Congenital conductive hearing loss and multiple synostosis syndrome with analysis of temporal bone CT scan findings

We present the case of a mother and four children displaying signs of Multiple Synostosis Syndrome (SYNS1) associated with conductive hearing loss. The intra-familial phenotypic variation is due to variable penetrance, which is typical of this syndrome. The child with the most significant hearing loss showed lucency of the otic capsule on temporal bone CT. There is no evidence of this phenomenon associated with SYNS1 in the literature. CT scanning can diagnose certain ossicular chain abnormalities, removing the need for tympanotomy under general anaesthetic. Syndromic hearing loss is progressive and should be monitored where appropriate.     

Cost analysis of transanal endoscopic microsurgery for rectal tumours

OBJECTIVE: Transanal endoscopic microsurgery (TEM) is considered to be a safe and effective treatment for selected rectal neoplasms. We demonstrate that in addition to the recognized clinical benefits of the less invasive TEM approach, there are substantial economic benefits. METHOD: We reviewed our prospective database of patients undergoing TEM excision of a rectal lesion between July 1997 and December 2003. A cost analysis was undertaken, including procedural and related costs of TEM and compared with the relevant open procedures. RESULTS: 124 patients (80 men, 44 women) with a median age of 71.5 years underwent TEM excision of rectal lesions (52 cancers and 72 adenomas). The morbidity rate was 8% and mortality was zero. A controlled case series of 52 patients undergoing open resection for early rectal cancers with similar characteristics as above was compared in terms of clinical outcome. The morbidity rate in these patients was 29.5%. The cost analysis comparison was undertaken using National Health Service mean reference costs for major large intestinal surgery, Intensive care unit/high dependency unit and hospital accommodation for each procedure. The average cost of open resection was 4135 pound, vs 567 pound for TEM excision. Our total saving over the series was 525,576 pound. Although the initial capital cost of the TEM equipment is high at approximately 40,000 pound given the massive cost savings, these initial equipment costs are recovered within a rapid time frame. CONCLUSION: This study has shown that TEM is a safe and extremely cost-effective approach for excision of selected rectal tumours including rectal adenomas and early well differentiated rectal cancers (pTis & pT1).     

Modes of action of aspirin-like drugs: Salicylates inhibit Erk activation and integrin-dependent neutrophil adhesion

The anti-inflammatory effects of high-dose salicylates are well recognized, incompletely understood and unlikely due entirely to cyclooxygenase (COX) inhibition. We have previously reported a role for activation of the kinase Erk in CD11b/CD18 integrin-dependent adhesiveness of human neutrophils, a critical step in inflammation. We now report the effects of salicylates on neutrophil Erk and adhesion. Exposure of neutrophils to aspirin or sodium salicylate (poor COX inhibitor) inhibited Erk activity and adhesiveness of formylmethionyl-leucyl-phenylalanine- and arachidonic acid-stimulated neutrophils, consistent with anti-inflammation but not COX inhibition (IC₅₀s = 1–8 mM). In contrast, indomethacin blocked neither Erk nor adhesion. Inhibition of Mek (proximal activator of Erk) also blocked stimulation of Erk and adhesion by formylmethionyl-leucyl-phenylalanineand arachidonic acid. Salicylate inhibition of Erk was independent of protein kinase A activation and generation of extracellular adenosine. These data are consistent with a role for Erk in stimulated neutrophil adhesion, and suggest that anti-inflammatory effects of salicylates may be mediated via inhibition of Erk signaling required for integrin-mediated responses.     

Designing and Implementing INTREPID,an Intensive Program in Translational Research Methodologies for New Investigators

Senior housestaff and junior faculty are often expected to perform clinical research, yet may not always have the requisite knowledge and skills to do so successfully. Formal degree programs provide such knowledge, but require a significant commitment of time and money. Short‐term training programs (days to weeks) provide alternative ways to accrue essential information and acquire fundamental methodological skills. Unfortunately, published information about short‐term programs is sparse. To encourage discussion and exchange of ideas regarding such programs, we here share our experience developing and implementing INtensive Training in Research Statistics, Ethics, and Protocol Informatics and Design (INTREPID), a 24‐day immersion training program in clinical research methodologies. Designing, planning, and offering INTREPID was feasible, and required significant faculty commitment, support personnel and infrastructure, as well as committed trainees.     

Prevalence of contraindications and prescription of pharmacologic therapies for gout

Background

Patients with gout have comorbidities, but the impact of these comorbidities on treatment has not been studied.

Methods

A total of 575 patients with gout were stratified according to certainty of diagnosis according to International Classification of Diseases, 9th Revision, Clinical Modification code alone (cohort I), American College of Radiology criteria (cohort II), and crystal diagnosis (cohort III). Comorbid conditions were defined according to International Classification of Diseases, 9th Revision, Clinical Modification codes, and stratified as either moderate or severe. Drug contraindications were defined as moderate or strong, based on Food and Drug Administration criteria and severity of disease.

Results

The most common comorbidity was hypertension (prevalence 0.89). The presence of comorbidities resulted in a high frequency of contraindications to approved gout medications. More than 90% of patients had at least 1 contraindication to nonsteroidal anti-inflammatory drugs. Many patients demonstrated multiple contraindications to 1 or more gout medications. Frequently, patients were prescribed medications to which they harbored contraindications. The prevalence of patients prescribed colchicine despite having at least 1 strong contraindication was 30% (cohort I), 37% (cohort II), and 39.6% (cohort III).

Conclusion

Patients with gout typically harbor multiple comorbidities that result in contraindications to many of the medications available to treat gout. Frequently, despite contraindications to gout therapies, patients are frequently prescribed these medications.     

The Role of Uric Acid and Other Crystals in Osteoarthritis

Clinicians have long assumed that an association exists between crystal arthropathies and the presence of osteoarthritis (OA). However, studies establishing an independent association between calcium pyrophosphate or uric acid crystal disease and OA are sparse. Even less is known about a possible pathogenic relationship. Whereas some studies suggest that the relationships between crystals and OA may not be incidental and that crystal deposition may contribute to the onset and/or acceleration of OA joint damage, other authors have challenged this assertion. In this review, we provide an overview of past and current research elucidating the role of crystal deposition, including monosodium urate, calcium pyrophosphate, and other crystals, in OA. Given the clinical frequency of gout and that agents exist to modulate serum UA levels, special attention is given to the role of monosodium urate crystals.     

Randomized clinical trial of suction versus standard clearance of the diathermy plume

BACKGROUND: Diathermy smoke contains complex hydrocarbons and organic material, and may contain viable tumour cells or viral particles. These particles measure from 0.05 to more than 25 microm, and long-term exposure to such particles may have adverse effects on health. This study investigated whether a suction clearance device reduces the amount of smoke reaching the surgeon's mask. METHODS: This was a randomized clinical trial in which subjects were randomized to standard diathermy equipment (group 1) or a diathermy smoke extraction system (group 2). All patients underwent thyroid or parathyroid surgery with standard anterior cervical collar incision and division of the strap muscles. The difference in the amount of smoke reaching the level of the operator's mask was measured by means of an aerosol monitor. RESULTS: Fifteen patients were randomized to each group. The mean amount of smoke detected at the level of the operator's mask was 0.137 mg/m(3) in group 1 and 0.012 mg/m(3) in group 2 (P < 0.001). The maximum amount detected was 2.411 and 0.255 mg/m(3) respectively (P < 0.001). There were no significant differences between the groups in terms of incision time or background particles measured before and after surgery. There was no correlation between gland weight and incision time or amount of smoke detected. CONCLUSION: Suction clearance of the diathermy plume resulted in a significant reduction in the amount of smoke reaching the level of the operator's mask. Although the risk of diathermy smoke inhalation is currently unknown, use of such a system appears advisable.     

Adenosine A(2A) receptors play a role in the pathogenesis of hepatic cirrhosis

1. Adenosine is a potent endogenous regulator of inflammation and tissue repair. Adenosine, which is released from injured and hypoxic tissue or in response to toxins and medications, may induce pulmonary fibrosis in mice, presumably via interaction with a specific adenosine receptor. We therefore determined whether adenosine and its receptors contribute to the pathogenesis of hepatic fibrosis. 2. As in other tissues and cell types, adenosine is released in vitro in response to the fibrogenic stimuli ethanol (40 mg dl(-1)) and methotrexate (100 nM). 3. Adenosine A(2A) receptors are expressed on rat and human hepatic stellate cell lines and adenosine A(2A) receptor occupancy promotes collagen production by these cells. Liver sections from mice treated with the hepatotoxins carbon tetrachloride (CCl(4)) (0.05 ml in oil, 50 : 50 v : v, subcutaneously) and thioacetamide (100 mg kg(-1) in PBS, intraperitoneally) released more adenosine than those from untreated mice when cultured ex vivo. 4. Adenosine A(2A) receptor-deficient, but not wild-type or A(3) receptor-deficient, mice are protected from development of hepatic fibrosis following CCl(4) or thioacetamide exposure. 5. Similarly, caffeine (50 mg kg(-1) day(-1), po), a nonselective adenosine receptor antagonist, and ZM241385 (25 mg kg(-1) bid), a more selective antagonist of the adenosine A(2A) receptor, diminished hepatic fibrosis in wild-type mice exposed to either CCl(4) or thioacetamide. 6. These results demonstrate that hepatic adenosine A(2A) receptors play an active role in the pathogenesis of hepatic fibrosis, and suggest a novel therapeutic target in the treatment and prevention of hepatic cirrhosis.