Peripheral Blood Lymphocyte Surface Antigen Expression and Prognosis in Myeloma: Australian Leukaemia Study Group Study

The Australian Leukaemia Study Group myeloma study (MM1) aimed to determine the prognostic significance of clinical and immunophenotypic markers in patients with multiple myeloma. All patients were treated with standard dose melphalan and prednisone. Seventy-four patients were entered and the median survival was 27 months. Serum beta 2-microglobulin (βM) and albumin levels were the only significant clinical factors influencing survival (p = 0.007 and p = 0.008, respectively). Patients with raised levels of CD38+ lymphocytes at presentation had a significantly shorter survival than patients with normal levels (p = 0.01, logrank test, median 19 months vs 33 months). CD38 antigen expression was independent of β2M but patients with raised levels of CD38 had significantly lower levels of albumin than patients with normal levels (p = 0.001) which may explain their poorer survival. Salmon and Durie stage was not associated with antigen expression. No other B-cell antigens (CD10, CD19, CD20, CD21, CD22, CD23, FMC1 or FMC7) or plasma cell antigens tested (PCA-1) were found to be associated with prognosis. Patients who achieved plateau phase had a better prognosis than those who did not (p = 0.04 in a landmark analysis). Patients who achieved plateau phase following an objective response appeared to have a better prognosis than those who were in plateau phase at presentation (p = 0.09 in a landmark analysis). Light chain isotype suppression (LCIS) was not associated with a significant survival advantage and did not correlate with any known prognostic indicator. We conclude that phenotypic analysis of peripheral blood lymphocytes for CD38 antigen at diagnosis may be useful as a prognostic indicator in patients with myeloma.     

Neuropsychological efficiency measures in male and female alcoholics.

The role of time in performance on many neuropsychological tests has been relatively neglected in the literature to date. Neuropsychological functioning in 90 male and female alcoholics and 65 peer controls was examined using both accuracy and time measures for four basic types of neuropsychological functioning: verbal skills, learning and memory, problem-solving and abstracting, and perceptual-motor skills. Alcoholics had significantly lower efficiency ratios (accuracy/time) than controls in each of the four areas, and had significantly lower overall accuracy and time scores. There were no significant Group x Gender interactions for efficiency, speed or accuracy scores, indicating that male and female alcoholics have similar deficits as a result of chronic alcoholism. The study is the first to apply systematically an empirical measure of neuropsychological efficiency to different areas of cognitive function; the results have implications for neuropsychological testing procedures.     

Natural history of colonization with vancomycin-resistant enterococci, methicillin-resistant Staphylococcus aureus, and resistant gram-negative bacilli among long-term-care facility residents.

OBJECTIVE: To determine the natural history of colonization with vancomycin-resistant enterococci (VRE), methicillin-resistant Staphylococcus aureus (MRSA), and resistant gram-negative bacilli among long-term-care facility (LTCF) residents. DESIGN: Observational cohort study. SETTING: A 355-bed LTCF with a ventilator unit and a subacute unit. PARTICIPANTS: Residents with colonization or infection with VRE, MRSA, or resistant gram-negative bacilli housed at the LTCF between December 1, 1999, and February 29, 2000. METHODS: Cultures of clinical and surveillance sites were performed at regular intervals. Charts were reviewed for clinical characteristics associated with clearance of colonization. Kaplan-Meier curves were constructed to analyze the number of days to clearance of colonization. RESULTS: Forty-nine residents had 65 episodes of colonization (27 VRE, 30 MRSA, and 8 resistant gram-negative bacilli). Eighteen (28%) of the episodes cleared. The clearance rate was 2.7 episodes per 1,000 person-days. Clearance occurred significantly more often with resistant gram-negative bacilli colonization compared with VRE or MRSA colonization (6 [75%] vs 12 [21%]; P = .007; relative risk, 4.17; 95% confidence interval, 1.26 to 11.8). There was a trend toward longer use of antimicrobial agents among residents with persistent colonization. Infections occurred most frequently with MRSA. The urinary tract was the most common site of infection. CONCLUSION: Among LTCF residents, colonization with resistant gram-negative bacilli is four times more likely to clear than colonization with VRE or MRSA. Performance of surveillance cultures at regular intervals may reduce the need for contact precautions for LTCF residents with resistant gram-negative bacilli colonization.     

Optic chiasm glioma associated with inappropriate secretion of antidiuretic hormone,cerebral ischemia,nonobstructive hydrocephalus and chronic ascites following ventriculoperitoneal shunting

An optic chiasm glioma may cause loss of vision, endocrine disturbances, hydrocephalus and cerebral ischemia due to its proximity to the pituitary, hypothalamus, III ventricle and internal carotids. A 3-month-old infant with optic chiasm glioma developed hypopituitarism and inappropriate secretion of antidiuretic hormone with plasma hypo-osmolality. The cerebrospinal fluid (CSF) protein concentration was markedly elevated. The impairment of fluid absorption via arachnoid villi and peritoneum by the high protein content, and reversed osmotic gradient between protein-rich CSF and hypo-osmolar plasma may have contributed to both nonobstructive hydrocephalus and recurrent ascites following ventriculoperitoneal shunting. Cerebral ischemia from carotid compression may have led to cerebral atrophy.     

Impact of Shorter-acting Neuromuscular Blocking Agents on Fast-track Recovery of the Cardiac Surgical Patient

Background: Residual paralysis associated with the use of long-acting muscle relaxants can delay recovery from anesthesia and surgery. The authors tested the hypothesis that use of shorter-acting neuromuscular blocking agents is associated with reductions in tracheal extubation times and intensive care unit (ICU) length of stay in patients undergoing cardiac surgery with cardiopulmonary bypass.

Methods: One hundred ten patients scheduled for elective coronary artery bypass grafting or single valve surgery were randomized prospectively to receive either pancuronium or rocuronium intraoperatively. Anesthetic management and muscle relaxant maintenance dosing were standardized. In the ICU, the time required to wean ventilatory support, the duration of tracheal intubation, and length of stay were recorded. Subjects were asked to quantify generalized muscle weakness as they awakened in the ICU and again after tracheal extubation.

Results: Complete data were collected on 51 patients in the pancuronium group and 52 patients in the rocuronium group. No differences were found between the groups in anesthetic, surgical, or ICU management. Significant increases in the duration of weaning of ventilatory support were observed in patients who received pancuronium (median, 180 min; range, 50-780 min) compared with the rocuronium group (median, 110 min; range, 45-250 min). Tracheal extubation was significantly delayed in the pancuronium group (median, 500 min; range, 240-1,305 min) compared with the rocuronium group (median, 350 min; range, 210-1,140 min). Subjects in the pancuronium group experienced more mild to severe weakness in the ICU. However, the choice of muscle relaxant did not influence ICU length of stay.     

Photodynamic therapy inhibits transforming growth factor β activity associated with vascular smooth muscle cell injury

Purpose: The multifunctional cytokine, transforming growth factor β1 (TGF-β), plays an important role in the development of injury-associated intimal hyperplasia (IH). Strategies to suppress local TGF-β activity may have a clinical potential to prevent restenosis caused by IH. Photodynamic therapy (PDT) involves the local generation of cytotoxic free radicals by light activation of photosensitizer dyes and has been shown to inhibit experimental IH. This study investigated whether PDT-generated free radicals can affect TGF-β activity in a biologic system using vascular smooth muscle cells (SMCs).Methods: The release and activation of TGF-β by injured SMCs in culture was compared between mechanical injury and PDT. Mechanical injury was induced with a rubber policeman, and PDT was performed with the photosensitizer chloroaluminum sulfonated phthalocyanine (5 μg/ml) and 675 nm laser light at subtherapeutic 10 J/cm² and the in vivo therapeutic dose of 100 J/cm². Cell viability was assessed by the tetrazolium salt conversion assay, and active and total (active + latent) TGF-β was determined by enzyme-linked immunosorbent assay in the conditioned media of SMCs 24 hours after treatment. Functional TGF-β activity was assessed by inhibition of endothelial cell mitogenesis.Results: Both forms of injury severely reduced (p < 0.0005) SMC viability to less than 15%. In untreated SMC conditioned media, only 14.5% of the total TGF-β was active (27.7 ± 8.7 pg per 1 × 10⁵ cells). However, after mechanical injury and PDT with 10 J/cm², there was a significant increase (p < 0.02) in active TGF-β (60.1 ± 10.1 pg and 48.6 ± 21.0 pg, respectively), despite a total reduction of approximately 50%. In contrast to this result, PDT with 100 J/cm² did not result in increased levels of active TGF-β (8.1 ± 3.5 pg), despite having similar levels of total TGF-β. Consequently, the conditioned media of SMCs that had 100 J/cm² PDT did not inhibit endothelial cell mitogenesis as compared with the conditioned media of SMCs with mechanical injury and 10 J/cm² PDT (p < 0.0002).Conclusions: This report describes two novel findings: (1) injury to SMCs in vitro induces the conversion of biologically latent TGF-β to active TGF-β; and (2) the therapeutic PDT dose interferes with this injury activation process. This study substantiates the concept of local cytokine inhibition by PDT in a biologic system and provides new insights into the mechanisms of PDT-mediated inhibition of experimental IH. (J Vasc Surg 1997;25:1033-43.)