Hydrogen peroxide-enhanced three-dimensional endoanal ultrasonography and endoanal magnetic resonance imaging in evaluating perianal fistulas: agreement and patient preference

OBJECTIVES: To determine agreement between hydrogen peroxide-enhanced three-dimensional endoanal ultrasonography (3D HPUS) and endoanal magnetic resonance imaging (MRI) in preoperative assessment of perianal fistulas, and to assess patient preference with regard to these techniques. METHODS: Forty patients (31 males, aged 21-70 years) with symptoms of a perianal fistula and a visible external opening underwent preoperative 3D HPUS and endoanal MRI. The results were assessed separately by experienced observers. Fistulas were described according to the following characteristics: classification of the primary fistula tract according to Parks, location of the internal opening, presence of secondary tracts and fluid collections. Patients were asked to score the amount of discomfort experienced during both procedures and express their preference for either method. RESULTS: The median time interval between 3D HPUS and endoanal MRI was 14 days (range, 0-91 days). The methods agreed in 88% (35/40, kappa = 0.45) for the primary fistula tract, in 90% (36/40, kappa = 0.83) for the location of the internal opening, in 78% (31/40, kappa = 0.62) for secondary tracts, and in 88% (35/40, kappa = 0.63) for fluid collections. Both methods were associated with similar discomfort, and there was no patient preference for one procedure over the other. CONCLUSIONS: 3D HPUS and endoanal MRI are equally adequate for the evaluation of perianal fistulas. Both methods are associated with similar discomfort and patients have no preference for either procedure.     

Poly-use of cannabis and other substances among juvenile-justice involved youth: variations in psychological and substance-related problems by typology

Background: Adolescent cannabis use is associated with increased risk for psychological problems, with evidence for more severe problems among youth who use cannabis in combination with other substances (i.e., polysubstance use). Juvenile offenders engage in both cannabis use and polysubstance use at higher rates than the general adolescent population. Yet, limited research has examined the relationship between cannabis poly-use (e.g., cannabis and alcohol use) and functional or psychological problems among juvenile offenders.

Objectives: The current study addresses this gap by examining the association of polysubstance use of cannabis compared to cannabis only use with cognitive functioning, psychological distress, and substance-related problems among juvenile detainees.

Methods: Participants were 238 detained youth ages 12–18 (80.4 % male, 77.3% non-White) who completed assessments of substance use, intellectual functioning, psychological symptoms, and substance-related problems. Youth were also assessed by a clinical psychologist for substance use disorder.

Results: Four cannabis-use typologies were identified; cannabis and alcohol use was the largest class, followed by cannabis only use, cannabis, alcohol and other drug use, then cannabis and other drug use. Polysubstance use was associated with lower scores on measures of intellectual functioning, more externalizing and internalizing symptomology, and more substance-related problems relative to cannabis only use. However, the relationship between polysubstance use and problems varied by typology.

Conclusions: Findings suggest that justice-involved youth engaged in polysubstance use may be at greater need for concurrent academic, affective, and behavioral support in their rehabilitation and transition back to the community.     

Anal inspection and digital rectal examination compared to anorectal physiology tests and endoanal ultrasonography in evaluating fecal incontinence

Background Anal inspection and digital rectal examination are routinely performed in fecal incontinent patients but it is not clear to what extent they contribute to the diagnostic work-up. We examined if and how findings of anal inspection and rectal examination are associated with anorectal function tests and endoanal ultrasonography. Methods A cohort of fecal incontinent patients (n=312, 90% females; mean age 59) prospectively underwent anal inspection and rectal examination. Findings were compared with results of anorectal function tests and endoanal ultrasonography. Results Absent, decreased and normal resting and squeeze pressures at rectal examination correlated to some extent with mean (±SD) manometric findings: mean resting pressure 41.3 (±20), 43.8 (±20) and 61.6 (±23) Hg (p<0.001); incremental squeeze pressure 20.6 (±20), 38.4 (±31) and 62.4 (±34) Hg (p<0.001). External anal sphincter defects at rectal examination were confirmed with endoanal ultrasonography for defects <90 degrees in 36% (37/103); for defects between 90-150 degrees in 61% (20/33); for defects between 150-270 degrees in 100% (6/6). Patients with anal scar tissue at anal inspection had lower incremental squeeze pressures (p=0.04); patients with a gaping anus had lower resting pressures (p=0.013) at anorectal manometry. All other findings were not related to any anorectal function test or endoanal ultrasonography. Conclusions Anal inspection and digital rectal examination can give accurate information about internal and external anal sphincter function but are inaccurate for determining external anal sphincter defects <90 degrees. Therefore, a sufficient diagnostic work-up should comprise at least rectal examination, anal inspection and endoanal ultrasonography.     

Salmonella enterica Serovar Typhi-Specific Immunoglobulin A Antibody Responses in Plasma and Antibody in Lymphocyte Supernatant Specimens in Bangladeshi Patients with Suspected Typhoid Fever

Many currently available diagnostic tests for typhoid fever lack sensitivity and/or specificity, especially in areas of the world where the disease is endemic. In order to identify a diagnostic test that better correlates with typhoid fever, we evaluated immune responses to Salmonella enterica serovar Typhi (serovar Typhi) in individuals with suspected typhoid fever in Dhaka, Bangladesh. We enrolled 112 individuals with suspected typhoid fever, cultured day 0 blood for serovar Typhi organisms, and performed Widal assays on days 0, 5, and 20. We harvested peripheral blood lymphocytes and analyzed antibody levels in supernatants collected on days 0, 5, and 20 (using an antibody-in-lymphocyte-supernatant [ALS] assay), as well as in plasma on these days. We measured ALS reactivity to a serovar Typhi membrane preparation (MP), a formalin-inactivated whole-cell preparation, and serovar Typhi lipopolysaccharide. We measured responses in healthy Bangladeshi, as well as in Bangladeshi febrile patients with confirmed dengue fever or leptospirosis. We categorized suspected typhoid fever individuals into different groups (groups I to V) based on blood culture results, Widal titer, and clinical features. Responses to MP antigen in the immunoglobulin A isotype were detectable at the time of presentation in the plasma of 81% of patients. The ALS assay, however, tested positive in all patients with documented or highly suspicious typhoid, suggesting that such a response could be the basis of improved diagnostic point-of-care-assay for serovar Typhi infection. It can be important for use in epidemiological studies, as well as in difficult cases involving fevers of unknown origin.Salmonella enterica serovar Typhi (serovar Typhi) is the cause of typhoid fever, an illness that affects over 20,000,000 individuals worldwide each year, killing over 200,000 (5, 8, 16). The largest burden of typhoid fever is borne by impoverished individuals in resource-poor areas of the world. Serovar Typhi is a human-restricted invasive enteric pathogen which, after ingestion, crosses the intestinal mucosa, is taken up by gut-associated lymphoreticular tissues, and enters the systemic circulation. Both mucosal and systemic host immune responses are stimulated after infection. Serovar Typhi is an intracellular pathogen, and antibody and cell-mediated immune responses occur after infection or immunization with live oral attenuated typhoid vaccines (10, 25, 34).Diagnostic tests for typhoid fever often lack sensitivity and/or specificity, especially in areas of the world that are endemic for typhoid fever, where clinically distinguishing typhoid fever from other febrile illnesses is difficult (5, 17, 39). Microbiologic culturing of blood is approximately 30 to 70% sensitive, with the highest sensitivity being associated with an absence of prior use of antibiotics and the culturing of larger volumes of blood, features that complicate this mode of diagnosis in young children (5, 6, 8, 36). Microbiologic culturing of bone marrow aspirates is more sensitive than blood but often clinically impractical (1, 11, 12). Serum Widal assay titers are often nonspecific in endemic settings and are of limited value unless titers are markedly elevated or are analyzed for changes from acute to convalescent phases of illness (18, 33, 38). Molecular diagnostic assays including PCR are promising, but issues of practicality, contamination, and quality control have limited their use in many resource-poor areas of the world (14).Since serovar Typhi interacts with both the mucosal and the systemic immune systems, we were interested to determine whether analyses of mucosal immune responses would give improved insight into this human-restricted infection. Activated mucosal lymphocytes migrate from intestinal tissue and circulate within peripheral blood before rehoming to mucosal tissues (20, 31). This migration peaks 1 to 2 weeks after intestinal infection and may be measured by using peripheral blood mononuclear cells (PBMC) in an antibody-secreting cell (ASC) assay (19, 26) or in supernatants recovered from harvested PBMC (the “antibody in lymphocyte supernatant” [ALS] assay) (7, 31). Although ALS and ASC responses have previously been measured after immunization with oral live attenuated typhoid vaccines, detailed analyses of ALS or ASC responses in individuals with wild-type typhoid fever are lacking (21, 24). In order to gain further insight into mucosal immune responses during wild-type serovar Typhi infection, we undertook a study to characterize the serum and ALS responses to serovar Typhi among individuals with suspected typhoid fever in Bangladesh.     

Influence of gender,parity, and caloric load on gastrorectal response in healthy subjects: a barostat study

The gastrocolonic response consists of a prompt increase in colonic tone after a meal. With a barostat and a high compliant air-filled bag, it is possible to measure rectal tone by recording changes in volume at a constant intrabag pressure. The aim of this study was to evaluate the gastrorectal response in males and females as well as the effect of different caloric loads on the gastrorectal response. In 33 volunteers a barostat procedure during basal conditions and after a 600-kcal meal was performed. In 26 volunteers the procedure was repeated with a 1000-kcal meal. A meal response was defined as a decrease in volume of more than 10%. Phasic volume events (PVE) were defined as a 10% decrease in volume of 15–60 sec duration. After a 600-kcal meal, the decrease in volume after 1 hr was 28 ± 7% (mean ± SEM, P < 0.001). A meal response was found in 64% of the subjects. Parous females had a diminished meal response compared with nulliparous females (2 ± 5% and 48 ± 11%, P < 0.001). After the 600-kcal meal, PVEs increased from 3 to 10/hr (P = 0.001). In the 26 subjects, volume decrease was 40 ± 9% after the 1000-kcal meal and 20 ± 7% after the 600-kcal meal (P = 0.28). In the high-calorie meal, 18 subjects (69%) had a response versus 14 (54%) in the low-calorie meal (NS). Enhancing the caloric load of the meal did not increase the amounts of PVEs. In conclusion, a gastrorectal response occurs in 64% of the healthy subjects after a 600-kcal meal. The gastrorectal response can be measured to a similar extent in men and nulliparous women; however, the response is significantly impaired in parous women. This is possibly due to neurogenic damage during childbirth. Increasing the caloric load did not increase the gastrorectal response. Therefore, to study gastrorectal meal response with the barostat, a meal of 600-kcal is sufficient and a correction for parity should be made when results are compared.     

Entitling the student doctor

Oscar Thompson, a third-year medical student on a shift in the emergency department, is eager to participate in as many procedures as possible. According to the triage nurse’s history, the next patient to be seen is a 58-year-old man who has had fever, headache, and neck stiffness. Anticipating his first lumbar puncture, Oscar approaches the room with enthusiasm. The nurse whispers that the patient is irritated and can’t wait to see the doctor. The student pauses, draws back the curtain, and says, “Hello, I’m Dr. Thompson, how can I help you today?”     

The effects of aging on muscarinic receptor/G-protein coupling in the rat hippocampus and striatum

In the striatum and hippocampus, there is a loss of sensitivity to muscarinic agonists with age which has been traced to events early in the signal transduction pathway. Our laboratory has therefore focussed on investigations at this level. The current experiments investigate the effects of age on G-protein/receptor interactions by using competitive binding assays to measure the ability of GppNHp to decrease the proportion of receptors bound to G-proteins in the absence and the presence of added Mg2+. L-[3H]Quinuclidinyl benzilate was used as a nonselective ligand and [3H]pirenzepine as an M1 selective ligand. We find that: (1) muscarinic receptors and G-proteins in the striatum appear to become loosely coupled with age, with no change in Mg2+ sensitivity. (2) M1-receptor/G-protein complexes in the hippocampus display increased sensitivity to the presence of Mg2+ with age, with those from old but not young tissue requiring added Mg2+ in order to uncouple. This effect, however, may not be M1 specific.