The influence of the rearing period on intramammary infections in Swiss dairy heifers: A cross-sectional study.

Healthy replacement heifers are one of the foundations of a healthy dairy herd. Farm management and rearing systems in Switzerland provide a wide variety of factors that could potentially be associated with intramammary infections (IMI) in early lactating dairy heifers. In this study, IMI with minor mastitis pathogens such as coagulase-negative staphylococci (CNS), contagious pathogens, and environmental major pathogens were identified. Fifty-four dairy farms were enrolled in the study. A questionnaire was used to collect herd level data on housing, management and welfare of young stock during farm visits and interviews with the farmers. Cow-level data such as breed, age at first calving, udder condition and swelling, and calving ease were also recorded. Data was also collected about young stock that spent a period of at least 3 months on an external rearing farm or on a seasonal alpine farm. At the quarter level, teat conditions such as teat lesions, teat dysfunction, presence of a papilloma and teat length were recorded. Within 24h after parturition, samples of colostral milk from 1564 quarters (391 heifers) were collected aseptically for bacterial culture. Positive bacteriological culture results were found in 49% of quarter samples. Potential risk factors for IMI were identified at the quarter, animal and herd level using multivariable and multilevel logistic regression analysis. At the herd level tie-stalls, and at cow-level the breed category "Brown cattle" were risk factors for IMI caused by contagious major pathogens such as Staphylococcus aureus (S. aureus). At the quarter-level, teat swelling and teat lesions were highly associated with IMI caused by environmental major pathogens. At the herd level heifer rearing at external farms was associated with less IMI caused by major environmental pathogens. Keeping pregnant heifers in a separate group was negatively associated with IMI caused by CNS. The odds of IMI with coagulase-negative staphylococci increased if weaning age was less than 4 months and if concentrates were fed to calves younger than 2 weeks. This study identified herd, cow- and quarter-level risk factors that may be important for IMI prevention in the future.

[Drug-induced toxic hepatitis]. / Medikamentös-toxische Hepatitis.

A 55-year-old male patient was hospitalized with severe nausea, vomiting and icterus. Laboratory testing showed hepatocellular damage. After exhaustive testing, the exclusion diagnosis of a toxic hepatitis was reached. There was a strong temporal correlation with the ingestion of Hong Hua 29, a preparation from Traditional Chinese Medicine (TCM). This medication had been started twelve days prior to the first appearance of symptoms. The existing drug regimen included gabapentin (Neurontin), esomeprazole (Nexium) and prednisone (Prednison Streuli) for the therapy of an acute sensory and motor neuropathy of unknown aetiology. After cessation of Hong Hua 29, gabapentin and esomeprazole, transaminase levels started to declined and normalized within three months. According to the Swissmedic criteria of imputability, a causal correlation between the observed symptoms and the administration of Hong Hua 29 is possible.

[Zoledronate-associated end stage renal failure and hypocalcaemia]. / Zoledronat-assoziierte terminale Niereninsuffizienz und Hypokalzämie.

In an 81-year-old patient with a history of long-standing stable chronic renal failure a diagnosis of multiple myeloma was made. After an initial chemotherapy, a therapy with intravenous pamidronate, 90 mg monthly, was initiated. After four years of well tolerated therapy, pamidronate was stopped and zoledronate, 4 mg intravenously every four weeks, was started. After approximately one year, an elevated plasma creatinine was noted for the'first time, progressing to end stage renal failure within the next months. At admission, besides end-stage renal failure, severe asymptomatic hypocalcemia was noted. Renal biopsy findings included severe tubulointerstitial damage compatible with drug-induced tubular injury. Prerenal and postrenal failure could be excluded as well as myeloma kidney. The diagnosis of zoledronate-associated end-stage renal failure was made and treatment with hemodialysis was started. Hypocalcemia was treated with calcium and vitamin D3 supplements. After two years of follow up, the patient still required hemodialysis.

Immune enhancing effects of dehydroepiandrosterone and dehydroepiandrosterone sulphate and the role of steroid sulphatase.

Steroid hormones, such as glucocorticoids (GC), influence immune and inflammatory responses through their suppressive actions. Recent evidence suggests that another steroid hormone, dehydroepiandrosterone (DHEA), provides an immunostimulatory influence opposing the effect of GC. DHEA circulates in its inactive sulphated form, DHEAS, requiring conversion to DHEA by a steroid sulphatase (SS) enzyme for biological activity. Therefore, inhibition of SS activity may affect immune responses, allowing endogenous GC effects to predominate. We have shown that administration of DHEA and DHEAS in contact sensitization (CS) augments ear swelling by 39 and 46% respectively (P < 0.001). DHEAS at doses of 0.5, 5 and 50 mg/kg reverses the inhibitory effect of corticosterone (5 mg/kg) (P < 0.01). In CS, CT2251 (SS inhibitor) at 10 and 0.1 mg/kg inhibited ear swelling by 61 and 38% (P < 0.05) respectively. In addition, it inhibited DHEAS-augmented responses by 49 and 35% respectively (P < 0.05), with no effect on DHEA-augmented responses. DHEAS reversed CT2251 inhibition of the CS response with complete reversal at 50 mg/kg (P < 0.05). DHEAS and CT2251 appear to affect cellular infiltration into the ear, since DHEAS increased the number of lymphocytes by 63.8% and macrophages by 107% (P < 0.001), whereas CT2251 at 0.1 mg/kg decreased the number of lymphocytes by 65% (P < 0.001) and macrophages by 80% (P < 0.001). DHEAS, CT2251 and dexamethasone had no effect on oedema in the ear. From our data we have shown that steroid hormones, such as DHEA, have the potential to act as immunostimulatory factors in vivo. Inhibiting the conversion of DHEAS to DHEA by SS enzyme leads to an anti-inflammatory effect.

Preclinical review of anti-tumor necrosis factor monoclonal antibodies.

OBJECTIVE: To review the preclinical evidence for the role of tumor necrosis factor (TNF) in the pathogenesis of septic shock and to assess the preclinical efficacy of anti-TNF therapies for this clinical problem. DATA SOURCES: The international English language literature from 1986 to the present formed the basis of this review. MEDLINE was used to identify pertinent in vitro and animal studies pertaining to the pathobiology of TNF and the use of anti-TNF therapies, with special emphasis on antibody approaches. STUDY SELECTION: Those studies that focused on the mechanisms of action of TNF, its role in the inflammatory cascade, and the potential uses of anti-TNF therapies were emphasized. Investigations that described animal and human results served as the primary database. DATA EXTRACTION: Animal studies were selected based on the relevance of the model to the pathogenesis of the human clinical sepsis syndrome. Where they provided supportive evidence, patient studies were selected on the basis of study design. DATA SYNTHESIS: The administration of anti-TNF antibodies in baboons, monkeys, and other species that were administered lethal doses of bacteria or endotoxin suggest that this approach may limit organ damage and decrease the mortality rate caused by the septic shock syndrome. Therapy with anti-TNF monoclonal antibodies is reviewed. CONCLUSIONS: Bacterial challenge induces the release of TNF (among other mediators), which exerts both physiologic and toxic effects that may ultimately lead to organ dysfunction and death. New anti-TNF therapies such as anti-TNF antibodies appear to attenuate the injurious effects of TNF and promote survival in otherwise lethal septic shock animal models, suggesting a similar benefit might be obtained in the treatment of human septic shock.

Efficacy of a monoclonal antibody directed against tumor necrosis factor in protecting neutropenic rats from lethal infection with Pseudomonas aeruginosa.

A monoclonal antibody directed against murine tumor necrosis factor-alpha (TNF) was studied in a neutropenic rat model to determine its efficacy in protecting animals from lethal infection with Pseudomonas aeruginosa. Anti-TNF monoclonal antibody at a dose of 20 mg/kg given intravenously at 0 and 120 h resulted in a 53% survival rate (8/15) compared with no survival in control animals (0/15) (P less than .005). The combination of anti-TNF monoclonal antibody and oral ciprofloxacin at a suboptimal dose of 2.5 mg/kg/day resulted in a 100% survival rate in neutropenic animals (16/16), while ciprofloxacin alone produced only a 67% survival rate (10/15) during the 7-day period of neutropenia (P less than .05). Thus anti-TNF monoclonal antibody alone or in addition to antimicrobial agents improved survival in neutropenic animals after infection with P. aeruginosa.