Improvements in the diagnostic approach for patients with suspected deep vein thrombosis or pulmonary embolism

Recent advances in the management of patients with suspected VTE have resulted in improvements in the diagnostic testing accuracy and the development of management algorithms that are safer and more accessible. Ongoing clinical trials are evaluating whether these diagnostic management strategies can be made even simpler and less expensive. Diagnostic procedures for VTE continue to be refined, and modalities, such as magnetic resonance imaging and spiral CT, have the potential to further increase the accuracy of the investigation approach. There is still need to improve management strategies for the diagnosis of recurrent venous thrombosis and to determine whether diagnostic testing results may be correlated with long-term patient treatment needs.     

Dementing Illnesses in Rural Populations: The Need for Research and Challenges Confronting Investigators

Expansion of the world's elderly populations has increased concerns about aging-related medical disorders like Alzheimer's disease and other dementias. In the United States, one fourth of those older than age 65 and at greatest risk for developing dementia live in rural environments that may influence its manifestation. The objectives of this study were to determine the need for and potential benefits of further epidemiological research concerning dementia and similar disorders in rural U.S. populations and to identify pertinent methodological issues related to rural dementia research. This study employed a National Library of Medicine (MEDLINE) document search based on the key words "cognitive disorders," "dementia," "Alzheimer's disease," and "rural," followed by recovery of literature resources references in the bibliographies of selected articles. Nineteen studies focusing on dementia or related disorders in rural settings have been reported from around the world. While four of these were conducted in the United States, only one rural dementia prevalence study has been undertaken in this country. Because of methodological variability, comparisons of prevalence estimates between these rural studies, as well as with those from urban investigations, is difficult. Nonetheless, there is reason to believe that certain potentially dementing illnesses are more common in rural populations. There is also evidence to suggest that the screening instruments commonly used in such studies tend to misclassify rural elders as "false positive" dementia cases. Information regarding dementing disorders, particularly Alzheimer's disease, in rural populations is scarce. Preliminary observations that dementia may be more common in rural settings and that rural families are more likely to maintain their dementing elders in the community imply that further rural dementia research could yield important insights into the risk factors for these illnesses, the variables influencing their course, and the methods by which they can be more effectively managed. A determination of the reliability and validity of commonly used dementia screening instruments in rural populations would represent an important advancement in this area of research.     

Factors influencing the emigration of physicians from Canada to the United States.

OBJECTIVE: To determine whether location of postgraduate medical training and other factors are associated with the emigration of physicians from Canada to the United States. DESIGN: Case-control study, physicians were surveyed with the use of a questionnaire mailed in May 1994 (with a reminder sent in September 1994), responses to which were accepted until Dec. 31, 1994. PARTICIPANTS: Physicians randomly selected from the CMA database, 4000 with addresses in Canada and 4000 with current addresses in the United States and previous addresses in Canada. OUTCOME MEASURES: Sex, age, location of undergraduate and postgraduate medical training, qualifications, practice location, opinions concerning residence decisions, current satisfaction and plans. RESULTS: The overall response rate was 49.6% (50.0% among physicians in the United States and 49.2% among those in Canada). Age and sex distributions were similar among the 8000 questionnaire recipients and the nearly 4000 respondents. Physicians living in the United States were more likely to be older (mean 53.2 v. 49.6 years of age), male (87% v. 75%) and specialists (79% v. 52%) than those practising in Canada. Postgraduate training in the United States was associated with subsequent emigration (odds ratio 9.2, 95% confidence interval 7.8 to 10.7). However, in rating the importance of nine factors in the decision to emigrate or remain in Canada, there was no significant difference between the two groups in the rating assigned to location of postgraduate training. Professional factors rated most important by most physicians in both groups were professional/clinical autonomy, availability of medical facilities and job availability. Remuneration was considered an equally important factor by those in Canada and in the United States. Six of seven personal/family factors were rated as more important to their choice of practice location by respondents in Canada than by those in the United States. Current satisfaction was significantly higher among respondents in the United States. Most physicians in each group planned to continue practising at their current location. Of Canadian respondents, 22% indicated that they were more likely to move to the United States than they were a year beforehand, whereas 4% of US respondents indicated that they were more likely to return to Canada. CONCLUSIONS: Factors affecting the decision to move to the United States or remain in Canada can be categorized as "push" factors (e.g., government involvement) and "pull" factors (e.g., better geographic climate in the US). Factors can also be categorized by whether they are amenable to change (e.g., availability of medical facilities) or cannot be managed (e.g., proximity of relatives). An understanding of the reasons why physicians immigrate to the United States or remain in Canada is essential to planning physician resources nationally.     

Histamine and calcitonin release from medullary thyroid carcinoma

The secretagogue effect of histamine on calcitonin secretion has been studied in 15 patients with medullary thyroid carcinoma and compared with known stimuli: glucagon and calcium in combination with pentagastrin. The effect of concomitant histamine H2-receptor blockade on these responses has been studied in the same patients. Seven patients with undetectable basal plasma calcitonin concentrations had measurable responses to calcium/pentagastrin but not to histamine or glucagon. In the remaining eight subjects, significant responses were seen to all three test substances, calcium/pentagastrin proving to be the most potent secretagogue. Establishment of H2-receptor blockade with cimetidine had no effect on basal calcitonin concentrations and did not suppress responses to histamine, calcium or pentagastrin. The variable secretagogue effect of histamine could be mediated through H1-receptors, through nonspecific vascular dilation "washing out" preformed calcitonin, or through its destruction to varying degrees by histaminase, present in most medullary thyroid tumors. Histamine is unlikely to replace calcium/pentagastrin as the most discriminative, provocative diagnostic agent in medullary thyroid carcinoma, but correlation of secretory responses with tissue histaminase concentrations and attempted blockade with differing antihistamines will further our understanding of this tumor.     

The Multiple Endocrine Neoplasia syndromes

The Multiple Endocrine Neoplasia syndromes are familial disorders in which neoplastic changes develop in multiple endocrine tissues. Almost all of these diseases are inherited as autosomal dominant traits with complete penetrance but variable expressivity. Classification of the Multiple Endocrine Neoplasias is based on the pattern of endocrine organ involvement. Multiple Endocrine Neoplasia Type I (MEN-I) is characterized by the concurrence of pituitary adenomas, parathyroid hyperplasia and pancreatic islet cell neoplasms. Multiple Endocrine Neoplasia Type II (MEN-II or IIa) consists of medullary thyroid carcinoma (MTC), parathyroid hyperplasia and pheochromocytomas. Multiple Endocrine Neoplasia Type IIb (MEN-IIb) is similar to MEN-IIa in that affected patients have MTC and pheochromocytomas. Multiple mucosal neuromas and ganglioneuromatosis of the gastrointestinal tract are also present in patients with MEN-IIb, but these individuals rarely manifest hyperparathyroidism. The Multiple Endocrine Neoplasia syndromes have attracted a great deal of attention because of their characteristic clinical features and familial pattern of occurrence. By utilizing recently developed "provocative tests" it is possible through aggressive screening of kindred members at risk to detect certain of these diseases (particularly MTC and pancreatic islet cell neoplasia) at an early stage. Therapeutic intervention in selected patients is associated with a high cure rate.     

Evaluation of patients undergoing lung volume reduction surgery: ancillary information available from computed tomography

AIM: A number of imaging techniques have been used for the pre-operative assessment of patients for lung volume reduction surgery (LVRS). We evaluated whether data currently acquired from perfusion scintigrams and cine MR of the diaphragm are obtainable from high resolution CT (HRCT) of the thorax. MATERIALS AND METHODS: Thirty patients taking part in a randomized controlled trial of LVRS against maximal medical therapy were evaluated. HRCT examinations (n= 30) were scored for (i) the extent and distribution of emphysema; (ii) the extent of normal pulmonary vasculature; and (iii) diaphragmatic contour, apparent defects and herniation. On scintigraphy, (n= 28), perfusion of the lower thirds of both lungs, as a proportion of total lung perfusion (LZ/T(PERF)), was expressed as a percentage of predicted values (derived from 10 normal control subjects). On cine MR (n= 25) hemidiaphragmatic excursion and coordination were recorded. RESULTS: Extensive emphysema was present on HRCT (60% +/- 13.2%). There was strong correlation between the extent of normal pulmonary vasculature on HRCT and on perfusion scanning (r(s)= 0.85, P< 0.00005). Hemidiaphragmatic incoordination on MR was weakly associated with hemidiaphragmatic eventration on HRCT (P= 0.04). CONCLUSION: The strong correlation between lung perfusion assessed by HRCT and lung perfusion on scintigraphy suggests that perfusion scintigraphy is superfluous in the pre-operative evaluation of patients with emphysema for LVRS.     

Biophysical, histopathological and pharmacological characterization of crotamine isoforms F22 and F32.

Two major crotamine isoforms (F22 and F32) were obtained after three chromatographic steps and were assayed in mouse phrenic nerve-diaphragm preparations. F32 and F22 (0.5 microg/ml, n=4) produced a facilitatory effect, which increased isometric twitch-tension by 300 and 230%, respectively, after a 120 min incubation. At a concentration of 0.1 microg/ml, both isoforms increased the twitch-tension by about 160%. However, when the isoforms were co-incubated (final concentration, 0.5 microg/ml) for 30 min prior to testing, they did not cause the facilitation seen with > or =0.1 microg/ml of each isoform alone. Histologically, F32 and F22 at 0.5 and 1 microg/ml were quantitatively alike in inducing tissue myonecrosis. However, a mixture of the two isoforms (final concentration, 0.5 microg/ml) significantly attenuated the damage seen with either toxin alone. Mass spectrometry analysis showed that the isoforms had the same molecular mass (4.8 kDa) and that they existed as monomers with a highly stable structure. These results indicate that F22 and F32 acted on muscle cells of the mouse phrenic-nerve diaphragm preparation through similar mechanisms. Since the isoforms did not produce the expected summation in the increase in muscle twitch-tension, it is possible that they may have different affinities for the sodium channel subunits.     

Medullary Carcinoma of the Thyroid Gland

Medullary thyroid carcinoma (MTC) is an uncommon thyroid tumor that has attracted a great deal of interest because of its frequent presentation as a familial tumor and its primary involvement in the type II multiple endocrine neoplasia (MEN) syndromes MEN-IIA and MEN-IIB and familial medullary thyroid carcinoma (FMTC). The MTC tumor cells secrete the polypeptide hormone calcitonin, which serves as an excellent tumor marker, useful for defining the presence of disease, preoperatively or following thyroidectomy. The discovery that mutations in the RET proto-oncogene are associated with MEN-II syndromes was highly significant in that it demonstrated a clear correlation between genotype and phenotype; and most importantly it provided a mechanism whereby family members at risk could be identified by direct DNA analysis. Virtually all patients with MEN-IIA, MEN-IIB, and FMTC develop MTC; therefore there is a clear rationale for performing thyroidectomy as soon as a RET mutation has been identified. Because MTC appears to be much more aggressive in patients with MEN-IIB, thyroidectomy is performed during the first year of life in this setting, whereas in patients with MEN-IIA, where the tumor appears to be more indolent, the procedure can be safety delayed until age 5 years. Reoperative neck exploration in patients with evidence of persistent or recurrent MTC has been effective in a significant number of patients, although the success of the operation requires careful patient selection and preoperative assessment. MTC, as expressed in the MEN-II syndromes, is an excellent model to evaluate the usefulness of interventional therapy in patients demonstrated to have a genetic predisposition for cancer.