The effect of absolute lymphocyte count recovery kinetics on survival after autologous stem cell transplantation for non-Hodgkin's lymphoma

Absolute lymphocyte count (ALC) >or=500 cells/microl at day 15 after autologous stem cell transplantation (ASCT) is a powerful independent, prognostic indicator for survival in multiple hematological malignancies. A limitation in these studies was the selection of a single time point (day 15 post-ASCT) as the only discriminator of clinical outcome in relation to ALC recovery. We hypothesized there is a continuous and not discrete relationship between ALC recovery and clinical outcome post-ASCT in NHL. Therefore, we analyzed 274 consecutive patients who underwent ASCT for NHL between 1987 and 2001. The primary end point was to assess the impact of the kinetics of post-ASCT lymphocyte recovery>or=500 cells/microl (K-ALC) on overall survival (OS) and progression-free survival (PFS). K-ALC was a predictor of OS and PFS when the Cox proportional hazards model was used with K-ALC entered as a continuous variable (p<0.0001). Multivariate analysis demonstrated K-ALC recovery post-ASCT to be an independent prognostic indicator for OS and PFS. These data support our hypothesis that the K-ALC post-ASCT is associated with clinical outcome in NHL.     

Amyloidosis: diagnosis and management

Amyloidosis is a rare plasma cell proliferative disorder. The annual incidence in Olmsted County, Minnesota, is 8 in 1,000,000 patients. This is a difficult disorder to diagnose, because the symptoms at presentation are vague and include dyspnea, paresthesias, edema, weight loss, and fatigue. The clinical syndromes at the time of presentation include nephrotic-range proteinuria with or without renal failure, cardiomyopathy, "atypical multiple myeloma," hepatomegaly, and autonomic or peripheral neuropathy. The serum immunoglobulin free light chain assay has been an important step forward in classifying systemic amyloidosis as an immunoglobulin light chain form and in monitoring therapy. Recently, the importance of serum cardiac biomarkers in assessing outcome has been recognized. New therapies developed over the past 5 years include high-dose chemotherapy with stem cell reconstitution, combinations of alkylating agents with dexamethasone, and, most recently, thalidomide.     

Myeloablative chemotherapy and stem cell transplantation in myeloma or primary amyloidosis with renal involvement

BACKGROUND: High-dose chemotherapy and stem cell transplantation are being applied increasingly to the treatment of selected patients with multiple myeloma or primary systemic amyloidosis. Stem cell transplantation presents unique challenges to the nephrologist because of the high prevalence of renal involvement in myeloma and the issues that are associated with high-dose chemotherapy in patients with the nephrotic syndrome due to renal amyloid. METHODS: We review the published literature on stem cell transplantation in patients with reduced renal function. RESULTS AND CONCLUSIONS: The specifics of transplantation pertaining to patients with renal amyloid nephrotic syndrome are discussed in detail.     

Right ventricular pressure-volume loops using simultaneous radionuclide angiography with a multiwire gamma camera and right heart catheterization

BACKGROUND: The purpose of this study was to generate right ventricular (RV) pressure-volume loops (PVLs) from time-activity curves obtained by first-pass radionuclide angiography (RNA) and RV pressures obtained by right heart catheterization. METHODS AND RESULTS: Short-lived tantalum 178 was used to obtain first-pass RNA at baseline (n = 31), after nitroglycerin (n = 5), or after the conclusion of cardiac catheterization (n = 13). From the radionuclide-derived RV ejection fraction and thermodilution stroke volume, the RV end-diastolic volume and end-systolic volume were measured. Special proprietary software was developed and used to integrate the pressure and the RNA data. The mean heart rate was 80 +/- 17 beats/min; RV ejection fraction, 39% +/- 12%; RV end-diastolic volume, 217 +/- 79 mL; RV end-systolic volume, 142 +/- 74 mL; and RV end-diastolic pressure, 10 +/- 7 mm Hg. The RV PVLs were of high quality and reproducible. CONCLUSIONS: This study provides proof of concept of the feasibility of generating RV PVL; the short half-life (10 minutes) and low energy (59 keV) of Ta-178 allow the generation of multiple loops at low radiation exposure. Such studies could be performed at the bedside and provide a wealth of information that may have clinical and research merits.     

Assessment of left ventricular function during upright treadmill exercise with tantalum 178 and multiwire gamma camera

BACKGROUND: Prior studies with first-pass radionuclide angiography (RNA) during treadmill exercise used a single-crystal (Anger) or multicrystal gamma camera and technetium 99m tracers. Motion correction, when done, used point sources, which limited correction to only plane movement. METHODS AND RESULTS: We examined the performance of a multiwire gamma camera (MWGC), generator-produced tantalum 178, and a novel method of motion correction during treadmill exercise testing. We studied 100 patients in whom rest and stress gated tomographic myocardial perfusion images were obtained. Eight patients were excluded because of incomplete data. There were 53 men and 39 women aged 52 +/- 12 years. The resting left ventricular (LV) ejection fraction (EF) was 61% +/- 12% by gated single photon emission computed tomography. Stress myocardial perfusion was normal in 83 patients and abnormal in 9 patients. The resting RNA EF in the upright position was 57% +/- 12% (r = 0.52, P = .0001 vs gated EF). At peak exercise, the EF by MWGC was 60% +/- 26% if uncorrected and 69% +/- 13% after motion correction. Among the 80 patients with normal perfusion and normal resting EF by gated single photon emission computed tomography, a normal response to exercise was seen in 52 (63%) without motion correction and 74 (89%) with motion correction (P < .05). CONCLUSION: Assessment of LV function is feasible with MWGC. The motion-corrected images significantly improved the results.     

Is Minimal Access Surgery for Cancer Associated with Immunologic Benefits?

Minimal-access surgical techniques have been shown to be beneficial to patients in terms of shorter convalescence, reduced pain, and improved cosmesis. Although systemic immune function is better preserved following laparoscopic procedures when compared with their respective open approaches, CO₂ pneumoperitoneum may significantly affect local (i.e., infra-abdominal) cellular immunity by reducing regional macrophage function. Results to date are conflicting with regard to the impact of closed and open methods on intraabdominal immunity. Impaired cellular immunity after CO₂ pneumoperitoneum may have significant undesirable intra-abdominal effects on tumor surveillance after oncological surgery; however, at present, there is no clinical evidence to support this position. The VATS techniques avoid the use of CO₂ insufflation, which may offer some advantages from the immune function perspective over laparoscopic procedures accomplished with CO₂ pneumoperitoneum. Better preservation of early postoperative cellular immune function and attenuated disturbance in the inflammatory mediators are likely contributing factors to the clinical benefits that follow laparoscopic surgery and VATS. Larger multi-center randomized trials are needed to confirm the potential benefits of minimal-access surgery on patient survival after cancer surgery. Future research should focus on the effects of minimal-access surgery on other mediators (such as MMP-9, IGFBP-3, IL-12, IL-17, and IL-23) that may be important in tumor cell dissemination, deposition, and propagation in the early postoperative period. Furthermore, additional searches for other factors or mediators, heretofore unrecognized, should be carried out. Such studies will, we hope, increase our knowledge and understanding of the impact of surgery on immune and other physiologic functions.     

Differential time course of glucagon's effect on glycogenolysis and gluconeogenesis in the conscious dog

The evanescence of glucagon's effect on glucose production (GP) is well documented, but it is unclear (1) whether this response involves both glycogenolysis and gluconeogenesis and (2) whether the liver becomes dependent on the increased glucagon level for the maintenance of a basal supply of glucose. To answer these questions, conscious overnight-fasted dogs were given somatostatin (0.8 microgram/kg . min) plus basal intraportal replacement amounts of insulin (273 microU/kg . min) and glucagon (0.65 ng/kg . min) for 2 h, after which the rate of glucagon infusion was increased fourfold for 3 h and then returned to basal for 1.5 h. GP was determined using a primed infusion of [3-3H]glucose, and gluconeogenesis (GNG) was estimated by determining the conversion rate of alanine and lactate to glucose. An increase in the plasma glucagon level from 55 to 206 pg/ml resulted in an initial 180% increase in GP, followed by a decline such that after 3 h of hyperglucagonemia GP was increased by only 41%. Contrary to overall GP, gluconeogenesis increased progressively throughout the hyperglucagonemic period, eventually reaching a rate 3 times basal. Restoration of the basal glucagon level (63 pg/ml) caused a marked decline in GP and GNG. In fact, GP fell to a level 29% below the initial control rate and consequently the plasma glucose level fell rapidly. The data suggest that (1) the downregulation of glucagon-stimulated GP is attributable to a decline in glycogenolysis and not gluconeogenesis, and (2) following adaptation to the hormone, the liver becomes dependent on the elevated glucagon concentration for the maintenance of basal glucose production.     

Coronary Atherosclerosis in Valvular Heart Disease

To evaluate the usefulness of routine coronary arteriography in patients undergoing cardiac catheterization for the evaluation of valvular heart disease, we performed coronary arteriographic studies routinely in a series of 201 patients primarily catheterized for such evaluation. Coronary artery obstructive lesions in excess of 50% of the lumen were present in 45 of the 201 patients. In 18 of the 45 there was no history of chest pain. Three of the 18 had three vessels involved while 2 had two vessels involved. A total of 27 patients (13.4%) had luminal obstruction greater than 70%, and 9 of these had no pain. In 35 of the 201 patients, classic angina pectoris existed in the absence of radiographically significant disease.Severe coronary disease was found to coexist with hemodynamically severe valvular heart disease and was not predictable noninvasively.     

Spontaneous retropharyngeal and cervical emphysema: a rare singer's injury

Spontaneous retropharyngeal and cervical emphysema is rare. We describe a case that was unusual in its etiology: the result of singing. Although this condition is usually benign, hospital admission for close observation and supportive therapy is prudent.