Viscous impedance is an important indicator of abnormal esophageal motility.

BACKGROUND: Non-obstructive Dysphagia (NOD) is one of the most common symptoms evaluated using esophageal manometry. Although manometry is considered the gold standard, many NOD patients have normal evaluations. Esophageal function testing with combined multichannel intraluminal impedance and esophageal manometry (MII-EM) is performed using ten 5-mL swallows of a liquid and a viscous material and provides supplemental information about bolus transit. The aim of this study was to evaluate esophageal function using combined MII-EM in patients with NOD who had normal evaluations with liquid manometry. METHODS: Multichannel intraluminal impedance and esophageal manometry was performed in consecutive patients presenting for evaluation of NOD. Patients were excluded if any abnormality was detected during liquid manometry. Viscous manometry and liquid and viscous impedance data were analyzed to detect manometric or bolus transit abnormalities. Patients referred for GERD evaluation without any swallowing complaints were used as patient controls and were subject to the same exclusion criteria as the NOD group. All swallow evaluations were performed with 10 liquid and 10 viscous swallows. KEY RESULTS: Data from 240 patients were evaluated, 129 with NOD and 111 patient controls. In the NOD group, 9% (12/129) had abnormal liquid impedance and 29% (37/129) had abnormal viscous impedance. In the control group, 4% (4/111) had abnormal liquid impedance and 16% (18/111) had abnormal viscous impedance. Chi-square analysis showed a significant difference between the two study groups for viscous impedance (P = 0.02) but not for liquid impedance (P = 0.12). CONCLUSIONS & INFERENCES: Our data support our belief that a normal liquid manometry with an abnormal viscous impedance analysis in a patient with NOD indicates abnormal esophageal motility. Therefore, viscous impedance should be performed on all patients during the evaluation of NOD.

Twice-daily proton pump inhibitor therapy does not decrease the frequency of reflux episodes during nocturnal recumbency in patients with refractory GERD: analysis of 200 patients using multichannel intraluminal impedance-pH testing.

Over half of patients with gastroesophageal reflux disease (GERD) report nocturnal symptoms. Proton pump inhibitors (PPIs) are the main medications used to treat GERD. Multichannel intraluminal impedance with pH (MII-pH) monitoring is the most sensitive method for detection and characterization of GERD. The aim of this study was to assess and compare reflux frequency in patients with refractory GERD symptoms on and off PPI therapy during the nocturnal recumbent period, as assessed by MII-pH testing. We analyzed 24-hour MII-pH studies performed in 200 patients monitored either on twice-daily (n = 100) or off (n = 100) PPI therapy. Demographic analysis of the on-therapy group revealed a mean age of 52 years (24-78 years) with 37% males, and the off-therapy group revealed a mean age of 49 years (18-84 years) with 40% males. All studies were interpreted to assess and characterize the number of acid and nonacid reflux episodes in the nocturnal recumbent period identified by each patient on an overnight recorder (Zephyr, Sandhill Scientific, Inc., Highlands Ranch, CO, USA). The nocturnal recumbent period was the period documented by patients during which they lie in the recumbent period at night to sleep with average periods lasting 456 and 453 minutes for patients on and off PPI therapy. There were more mean recumbent reflux episodes in the on-therapy group in comparison with the off-therapy group (3.76 mean reflux episodes [mre] per patient in the recumbent vs. 2.82 mre); the difference was not statistically significant (P = 0.187). When the reflux events are classified into acid and non-acid reflux episodes, the relative occurrence of acid reflux events is less in the on-therapy group (P = 0.047), while the off-therapy group have fewer nonacid reflux episodes (P = 0.003). PPIs decrease the acidity of esophageal refluxate but do not decrease the relative frequency of reflux episodes in the recumbent position in patients with refractory GERD despite twice-a-day treatment with PPI therapy. The explanation for the finding of numerically increased, although not statistically significant, amount of reflux episodes in the PPI treatment group in this study, and previous studies is unclear and warrants further evaluation.

Analysis of speech characteristics in children with velocardiofacial syndrome (VCFS) and children with phenotypic overlap without VCFS.

OBJECTIVE: To address two questions of theoretical importance regarding the profile and course of communication impairment associated with velocardiofacial syndrome (VCFS): (1) do speech characteristics of children with VCFS differ from a group of children with some of the phenotypic characteristics of VCFS who do not have the syndrome, and (2) do younger children with VCFS demonstrate speech patterns that differ from older children with VCFS? DESIGN: Prospective, cross-sectional study comparing two groups of children at two age levels. PATIENTS: Thirteen children with VCFS and eight children with some of the phenotypic features of VCFS who did not have the syndrome. Children ranged in age from 3 to 10 years. MAIN OUTCOME MEASURE: (1) Broad phonetic transcription of speech yielding measures of number of consonant types, Percent Consonant Correct, and percentage of glottal stops used; and (2) composite ratings of velopharyngeal function made from perceptual, aerodynamic, and endoscopic evaluations. RESULTS: Younger children with VCFS demonstrated greater speech impairment than older children with VCFS or the children without VCFS, such as smaller consonant inventories, greater number of developmental errors, greater severity of articulation disorder, and higher frequency of glottal stop use. The relationship between ratings of velopharyngeal function and the speech variables analyzed was not straightforward. CONCLUSIONS: Some young children with VCFS demonstrated speech impairment that is qualitatively and quantitatively different from older children with VCFS or children without VCFS. This finding supports the hypothesis that some children with VCFS demonstrate a profile of speech production that is different from normal but also may be specific to the syndrome.

Sexual abuse knowledge base among residents in family practice, obstetrics/gynecology, and pediatrics.

STUDY OBJECTIVE: To investigate resident physician knowledge about sexual abuse prevalence and understanding about potential perpetrators. DESIGN: Questionnaires were mailed to program directors in family practice, obstetrics and gynecology, and pediatric residency programs. PARTICIPANTS: The questionnaires were distributed to senior residents in their final months prior to graduation. INTERVENTIONS: Residents were asked to fill out the questionnaire anonymously and return it to our institution in the prepaid envelope provided. MAIN OUTCOME MEASURES: Demographic characteristics and knowledge of sexual abuse prevalence and perpetrator characteristics were assessed. Chi-square contingency table analysis was used to compare responses of the three specialties. RESULTS: The overwhelming majority (98.8%) of residents correctly identified a family member as the individual most likely to sexually abuse a child. Approximately half of the residents knew the correct prevalence of sexual abuse among females and among males. There was a weak understanding of the potential youthfulness of juvenile offenders. CONCLUSION: We believe that resident understanding of sexual abuse prevalence and about the youthfulness of juvenile offenders can be improved in all three specialties.

The influence of glucan polymer structure and solution conformation on binding to (1-->3)-beta-D-glucan receptors in a human monocyte-like cell line.

Glucans are (1-3)-beta-D-linked polymers of glucose that are produced as fungal cell wall constituents and are also released into the extracellular milieu. Glucans modulate immune function via macrophage participation. The first step in macrophage activation by (1-3)-beta-D-glucans is thought to be the binding of the polymer to specific macrophage receptors. We examined the binding/uptake of a variety of water soluble (1-3)-beta-D-glucans and control polymers with different physicochemical properties to investigate the relationship between polymer structure and receptor binding in the CR3- human promonocytic cell line, U937. We observed that the U937 receptors were specific for (1-->3)-beta-D-glucan binding, since mannan, dextran, or barley glucan did not bind. Scleroglucan exhibited the highest binding affinity with an IC(50)of 23 nM, three orders of magnitude greater than the other (1-->3)-beta-D-glucan polymers examined. The rank order competitive binding affinities for the glucan polymers were scleroglucan>>>schizophyllan > laminarin > glucan phosphate > glucan sulfate. Scleroglucan also exhibited a triple helical solution structure (nu = 1.82, beta = 0.8). There were two different binding/uptake sites on U937 cells. Glucan phosphate and schizophyllan interacted nonselectively with the two sites. Scleroglucan and glucan sulfate interacted preferentially with one site, while laminarin interacted preferentially with the other site. These data indicate that U937 cells have at least two non-CR3 receptor(s) which specifically interact with (1-->3)-beta-D-glucans and that the triple helical solution conformation, molecular weight and charge of the glucan polymer may be important determinants in receptor ligand interaction.

Long-term trends in susceptibility of Moraxella catarrhalis: a population analysis.

A retrospective, population analysis of antimicrobial susceptibility patterns was performed on Moraxella catarrhalis isolates recovered from a single medical centre to detect temporal trends and infer potential mechanisms of reduced susceptibility. The duration of this study, June 1984 to July 1994, encompassed the period during which the frequency of beta-lactamase production expanded from 30 to 96% in the population. MICs of penicillin G, cefamandole, ceftriaxone, amoxycillin/clavulanate, imipenem, clarithromycin, tetracycline, ciprofloxacin and trimethoprim/sulphamethoxazole for a representative sample of 375 isolates were determined. Analyses were conducted to test for variation in susceptibility among isolates, correlations of susceptibility levels among different antimicrobial agents, and temporal patterns in susceptibility. All antimicrobials except clarithromycin displayed significant differences among isolates within years, and mean MICs of all antimicrobial agents except tetracycline and clarithromycin varied significantly between years. Temporal trends to a reduction in susceptibility were detected to four of five beta-lactam antimicrobials (all except cefamandole). Significant correlations in MICs were uncovered among all pairs of four beta-lactam antimicrobials in both producers and non-producers of beta-lactamase. In contrast, cefamandole MICs were correlated only with ceftriaxone and penicillin, and these were limited to beta-lactam producing isolates; cefamandole and amoxycillin/clavulanate showed a correlation limited to non-producing isolates. For some antimicrobials, trends toward decreasing susceptibility may have been caused by an increased proportion of beta-lactamase producing isolates in the population, but the observation of significant decreases in susceptibility limited to beta-lactamase-producing isolates suggests that the underlying factors were different forms of beta-lactamase, beta-lactamase-dependent modifiers and/or additional factors.

Early speech and language development in children with velocardiofacial syndrome.

Speech-language impairment is one of the most common clinical features in velocardiofacial syndrome (VCFS). This report describes the speech and language development of four children with VCFS studied longitudinally from 6 to 30 months of age and compares their performance with three groups of children: (1) normally developing children, (2) children with cleft lip and palate, and (3) children with isolated cleft palate. The data show that young children with VCFS show a receptive-expressive language impairment from the onset of language. Further, speech and expressive language development were severely delayed beyond a level predicted by their other developmental or receptive language performance. The children with VCFS showed severe limitations in speech sound inventories and early vocabulary development that far exceeded those shown by the children with cleft lip and palate and children with isolated cleft palate. This study indicates that young children with VCFS emerge from a critical speech and language learning period with severe limitations in their communicative abilities. Further studies are required to describe the later course of these early speech and language impairments and to explore the relationship to learning disabilities described for older children with VCFS. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:714-723, 1999.

A survey of pregnant women's knowledge about sexual abuse.

STUDY OBJECTIVE: To assess pregnant women's understanding of sexual abuse prevalence and perpetrator characteristics. DESIGN: A multiple choice questionnaire concerning knowledge about sexual abuse prevalence and an understanding of potential perpetrators was presented to patients. Comparisons were made based on participant's age, educational status, and personal involvement in the care of children. SETTING: Prenatal clinic, Department of OB/GYN, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee. PARTICIPANTS: Patients presenting for new obstetrical evaluation (N = 289). MAIN OUTCOME MEASURES: Responses to the questionnaire. RESULTS: Less than half of the subjects correctly answered questions about sexual abuse prevalence. Only 22% of patients understood the potential youthfulness of juvenile sex offenders. Neither age nor child care responsibilities affected response. Subjects with greater than 12 years of formal education achieved significantly higher scores than those with less education, 59% of respondents were interested in more information. CONCLUSION: Pregnant women's knowledge about the dangers of sexual abuse was suboptimal in this population. The majority of patients were interested in more information.

Normalized forces and active range of motion in unilateral radial epicondylalgia (tennis elbow).

STUDY DESIGN: Single group pretest-posttest. BACKGROUND: There is a lack of consensus concerning the preferred assessment and treatment for radial epicondylalgia. OBJECTIVES: Determine whether deficiencies in muscle force, joint range of motion, or painful force threshold are detected when measurements from the involved upper extremity are normalized to values from the uninvolved extremity. METHODS AND MEASURES: Ten patients (70% men) 42 +/- 7 years in age with unilateral radial epicondylalgia participated. The visual analog pain scale and 6 measurements involving either muscle force, joint range of motion, or painful force threshold were examined. RESULTS: When comparing the initial assessments to final assessments, a significant improvement was found for the visual analog pain scale (5 +/- 3 vs 1 +/- 3) and for the following normalized scores: grip (78 +/- 26% vs 101 +/- 20%) and isometric wrist extension forces (68 +/- 24% vs 95 +/- 35%), painful force threshold over the lateral epicondyle (49 +/- 22% vs 94 +/- 14%), and active wrist extension range of motion (83 +/- 13% vs 96 +/- 10%). CONCLUSIONS: Normalized force and range of motion measurements following treatment for unilateral radial epicondylalgia are sensitive assessments of patient progress. In comparison with measurements of force and range of motion that are not adjusted to a baseline score, normalized measurements detect changes in patient responses when baseline scores vary.

Correlates of low back pain outcomes in a community clinic.

UNLABELLED: Both governmental and private agencies have focused on the multiple outcome variables that may affect patient treatment. Our investigation examined treatment-independent outcome variables and correlates in patients with the sole complaint of low back pain. Treatment was conducted in an outpatient physical therapy clinic serving a rural/suburban Tennessee population. METHODS: The review collected data on nine variables from 54 clinic records. The study group was 56% female, with ages for all subjects ranging from 26 to 84 years. Twenty-five patients carried private insurance, 14 were TennCare recipients (state Medicaid), 9 were covered by workers compensation, and 6 were Medicare based. The prescribed number of treatment sessions (Rx) varied from 1 to 3 visits to as many as 18. RESULTS: The Rx was not related to sex, age, or payer type. The compliance index (Cx) (mean = 76.3%, range = 6% to 150%) was related to payer type (P < .02), but not related to sex, age, or Rx. TennCare patients had lower compliance levels (mean Cx = 51.1) than all other insurer groups combined (mean Cx = 85.0). Self-assessed improvement by the patient (Patient Status) was related to Cx (P < 0.005) but not sex, age, payer type, or Rx. Completion by the patient of long-term physical therapy goals as determined by the therapist was related to Cx (P < .03) and self-assessed patient status (P < .02), while disposition at discharge was associated with Cx, self-assessed patient status, and payer type (P < .001). DISCUSSION: Compliance by patients significantly influences the outcome measures of self-assessed improvement, therapist assessment of achieving long-term treatment goals, and disposition at discharge. TennCare patients demonstrated both low compliance and poor outcome at discharge. These results suggest that the lower potential for positive treatment outcome may exist for the TennCare patient population.

Inhibiting early activation of tissue nuclear factor-kappa B and nuclear factor interleukin 6 with (1-->3)-beta-D-glucan increases long-term survival in polymicrobial sepsis.

BACKGROUND: Recent data implicate the activation of nuclear factor-kappa B (NF-kappa B) and nuclear factor interleukin 6 (NF-IL6) as important steps in the pathophysiologic mechanisms of adult respiratory distress syndrome and systemic inflammatory response syndrome. METHODS: This study evaluated the effect of immunomodulating polysaccharides on transcription factor activation, cytokine expression, and mortality in a murine cecal ligation and puncture (CLP) model. ICR/HSD mice were treated with glucan (50 mg/kg) 1 hour before or 15 minutes after CLP. Liver and lung tissue were harvested at 3 hours and mortality trends were observed for 20 days. RESULTS: CLP increased liver and lung NF-kappa B and NF-IL6 nuclear binding activity as well as tumor necrosis factor-alpha and interleukin 6 messenger RNA levels at 3 hours. Pretreatment or posttreatment with glucans inhibited tissue NF-kappa B and NF-IL6 nuclear binding activity and tissue cytokine messenger RNA levels. Prophylaxis with glucan phosphate or scleroglucan increased (P < .001) long-term survival (20% CLP vs 65% glucan phosphate, 75% scleroglucan). Posttreatment with glucan phosphate also increased (P < .05) long-term survival (20% vs 65%). CONCLUSIONS: Pretreatment or posttreatment with biologic response modifiers decreased tissue transcription factor nuclear binding activity and cytokine message in liver and lung of septic mice. Inhibiting early transcription factor activation and cytokine message expression correlates with improved outcome in polymicrobial sepsis as denoted by increased long-term survival.

Early activation of hepatic NFkappaB and NF-IL6 in polymicrobial sepsis correlates with bacteremia, cytokine expression, and mortality.

BACKGROUND: The role of transcription factor activation in the pathophysiology of sepsis syndrome has not been established. This study investigated the relation between tissue nuclear factor kappaB (NFkappaB) and nuclear factor interleukin 6 (NF-IL6 or C/EBP) activation and bacteremia, inflammatory cytokine expression, and mortality in a murine model of cecal ligation and puncture (CLP). METHODS: Transcription factor activation was assessed by the electrophoretic mobility shift assay. Cytokine mRNA levels were established by reverse transcription-polymerase chain reaction and quantified by scanning densitometry. Bacteremia was evaluated by standard aerobic and anaerobic microbiologic methods. RESULTS: CLP stimulated hepatic NFkappaB activation at 2, 3, 4, 5, 6, and 8 hours compared with control and sham-operated mice. Hepatic NFkappaB activation during CLP peaked at 4 hours (1114% vs. no surgery, 609% vs. sham). Hepatic NF-IL6 activation was observed at 3, 4, and 6 hours after CLP. Hepatic and splenic levels of tumor necrosis factor-alpha and IL-6 mRNA were also elevated after CLP. Bacteremia in CLP mice consisted of Bacteroides species and to a lesser extent facultative gram-negative bacilli and group D Enterococcus. CONCLUSIONS: Early activation of hepatic and splenic NFkappaB and NF-IL6 positively correlates with tissue cytokine mRNA expression and mortality in a surgical model of polymicrobial sepsis. The data suggest that transcription factor activation is an early event in the pathophysiology of sepsis.

Early activation of pulmonary nuclear factor kappaB and nuclear factor interleukin-6 in polymicrobial sepsis.

BACKGROUND: Transcription factor activation may be a pivotal step in the pathophysiology of sepsis syndrome and adult respiratory distress syndrome. This study investigated the activation of lung nuclear factor kappaB (NFkappaB) and nuclear factor interleukin-6 (NF-IL6) and how they correlate to proinflammatory cytokine expression and mortality in a murine model of cecal ligation and puncture (CLP). METHODS: Polymicrobial sepsis was induced by CLP. Transcription factor activation was assessed at 0, 1, 2, 3, 4, 5, 6, 8, and 24 hours after CLP by the electrophoretic mobility-shift assay. Lung cytokine mRNA levels were established by reverse transcriptase-polymerase chain reaction. RESULTS: CLP induced pulmonary NFkappaB activation at 3, 4, and 8 hours (p < 0.05). Lung NFkappaB activation peaked at 3 hours (533% vs. no surgery, 2,900% vs. sham treatment) after CLP. Supershift analysis revealed a predominance of p50 subunits in the lung nuclear extracts of septic mice 3 hours after CLP, indicating the presence of p50 homodimer. In contrast, liver nuclear extracts from septic mice indicated the presence of both p65 and p50 subunits at 3 hours. Lung NF-IL6 activation (p < 0.05) was observed at 4 hours (649% vs. no surgery, 296% vs. sham treatment) and 6 hours after CLP. Lung tumor necrosis factor-alpha mRNA levels were increased (p < 0.05) at all time intervals after CLP. Lung IL-6 mRNA levels were increased at 3, 6, and 8 hours after CLP. CONCLUSION: Early activation of lung NFkappaB and NF-IL6 and lung cytokine mRNA expression correlated with mortality in polymicrobial sepsis. Although IL-6 mRNA levels correlated with NFkappaB and NF-IL6 activation, tumor necrosis factor-alpha mRNA levels did not, in that they preceded transcription factor activation. These data suggest a potential role for NFkappaB and NF-IL6 activation in the initiation and propagation of acute lung injury.

Rubella serology in mentally retarded adults.

BACKGROUND: Rubella and congenital rubella syndrome remain a problem in the United States; institutionalized individuals are at higher risk. We assessed demographic variables and rubella serology in a population of institutionalized adults with mental retardation. METHODS: Subjects were 181 institutionalized adults with mental retardation. We reviewed charts to determine patient's age, sex, race, and fertility status (if female), cause of mental retardation, and rubella history. Serologic testing to determine rubella immunity was done. RESULTS: We found that 26.4% of subjects were nonimmune. Sex, cause of mental retardation, and history of rubella vaccination were not related to serologic immunity status. Of the 29 fertile female subjects, 8 (27.6%) were nonimmune to rubella. CONCLUSION: Subjects with unknown immunization status had a similar serologic profile to those whose medical records indicated immunization. Neither history of infection nor immunization was predictive of serology status.

Genetic diversity among strains of Moraxella catarrhalis: analysis using multiple DNA probes and a single-locus PCR-restriction fragment length polymorphism method.

Moraxella (Branhamella) catarrhalis, a causative agent of otitis media, sinusitis, and exacerbation of bronchitis, has acquired widespread ability to produce beta-lactamase and can be nosocomially transmitted. The typing methods used in epidemiological analyses of M. catarrhalis are not optimal for genetic analyses. Two methods, a multiple-locus Southern blot (SB) method and a single-locus PCR-restriction fragment length polymorphism (RFLP) method, were developed and used to assess genetic diversity and potential clinical and geographic relationships in M. catarrhalis. Nine randomly cloned M. catarrhalis DNA fragments were used as probes of SBs containing DNA from 54 geographically and clinically diverse strains. For comparison, a PCR-RFLP method was developed as a quick, inexpensive, and discriminating alternative. A highly variable 3.7-kb genomic region (M46) was cloned and sequenced, and 3.5 kb of the cloned DNA was targeted for PCR amplification. DNAs from the 54 strains were subjected to PCR-RFLP. SB analysis distinguished all strains that had no apparent epidemiological linkage (40 of 54), and PCR-RFLP distinguished fewer strains (21 of 54). Epidemiologically linked strains appeared genetically identical by both methods. PCR-RFLP was compared to pulsed-field gel electrophoresis (PFGE) for 8 of the 54 strains and 23 additional strains. PCR-RFLP distinguished fewer strains than PFGE typing (16 of 31 versus 20 of 31 strains), but PCR-RFLP was more useful for inferring interstrain relatedness. Separate cluster analyses of multilocus SB and single locus PCR-RFLP data showed high genetic diversity within and across geographic locations and clinical presentations. The resultant dendrograms were not entirely concordant, but both methods often gave similar strain clusters at the terminal branches. High genetic diversity, nonconcordance of cluster analyses from different genetic loci, and shared genotypes among epidemiologically linked strains support a hypothesis of high recombination relative to spread of clones. Single-locus PCR-RFLP may be suitable for short-term epidemiological studies, but the SB data demonstrate that greater strain discrimination may be obtained by sampling variation at multiple genomic sites.

Lymphoblastoid interferon-alpha inhibits T cell proliferation and expression of eosinophil-activating cytokines.

T cell-derived cytokines, such as interleukin-5 (IL-5) and granulocyte-macrophage colony-stimulating factor (GM-CSF) activate eosinophils, whereas other cytokines, such as tumor necrosis factor (TNF)-alpha and IL-13, determine eosinophil recruitment. Interferon-alpha (IFN-alpha), a leukocyte-derived cytokine, has been shown to have beneficial effects in eosinophil-mediated disorders, such as the hypereosinophilic syndrome and a murine model of allergic asthma, where it inhibited eosinophil recruitment. We tested the hypothesis that IFN-alpha acted in eosinophil-mediated disorders by modulating T cell cytokine expression. Peripheral blood mononuclear cells (PBMC) or human ragweed-specific TH1 (2B8) and TH2 (2D2) T cell clones were cultured in the presence of 5 micrograms/ml of phytohemagglutinin (PHA) or 25 micrograms/ml of antigen Amb a 1 (short ragweed allergen), respectively, and lymphoblastoid IFN-alpha (varying from 0 to 10,000 U/ml). We assessed T cell proliferation by [3H]thymidine incorporation and production of IL-5 and GM-CSF by ELISA. Expression of cytokine transcripts was analyzed by the reverse transcription-polymerase chain reaction technique (RT-PCR). IFN-alpha induced a dose-dependent suppression of T cell proliferation of both PBMC (p < 0.001) and the T cell clones (p < 0.001). IFN-alpha inhibited gene expression of IL-5, GM-CSF, TNF-alpha, and IL-13 in PBMC. Furthermore, IFN-alpha significantly inhibited mitogen-induced and antigen-induced production of IL-5 and GM-CSF. IFN-alpha may benefit eosinophil-mediated disorders by inhibiting T cell function and production of cytokines active on human eosinophils.

Immunohistochemical detection of a fatty acid synthase (OA-519) as a predictor of progression of prostate cancer.

Prostate cancer is the most common newly diagnosed non-skin cancer and the second leading cause of cancer death in men. It is a unique neoplasm because of the large discrepancy between its clinical incidence and the much higher incidence of latent cancer. Predicting the prognosis of prostate cancer, especially the cancers detected incidentally or by screening, remains a clinically important problem. Immunoreactivity for Onco-antigen 519 (OA-519), a recently described fatty acid synthase (FAS), has been associated with poor prognosis in breast cancers. The authors have previously shown that its detection in prostate cancer correlated with high-grade, large volume, and advanced stage tumors. This study examines the association between OA-519 immunoreactivity in primary prostate cancer and disease progression. The authors used immunohistochemistry with an affinity-purified anti-OA-519 antibody and examined primary prostate cancers (stages A1 to D1) from 99 men with a mean follow-up of 4 years (range = 2 to 9.3). Survival analysis was used to evaluate differences in progression-free survival. OA-519 immunoreactivity was seen in 56 (57%) of the 99 primary prostate cancers examined. OA-519-positive cancers were more likely to progress than the OA-519-negative cancers (P < .04). Univariate survival analysis showed that OA-519 (FAS), histological grade (Gleason score), and clinical stage were significant predictors of disease progression. Multivariate analyses of all cases showed that only histological grade was significant. However, multivariate analysis of the 85 cancers with Gleason scores 2-7 (ie, low to intermediate grade) showed OA-519 (FAS) immunoreactivity to be the only statistically significant predictor of cancer progression (P < .02). Expression of the fatty acid synthase OA-519 by prostate cancers is potentially a clinically useful predictor of disease progression. It appears to be independent of histological grade (Gleason score), at least in cancers with low to intermediate grades. Further studies are needed to evaluate the role of fatty acid synthase in malignancy and the potential therapeutic implications of enzyme blockers.

Antibiotic susceptibility patterns of community-acquired respiratory isolates of Moraxella catarrhalis in western Europe and in the USA. The Alexander Project Collaborative Group.

Eight hundred and eighteen Moraxella catarrhalis strains, isolated in 1992 and 1993 at 15 centres in Western Europe and the USA were tested for beta-lactamase production and resistance to 15 antibiotics. The proportion of beta-lactamase producing strains in Europe rose significantly from 70% in 1992 to 82% in 1993, whilst in the USA the increase (85-92%) was not significant. Penicillin and amoxycillin resistance was more prevalent in the USA than in Europe. All penicillin-resistant strains isolated in the USA exhibited beta-lactamase activity, whilst 8% of beta-lactamase-negative strains isolated in Europe were also penicillin resistant. All but three isolates were sensitive to cefaclor, cefuroxime, cefixime and ceftriaxone, all but one were sensitive to ofloxacin and all were sensitive to ciprofloxacin and amoxycillin cluvulanate. Resistance to erythromycin was not encountered, although 19 strains had MICs > or = 0.5 mg/L. Of these, 15 came from European centres. Almost all strains were highly susceptible to clarithromycin, azithromycin, doxycycline and co-trimoxazole.

Highly variable gastric emptying in patients with insulin dependent diabetes mellitus.

Some diabetic patients--particularly those with nausea and vomiting--frequently have evidence of delayed gastric emptying while other diabetic patients may in fact exhibit accelerated gastric emptying. Whether the presence or absence of symptoms of upper gastrointestinal dysfunction correlated with objective measures of gastric emptying in insulin dependent diabetic subjects was investigated. Twenty one insulin dependent diabetic patients underwent a solid phase gastric emptying scintiscan using in vivo labelled chicken liver. Thirteen patients had symptoms suggestive of gastrointestinal dysfunction (nausea, vomiting, early satiety, or constipation), while eight patients had no gastrointestinal symptoms. Eleven patients had orthostatic hypotension. All patients had been diabetic since childhood or adolescence. As a group, the diabetic patients showed a half time (T50) of gastric emptying (mean (SD) 150.0 min (163.7) that was not significantly different from that of 12 healthy control subjects (148.1 min (62.4)). Those diabetic patients without gastrointestinal symptoms and without orthostatic hypotension, however, showed a gastric emptying half time (70.1 min (41.6)) that was significantly faster than that of the control subjects. Conversely, those diabetic patients with nausea, vomiting, and early satiety (or early satiety alone) showed T50 values that were significantly greater than those of the diabetic patients without these symptoms. No correlation was found between the T50 value and the duration of diabetes, the fasting blood glucose at the time of study, or the respiratory variation in heart rate (E:I ratio). These observations indicate that highly variable rates of gastric emptying occur in insulin dependent diabetic patients, and that accelerated gastric emptying may occur in diabetic patients who have no symptoms of gastrointestinal dysfunction.

Enhanced oral activity responses to intrastriatal SKF 38393 and m-CPP are attenuated by intrastriatal mianserin in neonatal 6-OHDA-lesioned rats.

Enhanced oral activity is induced in neonatal 6-hydroxydopamine- (6-OHDA-) lesioned rats by systemic administration of the dopamine (DA) D1 receptor agonist SKF 38393 and serotonin (5-HT) 5-HT2A,2C agonist m-chlorophenylpiperazine (m-CPP). The DA D1 receptor antagonist SCH 23390 effectively attenuates the effect of SKF 38393 but not m-CPP. The 5-HT2 antagonist mianserin attenuates the effects of both m-CPP and SKF 38393, suggesting that DA agonist effects are mediated by 5-HT neurochemical systems. To test whether DA and 5-HT agonist effects and interactions might occur within the neostriatum, rats were implanted with permanent injection cannulae, with tips in the ventral striatum. One group of rats was lesioned at 3 days after birth with 6-OHDA HBr (100 micrograms salt form, in each lateral ventricle; desipramine HCl pretreatment, 20 mg/kg IP, base form, 1 h), while controls received the vehicle in place of 6-OHDA. Cannulae were implanted when rats weighed 200-250 g. During a 1-h observation session SKF 38393 (5 nmol per side) produced 74.3 +/- 19.2 oral movements in intact rats and 310.7 +/- 97.0 oral movements in 6-OHDA-lesioned rats. m-CPP (10 nmol per side) produced 72.6 +/- 15.1 and 274.5 +/- 65.0 oral movements in these respective groups. These responses were several-fold greater than the 25.3 +/- 7.3 and 41.8 +/- 9.5 oral movements in the same groups after saline (0.5 microliter per side) (P < 0.05). Mianserin (6 nmol per side) alone had no effect on oral activity but attenuated responses to both SKF 38393 and m-CPP in intact and 6-OHDA-lesioned rats.(ABSTRACT TRUNCATED AT 250 WORDS)