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Biomedical subjects

William E Whitehead

Publications and source records attributed to William E Whitehead.

At least 19 recordsLinked to original sources

Validity and reliability of the Modified Manchester Health Questionnaire in assessing patients with fecal incontinence.

PURPOSE: To date, no measures of fecal incontinence severity or its impact on quality of life have been validated for telephone interview. This study was designed to 1) compare responses of a self-administered and a telephone-administered Fecal Incontinence Severity Index; 2) compare a self-administered Fecal Incontinence Quality of Life Scale to the Manchester Health Questionnaire after modifying the latter for telephone administration and American English (Modified Manchester Health Questionnaire); 3) assess test-retest reliability of the telephone-administered Modified Manchester Health Questionnaire; and 4) assess the internal consistency of the Modified Manchester Health Questionnaire subscales. METHODS: Consecutive, English-speaking, nonpregnant females known to have fecal incontinence were invited to participate. Two validated paper questionnaires accompanied the letter informing them of the study: Fecal Incontinence Severity Index and Fecal Incontinence Quality of Life Scale. Consenting patients were contacted for the initial telephone administration of the Modified Manchester Health Questionnaire, and patients who agreed to continue the study were contacted for a repeat telephone administration of the Modified Manchester Health Questionnaire two to four weeks after completing the first interview. RESULTS: Fifty-one females were invited to participate in the study; however, 13 declined or were ineligible. Thirty females, aged 49.3 +/- 10.3 years, returned self-administered questionnaires and completed the first telephone interview, and 21 completed a second telephone interview after an average interval of 23 days. The telephone-administered Fecal Incontinence Severity Index scores were significantly lower than those yielded by the self-administered Fecal Incontinence Severity Index, (6.19 vs. 9.85; P < 0.001), but the telephone and written administrations were significantly correlated (r = 0.5; P < 0.02). Correlations between the Modified Manchester Health Questionnaire quality of life subscales and the paper Fecal Incontinence Quality of Life subscales ranged from 0.6 to 0.9 (median, r = 0.81). The correlation between the total score for the Fecal Incontinence Quality of Life and the total score for the Modified Manchester Health Questionnaire quality of life scales was 0.93 (P < 0.001). Test-retest reliability for the eight Modified Manchester Health Questionnaire subscales ranged from 0.55 to 0.98 (median, r = 0.83), and test-retest reliability for the two telephone administrations of the Fecal Incontinence Severity Index was r = 0.75. Cronbach's alpha for the eight Modified Manchester Health Questionnaire subscales ranged from 0.79 to 0.92 (median, alpha = 0.85). CONCLUSIONS: Telephone-administered versions of the Modified Manchester Health Questionnaire showed good-to-excellent validity, internal consistency, and test-retest reliability. The telephone-administered Fecal Incontinence Severity Index yielded lower severity scores than the written Fecal Incontinence Severity Index; however, the difference (3.66 units) was not clinically significant.

Adult↗

Biofeedback benefits only patients with outlet dysfunction, not patients with isolated slow transit constipation.

BACKGROUND & AIMS: Biofeedback is reported to be as effective for slow transit constipation as for pelvic floor dyssynergia and no more effective than education. We aimed to test the hypothesis that biofeedback benefits only patients with pelvic floor dyssynergia, describe the physiologic mechanism of treatment, and identify predictors of success. METHODS: Fifty-two patients (49 women; average age, 35 years), all with delayed whole gut transit, included 34 with pelvic floor dyssynergia, 12 with slow transit only, and 6 who met only 1 of 2 criteria for pelvic floor dyssynergia. All received 5 weekly biofeedback sessions directed at increasing rectal pressure and relaxing pelvic floor muscles during straining plus practice defecating a balloon. Patients were retested by questionnaire; symptom diary; balloon defecation; transit study at 1, 6, 12, and 24 months; and anorectal manometry at 1 and 6 months. RESULTS: At 6 months, greater improvements were seen in pelvic floor dyssynergia compared with slow transit only; 71% versus 8% reported satisfaction ( P = .001), and 76% versus 8% reported >/=3 bowel movements per week ( P < .001). Improvements were maintained at 24 months of follow-up. Biofeedback eliminated dyssynergia in 91% and enabled 85% to defecate the balloon. Satisfaction was correlated with improved ability to defecate the balloon (rho = .73; P < .001), reductions in dyssynergia (rho = .69; P < .001), and increased rectal pressure during straining (rho = .36; P < .01). Success was predicted by pelvic floor dyssynergia, milder constipation, and less frequent abdominal pain at baseline. CONCLUSIONS: Biofeedback is an effective treatment for pelvic floor dyssynergia but not slow transit constipation.

Abdominal Pain↗

"Keystone" approach for intracranial nasofrontal dermoid sinuses.

Nasofrontal dermoid sinus tracts that extend intracranially through the foramen cecum or ethmoid can be difficult to completely resect. Complete extirpation of nasofrontal dermoid sinus cysts is essential for effective treatment of this problem to minimize the chance of recurrence. The authors describe a new technique based on parasagittal osteotomies through the supraorbital bar, or bandeau, that ensures that the resection of the nasofrontal dermoid sinus cysts is complete. This technique also limits the size of the external nasal incision and enhances the surgeon's exposure of the anterior cranial base for resection of intradural extension. This approach also enhances exposure for the direct repair of the dura and the cranial vault.

Child↗

Clinical response to tricyclic antidepressants in functional bowel disorders is not related to dosage.

BACKGROUND: As shown in the per protocol analysis of a recent randomized, controlled trial, when tolerated, Desipramine (DES) is effective over placebo (PLA) in treating moderate-to-severe functional bowel disorders (FBD). Clinical experience suggests that the benefit from tricyclic antidepressants (TCA) in FBD can be achieved at doses lower than those used to treat major depression. Within psychiatry, when using higher dosage of TCAs, plasma levels can be used to adjust daily dosage to optimize a treatment response. However, in FBD, it is not known whether plasma levels at the lower dosage are similarly related to a clinical response. AIM: To determine in treating FBD, whether DES blood levels or dose taken can predict a clinical response. METHODS: As part of a study of 12 wk of antidepressant and psychological treatment in 431 patients with FBD at UNC and U of Toronto, we studied those participants who completed treatment (per protocol analysis) taking DES (N = 97, dose 50-150 mg/day) or pill placebo (PLA) (N = 55 1-3 pills/day). The primary outcome measure was defined as a composite score (Satisfaction with Treatment, McGill Pain Questionnaire, Global Well-being, and IBS-QOL). The composite score was correlated with: (i) DES plasma levels at week 6, and (ii) number of pills taken over the duration of the 12-wk treatment period. In addition, we also compared DES dose with DES plasma levels. RESULTS: There was a modest correlation between mean DES dose at weeks 5 and 6 and DES blood level at week 6 (R = 0.2 p < 0.07). However, there were no significant correlations between the composite score either with DES dose or with DES blood levels. CONCLUSIONS: Detectable blood levels of DES are associated with a clinical response in FBD. However, with dosages up to 150 mg, there is no relationship between total dose or plasma level and the clinical response.

Adolescent↗

Biofeedback treatment for functional anorectal disorders: a comprehensive efficacy review.

This review aimed to critically evaluate the literature on the efficacy of biofeedback for functional anorectal disorders, rate these biofeedback applications according to established guidelines, and make recommendations for this field based on the literature. The Medline and PsychInfo databases were searched to obtain all papers published from 1975 to 2003 that included the terms "biofeedback" and either "constipation" "pelvic floor dyssynergia" "fecal incontinence" or "anorectal pain." Adult and pediatric papers in any language were screened. Prospective studies with five or more participants and a description of the treatment protocol and outcome were selected for review. Seventy-four studies qualified for review: 33 trials on fecal incontinence (FI), 38 on pelvic floor dyssynergia (PFD) or functional constipation, and 3 on anorectal pain. Only 20% of studies were controlled outcome trials. Treatment protocols, etiological subgroups studied and outcome measures varied greatly. The overall average probability of successful treatment outcome for patients treated with biofeedback was 67.2% for functional FI and 62.4% for constipation. There were insufficient data to warrant such calculation for anorectal pain. According to standard efficacy rating criteria, biofeedback treatment is efficacious for functional constipation or PFD in children and probably efficacious in adults; probably efficacious for functional FI; and possibly efficacious for anorectal pain. Utilizing data from all applicable studies, we found that success rate per subject is significantly higher for biofeedback treatment than for standard medical care for PFD/functional constipation, and FI (p < .001 for both). Biofeedback treatment may therefore be viewed as a valuable adjunct to medical management of functional PFD/constipation and incontinence. A number of recommendations for future investigations are made based on the review.

Adult↗

Patients and nonconsulters with irritable bowel syndrome reporting a parental history of bowel problems have more impaired psychological distress.

Little is known about the prevalence and risk factors for development of irritable bowel syndrome (IBS) in Japan. In the United States, it is reported that heredity and social learning contribute to the development of IBS. Our aims were (1) to estimate the prevalence of IBS, (2) to confirm that subjects with IBS are more likely to have parents with a history of bowel problems, (3) to confirm that gastroenteritis is a risk factor for IBS, and (4) to determine whether these two risk factors interact with psychological distress. Prevalence was estimated from a sample of 417 young adults seen for annual health screening examinations. To evaluate risk factors related to consulting physicians, the 46 subjects who fulfilled Rome II diagnostic criteria for IBS but denied ever having seen a physician about these symptoms (IBS non-consulters) were compared to the 317 subjects who did not meet the criteria for IBS (controls) and to a group of 56 patients diagnosed with IBS by gastroenterologists (IBS patients). All subjects completed the Gastrointestinal Symptoms Rating Scale, the State-Trait Anxiety Inventory, the Self-Rating Depression Scale, the Perceived Stress Scale, and the SF-36 quality of life scale. Fourteen and two-tenths percent (15.5% of females and 12.9% of males) of the community sample met the criteria for IBS diagnosis, of whom 22% consulted physicians. IBS patients and IBS nonconsulters were more likely than controls to have a parental history (33.9 vs. 12.6%, P < 0.001, for patients and 26.1 vs. 12.6%, P < 0.01, for nonconsulters) and were more likely to report an infective history compared to controls (44.6 vs. 16.1%, P < 0.001, for patients and 32.6 vs. 16.1%, P < 0.01, for nonconsulters). Two-way analysis of variance showed that the parental history was associated with a significantly greater impact on symptoms of indigestion, diarrhea, constipation, state and trait anxiety, and the SF-36 scales for social functioning and role emotional and that an infective history was associated with a greater impact on bodily pain. Both a parental history of bowel problems and a history of acute gastroenteritis are significant risk factors for development of IBS in Japan, as reported for the United States. Moreover, patients with such a family history show more psychological distress than other patients.

Adult↗

Elevated vasoactive intestinal peptide concentrations in patients with irritable bowel syndrome.

The aim was to assess the roles of gut hormones and immune dysfunction in irritable bowel. In Study I, rectal mucosal samples examined blindly showed no histological evidence of inflammation in 16 irritable bowel patients compared to 17 healthy controls. The proinflammatory mediators interleukin-1beta and prostaglandin E2 also failed to show evidence of inflammation. Vasoactive intestinal peptide was elevated in irritable bowel (P = 0.01), but substance P, calcitonin gene-related peptide, and somatostatin levels were similar to control values. In Study II, 30 irritable bowel patients had elevated (P = 0.002) plasma concentrations of vasoactive intestinal peptide compared to 30 controls, and peptide levels were unrelated to whether the patient's predominant bowel habit was constipation, diarrhea, or both in alternation. In conclusion, no evidence of inflammation was detected in irritable bowel patients, but elevated vasoactive intestinal peptide concentrations were observed in both studies and might represent a potential diagnostic tool for irritable bowel syndrome.

Adult↗

Control groups appropriate for behavioral interventions.

There are 4 sources of bias in clinical trials: investigator bias, patient expectation (placebo response), ascertainment bias (inadvertent selection of an unrepresentative sample), and nonspecific effects such as the normal waxing and waning of symptoms over time and the quality of the doctor-patient relationship. In drug trials, these biases are adequately controlled by comparing active to inert pills, randomly assigning subjects to treatments, blinding both the investigator and subject to group assignment, and testing subjects at multiple sites. However, there are special problems with conducting clinical trials of behavioral or psychological interventions that render these controls inadequate. It is impossible to blind the experimenter to which treatment is active, it is difficult to identify a control treatment that is inactive but just as credible to the subject, and doctor-patient relationship variables are more important than in drug trials. The inability to blind the experimenter can be circumvented by having an independent, blinded investigator assess the outcome, and doctor-patient effects can be controlled by using multiple, experienced therapists. The most difficult problem, identifying an appropriate control treatment, can be solved by adhering to 2 principles: the control treatment should be plausible, and it should not have a significant impact on the mechanism that is thought to explain the effectiveness of the investigational treatment. Investigators should confirm that these 2 goals have been achieved by monitoring expectation of benefit with a treatment credibility questionnaire, measuring changes in process variables (variables that reflect the presumed mechanism of treatment), and monitoring differential dropout rates.

Bias↗

Priorities for treatment research from different professional perspectives.

The consensus conference "Advancing the Treatment of Fecal and Urinary Incontinence Through Research" had as one of its goals the development of a comprehensive list of research priorities. Experts from all disciplines that treat incontinence-gastroenterology, pediatric gastroenterology, urology, urogynecology, colorectal surgery, geriatrics, neurology, nursing, and psychology-and patient advocates were asked to identify their highest priorities for treatment-related research. Meeting participants were shown the aggregated list and invited to propose additional priorities. Treatments for fecal incontinence (biofeedback, sphincteroplasty, antidiarrheal and laxative medications, and sacral nerve stimulation) require validation by randomized, controlled trials. For urinary incontinence, the greatest need is to compare pharmacological, behavioral, and surgical treatments. Trials assessing combined treatments (e.g., biofeedback plus surgery vs. surgery alone or biofeedback alone) are also needed. New drugs are needed that target anal canal resting pressure in fecal incontinence and hypersensitivity to distention in urge urinary incontinence. It may be possible to substantially reduce the incidence of incontinence through modification of obstetric practices (e.g., avoiding episiotomies or offering elective cesarean delivery to high-risk patients), providing pelvic floor exercises before childbirth, and educating patients to avoid straining during defecation. For the elderly, practical behavioral and pharmacological treatments are needed that can postpone or avoid institutionalization. Social science research may identify ways to counteract the social stigma of fecal incontinence and assist physicians in providing patients with more comprehensive and understandable information on the risks associated with different treatment options.

Clinical Trials as Topic↗

Increased somatic complaints and health-care utilization in children: effects of parent IBS status and parent response to gastrointestinal symptoms.

OBJECTIVES: Irritable bowel syndrome (IBS) runs in families. The aims of this study were (i) to exclude biased perception by a mother with irritable bowel as the explanation for increased gastrointestinal (GI) symptoms in their children, (ii) to determine whether non-GI as well as GI symptoms run in families, and (iii) to determine whether parent IBS status and solicitous responses to illness exert independent effects on children's symptom reports, medical clinic visits, and school absences. METHODS: Two hundred and eight mothers with irritable bowel and their 296 children (cases: average age 11.9 yr; 48.6% male) and 241 nonirritable bowel mothers and their 335 children (controls: 11.8 yr; 49.0% male) were interviewed. Other factors assessed were stress, mother's and child's psychological symptoms, child's perceived competence, pain coping style, age, and sex. Children were interviewed apart from their parents. RESULTS: Case children independently reported more frequent stomach aches (F(591) = 9.22; p= 0.0025) and non-GI symptoms (F(562) = 21.03; p < 0.001) than control children. Case children also had more school absences (F(625) = 26.53; p < 0.0001), physician visits for GI symptoms (F(602) = 8.09; p= 0.005), and non-GI clinic visits (F(602) = 27.92; p < 0.001) than control children. Children whose mothers made solicitous responses to illness complaints independently reported more severe stomach aches (F(590) = 11.42; p < 0.001), and they also had more school absences for stomach aches (F(625) = 5.33; p < 0.05), but solicitous behavior did not significantly impact non-GI symptom reporting, clinic visits, or school absences. Differences between cases and controls remained significant after adjusting for potential moderators. CONCLUSIONS: (i) Frequent GI complaints in children whose mothers have irritable bowel are not explained by the mother's biased perceptions; (ii) children of mothers with irritable bowel have more non-GI as well as GI symptoms, disability days, and clinical visits; (iii) and parent IBS status and solicitous responses to illness have independent effects on the child's symptom complaints.

Absenteeism↗

A functional interferon regulatory factor-1 (IRF-1)-binding site in the upstream regulatory region (URR) of human papillomavirus type 16.

We recently identified a new enhancer element (HIRE-1, HPV-Interferon Responsive Element-1) in the upstream regulatory region (URR) of human papillomavirus (HPV) type 16. HIRE-1 is located upstream from and in close proximity to the TATA box. HIRE-1 is 1 nt shorter in its 5' sequence in comparison to a consensus IRF-1 binding site (IRF-E). Gel shift analyses clearly demonstrated that HIRE-1 is capable of binding IRF-1 in response to interferon-gamma (IFN-gamma) treatment. In a reporter system, HIRE-1 stimulated transcription in response to IRF-1 or IFN gamma from both a heterologous or the homologous (p97) promoter in a dose-dependent manner. Mutations in the core binding sequence strongly decreased this enhancer activity. Interestingly, HIRE-1 stimulated transcription in the context of the full URR in a cell-type-specific manner, thereby suggesting the role of other cell-type-specific factors that might counteract with its function. Thus, our results may explain the inconsistent clinical and experimental results observed following IFN treatment of cervical lesions or cells. Also, this new enhancer may have an important function during inflammatory responses against HPV type 16.

5' Flanking Region↗

Rapid determination of domoic acid in serum and urine by liquid chromatography-electrospray tandem mass spectrometry.

A rapid, selective, and sensitive LC-MS/MS method was developed for the quantitative determination of domoic acid in serum and urine samples. Samples were prepared for analysis using an Oasis HLB SPE column. Determination was by a reversed phase HPLC using a mixture of methanol, acetonitrile, and water containing 1% acetic acid and an electrospray ionization (ESI) ion-trap mass spectrometer (Finnigan LCQ). The method was validated by analyzing five replicates each of negative control bovine serum or urine fortified with domoic acid at the 0.005 microg/g method detection limit (MDL) and at the 0.05 microg/g level. Recoveries ranged from 90 to 95% for fortifications at the MDL and from 92 to 98% for fortifications 10 times higher than the MDL. The diagnostic utility of the method was tested by analyzing samples from live animals showing clinical signs suggestive of domoic acid poisoning submitted to the veterinary toxicology laboratory.

Animals↗

Biofeedback treatment of constipation: a critical review.

PURPOSE: This review was designed to 1) critically examine the research design used in investigations of biofeedback for pelvic floor dyssynergia, 2) compare the various biofeedback treatment protocols for pelvic floor dyssynergia-type constipation used in this research, 3) identify factors that influence treatment outcome, and 4) identify goals for future biofeedback research for pelvic floor dyssynergia. METHODS: A comprehensive review of both the pediatric and adult research from 1970 to 2002 on "biofeedback for constipation" was conducted using a Medline search in all languages. Only prospective studies including five or more subjects that described the treatment protocol were included. In addition, a meta-analysis of these studies was performed to compare the outcome of different biofeedback protocols for treating constipation. RESULTS: Thirty-eight studies were reviewed, and sample size, treatment protocol, outcome rates, number of sessions, and etiology are shown in a table. Ten studies using a parallel treatment design were reviewed in detail, including seven that randomized subjects to treatment groups. A meta-analysis (weighted by subjects) was performed to compare the results of two treatment protocols prevalent in the literature. The mean success rate of studies using pressure biofeedback (78 percent) was superior (P = 0.018) to the mean success rate for studies using electromyography biofeedback (70 percent). However, the mean success rates comparing studies using intra-anal electromyography sensors to studies using perianal electromyography sensors were 69 and 72 percent, respectively, indicating no advantages for one type of electromyography protocol over the other (P = 0.428). In addition to the varied protocols and instrumentation used, there also are inconsistencies in the literature regarding the severity and etiology of symptoms, patient selection criteria, and the definition of a successful outcome. Finally, no anatomic, physiologic, or demographic variables were identified that would assist in predicting successful outcome. Having significant psychological symptoms was identified as a factor that may influence treatment outcome, but this requires further study. CONCLUSION: Although most studies report positive results using biofeedback to treat constipation, quality research is lacking. Specific recommendations are made for future investigations to 1) improve experimental design, 2) clearly define outcome measures, 3) identify the etiology and severity of symptoms, 4) determine which treatment protocol and which component of treatment is most effective for different types of subjects, 5) systematically explore the role of psychopathology in this population, 6) use an adequate sample size that allows for meaningful analysis, and 7) include long-term follow-up data.

Adult↗

Cognitive-behavioral therapy versus education and desipramine versus placebo for moderate to severe functional bowel disorders.

BACKGROUND & AIMS: Studies of antidepressants and psychological treatments in functional bowel disorders (FBD) are methodologically limited. The aim of this study was to assess the clinical efficacy and safety of cognitive-behavioral therapy (CBT) against education (EDU) and desipramine (DES) against placebo (PLA) in female patients with moderate to severe FBD (irritable bowel syndrome, functional abdominal pain, painful constipation, and unspecified FBD). We also evaluated the amenability of clinically meaningful subgroups to these treatments. METHODS: This randomized, comparator-controlled, multicenter trial enrolled 431 adults from the University of North Carolina and the University of Toronto with moderate to severe symptoms of FBD. Participants received psychological (CBT vs. EDU) or antidepressant (DES vs. PLA) treatment for 12 weeks. Clinical, physiologic, and psychosocial assessments were performed before and at the end of treatment. RESULTS: The intention-to-treat analysis showed CBT as significantly more effective than EDU (P = 0.0001; responder rate, 70% CBT vs. 37% EDU; number needed to treat [NNT ], 3.1). DES did not show significant benefit over PLA in the intention-to-treat analysis (P = 0.16; responder rate, 60% DES vs. 47% PLA; NNT, 8.1) but did show a statistically significant benefit in the per-protocol analysis (P = 0.01; responder rate, 73% DES vs. 49% PLA; NNT, 5.2), especially when participants with nondetectable blood levels of DES were excluded (P = 0.002). Improvement was best gauged by satisfaction with treatment. Subgroup analyses showed that DES was beneficial over PLA for moderate more than severe symptoms, abuse history, no depression, and diarrhea-predominant symptoms; CBT was beneficial over EDU for all subgroups except for depression. CONCLUSIONS: For female patients with moderate to severe FBD, CBT is effective and DES may be effective when taken adequately. Certain clinical subgroups are more or less amenable to these treatments.

Adult↗

Regional brain activation in response to rectal distension in patients with irritable bowel syndrome and the effect of a history of abuse.

Previous studies have demonstrated alterations in brain response to rectal distension in patients with irritable bowel syndrome (IBS) compared to controls. Our aim was to compare regional brain activity in response to rectal balloon distension in patients with IBS and healthy controls. We studied six patients with IBS and six healthy controls. Positron emission tomography scans were obtained during rectal balloon distensions. Statistical parametric mapping and region of interest analysis were performed to identify and compare differences in regional cerebral blood flow (CBF) for each distension pressure within and between the groups of interest. In post-hoc analyses, patients with a history of sexual or physical abuse were compared to patients without abuse. In response to rectal distension, controls exhibit a greater increase in anterior cingulate cortex (ACC) activity compared to the IBS group (Z = 3.2, P = 0.001). Thalamic activity was higher in the IBS patients relative to the control group (Z = 3.3, P < 0.001). Increased ACC activity was observed in IBS patients with no history of abuse (Z = 5.2, P < 0.001) similar to controls, whereas no such increased activity was noticed in the abused group. In conclusion, this study replicates previous findings showing alterations in brain response to rectal distension in patients with IBS. The observations on the effect of abuse suggest a possible modulating role of abuse history on this brain response.

Adolescent↗