The 11th edition of Harrison's Principles of Internal Medicine welcomes Anthony Fauci to its editorial staff, in addition to more than 85 new contributors. While the organization of the book is similar to previous editions, major emphasis has been placed on disorders that affect multiple organ systems. Important advances in genetics, immunology, and oncology are emphasized. Many chapters of the book have been rewritten and describe major advances in internal medicine. Subjects that received only a paragraph or two of attention in previous editions are now covered in entire chapters. Among the chapters that have been extensively revised are the chapters on infections in the compromised host, on skin rashes in infections, on many of the viral infections, including cytomegalovirus and Epstein-Barr virus, on sexually transmitted diseases, on diabetes mellitus, on disorders of bone and mineral metabolism, and on lymphadenopathy and splenomegaly. The major revisions in these chapters and many

Harrison's Principles of Internal Medicine

Excess body weight is associated not only with an increased risk of type 2 diabetes and cardiovascular disease (CVD)butalsowithvarioustypesofmalignancies.Adiponectin,themostabundantproteinsecretedbyadipose tissue, exhibits insulin-sensitizing, antiinflammatory, antiatherogenic, proapoptotic, and antiproliferative properties.Circulatingadiponectinlevels,whicharedeterminedpredominantlybygeneticfactors,diet,physical activity, and abdominal adiposity, are decreased in patients with diabetes, CVD, and several obesity-associated cancers. Also, adiponectin levels are inversely associated with the risk of developing diabetes, CVD, and several malignancies later in life. Many cancer cell lines express adiponectin receptors, and adiponectin in vitro limits cell proliferation and induces apoptosis. Recent in vitro studies demonstrate the antiangiogenic and tumor growth-limiting properties of adiponectin. Studies in both animals and humans have investigated adiponectin and adiponectin receptor regulation and expression in several cancers. Current evidence supports a role of adiponectin as a novel risk factor and potential diagnostic and prognostic biomarker in cancer. In addition, either adiponectin per se or medications that increase adiponectin levels or up-regulate signaling pathways downstream of adiponectin may prove to be useful anticancer agents. This review presents the role of adiponectin in carcinogenesis and cancer progression and examines the pathophysiological mechanisms that underlie the association between adiponectin and malignancy in the context of a dysfunctional adipose tissue in obesity. Understanding of these mechanisms may be important for the development of preventive and therapeutic strategies against obesity-associated malignancies. (Endocrine Reviews 33: 547–594, 2012)

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The Role of Adiponectin in Cancer: A Review of Current Evidence

Robbins Pathologic Basis of Disease

Hyponatremia

A novel, externally validated inflammation-based prognostic algorithm in hepatocellular carcinoma: the prognostic nutritional index (PNI)

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Acute-phase response proteins (APRP), cytokines and hormones have been claimed to be an independent prognostic factor of malignancies, however the basis for their association with prognosis remains unexplained. We suggest that in colon malignancies, as similar to pancreatic and lung cancers, changes in APRP are associated with angiogenesis. C-reactive protein (CRP), albumin, IL-1α, IL-1β, IL-6, IL-8, IL-10, TNF-α, midkine, VEGF-A, VEGF-C, leptin, adiponectin, and ghrelin serum levels are studied in 126 colon cancer patients and 36 healthy subjects. We found statistically significant difference and correlations between two groups. We found significantly higher serum CRP, IL-1α, IL-1β, IL-6, IL-8, IL-10, TNF-α, VEGF-A, VEGF-C and leptin concentrations in patients relative to controls (p < 0.001). We found lower levels of the serum albumin, midkine, adiponectin and ghrelin in patients compared to control subjects (p < 0.001). Cachexia in patients with colon cancers is associated with changes in APRP, cytokines and hormone concentrations. These biomarkers and cachexia together have a direct relationship with accelerated angiogenesis. This may lead to a connection between the outcomes in malignancies and the biomarkers.

/pdf/the-relationship-among-acute-phase-response-proteins-50hnznkifp.pdf

The relationship among acute-phase response proteins, cytokines and hormones in cachectic patients with colon cancer.

Data on the antioxidant levels enzyme in patients with hyperthyroidism are limited and conflicting. Therefore, the objective of this study was to evaluate the oxidative status using an automated method in patients with hyperthyroidism. Thirty-six subjects with hyperthyroidism and 30 healthy controls were enrolled in this study. Serum oxidative status was determined via measurement of total antioxidant capacity (TAC) and total oxidant status (TOS) and calculation of oxidative stress index (OSI). Serum TAC levels were significantly lower in patients with hyperthyroidism than controls (P = 0.002), while serum TOS levels and OSI values were significantly higher (P = 0.008, 0.004; respectively). Serum TAC levels were correlated with TSH levels (rho = 0.223, P = 0.032), FT3 levels (rho = −0.434, P = 0.002) and FT4 levels (rho = −0.363, P = 0.003) in patients. Further, TOS levels and OSI values were correlated with TSH levels (rho = −0.245, P = 0.037; rho = −0.312, P = 0.011, respectively), FT3 levels (rho = 0.293, P = 0.017, rho = 0.505, P = 0.002, respectively), and FT4 levels (rho = 0.302, P = 0.006, rho = 0.321, P = 0.008, respectively) in patients. Duration of disease was significantly correlated with OSI values in patients (rho = 0.420, P = 0.011), while no correlation with serum TAC levels and TOS levels (P > 0.05). Oxidants are increased and antioxidants are decreased in patients with hyperthyroidism; as a result, the oxidative–antioxidative balance is shifted to the oxidative side. Increased oxidative stress may play a role in the pathogenesis of hyperthyroidism. It is believed that supplementation of antioxidant vitamins such as vitamins C and E may be helpful for these patients.

Evaluation of oxidative status in patients with hyperthyroidism.

Human dicrocoeliosis is reported sporadically in various parts of the world. We report a case in a 21-year-old male, who had right upper abdominal pain, weight loss, and chronic relapsing watery di...

Human infection with Dicrocoelium dendriticum in Turkey.

AIM: To represent our clinical experience in the treatment of intestinal perforation arising from typhoid fever.

METHODS: The records of 22 surgically-treated patients with typhoid intestinal perforation were evaluated retrospectively.

RESULTS: There were 18 males and 4 females, mean age 37 years (range, 8-64 years). Presenting symptoms were fever, abdominal pain, diarrhea or constipation. Sixteen cases were subjected to segmental resection and end-to-end anastomosis, while 3 cases received 2-layered primary repair following debridement, one case with multiple perforations received 2-layered primary repair and end ileostomy, one case received segmental resection and end-to-end anastomosis followed by an end ileostomy, and one case received segmental resection and end ileostomy with mucous fistula operation. Postoperative morbidity was seen in 5 cases and mortality was found in one case.

CONCLUSION: Intestinal perforation resulting from Salmonella typhi is an important health problem in Eastern and Southeastern Turkey. In management of this illness, early and appropriate surgical intervention is vital.

Outcome of surgical treatment of intestinal perforation in typhoid fever.

PURPOSE We aimed to evaluate the effectiveness of diffusion-weighted magnetic resonance imaging (DW-MRI) and apparent diffusion coefficient (ADC) values in the diagnosis of acute appendicitis and differentiation of perforated and nonperforated appendicitis cases, with histopathologic correlation. MATERIALS AND METHODS Sixty consecutive patients (34 males, 26 females; mean age, 35.6±15.5 years; range, 17-83 years) with a presumptive diagnosis of acute appendicitis were included in this prospective study. With a 1.5 Tesla MRI unit, DW-MRI examinations were performed with b values of 50, 400, and 800 s/mm(2). The mean ADC values of case and control groups, as well as in perforated and nonperforated groups were compared. RESULTS Of the 60 cases, 44 had a radiological diagnosis of acute appendicitis, and 16 were regarded as normal. Of the 40 patients who underwent surgical operation, 12 had a histopathological diagnosis of perforated appendicitis, and 28 had nonperforated appendicitis. Mean ADC value in patients with acute appendicitis (1.01±0.26×10(-3) mm(2)/s) was lower than the control group (1.85±0.13×10(-3) mm(2)/s) (P < 0.001). Mean ADC value of the perforated group (0.79±0.19×10(-3) mm(2)/s) was lower than the nonperforated group (1.11±0.22×10(-3) mm(2)/s) (P < 0.001). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy rate of DW-MRI in the diagnosis of acute appendicitis were 97.5%, 100%, 97.5%, 100%, and 98.1%, respectively. CONCLUSION DW-MRI and ADC quantification are effective in the diagnosis of acute appendicitis, both in perforated and nonperforated cases.

The value of diffusion-weighted imaging and apparent diffusion coefficient quantification in the diagnosis of perforated and nonperforated appendicitis.

Ahmet Cumhur Dülger

Papers

The relationship among acute-phase response proteins, cytokines and hormones in cachectic patients with colon cancer.

Evaluation of oxidative status in patients with hyperthyroidism.

Human infection with Dicrocoelium dendriticum in Turkey.

Outcome of surgical treatment of intestinal perforation in typhoid fever.

The value of diffusion-weighted imaging and apparent diffusion coefficient quantification in the diagnosis of perforated and nonperforated appendicitis.