Systemic hematologic effects of PEG-rHuMGDF-induced megakaryocyte hyperplasia in mice

PEG-rHuMGDF injected daily in normal mice causes a rapid dose-dependent increase in megakaryocytes and platelets. At the same time that platelet numbers are increased, the mean platelet volume (MPV) and platelet distribution width (PDW) can be either decreased, normal, or increased depending on the dose and time after administration. Thus, PEG-rHuMGDF at a low dose causes decreases in MPV and PDW, MGDF at an intermediate dose causes an initial increase followed by a decrease in MPV and PDW, and PEG-rHuMGDF at higher doses causes an increase in MPV and PDW followed by a gradual normalization of these platelet indices. In addition to the expected thrombocytosis after 7 to 10 days of daily injection of high doses of PEG-rHuMGDF, a transient decrease in peripheral red blood cell numbers and hemoglobin is noted accompanied in the bone marrow by megakaryocytic hyperplasia, myeloid hyperplasia, erythroid and lymphoid hypoplasia, and deposition of a fine network of reticulin fibers. Splenomegaly, an increase in splenic megakaryocytes, and extramedullary hematopoiesis accompany the hematologic changes in the peripheral blood and marrow to complete a spectrum of pathologic features similar to those reported in patients with myelofibrosis and megakaryocyte hyperplasia. However, all the PEG-rHuMGDF-initiated hematopathology including the increase in marrow reticulin is completely and rapidly reversible upon the cessation of administration of PEG-rHuMGDF. Thus, transient hyperplastic proliferation of megakaryocytes does not cause irreversible tissue injury. Furthermore, PEG-rHuMGDF completely ameliorates carboplatin-induced thrombocytopenia at a low-dose that does not cause the hematopathology associated with myelofibrosis.     

Colorectal cancer extracellular acidosis decreases immune cell killing and is partially ameliorated by pH-modulating agents that modify tumor cell cytokine profiles

Tumor cells upregulate myriad proteins that are important for pH regulation, resulting in the acidification of the extracellular tumor microenvironment (TME). Abnormal pH is known to dampen immune function, resulting in a worsened anti-tumor immune response. Understanding how extrinsic alterations in pH modulate the interactions between immune cells and tumors cells will help elucidate opportunities for new therapeutic approaches. We observed that pH impacts the function of immune cells, both natural killer (NK) and T cells, which is relevant in the context of a highly acidic TME. Decreased NK and T cell activity was correlated with decreasing pH in a co-culture immune cell-mediated tumor cell-killing assay. The addition of pH-modulating drugs cariporide, lansoprazole, and acetazolamide to the co-culture assay was able to partially mitigate this dampened immune cell function. Treatment of colorectal cancer (CRC) cells with NHE1 inhibitor cariporide increased CRC cell-secreted cytokines involved in immune cell recruitment and activation and decreased cytokines involved in epithelial-mesenchymal transition (EMT). Cariporide treatment also decreased CRC cell shed TRAIL-R2, TRAIL-R3, and PD-L1 which is relevant in the context of immunotherapy. These experiments can help inform future investigations into how the pH of the tumor microenvironment may be extrinsically modulated to improve anti-tumor immune response in solid tumors such as colorectal cancer.     

Simultaneous measurement of gallbladder emptying with cholescintigraphy and US during infusion of physiologic doses of cholecystokinin: a comparison

Both ultrasonography (US) and cholescintigraphy are used to study gallbladder dynamics. The present study was undertaken to determine whether the two methods provide the same or different information relating to gallbladder emptying. Emptying was simultaneously studied with both methods during infusion of graded physiologic doses of cholecystokinin (CCK) in six healthy subjects. Infusion of stepwise increasing doses of CCK, ranging from 0.03 to 0.5 Ivy dog units per kilogram of body weight per hour (IDU/kg.h), induced significant dose-related increases in plasma CCK, decreases in gallbladder volume assessed with US, and gallbladder emptying assessed with cholescintigraphy. The threshold dose for inducing significant gallbladder emptying was 0.13 IDU/kg.h, as determined with both techniques, indicating similar detection limits. There was a highly significant correlation between decreases in gallbladder volume and decreases in radioactive counts over the gallbladder region, with a tendency toward greater gallbladder responses at sonography during the early phase of gallbladder contraction and toward greater responses at cholescintigraphy during the later phase of gallbladder contraction. It is concluded that these methods can be used interchangeably for the quantitation of gallbladder emptying.     

Simultaneous combined use of flexible ureteroscopy and percutaneous nephrolithotomy to reduce the number of access tracts in the management of complex renal calculi

OBJECTIVE: To present early experience in managing complex renal calculi using a combined ureteroscopic and percutaneous approach, as complex and branched renal calculi often require multiple access tracts during percutaneous nephrolithotomy (PNL), and the combined use of flexible ureteroscopy and PNL has the potential to reduce the inherent morbidity of several tracts. PATIENTS AND METHODS: The study included seven patients (mean age 54 years) with multiple, branched, large-volume renal calculi suitable for management with PNL. Preoperative data, including patient demographics, stone location and stone surface area, were recorded. After informed consent, the patients underwent combined PNL and ureteroscopy in one session. Intraoperative data, including the location of PNL puncture sites, operative duration and complications, were analysed. Stone-free rates were determined by follow-up imaging at 3 months. RESULTS: All patients had either two or more stones in separate locations in the collecting system, or staghorn stones involving multiple calyces. The mean stone burden was 666 mm(2). All patients had only one percutaneous access tract. The mean operative duration was 142 min and the mean blood loss 79 mL. Two patients had small residual stones (< 3 mm), that required ureteroscopic intervention as they failed to pass spontaneously by 3 months after the initial combined procedure. The convalescence was similar to that in our current PNL practice; imaging showed that five of the patients were stone-free. CONCLUSIONS: Combined PNL and ureteroscopic management can effectively reduce the number of percutaneous access tracts which would otherwise be required for managing complex and branched renal calculi, as stones in an unfavourable location relative to the access tract can be relocated and fragmented within easy reach of the single nephrostomy tract. This manoeuvre reduces potential patient morbidity and blood loss but with no significant effect on stone-free rates and operative durations.     

Major motor atrophic patterns in the face and neck: CT evaluation

Cranial nerve deficits from various pathologic processes of the head and neck may result in characteristic patterns of denervation muscular atrophy. Such atrophic patterns may be clues to the location and extent of the lesion, particularly when cranial nerves are involved early in the course of the disease process. Thirty-six patients with computed tomographic (CT) evidence of muscular atrophy secondary to pathologic conditions involving the motor division of cranial nerves were examined. Five characteristic denervation muscular atrophy patterns seen on CT scans were identified. In several patients, identification of the muscular atrophy pattern was the only clue to the presence of a pathologic condition. Recognition of these atrophic patterns can prevent misinterpretation of their CT appearance and direct the CT examination to the course of the compromised cranial nerve from the brainstem to its peripheral innervation.     

Advanced imaging in stone management

PURPOSE OF REVIEW: Stone disease continues to plague humankind. Recent innovations in minimally invasive surgery, however, have decreased morbidity for the treatment of lithiasis, once only amenable to open surgical techniques. These advances in stone management have also been paralleled in the radiographic armamentarium. Herein, we describe the evolution of initial radiographic workup for urolithiasis, from abdominal radiograph to three-dimensional computed tomography and some of the novel applications thereof. RECENT FINDINGS: Previously, abdominal radiography was the only modality available for the visualization of calculi. Subsequently, the development of intravenous contrast aided in evaluating renal function, detecting the presence and location of obstruction, and in identifying filling defects. Most recently, prospective randomized trials have demonstrated improved sensitivity and specificity using noncontrast helical computed tomography rather than intravenous pyelogram with regard to the initial evaluation of acute flank pain. Further attempts to lower the overall radiation dose without compromising efficacy have also been introduced. Currently, the volume of calculus disease can be better quantified and somewhat qualified from three-dimensional computer software, thereby optimizing stone management. SUMMARY: Considerable progress has been made using minimally invasive techniques in the treatment of nephrolithiasis. Furthermore, advances in radiographic computer hard- and software applications allow for a rapid acquisition time and improved image quality without sacrificing diagnostic accuracy. In time, it is likely that the combination of these enhanced imaging modalities will lead to an improvement in stone localization, fragmentation and stone-free rates.     

脐部给药的多塞平栓研制及应用

目的：研制透皮制剂多塞平栓,考察其治疗各型急、慢性荨麻疹的临床疗效。方法：多塞平以甘油明胶为质,氮酮为促透剂,制成栓剂,经脐部给药,观察５０个病例,与口服多塞平片作对照,观察临床疗效。结果：多塞平栓治疗各型急、慢性荨麻疹,总有效率为９４．０％,经统计学分析,Ｐ〈０．０５,差异具显著性。结论：本品制备工艺可行,疗效确切,用药剂量小,无副作用,具有进一步研究、开发的价值。