The causal pathway model and cerebral palsy

This article reviews possible prenatal, perinatal, and postnatal causes of cerebral palsy. The interactive effects of various causes are evaluated. Groups of intervention strategies are then presented based on the causal pathway model.     

Hymenoptera venom protease allergens

BACKGROUND: Recent studies have shown the presence of additional allergenic proteins in honeybee and paper wasp venoms. Both venoms contain serine protease enzymes. OBJECTIVE: We isolated and obtained complete sequences of honeybee and Mediterranean paper wasp venom proteases, both of which have significant IgE binding activity. The structures are compared with bumblebee venom protease. METHODS: Venom proteases were chromatographically isolated from venoms and partial amino acid sequences determined. RT-PCR and rapid amplification of cDNA ends methods were used to clone cDNA, and complete sequences were determined for honeybee and a paper wasp venom protease. RESULTS: The venom proteases are all serine proteases of the trypsin type. The honeybee protease contains a complement, embryonic sea urchin protein, bone morphogenetic protein interaction domain as well as a linker and propeptide sequence, and a unique methionine residue near the active site. It has IgE binding activity. The paper wasp protease is a single trypsin domain and is an important allergen. The framework residues are poorly conserved among honeybee, bumblebee, and paper wasp enzymes. CONCLUSIONS: The 3 venom serine proteases have significant IgE binding activities. The structures are poorly conserved even among the Apidae , suggesting little cross-reactivity among the protein portions. The paper wasp venom proteases are important allergens.     

Cancer patients' expectations of experiencing treatment-related side effects: a University of Rochester Cancer Center--Community Clinical Oncology Program study of 938 patients from community practices

BACKGROUND: Adequate management of treatment-related side effects is important for patients and challenging for clinicians. Side effects generated by various treatments have been characterized reasonably well. However, to the authors' knowledge, less is known regarding what patients expect to experience regarding these side effects and how patient characteristics are related to these expectations. METHODS: Patients with cancer (n = 1015 patients) from 17 Community Clinical Oncology Program (CCOP) institutions affiliated with the University of Rochester Cancer Center CCOP Research Base were surveyed regarding their expectations of experiencing side effects associated with cancer treatment, with 938 patients providing evaluable data. Patients responded to the item, "Indicate your expectations of having this side effect" for 12 common side effects. Patients rated their expectations using a 5-point Likert scale, from 1 ("I definitely will not have this") to 5 ("I definitely will have this"). RESULTS: The median number of symptoms expected (characterized by any value other than one) was nine. The six most expected symptoms were fatigue, nausea, sleep disturbance, weight loss, hair loss, and skin problems. Patients age > 60 years expected to have fewer symptoms than younger patients; female patients expected more side effects than male patients; and patients who had some college education expected more side effects than patients who were high school graduates or had not completed high school. CONCLUSIONS: Patients with cancer clearly exhibit expectations regarding treatment-related side effects; and age, gender, and education level appear to influence these expectations. Further careful characterization of patient expectations and how expectations relate to experience may lead to earlier and more effective management of side effects.     

Severity of focal microgyria and associated rapid auditory processing deficits

Data from rodent models of induced microgyria suggest that bilateral damage leads to more severe rapid auditory processing deficits than unilateral damage. It is unclear whether this reflects the degree, or bilateral/unilateral nature, of damage. The current study evaluates the effects of microgyric severity by assessing rats with single- vs double-pair bilateral focal microgyric lesions, using auditory discrimination and MGN measures. Behavioral data show a significant auditory processing deficit on rapid processing tasks for microgyric as compared to control subjects, and also reveal more severe deficits for double- than for single-pair bilateral microgyrics. Greater disruptions are also seen in the MGN of double-pair compared to single-pair bilateral microgyric subjects.     

Antioxidants and oxidative stress in BAL fluid of atopic asthmatic children

Earlier studies in adults have indicated that increased oxidative stress may occur in the blood and airways of asthmatic subjects. Therefore the aim of this study was to compare the concentrations of antioxidants and protein carbonyls in bronchoalveolar lavage fluid of clinically stable atopic asthmatic children (AA, n = 78) with our recently published reference intervals for nonasthmatic children (C, n = 124). Additionally, lipid peroxidation products (malondialdehyde) in bronchoalveolar lavage fluid and several antioxidants in plasma were determined. Bronchoalveolar lavage concentrations (median and interquartile range) of ascorbate [AA: 0.433 (0.294-0.678) versus C: 0.418 (0.253-0.646) micromol/L], urate [AA: 0.585 (0.412-0.996) versus C: 0.511 (0.372-0.687) micromol/L], alpha-tocopherol [AA: 0.025 (0.014-0.031) versus C: 0.017 (0.017-0.260) micromol/L], and oxidized proteins as reflected by protein carbonyls [AA: 1.222 (0.970-1.635) versus C: 1.243 (0.813-1.685) nmol/mg protein] were similar in both groups (p > 0.05 in all cases). The concentration of protein carbonyls correlated significantly with the number of eosinophils, mast cells, and macrophages in AA children only. Concentrations of oxidized proteins and lipid peroxidation products (malondialdehyde) correlated significantly in AA children (r = 0.614, n = 11, p = 0.044). Serum concentrations of ascorbate, urate, retinol, alpha-tocopherol, beta-carotene, and lycopene were similar in both groups whereas alpha-carotene was significantly reduced in asthmatics. Overall, increased bronchoalveolar lavage eosinophils indicate ongoing airway inflammation, which may increase oxidatively modified proteins as reflected by increased protein carbonyl concentrations.     

Optimal management of septic shock. Rapid recognition and institution of therapy are crucial

Septic shock is a common problem in hospitalized patients. Optimal management depends on rapid recognition, aggressive restoration of circulating volume with fluid boluses, initiation of appropriate antibiotic therapy, implementation of adequate monitoring, and meticulous attention to the details of care. Mean arterial pressure should be increased to between 65 and 75 mm Hg as soon as possible to reduce the likelihood of multiorgan dysfunction. Despite these therapeutic maneuvers, however, mortality rates are likely to remain high until the development of therapies that better target the underlying mechanisms of sepsis.     

A phase I study of radiation therapy and twice-weekly gemcitabine and cisplatin in patients with locally advanced pancreatic cancer

PURPOSE: In vitro studies suggest that low-dose gemcitabine sensitizes cells to radiation therapy and that this effect persists for 48 h after drug exposure. Cisplatin is a radiation sensitizer and is also synergistic with gemcitabine in some in vitro tumor systems. Gemcitabine's radiosensitizing properties can theoretically be exploited by twice-weekly administration. This study assessed toxicity in patients with pancreatic cancer treated with radiation therapy, gemcitabine, and cisplatin. METHODS AND MATERIALS: Patients with locally advanced pancreatic or gastric cancer were eligible. Gemcitabine and cisplatin were given twice weekly for 3 weeks during radiation therapy (50.4 Gy in 28 fractions). The starting dose of gemcitabine was 5 mg/m(2) i.v. The starting dose for cisplatin was 5 mg/m(2). Chemotherapy doses escalated every 3 to 6 patients according to a standard Phase I study design. RESULTS: Twenty-four evaluable patients, all with pancreatic cancer, were treated on this protocol. Grade 3 neutropenia occurred in 2 patients, Grade 3 thrombocytopenia occurred in 2, and Grade 4 lymphopenia occurred in 1. There was no clear relationship between chemotherapy dose and hematologic toxicity. The most common Grade 3-4 nonhematologic toxic responses were vomiting (7 patients) and nausea (7 patients). Dose-limiting toxicity consisting of Grade 4 nausea and vomiting occurred in 2 of 3 patients at dose Level 6 (gemcitabine 45 mg/m(2) i.v. and cisplatin 10 mg/m(2) i.v.). Six patients were treated at dose Level 5 (gemcitabine 30 mg/m(2) i.v. and cisplatin 10 mg/m(2) i.v.) without dose-limiting toxicity. CONCLUSION: Gemcitabine 30 mg/m(2) i.v. twice weekly and cisplatin 10 mg/m(2) i.v. twice weekly may be given concurrently with radiation therapy (50.4 Gy in 28 fractions) with acceptable toxicity.     

Effect of specialty and nationality on panel judgments of the appropriateness of coronary revascularization: a pilot study

BACKGROUND: Appropriateness criteria are frequently used to assess quality of care. However, assessing care in one country with criteria developed in another may be misleading. One approach to measuring care across countries would be to develop common standards using physicians from different countries and specialties. OBJECTIVE: To identify the degree to which appropriateness ratings for coronary revascularization developed by a multinational panel differ by panelist specialty and nationality. METHODS: A 13-member panel of cardiothoracic surgeons and cardiologists from the Netherlands, Spain, Sweden, Switzerland, and the United Kingdom was convened to rate the appropriateness of 842 indications for percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass graft surgery (CABG) on a 1 (extremely inappropriate) to 9 (extremely appropriate) scale. MEASURES: Mean appropriateness ratings by panelist specialty and nationality. RESULTS: Surgeons' mean ratings for PTCA indications ranged from 0.64 points lower than the corresponding ratings of the cardiologists for acute myocardial infarction indications to 1.22 points lower for chronic stable angina indications. Conversely, their ratings for bypass surgery indications ranged from 0.59 points higher for chronic stable angina indications to 0.69 points higher for unstable angina indications. Although Spanish panelists' ratings were significantly higher than the mean for 3 of the 4 clinical conditions treated by PTCA, their ratings were similar for bypass surgery indications. No specific patterns were observed in the ratings of the panelists from the other countries. CONCLUSIONS: These findings support the use of physicians from multiple specialties on appropriateness panels because they represent more divergent views than physicians from a single specialty. Finding no systematic difference in beliefs regarding the appropriateness of PTCA and CABG among physicians from different countries will require confirmation before multinational panels supplant single country panels in future studies.