Morphology and muscle gene expression in GIFT and Supreme Nile tilapia varieties reared in two cultivation systems.

Tissue growth in most fishes occurs by muscular hyperplasia and hypertrophy, which are influenced by different regulatory factors, such as myostatin. The current study evaluated the influence of cultivation in hapas and earthen ponds on the diameter of white muscle fibers and on the myostatin (MSTN-1) gene in GIFT and Supreme varieties of tilapia. Fish of both varieties were reared for 204 days and then divided into four developmental stages. White muscle samples, corresponding to 100 fibers per slide, were collected from the middle region of fish of each variety and cultivation system, and were measured and divided into two classes representing hyperplasia and hypertrophy. Samples were subjected to real-time PCR to analyze gene expression. Hyperplasia decreased during the developing stages, coupled with increased hypertrophy. There was a higher rate of hypertrophy in fish raised in earthen ponds when compared to those raised in hapas, during juvenile and developing phases, and greater hypertrophic growth was observed in GIFT specimens when compared to Supreme specimens in earthen ponds. Since increased MSTN-1 gene expression was observed in GIFT specimens during the developing phase in pond cultivations, and in Supreme tilapia in hapas, MSTN-1 expression is related to greater hypertrophy. These results demonstrate the capacity for increased muscle growth in earthen pond cultivation in which the GIFT variety developed best. How the environment affects the growth of different tilapia varieties may be employed to optimize culture management and genetic improvement programs. Further investigations should aim to describe mechanisms affecting muscle growth and development.

High fat diet-induced modifications in membrane lipid and mitochondrial-membrane protein signatures precede the development of hepatic insulin resistance in mice.

OBJECTIVE: Excess lipid intake has been implicated in the pathophysiology of hepatosteatosis and hepatic insulin resistance. Lipids constitute approximately 50% of the cell membrane mass, define membrane properties, and create microenvironments for membrane-proteins. In this study we aimed to resolve temporal alterations in membrane metabolite and protein signatures during high-fat diet (HF)-mediated development of hepatic insulin resistance. METHODS: We induced hepatosteatosis by feeding C3HeB/FeJ male mice an HF enriched with long-chain polyunsaturated C18:2n6 fatty acids for 7, 14, or 21 days. Longitudinal changes in hepatic insulin sensitivity were assessed via the euglycemic-hyperinsulinemic clamp, in membrane lipids via t-metabolomics- and membrane proteins via quantitative proteomics-analyses, and in hepatocyte morphology via electron microscopy. Data were compared to those of age- and litter-matched controls maintained on a low-fat diet. RESULTS: Excess long-chain polyunsaturated C18:2n6 intake for 7 days did not compromise hepatic insulin sensitivity, however, induced hepatosteatosis and modified major membrane lipid constituent signatures in liver, e.g. increased total unsaturated, long-chain fatty acid-containing acyl-carnitine or membrane-associated diacylglycerol moieties and decreased total short-chain acyl-carnitines, glycerophosphocholines, lysophosphatidylcholines, or sphingolipids. Hepatic insulin sensitivity tended to decrease within 14 days HF-exposure. Overt hepatic insulin resistance developed until day 21 of HF-intervention and was accompanied by morphological mitochondrial abnormalities and indications for oxidative stress in liver. HF-feeding progressively decreased the abundance of protein-components of all mitochondrial respiratory chain complexes, inner and outer mitochondrial membrane substrate transporters independent from the hepatocellular mitochondrial volume in liver. CONCLUSIONS: We assume HF-induced modifications in membrane lipid- and protein-signatures prior to and during changes in hepatic insulin action in liver alter membrane properties - in particular those of mitochondria which are highly abundant in hepatocytes. In turn, a progressive decrease in the abundance of mitochondrial membrane proteins throughout HF-exposure likely impacts on mitochondrial energy metabolism, substrate exchange across mitochondrial membranes, contributes to oxidative stress, mitochondrial damage, and the development of insulin resistance in liver.

Practice of dilatation after surgical correction in anorectal malformations.

BACKGROUND: In order to prevent stricture of the neoanus after surgical correction, regular dilatation is recommended. There is a lack of knowledge about the performance of anal dilatation and the occurrence of pain. The aim of our investigation was to describe the practice of dilatation and to identify possible risk factors for painful procedures. METHODS: Congenital Uro-Rectal Malformations Network is a German interdisciplinary multicenter research network. With standard questionnaires, physicians interviewed 243 patients and/or their parents at home, additional 103 patients born since 2009 were assessed through their treating physicians. RESULTS: In total, 88 % of the patients received dilatations. Treatment lasted for 7 months in median (range 1-156 months), until the age of 13 months (range 1-171 months). In 69 % painful dilatation was reported; without a significant differences in age or gender. In 32 % bleeding was reported. In 30 % at least one dilatation was performed under general anesthesia. In 11 % some kind of analgesia was used. Type of fistula, dilatations lasting longer than 10 months and Hegar size above 15 were relevant factors for experience of pain. There were about 16 % postoperative strictures of the neoanus, without reported differences in dilatation procedures; but there was a relation to type of malformation. CONCLUSION: Considering the high number of painful treatments, predictors for painful dilatations should be further clarified through standardized documentation and prospective evaluation in order to improve follow-up.

Biliary atresia: lessons learned from the voluntary German registry.

INTRODUCTION: Aim of the study was to carry out a 5-year survey of German patients with biliary atresia (BA) and to launch a discussion regarding the feasibility of voluntary registries in unregulated healthcare systems. METHODS: A retrospective analysis of German BA patients born between 2001 and 2005, based on data collected from the voluntary European Biliary Atresia Registry (EBAR), was carried out and supplemented by data from all BA patients who underwent liver transplantation at the only 4 pediatric transplantation centers (pLTx) in Germany which are so far not registered at EBAR. Survival rates were calculated using Kaplan-Meier analysis and compared by Cox regression to determine the predictive value of age at surgery and the influence of the center size (fewer or more than 5 patients/study period) on overall survival and survival with native liver. RESULTS: A critical review of the 148 German EBAR charts revealed that 11 patients (7.4%) had no biliary atresia. The remaining 137 patients from EBAR together with 46 BA patients who underwent LTx without prior registration at EBAR were evaluated with a median follow-up of 39 months (range: 25-85 months). 29 hospitals performed a total of 159 Kasai procedures, but only 7 centers treated 5 or more patients (116 patients, range: 5-68), and 22 hospitals performed less than 5 KP (43 patients, range: 1-4). Primary LTx was performed in 21 patients (11.5%) and 3 patients died without surgical intervention. 16 patients were lost to follow-up (8.7%). Overall survival after 2 years was 83.3% (139 patients), including 105 patients (63%) who had undergone LTx and 34 patients (20.3%) with native liver. 28 patients died (16.7%), 8 after LTx (5.8%). The experience of the center was the only factor with a significant predictive value for jaundice-free survival with native liver (p=0.001). CONCLUSION: 25% of all German BA patients were not registered at EBAR, and 29 clinics were involved in the surgical management of BA patients. Therefore a new approach consisting of an internet-based decentralized registry for rare neonatal liver diseases is outlined which could improve the future management of patients with BA. The centralization of such patients at experienced centers with higher caseloads is necessary in Germany and would improve the outcome of patients with biliary atresia.

Preconceptional oral vaccination prevents experimental biliary atresia in newborn mice.

INTRODUCTION: Biliary atresia (BA) in humans resembles BA induced in Balb/c-mice by Rhesus Rotavirus (RRV). In mice, susceptibility to BA is ascribed to the lack of maternally derived immune protection. This study investigated whether vaccination of dams against RRV protected their offspring from developing BA. MATERIALS AND METHODS: Before mating, female mice were vaccinated orally with RotaTeq or Rotarix. Pups (n=243) from both test groups and a control group were intraperitoneally infected with RRV. Sacrifice of the animals was scheduled for days 7, 14 and 21 after infection. Then, gross and mircoscopia findings of the liver and the hepatoduodenal ligament gave evidence of BA, and hepatic viral load was tested by virus-specific real-time PCR, as well as plaque forming units. RESULTS: Two weeks after infection, the incidence of cholestasis was 100% in controls, 77% in pups of RotaTeq-vaccinated dams, and 56% in pups of Rotarix-vaccinated dams. However, in contrast to controls (incidence of BA: 82%) most pups in the test groups recovered (incidence of BA in pups of RotaTeq-vaccinated dams 11%; incidence of BA in pups of Rotarix-vaccinated dams 3%). Hepatic viral load was identical at various time-points in all pups, suggesting that differences in RRV clearance did not underlie this effect. CONCLUSION: In this mouse model, oral vaccination with RotaTeq and Rotarix prevented most RRV-induced BA. This provides a new approach to a better understanding of both the pathomechanism of BA development and the capabilities of the innate immune system. It also suggests a first approach for prophylaxis against BA.

[Predictive parameters in children with biliary atresia]. / Prognostische Marker bei Kindern mit Gallengangatresie.

Most children with biliary atresia require liver transplantation, and only about 20% survive in the long term with their native livers. Prognostic factors that determine disease progression are still lacking. This retrospective survey of 85 BA patients from 1993 to 2003 was aimed to evaluate prognostic factors using the log rank test. After 5 years 40% of the patients are alive with their native livers (35/85), 26 of them with normal bilirubin (31%). Age at Kasai operation (P=0.46), degree of liver fibrosis (P=0.95), and all laboratory test results before Kasai failed to correlate with outcome. Normal levels of bilirubin 3, 6, and 12 months after Kasai and of aspartate aminotransferase with gammaGT after 6 months are associated with survival with native liver. In conclusion our data demonstrate that a lack of predictive factors must prevent primary liver transplantation in BA patients.

Functional Mx protein does not prevent experimental biliary atresia in Balb/c mice.

Biliary atresia (BA) is a rare cholestatic disease, which manifests itself in the form of inflammation of the liver and bile ducts in newborns, with an unknown etiology and a poor outcome. Mx proteins, which are mediators of innate, antiviral resistance induced by type I interferon, were recently detected in the livers of children with BA. Therefore, the aim of this study was to examine whether the expression of Mx protein could affect the course of experimental BA in mice. A total of 185 newborn Balb/c mice (expressing dysfunctional Mx protein) and Balb/c-Mx+-A2G mice (with functional Mx protein) were intraperitoneally infected with rhesus rotavirus (RRV) or injected with saline solution as controls. They were sacrificed if they showed signs of cholestasis or at three weeks after infection. The expression of hepatic Mx protein was detected by immunostaining (POX) and the hepatic virus load was determined. There was no significant difference in the incidence of cholestasis between wild-type Balb/c mice and Balb/c-Mx+-A2G mice (67 % vs. 65 %). However, Mx protein was highly expressed in Balb/c-Mx+-A2G mice with BA phenotype, but not in wild type Balb/c mice or disease-free Balb/c-Mx+-A2G mice despite RRV infection. The difference in the hepatic virus load was not statistically significant in mice with BA. In conclusion, Mx protein does not prevent newborn Balb/c mice from developing biliary atresia after RRV infection. However, the expression of Mx protein is independent of the hepatic virus load and could be used as a marker of BA in humans, as well as in the RRV model.

European biliary atresia registries: summary of a symposium.

Biliary atresia (BA) is a rare but potentially devastating disease. The European Biliary Atresia Registry (EBAR) was set up to improve data collection and to develop a pan-national and interdisciplinary strategy to improve clinical outcomes. From 2001 to 2005, 100 centers from 22 countries registered with EBAR via its website (www.biliary-atresia.com). In June 2006, the first meeting was held to evaluate results and launch further initiatives. During a 5-year period, 60 centers from 19 European countries and Israel sent completed registration forms for a total of 514 BA patients. Assuming the estimated incidence of BA in Europe is 1:18,000 live births, 35% of the expected 1488 patients from all EBAR participating countries were captured, suggesting that reporting arrangements need improvement. At the meeting, the cumulative evaluation of 928 BA patients including patients from other registries with variable follow-up revealed an overall survival of 78% (range from 41% to 92%), of whom 342 patients (37%) have had liver transplants. Survival with native liver ranged from 14% to 75%. There was a marked variance in reported management and outcome by country (e.g., referral patterns, timing of surgery, centralization of surgery). In conclusion, EBAR represents the first attempt at an overall evaluation of the outcome of BA from a pan-European perspective. The natural history and outcome of biliary atresia is of considerable relevance to a European population. It is essential that there is further support for a pan-European registry with coordination of clinical standards, further participation of parent support groups, and implementation of online data entry and multidisciplinary clinical and basic research projects.

Minimally invasive repair of pectus excavatum - shifting the paradigm?

PURPOSE: The "minimally invasive repair of pectus excavatum" (MIRPE) has increasingly become the standard operation for the repair of pectus excavatum. The aim of the present study was to report on our first-line postoperative results, including a survey of patients and to elucidate the acceptance of MIRPE. PATIENTS AND METHODS: All MIRPE patients, who were operated on between 2000 and 2004 in our departments, were included in a retrospective study. In 2002, a retrospective questioning of 57 patients was initiated by sending identical questionnaires separately to both the patients and their parents asking for individual reasons for choosing and/or agreeing to MIRPE. RESULTS: Complications were seen in 25 out of 84 MIRPE patients (mean 14 years, range from 5 to 20 years), but most of them were minor. Removal of the bar was necessary in 6 cases, due to bar displacement, secondary haematothorax, pericardial effusion, and local infection, respectively. No major complications occurred in the age group between 9 and 14 years. More than 90 % of the patients and their parents were satisfied or highly satisfied with the MIRPE procedure. CONCLUSION: General and specific complications are similar to other series and they decrease with the surgeon's experience. The most severe problem, occurring in older patients, is how to avoid dislocation of the pectus bar. In the light of the complication rate, the acceptance of MIRPE is still high, especially in adolescents and young adults who had refused operation with the open techniques. In this way, a shifting of a paradigm is taking place.

Myoblast transplantation for heart repair: A review of the state of the field / 老年心脏病学杂志（英文版）

Over 200 humans have been treated with myoblast transplantation for heart muscle repair since June 2000. Bioheart sponsored percutaneous delivery studies began in May 2001 in Europe. Approximately one third of the patients have exhibited substantial improvement in left ventricular ejection fraction (LVEF) of over 30% and two heart failure class improvements. Over 80% of the patients have exhibited one heart failure class improvement with moderate improvement of LVEF. Clinical trials seem to demonstrate a marked reduction in emergency hospitalizations in myoblast treated patients. Many years of careful studies have lead to randomized controlled studies that are enrolling patients now at numerous centers worldwide. A firm conclusion on the safety and efficacy of myoblast transplantation cannot be determined until these randomized studies are completed. Final results from randomized controlled studies should be available soon. (J Geriatr Cardiol 2006;3:165-7.)

[Imaging characteristics of childhood lipoblastoma]. / Charakteristika in der Bildgebung kindlicher Lipoblastome.

PURPOSE: Lipoblastoma and lipoblastomatosis are very rare benign neoplasms, which almost exclusively occur in infants and young children. Despite their potential to local invasion and rapid growth, these tumors have an excellent prognosis, particularly if resected completely. Usually, the diagnosis is not taken into consideration preoperatively, and depends on histopathological evaluation. This study was done to determine imaging characteristics of lipoblastoma. MATERIALS AND METHODS: Eight cases of histopathologically proven lipoblastoma treated from 1988 to 2003 were reviewed, comprising four girls and four boys ranging in age from 17 months to nine years. The localization was chest wall (four times), abdominal wall (once), gluteal region (once), lower leg (once) and forearm (once). Ultrasound, MRI and CT scans were evaluated and correlated to clinical data of the patients. RESULTS: Ultrasound showed lipomatous echogenicity and echotexture. The tumors appeared signal intensive on T1-weighted MR images and had a mean intensive signal on T2-weighted MR images with fat suppression. They were markedly hypodense on CT. The growth pattern was invasive in all imaging methods, with extension into preformed spaces, such as intercostal spaces and neural foramina, but without infiltration into surrounding structures or metastases. CONCLUSION: Ultrasound and MRI are the methods of choice to diagnose lipoblastoma by revealing structures and local growth pattern that appear specific of this rare tumor entity. The imaging characteristics of the lipoblastoma have to be correlated with the age of patients to exclude other conditions in the differential diagnosis.

The role of reovirus type 3 infection in an established murine model for biliary atresia.

AIM OF THE STUDY: Infection of newborn Balb/c-mice with Rhesus rotavirus (RRV) leads to cholestasis and biliary atresia. In this current model, Reovirus Type 3 was investigated to ascertain whether Reovirus Type 3 causes the same or similar hepatobiliary lesions as RRV. METHODS: Newborn Balb/c-mice were infected with Reovirus Type 3 Dearing and Reovirus Type 3 Abney on the first day of life. Clinical observation followed for a period of at least 10 days. Cholestatic and/or dystrophic mice were prepared and specimens were taken for histological examination. RESULTS: Infection with RRV showed a 85 % morbidity for biliary atresia as described before. Clinical disease, following an infection with Reovirus T3 Dearing, showed neurological symptoms such as ataxia, and all mice died within 3 weeks. No obstructive or atretic changes of the hepatobiliary ducts could be seen either macroscopically or histomorphologically. 60 % of the mice having been infected with Reovirus T3 Abney showed signs of cholestasis and oily fur syndrome, but almost 15 % recovered from the disease. Although the histological findings did not reveal biliary atresia, inflammation and destruction of bile ducts could be observed. CONCLUSION: In comparison to the RRV infection in a Balb/c-mice model, where biliary atresia could be induced, infection with Reovirus T3 in this model did not lead to biliary atresia. But Reovirus T3 Abney infection revealed inflammatory signs as described in the literature before. The question as to why different hepatotrophic viruses lead to different changes in the murine hepatobiliary tract has to be investigated in further studies.

Immunological gap in the infectious animal model for biliary atresia.

BACKGROUND: Extrahepatic biliary atresia (EHBA), the etiology of which still remains unclear, occurs exclusively in newborns and has recently been simulated in an animal model. It is possible to trigger an EHBA corresponding to the human disease by means of intraperitoneal infection of newborn Balb/c mice with rhesus rotavirus (RRV). The aim of the present study was to determine the conditions and circumstances for inducing biliary atresia in this model focusing on first-line immunological aspects. METHODS: Newborn as well as pregnant Balb/c mice were intraperitoneally infected with RRV. RESULTS: The highest incidence of cholestasis (86%) was achieved by infection with 10(6) PFU/ml RRV within the first 12 h postpartum, resulting in EHBA with a lethality of 100%. However, the later the newborn mouse is infected, the less likelihood there is that EHBA is triggered. Additionally, the incidence of biliary atresia in this model depends on the quantity of the virus that is given intraperitoneally. However, the development of biliary atresia is not correlated to the virus in the liver. The antepartum infection of pregnant mice does not induce EHBA in the offspring. Female mice that are immunized against RRV protect their newborns from developing RRV-induced cholestasis and EHBA. This protection is transmitted transplacentally and not by breast milk. CONCLUSION: It is obvious that a temporary immunological gap is essential for virally induced EHBA. Further studies should focus on specific parameters of the immune system of newborn mice in this biliary atresia model.

[Post-traumatic osteoid osteoma. Case report and review of the literature]. / Posttraumatisches Osteoidosteom. Fallbericht und Literaturübersicht.

Osteoid osteoma is a painful benign bone neoplasm that is rarely described after trauma but should be suspected. A case of osteoid osteoma 19 years after a tibial fracture is presented. The patient had pain in the tibia for 6 years before the osteoid osteoma was confirmed. He had been operated on twice for suspected osteomyelitis although the clinical symptoms suggested an osteoid osteoma. The radiographic appearance as well as a bone scan confirmed the diagnosis. Removal of the nidus resulted in immediate pain relief. A precise preoperative diagnosis of the lesion based on clinical findings, standard radiographs, high-resolution CT, and bone scan is mandatory. It is important to recognize this uncommon entity to avoid morbidity associated with a prolonged delay in diagnosis.

Growth of Nile tilapia Oreochromis niloticus fed with different levels of alcohol yeast.

Two hundred and forty 45-day-old fingerlings of Nile tilapia (Oreochromis niloticus), sexually reverted with an initial average weight of 1.25 +/- 0.14 g, distributed in a totally casualized delineation, during 330 days. The effect of the substitution of 10%, 20% and 30% of the ration by distillery yeast (Saccharomiyces cerevisae) in balanced experimental rations on the development in the breeding of tilapias did not show a harmful effect up to the maximum tested level of 30%, showing that the choice of the yeast in the ration for these fishes depends on the availability and occasional cost. The yeast provides fish with good resistance to unfavorable environmental conditions, which could be verified since there were no statistical differences among the treatments with different levels of yeast and the witness. The long growth rate in terms of length and weight can be attributed to the little available space for each specimen, not obeying the limit of populational density, as well as reduction of food ingestion, which coincide with the winter season, above of the absence of natural feeding.

Vaccination against bovine herpes mammillitis virus infections in guinea pigs.

Bovine herpes mammillitis virus or bovine herpesvirus type 2 (BHV-2) causes ulcerative lesions on the teats and udders of infected cows. Since no commercial vaccine is available for this disease, we investigated certain experimental BHV-2 vaccines against this virus in infected guinea pigs. Vaginally infected guinea pigs get severe, self-limiting vaginal infections characterized by erythema and swelling and the production of measurable vaginal virus titers. Two vaccine approaches were investigated: vaccination with wild-type (WT) virus by the subcutaneous route, and vaccination either subcutaneously or intravaginally with a thymidine kinase (TK) deficient (TK-) virus. The TK- strain was prepared by passage of BHV-2 in the presence of the potent TK-dependent antiviral agent 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-methyluracil (FMAU). The antiviral activity of FMAU against the virus in plaque reduction assays changed from 0.05 to 2 microM at the same time that the TK activity of the mutant virus decrease to 7% of WT virus TK activity. Subcutaneous vaccination of guinea pigs with WT and TK- viruses did not induce vaginal infection. Primary vaginal infection (vaccination) with the TK- virus led to greatly reduced lesion severity compared to vaginal infection with the WT virus. However, the amount of vaginal virus titers recovered during these primary infections was similar for both TK- and WT viruses, indicating that both viruses had equal infecting potential. Thirty days after vaccination the animals were re-infected intravaginally with WT virus. The vaccinated animals showed dramatically reduced lesion severity and low recoverable virus titers compared to age-matched nonvaccinated animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of lethal Pichinde virus infections in weanling LVG/Lak hamsters with ribavirin, ribamidine, selenazofurin, and ampligen.

A lethal Pichinde (An 4763 strain) virus infection was produced in 3-week-old random-bred Golden Syrian (LVG/Lak strain) hamsters inoculated intraperitoneally with virus, causing mortality in 6-9 days. High virus titers (> or = 10(7.5) cell culture infectious doses/g) were present in visceral organs, serum, brain and salivary glands near the time of death. Intraperitoneal treatments with ribavirin (10 and 32 mg/kg) and ribamidine (32, 100, and 320 mg/kg) for 10 days starting 24 h after virus challenge significantly decreased mortality and reduced virus titers by 100- to > 10,000-fold in liver, spleen, brain, and serum. Serum alanine aminotransferase (an indicator of liver damage) was also reduced in animals treated with the two compounds (ribavirin at 32 mg/kg; ribamidine at 100 and 320 mg/kg). Intraperitoneal selenazofurin (1-100 mg/kg per day for 10 days) and ampligen (0.5 and 5 mg/kg every other day for 5 injections) treatments provided neither protection from the lethal infection nor increased mean survival times. In fact, selenazofurin was overtly toxic, causing death of uninfected hamsters at 32 and 100 mg/kg. The random-bred LVG/Lak hamster appears to be a viable and cost-effective model for evaluating new therapies for arenavirus infections.

Treatment of murine cytomegalovirus infections in severe combined immunodeficient mice with ganciclovir, (S)-1-[3-hydroxy-2-(phosphonylmethoxy)propyl]cytosine, interferon, and bropirimine.

Severe combined immunodeficient (SCID) mice were found to be highly susceptible to murine cytomegalovirus (MCMV) infection. Treatment of infected mice with ganciclovir (12.5, 25, and 50 mg/kg of body weight for 10 days) starting 24 h after virus challenge resulted in delays in death by 2 to 8 days, and no animals survived the infection. (S)-1-[3-Hydroxy-2-(phosphonylmethoxy)propyl]cytosine (HPMPC) was much more potent, with doses of 1, 3.2, and 10 mg/kg/day (for 10 days) increasing the mean survival time by 15 to 30 days. Twenty-day treatments with HPMPC starting 5 days after virus inoculation increased the mean survival time by 24 to 32 days, with once-weekly (50-mg/kg) treatments being equivalent to daily (10-mg/kg) treatments. Delays in the development of liver, lung, and spleen virus titers in ganciclovir- and HPMPC-treated groups correlated with extensions in the mean survival times relative to the survival times of the placebo controls. The two compounds were approximately equally toxic to uninfected BALB/c mice treated for 10 days, causing 80 to 100% mortality after a dose of 150 mg/kg and 0% mortality after a dose of 75 mg/kg. Thus, the relative therapeutic index of HPMPC was 50-fold greater than that of ganciclovir. Recombinant alpha interferon delta 4 alpha 1/alpha 2 (1 x 10(4) and 5 x 10(4) units per mouse per day) and bropirimine (100 and 300 mg/kg/day) provided no protection from the lethal MCMV infection. The severe combined immunodeficient mouse MCMV infection is an important new model that will permit chemotherapy regimens to be studied over several months.