Correlates of 1-Year Change in Quality of Life in Patients with Urologic Chronic Pelvic Pain Syndrome: Findings from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network.

PURPOSE: We evaluated and identified baseline factors associated with change in health related quality of life among patients with interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome. MATERIALS AND METHODS: A total of 191 men and 233 women with interstitial cystitis/bladder pain syndrome or chronic prostatitis/chronic pelvic pain syndrome (collectively referred to as urologic chronic pelvic pain syndrome) were followed for 12 months with bimonthly completion of the Short Form 12 to assess general mental and physical health related quality of life, and with biweekly assessment of condition specific health related quality of life using the Genitourinary Pain Index. A functional clustering algorithm was used to classify participants as improved, stable or worsened for each health related quality of life measure. Ordinal logistic regression was used to determine baseline factors associated with change. RESULTS: Physical health related quality of life improved in 22% of the participants, mental health related quality of life improved in 25% and condition specific health related quality of life improved in 47%. Better baseline physical health related quality of life, older age and the presence of nonurological symptoms were associated with lower likelihood of improvement in physical health related quality of life. Better baseline mental health related quality of life, female sex, and greater baseline depression and stress were associated with a lower likelihood of improvement in mental health related quality of life. Better baseline condition specific health related quality of life and more severe baseline urologic chronic pelvic pain syndrome pain symptoms were associated with a lower likelihood of improvement in condition specific health related quality of life. CONCLUSIONS: While several nonurologic chronic pelvic pain syndrome factors influenced the trajectory of general health related quality of life over time, only condition specific baseline health related quality of life and urologic chronic pelvic pain syndrome symptoms were associated with urologic chronic pelvic pain syndrome specific health related quality of life change. Significant differences in how urologic chronic pelvic pain syndrome impacts various aspects of health related quality of life suggest a multidisciplinary approach to assessment and treatment of these patients.

Spontaneous Lung Lesions in Aging Laboratory Rabbits ( Oryctolagus cuniculus).

Spontaneous age-related lesions of laboratory rabbits are not well documented in the contemporary scientific literature. A retrospective study of diagnostic necropsies of 36 rabbits >2 years of age found a number of common lung lesions. Fibromuscular intimal hyperplasia affected medium and to a lesser extent large pulmonary arteries and was present to a variable extent in all 36 rabbits >2 years of age. The lesions were characterized by fragmentation and/or reduplication of the internal elastic lamina (IEL), proliferation of smoothelin+/alpha-smooth muscle actin (α-SMA)+/vimentin- smooth muscle cells and fewer smoothelin-/α-SMA+/vimentin+ myofibroblasts, and intimal deposition of collagen without thrombosis, embolism, or evidence of pulmonary hypertension. Pulmonary emphysema, present in 30/36 rabbits, was characterized by the loss of alveolar septa; most affected rabbits did not have clinical signs of respiratory disease. In 8/13 rabbits of the inbred EIII/JC audiogenic strain, we identified a unique syndrome of granulomatous pneumonia containing hyaline brown to gray, globular to ring-like acellular material that was Alcian blue and periodic acid-Schiff positive. The material was immunoreactive for surfactant protein-A and had the ultrastructural appearance of multilamellar vesicles, suggesting a genetic defect in surfactant metabolism. Additionally, we found small benign primary lung tumors (fibropapillomas, 5 rabbits) not previously described. Other findings included heterotopic bone (5 rabbits), subacute to chronic suppurative bronchopneumonia, pyogranulomatous pneumonia with plant material, and pulmonary artifacts from barbiturate euthanasia solution.

Reinitiated expression of EJras transgene in targeted epidermal cells of transgenic rabbits by cottontail rabbit papillomavirus infection.

Transgenic rabbits carrying the EJras oncogene have been established in our laboratory (Am. J. Pathol. 155 (1999) 315). The expression of the ras gene is targeted to the epidermal keratinocytes using the upstream regulatory region (URR) of the cottontail rabbit papillomavirus (CRPV). All of the transgenic rabbits develop keratoacanthomas at multiple sites in the skin at 2-3 days after birth, and the tumors spontaneously regress in 1.5-2 months. With regression of the keratoacanthomas, the rabbits appear normal and EJras expression is undetectable in their skin. To determine if CRPV infection would reinitiate the expression of the EJras transgene and make the rabbits more sensitive to tumorigenesis, the rabbits were infected with CRPV at 2 months of age when the keratoacanthomas had regressed. This study shows that CRPV infection of the transgenic rabbit skin could shorten the latency required for CRPV papilloma initiation, and significantly increase the tumor growth and persistence rate compared with non-transgenic rabbits. Furthermore, EJras expression became detectable in the CRPV induced papillomas in transgenic rabbits, but not in the papillomas of non-transgenic rabbits. These results indicate that CRPV infection is able to reinitiate the expression of the CRPV URR controlled EJras oncogene carried by the transgenic rabbits and that the expression of EJras can enhance the tumorigenesis of CRPV infection.

Endocarditis and meningitis caused by Streptococcus suis after cardiac surgery in a sheep.

A female Dorset-cross sheep developed labored respirations and was anorexic, weak, ataxic and febrile (42.0 degrees C) 15 days after implantation of a cardiac device. Clinical pathologic evaluation identified a mild leukocytosis (11,800 cells/microl), neutrophilia (8,969 cells/microl), and hypokalemia (2.9 mmol/L). Despite intensive therapy, the animal was euthanized 7 days later. Necropsy of the sheep revealed meningitis and vegetative endocarditis associated with the cardiac device. Blood cultures collected antemortem and tissue cultures collected at necropsy yielded Streptococcus suis. Histopathology confirmed the diagnosis of bacterial valvular endocarditis and meningoencephalitis. A variety of environmental and host factors are proposed as contributing to the infection, and the zoonotic potential of S. suis is discussed.

Potassium-channel opener cardioplegia is superior to St. Thomas' solution in the intact animal.

BACKGROUND: In isolated hearts, the potassium-channel opener pinacidil is an effective cardioplegic agent. This study tested the hypothesis that pinacidil is superior to St. Thomas' solution in the more clinically relevant intact animal. METHODS: Sixteen pigs were placed on full cardiopulmonary bypass. Hearts underwent 2 hours of global ischemia (10 degrees to 15 degrees C). Either St. Thomas' or 100 micromol/L pinacidil was administered every 20 minutes (10 mL/kg). Preischemic and postreperfusion slopes of the preload-recruitable stroke work relationship were determined. Changes in myocardial adenine nucleotide levels and cellular ultrastructure were analyzed. RESULTS: Pinacidil cardioplegia resulted in an insignificant change in the slope of the preload-recruitable stroke work relationship (40.6+/-2.1 mm Hg/mm before ischemia and 36.5+/-3.7 mm Hg/mm after ischemia; p = 0.466). In contrast, St. Thomas' solution resulted in a significant decrease in the slope after reperfusion (34.3+/-5.5 mm Hg/mm and 13.5+/-2.3 mm Hg/mm; p = 0.003). Adenine nucleotide levels, myocardial tissue water, and ultrastructural changes were similar between groups. CONCLUSIONS: Pinacidil ameliorated myocardial stunning associated with traditional hyperkalemic cardioplegia without causing significant differences in cellular metabolism.

Development of keratoacanthomas and squamous cell carcinomas in transgenic rabbits with targeted expression of EJras oncogene in epidermis.

Activated ras genes have been frequently identified in both benign and malignant human tumors, including keratoacanthoma and squamous cell carcinoma. In this study, we developed two lines of transgenic rabbits in which the expression of EJras has been specifically targeted to the rabbit epidermal keratinocytes, using the upstream regulatory region of cottontail rabbit papillomavirus. All of the F1 transgenic progenies developed multiple keratoacanthomas at about 3 days after birth. The rabbits developed an average of 20 tumors, which usually reached the size of approximately 1 cm in diameter and then spontaneously regressed in about 2 months, similar to keratoacanthoma regression in humans. In addition, up to 18% of the rabbits then developed squamous cell carcinoma at about 5 months of age. The expression of EJras was detectable in all of the keratoacanthomas and squamous cell carcinomas. These results strongly support the involvement of the ras oncogene in both the initiation and regression of keratoacanthoma, and in the development of squamous cell carcinomas. These novel transgenic rabbits, with their consistent tumorigenic phenotype at an early age, high similarity to the human lesions, and easy accessibility for examination, manipulation, biopsy, and treatment, should provide a unique model system for studying ras activation-related tumor initiation, regression, and progression, and for evaluating antitumor therapies.

Human melanoma metastasis is inhibited following ex vivo treatment with an antisense oligonucleotide to protein kinase C-alpha.

To determine whether alteration of PKC alpha expression would affect the metastatic potential of human melanoma cells, replicate cultures of C8161 cells were treated in vitro with a phosphorothioate antisense oligodeoxynucleotide (ODN) that specifically inhibits PKC alpha expression (ISIS-3521). Control C8161 cultures were treated with a scrambled sequence ODN, cationic liposomes or were left untreated. Northern blots demonstrated 70% inhibition of PKC alpha mRNA in ISIS-3521-treated cells compared to controls. Metastasis was suppressed by 75% when ISIS-3521-treated cells were injected intravenously into athymic mice. These results show that PKC alpha expression is important in the regulation of human melanoma metastasis.

Rabbit genital tissue is susceptible to infection by rabbit oral papillomavirus: an animal model for a genital tissue-targeting papillomavirus.

Rabbit oral papillomavirus (ROPV) is a mucosatropic papillomavirus which naturally infects oral mucosal sites of domestic rabbits. In this study, we tested the hypothesis that rabbit genital mucosa is also susceptible to ROPV infection by using the athymic mouse xenograft system and adult immunocompetent rabbits. Subrenal xenografts of ROPV-infected rabbit vulvar and penile sheath tissues were strongly positive for ROPV infection by histologic, in situ hybridization, and Southern analyses. Direct inoculation of adult rabbit penises with infectious ROPV produced small raised lesions of approximately 1 by 1 by 1 mm that were ROPV positive by both in situ hybridization and Southern analyses and were also viral capsid antigen positive by immunohistological staining. Infection of rabbit genital tissues with ROPV may be a useful animal model for the study of genital tissue-targeting papillomaviruses.

In vivo accuracy of two radiographic systems in the detection of Björk-Shiley convexo-concave heart valve outlet strut single leg separations.

OBJECTIVE: Modified cineradiographic systems have been used clinically to detect partially broken outlet struts in normally functioning Björk-Shiley convexo-concave heart valves. Almost all such valves were explanted, presuming that full failure would likely follow. Inasmuch as the clinical setting only rarely permits examination of normally rated valves, the accuracy of radiographic detection cannot be clinically defined. This study uses the clinical radiographic technique in sheep implanted with known-status convexo-concave valves, comparing its accuracy and that of a newly developed, geometric image magnification radiography system. METHODS: Twenty-one sheep with mitral convexo-concave valves were studied on both systems. Five were used for extensive training. When operators were expert with both systems, images of four intact valves and 12 valves with outlet strut single leg separations, along with a seventeenth single leg separation valve used for calibration, were integrated into 112 image sets organized into a balanced incomplete block design for evaluation by eight trained, blinded reviewers. RESULTS: Cineradiography sensitivity was 24% versus 31% for direct image magnification. The odds ratio for detection of single leg separation by direct image magnification versus cineradiography was 2.0 (95% confidence interval, 0.76 to 5.9; p = 0.13). Cineradiography specificity was 93% versus 90% for direct image magnification. Sensitivity and specificity varied markedly by reviewer, with sensitivity ranging from 8% to 55% and specificity from 51% to 100% for the combined technologies. CONCLUSIONS: The data support the need for more intensive training for convexo-concave valve imaging and further investigation of unconventional radiographic technologies. Clinical cineradiography of convexo-concave valves may detect as little as 25% of valves having a single leg separation, underestimating the prevalence of single leg separations and thereby implying more rapid progression to full fracture than is actually the case.

Fatal trematodiasis in research turtles.

During a 5-year period, 16 freshwater turtles (Trachemys scripta elegans and Chrysemys picta) that were purchased for research purposes died spontaneously. Clinical signs of disease included lethargy, constant swimming, swimming sideways, hemiplegia, and ulcerative lesions on the carapace. At necropsy, subcutaneous edema, hepatic necrosis, pancreatic necrosis, splenic necrosis, and intestinal parasites were identified. Histologically, trematode eggs were seen within the liver, brain, spleen, kidney, myocardium, lung, pancreas, testes, and bladder, and were associated with granulomatous reactions. The size and distribution of the eggs were consistent with Spirorchis sp. infection, although adults could not be found to confirm the species. Spirorchid flukes are 1 to 2 mm long and inhabit the heart and blood vessels where they produce eggs. Spirorchis parvus are capable of invading various tissues, including pancreas and the central nervous system. The pathogenicity of the flukes seems to be related to widespread deposition of the eggs, which may block small blood vessels within the intestines, causing necrosis and bacteremia. Antemortem diagnosis is made by direct examination of fecal smears for eggs. Postmortem diagnosis is accomplished by examination of tissues for adult parasites and microgranulomas associated with the fluke eggs. The parasite requires a snail intermediate host to complete its life cycle. Intramuscular or oral administration of praziquantel is reported to be an effective treatment.

A simian virus 40 large T-antigen segment containing amino acids 1 to 127 and expressed under the control of the rat elastase-1 promoter produces pancreatic acinar carcinomas in transgenic mice.

The simian virus 40 large T antigen induces tumors in a wide variety of tissues in transgenic mice, the precise tissues depending on the tissue specificity of the upstream region controlling T-antigen expression. Expression of mutant T antigens that contain a subset of the protein's activities restricts the spectrum of tumors induced. Others showed previously that expression of a mutant large T antigen containing the N-terminal 121 amino acids (T1-121) under control of the lymphotropic papovavirus promoter resulted in slow-growing choroid plexus tumors, whereas full-length T antigen under the same promoter induced rapidly growing CPR tumors, T-cell lymphomas, and B-cell lymphomas. In those instances, the alteration in tumor induction or progression correlated with inability of the mutant large T antigen to bind the tumor suppressor p53. In the study reported here, we investigated the capacity of an N-terminal T antigen segment (T1-127) expressed in conjunction with small t antigen under control of the rat elastase-1 (E1) promoter to induce pancreatic tumors. The results show that pancreases of transgenic mice expressing T1-127 and small t antigen display acinar cell dysplasia at birth that progresses to neoplasia. The average age to death in these mice is within the range reported for transgenic mice expressing full-length T antigen under control of the E1 promoter. These results indicate that sequestering p53 by binding is not required for the development of rapidly growing acinar cell carcinomas. In addition, we provide evidence that small t antigen is unlikely to be required. Finally, we show that the p53 protein in acinar cell carcinomas is wild type in conformation.

Optic neuropathy following simulation of orbital hemorrhage in the nonhuman primate.

The goal of the study was to determine, using a nonhuman primate (NHP) model, the minimum duration of elevated intraocular pressure (IOP) (induced by an inflated catheter) necessary to produce significant visual system deficits. In Old World monkeys (Macaca mulatta), a catheter was placed retrobulbarly in one orbit and inflated with saline for either 180 min (10 monkeys) or 240 min (six monkeys subjects). Baseline color fundus photographs, monochromatic photography, fluorescein angiography, and IOP measurements were performed preoperatively and at either 2, 4, or 6 weeks postoperatively on both eyes of each monkey prior to killing and histological analysis. Optic neuropathy was demonstrated in eight of these NHPs. In the two most severe cases (240 min inflation condition), complete nerve fiber atrophy with central retinal artery occlusion was observed. Sector nerve fiber atrophy, extending from the temporal disc to beyond the macula, was noted in the other six monkeys, five of which were in the 180 min inflation condition. Thus, optic neuropathy, sufficient to produce visual loss, was noted following increased IOP (> or = 50 mm Hg) for 180 min or 240 min. These data emphasize the need for timely intervention to mitigate the potential detrimental effects of retrobulbar hemorrhage when it occurs in humans.

Thymus-leukemia antigen interacts with T cells and self-peptides.

The functional role of the class Ib thymus-leukemia (TL) Ag expressed within the thymic cortex and intestinal mucosa of the mouse remains unknown. In an approach to elucidate the potential functionality of TL, we developed transgenic mice that ectopically express the H-2T18d gene product on essentially all nucleated cells through the control of a heterologous H-2Kb gene promoter. Transgenic mice demonstrated an increase in the number of CD4+ lymphocytes within the thymus and lymph nodes; these cells displayed an altered T cell receptor repertoire possibly suggesting a role for the ectopically expressed TL protein. The TL protein additionally displayed the characteristics of a bona fide transplantation Ag, because skin grafts from transgenic animals onto MHC- and minor histocompatibility Ag-matched nontransgenic recipient mice resulted in a rapid and vigorous immunologic rejection of the allograft. In MLR studies, transgenic stimulator cells induced the proliferation of responders to a level intermediate between genetically identical and H-2-disparate responder-stimulator combinations. The TL protein was also capable of stimulating cytotoxic T lymphocytes, thereby resulting in specific lysis of TL+ target cells. Further data demonstrated that the TL protein assembles with peptides that are modified at the amino terminus, and that TL retains these molecules at the cell surface. Together, these data suggest that H-2T18d is capable of interacting with T cells via a bound peptide. These data further support the possibility that TL may subserve a specialized function within the immunologic system.

Comparison of the effects of five adjuvants on the antibody response to influenza virus antigen in guinea pigs.

Five adjuvants were tested for their effect on the immune response in guinea pigs to the hemagglutinin antigen of influenza virus strain B/Panama. Vaccines containing 924 micrograms of hemagglutinin antigen/ml were prepared at high and low doses of Freund's complete and incomplete adjuvants, Syntex adjuvant, RIBI's adjuvant, TiterMax adjuvant, and aluminum phosphate adjuvant. Responses to these vaccines were compared with those to a control vaccine containing influenza virus B/Panama hemagglutinin antigen and saline. On day 28, vaccines containing the following adjuvant doses had significantly higher titers than the titer for the control: Freund adjuvants at high and low doses, RIBI at high dose, TiterMax at high and low doses, and aluminum phosphate at high dose. On day 42, vaccines containing the following adjuvant doses had significantly higher titers than that for the control: Freund adjuvants at high and low doses, RIBI at high dose, TiterMax at high dose, and aluminum phosphate at high dose. Freund adjuvants at high and low doses, RIBI adjuvant at high dose, and aluminum phosphate at high dose caused significantly greater swelling at the inoculation site than did the control vaccine. TiterMax adjuvant at high and low doses, and aluminum phosphate at low dose caused minor swelling at the inoculation site, but it was not significantly different from the swelling caused by the control vaccine. Syntex adjuvant at high and low doses, RIBI at low dose, and control (saline/antigen) at high and low doses caused no swelling after inoculation. Overall, the high dose of adjuvants caused greater tissue swelling than did the low dose of adjuvants.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of anesthesia induced by ketamine-fentanyl combination and maintained by propofol or etomidate in New Zealand white rabbits.

Ketamine-fentanyl-propofol and ketamine-fentanyl-etomidate combinations were administered intravenously to four groups of rabbits. Each group received ketamine (30 mg/kg of body weight) and fentanyl (0.025 mg/kg) for anesthesia induction. Either propofol or etomidate was administered by an infusion pump to maintain anesthesia. The rabbit's responses to noxious stimuli were determined before anesthesia was induced and at 10-min intervals thereafter until the rabbit recovered. The effects of the anesthetic combinations on the cardiopulmonary system were measured by monitoring respiratory and heart rates, blood pressure, and arterial blood gas tensions. Etomidate infused at the rate of 0.2 or 0.1 mg/kg/min could maintain surgical anesthesia with fewer effects on the cardiopulmonary system for 40 and 30 min respectively. However, the high mortality and side effects such as hemolysis in these two groups preclude the clinical use of etomidate for anesthesia maintenance. Propofol administered intravenously at rates of 0.8 and 0.4 mg/kg/min could maintain surgical anesthesia for 40 and 30 min respectively. However, relatively severe hypotension, hypercapnia, and respiratory acidosis were associated with this drug. Recovery from the propofol infusion was very rapid. Ketamine-fentanyl-etomidate combination is not recommended for clinical anesthesia in rabbits. Ketamine-fentanyl-propofol combination at a dosage of 30-0.025-0.4 mg/kg/min can be safely used for short-term surgery.

Evaluation of a second-generation tantalum biliary stent in a canine model.

PURPOSE: To evaluate the safety and feasibility of use of a balloon-expandable tantalum (Tantaflex) stent in the biliary tree in a canine model. MATERIALS AND METHODS: In this prospective, randomized trial, 10 tantalum stents were placed in eight dogs (two telescoping stents in two dogs), and six Wallstents were placed in six dogs as controls. Stents were deployed into the common bile duct via a cholecystostomy at laparotomy under fluoroscopic and cholangiographic guidance. Two dogs from each stent group were killed at 4, 12, and 26 weeks; the two dogs with telescoping stents were killed at 12 weeks. Premortem patency was confirmed cholangiographically. Postmortem stent explants were inspected grossly, and tissues were examined histologically. Bacteriologic evaluation of bile was performed. RESULTS: All 14 dogs survived until they were scheduled to be killed without clinical complication or evidence of jaundice. Patency was demonstrated at terminal cholangiography in 12 of 14 dogs and at explantation in 13 of 14 dogs. One Wallstent placed across the ampulla in a dog killed at 26 weeks became obstructed. In another dog, the presence of a cholelith in the cystic duct precluded filling of the common bile duct from the cholecystotomy. Only mild inflammatory changes were present in the bile ducts. CONCLUSION: The tantalum stent can be used safely and effectively in the common bile duct in normal dogs. Performance of a clinical trial in humans is supported finding of this study.

An animal model of visual loss from orbital hemorrhage.

Intraorbital hemorrhage may arise spontaneously or following orbital or periorbital surgery or trauma and may be associated with visual loss or impairment. This project was designed to evaluate the ophthalmic effects and underlying mechanism(s) associated with visual impairment secondary to intraorbital hemorrhage. An experimental surgical procedure was developed to simulate intraorbital hemorrhage. A reversible state of unilateral visual loss secondary to acutely increased intraorbital volume was induced and maintained under general anesthesia for either 90, 120, or 180 min duration in nine adult nonhuman primates (NHPs) (Macaca arctoides). Color funduscopic photography, i.v. fluorescein angiography, electrophysiological testing, and tonometry were obtained during baseline, experimental, and follow-up procedures. The globes and optic nerves were obtained for histopathologic evaluation. One of three animals in the 180 min experimental group exhibited clinical and histopathological changes of optic neuropathy 6 weeks after the experimental procedure. Optic neuropathy is one of several proposed etiologies for producing visual loss secondary to intraorbital hemorrhage. This study offers a reliable, safe, and reversible technique to study the effects of acutely increased intraorbital volume in nonhuman primates. The animal model described may be useful for evaluating mechanism(s) involved with visual impairment in other acquired optic neuropathies.

Cystitis, urolithiasis and cystic calculi in ageing guineapigs.

Nineteen cases of cystitis were diagnosed at necropsy and/or by histology in a group of 170 (96 females, 74 males) guineapigs (11.2%). Seventeen of the 19 cases (89.4%) were females. The mean age of guineapigs with cystitis was 34.7 months, which was higher than the mean age of 24 months of the 170 members of the study group. In addition, 6 cases of urolithiasis and cystic calculi in 5 females and one male were also found in the 170 guineapigs (3.5%). The mean age of the 6 cases was 30 months, which was also higher than the mean age of the 170 animals. The study suggests that aged female guineapigs were much more predisposed to cystitis and urolithiasis or cystic calculi than male and young guineapigs. The cause may be related to infection with Escherichia coli and Staphylococcus sp, cystic calculi, diabetes mellitus and female guineapig urogenital anatomy and function.

Exacerbation of doxorubicin cardiotoxicity by digoxin administration in an experimental rabbit model.

The relationship between digoxin administration and the development of doxorubicin cardiomyopathy was evaluated in a chronic experimental rabbit model. We graded the myocardial pathology by conventional light microscopic histologic techniques. Additionally, myocardial fibrosis was quantified by hydroxyproline determinations and myocardial cellular damage by technetium-99m pyrophosphate uptake. Twenty-four rabbits were studied: 6 control, 6 doxorubicin-treated, and 12 digoxin-doxorubicin-treated. Mortality in the digoxin-doxorubicin group was 50%. All other rabbits lived throughout the entire experiment. The severest grades of histologic lesions were seen only in the digoxin-doxorubicin group. Myocardial hydroxyproline content was greater (p less than 0.05) in the digoxin-doxorubicin group than in the doxorubicin or control groups. Myocardial technetium-99m pyrophosphate content was also significantly greater (p less than 0.05) in the digoxin-doxorubicin group than in controls. In conclusion, the pretreatment and continued administration of digoxin, together with doxorubicin, increased the severity of myocardial damage and reduced longevity in this experimental model of doxorubicin cardiotoxicity.

Spontaneous reproductive tract leiomyomas in aged guinea-pigs.

Seven of 83 female guinea-pigs were found to have reproductive tract leiomyomas at necropsy. Sixty-three of these guinea-pigs also had cystic rete ovarii. Eleven separate leiomyomas were identified, the most common site of formation being the uterine body or horn. The tumours contained histological evidence of smooth muscle, abundant fibrous connective tissue and occasional foci of fibrocartilage and bone. Mitotic figures were identified in only one tumour. The mean age of guinea-pigs with leiomyomas was 47.6 months, and the mean age of the study population was 33.1 months. Two other reproductive tract tumours identified in the 83 guinea-pigs were an ovarian teratoma and a cavernous haemangioma. These data indicate that leiomyomas are the most common reproductive tract tumour in this colony of aged female guinea-pigs and that they are frequently seen in conjunction with cystic rete ovarii.