Biomedical subjects

Dirk R Larson

Publications and source records attributed to Dirk R Larson.

At least 19 recordsLinked to original sources

PubMed2006

Immunoglobulin free light chains and solitary plasmacytoma of bone.

An abnormal serum immunoglobulin free light chain (FLC) ratio at diagnosis may identify risk of progression to myeloma in patients with solitary bone plasmacytoma (SBP). In the cohort of 116 patients, 43 have progressed to myeloma, with a median time to progression of 1.8 years. The FLC ratio was determined in all 116 patients on serum collected at time of diagnosis and was abnormal in 54 patients (47%). An abnormal FLC ratio was associated with a higher risk of progression to myeloma (P = .039). The risk of progression at 5 years was 44% in patients with an abnormal serum FLC ratio at diagnosis compared with 26% in those with a normal FLC ratio. One to 2 years following diagnosis, a persistent serum M protein level of 5 g/L (0.5 g/dL) or higher was an additional risk factor for progression. A risk stratification model was constructed using the 2 variables of FLC ratio and M protein level: patients with a normal FLC ratio at baseline and M protein level less than 5 g/L (0.5 g/dL) at 1 to 2 years following diagnosis (low risk, n = 31); with either risk factor abnormal (intermediate risk, n = 26); and with both an abnormal FLC ratio and M protein level of 5 g/L (0.5 g/dL) or higher (high risk, n = 18). The corresponding progression rates at 5 years were significantly different in the low, intermediate, and high groups: 13%, 26%, and 62%, respectively (P < .001).

Adult↗

PubMed2006

Prevalence of monoclonal gammopathy of undetermined significance.

BACKGROUND: The prevalence of monoclonal gammopathy of undetermined significance (MGUS), a premalignant plasma-cell disorder, among persons 50 years of age or older has not been accurately determined. We used sensitive laboratory techniques to ascertain the prevalence of MGUS in a large population in a well-defined geographic area. METHODS: We identified all living residents of Olmsted County, Minnesota, as of January 1, 1995. We obtained serum that remained after the performance of routine clinical tests at Mayo Clinic or asked subjects for whom such serum was unavailable to provide a sample. Agarose-gel electrophoresis was performed on all serum samples, and any serum sample with a discrete band of monoclonal protein or thought to have a localized band was subjected to immunofixation. RESULTS: Serum samples were obtained from 21,463 of the 28,038 enumerated residents 50 years of age or older (76.6 percent). MGUS was identified in 694 (3.2 percent) of these persons. Age-adjusted rates were higher in men than in women (4.0 percent vs. 2.7 percent, P<0.001). The prevalence of MGUS was 5.3 percent among persons 70 years of age or older and 7.5 percent among those 85 years of age or older. The concentration of monoclonal immunoglobulin was less than 1.0 g per deciliter in 63.5 percent and at least 2.0 g per deciliter in only 4.5 percent of 694 persons. The concentration of uninvolved immunoglobulins was reduced in 27.7 percent of 447 persons tested, and 21.5 percent of 79 tested had a monoclonal urinary light chain. CONCLUSIONS: Among residents of Olmsted County, Minnesota, MGUS was found in 3.2 percent of persons 50 years of age or older and 5.3 percent of persons 70 years of age or older.

Age Distribution↗

PubMed2006

Long-term functional and quality of life outcomes after coloanal anastomosis for distal rectal cancer.

PURPOSE: This study was designed to evaluate the long-term functional and quality-of-life outcomes of patients after coloanal anastomosis for distal rectal cancer. METHODS: A total of 192 patients underwent coloanal anastomosis between 1982 and 2001 at two tertiary referral institutions. Standardized and validated questionnaires to assess functional and quality-of-life outcomes were mailed to 151 patients, of which 121 patients responded (median follow-up, 65 months). RESULTS: Patients receiving pelvic radiotherapy had more bowel function problems than patients who did not receive pelvic radiotherapy. No significant differences in relevant functional and quality-of-life outcomes were seen among patients who received preoperative or postoperative pelvic radiotherapy. Patients requiring permanent diversion as a result of complications of the surgery had decreased quality of life. CONCLUSIONS: Coloanal anastomosis for distal rectal cancer has favorable long-term outcomes. Pelvic radiotherapy has an adverse effect on subsequent bowel function (whether given preoperatively or postoperatively) in patients who maintain intestinal continuity. Loss of intestinal continuity after a coloanal anastomosis is associated with diminished quality of life.

Adenocarcinoma↗

PubMed2006

Gynecologic cancers: factors affecting survival after pulmonary metastasectomy.

BACKGROUND: Little information is available regarding long-term survival after pulmonary metastasectomy for gynecologic malignancies. METHODS: All patients who underwent pulmonary resection for gynecologic malignancies at our institution between January 1985 and June 2001 were reviewed. Factors affecting long-term survival were analyzed. RESULTS: There were 103 patients, 70 of whom had metastatic disease limited to the lungs. Median age of these 70 patients was 59.4 years (range, 31 to 80 years). The primary tumor originated in the uterine corpus in 37 patients, endometrium in 23, cervix in 7, ovaries in 2, and vagina in 1. Histopathology was leiomyosarcoma in 29 patients, adenocarcinoma in 23, other sarcoma in 11, squamous cell carcinoma in 5, and choriocarcinoma and endolymphatic stromal myosis in 1 each. The median time interval between the first gynecologic procedure and pulmonary resection was 24 months (range, 0 to 237 months). A wedge excision was performed in 44 patients, lobectomy in 14, bilobectomy in 2, pneumonectomy in 1, and a combination in 9. Five patients (7%) had an incomplete resection. Eighteen patients (25.7%) developed at least one complication and 1 died (operative mortality, 1.4%). At last follow-up, 35 had died, and the median follow-up among those who were still alive was 36 months (range, 6 months to 13 years). Five-year and 10-year survival was 46.8% (95% confidence interval, 34.2% to 63.0%) and 34.3% (95% confidence interval, 19.7% to 52.5%), respectively. Factors that adversely affected survival include a disease-free interval between the first gynecologic procedure and pulmonary resection of less than 24 months (p = 0.004) and a primary site located in the cervix (p < 0.001). CONCLUSIONS: Pulmonary resection for metastatic gynecologic cancer in selected patients is safe and effective. Both a short disease-free interval between the primary gynecologic procedure and pulmonary metastasectomy, and a primary cervical tumor had an adverse effect on survival.

Adenocarcinoma↗

PubMed2006

Ileorectal anastomosis for slow transit constipation: long-term functional and quality of life results.

The results of colectomy and ileorectal anastomosis (IRA) in patients diagnosed by physiologic testing as having slow transit constipation (STC) have been reported. The durability of functional results and long-term quality of life (QoL) in these patients, however, has not been established. Between 1987 and 2002, 3670 patients were evaluated for constipation at our institution; 110 (3%) fulfilled the criteria for STC and underwent an IRA. Patients were prospectively followed and functional outcomes assessed annually by standardized questionnaires. After a median follow-up of 11 years, 104 eligible patients were mailed validated questionnaires to assess functional outcomes and QoL (Knowles-Eccersley-Scott Symptom [KESS] score, the Irritable Bowel Syndrome Quality of Life [IBS-QOL], and the SF-12 health survey). Prospectively assessed functional data was available on 85 of 104 (82%) eligible patients. At last follow-up, improvement of constipation and satisfaction with bowel function was reported by 98% and 85% of patients, respectively. Performance measures including social activity, household work, sexual life, and family relationships were reported to have improved or were not affected as a result of surgery by 75%, 86%, 81%, and 86% of the patients respectively. Fifty-nine patients (57%) responded to the study questionnaires. All 59 patients reported their constipation to be better since IRA, 83% did not require any medication, and 85% reported being satisfied with bowel function. The KESS scores of patients undergoing IRA for STC (median 6, range 0-35) were lower than reported scores of STC patients not operated upon (median 21, range 11-35, P<0.001) indicating symptomatic improvement after surgery. Mean IBS-QOL scores were similar to reported scores of patients undergoing IRA for other conditions [80 (23) versus 84 (16)], P=0.7). Mean SF-12 physical and mental summary scores were similar to reported SF-12 scores of the normal population (49.5 versus 50 and P=0.70, 48.7 versus 50, P=0.42, respectively). Ileorectal anastomosis in appropriately selected patients with slow transit constipation results in durable symptomatic relief and a long-term quality of life indistinguishable from the general population.

Adult↗

PubMed2006

Revision of thumb trapeziometacarpal arthroplasty.

PURPOSE: To determine the incidence of revision surgery after thumb trapeziometacarpal joint arthroplasty and to present the expected results of future surgical treatment. METHODS: We reviewed the patient database at our medical center and found 654 procedures performed between 1988 and 2000 for the treatment of thumb basal joint arthritis. From the database we found that revision arthroplasties were performed on 15 patients with 17 arthroplasties in the treatment of mechanical pain related to instability or bone impingement. Referred patients with primary surgery performed elsewhere and patients with neurogenic pain were reviewed but not included as a primary focus of this study. The revision surgical procedures included soft-tissue interposition alone or soft-tissue interposition with ligament reconstruction for mechanical symptoms and neurolysis of peripheral nerves for associated neurogenic pain. The assessment included preoperative and postoperative patient chart review, measurement of pinch and grip strengths, radiographic assessment, and patient contact to provide complete medical information including any further medical or surgical treatment. RESULTS: Based on a grading system previously used to evaluate thumb revision surgery, objective good (or satisfactory) results were found in 13 of 17 revision procedures. The method of soft-tissue revision (resection with soft-tissue interposition or resection with ligament reconstruction) did not influence the outcome of good versus fair or poor results. Persistent failures (2 fair, 2 poor) resulted from both soft-tissue interposition alone and revision with ligament support arthroplasties. Revision arthroplasty with soft-tissue procedures for mechanical pain provided predictably good results unless a nerve injury occurred at the time of the revision surgery. CONCLUSIONS: Failure of primary thumb trapeziometacarpal arthroplasty can be salvaged by a second surgery with ligament reconstruction procedures combined with soft-tissue interposition and provides satisfactory patient outcomes in more than 75% of cases studied. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic, Level IV.

Aged↗

PubMed2006

A quantitative composite scoring tool for orthopaedic residency screening and selection.

The ability to accurately screen and select orthopaedic resident applicants with eventual successful outcomes has been historically difficult. Many preresidency selection variables are subjective in nature and a more standardized objective scoring method seems desirable. A quantitative composite scoring tool (QCST) to be used in a standardized manner to help predict orthopaedic residency performance from application materials was developed. In 64 orthopaedic residents, four predictors (United States Medical Licensing Examination [USMLE] Part I scores, Alpha Omega Alpha status, junior year clinical clerkship honors grades, and the QCST score) were analyzed with respect to four residency outcomes assessments. The outcomes included three standardized assessments, the orthopaedic in-training examination scores (OITE), the American Board of Orthopaedic Surgery (ABOS) written and oral examinations, and an internal outcomes assessment, attainment of satisfactory chief resident associate (CRA) status. Collectively, the QCST score had the strongest association as a predictor for all three standardized outcomes assessments (p < 0.001). Honors grades during junior years clinical clerkships was most strongly associated with satisfactory CRA status (p < 0.001). A composite scoring tool that is an effective predictor of orthopaedic resident outcomes can be developed. Additional work is still required to refine this scoring tool for orthopaedic residency screening and selection.

Clinical Competence↗

PubMed2006

Diverticulitis: a progressive disease? Do multiple recurrences predict less favorable outcomes?

INTRODUCTION: Our understanding of complicated diverticulitis is based on outdated literature. Antecedent episodes of diverticulitis are felt to increase the risk of developing complicated diverticulitis, as well as its subsequent morbidity and mortality. Practice parameters recommend elective resection after 2 episodes of diverticulitis to reduce this morbidity and mortality. METHODS: A total of 150 patients with prior episodes of diverticulitis who were hospitalized with complicated diverticulitis were retrospectively analyzed. Statistical analysis was conducted using chi and Fisher exact test tests. RESULTS: Patients were separated into 2 groups for analysis: group A = those with 1 or 2 prior diverticulitis episodes (n = 118) versus group B = patients with more than 2 prior episodes (n = 32). Characteristics of the groups were similar for age and preexistent comorbid conditions. The majority of patients presented with pericolonic abscess and inflammatory phlegmon. Perforated diverticulitis occurred more often in group A compared with patients with >2 episodes of diverticulitis. Because of the higher rate of perforation, patients in group A underwent surgical diversion more often than group B patients. No significant differences in operative complications, morbidity, or mortality rates were identified between the groups. CONCLUSION: Patients with multiple (>2) episodes of diverticulitis are not at increased risk for poor outcomes if they develop complicated diverticulitis. Morbidity and mortality rates are not significantly different between patients with multiple episodes of diverticulitis compared with those with 1 or 2 prior attacks. Reevaluation of the practice of elective resection as a strategy for reducing the mortality and morbidity from complicated diverticulitis is needed.

Aged↗

PubMed2006

Prognostic model for disease-specific and overall mortality in newly diagnosed symptomatic patients with Waldenstrom macroglobulinaemia.

We sought to define prognostic factors for survival in Waldenstrom macroglobulinaemia (WM). Of 585 patients diagnosed with WM and seen at Mayo Clinic between 1960 and 2001, 337 symptomatic patients met the inclusion criteria and were analysed for overall and disease-specific survival. The median survival from the time of diagnosis was 6.4 years. The median disease-specific survival was 11.2 years. Univariate analysis for overall survival identified the following adverse prognostic factors: age >65 years (P < 0.001), organomegaly (P < 0.001), elevated beta2-microglobulin (<0.001), anaemia (Hb < 10.0 g/dl) (P = 0.01), leucopenia (<4.0 x 10(9)/l) (P = 0.03), thrombocytopenia (<150 x 10(9)/l) (P = 0.01), serum albumin <40 g/l (P = 0.001), and quantitative IgM < 0.4 g/l (P = 0.04). On multivariate analysis, age >65 years and organomegaly were associated with poor prognosis. A prognostic model was built based on these two variables. Patients at high risk (1-2 risk factors, median survival 4.2 years) experienced worse survival than patients at low risk (0 risk factors, median survival 10.6 years), P < 0.001. The prognostic model was validated in 204 patients who were not included in the analysis cohort. Beta2-microglobulin > or =4 mg/l was associated with a threefold increase in the risk of death when added to the prognostic model. We describe a simple prognostic model for overall survival for newly diagnosed patients with WM.

Adult↗

PubMed2006

Elimination of the need for urine studies in the screening algorithm for monoclonal gammopathies by using serum immunofixation and free light chain assays.

OBJECTIVE: To determine the relative diagnostic contribution of urine assays as part of the screening algorithm for monoclonal gammopathies. PATIENTS AND METHODS: We identified 428 patients with a monoclonal gammopathy and monoclonal urinary protein at initial diagnosis of plasma cell dyscrasia who had also undergone serum immunofixation and serum free light chain quantitation within 30 days of diagnosis. The laboratory results for serum protein electrophoresis, serum immunofixation, serum free light chain, urine protein electrophoresis, and urine immunofixation were reviewed. RESULTS: The patients had diagnoses of multiple myeloma, primary amyloid, monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, solitary plasmacytomas, and other less frequently detected monoclonal gammopathies. All 428 had a monoclonal urine protein, 85.7% had an abnormal serum free light chain kappa/lambda ratio, 80.8% had an abnormal serum protein electrophoresis, and 93.5% had an abnormal serum immunofixation result. All 3 serum assays were normal in only 2 patients, 1 of whom had monoclonal gammopathy of undetermined significance (idiopathic Bence Jones proteinuria) and 1 whose urine sample contained an intact monoclonal immunoglobulin but whose serum and subsequent urine samples showed no evidence of a monoclonal gammopathy. CONCLUSION: Discontinuation of urine studies and reliance on a diagnostic algorithm using only serum studies (protein electrophoresis, immunofixation, and free light chain quantitation) missed 2 (0.5%) of the 428 monoclonal gammopathies with urinary monoclonal proteins, and these 2 cases required no medical intervention.

Algorithms↗

PubMed2006

Essential thrombocythemia beyond the first decade: life expectancy, long-term complication rates, and prognostic factors.

OBJECTIVE: To describe the long-term natural history of essential thrombocythemia (ET) in terms of life expectancy, risk of disease transformation Into a more aggressive myeloid disorder, and prognostic factors for both survival and disease complications. PATIENTS AND METHODS: The study population consisted of a consecutive cohort of patients seen at the Mayo Clinic In Rochester, Minn, in whom a diagnosis of ET was established before 1992, thus allowing a minimum of 10 years of potential follow-up. The conventional criteria-based diagnosis was confirmed by bone marrow biopsy in all Instances. RESULTS: A total of 322 patients were studied (median age, 54 years; median follow-up, 13.6 years). With a median survival time of 18.9 years, survival in the first decade of disease was similar to that of the control population (risk ratio, 0.72; 95% confidence interval, 0.50-0.99) but became significantly worse thereafter (risk ratio, 2.21; 95% confidence Interval, 1.74-2.76). Multivariable analysis identified age at diagnosis of 60 years or older, leukocytosis, tobacco use, and diabetes mellitus as Independent predictors of poor survival. A 2-variable model based on an age cutoff of 60 years and leukocyte count of 15 x 10(9)/L resulted in 3 risk groups with significant difference in survival. In addition, age at diagnosis of 60 years or older, leukocytosis, and history of thrombosis were independent predictors of major thrombotic events. The risk of leukemic or any myeloid disease transformation was low in the first 10 years (1.4% and 9.1%, respectively) but increased substantially in the second (8.1% and 28.3%, respectively) and third (24.0% and 58.5%, respectively) decades of the disease. CONCLUSION: Life expectancy in patients with ET is significantly worse than that of the control population. Leukocytosis is identified as a novel independent risk factor for both inferior survival and thrombotic events.

Adolescent↗

PubMed2005

Serum free light chain ratio is an independent risk factor for progression in monoclonal gammopathy of undetermined significance.

We hypothesized that the presence of monoclonal free kappa or lambda immunoglobulin light chains in monoclonal gammopathy of undetermined significance (MGUS), as detected by the serum free light chain (FLC) assay increases the risk of progression to malignancy. Of 1384 patients with MGUS from Southeastern Minnesota seen at the Mayo Clinic from 1960 to 1994, baseline serum samples obtained within 30 days of diagnosis were available in 1148. At a median follow-up of 15 years, malignant progression had occurred in 87 (7.6%) patients. An abnormal FLC ratio (kappa-lambda ratio < 0.26 or > 1.65) was detected in 379 (33%) patients. The risk of progression in patients with an abnormal FLC ratio was significantly higher compared with patients with a normal ratio (hazard ratio, 3.5; 95% confidence interval [CI], 2.3-5.5; P < .001) and was independent of the size and type of the serum monoclonal (M) protein. Patients with an abnormal serum FLC ratio, non-immunoglobulin G (non-IgG) MGUS, and a high serum M protein level (> or = 15 g/L) had a risk of progression at 20 years of 58% (high-risk MGUS) versus 37% with any 2 of these risk factors (high-intermediate risk), 21% with one risk factor (low-intermediate risk), and 5% when none of the risk factors were present (low risk).

Aged↗

PubMed2005

Effects of a hospitalist model on elderly patients with hip fracture.

BACKGROUND: Hospitalists' increased role in perioperative medicine allows for examination of their effects on surgical patients. This study examined the effects of a hospitalist service created to medically manage elderly patients with hip fracture. METHODS: During a 2-year historical cohort study of 466 patients 65 years or older admitted for surgical repair of hip fracture, we examined outcomes 1 year prior to and subsequent to the change from the standard to the hospitalist model. RESULTS: The mean (SD) time to surgery (38 [47] vs 25 [53] hours; P<.001), time from surgery to dismissal (9 [8] vs 7 [5] days; P = .04), and length of stay (10.6 [9] vs 8.4 [6] days; P<.001) were shorter in the hospitalist group. Predictors of shorter time to surgery were care by the hospitalist group (P = .002), older age (P = .01), and fall as the mechanism of fracture (P<.001), while American Society of Anesthesia scores of 3 and 4 were associated with increased time to surgery (P<.001). Receiving care by the hospitalist group (P<.001) and diagnosis of delirium (P<.001) were associated with increased chance of earlier dismissal, while admission to the intensive care unit decreased this chance (P<.001). Diagnosis of delirium was more frequent in the hospitalist group (74 [32.2%] of 230 vs 42 [17.8%] of 236; P<.001). There were no differences in inpatient deaths or 30-day readmission rates. CONCLUSION: In elderly patients with hip fracture, a hospitalist model decreased time to surgery, time from surgery to dismissal, and length of stay without adversely affecting inpatient deaths or 30-day readmission rates.

Aged↗

PubMed2005

Ileal pouch-anal anastomosis: does age at the time of surgery affect outcome?

HYPOTHESIS: Functional outcome and quality of life in older patients (>55 years) undergoing ileal pouch-anal anastomosis (IPAA) for ulcerative colitis or familial adenomatous polyposis have been incompletely studied. Our aim was to update our understanding on how the age of the patient at the time of surgery influences functional outcome and quality of life after IPAA. METHODS: From January 1, 1981, to December 31, 2000, two thousand two patients who underwent IPAA were studied. Patients were grouped by age at operation: 45 years or younger (n = 1688), between 46 and 55 years (n = 249), and older than 55 years (n = 65). Mean age was 33.5 years. Postoperative complications, function, and quality of life were assessed with a questionnaire administered annually. RESULTS: Follow-up for patients older than 55 years was a mean +/- SD of 8.1 +/- 4.8 years. Overall, follow-up was a mean of 10.1 +/- 5.7 years. The pouch failure rate for patients older than 55 years was 1.6% at 10 years. No statistically significant difference in pouch failure between age groups was observed. Overall, frequent daytime and nighttime incontinence, respectively, occurred in 5.6% and 13.3% of the patients at 10 years. Incontinence was more common in older patients (P = .002 at 3 years). Quality of life as assessed by social activities, work, travel, sexual activity, family relationships, and sports and recreation was not significantly different among age groups. Most patients felt that their condition had improved or that they had no restrictions after IPAA. CONCLUSIONS: Postoperative complications after surgery seem to be unrelated to age at the time of surgery. Although incontinence may occur more frequently in older patients, IPAA does not adversely affect quality of life in patients older than 55 years.

Adenomatous Polyposis Coli↗

PubMed2005

Quality of life after ileal pouch-anal anastomosis and ileorectal anastomosis in patients with familial adenomatous polyposis.

PURPOSE: Differences in conventional outcomes such as functional results and the rate of complications have caused a controversy about whether the ileal pouch anal anastomosis or the ileorectal anastomosis is the preferred surgical treatment for patients with familial adenomatous polyposis. We therefore sought to ascertain not only the surgical results but also the perceptions of patients about their outcomes. METHODS: Between 1981 and 1998, 152 patients at our institution had an ileal pouch-anal anastomosis and 32 patients had an ileorectal anastomosis for familial adenomatous polyposis. Of these 184 patients, 173 were sent a study-specific quality-of-life questionnaire and the Short Form 36 health survey to determine their health-related quality of life. RESULTS: Ninety-four ileal pouch patients and 21 ileorectal patients returned the surveys. No difference was found in early postoperative complications, 5-year probability for complications, or functional results after either procedure. On the Short Form 36 health survey, the ileorectal patients had a lower mental health summary score compared with that of the ileal pouch patients but a similar physical health summary score. The study-specific questionnaire found both groups to have a comparable quality of life. CONCLUSION: Because ileal pouch-anal anastomosis has the advantage of removing as much at-risk tissue as possible with similar functional results and better mental health, it may be considered the preferred operation for most patients with familial adenomatous polyposis.

Adenomatous Polyposis Coli↗

PubMed2005

Obstructive intramural coronary amyloidosis and myocardial ischemia are common in primary amyloidosis.

PURPOSE: The purpose of this study was to determine the prevalence of clinical syndromes and pathologic changes of myocardial ischemia due to obstructive intramural coronary amyloidosis among patients with primary amyloidosis and cardiac involvement. SUBJECTS AND METHODS: Medical records and pathologic specimens were reviewed from 96 patients with primary amyloidosis and cardiac involvement at autopsy or after cardiac transplantation during a 20-year period. Medical records were reviewed for patient demographic and clinical characteristics, including evidence for syndromes of myocardial ischemia. Pathologic specimens were examined for obstructive intramural coronary amyloidosis and microscopic changes of myocardial ischemia. RESULTS: Obstructive intramural coronary amyloidosis was present in 63 of 96 patients (66%). Microscopic changes of myocardial ischemia were more common in patients with obstructive intramural coronary amyloidosis (86%) than in those without (52%) (P <.001). In the 76 patients without coexistent severe epicardial coronary atherosclerosis, changes of myocardial ischemia were more common in those with obstructive intramural coronary amyloidosis (83%) than in those without (45%) (P <.001). In patients who had tissue available for review, none had obstruction of epicardial coronary arteries from amyloid. Syndromes of myocardial ischemia affected 16 patients (25%) with obstructive intramural coronary amyloidosis but only 2 patients (6%) without (P=.027). For 11% of the patients with obstructive intramural coronary amyloidosis, a syndrome of myocardial ischemia consisting of acute myocardial infarction or angina pectoris was the first manifestation of primary amyloidosis. CONCLUSION: Most patients with primary systemic amyloidosis and cardiac involvement have obstructive intramural coronary amyloidosis and associated microscopic changes of myocardial ischemia. Syndromes of myocardial ischemia may occur in these patients.

Adult↗

PubMed2005

Focal and segmental glomerulosclerosis and plasma cell proliferative disorders.

BACKGROUND: Focal and segmental glomerulosclerosis (FSGS) is a common histological finding in patients with proteinuria. The natural history of the condition varies, and although it may be responsive to therapy, FSGS is an important cause of end-stage renal disease. FSGS can be caused by a variety of conditions, but it has been reported rarely in association with a plasma cell disorder. METHODS: Mayo Clinic databases were queried and cross-referenced for FSGS and plasma cell disorders. The diagnoses were confirmed, and relevant clinical and laboratory data were abstracted. RESULTS: A cohort of 13 patients with "idiopathic" FSGS and a monoclonal plasma cell disorder were identified. Four patients had myeloma, and 9 patients had monoclonal gammopathy of undetermined significance. Patients treated for myeloma experienced improvement in their renal lesion, and the latter relapsed when the myeloma relapsed. CONCLUSION: We show that FSGS and plasma cell disorders are temporally and epidemiologically linked. Therapy for the underlying plasma cell disorder can lead to resolution of FSGS. The emerging molecular pathogenesis of both FSGS and myeloma also provides potential mechanisms that link the 2 conditions together. Thus, physicians must rule out a plasma cell proliferative disorder in patients with FSGS before concluding that the renal lesion is idiopathic. Moreover, FSGS may respond favorably after the underlying plasma cell disorder is controlled.

Aged↗

PubMed2005

Multicentre versus single centre approach to rare diseases: the model of systemic light chain amyloidosis.

BACKGROUND: Early diagnosis and supportive therapy are important in primary systemic amyloidosis (AL). In 1986, a national network was started in Italy to increase the awareness of medical professionals, achieve early diagnoses, and provide locally qualified care. We compared the AL patient population observed at a referral center, Mayo Clinic, with that recruited through the Italian network. METHODS: All the patients diagnosed with AL between 1988 and 1998 at Mayo Clinic or in any of the centers of the Italian Amyloidosis Study Group were included. FINDINGS: The median survival of Italian patients was 30 months versus 12 months in the Mayo cohort (P<0.001). Mayo Clinic patients were older (66.4 vs. 60.1 y, P<0.001). In the Italian cohort, dominant kidney involvement was more frequent (49.3% vs. 27.8%, P<0.001), while in the Mayo group more patients had dominant cardiac amyloidosis (37.4% vs. 27.8%, P=0.03). Italian patients were more likely to have kidney involvement without heart involvement (43.7% vs. 19.6%, P<0.001). Among Italian patients, 78.9% received alkylating agents versus 60.9% in the Mayo cohort (P<0.001). The multivariate analysis showed that age, performance status, dominant heart involvement, >or=2 organs involved, and treatment with alkylating agents independently predicted survival. This study shows that AL patient populations may differ significantly between centers according to their accrual systems, with possible impact on treatment trials.

Amyloidosis↗