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Biomedical subjects

M L Brigden

Publications and source records attributed to M L Brigden.

At least 19 recordsLinked to original sources
PubMed2001

Detection, education and management of the asplenic or hyposplenic patient.

Fulminant, potentially life-threatening infection is a major long-term risk after splenectomy or in persons who are functionally hyposplenic as a result of various systemic conditions. Most of these infections are caused by encapsulated organisms such as pneumococci, Haemophilus influenzae and meningococci. A splenectomized patient is also more susceptible to infections with intraerythrocytic organisms such as Babesia microti and those that seldom affect healthy people, such as Capnocytophaga canimorsus. Most patients who have lost their spleens because of trauma are aware of their asplenic condition, but some older patients do not know that they are asplenic. Other patients may have functional hyposplenism secondary to a variety of systemic diseases ranging from celiac disease to hemoglobinopathies. The identification of Howell-Jolly bodies on peripheral blood film is an important clue to the diagnosis of asplenia or hyposplenia. Management of patients with these conditions includes a combination of immunization, antibiotic prophylaxis and patient education. With the increasing prevalence of antibiotic-resistant pneumococci, appropriate use of the pneumococcal vaccine has become especially important.

Anti-Bacterial Agents↗
PubMed2001

Hematologic and oncologic emergencies. Doing the most good in the least time.

Broad categories of emergency hematologic and oncologic situations are metabolic crises, compressions and obstructions, and symptomatic cytopenias. In each instance, a decision to intervene should be made on the basis of findings on diagnostic assessment in combination with prognostic information. Management should be directly proportional to the possibility for cure, significant remission, or improved quality of life. Numerous diseases, including potentially curable cancer, can be modified and patients' quality of life substantially improved with appropriate emergency intervention. Fortunately, the modern therapeutic arsenal provides many specific measures to manage these challenging clinical situations.

Algorithms↗
PubMed2001

Practising physician's knowledge and patterns of practice regarding the asplenic state: the need for improved education and a practical checklist.

OBJECTIVE: To examine physicians' knowledge and actions regarding the asplenic state and to develop a practical checklist to aid in the systematic education and management of asplenic patients. DESIGN: A prospective cohort survey utilizing an experienced nurse practitioner and a survey questionnaire with on-site interviews. SETTING: The Okanagan Valley, British Columbia. SUBJECTS: A cohort of 122 physicians serving a population base of 350,000. MAIN OUTCOME MEASURES: Beliefs and practices relating to vaccination and precautions necessary for adult and pediatric splenectomized patients. PRINCIPAL RESULTS: The majority of physicians appeared to be knowledgeable about potential conditions affecting splenic function, except in the case of severe liver disease with portal hypertension and collagen vascular disease. There appeared to be good understanding on the part of most physicians of the risks associated with various infectious diseases and the asplenic state, except in the case of Capnocytophaga canimorsus infection linked to dog bites and the increased susceptibility of asplenic patients to intraerythrocytic parasites. Although a majority of physicians were cognizant of the need for pneumococcal vaccination and other immunizations in adults, there was marked uncertainty in relation to the need and the appropriate time interval for revaccination. In the case of children there appeared to be uncertainty regarding the role of antibiotic prophylaxis. There were discrepancies between physicians' expressed attitudes and the actions actually taken for asplenic patients in individual practices. CONCLUSIONS: Further education is required concerning the management of asplenic patients. The systematic use of a practical checklist may facilitate this process.

Adult↗
PubMed2000

Pneumococcal vaccine administration associated with splenectomy: the need for improved education, documentation, and the use of a practical checklist.

An audit was performed of the documentation of pneumococcal vaccination in splenectomy patients in three major hospitals involving a geographical population base of 350,000 patients in British Columbia, Canada. Overall, 111 of the 164 hospitalized splenectomy patients (68%) had received pneumococcal vaccination. Of elective splenectomy cases, only 11 of 55 (20%) had been vaccinated prior to surgery, as is currently recommended. One hundred fifty-five patients (95%) had splenectomy status mentioned in the discharge summary. However, only 35 (21%) had mention of vaccination status, 10 (6%) mention of the need for future revaccination, and only 8 (5%) notation of the possibility of future infectious risks. The rate of pneumococcal vaccination was as satisfactory as any reported in the literature to date. However, there is need for improved education in relation to the timing of vaccination and discharge summary documentation. A checklist for potential splenectomy patients may aid in improving this situation as may geographically based splenectomy registries.

Adolescent↗
PubMed2000

A survey of aPTT reporting in Canadian medical laboratories. The need for increased standardization. Thrombosis Interest Group of Canada.

A survey of all licensed medical laboratories performing activated partial thromboplastin time (aPTT) testing in Canada was undertaken; the response rate was 50.7%. Preanalytic phase of testing seemed generally satisfactory, although 46% of laboratories were still using 3.8% or a 129-mmol/L concentration of citrate, and only 59% of institutions routinely performed testing to verify the platelet-poor status of the plasma used for aPTT testing. There were also concerns relating to the speed and duration of centrifugation for specimen preparation. While more than 67% of institutions had established an individual therapeutic range for aPTT testing, only 47% of laboratories verified this range with heparinized samples. Approximately 67% of the institutions that had verified the range had done this by spiking heparin concentrations into pooled plasma rather than using ex vivo specimens from patients receiving heparin therapy. There seemed to be a need for increased education about circumstances under which the therapeutic range should be rechecked and current standards for screening for the lupus anticoagulant. More than 71% of Canadian institutions surveyed used low-molecular-weight heparin, which may obviate many of the issues surrounding aPTT testing. Overall performance as documented by survey results seemed similar to that reported for the United States and Australasia.

Blood Specimen Collection↗
PubMed2000

Problems in interpreting laboratory tests. What do unexpected results mean?

It is always important that physicians not overreact to apparently abnormal laboratory values by undertaking inappropriate further investigations or clinical treatments. When confronted with unexpected differing test results from repeat testing in the same individual, physicians should be aware of explanations other than laboratory error and change in the patient's clinical status. While test-related variables may be factors, intraindividual biologic variation is much more common and may be the explanation for discrepant results. For this reason, physicians need to know which laboratory tests are associated with significant intraindividual biologic variation as well as the magnitude of possible changes. Age-associated physiologic changes may significantly alter certain laboratory values in the elderly without constituting a pathologic process. Laboratory values that may appear abnormal in 10% or more of the healthy elderly without necessarily representing a pathologic process include serum alkaline phosphatase, fasting blood glucose, 2-hour postprandial glucose, erythrocyte sedimentation rate, hemoglobin, and a normal serum creatinine level in the face of a markedly decreased creatinine clearance. To ensure proper assessment of the geriatic patient, the clinician needs to be aware of these age-related changes and possible effects on laboratory values. More clinical research is needed to establish appropriate reference ranges, especially for those over the age of 75 years.

Adolescent↗
PubMed2000

Proportion positive for Epstein-Barr virus, cytomegalovirus, human herpesvirus 6, Toxoplasma, and human immunodeficiency virus types 1 and 2 in heterophile-negative patients with an absolute lymphocytosis or an instrument-generated atypical lymphocyte flag.

OBJECTIVES: To determine the proportion of patients with evidence of an acute infection due to Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus 6 (HHV-6), Toxoplasma, or human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) in heterophile-negative patients with an absolute lymphocytosis or an instrument-generated atypical lymphocyte flag, and to develop a cost-effective testing algorithm for managing such heterophile-negative patients. DESIGN: We conducted a prospective investigation of 70 selected outpatients who tested negative for heterophile antibody in association with an absolute lymphocytosis or instrument-generated atypical lymphocyte flag. The control population consisted of 50 patients who were heterophile negative and had a normal absolute lymphocyte count and no instrument-generated atypical lymphocyte flag. SETTING: A large outpatient laboratory system. INTERVENTION: Viral serology for HHV-6 was performed by immunofluorescence, and all other serologies were performed by enzyme-linked immunoassay. All testing was for immunoglobulin (Ig) M antibodies, except in the case of HIV. RESULTS: The proportion of study patients positive for EBV was 40% (28/70); for CMV, 39% (27/70); for HHV-6, 25% (16/65); for Toxoplasma, 3% (2/70); and for HIV, 0% (0/70). All 50 control patients were negative for EBV IgM antibodies. When patients with more than 1 positive viral test were excluded from analysis, positivity was 20% (9/45) for EBV, 22% (10/45) for CMV, 9% (4/45) for HHV-6, and 2% (1/45) for Toxoplasma. Utilizing hypothesis-generating logistic regression models, Downey type II atypical lymphocytes were significantly associated with EBV positivity (P =.006), while Downey type III lymphocytes were significantly associated with HHV-6 positivity (P =.016), and there was a trend for the association of Downey type I lymphocytes with CMV positivity (P =.097). CONCLUSIONS: A positive viral serology was identified in 70% of study patients. Multiple positive serologies complicate establishing a definitive diagnosis. Potential cost savings may be associated with the use of an appropriate testing algorithm.

Adolescent↗
PubMed1999

Clinical utility of the erythrocyte sedimentation rate.

The erythrocyte sedimentation rate (ESR) determination is a commonly performed laboratory test with a time-honored role. However, the usefulness of this test has decreased as new methods of evaluating disease have been developed. The test remains helpful in the specific diagnosis of a few conditions, including temporal arteritis, polymyalgia rheumatica and, possibly, rheumatoid arthritis. It is useful in monitoring these conditions and may predict relapse in patients with Hodgkin's disease. Use of the ESR as a screening test to identify patients who have serious disease is not supported by the literature. Some studies suggest that the test may be useful as a "sickness index" in the elderly or as a screening tool for a few specific infections in certain settings. An extreme elevation of the ESR is strongly associated with serious underlying disease, most often infection, collagen vascular disease or metastatic malignancy. When an increased rate is encountered with no obvious clinical explanation, the physician should repeat the test after an appropriate interval rather than pursue an exhaustive search for occult disease.

Arteritis↗
PubMed1999

Improving survival in metastatic carcinoma of unknown origin.

Metastatic carcinoma from an unknown primary site accounts for 3% to 5% of all newly diagnosed malignant lesions. Although 85% of patients who receive this diagnosis are dead within a year, 5% to 10% may be long-term survivors. Close cooperation between an experienced pathologist and the referring physician is essential in the management of these patients. One important task for the physician is to recognize those subgroups of patients who may have a better prognosis and thus may be treated in a different fashion. A second challenge is not to overinvestigate or overtreat patients who fall into the poor prognosis category. Empirical chemotherapy should not be given simply for the sake of doing something. Rather, proper emphasis should be placed on regional therapy, symptomatic treatment, and the best palliative care. Patients may be confused and frustrated when confronted with the news that the source of their tumor is not apparent. They should be reassured that this lack does not preclude development of a rational treatment plan and that those cancers for which highly effective systemic therapy exists have been excluded. A caring, informed physician may help empower the patient to make educated and informed choices.

Algorithms↗
PubMed1999

Prevention and management of overwhelming postsplenectomy infection--an update.

OBJECTIVES: To review the diagnosis and management of overwhelming postsplenectomy infection and to discuss various preventative measures. DATA SOURCES: Data used to prepare this article were drawn from published articles and work in progress. STUDY SELECTION: Articles were selected for relevance to the subject after location by a MEDLINE key word search. DATA EXTRACTION: The literature was reviewed to summarize the etiology and pathophysiology of postsplenectomy sepsis. Preventative strategies were outlined with a particular emphasis on education, immunoprophylaxis, and chemoprophylaxis. DATA SYNTHESIS: Although physicians have become increasingly aware of overwhelming postsplenectomy infection in children, many remain unaware of the risk to asplenic or hyposplenic adults who may have no underlying medical problems. Recent studies have shown that many patients who have had splenectomies have had neither appropriate vaccinations nor teaching that would explain the lifelong nature of their risk. The increasing incidence of penicillin-resistant pneumococci represents a major area of therapeutic and prophylactic concern. The identification of Howell-Jolly bodies on a peripheral blood smear should alert physicians to the need for follow-up to document possible hyposplenism. Attention has focused on a three-pronged attack to this problem, including education, immunoprophylaxis, and chemoprophylaxis. CONCLUSIONS: Overwhelming postsplenectomy infection should be largely preventable if appropriate precautions are taken. Physicians need to know of the spectrum of diseases associated with hyposplenism and how patients noted to have Howell-Jolly bodies should be investigated. They should also be aware of appropriate guidelines for management of patients with asplenia or hyposplenism.

Adult↗
PubMed1999

A practical workup for eosinophilia. You can investigate the most likely causes right in your office.

The vast majority of cases of eosinophilia in North America are caused by allergic processes. In individual cases, a short differential diagnosis of the most likely causes can be formulated on the basis of the absolute eosinophil count. The extensive laboratory workup previously recommended by some authorities is probably not justified unless detailed history taking and physical examination indicate a need for specific investigations. Although the possibility of missing an occult neoplasm has been used to justify extensive investigation, this is usually not necessary because most tumor-associated eosinophilia is accompanied by widely metastatic disease. History taking should emphasize the possibility of drug-induced or helminth-associated eosinophilia. If the history indicates travel, dietary, or other exposure risks, stool examination for ova and parasites is worthwhile. If a possible allergic cause is suspected, testing for evidence of atopy may be performed concomitantly with testing for parasitic infection. A follow-up white blood cell count with differential is recommended to ascertain whether eosinophilia has resolved. When an absolute eosinophil count of more than 1.5 x 10(9)/L persists for longer than 6 months, idiopathic hypereosinophilic syndrome must be ruled out.

Eosinophilia↗
PubMed1999

The search for meaning in monoclonal protein. Is it multiple myeloma or monoclonal gammopathy of undetermined significance?

Multiple myeloma and MGUS are the two most common causes of monoclonal protein in serum or urine. The usually accepted diagnostic triad for multiple myeloma consists of a significant paraprotein in the serum or urine, more than 10% to 15% plasma cells in bone marrow, and the presence of bony lesions. Patients who meet the first two criteria but have no bony lesions, cytopenias, renal failure, or hypercalcemia may have smoldering myeloma, which often can be observed for a period of time before therapy is required. MGUS is characterized by a serum IgG monoclonal protein less than 3.5 g/dL or IgA paraprotein less than 2 g/dL, with no or only a small amount of protein in urine (Bence Jones protein < 1 g/24 hr). Less than 10% plasma cells are present in bone marrow, and patients have no lytic bony lesions, anemia, hypercalcemia, or renal insufficiency. Another important criterion for MGUS is stability of the monoclonal protein over time. Nonetheless, during long-term follow-up, an associated malignant process develops in about 30% of MGUS patients. Since none of the features defining MGUS is uniformly helpful in predicting the risk for malignant disease, patients should be followed up on a regular basis indefinitely.

Humans↗
PubMed1999

Infectious mononucleosis in an outpatient population: diagnostic utility of 2 automated hematology analyzers and the sensitivity and specificity of Hoagland's criteria in heterophile-positive patients.

OBJECTIVES: To determine the sensitivity and specificity of 2 modern hematology analyzers in flagging heterophile-positive patients; to determine if heterophile-positive, instrument-flagged specimens contain a larger number or a different spectrum of atypical lymphocytes; to document the overall sensitivity and specificity of Hoagland's morphologic criteria in identifying heterophile-positive patients in an outpatient population with a clinical diagnosis of mononucleosis; and to examine whether individual morphologic features might aid in the diagnosis of suspected infectious mononucleosis. DESIGN: A prospective study of patients referred with a clinical diagnosis of infectious mononucleosis who subsequently tested positive for the heterophile antibody. The control group consisted of a similar population of patients who tested negative for the heterophile antibody. INTERVENTION: Hematology profiles of peripheral blood samples were determined with Coulter STKS and Sysmex NE-8000 analyzers. A corresponding Wright-Giemsa-stained blood smear was subsequently examined by a single skilled technologist, who performed a 200-cell white blood cell differential and a 200-cell lymphocyte differential. A specific morphologic search was made for the presence of smudge cells or lymphocytes with cloverleaf nuclei. RESULTS: Using a combination of all flagging criteria, the 2 analyzers identified 156 (86.2%) of 181 heterophile-positive patients as meriting further review. The sensitivity and specificity values of the Coulter analyzer in predicting positive heterophile status for the blast flag were 41% and 97.1%, respectively; for the variant lymphocyte flags, 72.4% and 79.1%, respectively; and for both flags, 40% and 98.1%, respectively. For the Sysmex analyzer, the sensitivity and specificity values in predicting positive heterophile status for the blast flag were 43.4% and 88.6%, respectively; for the variant lymphocyte flag, 15.8% and 90.8%, respectively; and for both flags, 10.5% and 96%, respectively. Considering the classic criteria developed by Hoagland, a lymphocytosis of at least 50% was present in 120 (66.3%) heterophile-positive patients, while an atypical lymphocytosis of at least 10% of the total WBC count was noted in 135 patients (74.6%). The sensitivity and specificity values of a lymphocytosis > or =50% for diagnosing heterophile-positive status were 66.3% and 84.5%, respectively, while the sensitivity and specificity of an atypical lymphocytosis > or =10% were 74.6% and 92.3%, respectively. The presence of smudge cells or cloverleaf lymphocyte nuclei was verified as having high specificity but low sensitivity for suggesting a diagnosis of infectious mononucleosis. CONCLUSION: Although a number of patients did not meet Hoagland's criteria for the diagnosis of infectious mononucleosis, the flagging systems of modern hematology analyzers successfully identified most cases as requiring further review.

Adolescent↗
PubMed1998

Audit of the frequency and clinical response to excessive oral anticoagulation in an out-patient population.

A retrospective review of over-anticoagulated patients with critical international normalized ratios (INRs) was undertaken in a large outpatient laboratory. In the six-month study period, 85 prothrombin times (PTs) were identified with an INR of > or = 6.0, an overall incidence of elevated PTs of 0.2% or two per 1,000 INR tests. Complete follow-up data was available on 65 patients. When compared to an age- and gender-matched control group without INR > or = 6.0, high-INR patients were significantly more likely to manifest the presence of alcoholism or liver disease, to have been anticoagulated for less than six months, to have experienced more frequent warfarin dosage changes, and to have had the addition of a medication known to interact with warfarin. In the high-INR group, a likely cause for the specific critical INR was identified in 44 patients (68%). Drug interactions followed by compliance problems were the most common factors identified. The 13 patients (20%) who received vitamin K therapy experienced no difference in the clinical outcome compared with those managed conservatively. Conservative management of critically high INR values appeared to be as efficacious as intervention with vitamin K therapy.

Administration, Oral↗
PubMed1998

INR reporting in Canadian medical laboratories: an update. Thrombosis Interest Group of Canada.

A written survey of all licensed medical laboratories performing coagulation testing in Canada was undertaken in 1996 as a follow-up to a study performed in 1992. The an overall response rate was 77.4% of the laboratories surveyed. During the 4-year period between surveys, the percentage of responding laboratories using some format for international normalized ratio (INR) reporting increased from 57% to 98%. The mean International Sensitivity Index (ISI) of the various thromboplastins used had decreased from 2.07 to 1.63. However, only 35% of responding laboratories used a thromboplastin with an ISI of 1.2 or less as recommended by the American College of Chest Physicians. In 92% of cases, the ISI was said to be specified for the type of instrument, ie, optical density vs mechanical. However, in only 52% of cases was the ISI known to be specific for the particular reagent-analyzer combination used in the individual laboratory. Nine percent of the laboratories were still using an inappropriate denominator for the INR calculation. While 87% of laboratories quoted a therapeutic INR range of 2.0 to 3.0 for venous thromboembolism, there was much greater variation in the range reported for patients undergoing heart valve replacement. The situation in Canada has improved in using the INR system for prothrombin time reporting. However, additional education is required, as is greater use of thromboplastins with a lower ISI.

Animals↗
PubMed1997

Prothrombin time determination. The lack of need for a discard tube and 24-hour stability.

The National Committee for Clinical Laboratory Standards (NCCLS) recommends that all coagulation studies be done on a specimen from the tube drawn second or later. For patients receiving long-term anticoagulant therapy, this may require that the first tube of blood drawn be discarded for each prothrombin evaluation. In a prospective study we compared the prothrombin times (PTs) as international normalized ratios (INRs) from a series of three tubes obtained from 241 patients receiving consistent dosages of oral anticoagulant therapy to determine the need for discarding the first tube drawn, as well as the stability of PT determinations over a 24-hour period. Tube one was treated as the discard tube. Tubes one and two were analyzed within the laboratory's standard 4-hour time frame, while tube three was kept stoppered at room temperature, centrifuged a half hour before PT determination, and analyzed after a 24-hour delay. Comparisons of the INRs were made in four ranges comprising 1.2 to 2.0, 2.1 to 3.5, 3.6 to 5.9, and 6.0 or more. Most INR comparisons were less than the 10% maximum variance listed as acceptable by the NCCLS. A comparison of INR results between tube two and tube one showed a statistically significant difference only for the INR range of 6.0 or more. The comparison of the 24-hour specimen with tube one showed statistically significant differences in paired t testing for the first three INR cohorts. However, the 95% confidence intervals demonstrated that these mean differences were probably too small to be clinically significant. For the fourth cohort (INR > or = 6.0) the mean difference was not significantly different on paired t testing, but the 95% confidence interval was larger at -0.07 to 0.839. In this sample of outpatients receiving consistent dosages of oral anticoagulant therapy the use of a discard tube seemed unnecessary, and the 24-hour stability of PT determinations was documented.

Adult↗
PubMed1997

The hypercoagulable state. Who, how, and when to test and treat.

Patients with a family history of thrombosis, early-onset or recurring thrombosis, thrombosis at unusual sites, or warfarin-induced skin necrosis should be investigated for a possible underlying inherited hypercoagulable disorder. These include AT-III deficiency, protein C and S deficiencies, and APC resistance. Many patients should also be evaluated for the antiphospholipid syndrome, an acquired disorder. Functional assays are more useful than immunologic assays for diagnosing AT-III deficiency, protein C and S deficiencies, and APC resistance. A molecular probe is now available for the abnormal factor V most often responsible for APC resistance. Testing for the antiphospholipid syndrome involves assays for the lupus anticoagulant and anticardiolipin antibodies. AT-III and protein C concentrates are now available for short-term therapy. Long-term prophylactic administration of warfarin may have to be considered for some symptomatic patients with proven abnormalities, especially after more than one thrombotic event. While the management of asymptomatic persons remains controversial, the use of prophylactic anticoagulation should be anticipated for trauma, surgery, pregnancy, or other high-risk situations.

Anticoagulants↗