Triploidy and intersexuality in adult commercial layers

The cause of masculinisation of the left ovary and the outgrowth of the vestigial right gonad was investigated in intersexual hens. Tumour-like cell masses, resembling mouse tubular adenomas of the ovary, were observed in the majority of masculinised left gonads. Except for one male and two intersexuals, testosterone concentrations were below detectable levels. For oestrogen, progesterone and the oestrogen : progesterone ratio all differences were significant, except for the difference between the intersex and the male. Histochemically this cell mass showed weak androgen-synthesising activity. These intersexual gonads showed similarities to normal testicular tissue. Karyotyping revealed 3n-autosomes and a ZZW sex chromosome constitution. The early and almost complete absence of cortical follicular structures was most notable and may have been the cause of the sex reversal.     

Epidural fentanyl and sufentanil for intra- and postoperative analgesia

In a double-blind, randomized study the efficacies of concentrated fentanyl and sufentanil injections as intraoperative epidural analgesics were compared. Also, the equivalent dose of fentanyl and sufentanil administered by continuous infusion during the first. 24 h postoperatively, expressed in analgesia and also considering the side-effects was determined. 53 Patients undergoing elective thoracotomy, aortic surgery and bowel surgery were randomized and treated double-blind with fentanyl 0.250 mg/ml or sufentanil 0.05 mg/ml. Preoperatively, 0.5–1 ml study medication was administered, followed by increments of 0.2–0.5 ml during surgery guided by heart rate and systolic: blood pressure. Postoperatively, study medication diluted in 1.25 mg/l bupivacaine was administered by continuous epidural infusion. The infusion rate was adjusted to optimize analgesia. Dose, heart rate and systolic: blood pressure were measured infra- and postoperatively. Pain, sedation, nausea and pruritus were assessed on a 10 cm visual analogue scale. There were no differences in required volume of study medication, heart rate and systolic blood pressure nor in the parameters assessed postoperatively. Administered doses were 27.5g/h fenlanyl and 5.5g/h sufentanil. It was concluded that 0.250 mg/ml (0.74mol/ml) fentanyl is clinically equivalent to 0.050 mg/ml (0.13 mol/ml) sufentanil.     

A tradeoff between immunocompetence and sexual ornamentation in domestic fowl

Females often select their mates on the basis of the size or intensity of sexual ornaments, and it is thought that such traits are reliable indicators of male quality because the costliness of these traits prevents cheating. The immunocompetence handicap hypothesis is a recently proposed mechanistic explanation of these costs and states that males carry ornaments at the expense of their resistance to disease and parasites. The tradeoff between immunocompetence and sexual ornamentation was hypothesized to arise as a consequence of the dual effect of androgens on ornamentation (+) and immune function (-). To test this hypothesis, we compared comb size between male domestic chickens Gallus domesticus of lines divergently selected for antibody responses to sheep erythrocytes (three lines: selected for low response or high response and a control line). The importance of comb size in inter- and intrasexual selection is well established, and comb size is strongly dependent on testosterone level. Comb size was larger in the males of the low line than in the high line, and comb size of control males was intermediate, indicating a tradeoff between ornamentation and immunocompetence. Testosterone (T) levels varied in a similar fashion (TLow > TControl > THigh), suggesting that this hormone could mediate the tradeoff between ornamentation and immunocompetence. These results support the idea that a tradeoff with immune function may constrain the expression of secondary sexual ornaments.     

Dysregulated luminal bacterial antigen-specific T-cell responses and antigen-presenting cell function in HLA-B27 transgenic rats with chronic colitis

HLA-B27/beta2 microglobulin transgenic (TG) rats spontaneously develop T-cell-mediated colitis when colonized with normal commensal bacteria, but remain disease-free under germ-free conditions. We investigated regulation of in vitro T-cell responses to enteric bacterial components. Bacterial lysates prepared from the caecal contents of specific pathogen-free (SPF) rats stimulated interferon-gamma (IFN-gamma) production by TG but not non-TG mesenteric lymph node (MLN) cells. In contrast, essentially equivalent amounts of interleukin-10 (IL-10) were produced by TG and non-TG cells. However, when cells from MLNs of non-TG rats were cocultured with TG MLN cells, no suppression of IFN-gamma production was noted. Both non-TG and TG antigen-presenting cells (APC) pulsed with caecal bacterial lysate were able to induce IFN-gamma production by TG CD4+ cells, although non-TG APC were more efficient than TG APC. Interestingly, the addition of exogenous IL-10 inhibited non-TG APC but not TG APC stimulation of IFN-gamma production by cocultured TG CD4+ lymphocytes. Conversely, in the presence of exogenous IFN-gamma, production of IL-10 was significantly lower in the supernatants of TG compared to non-TG APC cultures. We conclude that commensal luminal bacterial components induce exaggerated in vitro IFN-gamma responses in HLA-B27 TG T cells, which may in turn inhibit the production of regulatory molecules, such as IL-10. Alterations in the production of IFN-gamma, and in responses to this cytokine, as well as possible resistance of TG cells to suppressive regulation could together contribute to the development of chronic colitis in TG rats.     

Reduction of colitis by prebiotics in HLA-B27 transgenic rats is associated with microflora changes and immunomodulation

HLA-B27 transgenic rats develop spontaneous colitis under specific pathogen-free conditions (SPF) but germ-free rats remain disease-free, emphasizing a role for intestinal bacteria in the pathogenesis of chronic intestinal inflammation. Prebiotics are dietary substances that affect the host by stimulating growth and/or activity of potentially health promoting bacteria. The aims of this study were to investigate whether prebiotics can prevent colitis in SPF HLA-B27 rats, and secondly, to explore mechanisms of protection. SPF HLA-B27 transgenic rats received orally the prebiotic combination long-chain inulin and oligofructose (Synergy 1), or not, prior to the development of clinically detectable colitis. After seven weeks, cecal and colonic tissues were collected for gross cecal scores (GCS), histologic inflammatory scores (scale 0-4), and mucosal cytokine measurement. Cecal and colonic contents were collected for analysis of the gut microbiota by PCR-denaturing gradient gel electrophoresis (PCR-DGGE) and fluorescent in-situ hybridization (FISH), and analysis of short-chain fatty acid composition. Prebiotic treatment significantly decreased GCS and inflammatory histologic scores in the cecum and colon. Prebiotic treatment also decreased cecal IL-1beta, but increased cecal TGF-beta concentrations. Inulin/oligofructose altered the cecal and colonic PCR-DGGE profiles, and FISH analysis showed significant increases in cecal Lactobacillus and Bifidobacterium populations after prebiotic treatment compared with water-treated rats. In conclusion, the prebiotic combination Synergy 1 reduced colitis in HLA-B27 transgenic rats, which effect was associated with alterations to the gut microbiota, decreased tissue proinflammatory cytokines and increased immunomodulatory molecules. These results show promise for prebiotics as primary or adjuvant maintenance therapy for chronic inflammatory bowel diseases.     

Urological complaints in relation to indinavir plasma concentrations in HIV-infected patients

OBJECTIVE: To assess the relationship between indinavir-associated urological complaints and indinavir plasma concentrations. DESIGN: Case series, comparing indinavir plasma concentrations in cases with average concentrations in a control group. METHODS: Patients taking 800 mg indinavir three times a day (tid), who presented with overt urological complaints (renal colic, flank pain or haematuria) were selected for the study. Plasma indinavir concentrations were measured by means of a standardized high performance liquid chromatography (HPLC) method. Plasma samples taken at 1.5-8 h after the last indinavir ingestion were included for evaluation. Results were compared with the full pharmacokinetic curves of indinavir plasma concentrations from a control group of 14 patients taking 800 mg indinavir tid without urological complaints, and were expressed as concentration ratios. A ratio of 1 indicated a plasma concentration equalling the average concentration in the control population at the same point in time after the ingestion of indinavir. RESULTS: Seventeen patients (five women) were enrolled and the indinavir concentrations of 15 patients could be evaluated. Fourteen (93%) patients had a concentration above the mean of the controls, 12 (80%) patients had a concentration above the upper 95% confidence limit, and one (7%) patient had a concentration below the lower 95% confidence limit. The mean indinavir concentration in patients with urological complaints (ratio range 0.55-11.49) was significantly higher than the average concentration and the upper 95% confidence limit of the control group (P < 0.05). The results could not be explained by differences in weight, sex or drug interactions. Two patients had chronic active hepatitis B infection. In six patients with indinavir concentrations above the upper 95% limit, indinavir was reduced to 600 mg tid. Upon repeat measurement after the dose adjustment, their indinavir plasma concentrations fell within the 95% confidence interval around the mean of the control population. All six patients remained asymptomatic and had viral loads of less than 500 copies per ml after a follow-up of 5-16 months. CONCLUSIONS: Urological complications occurring during indinavir treatment were associated with elevated indinavir plasma concentrations in 80% of patients in this study. Indinavir plasma concentrations should be monitored upon presentation of urological complaints, on the basis of which dose reductions may be applied if brief interruption and increased hydration are ineffective.     

Lipodystrophy and 'buffalo hump' during treatment with HIV protease inhibitors

In three patients, a 36-year-old HIV seropositive homosexual man and two women aged 35 and 59 years who had acquired HIV infection through heterosexual contact, signs of lipodystrophy developed after prolonged anti-HIV triple therapy. The observed syndrome is seen after prolonged use of HIV protease inhibitors: it is characterized by peripheral fat wasting, central fat accumulation, hyperlipidaemia and insulin resistance. Typically the subcutaneous fatty tissue disappears resulting in prominent zygomata, veins and muscles and thinning of extremities and buttocks. In addition to abdominal fat accumulation, there have been reports on the occurrence of a dorsocervical fat pad, the so-called buffalo hump. Lipodystrophy caused by protease inhibitors is a risk factor for cardiovascular disease. Recognition of the syndrome is essential for adequate follow-up and possible treatment.     

Cone-beam CT in the assessment of mandibular invasion by oral squamous cell carcinoma: results of the preliminary study

This preliminary retrospective study evaluates the diagnostic value of cone-beam computed tomography (CBCT), as a potential standard preoperative procedure, in assessing mandibular invasion by oral squamous cell carcinoma (OSCC) compared with conventional preoperative panoramic radiography (PR), magnetic resonance imaging (MRI) and histological examination of the resection specimen (the golden standard). Between September 2006 and September 2009, 23 patients with histology proven primary OSCC, adjacent to or fixed to the mandible were included. The tumours were classified into four groups, ranging from no bone invasion to evident bone invasion. Sensitivity and specificity for PR were 55% (95% CI [0.350;0.619]) and 92% (95% CI 0.737;0.984]), respectively, both were significantly lower than the 91% (95% CI [0.740;0.909]) and 100% (95% CI [0.845;1]), respectively, for CBCT. MRI showed 82% sensitivity (95% CI [0.608;0.941]) and 67% specificity (95% CI [0.474;0.779]). CBCT has the potential to become a new diagnostic tool in the OSCC screening procedure to predict mandibular invasion or erosion, but its value may be limited by its relatively low sensitivity. A prospective study will start on 64 patients (α = 0.05; power 0.8; effect size 0.5) to improve these results statistically.     

CD4(+) T lymphocytes mediate colitis in HLA-B27 transgenic rats monoassociated with nonpathogenic Bacteroides vulgatus

BACKGROUND: HLA-B27/beta2 microglobulin transgenic (TG) rats develop spontaneous colitis when raised under specific pathogen-free (SPF) conditions or after mono-association with Bacteroides vulgatus (B. vulgatus), whereas germ-free TG rats fail to develop intestinal inflammation. SPF HLA-B27 TG rnu/rnu rats, which are congenitally athymic, remain disease free. These results indicate that commensal intestinal bacteria and T cells are both pivotal for the development of colitis in TG rats. However, it is not known if T cells are also required in the induction of colitis by a single bacterial strain. The aim of this study was therefore to investigate the role of T cells in the development of colitis in B. vulgatus-monoassociated HLA-B27 TG rats. METHODS: HLA-B27 TG rnu/rnu and rnu/+ rats were monoassociated with B. vulgatus for 8-12 weeks. CD4(+) T cells from mesenteric lymph nodes (MLNs) of B. vulgatus-monoassociated rnu/+ TG donor rats were transferred into B. vulgatus-monoassociated rnu/rnu TG recipients. RESULTS: B. vulgatus-monoassociated rnu/+ rats showed higher histologic inflammatory scores and elevated colonic interferon-gamma mRNA, cecal myeloperoxidase, and cecal IL-1beta levels compared to those in rnu/rnu TG rats that did not contain T cells. After transfer of CD4(+) cells from colitic B. vulgatus-monoassociated rnu/+ TG donor rats, B. vulgatus-monoassociated rnu/rnu TG recipients developed colitis that was accompanied by B. vulgatus-induced IFN-gamma production by MLN cells in vitro and inflammatory parameters similar to rnu/+ TG rats. CONCLUSIONS: These results implicate CD4(+) T cells in the development of colitis in HLA-B27 TG rats monoassociated with the nonpathogenic bacterial strain B. vulgatus.