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.     

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.     

Inhalation toxicity of 1,6-hexanediamine dihydrochloride in F344/N rats and B6C3F1 mice

1,6-Hexanediamine (HDA) is a high production volume chemical which is used as an intermediate in the synthesis of paints, resins, inks, and textiles and as a corrosion inhibitor in lubricants. Two- and 13-week studies of the toxicity of the dihydrochloride salt of HDA (HDDC) were conducted in male and female Fischer 344/N rats and B6C3F1 mice using whole-body inhalation exposure. Both species were evaluated for histopathologic and reproductive effects, and rats were examined for clinical chemistry and hematologic changes. In the 2-week inhalation studies, animals were exposed to 10-800 mg HDDC/m3, 6 hr per day. All rats, all female mice, and two of five male mice in the high-exposure group died before the end of the study. Surviving mice in this group had a dose-dependent depression in body weight gain. Clinical signs were primarily related to upper respiratory tract irritation and included dyspnea and nasal discharge in both species. Treatment-related histopathologic lesions included inflammation and necrosis of the laryngeal epithelium of both species and the tracheal epithelium of mice, as well as focal inflammation and ulceration of the respiratory and olfactory nasal mucosa. In the 13-week inhalation studies, animals were exposed to HDDC at concentrations of 1.6-160 mg/m3 for 6 hr per day, 5 days per week. In addition to the base study groups, a supplemental group of rats at each exposure level was included to assess the effect of HDDC on reproduction. No treatment-related changes in organ weights or organ-to-body-weight ratios occurred in rats, and no treatment-related clinical signs or gross lesions were seen in either species. Chemical-related microscopic lesions were limited to the upper respiratory tract (larynx and nasal passages) in the two highest exposure groups and were similar in both species. These lesions included minimal to mild focal erosion, ulceration, inflammation, and hyperplasia of the laryngeal epithelium, in addition to degeneration of the olfactory and respiratory nasal epithelium. HDDC caused no significant changes in sperm morphology or vaginal cytology and no significant adverse effects on reproduction in rats or mice. Hematologic and clinical chemistry changes in rats were minor and sporadic and were not accompanied by related histologic findings. HDDC did not increase the frequency of micronucleated erythrocytes in mice.(ABSTRACT TRUNCATED AT 400 WORDS)     

Head scatter modelling for irregular field shaping and beam intensity modulation

Scattered radiation from within the treatment head can contribute significant dose to all parts of a radiotherapy treatment field. A multileaf collimator may be used to create an arbitrarily shaped field, and may also be used, under dynamic control, to modulate the beam intensity over the field. This method of intensity modulation is effectively a superposition of a large number of fields which have the same beam direction, but different shapes, and some of these shapes may have unusually small dimensions, particularly in the direction of the leaf movement. Two models for predicting the head scatter under these conditions have been investigated. These are a first-order Compton scatter approximation from the flattening filter, and an empirical fit to measured data using an exponential function. The first model only considers scatter from the flattening filter and has been applied to field sizes between 2 cm by 2 cm and 10 cm by 10 cm, where agreements are all within 1%. However it is not satisfactory at larger field sizes where small scatter contributions, from scattering sources other than the flattening filter, are integrated over large areas. The second model uses measured data between 4 cm by 4 cm and 30 cm by 30 cm to optimize the exponential function and is used to calculate the head scatter contribution for all field sizes. In this case good agreement is achieved over the full field size range, and hence this is a more generally applicable model. Results are presented for static irregularly shaped fields and intensity modulated beams created using a Philips multileaf collimator.