Insulin resistance and the endothelium

There is increasing evidence of a parallel progression between insulin resistance and endothelial dysfunction, suggesting a close association between insulin action and the endothelium. Numerous studies have demonstrated that endothelial dysfunction occurs early in the insulin-resistant state and is predictive of future cardiovascular events. Similarly, insulin resistance has been associated with the metabolic syndrome, which also increases the risk of adverse cardiovascular outcomes. Approaches that improve endothelial dysfunction, such as treatment with statins, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or peroxisome proliferator-activated receptor gamma ligands, have been shown to prevent both diabetes and cardiovascular disease. This article reviews the relation between endothelial dysfunction and cardiovascular disease, assesses the endothelium in the spectrum of insulin resistance, and examines the effect of the thiazolidinediones on endothelial function.     

Stage-dependent role of growth differentiation factor-9 in ovarian follicle development

GDF-9 was shown to be essential for follicle progression and is the only factor secreted by the oocyte shown to increase the number of primordial and primary follicles in vivo. Furthermore, GDF-9 is a major growth factor involved in the oocyte control of granulosa cell differentiation. A concentration gradient of the paracrine factor GDF-9 established by the oocyte could provide the basis to explain the stratification of granulosa cells in antral and preovulatory follicles. The stimulatory effects of GDF-9 on early follicle development provide a basis for the use of GDF-9 in the treatment of infertility.     

Severe community-acquired pneumonia due to Acinetobacter baumannii

STUDY OBJECTIVES: To investigate the clinical, epidemiologic, and microbiological characteristics of community-acquired pneumonia (CAP) due to Acinetobacter baumannii. METHODS: Retrospective chart and radiographic reviews of all patients who were admitted to National Taiwan University Hospital from January 1993 to August 1999, fulfilled the criteria for CAP, and had an isolate of A. baumannii from blood or pleural fluid at hospital admission. RESULTS: Thirteen patients (9 men and 4 women; age range, 37 to 85 years) met the criteria. Conditions associated with the infection included male gender, old age, alcoholism, malignancy, cerebrovascular disease, diabetes mellitus, renal disease, and liver cirrhosis. Eleven patients (85%) acquired the infection during the warmer months of April to October. Twelve patients (92%) had a fulminant course presenting with septic shock and respiratory failure, and 11 patients (85%) needed ventilator support and were treated in an ICU. Six patients (46%) had leukopenia. Lobar consolidations were found in 12 patients (92%), and pleural effusions were present in 4 patients (31%). All patients had positive blood culture results, two patients (15%) had positive pleural effusion culture findings, and nine patients (69%) positive sputum culture results. All the isolates were susceptible to imipenem, and most were susceptible to aminoglycosides, ceftazidime, ciprofloxacin, and extended-spectrum penicillins. Eight patients (62%) died. Four of the five survivors were initially treated with combination of a third-generation cephalosporin and an aminoglycoside. CONCLUSION: A. baumannii should be considered as a possible etiologic agent in community-acquired lobar pneumonia when (1) patients with a fulminant course present during the warmer and more humid months of the year, and (2) patients are younger alcoholics. A good sputum smear, defined as a Gram stain smear of an adequate sputum specimen that comes from the lower respiratory tract and contains > 25 leukocytes per high-power (100x) field on microscopic examination, can help early diagnosis and treatment. A combination of a third-generation cephalosporin and an aminoglycoside may be appropriate empirical therapy.     

Familial factors in the antihypertensive response to lisinopril

BACKGROUND: Although it is widely recognized that there are familial elements in the pathogenesis of hypertension, remarkably little is known about the influence of family history on response to specific antihypertensive agents. METHODS: This study was designed to address that issue by comparing the depressor response to lisinopril in a dose range of 10 to 40 mg in 74 patients enrolled as sibling pairs. Because all patients were treated with lisinopril, ambulatory blood pressure monitoring (ABPM), an objective measure not influenced by the investigators, was used to assess the primary blood pressure (BP) outcome variable. RESULTS: Diastolic BP was highly correlated between sibling pairs at baseline (r = 0.476; P < .03) and on treatment (r = 0.524; P = .0021). Ethnicity/race had a striking influence on lisinopril dose and response rate. Among African American patients, 23 of 28 reached the top dose of 40 mg/day, whereas only 14 of 36 Caucasian patients reached that dose level. Among Caucasians, 92% responded, and only 48% of African Americans. Responders were characterized by being younger and heavier, having significantly lower microalbuminuria at baseline, higher baseline renal plasma flow (RPF), and higher urinary kallikrein. CONCLUSION: Among Caucasians, the presence of a hypertensive sibling predicts a striking therapeutic response to angiotensin converting enzyme inhibition.     

Papillary thyroid carcinomas with lung metastases.

BACKGROUND: Limited information is available on the presentation, treatment outcomes, and prognostic factors of papillary thyroid carcinoma with lung metastases. METHODS: This study retrospectively analyzed the data of 2003 patients with thyroid cancer who were treated and followed up at Chang Gung Memorial Hospital from January 1979 to December 2002. In total, 1516 papillary thyroid carcinomas were enrolled. One hundred two (6.7%) papillary thyroid carcinomas with lung metastases were followed including 57 women with mean age of 41.7 +/- 17.3 years and 45 men with mean age of 49.6 +/- 17.2 years. These patients included 52 patients with papillary thyroid carcinoma who presented with lung metastases at the time of diagnosis. The 102 cases of papillary thyroid carcinomas with lung metastases included 72 cases with lung metastases only, and 30 cases with other organ involvement. RESULTS: After mean follow-up periods of 8.8 +/- 0.6 years, 28 (27.5%) of the patients with lung metastasis died, while 6 improved to clinical stage I. The 5-, 10-, 15-, and 20-year survival rates in patients with papillary thyroid carcinoma without distant metastasis and in the lung metastases groups were 99.0%, 98.5%, 98.0%, 98.0%, and 91.3%, 75.0%, 64.0%, 51.2%, respectively. Comparing the Kaplan-Meier survival curves between the patients with papillary thyroid carcinomas with lung metastases only and those with multiorgan metastases demonstrates no statistically significant difference in mortality rates. However, age, gender, postoperative thyroglobulin (Tg) level and tumor size displayed statistically significant differences between the lung metastases and no distant metastasis groups. Fifty of the 102 patients with papillary thyroid carcinomas with lung metastases developed lung metastases during follow-up. Larger amounts of remnant thyroid tissues with higher Tg levels were noted in these patients compared to those without distant metastasis. CONCLUSIONS: The prognosis of patients with papillary thyroid carcinoma with lung metastases at time of diagnosis is the same as for those whose lung metastases are discovered later. Survival analysis demonstrates no difference between lung metastases and multiorgan metastases.     

Initial and cyclic recruitment of ovarian follicles

Mammalian ovaries consist of follicles as basic functional units. The total number of ovarian follicles is determined early in life, and the depletion of this pool leads to reproductive senescence. Each follicle develops to either ovulate or, more likely, to undergo degeneration. The dynamics of ovarian follicle development have interested endocrinologists and developmental biologists for many years. With the advent of assisted reproductive techniques in humans, the possibility of regulating follicle development in vivo and in vitro has gained clinical relevance. In this review, we focus upon key branching points during the development of ovarian follicles as well as factors involved in determining the eventual destiny of individual follicles. We discuss inconsistencies in the literature regarding the definitions of follicle recruitment and selection and propose to name the two major steps of follicle development as initial and cyclic recruitment, respectively. Because some of these disparities have arisen due to differences in the animal systems studied, we also compare the development of the ovarian follicles of both humans and rats. We also review the status of knowledge of several puzzling clinical issues that may provide important clues toward unlocking the mechanisms of follicle development.     

Acinar cell carcinoma of the pancreas. Report of two cases with complex histomorphologic features causing diagnostic problems.

Two pancreatic acinar cell carcinomas with distinctive morphologic features are described. Both tumors showed a variable combination of different histomorphologic patterns formed by tumor cells in different degrees of acinar differentiation. They caused diagnostic problems involving differential diagnosis from normal pancreas and from mixed acinar-endocrine tumor. The presence of mitosis, nuclear atypia, and tumor necrosis are helpful for recognizing its neoplastic nature, and the ultrastructural finding of zymogen-like but not neurosecretory granules prevented the misdiagnosis of a mixed acinar-endocrine tumor. Immunohistochemical studies revealed variable immunostaining patterns corresponding to different types of tumor cell present. Both tumors were found to be aneuploid by flow cytometric DNA study. Our study confirmed previous observations that pancreatic acinar cell carcinomas are highly malignant tumors in spite of the fact that they can differentiate into highly differentiated acinar cells.     

Ticlopidine-associated aplastic anemia

 Serious hematologic complications associated with ticlopidine have been reported, including aplastic anemia. We report here an additional case of fatal aplastic anemia due to ticlopidine. A 66-year-old male patient developed fever and pancytopenia 2 months after ticlopidine was started. Despite the administration of granulocyte colony-stimulating factor (G-CSF) and broad-spectrum antibiotics, as well as aggressive red cell and platelet transfusions, the patient died 16 days after admission due to septic shock. Eighteen other cases of ticlopidine-induced aplastic anemia published in the English literature are also reviewed and presented here. Eight of the total 19 patients (including the one reported here) have died, mostly due to infection. Of the seven who received supportive treatment only, four had spontaneous recovery. Nine cases were treated with G-CSF or granulocyte-macrophage colony-stimulating factor (GM-CSF), and response was observed in only four of them. Several other cases were treated with high-dose corticosteroids or androgens; however, it was not possible to evaluate the efficacy of these treatments because of the limited number of cases. In the absence of satisfactory treatment for ticlopidine-induced aplastic anemia at present, it may be reasonable to try antilymphocyte globulin or cyclosporine. Also, great efforts should be made in the prevention and management of infection accompanying this disease. Received: 2 November 1997 / Accepted: 12 January 1998