Tumour necrosis factor receptor I blockade shows that TNF‐dependent and TNF‐independent mechanisms synergise in TNF receptor associated periodic syndrome

TNF receptor associated periodic syndrome (TRAPS) is an autoinflammatory disease involving recurrent episodes of fever and inflammation. It is associated with autosomal dominant mutations in TNF receptor superfamily 1A gene localised to exons encoding the ectodomain of the p55 TNF receptor, TNF receptor‐1 (TNFR1). The aim of this study was to investigate the role of cell surface TNFR1 in TRAPS, and the contribution of TNF‐dependent and TNF‐independent mechanisms to the production of cytokines. HEK‐293 and SK‐HEP‐1 cell lines were stably transfected with WT or TRAPS‐associated variants of human TNF receptor superfamily 1A gene. An anti‐TNFR1 single domain antibody (dAb), and an anti‐TNFR1 mAb, bound to cell surface WT and variant TNFR1s. In HEK‐293 cells transfected with death domain‐inactivated (R347A) TNFR1, and in SK‐HEP‐1 cells transfected with normal (full‐length) TNFR1, cytokine production stimulated in the absence of exogenous TNF by the presence of certain TNFR1 variants was not inhibited by the anti‐TNFR1 dAb. In SK‐Hep‐1 cells, specific TRAPS mutations increased the level of cytokine response to TNF, compared to WT, and this augmented cytokine production was suppressed by the anti‐TNFR1 dAb. Thus, TRAPS‐associated variants of TNFR1 enhance cytokine production by a TNF‐independent mechanism and by sensitising cells to a TNF‐dependent stimulation. The TNF‐dependent mechanism requires cell surface expression of TNFR1, as this is blocked by TNFR1‐specific dAb.     

A descriptive review of malpractice claims for health care-acquired infections in Philadelphia

BACKGROUND: Philadelphia's rate of malpractice filings per population is just over double the national median. Plaintiffs prevail in 44% of verdicts in Philadelphia compared with 20% for all US jury verdicts, with 24% of awarded verdicts in excess of $1 million. OBJECTIVE: To determine patient and procedure demographic data for malpractice claims involving health care-acquired infections (HAIs) in Philadelphia. METHODS: Risk managers representing 60 acute care hospitals, members of Pennsylvania Trial Lawyers Association, and a random sample of 560 lawyers representing plaintiff and defense cases obtained from the Philadelphia Court of Common Pleas database (1996-2002) were surveyed. The survey included the following: number of HAI cases by specialty, body site, isolate, and outcome. RESULTS: Overall response rate was 25% (n = 154 cases). The highest numbers of cases were in the specialties of orthopedics (69), general surgery (20), and cardiothoracic (20). Sites infected most often were as follows: knees (26), back (26), sternum (18), and harvest site (10). Methicillin-resistant Staphylococcus aureus (MRSA) was responsible for 45 of cases, S epidermidis for 27, methicillin-susceptible S aureus (MSSA) for 14, and Pseudomonas for 16. Twenty-seven of the cases were withdrawn, 27 settled, 11 pending, 9 plaintiff verdict, and 5 defense verdict. CONCLUSIONS: Although 72% of HAI malpractice cases in Philadelphia were either withdrawn or settled, when brought to trial, the plaintiff was more likely to succeed with a verdict. Our findings also suggest that the most frequent type of infection (class I-surgical site) and isolate (MRSA) are more likely to be seen as preventable HAIs because of National Nosocomial Infection Surveillance data showing lower infection rates for this class of surgery and therefore seen as easier for the plaintiff to show that the defendant failed to adhere to the standard of care for infection control.     

Analysis of left ventricular systolic function using midwall mechanics in patients >60 years of age with hypertensive heart disease and heart failure

Normal ejection fraction (EFs) is often equated with normal systolic function. However, midwall mechanics reveal systolic dysfunction in hypertensive heart disease accompanied by hypertrophic remodeling. Midwall mechanics are unstudied in patients with acute diastolic heart failure (HF). This study analyzed left ventricular (LV) midwall stress-shortening relations in 61 patients aged >60 years with hypertensive heart disease, HF, and normal EF. Sixty-one hypertensive patients (mean age 78 +/- 10 years) who presented with HF, each with an EF >50%, underwent echocardiography. Midwall mechanics were compared with those of 79 controls (mean age 75 +/- 8 years) without structural heart disease. Relative wall thickness (0.63 +/- 0.11 vs 0.46 +/- 0.10 mm) and LV mass (237 +/- 67 vs 177 +/- 57 g) were significantly greater in patients with HF compared with controls. Mean EFs were similar in patients with HF and controls (64 +/- 9% vs 67 +/- 9%). Although mean endocardial fractional shortening (35 +/- 7% vs 37 +/- 7%) was not significantly different, midwall shortening in patients with HF was significantly less compared with controls (16 +/- 2% vs 19 +/- 3%, p <0.05). Eighteen of the 61 patients with HF (30%) had midwall shortening that was <95% confidence intervals of the normal midwall stress-shortening relations. By this criterion, these patients had systolic dysfunction despite normal EF; they had smaller LV chambers (in dimension and volume), greater relative wall thickness, and smaller stroke volumes. In conclusion, almost 1/3 of patients hospitalized with diastolic HF had systolic dysfunction, characterized by abnormal midwall stress-shortening relations.     

Disorders of the Rectus Abdominis Muscle and Sheath: A 22-Year Experience

Objectives : To determine the spectrum of diseases that can involve the rectus abdominis muscle and sheath (RMS) and to describe the clinical features of these conditions. Method : A retrospective medical record review of RMS disorders seen at The New York Hospital— Cornell Medical Center from 1971 to 1992. Results : A total of 40 patients with diseases of the RMS were identified. Thirty patients had primary diseases of the K MS, most commonly desmoid tumor and hematoma. Secondary disorders of the RMS included abscesses from di-verticulitis, a perforated sigmoid carcinoma, gallbladder empyema, and disseminated actinomycosis. Eleven of 18 patients with desmoid tumors had familial adenomatous polyposis (FAP). The desmoid tumors in patients with FAP resulted in greater morbidity and mortality than those in patients without FAP. All patients with hema-tomas were on anticoagulation or had a history of trauma, vigorous coughing, or physical exertion. Conclusions : 1) RMS disease should be suspected in patients with a palpable abdominal mass and a history of familial adenomatous polyposis, trauma, anticoagulation, or vigorous coughing or exercise. 2) The most common non-neoplastic condition of the RMS is a hematoma. 3) The desmoid tumor is the most common neoplasm of the RMS. 4) Abdominal ultrasonography and CT readily distinguish RMS disease from intraabdominal pathology-