[Cardiomyopathy in a 22-year-old man with a long history of methamphetamine abuse]. / Kardiomyopathie bei einem 22-Jährigen mit langjährigem Methamphetaminkonsum.

This article presents the case of a 22-year-old male patient with cardiomyopathy associated with a long history of methamphetamine abuse. Echocardiography revealed a dilated cardiomyopathy with highly reduced systolic pump function and severe mitral valve regurgitation. Inotropic treatment and MitraClip® (Abbott Vascular, Santa Clara, CA, USA) implantation resulted in enhancement of hemodynamics. The rising prevalence of methamphetamine abuse should give reason to raise awareness for the diagnostic work-up and patient history particularly in cases of unexplained cardiomyopathy in young patients.

AAV-9 mediated phosphatase-1 inhibitor-1 overexpression improves cardiac contractility in unchallenged mice but is deleterious in pressure-overload.

The downregulation of ß-adrenergic receptors (ß-AR) and decreased cAMP-dependent protein kinase activity in failing hearts results in decreased phosphorylation and inactivation of phosphatase-inhibitor-1 (I-1), a distal amplifier element of ß-adrenergic signaling, leading to increased protein phosphatase 1 activity and dephosphorylation of key phosphoproteins, including phospholamban. Downregulated and hypophosphorylated I-1 likely contributes to ß-AR desensitization; therefore its modulation is a promising approach in heart failure treatment. Aim of our study was to assess the effects of adeno-associated virus serotype 9 (AAV9) - mediated cardiac-specific expression of constitutively active inhibitor-1 (I-1c) and to investigate whether I-1c is able to attenuate the development of heart failure in mice subjected to transverse aortic constriction (TAC). 6-8 week old C57BL/6 N wild-type mice were subjected to banding of the transverse aorta (TAC). Two days later 2.8 × 1012 AAV-9 vector particles harbouring I-1c cDNA under transcriptional control of a human troponin T-promoter (AAV9/I-1c) were intravenously injected into the tail vein of these mice (n=12). AAV9 containing a Renilla luciferase reporter (AAV9/hRluc) was used as a control vector (n=12). Echocardiographic analyses were performed weekly to evaluate cardiac morphology and function. 4 weeks after TAC pressure- volume measurements were performed and animals were sacrificed for histological and molecular analyses. Both groups exhibited progressive contractile dysfunction and myocardial remodeling. Surprisingly, echocardiographic assessment and histological analyses showed significantly increased left ventricular hypertrophy in AAV9/I-1c treated mice compared to AAV9/hRluc treated controls as well as reduced contractility. Pressure-volume loops revealed significantly impaired contractility after AAV9/I-1c treatment. At the molecular level, hearts of AAV9/I-1c treated TAC mice showed a hyperphosphorylation of the SR Ca2+-ATPase inhibitor phospholamban. In contrast, expression of AAV9/I-1c in unchallenged animals resulted in selective enhancement of phospholamban phosphorylation and augmented cardiac contractility. Our data suggest that AAV9-mediated cardiac-specific overexpression of I-1c, previously associated with enhanced calcium cycling, improves cardiac contractile function in unchallenged animals but failed to protect against cardiac remodeling induced by hemodynamic stress questioning the use of I-1c as a potential strategy to treat heart failure in conditions with increased afterload.

Frequency of homozygous deletion at p16/CDKN2 in primary human tumours.

Many tumour types have been reported to have deletion of 9p21 (refs 1-6). A candidate target suppressor gene, p16 (p16INK4a/MTS-1/CDKN2), was recently identified within the commonly deleted region in tumour cell lines. An increasing and sometimes conflicting body of data has accumulated regarding the frequency of homozygous deletion and the importance of p16 in primary tumours. We tested 545 primary tumours by microsatellite analysis with existing and newly cloned markers around the p16 locus. We have now found that small homozygous deletions represent the predominant mechanism of inactivation at 9p21 in bladder tumours and are present in other tumour types, including breast and prostate cancer. Moreover, fine mapping of these deletions implicates a 170 kb minimal region that includes p16 and excludes p15.

Hexaminolevulinate-induced fluorescence colonoscopy versus white light endoscopy for diagnosis of neoplastic lesions in the colon.

BACKGROUND AND STUDY AIMS: To compare the rate of detection of colorectal neoplastic lesions using the selective photosensitizer precursor hexaminolevulinate (HAL) combined with a new fluorescence video endoscope system against that of standard white light endoscopy, and secondarily, to evaluate the safety profile of HAL-induced fluorescence colonoscopy. PATIENTS AND METHODS: This prospective phase II clinical pilot study from two hospital study centers included 25 patients with known or highly suspected colorectal neoplasia. They underwent sensitization with locally applied 500 ml HAL enemas at a concentration of 1.6 mmol/L. At 60 minutes after enteral HAL administration, fluorescence imaging was done using a special light source capable of delivering either white light or blue excitation light. Red fluorescence induced by illumination with blue light was detected via a prototype fluorescence video colonoscope. Biopsies were taken from suspicious areas found with white or blue light. RESULTS: Using histology as the gold standard, 55 / 93 of neoplastic lesions were detected with white light endoscopy, 53 / 93 with both white and blue light, 38 / 93 with blue light and second-pass white light, and 27/93 with blue light only. Of all neoplastic lesions, 91 / 93 revealed red fluorescence under fluorescence imaging ( P < 0.0001). Fluorescence mode showed 38.7 % (36 / 93) more neoplasms than did white light endoscopy. An isolated slight elevation of bilirubin, by a factor of 1.5, was noted after the administration of HAL. CONCLUSIONS: Administration of HAL as enema induces selective lesion fluorescence and increases lesion detection rate in patients with colorectal neoplasia, especially of flat, nonvisible adenomas.

Medical and endoscopic treatment in peptic ulcer bleeding: a national German survey.

OBJECTIVE: Peptic ulcers are the leading cause of upper gastrointestinal (GI) bleeding. The aim of this study was the evaluation of the recent clinical practice in drug therapy and endoscopic treatment of ulcer bleedings in Germany and to compare the results with the medical standard. METHODS: A structured questionnaire (cross-sectional study) was sent to 1371 German hospitals that provide an emergency service for upper GI bleeding. The project was designed similar to a nationwide inquiry in France in 2001. Forty-four questions concerning the following topics were asked: hospital organisation, organisation of emergency endoscopy service, endoscopic and drug therapy of ulcer bleeding, endoscopic treatment of variceal bleeding. Return of the questionnaires was closed in August 2004. RESULTS: Response rate was 675 / 1371 (49 %). Mean hospitals size was < 200 beds, 49 % (n = 325) had basic care level. 92 % provided a 24-hour endoscopy service, specialized nurses were available in 75 %. Fiberscopes were used only in 15 %. A mean of 10 +/- 12 (range: 0 - 160) bleeding cases/month were treated, 6 +/- 6 cases per month (60 %) were ulcer bleedings. Endoscopy was performed in 72 % immediately after stabilization but in all cases within 24 hours. The Forrest classification was used in 99 % whereas prognostic scores were applied only in 3 %. Forrest Ia,/Ib/IIa/IIb/IIc/III ulcers were indications for endoscopic therapy in 99 %/ 99 %/ 90 %/ 58 %/ 4 %/ 2 % respectively. Favoured initial treatment was injection (diluted epinephrine, mean volume 17 +/- 13 mL/lesion) followed by clipping. In re-bleedings, 93 % tried endoscopic treatment again. Scheduled re-endoscopy was performed in 63 %. PPI were used in 99.6 %, 85 % administered standard dose twice daily. PPI administration was changed from intravenous to oral with the end of fasting in nearly all hospitals. PPI administration schemes can be improved. Indications for Helicobacter pylori eradication followed rational principles. CONCLUSION: Medical and endoscopic treatment of bleeding ulcers reached a high standard, although some therapeutic strategies leave room for improvement. Bigger hospitals tend to be closer to the medical standard.

Molecular detection of primary bladder cancer by microsatellite analysis.

Microsatellite DNA markers have been widely used as a tool for the detection of loss of heterozygosity and genomic instability in primary tumors. In a blinded study, urine samples from 25 patients with suspicious bladder lesions that had been identified cystoscopically were analyzed by this molecular method and by conventional cytology. Microsatellite changes matching those in the tumor were detected in the urine sediment of 19 of the 20 patients (95 percent) who were diagnosed with bladder cancer, whereas urine cytology detected cancer cells in 9 of 18 (50 percent) of the samples. These results suggest that microsatellite analysis, which in principle can be performed at about one-third the cost of cytology, may be a useful addition to current screening methods for detecting bladder cancer.

Percutaneous endoscopic jejunostomy and jejunal extension tube through percutaneous endoscopic gastrostomy: a retrospective analysis of success, complications and outcome.

BACKGROUND: Percutaneous access to the jejunum is an important approach if gastrostomy feeding is not possible. OBJECTIVE: To analyze success, short- and long-term complications (STCs, LTCs) in patients with percutaneous endoscopic jejunostomy (PEJ) and jejunal access through percutaneous endoscopic gastrostomy (Jet-PEG). METHODS: A retrospective analysis of endoscopically placed PEJs and Jet-PEGs. Success rates, mortality, STCs and LTCs were investigated for risk factors comprising demographic data, underlying disease, previous surgery and experience of the endoscopist. RESULTS: 205 PEJ and 58 Jet-PEG placements were included in the study. PEJs and Jet-PEGs were successfully placed in 65.4 and 89.7%, respectively. Billroth II surgery predisposed in favor of a significantly higher success rate for PEJ placement (p = 0.014, OR = 2.27). Inexperienced examiners have a significantly (p = 0.040) lower success rate for tube insertion than examiners with a medium level of experience. STCs and LTCs occurred evenly in PEJ and Jet-PEG patients. Dislocation of the tube occurred significantly more frequently in Jet-PEG patients (33.3%, p = 0.005). Aspiration was most common for bedridden patients. CONCLUSION: PEJ has a significantly lower success rate for insertions, but fewer LTCs. The experience of the endoscopist correlates with the success rate of tube insertion.

Ex vivo and in vivo evaluation of residual chlorhexidine gluconate on skin following repetitive exposure to saline and wiping with 2% chlorhexidine gluconate/70% isopropyl alcohol pre-operative skin preparations.

BACKGROUND: Skin antisepsis is performed before surgery to minimize the risk of surgical site infections. Chlorhexidine gluconate (CHG) is routinely used in this application, but it may be removed during surgery when prepped areas are exposed to fluid and repeated blotting. AIM: This work evaluated the effect of adding a film-forming acrylate copolymer to a CHG-containing skin preparation on minimizing CHG loss during a simulated surgical irrigation and wiping procedure. The results were compared with those obtained with a commercially available water-soluble CHG preparation. METHODS: Two studies using excised porcine skin and one study on human volunteers were performed. In each study, the CHG preparations were applied and the treated sites were challenged with repetitive saline soaks and gauze dabbing to simulate surgical conditions. Challenged and unchallenged sites were analysed either for CHG content by high-performance liquid chromatography, or for bacterial log recovery after seeding an indicator organism (reflecting remaining CHG activity). FINDINGS: After irrigation and wiping, skin treated with the film-forming CHG preparation had more CHG remaining both on excised pig skin and in the human model. In the pig model, there was a lower recovery of inoculated bacteria with the CHG preparation containing the film-forming copolymer. No skin irritation or adverse events were reported in the human study. CONCLUSIONS: The addition of a film-forming copolymer has the potential to improve the retention of CHG on skin throughout a surgical procedure compared to a water-soluble preparation. This improved retention may lead to better antimicrobial activity.

Early detection of premalignant conditions in the colon by fluorescence endoscopy using local sensitization with hexaminolevulinate.

BACKGROUND AND STUDY AIMS: We aimed to determine the feasibility of obtaining selective fluorescence of precancerous/cancerous lesions in the colon with a new fluorescence video endoscope system in combination with the selective photosensitizer precursor hexaminolevulinate (HAL), and to carry out a dose-finding study with evaluation of the optimal dose and application time. PATIENTS AND METHODS: 12 patients with colorectal lesions underwent sensitization with locally applied HAL enemas in two concentrations (0.8 mmol and 1.6 mmol). The examination was conducted either 30 or 60 minutes after rectal administration of the sensitizer, using a special light source capable of delivering either white or blue excitation light. Red fluorescence induced by illumination with blue light was detected via a prototype fluorescence video colonoscope. Biopsies were taken from suspicious areas found with white or blue light. Corresponding endoscopic, fluorescence, and microscopic findings were compared. RESULTS: Using histological findings as the gold standard, 52/53 of the premalignant/malignant lesions showed red fluorescence under the photodynamic diagnosis (PDD) examination; 38/53 were detected with white-light endoscopy. The PDD mode showed 28 % more polyps than did white-light endoscopic imaging. The greatest fluorescence intensity in precancerous lesions was found with retention for 60 minutes of 500 ml of 1.6 mmol HAL. CONCLUSIONS: Administration of HAL enema induces selective lesion fluorescence and increases the lesion detection rate in patients with colorectal adenoma and early carcinoma.

Local infection after placement of percutaneous endoscopic gastrostomy tubes: a prospective study evaluating risk factors.

BACKGROUND: Due to its high efficacy and technical simplicity, percutaneous endoscopic gastrostomy (PEG) has gained wide-spread use. Local infection, occurring in approximately 2% to 39% of procedures, is the most common complication in the short term. Risk factors for local infection are largely unknown and therefore--apart from calculated antibiotic prophylaxis--preventive strategies have yet to be determined. OBJECTIVE: To assess the potential patient- and procedure-related risk factors for peristomal infection following PEG tube placement. METHODS: Potential patient-related (eg, age, sex, diseases, body mass index, concomitant antibiotic therapy) and procedure-related (endoscopist experience, institutional factors, findings on endoscopy) risk factors and their coincidence with local infection, defined as a positive peristomal infection three days after PEG tube placement, were evaluated at two institutions. A standardized antibiotic prophylaxis was not performed. The peristomal infection score was also evaluated in 390 patients. RESULTS: Using a multivariate binary regression analysis, four risk factors were established as relevant for local infection after PEG: clinical institution (OR 6.69; P = 0.0001), size of PEG tubes (15 Fr versus 9 Fr; OR 2.12; P = 0.05), experience of the endoscopist (more than 100 investigations versus less than 100 investigations; OR 0.54; P = 0.05) and the existence of a malignant underlying disease (OR 2.28; P = 0.019). CONCLUSIONS: Similar to other endoscopic interventions, local infection as a complication of PEG tube placement depends on the experience of the endoscopist. Institutional factors also play a significant role. Additional risk factors include PEG tube size and underlying diseases. These findings indicate that the local infection after PEG tube placement may be influenced by both endoscopy-associated factors and by the underlying disease status of the patient.

Effect of serotonin depletion on 5-HT2A-mediated learning in the rabbit: evidence for constitutive activity of the 5-HT2A receptor in vivo.

RATIONALE: Associative learning during Pavlovian eyeblink conditioning has been shown to be regulated by 5-HT2A receptors. The existence of inverse agonists that retard learning through an action at the 5-HT2A receptor suggests the existence of constitutive activity at that receptor and that depletion of serotonin should have minimal effects on learning. OBJECTIVES: We examined whether depletion of serotonin would impair trace eyeblink conditioning or the enhancement of conditioning produced by the agonist lysergic acid diethylamide (LSD) and the retardation of conditioning produced by the inverse agonist MDL11,939. METHODS: Animals received bilateral intraventricular injections of 5,7-dihydroxytryptamine (5,7-DHT) at doses of 760 or 1,140 microg/side (1.88 or 2.82 micromol/side) and were later exposed to eight daily conditioning sessions. RESULTS: Serotonin depletion produced by the lower dose of 5,7-DHT was 71 and 72% in cortex and hippocampus, respectively, with no change in 5-HT2A receptor density, no effect on learning, and no effect on the ability of LSD to enhance and MDL11,939 to retard learning. The higher dose of 5,7-DHT produced serotonin decreases of 85 and 90% in cortex and hippocampus, respectively, accompanied by a 96% decrease in the density of the serotonin transporter, but no significant effect on learning. CONCLUSIONS: Pavlovian trace eyeblink conditioning is regulated predominantly by the constitutive activity of the 5-HT2A receptor rather than by serotonin release onto the receptor during learning. It was suggested that the 5-HT2A receptor regulates learning by modulating the release of dopamine, acetylcholine, and glutamate, transmitters known to affect eyeblink conditioning.

p53 mutation and locoregional treatment failure in head and neck squamous cell carcinoma.

BACKGROUND: The p53 gene (also known as TP53) may be the most common genetic target involved in the malignant transformation of human cells. Direct sequence analysis has demonstrated that alteration of this gene occurs in approximately 45% of head and neck squamous cell carcinomas. The consequences of p53 mutations in these cancers with respect to tumor behavior and patient survival have not been rigorously determined. PURPOSE: We evaluated the implications of p53 mutations in relation to the control of locoregional disease and overall survival following radiation therapy. METHODS: Data from 110 consecutive patients with invasive disease who were treated with primary radiation therapy (given with curative intent) or with adjuvant radiation therapy (following complete surgical extirpation of gross disease) were included in the analysis. A 1.8-kilobase fragment of the p53 gene encompassing exons 5-9 was amplified from the DNA of stored (frozen) tumor specimens; the amplified DNA was cloned and sequenced by use of standard techniques. Overall survival and locoregional disease-free survival after the completion of radiation therapy were estimated by the Kaplan-Meier method; survival comparisons were made by use of the logrank test or proportional hazards regression models. Reported P values are two-sided. RESULTS: Fortyeight (44%) of the 110 tumors had cells bearing p53 mutations. The risk of locoregional recurrence following either primary or adjuvant radiation therapy was significantly greater (i.e., the time to recurrence was shorter) for patients whose tumors contained mutant p53 genes (univariate model hazard ratio [HR] for p53 mutation versus wild-type = 2.2; 95% confidence interval [CI] = 1.2-4.1; P = .02). The presence of regional lymph node metastases (presence versus absence, HR = 2.0; 95% CI = 1.0-4.2; P = .05) and treatment type (primary radiation therapy versus surgery plus adjuvant radiation therapy, HR = 2.3; 95% CI = 1.2-4.3; P = .01) were also associated with greater risks of locoregional failure. The presence of p53 mutations and lymph node metastases and treatment with primary, as opposed to adjuvant, radiation therapy remained significant risk factors in multivariate regression analysis. No relationship was demonstrated between p53 status and overall survival (mutant versus wild-type, HR = 1.1; 95% CI = 0.6-2.1; P = .66); however, a relationship was shown for tumor stage and overall survival (stages III and IV [more advanced] versus stages I and II [less advanced], HR = 3.3; 95% CI = 1.0-10.8; P = .05). Mutation of the p53 gene was not associated with patient age, sex, tumor stage, primary tumor site, regional lymph node status, degree of tumor cell differentiation, or treatment method. CONCLUSIONS: Mutation of the p53 gene is associated with an increased risk of locoregional failure in patients with invasive head and neck squamous cell carcinoma who are treated with radiation therapy.

Biliary secretion of moxifloxacin in obstructive cholangitis and the non-obstructed biliary tract.

BACKGROUND: Biliary secretion of antibiotic agents into the bile is considerably compromised by biliary obstruction, a precondition of bacterial cholangitis. Moxifloxacin may be advantageous according to secretion and antimicrobial spectrum. AIM: To establish the secretion of moxifloxacin into obstructed and non-obstructed bile. METHODS: Biliary excretion of moxifloxacin was determined in plasma and bile of 10 patients with biliary obstruction and cholangitis and 10 patients without biliary obstruction 30 min after administration of 400 mg of moxifloxacin intravenously. RESULTS: The plasma concentration of moxifloxacin was similar in both groups (4.45 +/- 1.58 microg/mL; 4.33 +/- 1.23 microg/mL). The concentration of moxifloxacin in the bile was significantly lower in patients with biliary obstruction than without (4.63 +/- 3.94 microg/mL; range 0.71-14.40; vs. 16.90 +/- 13.77 microg/mL; range 1.79-42.50; P = 0.043). Although significantly different, the penetration index was extensively high in those without biliary obstruction (4.41 +/- 4.40; range 0.35-14.45) but still sufficient in those patients with obstructive cholangitis (1.02 +/- 0.74; range 0.29-2.83; P = 0.035). CONCLUSION: These findings are suggestive of an active secretion mechanism for moxifloxacin into the obstructed bile, producing a biliary concentration sufficiently above the minimal inhibitory concentrations for most of the expected bacteria.

Different lipid profiles as constituencies of liquid formula diets do not influence pain perception and the efficacy of opioids in a human model of acute pain and hyperalgesia.

Nutritional support and pain control by medication are often used concomitantly, but interactions are hardly investigated. A randomised, double-blind, cross-over study in ten right-handed volunteers was performed evaluating the influence of cholecystokinin (CCK)-excretion on the perception of pain in a standardised model. CCK-excretion was induced by a liquid formula diet with either long- or medium-chain triglycerides (LCT, MCT). Plasma samples were drawn over a 60 min period in 15-min intervals and CCK and somatostatin (SMS) were measured by radioimmunoassay (RIA). Gastric emptying was evaluated by C-13-breath testing. Transcutaneous electrical stimulation at a high current density (5 Hz, 70.1+/-5.8 mA) was used to provoke acute pain and stable areas of secondary mechanical hyperalgesia and pinprick allodynia for 2 h. Ongoing pain ratings as well as extension of pinprick-hyperalgesia and allodynia were compared between both liquid formula diets. In a second series of experiments, alfentanil (4.1+/-0.5 mg) was administered for 90 min using target-controlled infusions and measurements were performed as stated above. Oral administration of LCT as well as MCT may lead to different CCK blood levels, but we found no evidence for CCK-induced effects on pain sensation, touch-evoked allodynia, secondary hyperalgesia or morphine-induced anti-nociception in humans. In our studies, liquid formula diets did not influence acute pain perception or the efficacy of opioids in a human model of pain.

p53 and p21(WAF1/CIP1/SDI1) gene products in Barrett esophagus and adenocarcinoma of the esophagus and esophagogastric junction.

The WAF1 (CIP1/SDI1) gene encodes a cyclin-dependent kinase inhibitor which is induced by wild-type, but not mutated, p53 gene product. WAF1 immunohistochemistry has been suggested to clarify the phenotype of overexpressed p53 gene product. We evaluated both p53 and WAF1 gene products by immunohistochemistry in 98 esophagectomy specimens with Barrett esophagus and/or adenocarcinoma of the esophagus and esophagogastric junction. Diffuse positive p53 staining was found in 40 of 88 adenocarcinomas (45%) and in dysplastic Barrett epithelium in 20 of 65 cases (31%), but not in Barrett mucosa without dysplasia (n = 36, P = .0004). Eighty-eight percent of cancers exhibited WAF1 expression, but there was no association with p53 and WAF1 staining. WAF1 protein was also identified in Barrett epithelium and in esophageal squamous and gastric epithelium. In contrast to carcinomas, a unique pattern of mutually exclusive p53 and WAF1 expression was found in five cases of dysplastic Barrett epithelium; a missense mutation at codon 175 of p53 was identified in one. p53 staining of adenocarcinoma was associated with shorter patient survival but was not independent of stage; WAF1 status added no prognostic information. Our findings show that WAF1 immunohistochemistry complements p53 immunohistochemistry in some cases of Barrett dysplasia but not in adenocarcinomas. Positive p53 immunostaining can serve to confirm a neoplastic process in Barrett mucosa. Positive staining of adenocarcinomas may be an indication of advanced stage.

Elevated hepatic apolipoprotein A-I transcription is associated with diet-induced hyperalphalipoproteinemia in rabbits.

Past studies have shown that a high saturated fatty acid diet containing coconut oil elevates plasma HDL cholesterol and apolipoprotein A-I (apoA-1) in rabbits through a mechanism involving increased synthesis. We have extended those studies by investigating expression of the hepatic apolipoprotein A-I gene and other lipid related genes in that model. Rabbits fed a diet containing 14% coconut oil for 4 weeks showed HDL-C elevations of 170% to 250% over chow-fed controls with peak differences occurring at 1 week. Plasma apoA-I levels were also increased over this time frame (160% to 180%) reflecting the HDL-C changes. After 4 weeks, there were no differences in plasma VLDL-C or LDL-C levels in chow versus coconut oil-fed rabbits. Hepatic levels of apoA-I mRNA in coconut oil-fed animals were elevated 150% after 4 weeks compared to chow-fed controls; hepatic mRNA levels for ten other genes either decreased slightly (apoB, LCAT, hepatic lipase, albumin, ACAT, and HMG CoA reductase) or were unchanged (CETP, apoE, LDL-receptor, and acyl CoA oxidase). Nuclear run-on transcription assays revealed that coconut oil feeding for 4 weeks caused a 220% increase in hepatic apoA-I transcription rate compared to controls; no change was observed for CETP and apoE. Treatment of cultured rabbit liver cells with various saturated fatty acids and sera from chow-fed and coconut oil-fed rabbits did not alter apoA-I mRNA levels as observed in vivo. These data demonstrate that coconut oil elevates plasma HDL-C and apoA-I by increasing hepatic apoA-I transcription while expression of other genes involved in lipid metabolism are reduced or unchanged in response to coconut oil feeding.

Interferon gamma enhances lymphokine-activated killer cell adhesion but not lysis of head and neck squamous cell carcinoma.

OBJECTIVES: To determine if treatment with recombinant human interferon gamma (rHuIFN-gamma) increases the adhesion to, and lysis of, head and neck squamous cell carcinoma (SCC) cells by lymphokine-activated killer (LAK) and peripheral blood mononuclear (PBM) effector cells in vitro and to evaluate the role of cell surface adhesion molecules in these processes. DESIGN: Two human SCC cell lines, JHU-020-SCC and JHU-022-SCC, were used. Lymphokine-activated killer cells were generated by interleukin-2 stimulation of PBM cells obtained from the hemapheresis blood donor packs of healthy individuals. Adhesion assays were performed to assess the level of binding of both effector populations to SCC cells, which were treated with either fresh media or rHuIFN-gamma (100 U/mL). Binding was measured by flow cytometric detection of effector cells labeled with fluorescein-conjugated anti-CD45 monoclonal antibody. Monoclonal antibodies to the cell adhesion molecules HLA-DR, lymphocyte function-associated antigen 1, and intercellular adhesion molecule 1 were used in blocking experiments to determine their contribution to the process of effector-SCC cell adhesion. Cytotoxicity experiments were performed using a colorimetric assay to determine the cytotoxic response generated by LAK and PBM cells against SCC cells, with and without prior rHuIFN-gamma treatment of the tumor cells. MAIN OUTCOME MEASURES: Effector cell binding level and percent cytotoxicity of SCC cells. RESULTS: Recombinant human interferon gamma treatment of JHU-020-SCC cells resulted in increased adhesion to both LAK cells and PBM cells (P < .001). The presence of anti-lymphocyte function-associated antigen 1 antibody resulted in elimination of the enhanced adhesion seen with rHuIFN-gamma pretreatment of SCC cells (P =.03), but antibody to intercellular adhesion molecule 1 and HLA-DR did not reduce the level of effector binding. The greatest cytotoxic response against both JHU-020-SCC and JHU-022-SCC was seen with LAK cells (P < or = .001). Pretreatment of tumor targets by rHuIFN-gamma (100 U/mL) resulted in no enhancement of cytotoxic response by either LAK or PBM cells; at the effector-target ratio of 30:1, there was a significant decrease in LAK cell-mediated cytotoxic response against rHuIFN-gamma-treated SCC cells (P < or = .02). CONCLUSIONS: Recombinant human interferon gamma treatment of head and neck SCC cells does increase binding of both LAK cells and PBM cells to tumor cells, in part via the lymphocyte function-associated antigen 1 ligand mechanism. The cytotoxic effect mediated by LAK cells against head and neck SCC cells is reduced after rHuIFN-gamma treatment, suggesting that the activity of this cytokine may be more important in regulating antigen-specific cytotoxic response mediated by cytotoxic T-lymphocytes.

Operative acute small bowel obstruction: admitting service impacts outcome.

Early surgical intervention in acute small bowel obstruction (SBO) has long been recognized as an important factor in preventing morbidity and mortality. Factors associated with surgically managed acute SBO were analyzed for delay in intervention and impact on outcome. A retrospective review of all patients evaluated for SBO on the surgical teaching service of the Greenville Hospital System from July 1, 1997 to June 30, 2000 was performed. Data were collected on patient demographics, admission information (date, admitting service, physical examination, and laboratory values), comorbidity, diagnostic studies, surgery date, operative findings, postoperative complications, operative mortality, and discharge date. Analysis of the data revealed 157 cases of presumed SBO of which 61 were managed nonoperatively and 96 required surgery. Acute SBO was diagnosed in 65 patients who constitute the basis for this review. Of these 65 patients 43 (66%) were admitted to the surgical service, 25 (38%) required small bowel resection, and 17 (26%) developed morbidity and/or mortality. When analyzed for morbidity and mortality the only characteristics that were statistically significant were the admitting service (P = 0.003) and length of stay (P = 0.003). On further analysis of admitting service and patient outcomes several factors were significant when we compared medical service admissions to surgical service admissions. These included days from admission to surgery (P = 0.003), length of stay (P = 0.019), morbidity (P = 0.004), mortality (P = 0.005), and combined morbidity and mortality (P = 0.003). Mortality of patients admitted to the medical service was 27 per cent compared with 2 per cent for the surgical service. There were no differences in morbidity and mortality when analyzed by the need for small bowel resection, patient age, etiology of obstruction, or presence of comorbidities. None of the factors studied were useful in predicting the need for small bowel resection. Our findings agree with those of previous investigators with regard to 1) lack of association between the preoperative evaluation and the need for small bowel resection and 2) the association between delay in diagnosis and increased morbidity and mortality. In addition we have found that one of the primary causes of delay in treatment for SBO was admission to the medical service. This delay led to significantly higher mortality in these patients. We recommend early surgical evaluation for any patient admitted with SBO as a differential diagnosis.

Today's impatient patient.

Fee-for-service dentists face the daily challenge of differentiating themselves from discount providers while delivering quality care to patients pressed for time. Some thoughts on how to make the best of limited time.