Surgeons' assessment of symptoms suggesting extrathoracic metastases in patients with lung cancer. Canadian Lung Oncology Group.

BACKGROUND: In patients with apparently operable non-small cell lung cancer (NSCLC), clinicians often omit investigation for M disease in asymptomatic patients. Previous investigations have not specified in detail what is meant by "symptomatic," and this could differ between surgeons. We have investigated the extent to which surgeons' criteria differ for presence of symptoms. METHODS: Participating surgeons from seven centers, enrolled patients they judged "asymptomatic" in a randomized trial of investigational strategies for NSCLC. Patients completed a structured questionnaire describing symptoms of the central nervous system (CNS). In 685 patients, we documented CNS symptom recurrence after resectional surgery over 1 year of follow-up. RESULTS: Two centers enrolled only patients without even the mildest symptoms. Three centers took an intermediate approach, occasionally classifying patients with mild symptoms as "asymptomatic" and thus enrolling them in the trial. Two centers classified an appreciable number of patients with minimal symptoms, and occasionally with more than minimal symptoms, as "asymptomatic." Patients with even mild CNS symptoms were more likely to subsequently present with CNS metastases. CONCLUSIONS: Thoracic surgeons differ in their ideas of what may constitute the symptoms of M disease. Patients with structured questionnaire results that suggest symptoms of CNS disease are more likely to have CNS symptom recurrence after resectional surgery.     

One-year study of spatial memory performance, brain morphology, and cholinergic markers after moderate controlled cortical impact in rats

Persistent cognitive deficits are one of the most important sequelae of head injury in humans. In an effort to model some of the structural and neuropharmacological changes that occur in chronic postinjury brains, we examined the longitudinal effects of moderate vertical controlled cortical impact (CCI) on place learning and memory using the Morris water maze (MWM) test, morphology, and vesicular acetylcholine (ACh) transporter (VAChT) and muscarinic receptor subtype 2 (M2) immunohistochemistry. Vertical CCI (left parietal cortex, 4 m/sec, 2.5 mm; n = 10) or craniotomy (sham) was produced in male Sprague-Dawley rats (n = 10). Place learning was tested at 2 weeks, 4 weeks, 3 months, 6 months, and 12 months postinjury with the escape platform in a different maze quadrant for each time point. At each interval, rats received 5 days of water maze acquisition (latency to find hidden platform), a probe trial to measure place memory, and 2 days of visible platform trials to control for nonspecific deficits. At 3 weeks, half the animals were sacrificed for histology. At these injury parameters, CCI produced no significant differences in place learning between injured and sham rats at 2 weeks, 4 weeks, or 6 months after injury. However, at 3 and 12 months, the injured rats took significantly longer to find the hidden platform than the sham rats. Probe trial performance differed only at 12 months postinjury between injured (25.73+/-2.1%, standard error of the mean) and sham rats (44.09+/-7.0%, p < 0.05). The maze deficits at 1 year were not due to a worsening of performance, but may have resulted from a reduced ability of injured rats to benefit from previous water maze experience. Hemispheric loss of 30.4+/-5.5 mm3 was seen at 3 weeks after injury (versus respective sham). However, hemispheric loss almost doubled by 1 year after injury (51.5+/-8.5 mm3, p < 0.05 versus all other groups). Progressive tissue loss was also reflected by a three- to fourfold increase in ipsilateral ventricular volume between 3 weeks and 1 year after injury. At 1 year after injury, immunostaining for VAChT was dramatically increased in all sectors of the hippocampus and cortex after injury. Muscarinic receptor subtype 2 (M2) immunoreactivity was dramatically decreased in the ipsilateral hippocampus. This suggests a compensatory response of cholinergic neurons to increase the efficiency of ACh neurotransmission. Moderate CCI in rats produces subtle MWM performance deficits accompanied by persistent alteration in M2 and VAChT immunohistochemistry and progressive tissue atrophy. The inability of injured rats to benefit from repeated exposures to the MWM may represent a deficit in procedural memory that is independent of changes in hippocampal cholinergic systems.     

Succeeding beyond the Year 2000: how to rise to the challenges of the new millennium. Interview by Jill L. Sherer.

Are you ready to take your organization into the 21st century? Do you fully grasp the implications of current and emerging trends in the field? Healthcare Executive talked with six healthcare experts and asked them what they saw as the greatest challenge for both executives and their organizations in the new millennium. Although the experts' opinions vary, their responses emphasize the importance of repairing old relationships and building new partnerships between those working in healthcare organizations, as well as bringing a consumer focus back to healthcare delivery.     

C-antineutrophil cytoplasmic antibody positivity in vasculitis patients is associated with the Z allele of alpha-1-antitrypsin, and P-antineutrophil cytoplasmic antibody positivity with the S allele

BACKGROUND.: Antineutrophil cytoplasmic antibodies (ANCA) in vasculitis haveeither cANCA or pANCA patterns as defined by immunofluorescence.The target autoantigen of cANCA is usually proteinase 3 (PR3),whereas that of pANCA is usually myeloperoxidase (MPO). Alpha-1-antitrypsin(1AT) is the major physiological inhibitor of PR3, while MPOis an inhibitor of 1AT. METHODS.: To determine whether there was an association between ANCA positivevasculitis, ANCA pattern, and 1AT deficiency alleles, we studied1AT phenotypes of 99 cANCA and 99 pANCA positive vasculitispatients by isoelectric focusing and immunoblotting, and comparedthem with 2310 controls from the same geographical area. RESULTS.: C-ANCA patients showed an increased frequency of the Z allele(0.055 versus 0.018 in controls), conferring a relative riskof 3. They showed no increase in frequency of the S allele.P-ANCA patients showed an increased frequency of the S allele(0.091 versus 0.046 in controls) conferring a relative riskof 2. The frequency of the Z allele also appeared to be increased(0.030 versus 0.018 in controls), but this was not statisticallysignificant. CONCLUSIONS.: These findings demonstrate an association between ANCA-positivevasculitis and deficiency phenotypes of 1AT, and suggest a rolefor 1AT in the development of systemic vasculitis.     

Does histologic acute rejection in lung allografts predict the development of bronchiolitis obliterans?

Clinical acute lung rejection (AR) occurs in lung allografts usually within 50 days after transplantation. While perivascular infiltrates characterize AR, with moderate-to-severe acute rejection small airway injury occurs. We investigated the significance of small airway injury in AR and its relationship to the development of bronchiolitis obliterans (OB) in 11 recipients of combined heart-lung or double-lung allografts. In general, the intensity and persistence of early acute rejection episodes associated with injury to bronchioles correlated with the development of histologic bronchiolitis obliterans. Early AR may "prime" lymphocytes for subsequent respiratory epithelial injury and airway fibrosis late in the postoperative period.     

Early tPA treatment and aeromedical transport of patients with acute myocardial infarction

Over a 2-year period 192 patients with acute myocardial infarction (AMI) were transported by helicopter and treated with recombinant tissue-plasminogen activator (tPA). All patients were entered into the Thrombolysis in Myocardial Infarction-Phase II (TIMI II) trial. Eighty-two of these patients were treated with tPA after aeromedical transport to a tertiary care center. One hundred ten patients had tPA treatment initiated by the flight crew prior to transport. The flight crews initiated therapy 28 +/- 11 minutes after arrival at the sending hospital. The post-flight treated patients received the tPA bolus 82 +/- 20 minutes after arrival at the sending hospital (P less than .0001), and 41 +/- 18 minutes after arrival at the receiving hospital (P less than .0001). Based on enzyme and electrocardiographic changes, all patients in the study had a confirmed diagnosis of AMI before discharge. Patients with inferior myocardial infarction (MI) treated with tPA in-flight were more likely to suffer from bradycardia and hypotension requiring atropine injection during transport than the post-flight treated patients or in-flight treated patients with anterior MI. There was no in-flight mortality in either group. Our experience indicates that patients with AMI can be transported safely during tPA therapy. Also, a trained team whose sole responsibility is the early evaluation and initiation of therapy in a patient with AMI can function as accurately and significantly more rapidly than tertiary care emergency department and ICU personnel following identical protocols.     

Ultrapure plasma factor VIII produced by anti-FVIIIc immunoaffinity chromatography and solvent/detergent viral inactivation. Characterization of the Method M process and Hemofil M antihemophilic factor (human)

Conclusions The Method M process was developed to reduce the risk of virus transmission associated with the therapeutic use of AHF products. The Method M process uses a powerful viral inactivation approach and consistently results in a high-purity F VIII preparation. The extent to which F VIII is purified in the Method M process is important in considering the reduction in virus. Protein contaminants such as fibrinogen and fibronectin in the final product provide easily measurable parameters of process efficiency in terms of contaminant reduction. However, it is essential to note that protein contaminant levels in the final product are meaningful only when the steps in the purification process are understood. Precipitation steps and/or ion-exchange steps that reduce protein contamination do not necessarily reflect virus reduction. With the exception of F VIII RAg, which appears to associate specifically with monoclonal-antibody-bound F VIII, all other protein and reagent contaminants are consistently reduced during the immunoaffinity step of the Method M process. Given the extent of viral inactivation that occurs during TNBP/detergent treatment and the extent of contaminant reduction that takes place during the immunoaffinity step, Hemofil M AHF is considered to be substantially safe with respect to viral contamination.     

The prosthetic ureter

Ureteral replacement has always been a challenge. Two approaches have been explored: in situ augmentation or replacement and extra-anatomic passage of a conduit. An in-situ prosthetic ureter is basically a simple al. loplastic tube connected to the urinary tract by end-to-end sutures or by intubation and closure. Antireflux devices and peristaltic mechanisms are not necessary. Among the in-situ designs, only those composed of silicone and silicone rubber have performed at all well. Tissue engineering and acellular matrix grafts have produced impressive early results. Subcutaneous ureteral replacement with alloplasts, including a coaxial assembly of an inner silicone and outer expanded polytetrafluoroethylene tube, has produced good results. In the future, we are likely to see bioengineered neotissue combined with highly porous and infection-resistant alloplasts to create better and more functional neo-organs.     

Relationship of mammographic parenchymal patterns to breast cancer risk factors and smoking in Alaska Native women.

The purpose is to determine breast cancer risk factors and correlates of mammographic parenchymal patterns among Alaska Native women. A retrospective review was performed of mammograms and mammogram records among 528 sequential screening mammogram examinations performed in Anchorage, Alaska. Mammogram density was classified by American College of Radiology (Breast Imaging Reporting and Data System) density patterns 1-4 (fat-->dense) and by percent density. Clinical data, including risk factors, ethnic group (Indian, Aleut, or Eskimo), and smoking status were obtained. Results were analyzed by univariate and multivariate analyses. Of 528 women, 164 were Indian, 155 were Aleut, and 209 were Eskimo. Mean age at first birth was lower and parity higher compared with published data in white women. Breast cancer risk factors were similar across ethnic groups. In multivariate analysis, patient age, parity, hormone replacement therapy, hysterectomy, and history of biopsy were associated, and smoking was not associated with density scores. Aleut and Indian women were less likely to have high-density mammograms than were Eskimo women (P = 0.0448). No significant differences were found between ethnic group for conventional breast cancer risk factors. Mammogram density was associated with age at screening, parity, hormone replacement therapy, hysterectomy, history of biopsy, and ethnicity but not smoking status. Eskimo women had higher mammogram density than Aleuts or Indians.