Clinical measurement of swallowing in health and in neurogenic dysphagia

We studied clinical features potentially related to dysphagia and three indices from a timed test of swallowing--average volume per swallow (ml), average time (s) per swallow and swallowing capacity (ml/s)--in 181 screened healthy adults and 30 patients with motor neurone disease (MND). In healthy adults, age, sex and height accounted for 44.3% and 55.6% of the variance of log average volume per swallow and log swallowing capacity, respectively. Symptoms and signs were more prevalent in the MND group and were associated with reduced swallowing capacity and reduced average volume per swallow; repeatability studies on these two indices in both groups showed that the median difference between the mean of two recordings on successive days and the mean of all recordings (6-15 over 3 days) was < 5% (maximum third quartile 12.8%, indices expressed as percent predicted according to age and sex). Using this simple bedside test, swallowing function can be quantified on a ratio scale and expressed as percent of that predicted by age and sex; such information may improve the predictive value of clinical assessment and provides a practical way of monitoring change in patients with dysphagia.      

A randomized, controlled trial of intravenous clodronate in patients with metastatic bone disease and pain

To evaluate the effectiveness of intravenous clodronate in ameliorating refractory bone pain in patients with metastatic bone disease, 60 patients with established osseous metastases and persistent bone pain were randomized to receive either clodronate (600 mg or 1500 mg in 500 mL of normal saline) or 500 mL of saline as placebo. After 2 weeks, the patients were crossed over to receive the alternate treatment. After another 2 weeks, each patient and investigator made a blinded choice. Daily visual analogue scales (VAS) and analgesic diaries were recorded throughout the study period. Forty-six patients were evaluable (77%). A treatment × period interaction was identified in the VAS and daily morphine equivalent dose (DATED) scores. First period analysis of the VAS scores for general pain, pain at rest, and pain upon movement demonstrated an average reduction of 13, 14, and 24 mm, respectively, from baseline, but were not significantly different from changes following placebo. The average change in DMED was −6 .4 (SE = 2.9) following clodronate and was +24.6 (SE = 14.9) following placebo (p = 0.03). In the blinded choice of which agent resulted in improvement in pain, 26 (57%) patients chose clodronate, 12 (26%) chose placebo, and eight (17%) had no preference (p = 0. 0021). For the investigators who also made a blinded selection, clodronate was chosen in 30 (65%) patients, placebo in ten (22%) patients, and no difference was apparent in six (13%) (p < 0.0001). Intravenous clodronate appeared to have analgesic effect in patients with refractory bone pain due to metastatic bone disease. The optimal dose and duration of effect require further evaluation, particularly in patients with stable disease and persistent bone pain.     

Significance of diastolic pulmonary artery pressure peaks

We describe a patient undergoing elective surgery for treatment of an abdominal aortic aneurysm in whom an abrupt change in the contour of the pulmonary artery pressure (PAP) trace indicated the development of an intermediate (20 mm Hg) V wave in the pulmonary artery wedge pressure (PAWP) trace. As the PAP trace is displayed continuously, attention to its contour may allow for early detection of changes to the underlying PAWP trace.FC Anaesth     

Kidney transplants in mice. An analysis of the immune status of mice bearing long-term, H-2 incompatible transplants

Kidney transplants between strains of mice which are incompatible at either the K or the D end of the H-2 complex usually function for prolonged periods supporting the lives of nephrectomized recipients. This occurs with no recipient treatment. With multiple H-2 and non-H-2 determined incompatibilities, transplants may be rejected but more slowly than skin grafts. In the strain combination studied most extensively in these experiments (B10.D2 to B6AF(1)) in which the incompatibility was confined to the K end of the H-2 region, about 70 percent of recipients survived for many weeks with normal blood urea nitrogen levels. Skin grafts between untreated members of these strains were rejected promptly (mean survival time of 13.5 +/- 1.1 days) as were kidney transplants to recipients of prior skin grafts. Donor strain skin grafts to recipients of kidney transplants after kidney transplantation enjoyed greatly prolonged survival whereas skin grafts from a third party (A.SW) were rejected normally. If kidney tissue was transferred in the form of free grafts without primary vascular union, it was rejected promptly leaving its recipient highly immunized. Cellular and humoral immunity to donor antigens declined over the first few weeks after transplantation, and the spleens of long-term recipients contained no “killer cells.” Recipient lymphoid cells could mount active graft versus host reactions to donor strain antigens on transfer to neonatal mice. Nevertheless, they were distinctly less able to respond specifically by the production of killer cells to donor strain antigens after sensitization in vitro. No evidence that this defect was associated with the presence of suppressor cells was forthcoming from several types of in vivo and in vitro tests.     

An update on the emergence of glycopeptide resistance in enterococci

Glycopeptide resistance may be either constitutive or transferable (on plasmids or as a transposon), and four phenotypes (van A, B, C, D) have been described to date. Recent data suggest solid media screening protocols appear to be insensitive at detecting low levels of carriage, and up to 40% of colonized patients may be falsely glycopeptide-resistant enterococci (GRE) negative. Managing GRE-colonized or -infected patients using contact precautions appears to be useful in controlling clonal outbreaks, but may be of limited utility once GRE is endemic. Alternate strategies to manage GRE-colonized patients with prolonged carriage and in outpatient or home health settings include using risk-based transmission assessment to limit the logistic and psychosocial difficulties associated with the use of continuous contact precautions. The therapeutic options for treating GRE infection remain limited. Attempts to decolonize GRE-colonized patients with bacitracin appear to be of limited utility.     

Omeprazole produces parietal cell hypertrophy and hyperplasia in humans

While there is evidence that omeprazole may induce changes in parietal cells, the effect of acid suppression on parietal cells in humans is poorly documented. This study was undertaken to evaluate the effects of omeprazole in human parietal cells over time. The light microscopic morphology of parietal cells in gastric biopsies from 17 patients on omeprazole were compared with those from 13 patients on ranitidine and 20 patients on no acid-lowering medication. Light microscopic and ultrastructural morphology of parietal cells was also evaluated in an additional 14 patients before and after omeprazole administration. Objective measurements of parietal cell height, mass and number were analyzed using analyses of variance. Electron microscopy was used to evaluate parietal cell enlargement. Twenty-five of 31 biopsies from patients on omeprazole, 1 of 13 from patients on ranitidine, and 0 of 20 from patients on neither drug showed parietal cell enlargement. Parietal cell height, mass, and number were increased in omeprazole-treated patients compared with ranitidine-treated patients and those on neither drug, and with the group also evaluated prior to beginning omeprazole treatment. Parietal cell height and mass were increased in patients on omeprazole longer than 12 months compared with biopsies from patients on the drug for less than 12 months. Resin-embedded sections and electron microscopy showed enlarged parietal cells with prominence of cytoplasmic tubulovesicles with sparse secretory canaliculi. Parietal cell hypertrophy and hyperplasia develops in patients on chronic omeprazole therapy; this can be recognized on routine examination of histologic sections. These morphologic changes increase with duration of therapy.     

Autoantibodies against bactericidal/permeability-increasing protein in patients with cystic fibrosis

Cystic fibrosis (CF), a genetic disorder, is characterized by chronic pulmonary infection/inflammation which leads to respiratory failure. The presence of anti-neutrophil cytoplasmic autoantibodies (ANCA) has previously been observed in the sera of patients with CF. In view of the known relationship of ANCA with primary vasculitis and of their putative pathogenetic role in these disorders, we studied the presence, specificity and isotype of ANCA and their clinical associations in 66 adult CF patients. None of the 66 CF samples had autoantibodies to the major ANCA antigens, proteinase 3 or myeloperoxidase. However, 60/66 (91%) CF samples contained IgG and 55/66 (83%) IgA, autoantibodies to bactericidal/permeability increasing protein (BPI), a recently characterized ANCA specificity. All the IgA anti-BPI-positive samples were also IgG anti-BPI-positive. The autoantibody specificity was confirmed by inhibition assay and immunoblotting of CF sera against a neutrophil granule preparation. Furthermore, in this cross-sectional study, anti-BPI levels were inversely correlated with the observed reductions in FEV1 and FVC (IgA anti-BPI and FEV1: r = 0.508, <it>p</it> &lt; 0.0001), and both IgG and IgA anti-BPI levels were higher in CF patients with secondary vasculitis (<it>n</it> = 6) than in those without (<it>p</it> &lt; 0.05). ANCA with specificity for BPI were present in the majority of CF sera in this study and autoimmune processes may be associated with the development of pulmonary injury in CF.