Intestinal dendritic cells increase T cell expression of alpha4beta7 integrin

The integrin alpha4beta7 binds to MAdCAM-1 and contributes to homing of lymphocytes to gut and other mucosal tissues. In humans, the alpha4beta7(hi) subset of circulating memory cells appears to have been primed in mucosal tissues. The factors that determine whether alpha4beta7(lo) naive cells become alpha4beta(hi) or alpha4beta7(-) cells upon differentiation are poorly understood but could include an influence of the activating antigen-presenting cell. To address this point, the induction of alpha4beta7 following activation of mouse cells with the APC-dependent stimulus soluble anti-CD3 has been examined. Almost all mouse T cells freshly isolated from mesenteric lymph nodes (MLN) and peripheral (PLN; axillary, brachial and inguinal) lymph nodes stained only weakly for alpha4beta7 but a subpopulation became alpha4beta7(hi) upon activation with anti-CD3 in a cell cycle- and accessory cell-dependent manner. A small proportion (approximately 1.5 %) of the starting cells gave rise to alpha4beta7(hi) cells after culture. A higher proportion of alpha4beta7(hi) cells were generated in MLN than PLN cultures. Peyer's patch cultures gave intermediate values. In crossover experiments, MLN dendritic cells (DC) induced higher proportions and numbers of alpha4beta7(hi) cells than PLN DC irrespective of the source of T cells. Therefore, in addition to their other immunoregulatory roles, DC have the potential to shape immune responses by influencing the homing of the lymphocytes they activate.     

Tourniquet inflation after intra-articular morphine and bupivacaine administration following knee arthroscopy

We performed a randomized doubled-blind study to evaluate whether there was a benefit in delay in tourniquet deflation with intra-articular administration of morphine and bupivacaine following operative arthroscopic surgery. In 34 patients the tourniquet was deflated immediately and in 38 patients the tourniquet remained inflated for 10 min following injection. The analgesic efficacy was assessed using pain scores and the amount of supplementary analgesia required. The results demonstrate no benefit in delay in tourniquet deflation.     

Evaluation of a rapid latex agglutination test (Directigen®) for the direct detection of group A streptococci from throat swabs

Summary A rapid group A beta-hemolytic streptococci (GAS) antigen detection test using latex agglutination (Directigen^®, Becton Dickinson) was compared with a conventional culture method for the direct detection of GAS from throat swabs. One throat specimen was collected from each of 229 patients. After standard inoculation onto sheep blood agar plates, all swabs were tested for GAS antigen. Of the 229 specimens tested, 46 (20%) were GAS-positive by culture. Direct latex agglutination agreed with culture in 222 of them (97%). The sensitivity of the test was 93% (43/46), the specificity 98% (179/183), the positive predictive value 91%, and the negative predictive value 98%. The detection of GAS antigen by coagglutination (Phadebact^®, Pharmacia) was also carried out. 81% (35/43) of the cultures and Directigen^®-positive specimens gave a positive coagglutination for GAS. 100% (179/179) of the cultures and Directigen^®-negative specimens were also negative by the coagglutination test. We conclude that the Directigen^® rapid latex agglutination test for the direct detection of GAS from throat swabs compares favorably with culture and has the advantage of providing same-day results.

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Zuverlässigkeit eines Schnelltests mittels Latexagglutination (Directigen^®) zum direkten Nachweis von Streptokokken der Gruppe A (SGA) im Rachenabstrich

Zusammenfassung In dieser Studie haben wir die Zuverlässigkeit eines Schnelltests mittels Latexagglutination (Directigen^®, Becton Dickinson) zum direkten Nachweis von -hämolysierenden Streptokokken der Gruppe A (SGA) im Rachenabstrich mit der konventionellen Kulturmethode verglichen. Bei 229 zufällig ausgewählten Patienten wurde jeweils ein Rachenabstrich entnommen. Alle Rachenabstriche wurden zuerst auf eine Schafblutagarplatte ausgestrichen und mittels Latex-Schnellagglutination auf das Vorhandensein von Antigenen von SGA getestet. 46 (20%) der 229 getesteten Rachenabstriche enthielten in der Kultur SGA. Das Resultat der direkten Latexagglutination stimmte in 222 Fällen (97%) mit der Kultur überein. Die Sensitivität des Tests betrug 93% (43/46), die Spezifität 98% (179/183), die positive Voraussagekraft des Tests 91%, die negative 98%. Wir haben zudem den Nachweis von SGA-Antigenen mittels Koagglutination (Phadebact^®, Pharmacia) durchgeführt. 81% (35/43) der Rachenabstriche, welche in der Kultur und im Directigen^®-Test positiv waren für SGA-Antigene, waren dies auch im Koagglutinationstest. 100% (179/179) der Rachenabstriche, welche keine SGA-Antigene in der Kultur und mittels Directigen^® aufgewiesen haben, waren mittels Koagglutinationstest ebenfalls negativ. Der Directigen^®-Schnelltest mittels Latexagglutination zum direkten Nachweis von SGA in Rachenabstrichen ist in seiner Zuverlässigkeit mit der Kulturmethode vergleichbar. Dieser Schnelltest hat den Vorteil, daß das Ergebnis am selben Tag vorliegt.

     

MR imaging with surface coils

The use of specialized coils to improve signal-to-noise ratios in magnetic resonance (MR) imaging is an important innovation. The role of surface coils has not yet been well defined, but it seems likely that they will be routinely used for clinical imaging of the orbit, neck, and spine. Surface coils have important limitations that make other designs, such as "closely coupled" volume coils, attractive for some applications, especially for limb imaging. With improvement in our ability to visualize anatomy with MR imaging, specialized radio frequency coils may provide new imaging capabilities for clinical problems that were not previously considered to be indications for diagnostic imaging.     

The use of natural interferon alpha conjugated to a monoclonal antibody anti mammary epithelial mucin (Mc5) for the treatment of human breast cancer xenografts

Summary An immunoconjugate composed of natural interferon (nIFN) bound in a noncleavable fashion to a monoclonal antibody (MoAb) recognizing a breast epithelial membrane mucin (Mc5) was used to treat xenografts of a human mammary carcinoma cell line (MCF-7) growing in nude mice. The immunoconjugate (nIFN/Mc5) was administered as 20 intralesional (i.l.) injections to 1 of 2 xenografts in each animal. It was found that nIFN/Mc5 produced a significant enhancement of the growth inhibitory actions of nIFN on the injected tumors. Further enhancement was obtained when nIFN or nIFN together with Mc5 (at a dose 10 times larger than that present in nIFN/Mc5) were added to the immunoconjugate. Biodistribution experiments showed that the uptake of¹²⁵I-nIFN/Mc5 by the tumors was greater and its elimination slower than for¹²⁵I-nIFN alone or conjugated to irrelevant mouse IgG₁. In addition, the immunoconjugate up-regulated the antigenic expression of a breast epithelial membrane mucin by the carcinoma cells, an up-regulation which was not significantly different from that produced by nIFN alone. The contralateral noninjected tumors exposed to systemic levels of the immunoconjugate showed an enhancement of antitumor effects, but to a lesser extent than the injected tumors. These findings suggest that the enhancement of the growth inhibitory action of the immunoconjugate was related to the specific binding of Mc5 which targeted the IFN to the carcinoma cells and impeded its elimination. It is likely that the targeting was favored by the IFN-mediated up-regulation of antigenic expression by the carcinoma cells, thereby producing a cascade of interrelated effects. The results of this study point out the feasibility and potential usefulness of IFN treatment by means of immunoconjugates as well as the worth of pursuing and improving this form of therapy.     

Current techniques in sentinel node mapping

The prognosis for patients with breast cancer or melanoma largely depends on the involvement of nearby lymph nodes. This article examines techniques used to identify and assess sentinel nodes--those that drain the cancerous area. Such techniques may permit more conservative, node-sparing treatment. Studies evaluating the use of both radiopharmaceuticals and colored dyes are described.     

Results of repeat anal sphincter repair

BACKGROUND: Patients with a poor outcome from anterior sphincter repair may be candidates for dynamic graciloplasty, artificial bowel sphincter implantation or a secondary repair. This study examines the outcome of repeat overlap repairs in these patients. METHODS: Twenty-six of 235 patients undergoing a sphincter repair (median age 43 (range 23-63) years) underwent repeat repair from May 1994 to April 1997. Twenty-three patients were available for follow-up. Clinical evaluation included a satisfaction scale from 1 to 10, the patient's assessment of percentage improvement, ability to defer defaecation before and after operation, and Wexner continence scores before and after operation. Manometric studies were performed in 21 patients before and 17 patients after operation, and anal ultrasonography was undertaken in 17 patients before and 14 patients after operation. External sphincter defects were present on all preoperative scans. RESULTS: At a median follow-up of 20 (range 5-42) months, 15 patients felt that they were 50 per cent or more improved after operation. On the satisfaction scale of 1-10 the median score was 7 (range 1-10). There was a significant improvement in the Wexner continence score from 19 (range 17-20) before operation to 12 (range 1-20) after operation (P < 0.001). Ability to defer defaecation improved significantly from less than 5 min in all patients before operation to greater than 15 min in six patients after operation. Ultrasonography showed good overlap of the external sphincter muscle in eight of 14 patients. All patients who failed to improve showed a residual defect on ultrasonography. CONCLUSION: Repeat anterior repair produces a significant improvement in continence score and ability to defer defaecation in patients with obstetric sphincter damage. Clinical improvement correlates closely with an improvement in the appearance on endoanal ultrasonography.     

Topical phenylephrine increases anal sphincter resting pressure

BACKGROUND: Phenylephrine is an alpha1-adrenergic agonist which causes contraction of human internal anal sphincter muscle in vitro. Its intra-arterial administration in animals has been shown to increase resting sphincter pressure in vivo. In this study the effect of topical application of phenylephrine on resting anal pressure in healthy human volunteers was investigated. METHODS: Twelve healthy volunteers had measurements of maximum resting sphincter pressure (MRP) and anodermal blood flow taken before and after topical application of increasing concentrations of phenylephrine gel to the anus. To determine the duration of effect of the agent, readings were taken throughout the day after a single application. RESULTS: There was a dose-dependent rise in the resting anal sphincter pressure, with a small 8 per cent rise after 5 per cent phenylephrine (P = 0.012) and a larger 33 per cent rise with 10 per cent phenylephrine (mean(s.d.) MRP 85(12) cmH2O before versus 127(12) cmH2O after treatment, P < 0.0001). Thereafter no additional response was noted with higher concentrations of phenylephrine. The median duration of action of a single application of 10 per cent phenylephrine was 7 (range from 6 to more than 8) h. CONCLUSION: Topical application of 10 per cent phenylephrine gel to the anus produces a significant rise in the resting anal sphincter pressure in healthy human volunteers. This represents a potential novel therapeutic approach to the treatment of passive faecal incontinence associated with a low resting anal sphincter pressure.     

Fat gram target to achieve high energy intake in cystic fibrosis

Higher fat and energy intakes confer a survival advantage in cystic fibrosis (CF). There is a need to develop effective nutrition programmes that ensure optimal energy intake in CF.

Methodology:

A cross-sectional measurement of clinical characteristics and energy and fat intakes in patients attending the CF outpatients clinic of the John Hunter Hospital, Newcastle was undertaken. Twenty-nine subjects, mean age 12 years (range 4.3–20.2), completed weighed food records to determine the contribution of fat to the percentage of the recommended energy intake obtained and to document use of pancreatic enzyme replacement therapy.

Results:

Diets with a high percentage of energy derived from fat did not guarantee that individuals with CF met their energy requirements. Subjects with total fat intakes of 100 g per day or greater, however, achieved in excess of 110% recommended daily intake (RDI) for energy. Up to 47% of subjects consumed more pancreatic enzyme replacement capsules than shown to give maximum effectiveness.

Conclusion:

Setting a 100 g daily fat target is a realistic way of ensuring high energy intakes in CF. Fat ready reckoners would identify the fat content of food and prescribe specific numbers of pancreatic enzyme replacement capsules to be consumed with each meal or food item.