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Multiple surgical techniques for posterior cruciate ligament reconstruction have been described and subsequently scrutinized. We describe a surgical technique using full-thickness quadriceps tendon-patellar bone autograft in single-bundle, all-inside posterior cruciate ligament reconstruction that offers the following advantages over traditional technique: This technique mitigates the risk of tunnel widening and convergence while preserving bone stock, eliminating the killer turn, allowing for suspensory cortical fixation to optimize stabilization, and using a bone plug that allows for faster graft incorporation., (© 2023 The Authors.)

Foliar stable isotopic signatures of nitrogen, carbon, and sulfur in mangrove vegetation from the Pacific coast of Panama were insensitive to inputs from watersheds with different area of forest land cover, and to seasonal, inter-annual, and global-scale-driven contrasts in rainfall and upwelling. N, C, and S content of mangrove vegetation were not affected by inputs from watersheds with different degrees of deforestation, but showed some influence of down-estuary transformations. While there was substantial variation that remained un-explained, isotopic signatures and nutrient contents were largely determined by species-specific features, and showed substantial small-scale variation reflecting local differences, within-estuary plant-sediment links. The ability of mangrove estuaries to erase effects of deforestation points out that conservation of these wetland ecosystems is important, because, at least in the sites we studied, transformations within mangrove estuaries were strong enough to protect water quality in receiving coastal waters., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Tyrosine kinase interacting protein (Tip) of Herpesvirus saimiri (HVS) activates the lymphoid-specific member of the Src family kinase Lck. The Tip:Lck interaction is essential for transformation and oncogenesis in HVS-infected cells. As there are no structural data for Tip, hydrogen-exchange mass spectrometry was used to investigate the conformation of a nearly full-length form (residues 1-187) of Tip from HVS strain C484. Disorder predictions suggested that Tip would be mostly unstructured, so great care was taken to ascertain whether recombinant Tip was functional. Circular dichroism and gel-filtration analysis indicated an extended, unstructured protein. In vitro and in vivo binding and kinase assays confirmed that purified, recombinant Tip interacted with Lck, was capable of activating Lck kinase activity strongly and was multiply phosphorylated by Lck. Hydrogen-exchange mass spectrometry of Tip then showed that the majority of backbone amide hydrogen atoms became deuterated after only 10 s of labeling. Such a result suggested that Tip was almost totally unstructured in solution. Digestion of deuterium-labeled Tip revealed some regions with minor protection from exchange. Overall, it was found that, although recombinant Tip is still functional and capable of binding and activating its target Lck, it is largely unstructured.

The ecological impact of different doses of ciprofloxacin was investigated in an experimental germ-free rat model into which human fecal flora was inoculated. Animals received oral doses (gavage) of 0, 0.25, 2.5, and 25 mg/kg body weight (bw) of ciprofloxacin once daily for 5 weeks. All doses of ciprofloxacin significantly reduced aerobic populations. Elimination of Enterobacteriaceae and reduction of bifodibacteria were noticed in the group treated with 25 mg/kg of the antibiotic. The rest of the intestinal flora was not affected. These effects were reversible after the treatment ended. The percentage of resistant enterococci increased in rats treated with 2.5 and 25 mg/kg; however, this increase was not statistically significant. There was a significant (P < 0.05) emergence of ciprofloxacin-resistant Bacteroides fragilis group with 25 mg/kg bw, which is equivalent to a human therapeutic dosage of the antibiotic. The MIC values and the percentage of resistance remained elevated 2 weeks after the end of treatment in this anaerobic population. Although sub-populations of enterococci and Enterobacteriaceae showed decreased susceptibility after ciprofloxacin administration, resistance was not evident. The ability of an exogenous strain of Salmonella to colonize the intestine of animals treated with 25 mg/kg of ciprofloxacin confirmed that the drug disrupted the colonization barrier effect of the indigenous flora at the high dose level tested. No changes in the metabolic parameters occurred during the antibiotic treatment. The results obtained in the HFA rat model were similar to those obtained in our previous study using the HFA mice model where ciprofloxacin at 0.125, 1.25, and 12.5 mg/kg bw induced a decrease of enterococci and Enterobacteriaceae populations. The high dose of ciprofloxacin also induced a decrease in bifidobacteria counts, an increase in levels of resistant B. fragilis group and a significant (P < 0.05) disruption of the colonization resistance of the barrier flora in HFA mice.

A chemostat model of the healthy human large bowel ecosystem was used to establish no effect levels for tetracycline, neomycin, and erythromycin. For each compound, the equivalent to four oral doses (0, 1.5, 15, and 150 mg/60 kg person/d) was studied. Concentrations of the test compounds in the chemostat medium were intended to simulate fecal levels that might be expected following consumption of food containing antibiotic residue and were based on published oral doses and fecal levels. We monitored the following parameters: short chain fatty acids, bile acids, sulfate reduction, azoreductase and nitroreductase activities, beta-glucosidase and beta-glucuronidase activities, a range of bacterial counts and, lastly, the susceptibility among sentinel bacteria to each test compound. Neomycin and erythromycin reduced bile acid metabolism. Neomycin elevated propionate levels and caused a marginal diminution in azoreductase activity. Based on our results, the no observed effect level (NOEL) of both tetracycline and erythromycin was 15 mg/60 kg person/d. The NOEL for neomycin was 1.5 mg/60 kg person/d.

A study was conducted to evaluate the effects of therapeutic and residual doses of ciprofloxacin on the human intestinal flora implanted into germ-free mice. Ciprofloxacin was administered daily via drinking water at concentrations to provide doses of 0, 0.125, 1.25, and 12.5mg/kg b.w. Changes in the intestinal flora composition, alteration in bacterial enzyme activities, fecal short chain fatty acid concentration and bacterial cellular fatty acid profiles, overgrowth of resistant bacteria, and disruption of the colonization barrier were the endpoints evaluated in the feces of human-flora-associated (HFA) mice. Ciprofloxacin at all tested doses decreased significantly the aerobic populations and particularly the population of Enterobacteriaceae. Selection of resistant Bacteroides fragilis group was noticed in HFA mice receiving 12.5mg/kg b.w. In mice challenged with a Salmonella strain, exogenous Salmonella persisted in the feces of all treated mice indicating that the flora responsible for the colonization barrier effect was disturbed by the antibiotic treatment. None of the studied metabolic parameters of the flora were affected by ciprofloxacin at any dose level. Under the experimental conditions of the study, the no-observed-effect level of ciprofloxacin was found to be less than 0.125 mg/kg b.w.

Background: Orthotopic liver transplantation for end-stage hepatitis-B-virus (HBV) infection is commonly complicated by recurrence of HBV. Lamivudine, a cytosine nucleoside analogue, has been shown to suppress HBV infection. We report the development of resistance to lamivudine in three patients who underwent transplantation for end-stage liver disease secondary to hepatitis B., Methods: Two of the patients received lamivudine for recurrent HBV infection after transplantation, whereas the third patient began treatment 1 month before transplantation in an attempt to prevent HBV recurrence after transplantation. The three patients initially responded well to treatment, but viral recurrence occurred after 9-10 months of treatment in all patients. HBV DNA was amplified from serum and sequenced through a conserved polymerase domain-the tyrosine, methionine, aspartate, aspartate (YMDD) locus. We assessed the susceptibility of HBV to lamivudine by infecting primary human hepatocytes with serum taken before the start of treatment and after recurrence in varying concentrations of lamivudine., Findings: DNA sequencing showed a common mutation within the YMDD locus of the HBV polymerase gene in all patients during lamivudine treatment. In hepatocyte cultures infected with pretreatment serum, HBV DNA concentrations were reduced to less than 6% of those in control cultures by addition of lamivudine in concentrations as low as 0.03 mumol/L. By contrast, in cultures treated with serum taken after recurrence, HBV DNA concentrations did not fall below 20% of control values, even with lamivudine at 30 mumol/L., Interpretation: Resistance to lamivudine has been reported in HIV patients with mutations in the YMDD locus of the polymerase gene. Our findings indicate a common mechanism of lamivudine resistance for HIV and HBV that involves similar point mutations in homologous domains of the viral polymerases.

This study was conducted to model the pattern of antibiotic drug uptake within yolks of developing follicles. In two separate experiments, 16 hens were divided into equal groups (n = 8) and injected only once with either 400 mg/kg ampicillin or 200 mg/kg oxytetracycline (OTC: total hens = 32) approximately 1 h after oviposition. Twenty-four hours following injections, hens were euthanatized and the ovaries were collected. Yolks were dissected free from the individual follicles with a blunt probe. Individual large yellow yolks (> or = 0.2 g) and a pool of 5 small yellow yolks (< 0.2 g) were collected for determination of ampicillin or OTC content. Samples were prepared and assayed using an agar diffusion microbiological method. Selected parameters were not different (P > 0.05) between Experiments 1 and 2 and the data were combined. Results indicate that short-term exposure in hens produced incorporation of drug residues in developing yolks in a specific pattern that does not appear to be drug dependent (P > 0.05). These incurred residues are contained in developing yolks that are days to weeks from being ovulated. Drug residues were greater (total microgram content) in some of the less mature yolks vs the largest preovulatory yolk. This may lead to a sequential release of eggs with increasing residue content, even after drug withdrawal. These data were used to construct a model to predict the pattern of incurred residues in formed eggs following a hen's exposure to drugs or other contaminants.

We studied 41 nonvegetarian and 34 vegetarian premenopausal women whom we closely screened. The two groups were indistinguishable with respect to height, weight, body mass index, and menarche. The incidence of menstrual irregularity was 4.9% among nonvegetarians and 26.5% among vegetarians (P = 0.009). The vegetarian group consumed significantly greater amounts of polyunsaturated fatty acids, carbohydrates, vitamin B-6, and dietary fiber whereas the nonvegetarians reported greater intakes of saturated fatty acids, protein, cholesterol, caffeine and alcohol. Logistic-regression analyses showed that the probability of menstrual regularity among all study subjects (n = 75) was positively associated with increasing protein/kJ and increasing cholesterol/kJ intakes. The probability of being menstrually regular was negatively associated with increasing dietary fiber/kJ and increasing magnesium/kJ intakes. These results are consistent with the notion that menstrual regularity can be influenced by specific dietary nutrients that may have direct effects or exert their effects by modulating circulating sex steroid status.

Fifty-one hyperandrogenic women had their lipoprotein lipid profiles determined. Free and albumin-bound testosterone was associated with triglycerides and with high-density lipoprotein cholesterol independent of fasting insulin levels, percent ideal body weight, and waist/hip ratio. To gain insight into mechanisms of these lipid alterations, the women were subgrouped according to apparent source of androgen excess. Whereas all groups had low levels of high-density lipoprotein-2 cholesterol and high triglyceride concentrations, only in those with high luteinizing hormone-to-follicle-stimulating hormone ratios was free and albumin-bound testosterone associated with triglycerides and high-density lipoprotein cholesterol independent of fasting insulin levels. Relationships between percent ideal body weight and waist/hip ratios, free and albumin-bound testosterone, sex hormone binding globulin, fasting insulin and 2-hour insulin levels and blood pressure are not significant in all subgroups, suggesting differing endocrinological influences and differing mechanisms for lipoprotein lipid alterations.

Human pancreas contains receptors for estrogens and androgens as well as aromatase activity. FAM chemotherapy was administered to 14 patients with pancreatic cancer (seven at Stage IV). The median survival of these patients was 24.4 +/- 4.8 weeks. FAM chemotherapy plus aminoglutethimide/hydrocortisone (AG/HC) (250 mg bid AG + 20 mg bid HC) was administered to 14 patients (seven at stage IV). The median survival of this group was 17.3 +/- 2.9 weeks (P = 0.74 vs FAM alone). We conclude that addition of AG/HC does not add to the survival of patients with carcinoma of the pancreas treated with chemotherapy.

Lipoprotein lipid and androgen profiles were compared after a 12-hour fast that involved 13 women with polycystic ovary syndrome and 13 who did not have the syndrome. All women were matched for percent ideal body weight. As expected, patients with polycystic ovary syndrome had significantly higher luteinizing hormone--to--follicle-stimulating hormone ratios, higher testosterone levels, higher free testosterone levels, higher dehydroepiandrosterone sulfate levels, and lower testosterone-estradiol-binding globulin binding capacity than the other women. Patients with polycystic ovary syndrome had significantly higher mean serum triglyceride levels, very-low-density lipoprotein cholesterol levels, and lower high-density lipoprotein cholesterol levels. Differences in body weight do not explain the male pattern of lipoprotein lipid concentrations in women with polycystic ovary syndrome. The association of hyperandrogenism with lipoprotein lipid abnormalities should be evaluated in regard to the influence of endogenous sex steroids on differences between the sexes in incidence of cardiovascular disease.

The study was designed to ascertain the relationship between visual loss in the central 30 degrees of vision and the density of the relative afferent pupillary defect (APD). The APD of 26 patients was quantified using a neutral log density filter. The mean threshold light sensitivity on Humphrey automated perimetry (Program 30-1) of one eye was substracted from the fellow eye total to yield the interocular visual field difference (VFD). A direct correlation was noted such that the log density of the APD increased linearly with an increase in VFD (r = 0.69, P = 0.0001). In the absence of ptosis or ocular media opacification, a VFD greater than 8.7 that is not associated with an APD is suggestive of functional visual loss. Four patients had an APD despite normal static automated perimetry, indicating that an APD may be one of the earliest signs of retinal ganglion cell or axonal dysfunction.

We present a method to display the results of linear regression when the independent variables are highly correlated. In this method the sum of squares of regression (SSR) for pairs of variables are partitioned into orthogonal and shared components. A shared component is the reduction in the SSR of one of the variables when the other variable is added to the regression equation. This method shows how the SSR for one variable depends on the other variables present in the regression equation and explains apparent inconsistencies between forward and backward stepwise regression. To demonstrate the potential usefulness of this method we reanalyzed previously reported data on the relationship between coronary heart disease (CHD) and diet. The analysis suggested that carbohydrate and alcohol intake are negatively associated with CHD because they are associated with greater caloric intake. Protein and fat intake are also associated with greater caloric intake, but in addition they are associated with factors that increase the risk of CHD.

Problem reporting rates of 180 persons with cancer (PWC) were compared with those of their closest in age same sex cancer-free siblings living outside their households for the same time periods. PWC had significantly higher reporting rates for physical, activities of daily living, nutrition, and emotional problems and a significantly lower rate for family problems. Sibling problem reporting rates, which indicate the likelihood that PWC would have experienced similar problems without a diagnosis of cancer, were highest for physical, emotional, employment, and family problems suggesting that noncancer factors are especially likely to play a role in those types of problems. Regression analyses showed that female and younger PWCs tended to report more problems than their siblings suggesting that they were more affected by cancer and its treatments than were other types of PWC.