A prospective study of trephined bone grafts of the tibial shaft and iliac crest

BACKGROUND: Our purpose was to analyze the expression of Fas antigen on CD4+ lymphocytes in the aqueous humor (AH) and cerebrospinal fluid (CSF) of patients with Vogt-Koyanagi-Harada disease (VKH). METHODS: Using three-color flow cytometry, we assessed T-lymphocyte subsets stained with fluorescence-conjugated anti-CD3, CD4, CD8, CD29, CD45RA, CD45RO, HLA-DR, and Fas monoclonal antibodies in AH, CSF and peripheral blood (PB) from 8 patients with active VKH. RESULTS: CD3+ T cells constituted the majority of lymphocytes in AH and CSF, in contrast to with PB. The percentages of CD4+ lymphocytes in uveitic AH and CSF were significantly higher than that in PB (P < 0.01). Activated CD4+ and CD8+ cells were significantly more frequent in AH than in CSF and PB (P < 0.01). Although the percentages of CD45RA+ cells within CD4+ cells in AH and CSF were extremely low compared with those in PB, the proportions of CD29+ and CD45RO+ (memory) cells within CD4+ were much higher than those in PB (P < 0.01). Fas antigen was also highly expressed on such CD4+ cells in AH, as in other uveitis patients and on such cells in CSF. Moreover, the percentages of Fas+ and memory cells in AH were significantly higher than those in CSF. CONCLUSIONS: The majority of CD4+ lymphocytes in AH and CSF from patients with active VKH were activated memory cells, on which Fas antigen was also highly expressed. Although this Fas expression may not be an apoptosis-related phenomenon, accumulation of Fas+ memory T lymphocytes in AH and CSF probably reflects the immunopathologic mechanism of VKH.     

The effects of knee reconstruction on combined anterior cruciate ligament and anterolateral capsular deficiencies

We tested the effect of intraarticular reconstructions of the anterior cruciate ligament alone and in combination with extraarticular reconstructions in 10 cadaveric knees. These knees had anterior cruciate ligament deficiency alone or in combination with anterolateral capsuloligamentous deficiencies. In the knees with combined injury, intraarticular reconstruction returned anterior stability to levels not significantly different from levels found for the knees deficient in the anterior cruciate ligament alone and treated with this procedure. After intraarticular reconstruction, rotational stability of the knee with combined injuries failed to return to the levels seen in the knee with isolated anterior cruciate ligament deficiencies that underwent the same treatment. When a tenodesis with either 0 N or 22 N of tension was added to the intraarticular reconstruction in the knee with combined injuries, we found that excessive internal rotation significantly decreased at all angles of flexion, except at full extension with 0 N of tension. In addition, the extraarticular reconstruction with 22 N of tension in the tenodesis overconstrained the knee in internal rotation between 30 degrees and 90 degrees of knee flexion. The tenodesis with 0 N of tension overconstrained the knee at only 60 degrees and 90 degrees of flexion. These results suggest extraarticular reconstruction as an adjunct to the intraarticular operation for the knee with anterior cruciate ligament and anterolateral structural injuries. The results also suggest that the surgeon can affect anterior and rotational laxity by adjusting the tension in the tenodesis.     

Intimal hyperplasia thickness at follow-up is independent of stent size: a serial intravascular ultrasound study

The purpose of this study was to determine whether the thickness of the intimal hyperplasia (IH) layer that accumulates within Palmaz-Schatz stents is dependent on stent size. Intravascular ultrasound (IVUS) and quantitative angiographic (QCA) studies were performed after stent implantation and at follow-up (5.4 +/- 3.8 months) in 161 patients with 177 lesions treated with 221 Palmaz-Schatz stents. Stent and lumen cross-sectional area (CSA) were measured. IH CSA and thickness at follow-up were calculated and compared with stent CSA and circumference. Maximum IH CSA and thickness were measured at the smallest follow-up lumen CSA; mean IH CSA and thickness was averaged over the length of the stent. Maximum IH CSA measured 4.8 +/- 2.4 mm2, and mean IH CSA measured 2.8 +/- 2.2 mm2. Maximum IH thickness (at the smallest follow-up lumen CSA) measured 0.60 +/- 0.36 mm, and mean IH thickness (over the length of the stent) measured 0.30 +/- 0.19 mm. There was a weak, but significant correlation between mean and maximum IH CSA versus stent CSA (r = 0.215, p <0.0001 and r = 0.355, p <0.0001, respectively). However, there was no correlation between mean or maximum IH thickness versus stent CSA (r = 0.018, p = 0.643 and r = 0.056, p = 0.463, respectively) or stent circumference (r = 0.002, p = 0.956 and r = 0.069, p = 0.361, respectively). IH thickness was found to be independent of the stent size. This explains the known higher frequency of restenosis in smaller stents compared with larger stents.     

Immunization with synthetic peptide segments of a sperm protein impair fertility in rats

The nucleotide sequence of the cDNA encoding a sperm protein (rSMP-B) was determined in a previous study. Two peptide segments corresponding to the extracellular domain of the deduced sperm polypeptide were synthesized as multiple antigen peptide (MAP) and designated as rSMP-229 and rSMP-230. Polyclonal antibodies were raised against the two MAPs. Sera obtained from rabbits immunized with rSMP-230 interacted with human and rabbit sperm membrane proteins with estimated molecular sizes of 72 and 20.1 kD, respectively. Adult female and male rats were immunized with the MAPs and their fertilities determined. Immunization of female rats with rSMP-229 and rSMP-230 induced infertility in 25% and 83% of the treated animals, respectively. All male rats immunized with rSMP-229 remained fertile; whereas animals immunized with rSMP-230 did not mate with normal cycling female rats. Three impotent male rats were found to regain their mating potency 45 days after the last booster injection. These findings demonstrated that immunization with rSMP-230 induced a reversible impotency in male rats. Serum testosterone and LH levels were reduced in rSMP-230-immunized male rats and were elevated in rSMP-229-immunized animals. Histopathological examination of sections of testes from male rats immunized with rSMP-230 showed impairment of spermatogenesis and sloughing of germ cells into the lumen of the seminiferous tubules. The testes of male rats immunized with rSMP-229 showed normal morphology and active spermatogenesis with scattered foci of nodular hyperplasia of Leydig cells in the interstitial areas. In conclusion, immunization with synthetic peptide segments corresponding to different domains of a deduced sperm protein induced infertility in a significant number of female rats and transient impotency in male rats.     

Genetic relationship between soxRS and mar loci in promoting multiple antibiotic resistance in Escherichia coli

Multiple antibiotic resistance in Escherichia coli has typically been associated with mutations at the mar locus, located at 34 min on the E. coli chromosome. A new mutant, marC, isolated on the basis of a Mar phenotype but which maps to the soxRS (encoding the regulators of the superoxide stress response) locus located at 92 min, is described here. This mutant shares several features with a known constitutive allele of the soxRS gene, prompting the conclusion that it is a highly active allele of this gene. The marC mutation has thus been given the designation soxR201. This new mutant was used to examine the relationship between the mar and sox loci in promoting antibiotic resistance. The results of these studies indicate that full antibiotic resistance resulting from the soxR201 mutation is partially dependent on an intact mar locus and is associated with an increase in the steady-state level of mar-specific mRNA. In addition, paraquat treatment of wild-type cells is shown to increase the level of antibiotic resistance in a dose-dependent manner that requires an intact soxRS locus. Conversely, overexpression of MarA from a multicopy plasmid results in weak activation of a superoxide stress response target gene. These findings are consistent with a model in which the regulatory factors encoded by the marA and soxS genes control the expression of overlapping sets of target genes, with MarA preferentially acting on targets involved with antibiotic resistance and SoxS directed primarily towards components of the superoxide stress response. Furthermore, compounds frequently used to induce the superoxide stress response, including paraquat, menadione, and phenazine methosulfate, differ with respect to the amount of protection provided against them by the antibiotic resistance response.     

Effect of glutamine on methotrexate efficacy and toxicity

OBJECTIVE: To examine the effect of oral glutamine (GLN) on the efficacy and toxicity of methotrexate (MTX). SUMMARY BACKGROUND DATA: The use of high-dose chemotherapy regimens is limited by the severity of their toxicities. Oral GLN has been shown to decrease the gut toxicity seen with MTX treatment while enhancing its tumoricidal effect. METHODS AND RESULTS: Studies were done in laboratory rats and in breast cancer outpatients. Fischer 344 rats were randomized to 48 hours of prefeeding with GLN (1 g/kg/day) or an isonitrogenous amount of glycine. Rats were killed 24 hours after receiving a 20-mg/kg intraperitoneal dose of MTX. In the GLN group, there was a threefold increase in total MTX in the tumor as compared with the control group, and this increase was in both the diglutamated and pentaglutamated MTX. Inversely, there was a significant decrease in the total polyglutamated MTX in the gut in the GLN group. Given the results of this preclinical study, the authors performed a phase I trial. Nine patients diagnosed with inflammatory breast cancer received GLN (0.5 g/kg/day) during MTX neoadjuvant therapy, escalating from doses of 40 mg/m2 to 100 mg/m2 weekly for 3 weeks, followed by a doxorubicin-based regimen. No toxicity of oral GLN was detected. No patient showed any sign of chemotherapy-related toxicity. One patient had a grade I mucositis. Except for one, all patients responded to the chemotherapy regimen. Median survival was 35 months. CONCLUSIONS: These studies suggest that GLN supplementation is safe in its administration to the tumor-bearing host receiving MTX. By preferentially increasing tumor retention of MTX over that of normal host tissue, GLN may serve to increase the therapeutic window of this chemotherapeutic age.     

The effect of narasin on apparent nitrogen digestibility and large intestine volatile fatty acid concentrations in finishing swine

In the mouse, both the mdr1a and the mdr1b gene encode drug-transporting P-glycoproteins. The mdr1a P-glycoprotein is expressed in epithelial cells of, among others, the liver and the intestine. Furthermore, the mdr1b gene product is found in the liver but is not detectable in the intestine. To establish the potential involvement of P-glycoprotein in the elimination of cationic amphiphilic drugs from the body, we investigated biliary, intestinal, and urinary excretion in mice with a homozygous disruption of the mdr1a gene (mdr1a(-/-) mice). These mice are fully viable under laboratory conditions and have normal bile flow. Cumulative biliary excretion (expressed as percent of the intravenously administered dose excreted over a 1-hour period) of several cationic compounds was decreased as follows in mdr1a(-/-) mice compared with the wild-type animals: tri-n-butylmethylammonium (TBuMA), 0.7% versus 2.1%; azidoprocainamide methoiodide (APM), 3.8% versus 7.6%; and vecuronium, 22.7% versus 41.3%. The luminal secretion of both TBuMA and APM in the small intestine was profoundly decreased, respectively 4.6-fold (1.8% vs. 8.2% in the wild-type) and 7.9-fold (1.6% vs. 10.3% in the wild-type) in mdr1a(-/-) mice. Thus mdr1a P-glycoprotein contributes substantially to the removal of a wide variety of cationic agents from the body through intestinal and hepatobiliary secretion, but it evidently acts in concert with other transport system(s). These processes probably provide a protective mechanism limiting the overall rate of absorption as well as the bioavailability of potentially toxic organic amines.     

The prevalence of rheumatic diseases in a Filipino urban population: a WHO-ILAR COPCORD Study. World Health Organization. International League of Associations for Rheumatology. Community Oriented Programme for the Control of the Rheumatic Diseases

Recent analysis of bladder tumors has correlated expression of the neurokine midkine (MK) with poor patient survival. To examine a role for MK and the related pleiotrophin (PTN) in tumorigenesis, they were overexpressed in MCF-7 breast carcinoma cells. Expression had no effect on in vitro growth but conferred a growth advantage in vivo. Enhanced tumor growth correlated with increased vascular density and endothelial proliferation, implicating an angiogenic role for MK and PTN. Angiogenic activity of MK and PTN was confirmed in the rabbit corneal assay. Our data therefore identify two novel targets for antiangiogenic drug development.     

The clinical significance of phasic duodenal intubation and ultrasonic monitoring of the gallbladder in healthy subjects

Hypoxic and low-temperature effects on the thermal regulation and the content of catecholamines (epinephrine--E and norepinephrine--NE) in mice have been compared. Continuous and repeated hypoxia brought about a significant drop of the rodent body temperature and heat content. Found was a significant elevation of catecholamines in the pituitary and adrenal tissues, and blood plasma with E prevalence after the continuous exposure. Repeated stimulus resulted in a more pronounced effect. Exception was the adrenal tissue where enhanced E and NE secretion into blood was noted. The uninterrupted and repeated cold conditions were also responsible for heat release. Continuous exposure to low temperature increased NE and decreased insignificantly E in blood and adrenal. Multiple stimulation increased sharply catecholamines concentration in blood plasma with the dominance of epinephrine in the pituitary gland, and norepinephrine in the adrenal.