C.B‐17 SCID mice develop epicardial calcinosis with unaltered cardiac function

Inbred mouse strains are the most widely used mammalian model organism in biomedical research owing to ease of genetic manipulation and short lifespan; however, each inbred strain possesses a unique repertoire of deleterious homozygous alleles that can make a specific strain more susceptible to a particular disease. In the current study, we report dystrophic cardiac calcinosis (DCC) in C.B‐17 SCID male mice at 10 weeks of age with no significant change in cardiac function. Acquisition of DCC was characterized by myocardial injury, fibrosis, calcification, and necrosis of the tissue. At 10 weeks of age, 38% of the C.B‐17 SCID mice from two different commercial colonies exhibited significant calcinosis on the ventricular epicardium, predominantly on the right ventricle. The frequency of calcinosis was more than 50% for mice obtained from Taconic's Cambridge City colony and 25% for mice obtained from Taconic's German Town colony. Interestingly, the DCC phenotype did not affect cardiac function at 10 weeks of age. No differences in echocardiography or electrocardiography were observed between the calcinotic and non‐calcinotic mice from either colony. Our findings suggest that C.B‐17 SCID mice exhibit DCC as early as 10 weeks of age with no significant impact on cardiac function. This strain of mice should be cautiously considered for the study of cardiac physiology.     

Simultaneous Bilateral Tibial Tuberosity Avulsions—Over 6-Year Follow-up

Abstract Simultaneous bilateral avulsions of the tibial tuberosity are rare injuries. The authors found only five reported cases in the orthopedic literature. We add a further case of bilateral avulsions of the tibial tuberosity with the longest reported follow-up.     

Disposition of leucovorin and its metabolites in dietary folic acid-deplete mice – comparison between tumor, liver and plasma

Purpose: A comprehensive pharmacokinetic study of leucovorin (5-formyltetrahydrofolate, 5-HCO-FH₄) and its metabolites was conducted in plasma, liver and implanted tumor tissue from mice maintained on a low folic acid diet. While it has been previously demonstrated that the antitumor activity of fluorouracil (FU) can be potentiated by 5-HCO-FH₄, the optimum time for administration of FU after 5-HCO-FH₄, to maximally elevate the active folate metabolite methylenetetrahydrofolate in tumor has not been established. Human plasma studies have defined the pharmacokinetics of circulating 5-HCO-FH₄ and its metabolites, but comparison with human tumor accumulation has not been practicable because of sampling difficulties. As an alternative, a mouse model system, based on low dietary folic acid, was used to evaluate plasma, liver and implanted tumor reduced folates after administration of 5-HCO-FH₄.Methods: Plasma and tissue samples were collected from folate-deplete mice over a 12-h period after intraperitoneal administration of 90 mg/kg [R, S ] 5-HCO-FH₄. Reduced folates were evaluated using a ternary complex assay. Results: The time at which max‐imal accumulation of parent compound and all metabolites, except 5-methyltetrahydrofolate (5-CH₃FH₄), occurred in tumor was the same as in plasma. Alternatively, peak liver accumulation was delayed relative to plasma for all folates except 5-CH₃FH₄. Conclusions: The results suggest that mouse plasma accumulation of reduced folates, with the exception of 5-CH₃FH₄, can predict tumor accumulation. Hence, evaluation of human plasma folate accumulation may potentially provide a means to improve the timing of the administration of FU relative to 5-HCO-FH₄ to achieve a superior therapeutic outcome. Received: 24 July 1996 / Accepted: 29 October 1996     

Immunoglobulin M antibody responses to Mycobacterium ulcerans allow discrimination between cases of active Buruli ulcer disease and matched family controls in areas where the disease is endemic

Buruli ulcer disease (BUD) is an emerging disease caused by Mycobacterium ulcerans. In the present study we have characterized the serological reactivities of sera from volunteer case patients with laboratory-confirmed BUD and controls living in three different regions of Ghana where the disease is endemic to determine if serology may be useful for disease confirmation. Our results showed highly reactive immunoglobulin G (IgG) responses among patients with laboratory-confirmed disease, healthy control family members of the case patients, and sera from patients with tuberculosis from areas where BUD is not endemic. These responses were represented by reactivities to multiple protein bands found in the M. ulcerans culture filtrate (CF). In contrast, patient IgM antibody responses to the M. ulcerans CF (MUCF) proteins were more distinct than those of healthy family members living in the same village. A total of 84.8% (56 of 66) of the BUD patients exhibited strong IgM antibody responses against MUCF proteins (30, 43 and 70 to 80 kDa), whereas only 4.5% (3 of 66) of the family controls exhibited such responses. The sensitivity of the total IgM response for the patients was 84.8% (95% confidence interval [CI], 74.3 to 91.6%), and the specificity determined with sera from family controls was 95.5% (95% CI, 87.5 to 98.4%). These studies suggest that the IgM responses of patients with BUD will be helpful in the identification and production of the M. ulcerans recombinant antigens required for the development of a sensitive and specific serological assay for the confirmation of active BUD.     

Thoracoscopy versus open lung biopsy in the diagnosis of interstitial lung disease: a randomised controlled trial

BACKGROUND: Some patients with diffuse lung disease require a lung biopsy for diagnosis. This study is aimed to compare the clinical results and the efficacy of video-assisted thoracoscopic lung biopsy with the open lung biopsy method for the diagnosis of interstitial lung disease. From January 1996 to December 1998, 61 patients were referred for diagnostic lung biopsy. Thirty two patients were randomly allocated to have a thoracoscopic lung biopsy and twenty nine had an open lung biopsy. Subsequently, various factors were analyzed and compared in both groups. RESULTS: There was no difference between the groups in age and pulmonary function test. Median operative time was 45 minutes for the thoracoscopic biopsies and 60 minutes for the open biopsies (P = 0.009). Median amount of analgesia (Demerol) in the first 24 hours postoperatively was 75 mg. for thoracoscopic biopsies and 150 mg. for open biopsies (P < 0.001). Median duration of insertion of a chest tube in days and 24 hours of pleural drainage was not statistically significant between the two groups. Duration of hospital stay was significantly less for the thoracoscopic biopsy (3 days) compared with an open biopsy (5 days) (P < 0.001). The diagnostic yield of each method was comparable (thoracoscopic biopsy 31/32; open biopsy 27/29) (P = 0.3). Complications occurred in 6/29 of patients undergoing open biopsies and 3/32 patients undergoing thoracoscopic lung biopsies (p = 0.28). There were 2 deaths among patients who had an open lung biopsy. CONCLUSION: Thoracoscopic lung biopsy has some clinical advantages over open biopsy. These findings suggest that thoracoscopic lung biopsy is an acceptable alternative to open lung biopsy for the diagnosis of diffuse interstitial lung diseases.     

Influenza vaccination and the risk of primary cardiac arrest

Influenza epidemics are associated with an excess of mortality not only from respiratory diseases but also from other causes, and cardiovascular mortality increases abruptly during influenza epidemics, with little evidence of a lag period. In a population-based case-control study, the authors examined whether influenza vaccination was associated with a reduced risk of out-of-hospital primary cardiac arrest (PCA), a major contributor to cardiovascular mortality in the community. Cases of PCA (n = 342) without prior heart disease or life-threatening comorbidity that occurred in King County, Washington, were identified from paramedic incident reports from October 1988 to July 1994. Demographically similar controls (n = 549) were identified from the community by using random digit dialing. Spouses of subjects were interviewed to assess treatment with influenza vaccine during the previous year and other risk factors. After adjustment for demographic, clinical, and behavioral risk factors, influenza vaccination was associated with a reduced risk of PCA (odds ratio = 0.51, 95 percent confidence interval: 0.33, 0.79). The authors suggest that while the association of influenza vaccination with a reduced risk of PCA is consistent with cohort studies of influenza vaccination and total mortality, further studies are needed to determine whether the observed association reflects protection or selection.