor. The students' perceptions of mistreatment were lowest for family medicine and highest for obstetrics-gynecology and surgery. Perceptions of mistreatment in departments varied significantly by gender and race-ethnicity. The nonwhite males reported the least favorable treatment in most departments. CONCLUSION: Marked variability in the students' perceptions of mistreatment within departments suggest that a variety of approaches will be required to improve the medical training environment.

Education, Medical, Undergraduate↗

Prevalence of cardioinhibitory carotid sinus hypersensitivity in patients 50 years or over presenting to the accident and emergency department with "unexplained" or "recurrent" falls.

To study the prevalence of Cardioinhibitory Carotid Sinus Hypersensitivity (CICSH) in patients 50 years or over presenting to casualty with "unexplained" or "recurrent" falls. The prospective study was from October 1, 1995 to April 30, 1996 in the Inner City Accident and Emergency Departments, Newcastle Upon Tyne, U.K. Ten thousand four hundred forty-three patients 50 years and over presented, of which 4,051 (39%) were fallers. Fallers were excluded if they lived over 15 miles from the hospital (81), were registered blind (17), were unable to speak English (22), were unable to previously walk (27), if there was a history of only one accidental fall (1,659) or were cognitively impaired (776: Mini Mental State Examination < 24 [30]) or if there was a clear attributable medical diagnosis for the fall (871). Five hundred ninety-eight "unexplained" or "recurrent" fallers (defined as three or more falls in the previous 12 months) were assessed for carotid sinus massage (CSM). One hundred forty-five patients declined CSM (24%), 70 (12%) had relative contraindications to CSM and 13 already had pacemakers in situ (2%). Two hundred seventy-nine underwent CSM, of whom 65 had CICSH (23%), which might be amenable to treatment with pacemakers. The prevalence of CICSH (a potentially treatable condition) in "unexplained" or "recurrent" fallers who present to the accident and emergency department is 23%. A randomized control study to assess benefit from pacemaker intervention in these patients is underway.

Accidental Falls↗

Pelvic floor electrical stimulation: a comparison of daily and every-other-day therapy for genuine stress incontinence.

OBJECTIVES: To compare the effectiveness of daily and every-other-day electrical stimulation in treating genuine stress incontinence. METHODS: Subjects with genuine stress incontinence were enrolled in a multicenter, prospective, nonrandomized study and underwent daily or every-other-day pelvic floor stimulation treatments for 15 minutes twice a day. Outcome measures assessed were (1) leakage episodes and pad count; (2) leakage amount, and (3) subject subjective assessment and quality of life. Thirteen subjects treated daily and 15 treated every other day completed the 20-week protocol. One-year follow-up data were available for 21 subjects. RESULTS: No significant differences in primary outcome variables were found between the groups. Subjects treated every other day had significant decreases in total leakage episodes (P = 0.04), pad count (P = 0.04), total voids (P = 0.02), and visual analog scale scores, with stress incontinence cured or improved by 50% in 73% (n = 11). Subjects treated every day had significant decreases in urge episodes (P = 0.03), pad count (P = 0.05), and visual analog scale scores, with 62% (n = 8) cured or improved by 50%. Compliance was higher for subjects treated every other day (P = 0.05). Satisfaction with therapy was 75% (n = 10) for daily treatment and 77% (n = 12) for every-other-day treatment. At 1 year, 70% (n = 7) of subjects who continued device use maintained their cure or improvement status. CONCLUSIONS: Both daily and every-other-day therapy with pelvic floor electrical stimulation are effective in treating genuine stress incontinence. Subjects who continue device use maintain a higher curve or improvement rate.

Electric Stimulation↗

Stability of orthognathic surgery: a review of rigid fixation.

The use of rigid fixation with orthognathic surgery was greeted by both excitement and healthy concern when it began to find its way into the literature approximately 10 years ago. The purpose of this paper is to review the literature and make comments based on the experience of the senior author on whether one of the early premises was true. Has rigid fixation improved stability with orthognathic surgery? The authors chose to examine mandibular advancements treated with a bilateral sagittal split osteotomy and maxillary osteotomies treated with a Le Fort I osteotomy. When compared to wire osteosynthesis, rigid fixation has improved stability; however, the individual move associated with the osteotomy must be considered. In some cases, auxiliary techniques should be used to ensure stability. Condylar resorption with mandibular advancement continues to be an area of concern.

Bone Plates↗

Ehlers-Danlos syndrome: relationship between joint hypermobility, urinary incontinence, and pelvic floor prolapse.

OBJECTIVE: To compare the incidence of joint hypermobility and prolapse in incontinent and continent women with Ehlers-Danlos syndrome (EDS). METHODS: Forty-six patients with EDS were evaluated by history and physical examination. The degree of joint mobility of shoulder, elbow, wrist, hip, knee, and ankle was evaluated by orthopedic surgeons and physical therapists. Joint range of motion measurements were obtained using an orthopedic goniometer. RESULTS: The two EDS groups, incontinent (n = 28) and continent (n = 18) women, had a statistically similar mean age, weight, and parity (p = NS). In the EDS population overall joint hypermobility averaged 34.3%. Individuals with EDS type 3 had significantly more joint hypermobility than those with type 1 and 2 EDS. However, logistic regression analysis demonstrated no significant relationship between prolapse and joint hypermobility. Wrist dorsiflexion (p < 0.05) and palmar flexion (p = 0.05) were the only variables related to incontinence. CONCLUSION: It has previously been reported that hypermobility was correlated with pelvic floor prolapse. Of 18 joint measures per patient, hypermobility of both wrist dorsiflexion and palmar flexion was associated with symptoms of incontinence. We were unable to document an association between joint hypermobility and prolapse in the EDS population.

Ehlers-Danlos Syndrome↗

Pelvic floor electrical stimulation in the treatment of genuine stress incontinence: a multicenter, placebo-controlled trial.

OBJECTIVE: Our purpose was to determine the efficacy of transvaginal electrical stimulation in treating genuine stress incontinence. STUDY DESIGN: This was a multicenter, prospective, randomized, double-blind, placebo-controlled 15-week trial comparing the use of an active pelvic floor stimulator with a sham device. Thirty-five women used an active unit and 17 control subjects used sham devices. Weekly and daily voiding diaries were recorded throughout the trial. Urodynamic testing, including pad test and subtracted cystometry, was done before and at the end of device use. Pelvic muscle strength was measured at baseline and at the end of the trial. Patients scored their symptoms on visual analog scales and completed quality-of-life questionnaires before and after therapy. RESULTS: Significant improvements from baseline were found in patients using active devices but not in controls. Comparisons of changes from baseline between active-device and control patients showed that active-device patients had significantly greater improvement in weekly (p = 0.009) and daily (p = 0.04) leakage episodes, pad testing (p = 0.005), and vaginal muscle strength (p = 0.02) when compared with control subjects. Significantly greater improvement was also found for both visual analog scores of urinary incontinence (p = 0.007) and stress incontinence (p = 0.02), as well as for subjective reporting of frequency of urine loss (p = 0.002), and urine loss with sneezing, coughing, or laughing (p = 0.02), when compared with controls. Pad testing showed that stress incontinence was improved by at least 50% in 62% of patients using an active device compared with only 19% of patients using sham devices (p = 0.01). Voiding diaries showed at least 50% improvement in 48% of active-device patients compared with 13% of women using the sham device (p = 0.02). No irreversible adverse effects were noted in either group. CONCLUSIONS: Transvaginal pelvic floor electrical stimulation was found to be a safe and effective therapy for genuine stress incontinence.

Double-Blind Method↗

Ethics in gynecologic surgical innovation.

J. Marion Sims' efforts in surgically curing vesicovaginal fistula are retold. The controversy surrounding his surgical innovation on black slaves is discussed in the context of the ethical principles of autonomy, beneficence, and justice. The relevance of his story to modern surgical innovation in incontinence surgery is emphasized in a discussion of the Pereyra, Gittes, and paravaginal procedures. A call is made to establish a gynecologic ethic to ensure that patients' rights are respected in all future surgical innovation.

Alabama↗

Obstetric and gynecologic dysfunction in the Ehlers-Danlos syndrome.

Women members of the newly formed Ehlers-Danlos National Foundation (EDNF) were surveyed with a very detailed questionnaire with 50 questions concerning family history and inheritance, past medical history, and obstetric and gynecologic problems. They entailed the largest extant database on Ehlers-Danlos Syndrome (EDS) patients. The mean age of the 68 women who responded to the survey was 42 years; most had EDS types I, III, IV and unknown. Forty-three women had 138 pregnancies; 13 women never married. The stillbirth rate was 3.15% (3/95); the preterm delivery rate was 23.1% (22/95), and the spontaneous abortion rate was 28.9% (40/138). There was a cesarean delivery rate of 8.4%, with 14.7% having perinatal bleeding problems. One woman (EDS type IV) had congestive heart failure. Common gynecologic problems were recurrent anovulation (41.3%), recurrent vaginal infections (53%), abnormal cytologic smears (19%), sexual dysfunction (61%), irregular menses (28%), endometriosis (15.8%), vaginal dryness (25%) and a need for hysterectomy (19.1%). In this largest series of pregnancies with EDS, we found relatively high rates of abortion, preterm delivery, pregnancy-related bleeding and stillbirth. Women with EDS also seem to have high frequency of anovulation, vaginal infections, abnormal cytologic smears and dyspareunia.

Abortion, Spontaneous↗

30-minute evaluation of incontinence in the older woman.

The key to successful management of urinary incontinence in the older woman is accurate diagnosis of the underlying condition. A simple 30-minute in-office evaluation answers the important questions that increase the likelihood of reaching the correct diagnosis. This core evaluation includes a history and physical exam, urinalysis and other basic lab tests, assessment of urethral angulation, and a simple cystometrogram. A patient voiding diary may also help to pinpoint the severity of incontinence. Further testing is required if symptoms fail to resolve after empiric therapy.

Adult↗