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.

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.

[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.

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.

The versatility of the nasolabial flap enhanced by the delay procedure.

BACKGROUND: The nasolabial flap is a versatile and effective option for the closure of nasal defects of the cheek and nasal sidewall following Mohs surgery. However, both extirpation of a tumor in the region of the base of the flap or previous use of the flap often destroy the proximal axial blood supply to the flap, excluding its immediate utilization. We describe a different use of the nasolabial flap and a technique for preserving its capacity in the case of reutilization OBJECTIVE: To describe the versatility of the nasolabial flap and a delay procedure that enables its exploitation despite prior disruption of the proximal blood supply. METHODS: Three different uses of the same nasolabial flap are demonstrated in one patient. The surgical techniques are discussed in detail. RESULTS: The reconstructive results were excellent. There were no postoperative complications. CONCLUSION: The nasolabial flap is a versatile and effective option for the closure of nasal defects of the cheek and nasal sidewall. When the nasolabial flap has been used before, or its blood supply compromised, the delay procedure can reestablish its applicability.

The microenvironment of human Peyer's patches inhibits the increase in CD38 expression associated with the germinal center reaction.

Analysis of B cells in the human tonsils identified CD38 expression as a hallmark of germinal center (GC) B cells. However, the signals responsible for the in vivo induction of CD38 have not been determined. The primary site for generation of memory and plasma cells in the gastrointestinal tract is the GCs of Peyer's patches (PP). PP and intestinal mucosa, but not tonsils or oral mucosa, express mucosal addressin cell adhesion molecule-1 (MAdCAM-1). The ligand for MAdCAM-1, integrin alpha(4)beta(7), is expressed on naive B cells and memory B cells that traffic to the gastrointestinal tract. In this study we determine that, unlike tonsil, human PP GC B cells do not express significant levels of CD38. PP B cells can be induced to express CD38 upon culture with CD40 ligand, anti-B cell receptor, and IFN-gamma. However, coculture of tonsil naive B cells with an Ab directed against integrin beta(7) inhibits IFN-gamma-induced CD38 hyperexpression. The absence of CD38 on PP GCs suggests that there are tissue-specific pathways of B cell development that differ between tonsil and PP. The differential expression pattern of MAdCAM-1, together with the observation that ligation of beta(7) can inhibit the induction of CD38 expression, suggests that ligation of alpha(4)beta(7) in vivo may contribute to a PP-specific GC phenotype.

The use of magnetic resonance imaging in the differential diagnosis between starch and fecal peritonitis.

Granulomatous peritonitis, caused by the starch from the surgeons' gloves, is a hypersensitivity reaction that can complicate abdominal surgery and mimic other causes of peritonitis. The diagnosis of this entity is difficult to make, and relies on a high index of suspicion. We suggest the use of magnetic resonance imaging to facilitate the diagnosis of this condition, based on an experimental animal model. 84 rats were subjected to laparotomy, and the abdominal cavity was exposed to either saline solution, talc solution, starch solution or fecal material by creating a cecal perforation. TI-weighted magnetic resonance images, with and without gadolinum enhancement, were taken after 3, 5 and 10 days. The animals were then sacrificed and the abdominal contents were evaluated both macroscopically and microscopically. Both talc and starch caused gross adhesions involving the entire abdominal viscera, and microscopy revealed signs of inflammation and fibrosis. Starch induced reactive granulomas. The adhesions in the cases of fecal peritonitis were confined to the area of the perforation. MR images of the starch peritonitis group was remarkable for a diffuse pathological process with enhancement of the omentum and the peritoneum after gadolinum injection. The MR readings of the fecal peritonitis group showed a localized process with no diffuse enhancement of the peritoneum. The striking differences between the magnetic resonance images of starch and fecal peritonitis in rats suggest that this modality is both sensitive and specific in diagnosing starch peritonitis in a rat model. Early non-invasive diagnosis of these separate entities would ease the establishment of the appropriate treatment. We are currently investigating the use of MRI imaging in suspected starch peritonitis in humans.

Photothermic treatment of pigmented B16 melanoma using a broadband pulsed light delivery system.

Pulsed photothermic treatment (PTT) of pigmented B16 mice melanoma tumors was carried out using a Photodyne incoherent light delivery system. Tumor heating with average temperature of 41-44 degrees C was observed during broadband photoirradiation (600-800 nm) at light doses of 60-120 J/cm(2) delivered using 0.6 J/cm(2) pulses (2 ms) at 1 Hz repetition rate. Electron microscopy of tumor samples revealed pronounced structural changes in microvasculature and melanosomes. Pulsed PTT caused damage to endothelial cells and vascular walls, swelling of mitochondria and melanosomal disruption without nuclear alteration. Significant tumor response with necrosis formation followed by tumor regression was observed by a tumor growth study after PTT at 120 J/cm(2).

Photodynamic therapy of cutaneous lymphoma using 5-aminolevulinic acid topical application.

BACKGROUND: Photodynamic therapy (PDT) with topical application of 5-aminolevulinic acid (ALA) is a new and effective modality for treatment of superficial basal and squamous cell carcinomas. OBJECTIVE: We present the kinetics of ALA-induced protoporphyrin IX (PP) accumulation and the results of ALA PDT treatment on two patients with different stages (stage I and stage III) of mycosis fungoides (MF)-type cutaneous T-cell lymphoma (CTCL). METHODS: ALA-Decoderm cream was applied to the lesions for 16 hours. Spectrofluorescence measurements of PP accumulation were carried out before, during, and 1 hour after photoirradiation (580-720 nm) using the VersaLight system. RESULTS: Different patterns of PP fluorescence kinetics were observed in patients with early and advanced stages of the disease. During photoirradiation the intensity of fluorescence decreased depending on the lesion thickness. One hour after the photoirradiation procedure no PP fluorescence was observed in the stage I MF lesion, while in the thick stage III MF lesions, PP fluorescence reappeared; after an additional 10-15 minutes of irradiation PP fluorescence disappeared. Complete response with excellent cosmetic results was observed in the stage I lesion after a single irradiation with a light dose of 170 J/cm2; in five stage III lesions, complete response was achieved after fractionated irradiation with a total light dose of 380 J/cm2 (follow-up at 27 and 24 months, respectively). CONCLUSION: The results showed a high response of both stage I and stage III MF lesions to ALA PDT. This modality appears to be very effective and can be used successfully for MF treatment.

Enhancement of ALA-PDT damage by IR-induced hyperthermia on a colon carcinoma model.

The interaction of photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) and hyperthermia is not well understood. In the present study, significant enhancement of tumor damage was observed after simultaneous application of ALA-PDT and IR-induced hyperthermia using a broad-band incoherent light source. One hour after systemic administration of ALA at a dose of 200 mg/kg, subcutaneously transplanted C26 colon carcinoma tumors were irradiated with two bands of the VersaLight system, red (R, 580-720 nm) and red plus IR (R + IR, 580-720 nm and 1250-1600 nm). Photoirradiation using the R + IR band at different fluence rates and exposures caused mild heating of the tumor to 39-43 degrees C at a 3 mm depth. Electron microscopy after ALA + R, ALA + R + IR and R + IR treatments showed early mitochondrial swelling that was more pronounced in the ALA + R + IR group. Tumor necrosis assessment, using histology and vital staining, revealed an enhancement of tumor necrosis depth in the ALA + R + IR group compared to ALA + R and R + IR. The results showed that subhyperthermic heating to 39-39.5 degrees C in the ALA + R + IR group decreased the threshold light dose required for 100% tumor necrosis from 210 J/cm2 (observed in the ALA + R group) to 140 J/cm2. A tumor growth delay test, based on tumor volume measurement, also revealed significant enhancement of antitumor effect after application of ALA + R + IR compared to ALA + R.

Turnover forehead flap combined with composite crus of helix graft for partial nasal reconstruction.

Partial lateral nasal defects challenge the plastic surgeon both technically and aesthetically. Many methods for reconstruction of these defects have been described. We have used a turnover forehead flap in conjunction with composite auricular graft for the reconstruction of nasal defects. The forehead flap is turned over so that the forehead skin serves as internal lining in the nose. The composite auricular graft serves as external nasal lining and provides mechanical support to the ala. The technique was used in seven patients and is presented here with illustrations, selected cases, results, and conclusions concerning patient selection.