Fryns syndrome: prenatal diagnosis and pathologic correlation

From 1988 to 1995, 96 patients (161 feet) underwent a modified Mitchell distal metatarsal osteotomy performed for mild-to-moderate hallux valgus. On AP x-rays of the standing foot, the average intermetatarsal angle was corrected from 15 degrees to 9 degrees, and the first metatarsophalangeal angles were corrected from an average of 41 degrees to 15 degrees. Criteria for evaluation of clinical results included relief of pain, appearance of foot, and shoe wear. After an average follow-up of 38 months, the overall satisfaction rate was 92.5%. Complications included 13 pin tract infections, two delayed unions, and two correction losses. The most common late sequela was transfer metatarsalgia of the lesser toes, which occurred in 20 feet (12.4%), leading to some dissatisfaction. The Mitchell osteotomy can be used on cases with less than 20 degrees of intermetatarsal angle, offering a stable construct with easy postoperative care.     

Combinatorial selection of a small RNA that induces amplification of IncFII plasmids in Escherichia coli

Patients with arteriovenous malformation (AVM)-associated aneurysms are a well-recognized subset of the cerebrovascular disease population. The origin of these dual lesions is likely multifactorial, with hemodynamic stresses having a dominant influence. In most patients who present with hemorrhage, the aneurysm is the usual source. Since aneurysm rupture continues to carry a more significant morbidity and mortality when compared to AVM hemorrhage, the authors recommend that the aneurysm be treated first or simultaneously with the AVM in the majority of cases. Treatment of the AVM first is primarily reserved for patients who have suffered bleeds from resectable AVMs.     

First record of host defence peptides in tadpoles. The magnificent tree frog Litoria splendida

We treated a 73-year-old man with a dural arteriovenous fistula (AVF) with cortical venous drainage of the left mastoid region using transarterial embolization of the middle meningeal and occipital arteries with n-butyl 2-cyanoacrylate (NBCA). The patient's clinical symptoms improved dramatically. Three months after the procedure, follow-up CT showed resolution of white matter edema and follow-up angiograms showed no evidence of a recurrent AVF. This report indicates that dural AVFs without sinus drainage can be cured solely with transarterial NBCA embolization.     

Isolation of translactone-containing triterpenes with thrombin inhibitory activities from the leaves of Lantana camara

Methanolic extracts prepared from the leaves of Lantana camara have been found to inhibit human thrombin. An assay, in which thrombin activity is measured as a function of clot formation from fibrinogen, was used to guide the fractionation and purification of five principal active constituents (1-5), which were all characterized as 5,5-trans-fused cyclic lactone-containing euphane triterpenes.     

Leukemic pleural effusion in B-cell prolymphocytic leukemia

BACKGROUND: Proinflammatory mediators that include tumor necrosis factor-alpha (TNF-alpha) and macrophage inflammatory protein-2 (MIP-2) and anti-inflammatory mediators such as interleukin-10 (IL-10) modulate the immune response to endotoxemia. IL-10 downregulates the production of TNF-alpha and MIP-2. Acute lung injury may occur secondary to neutrophil chemotaxis mediated by chemokine MIP-2. We studied the temporal relationship of TNF-alpha, MIP-2, and IL-10 in rat endotoxemia and correlation of MIP-2 concentrations with acute lung injury. METHODS: Ten ventilated rats were randomized to receive an intravenous infusion of 2 mg/kg Escherichia coli lipopolysaccharide (n = 6) or saline placebo (n = 4). Blood pressure was continuously monitored and arterial blood was obtained for lactate, blood gas, TNF-alpha, IL-10, and MIP-2 measurements at baseline, 2, 4, and 5.5 hours after LPS or saline infusion. RESULTS: Endotoxemia resulted in hypotension, lactic acidemia, and increased alveolar-arterial oxygen gradient (A-a O2 gradient) compared with the placebo group. TNF-alpha, MIP-2, and IL-10 levels were increased 2 hours after endotoxemia. Subsequently, TNF-alpha levels declined while IL-10 and MIP-2 levels remained elevated. Control rats had no significant increase in cytokine production at any time point. MIP-2 concentrations correlated with A-a O2 gradient, an indicator of lung injury (r = 0.56, p < 0.001). CONCLUSIONS: MIP-2, possibly released by TNF-alpha stimulation of macrophages, is associated with acute lung injury possibly by inducing neutrophil chemotaxis. IL-10 may exert its counter-inflammatory response by inhibiting the release of TNF-alpha in endotoxemia.     

An alternative route for multistep tumorigenesis in a novel case of hereditary renal cell cancer and a t(2;3)(q35;q21) chromosome translocation

Through allele-segregation and loss-of-heterozygosity analyses, we demonstrated loss of the translocation-derivative chromosome 3 in five independent renal cell tumors of the clear-cell type, obtained from three members of a family in which a constitutional t(2;3)(q35;q21) was encountered. In addition, analysis of the von Hippel-Lindau gene, VHL, revealed distinct insertion, deletion, and substitution mutations in four of the five tumors tested. On the basis of these results, we conclude that, in this familial case, an alternative route for renal cell carcinoma development is implied. In contrast to the first hit in the generally accepted two-hit tumor-suppressor model proposed by Knudson, the familial translocation in this case may act as a primary oncogenic event leading to (nondisjunctional) loss of the der(3) chromosome harboring the VHL tumor-suppressor gene. The risk of developing renal cell cancer may be correlated directly with the extent of somatic (kidney) mosaicism resulting from this loss.     

Opposing roles for dopamine D1 and D2 receptors in the regulation of hypothalamic tuberoinfundibular dopamine neurons

The purpose of the present study was to characterize pharmacologically dopamine D1 receptor-mediated inhibition of tuberoinfundibular dopamine neurons in males rats, and to determine if inhibitory dopamine D1 receptors oppose stimulatory dopamine D2 receptors and account for the inability of mixed dopamine receptor agonists to alter the activity of these neurons. Tuberoinfundibular dopamine neuronal activity was estimated by measuring the concentrations of the dopamine metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in the median eminence, the region of the hypothalamus containing terminals of these neurons. Administration of the dopamine D1 receptor agonist (+/-)-1 phenyl-2,3,4,5-tetrahydro-(1 H)-3-benzazepine-7,8-diol (SKF38393) decreased median eminence DOPAC and increased plasma prolactin concentrations, whereas administration of the dopamine D1 receptor antagonist ((-)-trans,6,7,7a,8,9,13b-hexahydro-3-chloro-2-hydroxy-N-methyl-5H -benzo[d]naphtho-[2,1 b]azepine (SCH39166) increased median eminence DOPAC concentrations but had not effect on plasma prolactin. The inhibitory effect of SKF38393 on median eminence DOPAC concentrations was blocked by SCH39166. These results demonstrate that acute activation of dopamine D1 receptors inhibits the activity of tuberoinfundibular dopamine neurons and thereby increases prolactin secretion, and that under basal conditions dopamine D1 receptor-mediated inhibition of tuberoinfundibular dopamine neurons is tonically active. Administration of the dopamine D2 receptor agonist (5aR-trans)-5,5a,6,7,8,9,9a,10-octahydro-6-propyl-pyridol[2, 3-g]quinazolin-2-amine (quinelorane) increased median eminence DOPAC concentrations, and SKF38393 caused a dose-dependent reversal of this effect. Administration of the mixed dopamine D1/D2 receptor agonist R(-)-10,11-dihydroxy-apomorphine (apomorphine) had no effect per se, but blocked quinelorane-induced increases in DOPAC concentrations in the median eminence. These results reveal that concurrent activation of dopamine D1 and D2 receptors nullifies the actions of each of these receptors on tuberoinfundibular dopamine neurons, which likely accounts for the lack of an acute effect of mixed dopamine D1/D2 receptor agonists on these hypothalamic dopamine neurons.     

AAEM minimonograph 32: the electrodiagnostic examination in patients with radiculopathies. American Association of Electrodiagnostic Medicine

The anatomy and pathophysiology of radiculopathies are reviewed, and the electrodiagnostic approaches used in evaluating patients with suspected root lesions are discussed. Such electrophysiologic procedures include motor and sensory nerve conduction studies, late-response studies, somatosensory and motor evoked potentials, nerve root stimulation, and needle electromyography. The value and limitations of these different procedures are considered. At the present time, needle electromyography is the single most useful approach. The findings in patients with radiculopathies at different levels are summarized.     

Human lung cancer antigens recognized by autologous antibodies: definition of a novel cDNA derived from the tumor suppressor gene locus on chromosome 3p21.3

Supplementation with high doses of alpha-tocopherol has increased the oxidation resistance of LDL in many clinical trials. There have been only a few placebo-controlled trials in healthy persons of alpha-tocopherol doses usually contained in dietary supplements. We carried out a single-blind, placebo-controlled, randomized trial to examine the effect of 200 mg RRR-alpha-tocopheryl acetate/d on the oxidation resistance of atherogenic lipoproteins (VLDL+LDL including intermediate-density lipoproteins) in 40 smoking men. VLDL+LDL oxidation resistance was assessed as conjugated dienes after copper induction and hemin degradation after hydrogen peroxide induction. Also, the LDL total peroxyl-radical trapping antioxidant parameter (LDL TRAP) and plasma malondialdehyde were measured at baseline and after 2 mo of supplementation. Plasma RRR-alpha-tocopherol concentrations were measured at 2-h intervals for 12 h at baseline and after 2 mo of supplementation. Compared with placebo, 200-mg RRR-alpha-tocopheryl acetate supplementation elevated plasma and VLDL+LDL alpha-tocopherol concentrations, LDL TRAP, and oxidation resistance of VLDL+LDL. Plasma alpha-tocopherol increased by 88% (P < 0.0001), VLDL+LDL alpha-tocopherol increased by 90% (P < 0.0001), and LDL TRAP by 58% (P < 0.0001). The time to the start of oxidation (lag time) was prolonged by 34% when assessed with a copper-induced method and by 109% when assessed with a hemin + hydrogen peroxide-induced method; the time to maximal oxidation was prolonged by 21% (copper-induced method) in the vitamin E-supplemented group. Changes in plasma alpha-tocopherol, lipid-standardized alpha-tocopherol, and VLDL+LDL alpha-tocopherol correlated significantly with changes in LDL TRAP, lag time, and time to maximal oxidation. Differences in changes between groups in the area under the curve for plasma alpha-tocopherol were significant (P < 0.009). Our results suggest that 200 mg oral RRR-alpha-tocopheryl acetate/d had a clear effect on the in vitro oxidation of VLDL+LDL in smoking men.     

Glycated hemoglobin reference limits obtained by high performance liquid chromatography in adults and pregnant women

Pentachlorophenol (PCP) and molybdate have been shown to inhibit the sulfoconjugation of various chemicals in rats and therefore are useful to examine the role of sulfoconjugation on the toxicity of a chemical. PCP inhibits sulfation by competing with substrates for phenol-sulfotransferases, but not hydroxysteroid-sulfotransferases. In contrast, molybdate decreases sulfation by limiting sulfate availability and thereby decreasing the synthesis of 3'-phosphoadenosine 5'-phosphosulfate (PAPS), which is the obligate cosubstrate for sulfation. Therefore, it was of interest to determine whether PCP or molybdate is effective in decreasing the in vivo sulfation of dehydroepiandrosterone (DHEA), which is a substrate for hydroxysteroid-sulfotransferases. PCP (40 micromol/kg ip) or molybdate (7.5 mmol/kg po) was given 45 min and 4 h, respectively, prior to the start of DHEA infusion. The effects of these two sulfation inhibitors on DHEA sulfation were dependent on the rate of DHEA infusion in rats. PCP had different effects on the sulfation of various infusion rates of DHEA in rats. PCP had little effect on the sulfation after the two lowest infusion rates of DHEA (12.5 and 25 mg/kg) and actually increased (233%) DHEA-sulfate serum concentrations with the highest DHEA infusion rate (50 mg/kg). Although molybdate had little affect on the sulfation of the lowest DHEA infusion rate, it significantly decreased (50-85%) DHEA-sulfate serum concentrations with the two higher DHEA infusion rates. These data indicate that molybdate, unlike PCP, decreases the sulfation of DHEA and may be a useful tool to decrease the sulfation of other substrates of hydroxysteroid-sulfotransferases.