Plasma polyphenols and antioxidants, oxidative DNA damage and endothelial function in a diet and wine intervention study in humans

Summary: An intervention study was performed to evaluate the influence of a Mediterranean diet, a high fat diet, and their supplementation with red wine in moderate amounts, on biochemical, physiological, and clinical parameters related to atherosclerosis and other chronic diseases. For 3 months two groups of 21 male volunteers each, received either a Mediterranean diet or a high fat diet; during the second month, red wine was added isocalorically, 240 ml/day. Participants were kept under close medical and nutritional surveillance. At days 0, 30, 60 and 90, clinical, physiological and biochemical evaluations were made. Plasma vitamin C was significantly decreased in the high fat diet group compared to the Mediterranean diet group. After wine supplementation to the Mediterranean diet, a significant 13.5% increase in plasma vitamin C was observed. Furthermore, when wine was added vitamin E decreased significantly in plasma, 15% in the high fat diet and 26% in the Mediterranean diet. Total plasma antioxidant capacity (total antioxidant reactivity) increased 28% above basal levels in the Mediterranean diet group, but not in the high fat diet group. In both groups, wine induced a marked increase in total antioxidant reactivity above basal levels, 56% and 23%, respectively. Oxidative DNA damage, detected as 8-hydroxydeoxyguanosine (8-OHdG) levels in blood leukocyte DNA, was markedly increased by the high fat diet; however, it was strongly reduced, to approximately 50% basal values, after wine supplementation, both in the high fat diet and Mediterranean diet groups. Endothelial function, evaluated noninvasively as flow-mediated vascular reactivity of the brachial artery, was suppressed by the high fat diet, and was normal after wine supplementation. These effects are attributed to oxidative stress associated with a high fat diet, and to the elevated plasma antioxidant capacity associated with wine consumption and the Mediterranean diet. The results presented support the following conclusions: a high fat diet induces oxidative stress; a diet rich in fruits and vegetables enhances antioxidant defenses; wine supplementation to a high fat or a Mediterranean diet increases plasma antioxidant capacity, decreases oxidative DNA damage, and normalizes endothelial function.

Comment: Despite environmental hazards and stressful lifestyles, technological advancements have been associated with immense economical achievements in industrialized countries. While developing countries have shared the global adverse effects of those technological advancements without enjoying its economical benefits. At present, coronary artery disease and cancer are the most common causes of death worldwide, and have their origin in environmental pollution and stressful lifestyles as a result of industrialization. On the other hand, epidemiological, clinical, and experimental studies indicate that traditional diets such as the Mediterranean diet with abundant fibers and antioxidant vitamins combined with regular exercise might fully or partially protect against these and several other common diseases such as morbid obesity, alimentary diseases, dyslipidemia and diabetes mellitus. Also lifestyle factors, such as maintenance of a traditional diet and an increased level of activity, can possibly override an apparent background of genetic susceptibility to these diseases. Nevertheless, the rapid pace of events in the global village is speedily changing the lifestyles of various nations. Thus, mass educational programs are needed worldwide, particularly in undeveloped countries to prevent harmful changes in the beneficial traditional diets and lifestyle patterns evolved during centuries among different nations.

Parviz Khajehdehi, MD., Department of Medicine, Shiraz University of Medical Sciences

Source: Leighton F, Cuevas A, Guasch V, Perez DD, Strobel P, San-Martin A, Urzua U, Diez MS, Foncea R, Castillo O, Mizon C, Espinoza MA, Urquiaga I, Rozowski J, Maiz A, Germain A. Drugs Exp Clin Res. 1999; 25(2-3): 133-41


MANDATORY SECOND OPINION OF PATHOLOGIC SLIDE, IS IT NECESSARY?

Summary: When patients are referred to one's own institution for therapy based on a histopathologic diagnosis rendered at another institution, many hospitals require a second opinion of the surgical pathology material. This quality assurance practice has been threatened in the era of managed care and cost containment. METHODS: The authors reviewed the impact of mandatory second opinion surgical pathology at The Johns Hopkins Hospital. Cases were collected prospectively over a 21-month period from April 1995 to December 1996. For the purposes of this study, a changed diagnosis was defined as a discordant diagnosis resulting in a major modification in therapy or prognosis. The majority of cases involved a change between benign and malignant or a major change in tumor classification. Changes involving a modification of tumor grade or stage were not included. RESULTS: Of 6171 cases reviewed, second opinion surgical pathology resulted in 86 changed diagnoses (1.4%). Compared with the entire group, 2 organ systems were significantly more likely to undergo a change in diagnosis: serosal surfaces (9. 5%) (P < 0.0001) and the female reproductive tract (5.1%) (P < 0. 0001). Organ systems that were not more likely to undergo a change in diagnosis than the group as a whole included the skin (2.9%); central nervous system (2.8%); breast (1.4%); genitourinary system (1.2%); gastrointestinal tract (1.2%); hematologic system (1.1%); ear, nose, and throat (1.0%); bone/soft tissue (0.9%); lung (0.6%); endocrine (0%); mediastinum (0%); and cardiovascular system (0%). CONCLUSIONS: Second opinion surgical pathology can result in major therapeutic and prognostic modifications for patients sent to large referral hospitals. Although the overall percentage of affected cases is not large, the consistent rate of discrepant diagnosis uncovered by second opinion surgical pathology may have an enormous human and financial impact. Accordingly, the authors recommend that review of the original histologic material should be undertaken prior to the institution of a major therapeutic endeavor.

Comment: In this study the authors report on the outcome of uniform second opinion reviews of extramural materials received at the Johns Hospital. In reviewing 6171 cases from outside surgical pathology cases, they have find that in 86 cases (1.4%) the second opinion diagnosis differed significantly from the initial diagnosis. Of the 86 patients, 47 were female and 39 were male. Of the 86 cases changed diagnosis 80 (93%) altered the treatment plan and 81 (94%) modified the prognosis. Six of the 86 cases involved a change in diagnostic category (carcinoma, sarcoma, melanoma and lymphoma).

Examples are, a malignant fibrous histiocytoma was reclassified as malignant lymphoma and two poorly differentiated carcinoma were melanoma. Two organ system have had significantly more likely changes in the diagnosis; serosal pathology (9.5%) and gynecology pathology (5.1%).

Optional second opinion in pathology has long been practiced in Iran. Despite the controversies regarding costs, additional time, and raising of doubts, mandatory second opinion proved to be helpful. Recently Graboys and colleagues reported that second medical opinions have been used to decrease the number of unnecessary medical procedures such as coronary angiography. There are many repots concerning the benefits of this practice when surgical pathology is the sole determining factors in choosing a treatment. As quoted by the authors, The Pathology Panel and Respiratory Centers for Lymphoma Clinical Studies reviewed 8915 lymphoma cases and found that in 16.7% of Hodgkin lymphoma cases and 27.3% of non-Hodgkin lymphoma cases there comparison with that of the submitting pathologists. Also, McGowan et al reviewed 339 cases of carcinoma of the ovary and found 43 incorrect diagnosis. In 15 cases an entirely benign diagnosis was rendered on review. We also found cases in the Department of Pathology of University of Tehran, which conflicted with the initial pathology report. Many others such instances can be found in the medical literature.

Two major arguments has been forwarded regarding mandatory second opinion.

  1. Material has been prepared and processed by an accredited laboratory and examined and interpreted by a board certified pathologists, so why does it need to be reviewed at an additional cost?
  2. If only 5% (on average) of the diagnosis are changed in a major way, 95% are not. The cost-benefit ratio does not support review in 100% of the cases (1). We must accept that more general laboratories. University hospitals are short of pathologist and many laboratories are running single handed and there is not sufficient interdepartmental consultations.

We must emphasize that the second opinion may be unnecessary in many cases. It is most applicable to cases where pathologic materials dictate a major therapeutic intervention, or the diagnostic procedure is the sole determining factor for such decision making.

Regarding the cost, numerous studies have shown that the financial benefits obtained by the second opinion is far more than the cost. It is our opinion that for the individual case and for the sake of patients, a second opinion before a major therapeutic intervention is a necessity. This is especially true in Iran where pathology costs are so low that they are not significant contributors to patient costs.

We should organize some referral institutions for equality assurance (QA) particularly at the University level and should encourage the establishment of subspecialty fellowships.

Either the patient or the treating physician can request a second opinion. As is mentioned by Tomaszoki and colleagues (1) effective implementation of the second opinion system requires a close cooperation between the clinician and the pathologist.

Moslem Bahadori MD FCCP, Consultant pathologist NRITLD

Source: Tomaszewski, JE, Livolsi VA, Cancer 1999; 86: 2198-200


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