Citations

Background— Although age-adjusted cardiovascular disease (CVD) mortality has declined over the past decades, controversies remain about whether this trend was similar across locations of death and disease categories and about the existence of age and sex disparities. Methods and Results— We examined CVD mortality trends in Olmsted County, Minnesota, between 1979 and 2003 using the categories defined by the American Heart Association, including coronary heart disease (CHD), non-CHD diseases of the heart, and noncardiac circulatory diseases. Data on demographics, cause, and location of death of all 6378 residents who died of CVD were analyzed. Although decreases in the age-adjusted rates occurred in all groups, the magnitude of the decline varied widely. Lesser annual declines were noted in out-of-hospital than in-hospital deaths (1.8% versus 4.8%; P <0.001), in older than in younger persons (1.5% at age ≥85 years versus 3.9% for those ≤74 years of age; P <0.001), and in women relative to men (2.5% versus 3.3%; P =0.007). Furthermore, although CHD showed a marked annual decrease (3.3%), more modest decrements were found for non-CHD diseases of the heart (2.1%) and noncardiac circulatory diseases (2.4%) ( P =0.02 and P =0.04 for the comparison with CHD decline, respectively). Conclusions— Over the past 25 years, CVD mortality declined markedly in the community, but there were large disparities in the magnitude of the decline, resulting in a shift in the distribution toward out-of-hospital and non-CHD deaths. Further reduction in CVD mortality will require strategies directed at elderly persons and women, in whom out-of-hospital rates have improved only minimally.

While “sinus” headache is a widely accepted clinical diagnosis, many medical specialists consider it to be an uncommon cause of recurrent headaches. Unnecessary diagnostic studies, surgical interventions, and medical treatments are often the result of the inappropriate diagnosis of sinus headache. Both the International Headache Society and the American Academy of Otolaryngology–Head and Neck Surgery have attempted to characterize conditions leading to headaches of rhinogenic origin. However, they have done so from different perspectives and in isolation from the other specialty groups. An interdisciplinary ad hoc committee recently convened to discuss the role of sinus disease and the nose in the etiology of headache and to review recent epidemiologic studies suggesting that sinus headache (headache of rhinogenic origin) and migraine are frequently confused with one another. Clinical trial data are presented which clearly indicate that the majority of sinus headaches can actually be classified as migraines. This committee reviewed scientific evidence available from multiple disciplines and concludes that considerable research and clinical study are needed to further understand and explain the role of nasal pathology and autonomic activation in migraine and headaches of rhinogenic origin. However, there was a consensus from this group that greater diagnostic and therapeutic attention needs to be given to patients complaining of sinus headache that may indeed be due to the nose.

AbstractUseful palliation can often be achieved when standard treatment approaches of external beam irradiation and chemotherapy with or without resection are used for locally advanced primary rectal malignancies. Local control and long‐term survival are achieved in only 10% to 50% of patients, however, due to the limited irradiation tolerance of surrounding organs and tissues. Encouraging trends exist in separate intra‐operative irradiation analyses from Massachusetts General Hospital and Mayo Clinic with regard to improvement in local control and possibly survival of locally advanced rectal lesions, warranting continued evaluation of such approaches. Disease control within the intra‐operative and external irradiation field is decreased, however, when the surgeon is unable to accomplish gross total resection. Therefore it seems reasonable to consistently add 5‐Fluorouracil with or without Leucovorin during external irradiation and to evaluate the use of dose modifiers, such as sensitizers or hyperthermia, in conjunction with intra‐operative irradiation. Since high systemic failure rates exist with both locally advanced primary and recurrent lesions, more effective chemotherapy needs to be evaluated during external irradiation as well as after completion of such. In view of survival advantages with 5‐Fluorouracil plus Leucovorin versus 5‐Fluorouracil alone for metastatic disease, this regimen is currently being employed. Even with locally recurrent lesions, the aggressive multimodality approaches including intra‐operative irradiation have resulted in improved local control, and long‐term survival rates of 20% to 25% versus an expected 5% with conventional techniques in historical series.

AbstractRelapses after “curative resection” of rectal cancer may be localized and thus amenable to surgical treatment. The risk of relapse may be higher than previously believed depending on adequacy and length of follow‐up, the diagnostic modalities used, and the number of autopsies performed. Technical refinements such as a distal margin >2 cm, radical pelvic lymphadenectomy, and high ligation of the inferior mesenteric artery at the aorta do not appear to diminish the risk of recurrence. A wider lateral margin and a more complete excision of the mesorectum may be beneficial, but this is yet unproven. Surgery for isolated, locally recurrent lesions should be limited to carefully selected patients and performed in tertiary centers using a team approach. Whether such radical “salvage” procedures are justifiable merits further careful evaluation.

AbstractApproximately 5% of rectal cancers are locally advanced with adherence to the vagina, uterus, bladder, prostate, or other structures. Sacral involvement is fortunately rare in primary cancers. In about 50% of patients there is histologic confirmation of tumor invasion in the area of adherence. It is important to recognize the nature of these tumors pre‐operatively so that the patient can be prepared for an exenterative procedure should this be necessary. When these tumors are removeden bloc, 5‐year survival rates of 50% can be obtained with survival depending on the presence or absence of regional metastasis and also the presence or absence of histologic tumor invasion into adjacent structures.

AbstractResults from epidemiologic studies have provided insights into the etiology of large bowel cancer. Markedly diverse incidences of colorectal cancer exist in various parts of the world and within different regions of a given country. Studies of migrant populations have revealed a role for environmental factors, particularly dietary, in the etiology of colorectal cancers. Genetic factors and inflammatory bowel disease also place certain individuals at increased risk. Sedentary lifestyle, cholecystectomy, and ureterosigmoidostomy may also increase the risk of developing large bowel cancer.

AbstractThe experience at the Mayo Clinic, Rochester, Minnesota, U.S.A., with abdominal colectomy, mucosal proctectomy, and ileo‐anal anastomosis is now approaching 600 patients. The procedure is safe and, with careful timing and selection of patients, can be performed with minimal mortality. Postoperative morbidity, however, is still considerable, even in the most experienced hands. Increasing experience with the procedure has been shown to be associated with a continuing decline in the incidence of postoperative complications, and a defunctioning ileostomy is still a necessity in the majority of patients.Long‐term functional results of the procedure are satisfactory and have been shown to improve both with the experience of the operator and with the passage of time after surgery. Patient acceptance remains the ultimate sanction, and it appears that the majority of patients are satisfied with their outcome after ileo‐anal anastomosis, with only very few being prepared to consider an alternative. The operation appears to provide a superior quality of life relative to that expected after proctocolectomy and Brooke ileostomy.Not all patients with chronic ulcerative colitis or adenomatosis coli are potential candidates for this procedure, however. The problems of age, obesity, indeterminate colitis and Crohn's disease, co‐existing colorectal neoplasia, technical difficulties at the time of the operation, and the wishes of the patient all must be taken into consideration when assessing the optimal operation in a particular situation. Proctocolectomy with Brooke ileostomy or continent ileostomy and total abdominal colectomy with ileo‐rectal anastomosis both still have roles in the management of diseases such as chronic ulcerative colitis and adenomatosis coli. For a patient who is young, relatively fit, and well motivated and in whom there is little or no doubt about the diagnosis, ileo‐anal anastomosis must be considered as the possible treatment of choice. Increasing experience with the procedure and improvements in functional results seem to be confirming this position.

Purpose Preclinical studies of mafosfamide, a preactivated cyclophosphamide analog, were performed to define a tolerable and potentially active target concentration for intrathecal (IT) administration. A phase I and pharmacokinetic study of IT mafosfamide was performed to determine a dose for subsequent phase II trials. Patients and Methods In vitro cytotoxicity studies were performed in MCF-7, Molt-4, and rhabdomyosarcoma cell lines. Feasibility and pharmacokinetic studies were performed in nonhuman primates. These preclinical studies were followed by a phase I trial in patients with neoplastic meningitis. There were five dose levels ranging from 1 mg to 6.5 mg. Serial CSF samples were obtained for pharmacokinetic studies in a subset of patients with Ommaya reservoirs. Results The cytotoxic target exposure for mafosfamide was 10 μmol/L. Preclinical studies demonstrated that this concentration could be easily achieved in ventricular CSF after intraventricular dosing. In the phase I clinical trial, headache was the dose-limiting toxicity. Headache was ameliorated at 5 mg by prolonging the infusion rate to 20 minutes, but dose-limiting headache occurred at 6.5 mg dose with prolonged infusion. Ventricular CSF mafosfamide concentrations at 5 mg exceeded target cytotoxic concentrations after an intraventricular dose, but lumbar CSF concentrations 2 hours after the dose were less than 10 μmol/L. Therefore, a strategy to alternate dosing between the intralumbar and intraventricular routes was tested. Seven of 30 registrants who were assessable for response had a partial response, and six had stable disease. Conclusion The recommended phase II dose for IT mafosfamide, administered without concomitant analgesia, is 5 mg over 20 minutes.

Background— In case series, mitral regurgitation (MR) increased the risk of death after myocardial infarction (MI), yet the prevalence of MR, its incremental prognostic value over ejection fraction (EF), and its association with heart failure and death after MI in the community is not known. Methods and Results— The prevalence of MR and its association with heart failure and death were examined among 1331 patients within a geographically defined MI incidence cohort between 1988 and 1998. Echocardiography was performed within 30 days after MI in 773 patients (58%), and MR was present in 50% of cases, mild in 38%, and moderate or severe in 12%. Among patients with MR, a murmur was inconsistently detected clinically. After 4.7±3.3 years of follow-up, 109 episodes of heart failure and 335 deaths occurred. There was a graded positive association between the presence and severity of MR and heart failure or death. Moderate or severe MR was associated with a large increase in the risk of heart failure (relative risk 3.44, 95% CI 1.74 to 6.82, P <0.001) and death (relative risk 1.55, 95% CI 1.08 to 2.22, P =0.019) among 30-day survivors independent of age, gender, EF, and Killip class. Conclusions— In the community, MR is frequent and often silent after MI. It carries information to predict heart failure or death among 30-day survivors independently of age, gender, EF, and Killip class. These findings, which are applicable to a large community-based MI cohort, suggest that the assessment of MR should be included in post-MI risk stratification.