Chemokine gene expression in rat pancreatic acinar cells is an early event associated with acute pancreatitis

BACKGROUND & AIMS: The molecular mechanisms underlying pancreatitis are largely unknown. The goal of this study was to identify an early genetic event that correlated with pancreatitis. METHODS: Differential display of messenger RNAs (mRNAs) was conducted on normal pancreas vs. those of animals with secretagogue-induced pancreatitis. Northern blots from normal animals and animals with experimental acute pancreatitis were probed with cloned complementary DNAs for chemokines. Pancreatitis was induced with cerulein and by retrograde injection of bile salts. Immunocytochemistry was used to identify the source of chemokine expression. Pyrrolidine dithiocarbamate was tested for effects on chemokine expression and pancreatitis. RESULTS: A differentially amplified band was consistently observed early after cerulein hyperstimulation. This band was identified as a portion of the mob-1 gene, an alpha-chemokine. Northern analysis indicated that mRNAs for mob-1 and another chemokine, mcp-1, were induced after cerulein hyperstimulation in vivo. mob-1 mRNA was also induced by retrograde injection of bile salts and by cerulein in acinar cells in vitro. mob-1 protein was localized to exocrine cells in pancreata of diseased animals. Pyrrolidine dithiocarbamate inhibited both chemokine gene expression and early inflammatory characteristics of pancreatitis. CONCLUSIONS: Chemokines are induced in acinar cells by treatments that induce pancreatitis and may play an important role in the early stages of the disease.     

Overnight closed suction drainage after axillary lymphadenectomy for breast cancer

Axillary lymphadenectomy in breast conservation surgery is associated with substantial morbidity in either seroma formation or infection. Seroma formation in the axilla requiring aspiration occurs in up to 42 per cent of patients treated without drainage. Prolonged outpatient suction drainage reduces but does not eliminate the incidence of seroma formation, while increasing cost, discomfort, and possibly infection rates. We studied the efficacy of overnight closed suction drainage in patients undergoing breast conservation surgery. Fifty consecutive patients undergoing a standard axillary dissection for breast cancer were studied. The axilla was drained with a 7-French closed suction drain. All drains were removed within 23 hours of surgery and prior to discharge from the outpatient surgical center. Patients were examined by the operating surgeon 7 to 10 days after surgery. One patient (2%) experienced a seroma postoperatively. No infections were observed in all 50 patients, and the remaining 49 patients did not experience visible or symptomatic seromas. The number of lymph nodes removed ranged between 5 and 33 with a mean of 15.5 +/- 0.6. Nine out of 50 (18%) patients had metastatic breast cancer to the axillary lymph nodes. Patients undergoing breast conservation surgery benefit from overnight closed suction drainage of the axilla. This short-term method reduces the incidence and the inherent morbidity of axillary seroma formation.     

Modeling statistical dopant fluctuations in MOS transistors

The impact of statistical dopant fluctuations on the threshold voltage V_T and device performance of silicon MOSFET's is investigated by means of analytical and numerical modeling. A new analytical model describing dopant fluctuations in the active device area enables the derivation of the standard deviation, σV_T , of the threshold voltage distribution for arbitrary channel doping profiles. Using the MINIMOS device simulator to extend the analytical approach, it is found that σV_T, can be properly derived from two-dimensional (2-D) or three-dimensional (3-D) simulations using a relatively coarse simulation grid. Evaluating the threshold voltage shift arising from dopant fluctuations, on the other hand, calls for full 3-D simulations with a numerical grid that is sufficiently refined to represent the discrete nature of the dopant distribution. The average V_T-shift is found to be positive for long, narrow devices, and negative for short, wide devices. The fast 2-D MINIMOS modeling of dopant fluctuations enables an extensive statistical analysis of the intrinsic spreading in a large set of compact model parameters for state-of-the-art CMOS technology. It is predicted that V_T-variations due to dopant fluctuations become unacceptably large in CMOS generations of 0.18 μm and beyond when the present scaling scenarios are pursued. Parameter variations can be drastically reduced by using alternative device designs with ground-plane channel profiles     

Report from the XVII Congress of the European Society of Cardiology, Stockholm, Sweden, August 1997

Cardiac dysrhythmias in septic patients often reflect hypovolaemia, hypokalaemia or endocarditis as cardiac manifestation of the infection, but may be indicative for underlying cardiac pathology previously undiagnosed. We report on the case of a patient with severe peritonitis, on whom transoesophageal echocardiography (TEE) had been performed intraoperatively due to progressive circulatory instability. TEE revealed first diagnosis of asymmetric hypertrophic cardiomyopathy, which complicated the features of septic syndrome. Further perioperative treatment to support the circulation was successfully adjusted on the grounds of this diagnosis.     

Perceptual learning of spatial localization: specificity for orientation, position, and context

Discrimination of simple visual attributes can improve significantly with practice. We have trained human observers to perform peripherally presented tasks involving the localization of short line segments and examined the specificity of the learning for the visual location, orientation, and geometric arrangement of the trained stimulus. Several weeks of training resulted in dramatic threshold reductions. The learning was specific for the orientation and location of the trained stimulus, indicating the involvement of the earliest cortical stages in the visual pathway where the orientation and location of stimuli are mapped with highest resolution. Furthermore, improvement was also specific for both the configuration of the trained stimulus and the attribute of the stimulus that was under scrutiny during training. This degree of specificity suggests that the learning cannot be achieved by cortical recruitment alone, as proposed in current models, but is likely to involve a refinement of lateral interactions within the cortex and possibly a gating of lower level changes by attentional mechanisms.     

High-dose busulfan, melphalan, thiotepa and peripheral blood stem cell infusion for the treatment of metastatic breast cancer

The purpose of this study was to determine the outcome of patients with metastatic breast cancer treated with high-dose busulfan (Bu), melphalan (Mel) and thiotepa (TT) followed by peripheral blood stem cell (PBSC) infusion. Fifty-one patients with chemotherapy refractory (n = 32) or responsive (n = 19) metastatic breast cancer received Bu (12 mg/kg), Mel (100 mg/m2) and TT (500 mg/m2) followed by PBSC collected after chemotherapy and growth factor (n = 43) or growth factor alone (n = 8). The 100 day treatment-related mortality was 8% including one death from cytomegalovirus pneumonia, one from aspiration pneumonia and two from regimen-related toxicity (RRT). Seven of 28 refractory (25%) and 5/7 (71%) responsive patients with evaluable disease achieved a complete response of all measurable disease or all soft tissue disease with at least improvement in bone lesions (PR*). Fifteen of 51 patients (29%) are alive and progression-free a median of 423 days (range 353-934) after treatment, 5/32 (16%) with refractory disease and 10/19 (53%) with responsive disease. The probabilities of progression-free survival (PFS) at 1.5 years for the patients with refractory (n = 32) and responsive (n = 19) disease were 0.24 and 0.53, respectively. These preliminary data suggest that high-dose Bu/Mel/TT has significant activity in patients with advanced breast cancer and may be superior to some previously published regimens.     

Far-infrared pump-probe measurement of the lifetime of the 2p−1 shallow donor level in n-GaAs

The low temperature lifetime of electrons excited in the 2p^?1 donor level of n-GaAs has been studied in a far-infrared pump-probe experiment. The measurement has been carried out using a pulsed far-infrared molecular gas laser working at a wavelength of 292µm, with the sample in a magnetic field of 5.1 T, resonant with the 1s_o?2p^?1 transition. Two FIR pulses are sliced from one FIR-laser pulse by means of optical switching techniques using two Q-switched Nd:YAG lasers. The first pulse is used to saturate the transition, while the second pulse probes the return of the population in the excited state towards thermal equilibrium as a function of the time delay after the excitation pulse. The value of 350±50 ns found for the lifetime falls in line with CW saturation results on materials with other doping concentrations.