Bispectral index in a 3-year old undergoing deep hypothermia and circulatory arrest

We report a 3-year-old girl who presented with Scimitar syndrome and underwent hypothermic circulatory arrest for correction of anomalous pulmonary veins and an atrial septal defect. In this case the Bispectral Index (BIS) correlated significantly with the gradual onset of hypothermia and circulatory arrest. However, BIS remained low during the rewarming phase of cardiopulmonary bypass, in spite of adequate pump flows and stable haemodynamics. We postulate that this significant lag in BIS during the rewarming phase of deep hypothermic circulatory arrest may represent neuronal bewilderment or perhaps stunning, and differs from previous studies that show significant increase in BIS during rewarming from mild hypothermia.     

Immune effects of escalating doses of granulocyte-macrophage colony-stimulating factor added to a fixed,low-dose,inpatient interleukin-2 regimen: a randomized phase I trial in patients with metastatic melanoma and renal cell carcinoma

Previous studies in cancer patients demonstrated that granulocyte-macrophage colony-stimulating factor (GM-CSF) upregulated the interleukin (IL)-2 receptor on T lymphocytes and monocytes suggesting that subsequently administered IL-2 would produce greater immune effects. The authors treated 21 patients with metastatic renal cell carcinoma and melanoma on a randomized phase I study to test this hypothesis. All 21 patients received a fixed dose of IL-2 (72,000 IU/kg every 8 hours for 5 days) administered intravenously as an inpatient. Patients were randomized to receive IL-2 alone or in combination with GM-CSF at a dose of 125 or 250 mcg/m /d (Sargramostim; Immunex Corporation, WA, U.S.A.) daily for 7 days by subcutaneous injection starting on day 1, the day before IL-2 treatment. The results from this study demonstrated that GM-CSF did not worsen the toxicities produced by IL-2 alone. Grade 3 confusion occurred in four patients, three who received IL-2 alone. No partial or complete tumor responses were seen. Assays of serum soluble IL-2 receptor (sIL2R) and neopterin, measures of T cell and monocyte activation, respectively, demonstrated a significant increase in sIL2R but not neopterin, 24 hours after the first dose of GM-CSF. In combination with IL-2, the higher dose of GM-CSF (250 mcg/m ) produced higher sIL2R levels on days 3 and 7 than the 125-mcg/m dose of GM-CSF or IL-2 alone. Although neopterin levels did not increase after 1 day of GM-CSF, the addition of IL-2 resulted in a significantly increased neopterin level on day 3 at the higher dose of GM-CSF. On day 7, neopterin levels in all three groups were similarly increased over baseline. Ten days after treatment, neopterin levels had returned to normal, but sIL2R levels remained markedly increased (12 fold) over baseline in the higher GM-CSF dose group. The authors conclude that 1) monocyte activation was not significantly enhanced by 1 day of GM-CSF treatment; 2) the 250-mcg/m GM-CSF dose plus IL-2 produced superior T cell activation compared with a lower dose of GM-CSF plus IL-2 or to IL-2 alone; and 3) the combination of GM-CSF and IL-2 was safe and tolerable but was not associated with any clinical responses.     

Improved remission induction rate with D-ZAPO but unimproved remission duration with addition of immunotherapy to chemotherapy in previously untreated children with ANLL

In 163 children with acute nonlymphocytic leukemia (ANLL), a D-ZAPO induction program consisting of daunomycin, 5-azacytidine, cytosine arabinoside, prednisone, and vincristine resulted in a remission rate of 71.8%. Immunologic therapy was employed during maintenance with the aim of prolonging remission and improving survival. The administration of immunotherapy consisting of a mixture of bacillus Calmette-Guérin (BCG) and allogeneic acute myelomonocytic leukemic cells injected intradermally on day 14 of each of the first three monthly cycles of 6-thioguanine for ten days, 5-azacytidine and cytosine arabinoside for four days, and vincristine for one day did not improve remission duration or survival compared to that due to chemotherapy alone. Important prognostic factors identified in this study included a remission induction rate significantly better for females than males (P = 0.04), for children between the ages of 5 and 10 years compared to those greater than this age group (P = 0.01), and a prolonged remission duration (P = 0.04), and survival (P < 0.01) for patients with initial white blood counts of <20 × 10⁹/liter.     

Thrombosis in Beh?et's disease: a retrospective survey from a single UK centre.

OBJECTIVE: To contribute to knowledge of vascular occlusion in Beh?et's disease (BD), prevalence and relative risk for thrombosis were ascertained retrospectively in a cohort of Caucasian patients with the disease. PATIENTS: The study included 73 BD patients (36 males, 37 females, mean age 45+/-11 yr) attending the Immunology/Rheumatology Department of Northwick Park Hospital. A group of 146 patients without BD, attending the same department, served as a control group. RESULTS: Thrombosis was more frequent in BD patients than in controls (23/73, 32% vs 7/146, 5%, P<0.001). This was accounted for by a higher prevalence of venous thrombosis in BD patients (18/73, 25% vs 4/146, 3%, P<0.001). Gender-adjusted data revealed an 11-fold risk of developing any thrombosis and a 14-fold risk of developing venous thrombosis in BD. After adjusting for differences in age at first symptoms, male BD patients showed a 6-fold higher risk of vein thrombosis. Males reported more often thrombophlebitis (13/36, 36% vs 0/0, P<0.001), folliculitis (8/36, 22% vs 1/37, 3%, P<0.01) and retinal vasculitis (13/36, 36%, vs 4/37, 11%, P=0.01) than females, in whom arthralgia prevailed (23/37, 62%, vs 12/36, 33%, P=0.01). CONCLUSION: In our population, BD confers a 14-fold risk of developing venous thrombosis. The risk is sixfold higher in male BD patients, who fare worse than females with regard to thrombophlebitis, folliculitis and retinal vasculitis.     

Psoriasis: is the impairment to a patient’s life cumulative?

Psoriasis is associated with significant physical and psychological burden affecting all facets of a patient’s life – relationships, social activities, work and emotional wellbeing. The cumulative effect of this disability may be self‐perpetuating social disconnection and failure to achieve a ‘full life potential’ in some patients. Health‐related quality of life studies have quantified the burden of psoriasis providing predominantly cross‐sectional data and point‐in‐time images of patients’ lives rather than assessing the possible cumulative disability over a patient’s lifetime. However, social and economic outcomes indicate there are likely negative impacts that accumulate over time. To capture the cumulative effect of psoriasis and its associated co‐morbidities and stigma over a patient’s life course, we propose the concept of ‘Cumulative Life Course Impairment’ (CLCI). CLCI results from an interaction between (A) the burden of stigmatization, and physical and psychological co‐morbidities and (B) coping strategies and external factors. Several key aspects of the CLCI concept are supported by data similar to that used in health‐related quality of life assessments. Future research should focus on (i) establishing key components of CLCI and determining the mechanisms of impairment through longitudinal or retrospective case–control studies, and (ii) assessing factors that put patients at increased risk of developing CLCI. In the future, this concept may lead to a better understanding of the overall impact of psoriasis, help identify more vulnerable patients, and facilitate more appropriate treatment decisions or earlier referrals. To our knowledge, this is a first attempt to apply and develop concepts from ‘Life Course Epidemiology’ to psoriasis research.     

Cyclophosphamide induces more chromosome damage than chlorambucil in patients with connective tissue diseases

The potential for damaging chromosomes of the powerful and widely-used immunosuppressive agent cyclophosphamide has been tested by measuring sister chromatid exchanges in blood lymphocytes of patients with connective tissue diseases. This agent induces more chromosome damage than chlorambucil emphasising the need for sensitive means of predicting patients at particular risk of drug-induced malignant disease.     

Musculoskeletal neoplasms after intraarterial chemotherapy: correlation of MR images with pathologic specimens

The most accurate prognostic indicator in patients with musculoskeletal sarcomas is the percentage of tumor necrosis after intraarterial chemotherapy. Magnetic resonance (MR) imaging was evaluated to determine its ability to indicate the percentage of necrosis in musculoskeletal neoplasms after treatment. Fourteen patients with musculoskeletal neoplasms underwent treatment protocols including intraarterial chemotherapy (n = 14), radiation therapy (n = 6), and systemic chemotherapy (n = 14). All patients underwent MR imaging before and after treatment, and all underwent either limb salvage surgery (n = 8) or amputation (n = 6) within 1 week of the last MR examination. Standard unehanced spin-echo T1-, spin-density-, and T2-weighted MR sequences were used. The MR images were compared with the pathologic specimens. On T2-weighted images, the signal intensities of viable tumor, tumor necrosis, edema, hemorrhage, and necrosis overlapped. With the unenhanced spin-echo technique, MR imaging cannot be used to predict the percentage of tumor necrosis in musculoskeletal neoplasms after intraarterial chemotherapy.     

A review of pruritus

This article reviews the neurophysiology of pruritus and presents evidence that itch is a separate modality from pain, rather than a submodality of pain. The numerous suggested pruritogens are reviewed, and evidence supporting each one is critically examined. The systemic causes of generalized pruritus are reviewed, with detailed review of the literature on uremic pruritus, cholestatic pruritus, and the pruritus associated with polycythemia vera. The specific treatments used for each of these conditions are reviewed, as well as the use of antihistamines in generalized pruritus. An approach to the workup of a patient with pruritus is suggested.     

Percutaneous drainage of chest abscesses in children

Seven patients ranging in age from 3 to 18 years underwent percutaneous drainage of eight intrathoracic abscesses. Five of the abscesses were mediastinal or paramediastinal and resulted from esophageal perforation or esophageal anastomotic leakage. The abscesses resolved in each case, with a mean catheter drainage time of 28 days and no need for surgical intervention. Three of the abscesses were intrapulmonary, and each lay adjacent to a pleural surface. All three lung abscesses resolved within 19-24 days, without thoracotomy or wedge resection.     

Minimal spinal hyperostosis with low-dose isotretinoin therapy

Skeletal abnormalities have been reported on numerous occasions in patients who have received high doses of vitamin A and its derivatives. Recently, a new derivative, isotretinoin (Accutane, Hoffman-LaRoche, Inc.), has become available for the treatment of cystic acne. Ninety-six patients treated for a minimum of four months with low doses of this drug at two University centers have shown overall good to excellent clinical responses. However, ten of these patients have developed small pointed excrescences on the anterior margins of cervical, thoracic, or lumbar vertebral bodies. The findings are of unknown clinical significance but show some similarities to the spinal findings in DISH syndrome. Follow-up studies will be obtained, but, at the present time, the drug still can be recommended for patients who have severe cystic acne because of the excellent clinical response.