Comparison of ionised calcium measured using a portable analyser to a reference method in healthy dogs.

OBJECTIVES: To compare the ionised calcium measured on a portable analyser (iSTAT, Abbott) to a reference method. MATERIALS AND METHODS: Blood samples from 39 apparently healthy dogs were analysed in duplicate using a portable analyser and a reference method (Radiometer ABL800 FLEX). Bland-Altman plots and Passing-Bablok regression were used to assess constant and proportional bias between the two instruments. A within-assay percentage coefficient of variation and total error (TE) was calculated for both analysers. The reference interval was calculated for the portable analyser using the robust method with confidence interval bootstrapping. RESULTS: The Bland-Altman plot showed a -0.036 mmol/L difference between the two instruments (95% confidence limit -0.08 to 0.01 mmol/L; limits of agreement -0.07 to 0.006 mmol/L). Neither the Bland-Altman plot nor the Passing-Bablock regression (slope -0.03; 95% confidence interval -0.08 to 0.19 and intercept 1; 95% confidence interval 0.83 to 1.2) showed significant proportional bias. The coefficient of variation for the portable analyser was 1.08%, compared to 0.78% for the reference method with a total error of 3.5% for the portable analyser. The estimated population-based reference interval for ionised calcium using the portable analyser is 1.23 to 1.42 mmol/L. CLINICAL SIGNIFICANCE: For the healthy dogs in this study, compared to the reference method, the portable analyser showed no significant bias for measurement of ionised calcium. Further studies including hyper and hypocalcaemic dogs are required to determine clinical impact of the use of this analyser.

Effectiveness, safety and acceptability of no-test medical abortion (termination of pregnancy) provided via telemedicine: a national cohort study.

OBJECTIVE: To compare outcomes before and after implementation of medical abortion (termination of pregnancy) without ultrasound via telemedicine. DESIGN: Cohort analysis. SETTING: The three main abortion providers. POPULATION OR SAMPLE: Medical abortions at home at ≤69 days' gestation in two cohorts: traditional model (in-person with ultrasound, n = 22 158) from January to March 2020 versus telemedicine-hybrid model (either in person or via telemedicine without ultrasound, n = 29 984, of whom 18 435 had no-test telemedicine) between April and June 2020. Sample (n = 52 142) comprises 85% of all medical abortions provided nationally. METHODS: Data from electronic records and incident databases were used to compare outcomes between cohorts, adjusted for baseline differences. MAIN OUTCOME MEASURES: Treatment success, serious adverse events, waiting times, gestation at treatment, acceptability. RESULTS: Mean waiting time from referral to treatment was 4.2 days shorter in the telemedicine-hybrid model and more abortions were provided at ≤6 weeks' gestation (40% versus 25%, P < 0.001). Treatment success (98.8% versus 98.2%, P > 0.999), serious adverse events (0.02% versus 0.04%, P = 0.557) and incidence of ectopic pregnancy (0.2% versus 0.2%, P = 0.796) were not different between models. In the telemedicine-hybrid model, 0.04% were estimated to be over 10 weeks' gestation at the time of the abortion; all were completed safely at home. Within the telemedicine-hybrid model, effectiveness was higher with telemedicine than in-person care (99.2% versus 98.1%, P < 0.001). Acceptability of telemedicine was high (96% satisfied) and 80% reported a future preference for telemedicine. CONCLUSIONS: A telemedicine-hybrid model for medical abortion that includes no-test telemedicine and treatment without an ultrasound is effective, safe, acceptable and improves access to care. TWEETABLE ABSTRACT: Compelling evidence from 52 142 women shows no-test telemedicine abortion is safe, effective and improves care.

An example of psychological adjustment in chronic illness: Hirschsprung's disease.

The aim of this study was to investigate the outcomes after definitive surgical correction for children with Hirschsprung's disease (HD) and the psychosocial impact of HD on the child and family. The total sample comprised 72 children with HD along with their families. The development of a condition-specific questionnaire measured the functional and psychosocial outcomes for children with HD with parental perception of their child's condition. Psychiatric measures were also examined to assess psychiatric morbidity. The greatest functional problem after definitive surgery for HD was faecal soiling (76%). The principle findings of the study were that (1) HD did not have a significant impact on the child's rate of psychiatric morbidity and levels of hopefulness in comparison to the normal population, (2) surgical and psychosocial functioning improved with increasing age and, (3) families remain troubled about their future with HD and dealing with psychosocial difficulties related to the condition (such as distress because of faecal soiling). Specifically, faecal soiling was found to be physically, emotionally and psychosocially distressing complication. Bowel functioning and psychosocial distress improves with increasing age and parental and medical professional support. Despite the significant impairment of faecal continence, we found that children/young adults with HD have minimal psychiatric morbidity, yet experience condition-specific psychosocial problems (e.g. embarrassment and distress/discomfort). HD does not increase the rate of clinical psychiatric morbidity in children and families with HD, but does determine the context of their daily distress and concern.

Life after definitive treatment for children with Hirschsprung's disease.

PURPOSE: The aim of this study was to investigate the long-term outcomes after definitive surgical correction for children with Hirschsprung's Disease (HD) and the psychosocial impact HD has on the child and family. METHODS: A clinical-based database of seventy-two children and young people aged between one to twenty-four years with HD, along with their families were investigated. This study involved the development of a condition-specific questionnaire in order to assess the functional and psychosocial outcomes for children with HD at different age groups, combined with parental perception of their child's condition in the long-term. RESULTS: The greatest functional problem after definitive surgery for HD was faecal soiling (n = 29/38: 76.3%). Children < or = 12 years experienced more embarrassment, distress/discomfort and family difficulties (n = 53/72; 73.6%) due to bowel dysfunctioning (such as faecal soiling) in comparison to children 12 years (n = 19/72; 26.3%) (p < 0.05). Young adults with HD (> 12 years) remained confident and 62.5% hopeful about their future with HD. Nine (12.5%) of the parents reported that HD had a negative impact on their marital relationship due to the daily stressors. Yet, 58.3% (n = 42) families remain confident and 70.8% (n = 42) hopeful about their child's future with HD. CONCLUSION: Bowel functioning and psychosocial distress improves with increasing age and parental and medical professional support. Psychosocial difficulties found in the child and family with HD are condition-specific--thus improving complications such as faecal soiling will further enhance better psychosocial adjustment.

Arzoxifene, a new selective estrogen receptor modulator for chemoprevention of experimental breast cancer.

Arzoxifene ([6-hydroxy-3-[4-[2-(1-piperidinyl)-ethoxy]phenoxy]-2-(4-methoxyphenyl)]benzo[b]thiophene) is a selective estrogen receptor modulator (SERM) that is a potent estrogen antagonist in mammary and uterine tissue while acting as an estrogen agonist to maintain bone density and lower serum cholesterol. Arzoxifene is a highly effective agent for prevention of mammary cancer induced in the rat by the carcinogen nitrosomethylurea and is significantly more potent than raloxifene in this regard. Arzoxifene is devoid of the uterotrophic effects of tamoxifen, suggesting that, in contrast to tamoxifen, it is unlikely that the clinical use of arzoxifene will increase the risk of developing endometrial carcinoma.

Reversal of multidrug resistance by the P-glycoprotein modulator, LY335979, from the bench to the clinic.

Multidrug resistance may be conferred by P-glycoprotein (Pgp, ABCB1) or the multidrug resistance associated protein (MRP). These membrane proteins are members of the ATP binding cassette transporter superfamily and are responsible for the removal from the cell of several anticancer agents including doxorubicin. Modulators can inhibit these transporters. LY335979 is among the most potent modulators of Pgp with a Ki of 59 nM. LY335979 is selective for Pgp, and does not modulate MRP-mediated resistance by MRP1 (ABCC1) and MRP2 (ABCC2). LY335979 significantly enhanced the survival of mice implanted with Pgp-expressing murine leukemia (P388/ADR) when administered in combination with either daunorubicin, doxorubicin or etoposide. Coadministration of LY335979 with paclitaxel compared to paclitaxel alone significantly reduced the tumor mass of the Pgp-expressing UCLA-P3.003VLB lung carcinoma in a xenograph model and delayed the development of tumors in mice implanted with the parental drug-sensitive UCLA-P3 tumor. LY335979 was without significant effect on the pharmacokinetics of these anticancer agents. This may be due impart to its poor inhibition of four major cytochrome P450 isozymes important in metabolizing doxorubicin and other oncolytics. The selectivity and potency of this modulator allows the clinical evaluation of the role of Pgp in multidrug resistance. LY335979 is currently in clinical trials.

Long-term evaluation of rectus fascial wrap in patients with spina bifida.

PURPOSE: We evaluated patients with spina bifida to determine long-term results of the rectus fascial wrap, a modification of the rectus fascial sling MATERIALS AND METHODS: We assessed patients with spina bifida 3 years after a rectus fascial wrap procedure using an outcome questionnaire, renal ultrasound and urodynamics. RESULTS: The 15 patients who completed the outcome questionnaire indicated that significant improvement over preoperative status was maintained a mean of 58 months postoperatively. Ultrasound in 14 cases showed no postoperative increase in hydronephrosis. Urodynamic study in 13 patients revealed a mean bladder capacity of 583 cc and mean maximum detrusor pressure of 39 cm. water, while 11 had no urine leakage when Valsalva leak point pressure was measured. CONCLUSIONS: Three years postoperatively the rectus fascial wrap provides dryness comparable to that of other bladder neck sling procedures in patients with spina bifida.

Reversal of resistance in multidrug resistance protein (MRP1)-overexpressing cells by LY329146.

The benzothiophene LY329146 reverses the drug resistance phenotype in multidrug resistance protein (MRP1)-overexpressing cells when dosed in combination with MRP1-associated oncolytics doxorubicin and vincristine. Additionally, LY329146 inhibited MRP1-mediated uptake of the MRP1 substrate LTC4 into membrane vesicles prepared from MRP1-overexpressing cells.

Carcinoid tumor of the cystic duct.

A 69-year-old male was admitted to an outside institution for severe right abdominal pain radiating to the flank. An extensive work-up, including lower GI series, IVP, and ultrasound of the kidneys were normal. Ultrasound of the liver demonstrated a thickened gallbladder as well as cholelithiasis. Despite some improvement, his symptoms returned intermittently and cholecystectomy was performed. Pathologic examination of the gallbladder showed a carcinoid tumor, 5.4 mm in maximum diameter, in the cystic duct. A small metastatic focus was also found in the cystic duct lymph node. In this paper we compare the clinical presentation, pathological findings and outcome of this case to the previously reported six cases of cystic duct carcinoid. A comparison is also made between the general features of carcinoid at this rare location and the more common gastrointestinal carcinoid.

Selectivity of the multidrug resistance modulator, LY335979, for P-glycoprotein and effect on cytochrome P-450 activities.

Overexpression of ATP-dependent drug efflux pumps, P-glycoprotein (Pgp) or multidrug resistance-associated protein (MRP), confers multidrug resistance to tumor cells. Modulators of multidrug resistance block the action of these pumps, thereby sensitizing cells to oncolytics. A potent Pgp modulator is LY335979, which fully sensitizes Pgp-expressing cells at 0.1 microM in cytotoxicity assays and for which Pgp has an affinity of 59 nM. The present study examines its effect on MRP1-mediated drug resistance and cytochrome P-450 (CYP) activity and its ability to serve as a Pgp substrate. Drug resistance was examined with HL60/ADR and MRP1-transfected HeLa-T5 cells. Drug cytotoxicity was unaffected by 1 microM LY335979; leukotriene C4 uptake into HeLa-T5 membrane vesicles was unaffected. Because the substrate specificity of Pgp and CYP3A overlap, the effect of LY335979 on the 1'-hydroxylation of midazolam by CYP3A in human liver microsomes was examined. The apparent K(i) was 3.8 microM, approximately 60-fold higher than the affinity of Pgp for LY335979. The modulator's effect on Pgp was evaluated with Pgp-overexpressing CEM/vinblastine (VLB)(100) and parental CCRF-CEM cells. Both cell lines accumulated [(3)H]LY335979 equally well and did not efflux [(3)H]LY335979 during a 3-h incubation, indicating that it is not a substrate of Pgp. Equilibrium-binding studies with CEM/VLB(100) plasma membranes and [(3)H]LY335979 showed that Pgp had a K(d) of 73 nM, which is in good agreement with the previously determined K(i) value. Thus, LY335979 is an extremely potent Pgp, and not MRP1 or MRP2, modulator and has a significantly lower affinity for CYP3A than for Pgp.

Mesh inguinodynia: a new clinical syndrome after inguinal herniorrhaphy?

BACKGROUND: Chronic inguinodynia or neuralgia after conventional inguinal herniorrhaphy is rare, and diagnosing the exact cause is difficult. Treatment has ranged from local injection to remedial surgery with variable results. The increasing popularity of prosthetic mesh repairs (tension free, plug, or laparoscopic) has not eliminated these pain syndromes from occasionally occurring. Recommended management in these situations is extremely difficult. STUDY DESIGN: Since 1994, 117 inguinal reexplorations have been performed for inguinodynia and 20 of these patients had primary mesh herniorrhaphy. All 20 patients had mesh removal. Records were reviewed and patients contacted to evaluate outcomes. RESULTS: All 20 patients were evaluated (15 by telephone or direct contact, 5 by chart review). Three patients had their initial repair performed laparoscopically. Symptoms persisted for 12.2 +/- 1.7 months before remedial surgery. Four patients underwent inguinal reexploration and mesh removal; 16 had mesh removal plus ilioinguinal or iliohypogastric neurectomy. Good to excellent results were achieved in 12 out of 20 patients (60%). Average followup time was 15.9 +/- 3.1 months. Two of 3 patients who had laparoscopic herniorrhaphy had favorable outcomes (67%). Ten of the 16 patients who had mesh removal plus neurectomy reported good to excellent results (62%) compared with 2 of 4 reporting the same with mesh excision only (50%). Eleven patients had pain relief with preoperative nerve block. Of these, 9 had elective neurectomy resulting in good to excellent results in 5 (56%). CONCLUSIONS: Remedial inguinal exploration and mesh removal with or without neurectomy resulted in favorable outcomes in 60% of patients with mesh herniorrhaphy chronic inguinodynia (neuralgia). It appears that coincident neurectomy affords better results than mesh removal alone. Relief with nerve block did not predict favorable outcomes. Despite the popularity and favorable outcomes of prosthetic mesh repairs, persistent postoperative pain still occurs in a small cohort of patients. This may become more evident with the rising interest in laparoscopy. Correcting this problem once presented can be a formidable task. Remedial inguinal surgery with mesh removal and neurectomy will cure selected patients.

Tertiary hyperparathyroidism after renal transplantation: surgical strategy.

BACKGROUND: An analysis of our experience with tertiary hyperparathyroidism (III HPT) in renal transplantations between 1981 and 1996 was reviewed to examine a variety of laboratory and clinical variables in this population. METHODS: A total of 3233 kidney transplantations were performed; 48 patients underwent parathyroidectomy for III HPT. Five patients were excluded from analysis due to the development of renal dysfunction. The index 43 patients were divided into two groups. Group I consisted of 31 patients (72%) with either enlargement of all parathyroid glands (n = 26) or 3/4 gland enlargement (n = 5). These patients were assumed to have hyperplasia and underwent subtotal parathyroidectomy or total parathyroidectomy. Group II consisted of 12 patients (28%) with single (7/12; 58%) or two-gland enlargement (5/12; 42%). Group II patients underwent resection of only the enlarged glands. RESULTS: Laboratory and clinical parameters showed no difference between the groups during long-term follow-up. Most patients in groups I and II were eucalcemic after parathyroidectomy. However, postoperative hypercalcemia and hypocalcemia did occur in group I (mean postoperative calcium: group I = 9.29 +/- 0.63 mg/dL; group II = 9.42 +/- 0.58 mg/dL). CONCLUSIONS: Four gland parathyroid enlargement is a frequent finding in III HPT, although asymmetric enlargement can occur. Histologically, this represents sporadic adenomas and asymmetric hyperplasia. Intraoperative findings should dictate surgical strategy; with asymmetric enlargement only the enlarged parathyroid glands should be resected.

Minimally invasive therapies for the treatment of symptomatic benign prostatic hyperplasia: the University of Florida experience.

OBJECTIVE: To describe the University of Florida experience with minimally invasive therapies in the surgical treatment of benign prostatic hyperplasia (BPH). BACKGROUND DATA: Typically, the standard surgical treatment for symptomatic benign prostatic hyperplasia (BPH) has been transurethral resection of the prostate (TURP). Due to the morbidity associated with TURP, several minimally invasive therapies, such as laser, microwaves, high intensity focused ultrasound, and radiofrequency needle ablation, have been utilized to treat BPH. METHODS: The authors review their experience, along with that of others, with various forms of heat therapy in the treatment of BPH. RESULTS AND CONCLUSIONS: Although high intensity focused ultrasound (HIFU), interstitial laser, and microwaves procedures have been shown to be effective in the treatment of BPH, our experience has been with laser, VaporTrode, and TUNA. We found that VaporTrode and TUNA currently offer several advantages over many of the other modalities.

Physiologic evaluation and surgical management of failed ileoanal pouch.

BACKGROUND: Following proctocolectomy and ileal pouch-anal anastomosis, a small percentage of patients will have poor functional results attributable to pouchitis or anastomotic or septic complications. Additionally, functional failures can occur secondary to limited pouch capacity and compliance. We present five such patients managed with operative conversion to W-ileal pouch-anal anastomosis and examined physiologic parameters important for improving functional results. METHODS: Five female patients (mean age, 30 (range, 24-39) years) with poorly functioning J-ileal pouch-anal anastomoses were referred for evaluation with symptoms of high stool frequency and incontinence problems. Three had severe nocturnal incontinence, and the remaining two patients experienced minor nocturnal incontinence. Preoperative and postoperative evaluation included barium pouch studies, flexible sigmoidoscopy, anal manometry, evacuation volume, and pouch compliance. Pouch-to-anal pressure gradients were calculated. To improve reservoir capacity and compliance, all five patients underwent conversion to W-ileal pouch-anal anastomoses. RESULTS: Twenty-four hour and nocturnal stool frequencies decreased from 13.8+/-1.7 and 3+/-1.3 to 5.8+/-0.3 and 0.3+/-0.2 postconversion (P < 0.05). Mean pouch evacuation volume increased from 83+/-27 to 290+/-29 ml postoperatively (P < 0.05). Pouch compliance increased from 2.7+/-0.5 mmHg/ml to 7.7+/-0.6 mmHg/ml postconversion (P < 0.05). Improvement in postconversion stool frequency correlated with an increase in pouch evacuation volume (r=-0.87). All patients reported improved day and nocturnal continence, despite no significant change between preoperative and postoperative anal manometric pressures. Improved continence correlated with a significant widening of the pouch-to-anal pressure gradients, which increased from 5 to 25 mmHg at 150 ml following pouch conversion. CONCLUSIONS: Poorly functioning ileal reservoirs secondary to limited capacity and compliance can be successfully managed with conversion to W-ileal pouch-anal anastomosis. The increased pouch capacity is associated with improvement in compliance and widening of the pouch-to-anal pressure gradients, providing excellent functional results.

Experience, knowledge and attitudes of child psychiatrists regarding electroconvulsive therapy in the young.

OBJECTIVE: To ascertain the experience, knowledge and attitudes of Australian and New Zealand child psychiatrists in relation to electroconvulsive therapy (ECT) in the young in order to determine whether they would be willing and able to provide an opinion if consulted about children or adolescents in whom ECT is proposed. METHOD: A 28-item questionnaire was posted to all members of the Faculty of Child and Adolescent Psychiatry living in Australia or New Zealand. RESULTS: Eighty-three percent (n = 206) answered the questionnaire. Forty percent rated their knowledge about ECT in the young as nil or negligible. Having had patients treated with ECT was the best predictor of possessing some knowledge. Thirty-nine percent believed that ECT was unsafe in children compared to 17% for adolescents and 3% for adults. Almost all (92%) respondents believed child psychiatrists should be consulted in all cases of persons under 19 in whom ECT was recommended. The vast majority believed the Faculty or College should have guidelines relating to ECT use in this group and that it would be useful to have a national register of young persons treated with ECT. CONCLUSIONS: Child and adolescent psychiatrists wish to be involved in the process of ECT treatment in young people. At the same time, there are gaps in their knowledge. This will need to be remedied, particularly if formal guidelines advocating their involvement are introduced.

Avaliaçäo da semente de maracujá (Passiflora edulis) em ensaio de digestibilidade aparente em ovinos. I. Consumo de matéria seca e coeficientes de digestibilidade da matéria seca, fibra detergente neutro, fibra detergente ácido, hemicelulose e celulose / Nutritional evaluation of passion fruit (Passiflora edulis) in apparent digestibility trial. I. Intake and digestibility coefficient of dry matter and fibrous components

Cinco carneiros adultos foram submetidos a um experimento para avaliar o valor nutritivo da semente de maracujá (Passiflora edulis) e o nível ótimo de sua inclusäo em raçöes para ruminantes. Estudou-se a digestibilidade aparente da semente de maracujá e do feno de capim Gordura, segundo um delineamento em blocos casualizados. Os tratamentos experimentais foram constituídos por cinco dietas 1 (feno); 2 (feno + 8 por cento de semente); 3 (feno + 16 por cento de semente); 4 (feno + 24 por cento de semente) e 5 (feno + 32 por cento de semente). O maior consumo voluntário de matéria seca (53,5g/kg elevado a 0,75) ocorreu com a inclusäo de 8,8 por cento de semente de maracujá na dieta, mas näo se traduziu em maior consumo de matéria seca digestível (23,6g/kg elevado a 0,75). Houve declínio na digestibilidade da matéria seca (46,9; 44,2; 39,3; 40,7 e 39,0 por cento e dos componentes fibrosos da dieta FDN = 53,0; 48,0; 43,0; 44,1 e 35,2 por cento; FDA = 51,4; 47,1; 39,2; 42,2 e 33,6 por cento para os tratamentos 1, 2, 3, 4 e 5, respectivamente) a partir da adiçäo inicial de semente de maracujá na dieta

Avaliaçäo da semente de maracujá (Passiflora edulis) em ensaio de digestibilidade aparente em ovinos. II. Consumo e coeficiente de digestibilidade da energia bruta, extrato etéreo e proteína bruta e balanço de nitrogênio / Nutritional evaluation of passion fruit (Passiflora edulis) in apparent digestibility trial. II. Intake and digestibility coefficient of crude energy, ether extract and crude protein and nitrogen balance

Cinco carneiros adultos foram submetidos a um experimento para avaliar o valor nutritivo da semente de maracujá (Passiflora edulis) e o nível ótimo de sua inclusäo em raçöes para ruminantes. Estudou-se a digestibilidade aparente da semente de maracujá e do feno de capim Gordura, segundo um delineamento em blocos casualizados. Os tratamentos experimentais foram constituídos por cinco dietas: 1 (feno); 2 (feno + 8 por cento de semente); 3 (feno + 16 por cento de semente); 4 (feno + 24 por cento de semente) e 5 (feno + 32 por cento de semente). O maior consumo voluntário de matéria seca (53,5g/kg elevado a 0,75) ocorreu com inclusäo de 8,8 por cento de semente de maracujá na dieta, mas näo se traduziu em maior consumo de energia metabolizável (89,0kcal/kg elevado a 0,75). O nível de semente na dieta näo modificou a digestibilidade da proteína bruta que foi alta (70 por cento), nem o balanço de nitrogênio que foi positivo em todos os tratamentos (6,77g/kg elevado a 0,75). Os coeficientes de digestibilidade do extrato etéreo aumentaram (40,9; 63,7; 59,0; 70,9 e 84,9 por cento para os tratamentos 1, 2, 3, 4 e 5, respectivamente à medida que aumentou a proporçäo de semente de maracujá na dieta

Pharmacological characterization of LY335979: a potent cyclopropyldibenzosuberane modulator of P-glycoprotein.

The above data indicate that LY335979 displays the following characteristics of an 'ideal modulator' of Pgp-mediated multidrug resistance: high affinity binding to Pgp, high potency for in vitro reversal of drug resistance, high therapeutic index (activity was demonstrated at doses ranging from 1-30 mg/kg) observed in in vivo antitumor efficacy experiments, and a lack of pharmacokinetic interactions that alter the plasma concentration of coadministered oncolytic agents. These desirable features strongly suggest that LY335979 is an exciting new clinical agent to test the hypothesis that inhibition of P-glycoprotein activity will result in reversal of multidrug resistance in human tumors.

Human HLA-B27 gene enhances susceptibility of rats to oral infection by Listeria monocytogenes.

Germfree rats transgenic for the human genes HLA-B27 and beta 2-microglobulin were colonized with hemolysin-positive (Hly+) or hemolysin-negative (Hly-) strains of Listeria monocytogenes. HLA-B27 rats were very susceptible to infection with Hly+ L monocytogenes none survived beyond 6 days. Conversely, nontransgenic control rats survived alimentary tract colonization with the Hly+ strain, and both transgenic and nontransgenic rats survived colonization with the Hly- strain of L monocytogenes. After colonization with Hly+ L monocytogenes, both transgenic and nontransgenic rats developed severe bowel inflammation which consisted histologically of microab scesses, granulomatous lesions, and ulcers; however, whereas the transgenic rats died within 6 days, only very mild intestinal lesions were seen in nontransgenic rats 10 to 42 days after colonization. Liver and splenic lesions were small and transient in nontransgenic rats. Transgenic and nontransgenic control rats infected with Hly- Listeria developed mild transient diarrhea but showed no histological changes in the intestine. This study thus documents an association between a particular bacterial product (hemolysin produced by L monocytogenes) and the induction of severe inflammatory disease and death in rats expressing HLA-B27 and beta 2-microglobulin.