Compliance with the recommendations of medical consultants

Compliance with the consultant’s recommendations is one measure of the effectiveness of a consultation. A previous study showed that compliance was better when fewer recommendations were made. In the subsequent year, consultants were encouraged to limit their recommendations to five or fewer. Despite a significant decrease in the number of recommendations, compliance rates remained essentially unchanged (72%). Multivariate analysis demonstrated that the clinical severity of the patient’s disease and the number of associated problems, as well as the types of recommendations, were significant predictors of compliance. Compliance was best for recommendations involving medications (84%) and worst for recommendations involving diagnostic tests (62%). Compliance was also evaluated in the context of a surgeon’s view of the appropriateness of the recommendations. For recommendations felt to be essential to patient care the compliance rate was 75%, but it was only 44% for recommendations judged non-essential (p<0.001). The consulting internist should be aware that the surgeon’s view of the relevance of the recommendations to patient care needs may have an important effect on compliance. Received from the Departments of Medicine and Surgery, Cornell University Medical College, New York, New York. Dr. Ballard was a Henry J. Kaiser Foundation Fellow in General Internal Medicine. Dr. Gold is a Fellow in Cardio-Thoracic Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts. Dr. Charlson is a Henry J. Kaiser Family Foundation Faculty Scholar in General Internal Medicine.     

Effect of particle size on hydroxyapatite crystal-induced tumor necrosis factor alpha secretion by macrophages

Macrophages may promote a vicious cycle of inflammation and calcification in the vessel wall by ingesting neointimal calcific deposits (predominantly hydroxyapatite) and secreting tumor necrosis factor (TNF)alpha, itself a vascular calcifying agent. Here we have investigated whether particle size affects the proinflammatory potential of hydroxyapatite crystals in vitro and whether the nuclear factor (NF)-kappaB pathway plays a role in the macrophage TNFalpha response. The particle size and nano-topography of nine different crystal preparations was analyzed by X-ray diffraction, Raman spectroscopy, scanning electron microscopy and gas sorbtion analysis. Macrophage TNFalpha secretion was inversely related to hydroxyapatite particle size (P=0.011, Spearman rank correlation test) and surface pore size (P=0.014). A necessary role for the NF-kappaB pathway was demonstrated by time-dependent I kappaB alpha degradation and sensitivity to inhibitors of I kappaB alpha degradation. To test whether smaller particles were intrinsically more bioactive, their mitogenic activity on fibroblast proliferation was examined. This showed close correlation between TNFalpha secretion and crystal-induced fibroblast proliferation (P=0.007). In conclusion, the ability of hydroxyapatite crystals to stimulate macrophage TNFalpha secretion depends on NF-kappaB activation and is inversely related to particle and pore size, with crystals of 1-2 microm diameter and pore size of 10-50 A the most bioactive. Microscopic calcific deposits in early stages of atherosclerosis may therefore pose a greater inflammatory risk to the plaque than macroscopically or radiologically visible deposits in more advanced lesions.     

Endorectal ultrasound and magnetic resonance imaging in rectal cancer staging

The majority of rectal cancers have local disease only at presentation, but despite meticulous surgery, a number of factors will influence outcome. Preoperative identification of adverse prognostic factors provides a rational basis for selecting preoperative therapy. Thin section MRI can influence preoperative therapeutic algorithms by T and N staging, demonstrating operability, and the potential risk of circumferential margin involvement. Endosonography may contribute to this, but has a greater role in determining intramural invasion for early tumors. The assessment of residual tumor after chemoradiotherapy remains difficult; PET scanning has been used in this situation [32], but has not been compared with MRI and is unlikely to show only residual cells with extensive fibrosis.     

Circulating immune complexes in Hodgkin's disease

Levels of circulating immune complexes (CIC) in the serum of patients with Hodgkin's disease were measured by the Raji cell radioimmunoassay. Elevated levels of immune complexes (mean value of 49 μg/ml ± 21 SE) were detected in 20 of 40 (50 per cent) untreated patients. After treatment, the level of CIC was normal (< 15 μg/ml) in 39 of 41 patients. Recurrent disease developed in two of the 39 patients with normal post-treatment levels of CIC and in one of the two patients with elevated post-treatment levels during the follow-up period of six months to six years. Elevated levels of CIC were detected in patients with Hodgkin's disease in stages I, II and III but not in stage IV. No significant correlations were found in the frequency of elevated levels of CIC or the values observed, and the presence or absence of symptoms (fever, sweats, weight loss) or the histologic subtype of the tumor. Our data indicate that the measurement of CIC by the sensitive and specific Raji cell assay may prove useful in the management of patients with Hodgkin's disease. In particular, serial measurement of the level of CIC could be employed to monitor the response to treatment and to detect recurrent diseases.     

Dexamethasone, paclitaxel, etoposide, cyclophosphamide (d-TEC) and G-CSF for stem cell mobilisation in multiple myeloma

Forty-one patients with multiple myeloma were treated with a novel stem cell mobilisation regimen. The primary end points were adequate stem cell mobilising ability (>1% circulating CD34-positive cells) and collection (> or = 4 x 10(6) CD34-positive cells/kg), and safety. The secondary end point was activity against myeloma. The regimen (d-TEC) consisted of dexamethasone, paclitaxel 200 mg/m(2) i.v., etoposide 60 mg/kg i.v., cyclophosphamide 3 g/m(2) i.v., and G-CSF 5-10 microg/kg/day i.v. A total of 84 cycles were administered to these 41 individuals. Patient characteristics included a median age of 53 years, a median of five prior chemotherapy cycles, and a median interval of 10 months from diagnosis of myeloma to first cycle of d-TEC. Seventy-five percent of the patients had stage II or III disease, 50% had received carmustine and/or melphalan previously, and 25% had received prior radiation therapy. Eighty-eight percent of patients mobilised adequately after the first cycle of d-TEC and 91% mobilized adequately after the second cycle. An adequate number of stem cells were collected in 32 patients. Of the remaining nine patients, three mobilised, but stem cells were not collected, two mobilised but stem cell collection was < 4 x 10(6) CD34-positive cells/kg, three did not mobilise, and one died of disease progression. Major toxicities included pancytopenia, alopecia, fever and stomatitis. One patient died from multi-organ failure and progressive disease. Fifty percent of evaluable patients demonstrated a partial response and 28.6% of patients had a minor response. This novel dose-intense regimen was safe, capable of stem cell mobilisation and collection, even in heavily pre-treated patients, and active against the underlying myeloma.     

Thalmic vaciuation in acute Wernicke's encephalopathy

Two patients with acute Wemicke's encephalopathy, with the diagnosis confirmed pathologically at autopsy, showed substantial vacuolation and neuronal degeneration in discrete nuclei of the thalamus. Thalamic vacuolation has not been described previously in acute Wernicke's encephalopathy. The use of frozen sections to minimize processing artifact was fundamental in demonstrating this pathology. The pathogenic mechanism underlying this change appears to be different to that seen in the more typical periventricular, mamillary body and brainstem lesions. We hypothesize that a specific neural pathway may be involved and suggest that this pathway could be the ascending nitric oxide-containing cholinergic pathway from the brainstem.