Possibility of selection against mtDNA mutations in tumors

Several studies of tumors have revealed substantial numbers of clonally expanded somatic mutations in mitochondrial DNA (mtDNA), not observed in adjacent intact tissues. These findings were interpreted as indicating the involvement of mtDNA mutations in tumorigenesis. Such comparisons, however, ignore an important confounding factor: the monoclonal origin of tumors as opposed to the highly polyclonal nature of normal tissues. Analysis of recently published data on the incidence of somatic mutations in nontumor monoclonal cells suggests that, contrary to the prevailing view, the process of tumorigenesis may be accompanied by active selection against detrimental mtDNA mutations.     

Use of the SF-8 to assess health-related quality of life for a chronically ill,low-income population participating in the Central Louisiana Medication Access Program (CMAP)

Objectives: The utility of the SF-8 for assessing health-related quality of life (HRQL) is demonstrated. Race and gender differences in physical component (PCS) and mental component (MCS) summary scores among participants in the CENLA Medication Access Program (CMAP), along with comparisons to the United States population are made. Methods: Age-adjusted multiple linear regression analyses were used to compare 1687 CMAP participants to the US population. Internal race and gender comparisons, adjusting for age and the number of self reported diagnoses, were also obtained. The paired t-test was used to assess 6-month change in PCS and MCS scores for a subset of 342 participants. Results: CMAP participants have PCS and MCS scores that are significantly 10–12 points lower than the US population, indicating lower self-reported HRQL. Females have significantly higher PCS and significantly lower MCS than males. African–Americans have significantly higher MCS than Caucasians. Significant increases in both PCS and MCS were observed for the subset of participants after 6months of intervention. Conclusions: The expected lower baseline PCS and MCS measures and the expected associations with age and number of diagnoses indicate that the SF-8 survey is an effective tool for measuring the HRQL of participants in this program. Preliminary results indicate significant increases in both PCS and MCS 6months after intervention.     

Serum glycoproteins in diagnosis and monitoring of patients with large-bowel cancer

The profile of serum glycoproteins is altered in malignancy with a relative increase in acute phase reactant proteins. A prospective study has been performed to investigate three sugar moieties (hexose, hexosamine and sialic acid) of these glycoproteins in the serum of large-bowel cancer patients as a possible guide to recurrence, and to compare these three variables with carcinoembryonic antigen (CEA). The three variables indicated the presence of colorectal cancer in over 65 per cent of 107 cancer-bearing subjects. Furthermore, the appearance of metastatic disease was associated with abnormalities in these variables in 10 of 11 patients, and appears more accurately reflected than with CEA. However, the three variables and CEA are cumulative in their value for predicting recurrent cancer. Monitoring of acute phase reactant proteins may therefore be of potential clinical benefit for monitoring of colorectal cancer patients at high risk of recurrence.     

Analysis of surgical versus medical therapy in active complicated native valve infective endocarditis

From 1972 to 1980, 23 patients (Group A) with native valve infective endocarditis underwent surgical intervention, often for multiple indications, during the active stage of the infective process because of progressive class III and IV (New York Heart Association) heart failure (12 patients), persistent severe hypotension (3 patients), uncontrolled infection for over 21 days (11 patients), aortic root abscess (2 patients), and pericarditis (1 patient). Eighty-five patients (Group B) with active native valve endocarditis, matched for severity of illness, were treated medically. Two patients (9%) in Group A and 43 patients (51%) in Group B died during the hospital admission (p < 0.001). Any difference in long-term cumulative survival rate between the 2 groups was largely due to the beneficial impact of surgical management on the hospital mortality. Of 23 patients in Group A, 11 (48%) had an entirely uncomplicated postoperative course. Long-term mortality rates in those with aortic valve endocarditis treated medically (79%) were significantly higher than in those with mitral valve involvement (47%) (p < 0.05). Patients with aortic valve involvement treated surgically had a better hospital (p < 0.005) and long-term (p < 0.005) survival rate than those treated medically. Two groups at risk for postoperative complications were identified; 3 of 11 patients (27%) with uncontrolled infection had an early postoperative recurrence, and 4 of 7 patients (57%) with an aortic root abscess had postoperative prosthetic paravalvular regurgitation.

Surgery therefore effects a substantial reduction in hospital mortality in patients with complicated active infective endocarditis (9% versus 51%), but patients with preoperative prolonged periods of uncontrolled infection or with aortic root abscess are liable to postoperative complications.     

Double outlet right ventricle: clinical and anatomical spectrum.

Thirty-two patients with double outlet right ventricle (DORV) were studied between 1960 and 1976. Associated congenital defects frequently compounded the difficulty of clinical diagnosis. Cardiac catheterisation was performed in 27 patients, and the ventriculograms were studied with particular regard to the relative positions of the great vessels to each other and to the ventricular septal defect. These relationships determine which corrective operation is possible. Correction has been performed in 12 patients with a perioperative mortality of 25%. Although mitral-aortic discontinuity was demonstrated in all cases, consideration of the anatomical spectrum included in the term DORV suggests that discontinuity is not an essential feature. In common with other clinical data and in contrast with necropsy studies, none of our patients was found to show the normal relationship of the great vessels to each other, in which the aorta lies posterior and to the right of the pulmonary artery. The reason for this difference between the clinical and necropsy findings is not apparent. A similar disparity was shown with regard to pulmonary stenosis, which was demonstrated at catheterisation in 68% of the 27 patients (mean gradient 68 +/- 3 mmHg), in contrast with incidences of 18% and 25% in recent necropsy series. Patients in the necropsy studies were frequently neonates or infants, in whom death may have been the result of intractable cardiac failure secondary to excessive pulmonary blood flow. In older patients without pulmonary stenosis and with pulmonary hypertension, frequent observation is imperative so that surgical treatment can be instituted before the development of irreversible pulmonary vascular disease.