A micropuncture study of renal sodium retention in nephrotic syndrome in rats: evidence for increased resistance to tubular fluid flow

Micropuncture studies were carried out in surface nephrons of rats with nephrotoxic-serum (NTS)-induced nephrotic syndrome during a period of active sodium and water retention. It was found that hydrostatic pressure and tubular diameter were increased in the proximal tubules (13.4 +/- 0.2 vs. 10.4 +/- 0.2 mm Hg; 31.3 +/- 0.9 vs. 18.4 +/- 0.7 mu), whereas pressure and tubular diameter were normal in the distal tubules. Single nephron glomerular filtration rate (SNGFR) was decreased and fractional reabsorption of fluid was markedly increased in the proximal tubules (74.1 vs. 61.7%). The increased pressure gradient between the proximal and distal tubules suggests a condition of increased resistance to flow between the proximal and distal tubules. Microinfusion of proximal tubules with an isotonic "equilibrium" solution led to little or no rise in intratubular pressure in normal rats but it led to a significant rise in nephrotic rats. When proximal tubules of normal rats were infused with a solution containing 100 mg/100 ml albumin, pressure rose to levels observed in nephrotic rats. The mechanism of the increased resistance to flow appeared to be related, therfore, to the presence of protein in the tubular fluid. Sodium retention in the nephrotic animals might be attributed to the reduction in GFR. In other types of renal disease in animals and man with comparable or greater reductions in GFR, sodium retention does not occur, however, and fractional excretion of sodium in the urine is increased in proportion to the reduction in GFR. Thus, the rise in proximal fractional reabsorption secondary to impaired fluid flow could be an important factor in the sodium retention of this disease.     

小细胞肺癌多药耐药基因的检测及临床应用研究

目的：探讨多药耐药集团（MDR1）在小细胞肺癌化疗中的作用和地位，方法：采用逆转录－多聚酶链式反应技术（RT／PCR）和免疫细胞化学染色法，检测了32例（初治原发癌21例和复治转移癌11例）小细胞肺癌患者血液中的MDR1mRNA水平和多药耐药蛋白（P－170）的表达，并对两种方法进行了比较。结果：初治的原发癌MDR1基因阳性表达率为14．29％，P－170蛋白阳性表达为14．27％，复治转移癌的MDR1基因阳性表达率为72．73％，P－170蛋白阳性表达为63．64％（P＜0．01），有显著性差异。MDR1的基因和蛋白两种而检测方法具有一定的一致性，以RT／PTR方法具有更强的敏感性，结论：复治转移癌组比初治组具有更普遍的抗药性，且主要是获得性抗药，MDR1基因表达可作为临床合理地制定化疗方案，预测化疗效果的重要参考指标。     

Left ventricular assist device bridge therapy for acute myocardial infarction

BACKGROUND: Patients with acute myocardial infarction (AMI) complicated by cardiogenic shock have a high mortality rate. Current treatment modalities remain suboptimal for these patients. METHODS: From April 1995 to March 1998, 7 patients were identified as having AMI associated with cardiogenic shock. All received intraaortic balloon pump assistance, in addition to maximal inotropic support. RESULTS: The mean preoperative cardiac index was 2.0+/-0.3 L/min/m2 and pulmonary capillary wedge pressure was 23+/-6 mm Hg. Three patients received thrombolytic therapy and 4 patients underwent percutaneous transluminal coronary angioplasty without success. Left ventricular assist devices (LVADs) were implanted as bridge therapy to heart transplantation. One patient died from recurrence of a ventricular septal defect during LVAD support. Six patients were transplanted successfully after mean LVAD support of 59+/-33 days. Five patients are alive and well at a mean follow-up of 898+/-447 days. One patient died 3 days after transplantation from acute allograft dysfunction. CONCLUSIONS: Timely application of LVADs as bridge therapy to heart transplantation in these critically ill patients can be lifesaving, and should be investigated further.     

Effectiveness of Cardiac Resynchronization Therapy in Diabetic Patients with Ischemic and Nonischemic Cardiomyopathy

Background: Diabetes mellitus (DM) increases the risk for the development of both ischemic and nonischemic cardiomyopathy. We aimed to identify differences in response to cardiac resynchronization therapy with a defibrillator (CRT‐D) among DM patients with ischemic or nonischemic cardiomyopathy. Methods: Cox proportional hazards regression modeling was used to assess clinical response to CRT‐D (defined as CRT‐D vs. defibrillator‐only reduction in the risk of heart failure [HF] or death) and echocardiographic response (defined as percent reduction in left ventricular end diastolic and systolic volume [LVEDV and LVESV, respectively] at 12 month of follow‐up compared with baseline values) among 552 diabetic patients with ischemic (n = 367) or nonischemic (n = 185) cardiomyopathy enrolled in MADIT‐CRT. Results: The clinical benefit of CRT‐D was more pronounced among nonischemic patients (HR = 0.30 [P < 0.001] than among ischemic patients (HR = 0.59 [P = 0.004]; P for interaction = 0.10). Nonischemic patients also experienced significantly greater reductions in LVESV and LVEDV at 12 months with CRT‐D compared with ischemic patients (P < 0.001 for both). Subgroup analysis showed that the most pronounced reduction in HF or death with CRT‐D therapy occurred in nonischemic patients who were women (83% risk‐reduction [P < 0.001]), had a lower BMI (<30/kg/m²: 79% risk‐reduction [P < 0.001]), or had left bundle branch block at enrollment (82% risk‐reduction [P < 0.001]). Conclusions: The present study shows that treatment with CRT‐D in at‐risk cardiac patients with DM is associated with substantial reductions in the risk of HF or death and improvement in cardiac remodeling in those with ischemic and nonischemic cardiomyopathy, with a more pronounced benefit in patients with nonischemic disease. Ann Noninvasive Electrocardiol 2012;17(1):14–21     

Heavy Metal Concentrations in Two Populations of Mopane Worms (Imbrasia belina) in the Kruger National Park Pose a Potential Human Health Risk

Metal concentrations in Mopane worms from Phalaborwa and Shangoni sites in the Kruger National Park were determined. Metal concentrations were evaluated by inductively coupled plasma optical emission spectroscopy (ICP-OES) and ICP-MS spectrometry after microwave digestion. The results indicate a substantial bioaccumulation of metals in Mopane worms. In Phalaborwa Cd concentrations were 15 times and Cu two times higher than the EU and UK recommended legal limits for human consumption, Zn levels were tolerable. Likewise, Cd, Cu and Zn concentrations at the Shangoni site were 26, 2.5 and 0.4 times over the EU and UK approved limits. Manganese concentrations were 20 and 67 times higher than FDA standards respectively. During the study the condition factor of the worms was determined. No significant difference between the condition factors indicated the worms at both sites are in similar condition. Potential sources of metals in the worms are either from the food they eat or pollution settling on the leaves.     

T‐cell receptor profiling in cancer

Immunosequencing is a platform technology that allows the enumeration, specification and quantification of each and every B‐ and/or T‐cell in any biologic sample of interest. Thus, it provides an assessment of the level and distribution of all the clonal lymphocytes in any sample, and allows “tracking” of a single clone or multiple clones of interest over time or from tissue to tissue within a given patient. It is based on bias‐controlled multiplex PCR and high‐throughput sequencing, and it is highly accurate, standardized, and sensitive. In this review, we provide evidence that immunosequencing is becoming an important analytic tool for the emerging field of immune‐oncology, and describe several applications of this approach, including the assessment of residual disease post therapy in lymphoid malignancies, the prediction of response to immunotherapeutics of solid tumors containing tumor infiltrating lymphocytes, the identification of clonal responses in vaccination, infectious disease, bone marrow reconstitution, and autoimmunity, and the exploration of whether there are population‐based stereotyped responses to certain exposures or interventions.     

Fusobacterium necrophorum findings in Denmark from 2010 to 2014 using data from the Danish microbiology database

Fusobacterium necrophorum findings in Denmark and estimation of the incidence of F. necrophorum bacteraemia was described using data from the nationwide Danish microbiology database (MiBa). All microbiological reports on any Fusobacterium species in Denmark were extracted for a period of 5 years from 2010 to 2014 from MiBa and from the local department of clinical microbiology. The overall incidence of F. necrophorum bacteraemia from 2010 to 2014 was 2.8 cases per million/year vs 9.4 in the age group 15–24 years. F. necrophorum was rare in blood cultures from children and middle‐aged patients and then raised again. However, 48 of 232 cases of Fusobacterium bacteraemia were not identified to species level, so the incidences of F. necrophorum bacteraemia may be underestimated in our study. F. necrophorum was found in throat swabs in the age group between 13 and 40 years and in otitis media in children below 2 years in those departments which performed anaerobic culture. The incidence of F. necrophorum bacteraemia found was comparable to earlier reported figures for Lemierre's syndrome. Fusobacterium bacteraemia should always be identified to species level.     

A cost-effectiveness analysis of identifying Fusobacterium necrophorum in throat swabs followed by antibiotic treatment to reduce the incidence of Lemierre’s syndrome and peritonsillar abscesses

The main purpose of this paper was to estimate the cost per quality-adjusted life year (QALY) saved by identifying Fusobacterium necrophorum in throat swabs followed by proper antibiotic treatment, to reduce the incidence of Lemierre’s syndrome and peritonsillar abscesses (PTA) originating from a pharyngitis. The second purpose was to estimate the population size required to indicate that antibiotic treatment has an effect. Data from publications and our laboratory were collected. Monte Carlo simulation and one-way sensitivity analysis were used to analyse cost-effectiveness. The cost-effectiveness analysis shows that examining throat swabs from 15- to 24-year-olds for F. necrophorum followed by antibiotic treatment will probably be less costly than most other life-saving medical interventions, with a median cost of US$8,795 per QALY saved. To indicate a reduced incidence of Lemierre’s syndrome and PTA in Denmark, the intervention probably has to be followed for up to 5 years. Identifying F. necrophorum in throat swabs from 15- to 24-year-olds followed by proper antibiotic treatment only requires a reduction of 20–25 % in the incidence of Lemierre’s syndrome and PTA to be cost-effective. This study warrants further examination of the effect of antibiotic treatment on the outcome of F. necrophorum acute and recurrent pharyngitis, as well as the effect on Lemierre’s syndrome and PTA.