Current perspectives on the diagnosis and treatment of functional esophageal disorders

Among the functional gastrointestinal disorders, functional disorders of the esophagus are second in prevalence only to irritable bowel syndrome. Progress has been made in recent years in our understanding of the pathophysiology of functional esophageal disorders. In this review we focus on recent advances in their diagnosis and treatment. Additionally, we critically appraise the current understanding of the various clinical aspects of each esophageal disorder. Finally, we highlight unanswered questions and areas of controversy.     

Pseudo-Behçet's disease

The conditions of complex aphthosis, EM, MMP, and the VVG variant of erosive oral LP may be confused by clinicians who refer patients for diagnosis and management of BD (Table 8). The mucocutaneous presentations or the presence of complex aphthosis, the hallmark of BD, can be confusing and lead to the referral of the patient for a diagnosis of BD. The astute clinician evaluating patients for BD considers pseudo-BD in the differential diagnosis of the mucocutaneous manifestations of BD.     

Burning mouth syndrome

Burning mouth syndrome is the occurrence of oral pain in a patient with a normal oral mucosal examination. It can be caused by both organic and psychologic or psychiatric factors, which can be broken down into local, systemic. psychologic or psychiatric, and idiopathic causes. The most frequently associated conditions are psychiatric (depression, anxiety, or cancerphobia); xerostomia; nutritional deficiency; allergic contact dermatitis; candidiasis; denture-related pain: and parafunctional behavior. Multiple different factors contributing to the oral pain are common, and a systematic approach to the evaluation is important. Identification of correctable causes of BMS should be emphasized and psychiatric causes should not be invoked without thorough evaluation of the patient. A directed history and careful oral examination must be completed to exclude local diseases and identify clues to potential causes. Assessment of medications, psychiatric history and background, and selected laboratory and patch tests may help identify the etiologies of these symptoms. Treatment should be tailored to each patient and may best be managed in a multidisciplinary approach with input from dermatologists, dentists, psychiatrists. otorhinolaryngologists, and primary care providers. A thoughtful and structured evaluation of the patient with BMS has been associated with improvement in about 70% of patients. The remaining patients may benefit from empiric therapy with a chronic pain protocol and continued supportive interactions.     

Modulation of Porphyromonas gingivalis proteinase activity by suboptimal doses of antimicrobial agents

BACKGROUND: Antimicrobial agents are sometimes used as adjuncts for the treatment of aggressive and refractory forms of periodontitis. In this study, we used a culture plate assay to investigate the effect of suboptimal doses of antimicrobial agents on proteinase activity of Porphyromonas gingivalis. METHODS: A culture plate assay using gelatin as the substrate, which allows a semiquantitative determination of proteinase activity, was developed. Suboptimal inhibitory concentrations of tetracycline, minocycline, doxycycline, metronidazole, penicillin G, or chlorhexidine were added to the medium, and proteolysis zones were determined following the growth of three strains of P. gingivalis. The effect of antimicrobials on outer membrane vesicle-associated gingipains also was determined. RESULTS: The gelatin plate assay was a convenient, simple procedure for investigating the effect of suboptimal inhibitory concentrations of antimicrobial agents on proteinases produced by P. gingivalis. The largest reduction (> 75%) in the proteolysis zones produced by three strains of P. gingivalis was obtained with minocycline. Tetracycline and doxycycline also reduced the proteolysis zones. A suboptimal inhibitory concentration of chlorhexidine increased the proteolysis zones by up to 70%. Metronidazole and penicillin G produced no noticeable effect. The suboptimal inhibitory concentrations of minocycline, tetracycline, and doxycyline did not reduce the activity of outer membrane vesicle-associated Arg- and Lys-gingipains. CONCLUSION: Results from this study suggest that sublethal concentrations of some antimicrobial agents in subgingival sites have the potential to affect the physiology of P. gingivalis, notably by increasing or decreasing the proteolytic activity of the bacteria.     

Effectiveness of medical resident education in mechanical ventilation

Specific methods of mechanical ventilation management reduce mortality and lower health care costs. However, in the face of a predicted deficit of intensivists, it is unclear whether residency programs are training internists to provide effective care for patients who require mechanical ventilation. To evaluate these educational outcomes, we administered a validated 19-item case-based test and survey to resident physicians at 31 diverse U.S. internal medicine residency programs nationwide. Of 347 senior residents, 259 (75%) responded. The mean test score was 74% correct (SD, 14%; range, 37 to 100%). Important items representing evidence-based standards of critical care answered incorrectly were as follows: use of appropriate tidal volume in the acute respiratory distress syndrome (48% incorrect), identifying a patient ready for a weaning trial (38% incorrect), and recognizing indication for noninvasive ventilation (27% incorrect). Most accurately identified pneumothorax (86% correct) and increased intrathoracic positive end-expiratory pressure (93% correct). Better scores were associated with "closed" versus "open" intensive care unit organization (76 versus 71% correct, p = 0.001), resident perception of greater versus lesser ventilator knowledge (79 versus 71% correct, p = 0.001), and graduation from a U.S. versus international medical school (75 versus 69% correct, p = 0.033). Although overall training satisfaction correlated strongly with program use of learning objectives (r = 0.89, p < 0.0001), only 46% reported being satisfied with their mechanical ventilation training. We conclude that senior residents may not be gaining essential evidence-based knowledge needed to provide effective care for patients who require mechanical ventilation. Residency programs should emphasize evidence-based learning objectives to guide mechanical ventilation instruction.     

Differential responses of HSPs to heat stress in slow and fast regions of rat gastrocnemius muscle

In a recent study, we showed that the rat slow soleus and fast plantaris muscles exhibited different time courses for the response of specific heat shock proteins (HSPs) after 1 h of heat stress. We hypothesized that these differential responses were related, in part, to the varying fiber type composition of these muscles. To further test this hypothesis, we now have determined the responses of Hsp60, Hsp72, and Hsc73 during the 60 h following exposure to a single bout of heat stress in the deep (relatively high percentage of slow fibers) and superficial regions (only fast fibers) of the adult rat gastrocnemius muscle. The temperature of the musculature in the left hindlimb was elevated to approximately 42 degrees C for 1 h, while the right hindlimb served as a control. Two hours after the heat stress, the Hsp60 levels were increased by 1.3- and 2.0-fold in the deep and superficial regions, respectively. The Hsp72 levels were increased (1.8-fold) in the deep region at 8 h after heat stress, whereas in the superficial region these levels were increased between 4 and 48 h (peak at 36 h by 10-fold) after the heat stress. No changes were observed for Hsc73 in either region of the muscle. Combined with our previous data, the results indicate that the responses of HSPs in the rat hindlimb muscles after a single exposure to heat stress are related to fiber type composition of the muscle or muscle region or to the inherent properties of each HSP. From a clinical viewpoint, these data indicate that specific regions (most likely based on fiber type composition) within a muscle may be affected differentially by any intervention inducing HSPs.     

Spleen hemostasis using high-intensity ultrasound: survival and healing

BACKGROUND: Previous studies have shown that high-intensity focused ultrasound (HIFU) can effectively control bleeding of incised livers and spleens and punctured vessels. This current study investigated the long-term safety of HIFU in splenic hemostasis. METHODS: A total of 21 rabbits were randomly assigned to two groups: HIFU treatment (n = 14), and sham treatment (n = 7). All animals underwent sterile laparotomy and splenic exposure. The HIFU-treated animals received splenic incisions, 8 to 10 mm long and 4 to 5 mm deep, and immediate 9.6-MHz HIFU until hemostasis was achieved. After recovery, ultrasound images, blood samples, and histologic samples were collected on days 0, 1, 3, 7, 14, 28, and 60. RESULTS: All 14 splenic injuries were hemostatic after an average of 96 seconds of HIFU application. There was evidence of rebleeding in one animal between days 3 and 7 posttreatment. Subsequent blood analysis showed no significant difference in serial hematologic or coagulation measures between HIFU and sham groups. Histologic examination up to 60 days posttreatment revealed scarring and spleen tissue regeneration at the treatment site. CONCLUSION: HIFU provides an effective and safe method of achieving hemostasis after acute splenic injury.     

Factors influencing the decision to amputate or reconstruct after high-energy lower extremity trauma

BACKGROUND: Factors thought to influence the decision for limb salvage include injury severity, physiologic reserve of the patient, and characteristics of the patient and their support system. METHODS: Eligible patients were between the ages of 16 and 69 with Gustilo type IIIB and IIIC tibial fractures, dysvascular limbs resulting from trauma, type IIIB ankle fractures, or severe open midfoot or hindfoot injuries. Data collected at enrollment relevant to the decision-making process included injury characteristics and its treatment, and the nature and severity of other injuries. Logistic regression and stepwise modeling were used to determine the effect of each covariate on the variable salvage/ amputation. RESULTS: Of 527 patients included in the analysis, 408 left the hospital with a salvaged limb. Of the 119 amputations performed, 55 were immediate and 64 were delayed. The multivariate analysis confirmed the bivariate analysis: all injury characteristics remained significant predictors of limb status with the exception of bone loss; and soft tissue injury and absence of plantar sensation were the most important factors in accounting for model validity. CONCLUSION: Soft tissue injury severity has the greatest impact on decision making regarding limb salvage versus amputation.