Repair of soft tissue to bone using a biodegradable suture anchor

A decrease in blood androgen levels is well documented in women who experience natural or surgical menopause. This change may be associated with various negative effects on bone metabolism in addition to psychosocial and sexuality aspects of life. A review of published information on androgen replacement therapy shows that major benefits may be achieved; unfortunately, only minimal quality information is available to help clinicians make decisions about this type of therapy. In this review, we point out the potential benefits and risks to bone, lipid and carbohydrate metabolism, and sexuality; in addition, we discuss potential risks of neoplasms and virilizing somatic changes. Long-term, physiologic, and well-designed androgen replacement studies should be performed to obtain the knowledge needed to guide therapy in this important area.     

Steady-state pharmacokinetic properties of pramipexole in healthy volunteers

Pramipexole is a dopamine receptor agonist that has proved effective in the treatment of Parkinson's disease. The pharmacokinetic properties of pramipexole at steady-state concentrations were studied in 16 healthy men and women at four dose levels throughout the range recommended for Parkinson's patients. Plasma and urine samples collected within the four dose intervals were assayed for concentrations of pramipexole, using high-performance liquid chromatography. The total oral clearance for all participants was 419 mL/min. The mean volume of distribution and elimination half-life for all participants was 486 +/- 93.2 L and 12.9 +/- 3.27 hours. Concentrations of pramipexole were proportional to dose, although the drug's pharmacokinetic properties differed between men and women. The area under the concentration-time curve for each dose level was 35% to 43% greater in women, mainly because of a 24% to 27% lower oral clearance. The mean creatinine clearance in men and women was 112 +/- 12.8 mL/ min/1.73 m2 and 80.9 +/- 15.6 mL/min/1.73 m2, respectively. The renal clearance of pramipexole accounts for approximately 80% of oral clearance, and there was a significant correlation between renal and creatinine clearances. The influence of gender could not be distinguished from the influence of age and the resulting reduced creatinine clearance, but the measurement of pharmacokinetic properties produced linear results in both men and women.     

Nutritional aspects of dissimilatory sulfate reduction in the human large intestine

Physical pain is a major trigger for changes in many homeostatic systems of the body physiology. Our aim was to study the relationship between blood pressure, metabolism and pain perception in subjects with chronic pain symptoms. This was undertaken in a population-based study in primary health care, including subjects with widespread pain (n = 16), or localized pain (n = 15), and pain-free controls (n = 14). The main outcome measures were office and ambulatory blood pressure, glucose, insulin, lipids, and beta-endorphin. Subjects with widespread pain were more obese and showed higher levels than controls (p < 0.05) of fasting glucose (4.9 vs 4.5 mmol/l), cholesterol (6.9 vs 5.8 mmol/l) and office systolic blood pressure (133 vs 120 mmHg), while the subjects reporting localized pain had values in-between. Ambulatory blood pressure, insulin and beta-endorphin levels did not differ between the groups. In conclusion, subjects with widespread and/or intense chronic pain have higher BMI, more pronounced metabolic disturbances and higher (office) systolic blood pressure, but not ambulatory blood pressure, than subjects without chronic pain. Future epidemiological studies are needed to test whether this is compatible with increased cardiovascular risk.     

Mutational analysis of the Yersinia enterocolitica virC operon: characterization of yscE, F, G, I, J, K required for Yop secretion and yscH encoding YopR

Pathogenic yersiniae secrete the Yop anti-host proteins using a type-III secretion pathway. The components of the secretion machinery are encoded by three loci on the pYV plasmid: virA, virB, and virC. In this paper we describe the characterization of eight non-polar mutants of the virC locus, constructed by allelic exchange. The yscE, FG, I, J and K mutants were defective in Yop secretion and independent of Ca2+ (CI) for their growth at 37 degrees C. Substitution of the 12 N-terminal amino-acid residues of YscF impaired secretion of YopB and YopD only and led also to a CI phenotype. The culture supernatant of the yscH mutant contained all the Yops except the 18 kDa YopR. Complementation experiments and an immunoblot analysis confirmed that YopR is encoded by the yscH gene. The LD50 for the mouse of the yscH mutant was 10-fold higher than that of the parental strain indicating that YopR is involved in pathogenesis. The phenotype of the yscM mutant was similar to that of the wild-type strain. However, overproduction of YscM from a multicopy plasmid in wild-type Yersinia enterocolitica prevented Yop secretion and synthesis. A hybrid YopH-LacZ' protein, encoded by a gene transcribed from the lac promoter, was secreted by a strain overexpressing YscM, showing that the secretion machinery was still functional. These results indicate that YscM plays a role in the feedback inhibition of Yop synthesis when secretion is compromised by acting as a negative regulator of Yop synthesis.     

A method for the separation and determination of neutral compounds in postmortem tissues

A convenient method for the extraction of neutral drugs in necrotic tissues is described. The procedure includes the use of hot dilute acid for isolating neutrals from tissue extract residues and of internal standard to facilitate quantitative and recovery measurement of the drugs by gas chromatography. The recovery of seven neutral compounds from liver ranged from 47.0% to 89.3%. The limit of detection of these drugs were 0.5 to 1.0 mg/kg.     

Upregulation of integrins alpha v beta 3 and alpha v beta 5 on human monocytes and T lymphocytes facilitates adenovirus-mediated gene delivery

Entry of human adenovirus into host cells involves interaction of virus particles with two distinct receptors. The initial binding event is mediated by the fiber protein, while subsequent interaction of the penton base protein with alpha v integrins promotes virus internalization and/or penetration. Although these interactions in epithelial and endothelial cells have been well characterized, relatively little is known as to whether these events occur during virus infection of human peripheral blood mononuclear cells. We demonstrate that freshly isolated peripheral blood monocytes and T lymphocytes express very small amounts of alpha v integrins and also are resistant to adenovirus infection. Exposure of monocytes to hematopoietic growth factors granulocyte-macrophage colony-stimulating factor and macrophage colony-stimulating factor induced expression of cell surface alpha v integrins, promoted the binding of penton base protein, and also rendered these cells susceptible to adenovirus-mediated gene delivery. Stimulation of T cells with a mitogen, phytohemagglutinin, or a cell-activating agent, phorbol myristate acetate, induced expression of alpha v integrins and also enhanced adenovirus-mediated gene delivery. These studies further indicate that alpha v integrins play a crucial role in adenovirus infection and also provide a useful strategy for enhancing adenovirus-mediated gene delivery into human peripheral blood mononuclear cells.     

Calculation and use of inbreeding coefficients for genetic evaluation of United States dairy cattle

Inbreeding coefficients are calculated routinely for all animals included in national genetic evaluations for yield traits. The base population for inbreeding is defined as animals born during 1960. Animals with unknown parents are assumed to have inbreeding coefficients that are equal to the mean of coefficients for animals with known parents born during the same year. Mean inbreeding coefficients reached .03 to .04 for recent years, and coefficients for some animals exceeded .50. The annual increase in level of inbreeding was highest for Milking Shorthorns, but the rate of change of that increase was greatest for Holsteins. Accounting for inbreeding in calculation of the inverse of the relationship matrix had only a small effect on evaluations. For Jersey, the maximum change in breeding value was 73 kg of milk for cows and 40 kg of milk for bulls with > or = 10 daughters. Estimates of inbreeding depression were similar across breeds for production traits and were -29.6 kg of milk, -1.08 kg of fat, and -.97 kg of protein per 1% of inbreeding for Holsteins. In January 1994, the USDA began considering the percentage of inbreeding when calculating inverses of relationship matrices, the largest matrix representing over 20 million Holsteins; this inbreeding percentage was released to the dairy industry for bulls.     

Colocare self-test versus Hemoccult II Sensa for fecal occult blood testing

OBJECTIVES: To compare the efficacy of ColoCARE Self-Test pads against Hemooccult II SENSA, a traditional guaiac-based card test, in the screening for colorectal neoplasia. METHODS: Prospective crossover analysis of 102 high-risk patients for screening of colorectal neoplasia with fecal occult blood testing, using ColoCARE Self-Test pads and Hemoccult II SENSA cards. RESULTS: Sixty-eight of the 102 patients (67%) had colorectal lesions diagnosed at colonoscopy. Of this group, 55 patients (81%) had either a polyp or cancer diagnosed at colonoscopy, with 13 of these 55 patients having polyps > or = 1 cm. ColoCARE detected 21% of all lesions, compared with 72% for Hemoccult II SENSA. ColoCARE detected only 16% of cases involving either a cancer or a polyp, and 24% of cases involving either a cancer or polyp > or = 1 cm in size. This compares with 75% and 95%, respectively, for Hemoccult II SENSA. Significantly more patients preferred ColoCARE (84%) to Hemoccult II SENSA (5%) (p < 0.00001), and patients found it easier to use ColoCARE (p < 0.01). However, 33% of patients did not feel comfortable interpreting the ColoCARE results, and 29% found it difficult to interpret the color change. CONCLUSION: These results indicate that patients may prefer the simplicity and convenience of ColoCARE; however, the test is not sensitive for the detection of colorectal neoplasia. Furthermore, patients do not feel comfortable interpreting ColoCARE results and prefer to have fecal occult blood testing interpreted by medical personnel.     

Use of double labeling and photo CD for morphometric analysis of injured skeletal muscle

We used computer-assisted analysis of myofiber cross-sectional areas to measure skeletal muscle responses to injury and disease. We developed a simple, inexpensive method for measuring myofiber size in human muscle samples using Kodak photo compact discs (CDs) as the image source. The photo CD serves as a permanent image storage medium and provides a high-resolution image that can be used to detect small myofibers. The use of double labeling for dystrophin and desmin allowed positive identification of both degenerating and regenerating fibers in a single biopsy specimen.     

Combined valve replacement and coronary bypass grafting in osteogenesis imperfecta

Open cardiac procedures in osteogenesis imperfecta have been associated with a high mortality rate. A patient with osteogenesis imperfecta underwent successful aortic valve replacement and coronary artery bypass grafting along with closure of a patent foramen ovale in preparation for a planned hip replacement.