The functional outcome of lower-extremity fractures with vascular injury

Salvage of lower-extremity Gustilo type IIIC fractures is difficult, time-consuming for the patients and physicians, and not universally successful because of poor functional outcomes. Even if successful with limb salvage, the functional result may be unsatisfactory because of mutilating injuries to muscle and nerve, bone loss, and the presence of chronic infection. From July 1991 until July 1994, revascularizations of open IIIC fractures were attempted for wounds with Mangled Extremity Severity Score (MESS) < or = 10. The functional results were evaluated at 2 years after injury. Thirty-six lower-extremity revascularizations were performed on 34 patients, including 1 patient with bilateral distal tibial IIIC fractures and a child with IIIC femoral fracture accompanied by ipsilateral distal tibial amputation. Excluded were patients with below-ankle IIIC fractures as well as patients who underwent immediate amputation at admission. After the revascularization, seven patients with IIIC fractures (7 of 36, 19.4%) underwent secondary amputation within 1 week. At the 2-year follow-up, the overall secondary amputation rate was 25% (9 of 36) and the salvage rate was 75% (27 of 36). Those were no deaths. Of the 29 salvaged limbs among these 27 patients, 23 limbs (23 of 29, 79.3%) required secondary coverage procedures that included 12 free flap transfers (12 of 29, 41.4%). Every patient needed subsequent reconstructive surgery to achieve an acceptable functional result. In this series, MESS was able to predict the secondary amputation rate and the functional result. Sixteen of the 17 limb-salvaged patients with MESS < or = 7 were able to achieve minimal functional requirements, whereas 3 of the 10 patients with MESS = 8 to 10 failed to achieve minimal functional requirements at the 2-year follow-up. Using statistical analysis, we found that the salvaged limbs with MESS < or = 9 exhibited a significant difference in achieving adequate function compared with limbs with MESS > 9. Using our protocol for treatment for IIIC fractures, the threshold for immediate amputation can be raised from MESS = 7 to MESS = 9. Our conclusions are (1) more severely injured limbs have poor functional results, (2) every patient needs subsequent reconstructive surgery, and (3) the MESS may be helpful in decision-making.     

Cell cycle-dependent establishment of a late replication program

DNA replication origins in chromosomes of eukaryotes are activated according to a temporal program. In the yeast Saccharomyces cerevisiae, activation of origins in early S phase appears to be a default state. However, cis-acting elements such as telomeres can delay origin activation until late S phase. Site-specific recombination was used to separate origin from telomere in vivo, thereby demonstrating that the signal for late activation is established between mitosis and START in the subsequent G1 phase. Once set, the signal can persist through the next S phase in the absence of the telomere. Establishment of the temporal program and of initiation competence of origins may be coincident events.     

Analysis of T cell receptor Vbeta gene usage during the course of disease in patients with chronic hepatitis B

Polyvinyl siloxane impression materials have applications in a variety of indirect procedures in prosthodontics and restorative dentistry. Favourable handling properties, good patient acceptance and excellent physical properties have resulted in their popularity in today's practice. In this review, the chemistry and important physical properties of polyvinyl siloxanes are summarized, and recent clinical questions of improved hydrophilics, tray adhesives, disinfection, and glove-induced polymerization inhibition are addressed.     

Localization and regulation of renal Na+/myo-inositol cotransporter in diabetic rats

We have examined the effect of diabetes on sodium/myo-inositol cotransporter (SMIT) mRNA levels and myo-inositol content in the kidney to test the hypothesis that diabetes-induced changes in renal myo-inositol levels are due to the regulation of SMIT mRNA levels. In streptozotocin-induced diabetic rats, after 3, 7 and 28 days of diabetes, SMIT mRNA levels in the whole kidney were increased three to fivefold, and remained increased by about twofold after six months of diabetes. Insulin treatment of diabetic rats normalized blood glucose levels and prevented the increase in SMIT mRNA levels. Treating diabetic rats with sorbinil, an aldose reductase inhibitor, corrected the abnormal accumulation of sorbitol but had no effect on the diabetes-induced increase in renal SMIT mRNA levels. The regional distribution of SMIT mRNA from normal rats showed a relative abundance in cortex, outer medulla, and inner medulla of 1.0:3.4:7.0. After seven days of diabetes, the levels of SMIT mRNA and myo-inositol content were significantly increased only in the outer medulla. In situ hybridization studies revealed that SMIT mRNA in the outer medulla was predominately localized to the medullary thick ascending limbs of Henle's loop and was not localized to any specific cell in the inner medulla. This distribution pattern was unchanged in diabetic rats. These studies show that diabetes causes an increase in renal SMIT mRNA, which is primarily localized to the outer medulla. Accumulation of myo-inositol by the thick ascending limb of Henle's loop may account for most of the increase caused by diabetes.     

6beta-Acetoxynortropane: a potent muscarinic agonist with apparent selectivity toward M2-receptors

A series of tropane derivatives, related in structure to baogongteng A (1), an alkaloid from a Chinese herb, were synthesized. 6beta-Acetoxynortropane (5) had weak affinity (Ki 22 microM) for central (M1) muscarinic receptors in a [3H]quinuclidinyl benzilate binding assay but had extremely high affinity (Ki 2.6 nM) and selectivity for M2-muscarinic receptors expressed in CHO cells. It had 13-fold lower affinity for M4-receptors, 260-fold lower affinity for M3-receptors, and 8200-fold lower affinity for M1-receptors expressed in CHO cells. The 6beta-carbomethoxy analogue (14) of baogongteng A had only weak affinity for M2-muscarinic receptors, as did 6beta-carbomethoxynortropane (13) and 6beta-acetoxytropane (4). In transfected CHO cells, 6beta-acetoxynortropane (5) was an agonist at M2-receptors, based on a GTP-elicited decrease in affinity, and a full agonist with an IC50 of 11 nM at M4-receptors, based on inhibition of cyclic AMP accumulation, while being a full agonist at M1-receptors with an EC50 of 23 nM and a partial agonist at M3-receptors with an EC50 of 3.6 nM, based in both cases on stimulation of phosphoinositide breakdown. All of the 16 tropane derivatives had weak affinities for central alpha4beta2-nicotinic receptors with 6beta-carbomethoxynortropane (13) having the highest affinity, which was still 150-fold less than that of nicotine. 6beta-Acetoxynortropane (5) represents a potent muscarinic agonist with apparent selectivity toward M2-receptors.     

Dens evaginatus on a wisdom tooth: a diagnostic dilemma. Case report

BACKGROUND: Skin manifestations have been described in 25% of patients with Mycoplasma pneumoniae infection. CASE REPORT: We report a case of Mycoplasma pneumoniae infection in a 29-year-old man who developed a polymorphous erythema-like reaction. Skin manifestations were associated with voluminous lymph node enlargement and high eosinophil levels both in serum and alveolar lavage. Seroconversion against Mycoplasma pneumoniae IgG was documented with ELISA. The clinical course was favorable with erythromycin. DISCUSSION: ELISA IgG seroconversion is sufficient to confirm the diagnosis of Mycoplasma pneumoniae infection as this test has an 80-90% specificity. This case was unusual by its clinical presentation and high eosinophil counts in serum and tissue samples, similar to what is found in drug-induced hypersensitivity.     

Evidence of multiple mechanisms of avermectin resistance in haemonchus contortus--comparison of selection protocols

The ginsenosides Rb1 and Rg1, the major components of ginseng saponin, inhibited not only methamphetamine-induced hyperactivity but also conditioned place preference (CPP) in mice following a single or repeated administration. Dopamine (DA) receptor supersensitivity, which developed in methamphetamine-induced CPP mice, was also inhibited by both Rb1 and Rg1. Therefore, the present results suggest that Rb1 and Rg1 may be the active components of ginseng saponin in the modulation of methamphetamine-induced dopaminergic behaviors such as hyperactivity and CPP, supporting our previous conclusion that ginseng saponin might modulate methamphetamine-induced dysfunction at both the pre- and postsynaptic DA receptors.     

Elevated nocturnal melatonin is a consequence of gonadotropin-releasing hormone deficiency in women with hypothalamic amenorrhea

Elevated nocturnal melatonin is found in women with idiopathic hypogonadotropic hypogonadism (IHH), but it is not known whether this is implicated in the etiology of their GnRH deficiency. It is unlikely that nocturnal melatonin can be implicated in the etiology of the GnRH deficiency of Kallmann's syndrome (KS), because this condition is caused by defective neuronal migration in embryonic life. We therefore measured nocturnal melatonin in women with IHH and KS to determine whether it was elevated in one or both conditions and thereby to determine whether it was implicated as cause or consequence of GnRH deficiency. Four women with IHH, 3 women with KS, and 7 individually matched (age and body size) controls were recruited. Frequent day- and nighttime samples were taken for LH pulsatility studies. All patients showed absent or diminished LH pulsatility, compared with their respective controls. Samples were also taken over 24 h for melatonin and 6-sulphatoxymelatonin (the principle metabolite of melatonin and an independent marker of its secretion). Melatonin and 6-sulphatoxymelatonin levels were elevated in 6 of 7 patients (compared with their matched controls) and were significantly elevated in the KS group (compared with their controls). The finding of elevated nocturnal melatonin (and its metabolite) in GnRH-deficient women with KS (as well as IHH) suggests that nocturnal melatonin is elevated as a consequence of GnRH deficiency, irrespective of its etiology.