Immunotherapy trial as diagnostic test in evaluating patients with presumed autoimmune gastrointestinal dysmotility.

BACKGROUND: Chronic gastrointestinal dysmotility greatly impacts the quality of life. Treatment options are limited and generally symptomatic. Neural autoimmunity is an under-recognized etiology. We evaluated immunotherapy as an aid to diagnosing autoimmune gastrointestinal dysmotility (AGID). METHODS: Twenty-three subjects evaluated at the Mayo Clinic for suspected AGID (August 2006-February 2014) fulfilled the following criteria: (1) prominent symptoms of gastrointestinal dysmotility with abnormalities on scintigraphy-manometry; (2) serological evidence or personal/family history of autoimmune disease; (3) treated by immunotherapy on a trial basis, 6-12 weeks (intravenous immune globulin, 16; or methylprednisolone, 5; or both, 2). Response was defined subjectively (symptomatic improvement) and objectively (gastrointestinal scintigraphy/manometry studies). KEY RESULTS: Symptoms at presentation: constipation, 18/23; nausea or vomiting, 18/23; weight loss, 17/23; bloating, 13/23; and early satiety, 4/23. Thirteen patients had personal/family history of autoimmunity. Sixteen had neural autoantibodies and 19 had extra-intestinal autonomic testing abnormalities. Cancer was detected in three patients. Preimmunotherapy scintigraphy revealed slowed transit (19/21 evaluated; gastric, 11; small bowel, 12; colonic, 11); manometry studies were abnormal in 7/8. Postimmunotherapy, 17 (74%) had improvement (both symptomatic and scintigraphic, five; symptomatic alone, eight; scintigraphic alone, four). Nine responders re-evaluated had scintigraphic evidence of improvement. The majority of responders who were re-evaluated had improvement in autonomic testing (six of seven) or manometry (two of two). CONCLUSIONS & INFERENCES: This proof of principle study illustrates the importance of considering an autoimmune basis for idiopathic gastrointestinal dysmotility and supports the utility of a diagnostic trial of immunotherapy.

Results of ambulatory pH monitoring do not reliably predict response to therapy in patients with eosinophilic oesophagitis.

BACKGROUND: The consensus statements for eosinophilic oesophagitis recommend that ambulatory pH monitoring is one means of determining if gastro-oesophageal reflux is the cause of oesophageal eosinophilia and should guide pharmacological therapy. AIM: To evaluate prospectively the accuracy of pH monitoring as a predictor of endoscopic, histological and symptomatic response in patients with oesophageal eosinophilia. METHODS: We conducted a prospective trial in which patients with oesophageal eosinophilic infiltration with ≥15 eos/hpf underwent a 24-h pH study and were placed in one of two treatment arms for 6 weeks based on positive or negative results. Patients with abnormal acid exposure were treated with esomeprazole 40 mg twice daily and others were treated with oral viscous budesonide 1 g twice daily. Response to treatment was assessed by oesophageal histology (<5 eos/hpf) and symptoms. RESULTS: A total of 51 patients were enrolled in the study. The average patient age was 39 years and 31 patients (61%) were male. The average number of eosinophils per hpf, prior to study enrolment was 41.2 (range 15-140, s.d. 27.7). Nineteen (37%) had positive pH studies and 32 (63%) had negative pH studies. Eighteen patients completed treatment with esomeprazole. Only eleven (61%) had histological response and, of these eleven, five (46%) had symptomatic improvement. A total of 28 patients with normal acid exposure completed treatment with budesonide. Only 16 (57%) had histological and 11 (69%) had symptomatic improvement. CONCLUSION: In this prospective trial of pH-guided treatment, neither positive nor negative results of initial pH monitoring accurately predicted response to therapy.

The efficacy of probiotics in the treatment of irritable bowel syndrome: a systematic review.

INTRODUCTION: Probiotics may benefit irritable bowel syndrome (IBS) symptoms, but randomised controlled trials (RCTs) have been conflicting; therefore a systematic review was conducted. METHODS: MEDLINE (1966 to May 2008), EMBASE (1988 to May 2008) and the Cochrane Controlled Trials Register (2008) electronic databases were searched, as were abstracts from DDW (Digestive Diseases Week) and UEGW (United European Gastroenterology Week), and authors were contacted for extra information. Only parallel group RCTs with at least 1 week of treatment comparing probiotics with placebo or no treatment in adults with IBS according to any acceptable definition were included. Studies had to provide improvement in abdominal pain or global IBS symptoms as an outcome. Eligibility assessment and data extraction were performed by two independent researchers. Data were synthesised using relative risk (RR) of symptoms not improving for dichotomous data and standardised mean difference (SMD) for continuous data using random effects models. RESULTS: 19 RCTs (18 papers) in 1650 patients with IBS were identified. Trial quality was generally good, with nine reporting adequate methods of randomisation and six a method of concealment of allocation. There were 10 RCTs involving 918 patients providing outcomes as a dichotomous variable. Probiotics were statistically significantly better than placebo (RR of IBS not improving=0.71; 95% CI 0.57 to 0.88) with a number needed to treat (NNT)=4 (95% CI 3 to 12.5). There was significant heterogeneity (chi(2)=28.3, p=0.001, I(2)=68%) and possible funnel plot asymmetry. Fifteen trials assessing 1351 patients reported on improvement in IBS score as a continuous outcome (SMD=-0.34; 95% CI -0.60 to -0.07). There was statistically significant heterogeneity (chi(2)=67.04, p<0.001, I(2)=79%), but this was explained by one outlying trial. CONCLUSION: Probiotics appear to be efficacious in IBS, but the magnitude of benefit and the most effective species and strain are uncertain.

Initiation of apoptosis by photodynamic therapy using a novel positively charged and water-soluble near infra-red photosensitizer and white light irradiation.

Our aim was to investigate the photophysical and photodynamic properties of a new, water-soluble positively charged and chemically stable photosensitizer: tetrahydroporphyrin tetratosylat (THPTS). Absorption, fluorescence and (1)H NMR spectra and the intracellular distribution of THPTS were measured. The apoptosis in choroidal melanoma cells was measured using cell death detection ELISA and caspase-8 activity assay. THPTS-PDT efficiency was studied in Balb/c mice bearing C26 colon carcinoma. Subcutaneously located tumors were irradiated with a white light source at a fluence rate of 100 mW/cm(2). THPTS was administrated 3 h before illumination. The tumoricidal effect was examined 24 h after THPTS-PDT by vital staining with 0.4-ml 1% Evans blue solution, intraperitoneally injected to each mouse. THPTS showed a strong absorption band at 760 nm. Its purity, measured by (1)H NMR, is better than 99%. At 24-h incubation period, CLSM revealed THPTS fluorescence in mitochondria and cell nucleus. THPTS possesses no toxic effect in preincubated CM cells without irradiation, and THPTS-PDT causes efficient apoptosis. THPTS-PDT using white light irradiation at a dose of 480 J/cm(2) caused necrosis with a depth of 8 mm in subcutaneously located C26 colon carcinoma in Balb/c-mice. In accordance with the present results, the THPTS seems to be of interest for further in vivo investigations with broad-band white light sources.

Does co-administration of a non-selective opiate antagonist enhance acceleration of transit by a 5-HT4 agonist in constipation-predominant irritable bowel syndrome? A randomized controlled trial.

Opioid neurons exhibit tonic restraint on intestinal motility; opioid antagonists stimulate peristalsis and increase transit. In vitro, 5-hydroxytryptamine (5-HT4) agonists combined with selective opioid antagonists significantly increased colonic propulsion relative to a 5-HT4 agonist alone. We hypothesized that the combination of 5-HT4 agonist and non-selective opioid antagonist enhances intestinal transit more than either treatment alone in female constipation-predominant irritable bowel syndrome (C-IBS) patients. Our aim was to examine the effect of tegaserod 6 mg b.i.d. alone and combined with naltrexone 50 mg on intestinal transit and stool characteristics in females with C-IBS. Forty-eight patients were randomized to tegaserod alone, naltrexone alone or in combination with tegaserod or placebo for 6 days. Small bowel, ascending colon half-life (in pharmacokinetics) (t1/2), and colonic geometric centre (8, 24, 48 h) were assessed by scintigraphy. Tegaserod increased small bowel (P < 0.01) and colon transit (P < 0.01). Naltrexone did not accelerate colonic transit relative to placebo. Combination treatment did not significantly accelerate transit relative to tegaserod alone. Tegaserod and tegaserod with naltrexone resulted in looser stool form (P < 0.01). In female C-IBS patients, tegaserod accelerates small bowel and colon transit and contributed to looser stool consistency. Use of naltrexone, 50 mg, does not support the hypothesis that combination of 5-HT4 agonist and non-selective opioid antagonist enhances intestinal transit.

Eosinophilic esophagitis: an update.

Eosinophilic esophagitis (EE) is a disease that is being recognized with increasing frequency. In children it is responsible for feeding disorders, vomiting, reflux symptoms and abdominal pain and in adults it causes dysphagia and esophageal food impactions. The diagnosis requires the histologic finding of > 20 eosinophils per high powered field in esophageal squamous mucosa. The most common treatment regimens in children and adults involve the ingestion of topical corticosteroids. Symptomatic relapse after one treatment course is common, and many patients require repeated courses of treatment. The long-term prognosis of EE is largely unknown.

Burn care standards in Israel: lack of consensus.

UNLABELLED: In recent years, the need for a national burn center based on ABA guidelines has emerged in Israel. The formation of such a center is now underway in the Chaim Sheba Medical Center. As a first step in the standardization of burn care in Israel, we have conducted a nation-wide survey among burn care personnel (physicians, nurses and other burn team members), regarding different aspects of the treatment of burn patients. METHODS: A questionnaire comprised of 30 questions regarding the severity of burns admitted, the site of initial management, wound care (both burn/skin-graft sites and donor sites), dressing changes protocols, sterility precautions, hydrotherapy, and pressure dressings was presented to 70 health-care professionals involved in the treatment of burns. RESULTS AND DISCUSSION: Seventy-seven percent of interviewed personnel participated in the survey. Consensus was found regarding most local (topical) wound care, (SSD for clean non-facial burns, Sulfamylon (mafenide-acetate) for contaminated non-facial burns, Threolone (chloramphenicol 3% and prednisolone 0.5%) or Bacitracin for facial burns, Paraffin gauzes with or without Sulfamylon for donor and graft sites). Dressing changes regimes were also agreed upon generally. However, there was no consensus regarding the ideal time for the removal of donor site dressings and this issue will need to be resolved. Other important findings are that both Edinborough University Solution of Lime (EUSOL), which has been deemed unsuitable for burn treatment due to toxic effects, and hydrotherapy, which has been proposed as a source of infection and contamination, are still widely used. We anticipate that these issues will be settled in our unified national burn care protocols (which are currently under development and revision).

Comparison of gastric volumes in response to isocaloric liquid and mixed meals in humans.

AIMS: To compare gastric volume responses to ingestion of isocaloric liquid or mixed (solid-liquid) meals and document the intra- and interindividual reproducibility of gastric volume measurement using single photon emission computed tomography (SPECT) imaging after i.v. 99mTc-pertechnetate. METHODS: Eight healthy volunteers performed two studies at least 9 months apart. Gastric volumes were measured after a 317 kcal liquid nutrient meal. Within 2 weeks of the second liquid meal study, participants performed a third study, ingesting an isocaloric mixed meal. The order of the mixed and second liquid meals was randomized; Bland-Altman plot displayed data on repeated studies with liquid meal and paired t-test compared gastric volumes after mixed or liquid isocaloric meals. RESULTS: Fasting and postprandial gastric volumes associated with the two liquid meals were not significantly different; inter- and intra-individual coefficients of variation were 13 and 13.8%. In response to the mixed meal, there was a lower absolute postprandial volume and lower change in gastric volume over fasting volume compared with the response to the liquid meal (P = 0.0001). CONCLUSION: The SPECT measurement of gastric volumes in response to a nutrient liquid meal is reproducible. The magnitude of the volume response is greater after the liquid meal compared with the isocaloric mixed meal.

[Silicone gel-filled breast implants and breast cancer--an update and safety].

Silicone gel-filled breast implants have long been an important method of breast reconstruction and breast augmentation. In 1992, the Food and Drug Administration (FDA), implemented a voluntary but strongly urged moratorium on the sale and use of silicone gel-filled breast implants. This was due to previous anecdotal reports regarding possible health hazards associated with these types of implants, including the emergence of breast cancer. The FDA allowed the use of silicone gel-filled breast implants for post-mastectomy reconstruction, and also in a small number of breast augmentation patients who were willing to enroll in a long-term prospective study. In this article, we review the current available literature that failed to produce any evidence associating the use of silicone breast implants with the increased risk of breast cancer.

Macrophage suspensions prepared from a blood unit for treatment of refractory human ulcers.

This paper presents an innovative method for the treatment of refractory wounds, starting with a blood unit, that is based on a biological approach. Local wound repair is one of the major unresolved clinical problems. Age, infection, clinical conditions such as diabetes mellitus, cardiac, renal, lung and liver failure, malnutrition and immunological deficiencies are among the reasons for wound repair delay or failure. Many chronic ulcers resist conventional treatment and do not heal for months and years, thus causing substantial morbidity and even mortality. The method for macrophage suspension treatment consists of introducing into the wound live cells that play a major role in the process of wound healing. The suspension is prepared from a blood unit of a healthy donor in a cost-effective, closed, sterile system. In the process of preparation, the macrophages are activated by hypo-osmotic shock to enhance their various functions in wound repair. The cells are applied to the wound either by local injection or by direct deposition into the wound. In most cases (90%), only one treatment is sufficient. Since 1995, macrophage suspensions have been used successfully in more than 1000 patients in several hospitals in Israel, without any side effects. Our results show that the use of a macrophage suspension is a safe and effective therapeutic strategy that shortens the healing period, reduces risk of complications and morbidity and improves the quality of life for long-suffering patients. This treatment requires no hospitalization and can be given on an ambulatory basis.

Interventional magnetic resonance imaging for guiding gene and cell transfer in the heart.

BACKGROUND: Interventional magnetic resonance imaging (iMRI) has the potential for guiding interventional cardiac procedures in real time. OBJECTIVES: To test the feasibility of iMRI guided gene and cell transfer to the heart and to monitor myocardial remodelling after myocardial infarction in a rat model. METHODS: The MRI contrast agent GdDTPA, together with either Evans blue dye, or a recombinant adenovirus encoding the LacZ gene, or primary fibroblasts tagged by BrdU, were injected into the myocardium of rats under iMRI guidance. Rats were killed seven days after the injection and the hearts sectioned to identify the blue dye, LacZ expression, or fibroblast presence, respectively. In a parallel study, left ventricular area was measured before and after myocardial infarction and in sham operated rats by T1 weighted MRI and by echocardiography. RESULTS: Location of GdDTPA enhancement observed with iMRI at the time of injection was correlated with Evans blue stain, beta-gal expression, and the primary fibroblast location in histological studies. iMRI and echocardiography measured a comparable increase in left ventricular area at seven and 30 days after myocardial infarction. A good correlation was found between the iMRI and echocardiographic assessment of left ventricular area (r = 0.70; p < 0.0001) and change in left ventricular area with time (r = 0.75; p < 0.0001). CONCLUSIONS: The results show the feasibility and efficiency of iMRI guided intramyocardial injections, and the ability to monitor heart remodelling using iMRI. Genes, proteins, or cells for tissue engineering could be injected accurately into the myocardial scar under iMRI guidance.

Effect of a somatostatin analogue on gastric motor and sensory functions in healthy humans.

BACKGROUND: Pharmacological approaches to alter satiation may have an impact on functional upper gastrointestinal disorders and potentially change food intake in obesity. AIM: Our aim was to compare the effects of two doses of octreotide and placebo on postprandial symptoms, gastric accommodation, and gastric emptying using validated non-invasive techniques. METHODS: In a randomised, parallel group, two dose, double blind, placebo controlled study, 39 healthy participants (13 per group) were randomised to 30 or 100 micro g octreotide or placebo, administered subcutaneously, 30 minutes before each study. Studies were performed on three separate days and included scintigraphic gastric emptying of solids and liquids, (99m)Tc SPECT imaging to measure fasting stomach volume and gastric accommodation following a 300 ml Ensure meal, and a standardised nutrient drink test to measure maximum tolerated volume and postprandial symptoms. RESULTS: Relative to placebo, both doses of octreotide delayed gastric emptying of solids (not liquids), increased fasting gastric volume, reduced the change in gastric volume post meal, and decreased the sensation of fullness after a satiating meal. CONCLUSION: The somatostatin analogue octreotide significantly alters human gastric functions, including inhibition of the normal reflex responses of gastric volume increase and emptying of the meal. These pharmacological effects suggest studies of the medication in disorders of satiation, including obesity and dyspepsia, are warranted.

Treatment of rhinophyma with Er:YAG laser.

BACKGROUND AND OBJECTIVE: Rhinophyma is a benign, disfiguring disorder of the nose which presents the end stage of acne rosacea, and can also occasionally result in nasal airway obstruction. We describe the first series of patients treated with Erbium laser. STUDY DESIGN/MATERIALS AND METHODS: Severe-to-moderate rhinophyma in six patients were treated at our institution between 1995 and 1996, using the Erbium:YAG (Erb:YAG) laser. RESULTS: All patients achieved marked cosmetic improvement, with no complications. Post-operative healing time was seven to fourteen days-significantly shorter than similar other modalities. CONCLUSIONS: The Erbium laser provides very accurate tissue ablation and allows the sculpturing of the hypertrophied areas, offering good cosmetic results, with a very short healing period as shown in our study.

The effect of reduction of the peripheral fat content by liposuction-assisted lipectomy (SAL) on serum leptin levels in the postoperative period: a prospective study.

The purpose of this study was to investigate the relationship between a decrease in the peripheral fat content by suction-assisted lipectomy (SAL) and serum leptin levels. Twenty-two healthy females who underwent SAL for aesthetic reasons participated in the study. The data included height, weight, dietary habits, and leptin levels before surgery and at 1 and 6 weeks postoperatively. The aspirate ranged between 1000 and 6000 ml, with an average of 2700 ml. Thirteen patients with an aspirate of over 2700 ml all experienced an immediate postoperative decrease in appetite which returned gradually by 12 to 17 days postoperatively. They lost an average of 7% of the total body weight at 6 weeks. The leptin levels 1 week postoperatively were significantly lower than the preoperative levels (p < 0.01); at 6 weeks the decrease in leptin level was not statistically significant. In conclusion, a reduction of the peripheral fat content of more than 2700 ml by SAL has an immediate effect on leptin levels that lasts at least 1 week and correlates with voluntary changes in energy intake.

Breast augmentation with fresh-frozen homologous fat grafts.

The purpose of this report is to present a patient who underwent breast augmentation with fresh-frozen fat homografts in Russia 10 years ago, despite the publication of major complications following this procedure.

Substance use among gay and lesbian adolescents.

Surveys at a Massachusetts high school used multiple items to identify gay, lesbian, and bisexual teenagers. Students with consistent homosexual preferences had greatly elevated rates of substance use. Those who displayed a homosexual preference but answered less consistently also had somewhat higher rates of substance use but were closer to heterosexual youths than to more consistent homosexual youths. The differences in substance use were least for alcohol use and greater for "hard" drugs.

Total lower lip reconstruction with innervated muscle-bearing flaps: a modification of the Webster flap.

BACKGROUND: Mohs surgery and other surgical techniques are used for the removal of squamous cell carcinoma of the lower lip and may leave a large defect in the vermilion and underlying tissue. When nearly the entire lower lip is excised, reconstruction of this defect is a challenge. Repair requires the matching of vermilion color, maintenance of oral sphincter function and mouth opening size, and retention of sensation. Several techniques have been suggested. We present a modification of the Webster flap for total lower lip reconstruction using innervated muscle-bearing flaps. OBJECTIVE: To present a surgical technique for the reconstruction of total lower lip defects after excision of squamous cell carcinoma. METHODS: Innervated muscle-bearing flaps are used and demonstrated in one case. The surgical technique is discussed in detail. RESULTS: The reconstructive results were excellent. There were no postoperative complications. CONCLUSION: The use of innervated muscle-bearing flaps is a useful and effective option for the reconstruction of total lower lip defects.

Monitoring response to convection-enhanced taxol delivery in brain tumor patients using diffusion-weighted magnetic resonance imaging.

Convection-enhanced drug delivery (CEDD) is a novel approach to enhance the delivery of drugs directly into brain tumors. We have used diffusion-weighted MRI (DWMRI) to monitor the effects of intratumoral CEDD in three brain tumor patients treated with Taxol. Clear changes in the images and the water diffusion parameters were observed shortly after the initiation of treatment. Initially, a bright area corresponding to decreased diffusion appeared, followed by the appearance of a dark area of increased diffusion within the bright area. The time to appearance of the dark area varied among the patients, suggesting different response rates. In this work, we have demonstrated the feasibility of using DWMRI as a noninvasive tool to achieve unique early tissue characterization not attainable by other conventional imaging methods.