Oesophagus in progressive systemic sclerosis: A clinical,radiological and manometric evaluation

Ten patients with progressive systemic sclerosis underwent clinical, radiological and manometric evaluation for oesophageal dysfunction. Seven had typical dermatological features of this disease. Eight had symptoms of gastroesophageal reflux. Barium oesophagogram showed sluggish or absent peristalsis with delayed emptying of barium in six. Motility disturbances noted on barium oesophagogram were confirmed by oesophageal manometry which proved to be the most sensitive test in diagnosis of progessive systemic sclerosis.     

Basal thumb arthritis

Basal thumb arthritis is a common condition seen in hand clinics across the United Kingdom and is often associated with other pathological conditions such as carpal tunnel syndrome and scaphotrapezial arthritis. Typically, patients complain of pain localised to the base of the thumb. This pain is often activity related, particularly after excessive use involving forceful pinch. A detailed history and examination is normally all that is needed to make the diagnosis. Provocative manoeuvres may be helpful in localising symptoms to the basal joint with degenerative changes or synovitis. Radiographs are useful for confirming the diagnosis and staging the disease in order to plan for surgery. The mainstay of initial treatment of basal thumb arthritis of any stage is activity modifications, rest, nonsteroidal anti-inflammatory drugs, exercises and splinting. A variety of surgical procedures are available to treat the condition when conservative measures have failed, in order to control symptoms and improve function. We review the current literature and discuss the clinical aspects of this condition, staging, and treatment options available, and the difficulties treating this group of patients.     

Hemodynamic characteristics of midazolam, propofol, and dexmedetomidine in healthy volunteers

Study Objective

To study the effect of intravenous (IV) sedation on blood pressure (BP), heart rate (HR), and respiratory rates (RR) to determine if IV sedatives differ with respect to their effect on BP, HR, and RR.

Design

Prospective, randomized, single-blinded, placebo-controlled study.

Setting

Monitored patient care room at a clinical research center.

Subjects

60 healthy ASA physical status 1 volunteers.

Interventions

Subjects were randomized to receive, in increasing doses, one of three IV sedatives: propofol, midazolam, or dexmedetomidine; or saline control.

Measurements

Blood pressure (systolic, diastolic), HR, and RR were recorded.

Main Results

A significant dose-dependent BP reduction occurred with dexmedetomidine and, to a lesser degree, with propofol; and there was good agreement of predicted versus measured drug concentrations for all sedatives. Blood pressure and HR of participants who received midazolam did not change.

Conclusions

When administered in sedative doses, dexmedetomidine and, to a lesser extent, midazolam, reduces BP in a dose-dependent fashion. Dexmedetomidine also reduces HR. Midazolam does not affect BP or HR.     

Intramural Metastatic Squamous Cell Carcinoma of Stomach

Intramural metastasis to the stomach (IMMS) from carcinoma esophagus, excluding direct invasion and spread to the stomach, is relatively uncommon. Diagnosis of IMMS is based on histological criteria, and it is associated with poor prognosis (Takubo et al. Cancer 65:1816–1819, 1990]. We report two patients of SCC oesophagus in whom intramural metastasis to stomach has occurred.     

Tumour gene expression predicts response to cetuximab in patients with KRAS wild-type metastatic colorectal cancer

Background:

Although it is accepted that metastatic colorectal cancers (mCRCs) that carry activating mutations in KRAS are unresponsive to anti-epidermal growth factor receptor (EGFR) monoclonal antibodies, a significant fraction of KRAS wild-type (wt) mCRCs are also unresponsive to anti-EGFR therapy. Genes encoding EGFR ligands amphiregulin (AREG) and epiregulin (EREG) are promising gene expression-based markers but have not been incorporated into a test to dichotomise KRAS wt mCRC patients with respect to sensitivity to anti-EGFR treatment.

Methods:

We used RT–PCR to test 110 candidate gene expression markers in primary tumours from 144 KRAS wt mCRC patients who received monotherapy with the anti-EGFR antibody cetuximab. Results were correlated with multiple clinical endpoints: disease control, objective response, and progression-free survival (PFS).

Results:

Expression of many of the tested candidate genes, including EREG and AREG, strongly associate with all clinical endpoints. Using multivariate analysis with two-layer five-fold cross-validation, we constructed a four-gene predictive classifier. Strikingly, patients below the classifier cutpoint had PFS and disease control rates similar to those of patients with KRAS mutant mCRC.

Conclusion:

Gene expression appears to identify KRAS wt mCRC patients who receive little benefit from cetuximab. It will be important to test this model in an independent validation study.