Neonatal experience interacts with adult social stress to alter acute and chronic Theiler's virus infection.

Previous research has shown that neonatal handling has prolonged protective effects associated with stress resilience and aging, yet little is known about its effect on stress-induced modulation of infectious disease. We have previously demonstrated that social disruption stress exacerbates the acute and chronic phases of the disease when applied prior to Theiler's virus infection (PRE-SDR) whereas it attenuates disease severity when applied concurrently with infection (CON-SDR). Here, we asked whether neonatal handling would protect adult mice from the detrimental effects of PRE-SDR and attenuate the protective effects of CON-SDR on Theiler's virus infection. As expected, handling alone decreased IL-6 and corticosterone levels, protected the non-stressed adult mice from motor impairment throughout infection and reduced antibodies to myelin components (PLP, MBP) during the autoimmune phase of disease. In contrast, neonatal handling X PRE/CON-SDR elevated IL-6 and reduced corticosterone as well as increased motor impairment during the acute phase of the infection. Neonatal handling X PRE/CON-SDR continued to exacerbate motor impairment during the chronic phase, whereas only neonatal handling X PRE-SDR increased in antibodies to PLP, MOG, MBP and TMEV. Together, these results imply that while handling reduced the severity of later Theiler's virus infection in non-stressed mice, brief handling may not be protective when paired with later social stress.

Perianal rhabdomyosarcoma presenting 21 months after hamartoma excision.

Perianal rhabdomyosarcoma is a rare type of tumor with a relatively poor prognosis. We present the case of a patient who presented with a cutaneous perianal hamartoma at the age of 6 weeks. 21 months latter a recurrent mass at the excision site proved to be an embryonal rhabdomyosarcoma involving the anal sphincter. A pathologic review of the two specimens confirmed their relatedness. This report highlights the need to maintain a high level of suspicion in cases of recurrence following excision of a benign lesion.

Diagnosis and management of pancreatic exocrine insufficiency (PEI) in primary care: consensus guidance of a Canadian expert panel.

BACKGROUND: Pancreatic exocrine insufficiency (PEI) results in maldigestion due to inadequate activity of pancreatic enzymes in the small bowel. PEI can arise from a variety of medical conditions that reduce enzyme synthesis within the pancreatic parenchyma or from secondary factors that may occur despite optimal parenchymal function, such as pancreatic duct obstruction or impaired or poorly synchronized enzyme release. PURPOSE: To provide practical guidance for primary care physicians managing patients who are at risk of PEI or who present with symptoms of PEI. METHODS: For each of six key clinical questions identified by the authors, PubMed searches were conducted to identify key English-language papers up to April 2017. Forward and backward searches on key articles were conducted using Web of Science. Clinical recommendations proposed by the co-chairs (P.D. and C.T.) were vetted and approved based on the authors? FINDINGS: The most characteristic symptom of PEI is steatorrhea ? voluminous, lipid-rich stools; other common signs and symptoms include unexplained weight loss and deficiencies of fat-soluble vitamins and other micronutrients. Pancreatic enzyme replacement therapy (PERT) can relieve symptoms and long-term sequelae of PEI. Diagnosis of PEI and initiation of PERT are usually the responsibility of gastroenterology specialists. However, primary care physicians (PCPs) are well positioned to identify potential cases of PEI and to participate in the collaborative, long-term management of patients already seen by a specialist. CONCLUSIONS: In this document, a panel of Canadian gastroenterologists has conducted a critical review of the literature on PEI and PERT and has developed practical diagnostic and treatment recommendations for PCPs. These recommendations provide guidance on identifying patients at risk of PEI, the triggers for PEI testing and referral, and best practices for co-managing patients with confirmed PEI.

Virtual reality therapy versus cognitive behavior therapy for social phobia: a preliminary controlled study.

Social phobia is one of the most frequent mental disorders and is accessible to two forms of scientifically validated treatments: anti-depressant drugs and cognitive behavior therapies (CBT). In this last case, graded exposure to feared social situations is one of the fundamental therapeutic ingredients. Virtual reality technologies are an interesting alternative to the standard exposure in social phobia, especially since studies have shown its usefulness for the fear of public speaking. This paper reports a preliminary study in which a virtual reality therapy (VRT), based on exposure to virtual environments, was used to treat social phobia. The sample consisted of 36 participants diagnosed with social phobia assigned to either VRT or a group-CBT (control condition). The virtual environments used in the treatment recreate four situations dealing with social anxiety: performance, intimacy, scrutiny, and assertiveness. With the help of the therapist, the patient learns adapted cognitions and behaviors in order to reduce anxiety in the corresponding real situations. Both treatments lasted 12 weeks, and sessions were delivered according to a treatment manual. Results showed statistically and clinically significant improvement in both conditions. The effect-sizes comparing the efficacy of VRT to the control traditional group-CBT revealed that the differences between the two treatments are trivial.

The determination of relevant goals and criteria used to select an automated patient care information system: a Delphi approach.

OBJECTIVES: To determine the relevant weighted goals and criteria for use in the selection of an automated patient care information system (PCIS) using a modified Delphi technique to achieve consensus. DESIGN: A three-phase, six-round modified Delphi process was implemented by a ten-member PCIS selection task force. The first phase consisted of an exploratory round. It was followed by the second phase, of two rounds, to determine the selection goals and finally the third phase, of three rounds, to finalize the selection criteria. RESULTS: Consensus on the goals and criteria for selecting a PCIS was measured during the Delphi process by reviewing the mean and standard deviation of the previous round's responses. After the study was completed, the results were analyzed using a limits-of-agreement indicator that showed strong agreement of each individual's responses between each of the goal determination rounds. Further analysis for variability in the group's response showed a significant movement to consensus after the first goal-determination iteration, with consensus reached on all goals by the end of the second iteration. CONCLUSION: The results indicated that the relevant weighted goals and criteria used to make the final decision for an automated PCIS were developed as a result of strong agreement among members of the PCIS selection task force. It is therefore recognized that the use of the Delphi process was beneficial in achieving consensus among clinical and nonclinical members in a relatively short time while avoiding a decision based on political biases and the "groupthink" of traditional committee meetings. The results suggest that improvements could be made in lessening the number of rounds by having information available through side conversations, by having other statistical indicators besides the mean and standard deviation available between rounds, and by having a content expert address questions between rounds.

Comparison of once-daily guanfacine and twice-a-day methyldopa in the treatment of mild to moderate hypertension.

Control of hypertension (ie, reduction of blood pressure to less than or equal to 160/90 mmHg) in 40 mild to moderate hypertensives not responding adequately to hydrochlorothiazide was achieved by the addition of guanfacine (once daily) or methyldopa (twice daily) in a 16-week, double-blind, parallel-group trial. Control occurred after two weeks (at 1 mg/day) in 50% of the guanfacine-treated patients and in most patients within four to six weeks of treatment. The final mean doses were 2.5 mg/day of guanfacine or 763 mg/day of methyldopa. Sixteen patients maintained control of hypertension with continued guanfacine therapy for one year.

Behavioral and biochemical effect of chronic treatment with D-1 and/or D-2 dopamine agonists in MPTP monkeys.

Monkeys developed a severe parkinsonian syndrome after intravenous administration of (MPTP). L-DOPA/carbidopa (D-1 and D-2) or bromocriptine (D-2) treatment relieved the parkinsonian symptoms, whereas SKF 38393 (D-1) was ineffective. No dyskinesia was seen in monkeys receiving bromocriptine or SKF 38393 as opposed to the L-DOPA-treated animals, in which the dyskinetic response appeared to increased with time. MPTP induced a significant increase (25%, P less than 0.01) in the number of [3H]spiperone binding sites (Bmax) in the caudate nucleus and in putamen. The Bmax of spiperone binding in the L-DOPA-treated monkeys was on average 18% lower (P less than 0.01) than that of the animals treated with MPTP alone. The Bmax for the bromocriptine-treated group was 29% (P less than 0.01) less than that in the MPTP-treated group or 11% (P less than 0.05) less than that in the L-DOPA-treated monkeys. The SKF 38393 treatment induced a 23% (P less than 0.01) decrease in the Bmax as compared to that of animals treated with MPTP alone, and no significant change compared to the L-DOPA- or bromocriptine-treated animals. These results suggest that stimulation of D-1 and D-2 dopamine receptors can differently influence the mechanisms controlling dopamine agonist-induced dyskinesia in MPTP-treated monkeys.

The development of an empirical psychosocial taxonomy for patients with diabetes.

The main purpose of this study was to develop and to cross-validate an empirically derived psychosocial taxonomy of patients with diabetes. In the first study, 101 patients with Type I or Type II diabetes completed the Multidimensional Diabetes Questionnaire. Cluster analysis identified three clusters, labeled adaptive copers, low support-low involvement, and spousal overinvolvement. In the second study, the taxonomy was cross-validated using an independent sample of 132 patients with long-standing Type II diabetes. The results confirmed that the multivariate classification system was unique and highly accurate. External validation, using general psychological as well as diabetes-specific measures, supported the validity and distinctiveness of the patients' profiles. These findings help establish a multiaxial psychosocial taxonomy of diabetes and may have significant implications for the management of patients with diabetes.

Hepatitis B and the dental profession: response to hepatitis B vaccine in Canadian dental personnel. A study by the Canadian Red Cross Collaborative Group.

Reports from North America and Western Europe based on the prevalence of hepatitis B virus markers and frequency of hepatitis B in dentists indicate that this professional group is at increased risk of HBV infection. We gave hepatitis B vaccine (Merck Sharp and Dohme) to 251 dental students and faculty/staff members at faculties of dentistry in three Canadian universities. Participants received three 20 micrograms doses of vaccine, at 0, 1 and 5.5 months. Anti-HBs was detected in 42.9 per cent of persons after the first dose of vaccine, in 96.8 per cent after the second dose and in 99.6 per cent after the third dose. A follow-up of 150 persons 22 months after the first dose of vaccine indicated that high or medium levels of anti-HBs were maintained in nearly 87 per cent of the participants and only six per cent had no detectable antibody. Female vaccinees in each age group developed anti-HBs more promptly, and more of them were in the high antibody-response range in comparison to male participants. There were no unacceptable reactions to the vaccine. Our favourable experience with this vaccine would support recommendations for its routine use among dental professionals in Canada and other countries where this group is at increased risk of HBV infection.

Exposure versus cognitive restructuring in the treatment of panic disorder with agoraphobia.

The aim of this study was to assess the rate of change on clinical, behavioral and cognitive variables during exposure therapy and cognitive restructuring in the treatment of panic disorder with agoraphobia. A total of 28 Ss who received a diagnosis of panic disorder with agoraphobia were randomly assigned to either of two treatment conditions: exposure therapy or cognitive restructuring. Treatment conditions were kept as distinct as possible from each other. Subjects were assessed on five occasions: pretreatment, after 5, 10, and 15 (posttreatment) sessions of treatment and at a 6-month follow-up. Analyses of outcome data revealed strong and significant time effects on all measures. However, no group x time interaction reached statistical significance, suggesting that both strategies operate at the same pace. Furthermore, power analyses suggest that any difference that might exist in the rate of improvement between exposure and cognitive restructuring in the treatment of panic disorder with agoraphobia is marginal.

Optimum symptomatic control of Parkinson's disease with dopaminergic therapy.

This paper presents a review of the literature on the therapeutic action and the side effects of the two main dopaminergic agents: L-DOPA/decarboxylase inhibitor (L-DOPA/DI) and bromocriptine (Parlodel used either as monotherapy or in combination in patients with Parkinson's disease. The combination of L-DOPA/DI and bromocriptine gives the best therapeutic efficacy (49% improvement) in the total score (bradykinesia, rigidity and tremor). However, treatment by monotherapy or combination gives the same pattern of activity: greatest improvement in tremor, followed by rigidity and bradykinesia. Improvement observed in the short term is not sustained over longer periods of time for monotherapy with either drug. The short-term side effects are similar for each treatment, whereas long-term complications (dyskinesia, end-of-dose deterioration and on-off phenomenon) appear only when levodopa is used, alone (high incidence) or in combination with bromocriptine (low incidence). The overall optimum treatment is obtained with a combination of L-DOPA/DI and bromocriptine.

A comparison of bromocriptine (Parlodel) and levodopa-carbidopa (Sinemet) for treatment of "de novo" Parkinson's disease patients.

Fifty-one patients were enrolled in a double-blind, parallel group, multicentre study conducted to assess short-term efficacy and tolerance of bromocriptine (Parlodel) or L-DOPA/carbidopa (Sinemet) in patients never treated with amantadine, ergot alkaloids or L-DOPA-based drugs. An attempt to use the lowest effective dose was made. The responder rate for each group was approximately 78%; the mean daily dose for responders was 22.5 mg of bromocriptine or 250 mg of L-DOPA/carbidopa. The overall clinical improvement in each group was 62% (bromocriptine) and 55% (L-DOPA/carbidopa) for neurological assessment and 36% (bromocriptine) and 31% (L-DOPA/carbidopa) for functional disability. Comparison between groups did not show any significant difference for both neurological and disability assessments. The most frequent side effect was nausea (L-DOPA, N = 3; bromocriptine, N = 6).

Treatment of spasticity with tizanidine in multiple sclerosis.

Spasticity is a frequent and often disabling symptom in MS patients. Current drugs used as antispastic agents include Dantrolene Sodium, Baclofen and Diazepam. Tizanidine (5-chloro-4-(2imidazolin-2 yl amino)-2,1,3-benzothialdiazole) is a new antispasticity agent that has purported central action. A double blind placebo controlled trial was performed to study the efficacy of this drug in MS patients. Sixty-six patients entered an eight week therapeutic trial and fifty-nine completed the trial. Patients were assessed at 0, 2, 3 and 8 weeks of therapy for clinical effects. Electrophysiologic tests were performed at 0 and 8 weeks. A statistically significant benefit was noted in spastic muscle groups in the legs with concomitant significant reduction in hyperactive stretch reflexes and ankle clonus. Side effects most frequently cited included dry mouth and drowsiness. Two patients developed elevated liver function test that decreased with cessation of therapy. Other clinical details, side effects and electrophysiologic data will be presented. Tizanidine appears to reduce clinical spasticity and hyperreflexia in MS patients although no change in functional status was detected. Tizanidine may well serve as an alternate antispastic agent, alone or in combination with other agents.

Bromocriptine in the management of end of dose deterioration in Parkinson's disease.

Thirty-three patients with advanced Parkinson's disease complicated by end of dose deterioration were treated with bromocriptine. The drug was slowly increased so that by treatment week 24 the mean daily dose of bromocriptine was 22mg and levodopa had been decreased by an average of 15 percent. The majority of improvement in daily fluctuations and Parkinsonian disability score was documented by 8 weeks, at which time the mean daily bromocriptine dose was only 12mg. End of dose deterioration was reduced in 78 percent of the patients (mean 43% improvement). Total Parkinsonian disability score was decreased by 33 percent. Adverse effects were minimal; the most common was mild transient early treatment nausea which occurred in 15 percent of the patients. The slow introduction of small doses of bromocriptine, combined with minimal levodopa reduction, can give Parkinsonian patients significant improvement in end of dose deterioration.

Tizanidine versus baclofen in the treatment of spasticity in patients with multiple sclerosis.

Tizanidine (Sirdalud) was compared to baclofen (Lioresal) in a randomized, double-blind, cross-over trial. Each medication was introduced over a three week titration period and then maintained at the highest tolerated dose for five weeks. The two treatment phases were separated by a one week drug withdrawal and a two week washout period. Sixty-six patients entered the trial and forty-eight completed both treatment phases. At the end of the trial, neurologists and physiotherapists thought that baclofen was superior on the basis of perceived efficacy and tolerance (p less than or equal to 0.05). Although the efficacy of tizanidine or baclofen was judged as good to excellent by 24 and 39% of patients respectively, this difference was not statistically significant. Muscle weakness was the most common adverse effect. This was significantly more troublesome in patients treated with baclofen. Somnolence and xerostomia were more common in patients treated with tizanidine. Both baclofen and tizanidine appear to be useful adjuncts in the treatment of spasticity in patients with multiple sclerosis. Preference of either drug is tempered principally by side-effects.

The assessment of panic using self-report: a comprehensive survey of validated instruments.

A repertoire of reliable and valid self-report instruments to assess panic and panic disorder would help both researchers and clinicians. This review presents a description and an analysis of the available instruments. Following a comprehensive search of the literature, 14 instruments with published information on reliability and validity were reviewed. The following information is reported for each instrument: brief description of the instrument and its development, mean and standard deviation for clinical and nonclinical samples, and psychometric properties. Four types of instruments are presented: general assessment and information (n = 2), severity of panic disorder (n = 2), body sensations (n = 2) and cognitive dimensions of panic (n = 8). Overall, it would seem that panic measures have moderate to excellent psychometric qualities. However, the comparison between the instruments is difficult because the amount of empirical support available varies widely from one instrument to the other.

Pediatric surgeons' activities and future plans.

OBJECTIVE: The authors aim was to survey members of the Canadian Association of Paediatric Surgeons (CAPS) on their demographics, practice, and future plans. MATERIALS AND METHODS: A questionnaire was mailed to 86 members. RESULTS: We received 60 questionnaires (70%), with a return rate including 85% men and 15% women. Seventeen percent of the respondents do not have children, 8% did not answer the question pertaining to children, and 8% expect to have more children. Among the 75% of surgeons with children, 16% have reduced the number of hours worked, from 2 hours to more than 1 day per week, for a number of years. Younger surgeons and women are more likely to reduce their work load for their family life. Most surgeons practice in an academic (64%) or a mixed setting (25%), with only 12% involved in private practice. On average, 69% of their time is devoted to patient care; teaching and research each take an average of 10% of the surgeon's time, while 9% of their time is spent on administrative duties. Study respondents work an average of 57 hours per week, and 45 weeks per year. Age significantly influenced the number of hours worked per week, and the number of weeks worked on a yearly basis. Gender and type of practices did not significantly influence the number of hours or weeks worked, whereas location of practice did. Spouse activity also had an impact on the number of hours and weeks worked. When asked about their preference for the next 5 years, 30% of surgeons would opt for a decrease in their level of activity, and 15% wish to retire. Irrespective of the age group or the type of practice, surgeons would prefer to decrease their level of activity. A recurring theme submitted by respondents is the need for increased time for teaching and research and less administrative work. Finally, 60% of surgeons were very satisfied with their work, 27% were satisfied, and 12% were unsatisfied. CONCLUSION: Lifestyle and family commitment have an impact on pediatric surgeons' activity and should be considered when analyzing work force requirements.

Perineal hemangioma, anorectal malformation, and genital anomaly: a new association?

Two patients presented as full-term baby girls with anorectal and genital malformations with extensive perineal hemangiomas. The first patient had a vestibular anus with a perineal hemangioma involving the bladder, rectal, and vaginal walls. Skin ulcerations required a transverse loop colostomy for wound care. The vulva, urethral opening, and clitoris were deviated to the left, labia minora were absent, and the labia majora were abnormal. The second patient had an anus displaced anteriorly and deviated to the right. The external anal sphincter was hypertrophic on the left and atrophic on the right. Rectal examination showed agenesis of the right levator ani and a dentate line located at the skin level. She had a large perineal, sacral, vaginal, pararectal and retroperitoneal hemangioma and developed extensive skin ulcerations. She had only a hemiclitoris located to the left of the midline, near absence of labia minora, and hypertrophied labia majora. The urethra was displaced to the left and opened in the vestibule. Both patients had a spinal malformation (one with tethered cord and one with spina bifida) and a normal karyotype. Steroids and interferon allowed near-complete resolution of hemangiomas in both patients. The authors were impressed by the similarity of these two cases and could not find any previous description of this association.

The otolaryngologic manifestations of gastroesophageal reflux: when is a pH study indicated?

PURPOSE: The aim of this study was to evaluate the pertinence of pH studies for persistent ear, nose, and throat (ENT) symptoms and their eventual relationship to gastroesophageal reflux (GER). METHODS: Retrospective analysis was performed of age, reason for referral, pH study, treatment, and follow-up of patients with ENT symptoms suspected to have GER. RESULTS: Of 3,000 esophageal pH studies performed over 16 years, 105 children were referred for ENT symptoms by an otorhinolaryngologist to rule out GER. Mean age was 33 months; 65% were boys. Reasons for referral included (number and mean age): stridor (n = 31, 8 months), laryngomalacia (n = 18, 13 months), recurrent otitis (n = 12, 42 months), laryngitis (n = 16, 50 months), dysphonia (n = 14, 59 months), laryngeal papillomatosis (n = 8, 62 months), sinusitis (n = 5, 56 months), and dysphagia (n = 1). Overall, 41% of study results were positive: stridor (58%), laryngomalacia (61%), laryngitis (56%) and sinusitis (40%). Patients with otitis, dysphonia and laryngeal papillomatosis had GER in 1%, 14%, and 25%, respectively. Follow-up in the three larger groups of patients showed resolution of the ENT symptoms after medical treatment of the reflux in 83% of patients with stridor and reflux, 86% with laryngitis and reflux, and 80% with laryngomalacia and reflux. Four fundoplications were performed: one neurologically impaired patient, and four nonresponders. CONCLUSIONS: The authors recommend that a pH study be performed in children with stridor, laryngomalacia, laryngitis, and sinusitis when faced with failure of the usual treatment. However, a pH study does not seem as beneficial for recurrent otitis, dysphonia, or laryngeal papillomatosis.

Expression of neuropeptides in normal and abnormal appendices.

BACKGROUND/PURPOSE: Increased neuroproliferation in the appendix associated with an increase in substance P (SP), vasoactive intestinal polypeptide (VIP), and growth-associated protein-43 (GAP-43) has been documented in appendices of adults with acute right lower quadrant (RLQ) abdominal pain and absence of gross or histologic signs of appendiceal inflammation. The authors tested whether these findings were present in children with RLQ pain and a normal appendix. METHODS: Immunohistochemistry staining of paraffin-embedded appendices was performed with GAP-43, VIP, and SP. The positive control group included appendices with acute inflammation (group I, n = 5); the negative control group included appendices removed incidentally (group II, n = 5); and the experimental group included appendices from children suspected to have acute appendicitis without histologic signs of inflammation (group III, n = 9). RESULTS: Group I: VIP was strongly expressed in the nerve plexuses. The lamina propria and muscularis showed absent or minimal VIP expression. SP staining was strong in all plexuses and was moderate to strong in the muscularis. SP expression in the epithelium and lamina propria was difficult to quantify secondary to inflammation. Group II: VIP expression was essentially undetectable in the epithelium, lamina propria, and muscularis, and was moderate in the nerve plexuses. Mild SP staining was detected in the nerve plexuses of most specimens, and absent to mild staining was found in the epithelium and muscularis. However, one specimen strongly expressed SP in all layers. Group III: VIP expression was moderate to strong in the lamina propria and muscularis of nearly all specimens, and strong expression was found in all nerve plexuses. All but one specimen strongly expressed SP in plexuses. There was moderate to strong expression of SP in the epithelium, lamina propria, and muscularis in over 50% of specimens. The immunostaining for GAP-43 was very weak and nonspecific and did not help discriminate between the 3 study groups. CONCLUSIONS: Increased neuroproliferation in the lamina propria and muscularis was evident in patients with abdominal pain and normal appendices compared with appendices removed incidentally. The VIP and SP expression in these patients was similar or higher than that observed in patients with acute inflammation on histology.