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Biomedical subjects

S S Shim

Publications and source records attributed to S S Shim.

At least 19 recordsLinked to original sources

C-reactive protein in umbilical cord blood: a simple and widely available clinical method to assess the risk of amniotic fluid infection and funisitis.

OBJECTIVE: The purpose of this study was to determine whether concentrations of C-reactive protein (CRP) in umbilical cord plasma at birth were elevated in neonates with sepsis, an inflammatory lesion of the umbilical cord (funisitis) or who were born to mothers with microbial invasion of the amniotic cavity. METHODS: Umbilical cord plasma was collected at birth from 313 singleton preterm neonates (20-35 weeks of gestation). The results of amniotic fluid culture performed within 5 days of birth, the occurrence of congenital neonatal sepsis and the presence of funisitis were assessed. Amniocentesis was performed in 152 patients within 5 days of birth. Amniotic fluid was cultured for aerobic and anaerobic bacteria and for mycoplasmas. The CRP concentration was measured with a highly sensitive immunoassay. RESULTS: The median cord plasma CRP concentration was significantly higher in neonates with a positive amniotic fluid culture than in those with negative culture (median 245.9 (range 11.6-4885.5) ng/ml vs. median 44.3 (range 2.3-7401.8) ng/ml; p < 0.001), in those with congenital proven sepsis than in those without this complication (median 789.5 (range 20.4-2584.3) ng/ml vs. median 41.5 (range 1.3-7401.8) ng/ml; p < 0.005) and in neonates with funisitis than in those without funisitis (median 403.8 (range 4.9-10897.4) ng/ml vs. median 31.0 (range 1.3-7401.8) ng/ml; p < 0.001). The sensitivity of CRP in the identification of amniotic fluid infection, neonatal sepsis and funisitis was similar to that of interleukin-6 (> 17.5 pg/ml). However, the specificity of CRP in the identification of neonatal sepsis and funisitis was significantly higher than that of interleukin-6 (74% vs. 69%, p < 0.05; 83% vs. 76%, p < 0.01). CONCLUSION: Umbilical cord plasma CRP concentrations were elevated in patients with amniotic fluid infection, congenital neonatal sepsis and funisitis.

Adult↗

Pharmacological characterization of interactions of RO 25-6981 with the NR2B (epsilon2) subunit.

We used ligand binding to ascertain whether the pharmacological actions of RO 25-6981 [(R:(*), S:(*))-alpha-(4-hydroxyphenyl)-beta-methyl-4-(phenylmethyl)-1-piperidinepropanol] match those of other NR2B (epsilon2) subunit specific agents. RO 25-6981 inhibited binding of 125I-MK801 [iodo-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohept-5,10-imine maleate] to receptors made from NR1a/epsilon2 but not NR1a/epsilon1. Increasing the concentration of spermidine did not change the efficacy of RO 25-6981 and minimally changed the IC(50) value. Chimeric epsilon1/epsilon2 receptors demonstrated that the structural determinants for high affinity actions of RO 25-6981 were contained completely within the first 464 amino acids, but no receptor retained wildtype features when the size of the epsilon2 component was decreased further. Epsilon1Q336R receptors were more inhibited by ifenprodil and RO 25-9681 than wildtype epsilon1 receptors in ligand binding assays but not in functional assays. Selected mutations of epsilon2E200 and epsilon2E201 also decreased the sensitivity of receptors to ifenprodil and RO 25-6981. These results suggest that RO 25-6981 shares structural determinants with ifenprodil and other modulators in the NR2B subunit.

Animals↗

An elevated amniotic fluid matrix metalloproteinase-8 level at the time of mid-trimester genetic amniocentesis is a risk factor for spontaneous preterm delivery.

OBJECTIVE: Strong evidence implicates chronic intra-amniotic inflammation in the etiology of mid-trimester abortion and spontaneous preterm delivery. The purpose of this study was to determine if concentrations of amniotic fluid matrix metalloproteinase-8, and cytokines such as interleukin-6 and angiogenin can identify patients at risk for spontaneous preterm delivery in patients undergoing mid-trimester amniocentesis. STUDY DESIGN: A case-control study was conducted to compare mid-trimester concentrations of amniotic fluid matrix metalloproteinase-8, interleukin-6, and angiogenin in patients who delivered at term and in those who delivered before term. The study included 19 cases with spontaneous preterm delivery and 95 matched controls with normal outcomes. Patients with abnormal fetal karyotypes or major anomalies were excluded. Matrix metalloproteinase-8, interleukin-6, and angiogenin were measured by using specific immunoassays. Mann-Whitney U tests, Fisher exact tests, and receiver-operating characteristic curves were used for statistical analysis. RESULTS: The median amniotic fluid matrix metalloproteinase-8, interleukin-6, and angiogenin concentrations of patients with spontaneous preterm delivery were significantly higher than those of control cases (matrix metalloproteinase-8: median, 3.1 ng/mL [range, 0.3-1954.9 ng/mL] vs median, 1.3 ng/mL [range, <0.3-45.2 ng/mL], P <.01; interleukin-6: median, 0.32 ng/mL [range, 0.04-2.52 ng/mL] vs median, 0.18 ng/mL [range, 0.01-1.81 ng/mL], P <.01; angiogenin: median, 11.1 ng/mL [range, 4.5-30.7 ng/mL] vs median, 6.7 ng/mL [range, 1.3-21.9 ng/mL], P <.001). Amniotic fluid matrix metalloproteinase-8 concentrations higher than 23 ng/mL had the highest specificity and odds ratio (sensitivity, 42% [8/19]; specificity, 99% [94/95]; OR, 68.4 [95% CI, 7.8-599.1]) in the identification of the patients with preterm delivery after genetic amniocentesis. CONCLUSIONS: Elevated mid-trimester concentrations of amniotic fluid matrix metalloproteinase-8, interleukin-6, and angiogenin are a risk factor for early spontaneous preterm delivery (<32 weeks). An elevated matrix metalloproteinase-8 level of >23 ng/mL is a powerful predictor of spontaneous preterm delivery (<32 weeks) with an odds ratio of 68.4. Amniotic fluid studies can be used to improve the risk assessment for preterm delivery in women who undergo mid-trimester amniocentesis for genetic indications.

Adult↗

Clinical significance of intra-amniotic inflammation in patients with preterm labor and intact membranes.

OBJECTIVE: The purpose of this study was to determine the frequency and clinical significance of intraamniotic inflammation in patients with preterm labor and intact membranes. STUDY DESIGN: Amniocentesis was performed in 206 patients with preterm labor and intact membranes. Amniotic fluid was cultured for aerobic and anaerobic bacteria and mycoplasmas. The diagnosis of intraamniotic inflammation was made in patients with a negative amniotic fluid culture on the basis of amniotic fluid concentrations of interleukin-6 (>2.6 ng/mL, derived from receiver operating characteristic curve analysis). Statistical analysis was conducted with contingency tables and survival techniques. RESULTS: Intra-amniotic inflammation (negative amniotic fluid culture but elevated amniotic fluid interleukin-6) was more common than intra-amniotic infection (positive amniotic fluid culture regardless of amniotic fluid interleukin-6 concentration; 21% [44/206 women] vs 10% [21/206 women]; P <.001). The amniocentesisto-delivery interval was significantly shorter in patients with intra-amniotic inflammation than in patients with a negative culture and without an inflammation (median, 20 hours [range, 0.1-2328 hours] vs median, 701 hours [range, 0.1-3252 hours], respectively; P <.0001). Spontaneous preterm delivery of <37 weeks was more frequent in patients with intra-amniotic inflammation than in those with a negative culture and without inflammation (98% vs 35%; P <.001). Patients with intra-amniotic inflammation had a significantly higher rate of adverse outcome than patients with a negative culture and without intra-amniotic inflammation. Adverse outcomes included clinical and histologic chorioamnionitis, funisitis, early preterm birth, and significant neonatal morbidity. There were no significant differences in the rate of adverse outcomes between patients with a negative culture but with intra-amniotic inflammation and patients with intra-amniotic infection (positive culture regardless of amniotic fluid interleukin-6 concentration). CONCLUSION: Intra-amniotic inflammation/infection complicates one third of the patients with preterm labor (32%; 65/206 women), and its presence is a risk factor for adverse outcome. The outcome of patients with microbiologically proven intra-amniotic infection is similar to that of patients with intra-amniotic inflammation and a negative amniotic fluid culture. We propose that the treatment of patients in preterm labor be based on the operational diagnosis of intra-amniotic inflammation rather than the diagnosis of intra-amniotic infection because the latter diagnosis cannot be undertaken rapidly.

Amniocentesis↗

The frequency and clinical significance of intra-amniotic inflammation in patients with a positive cervical fetal fibronectin.

OBJECTIVE: A positive fetal fibronectin result in cervicovaginal fluid is a powerful predictor of preterm delivery and is considered a marker for upper genital tract infection (ie, intrauterine infection). Treatment with antimicrobial agents is being considered in patients with a positive fetal fibronectin test of cervico/vaginal fluid. This study was undertaken to determine the frequency and clinical significance of intra-amniotic infection/inflammation in patients with a positive fetal fibronectin. STUDY DESIGN: A total of 1709 pregnant women (gestational age, 23-31 weeks) were screened for cervical fetal fibronectin. Patients with a positive fibronectin were offered amniocentesis for the diagnosis of intra-amniotic infection and treatment with antibiotics. Amniocentesis was performed in 58 patients with a positive fibronectin test (>50 ng/mL). Amniotic fluid was cultured for aerobic/anaerobic bacteria and mycoplasmas. Polymerase chain reaction assay for Ureaplasma urealyticum was performed. Interleukin-6 concentrations were measured by a specific immunoassay. Nonparametric statistics were used for analysis. RESULTS: None of the patients with a positive fibronectin had a positive amniotic fluid culture. U urealyticum was detected in 1 case (1.8%) with the polymerase chain reaction assay. Amniotic fluid IL-6 was elevated (>2.5 ng/mL) in 5.3% of patients (3/57 patients); all of these patients delivered preterm neonates. There was no relationship between amniotic fluid IL-6 and cervical fibronectin concentration (r = 0.14;P: >.1). Patients who delivered preterm (<34 weeks) had higher median amniotic fluid IL-6 and cervical fetal fibronectin concentrations than those patients who delivered after 34 weeks (IL-6: median, 2.1 ng/mL [range, 0.1-25.3 ng/mL] vs median, 0.3 ng/mL [0.03-2.4 ng/mL]; P <.05; fibronectin: median, 509 ng/mL [260->1000 ng/mL] vs median, 155 ng/mL [50-889 ng/mL]; P <.01). CONCLUSION: Intra-amniotic infection was detected in 1.8% of cases with a positive fibronectin in the cervical fluid; intra-amniotic inflammation was present in 5.3% of cases. All patients with a positive fetal fibronectin and intra-amniotic inflammation delivered preterm neonates.

Adult↗

Identification of p53 gene mutations in breast cancers and their effects on transcriptional activation function.

Somatic mutations in the p53 tumor suppressor gene are the most common genetic alterations found in human malignancies. In the present study, we studied 36 primary human breast carcinomas, using a polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and sequencing analysis of exons 2 through 9 for the presence of p53 gene mutations. Six of 36 (17%) breast cancers contained mutations within the core domain of the p53 protein responsible for sequence-specific DNA binding (codons 102-292); all 5 missense mutations clustered between codons 240 and 291 (codons 240, 243, 250, 285, and 291), whereas one nonsense mutation occurred at codon 199. By using recombinant PCR in vitro mutagenesis, we introduced point mutations at codons 199 from Gly to stop (gly199stop), 240 from Ser to Ile (ser240Ile), 250 from Pro to Ala (pro250ala), 285 from Glu to Lys (glu285lys), and 291 from Lys to Asn (lys291asn), and all the p53 sequences were subcloned into the CMVneoBam vector under the control of the cytomegalovirus (CMV) promoter. To test whether the mutants p53 were functionally wild-type (wt) or mutant, we transfected them to p53-null Saos-2 cells with a reporter plasmid containing a p53-responsive element, and performed chloramphenicol acetyltransferase (CAT) assay. Transient CAT assay for transcriptional activation revealed that one group, including gly199stop, ser240ile, glu285lys, and lys291asn, abolished the transcriptional activity, whereas the other group, including pro250ala, retained stronger transcriptional transactivation activity than that of wt p53.

Adult↗

Actions of butyrophenones and other antipsychotic agents at NMDA receptors: relationship with clinical effects and structural considerations.

Haloperidol inhibits NMDA receptors with higher affinity for NMDA receptors composed of NR1/2B compared with NR1/2A. To assess whether the clinical effects of haloperidol and other antipsychotic agents are mediated through this site on NMDA receptors and to examine structure activity relationships at this site, we examined the ability of a variety of drugs with neuroleptic actions to inhibit NMDA receptor function. Many antipsychotic agents inhibit 125I-MK 801 binding to the NMDA receptor with IC50 values in the micromolar range. The rank order of potency for inhibition of binding to adult rat forebrain was trifluperidol (TFP) > clozapine = fluphenazine = reduced haloperidol = spiperone = trifluoperazine = butaclamol >> pimozide = risperidone = sulpiride. These findings match the molecular biological specificity of the agents, with trifluperidol having a marked preference for NR1/2B (epsilon2) receptors. Mutations at epsilon2E201, which alter the effects of haloperidol, also decrease the affinity of TFP but not other modulators, showing that the effect of TFP but not other modulators is mediated by this residue of the NMDA receptor. The present results demonstrate that while TFP acts on NMDA receptors in a manner similar to haloperidol, other antipsychotic agents do not share the specific pharmacological properties of this action, suggesting that their clinical mechanism is not mediated by this receptor.

Animals↗

Effects of lesions in the medial prefrontal cortex on the activity of midbrain dopamine neurons.

To determine whether lesions in the prefrontal cortex (PFC) alter the activity of midbrain dopamine (DA) neurons, single unit recordings were made from DA neurons in control and lesioned rats. PFC lesions, obtained by local injection of ibotenic acid into the medial PFC, had no effect on either firing rate or bursting activity of DA neurons in the ventral tegmental area (VTA). However, the number of spontaneously active DA neurons in the VTA was significantly decreased. In the substantia nigra (SN), the same lesions increased the firing rate and had no effect on either the bursting activity of the number of active DA cells. These results suggest that PFC lesions alter the activity of DA neurons. However, VTA and SN DA neurons may respond differently to PFC lesions.

Animals↗

Blood supply of the knee joint. A microangiographic study in children and adults.

The knee joint blood supply is derived from a rich anastomosis of the five major constant arteries, namely, the superior medial and lateral, the middle (posterior), and the inferior medial and lateral genicular arteries. Anastomosis also occurs with descending genicular arteries and the anterior tibial recurrent artery. These branches form anastomoses in and around the knee joint, while each major vessel was noted to provide the respective major blood supply to specific areas. The most obvious difference between vascularization of child and adult knees was the separation of vessels and relative avascularity of epiphyseal plate areas; such persisted until closure of the epiphyseal plate. The regions representing the seals of plate closure had less rich vascularization. A rich intraosseous blood supply was defined in the femoral and tibial condyles and the patella. Similarly, the adjacent and superficial soft tissues, including major ligaments and peripheral parts of the menisci, were richly vascularized. Areas of separated vascularization in children may have relevance to epiphyseal injury, growth deformity, Osgood-Schlatter disease, and hematogenous osteomyelitis. In adults, such information may be relevant to high tibial osteotomy, meniscus and cruciate ligament repair, and surgery utilizing the semitendinosus tendon, fascia lata, or patella tendon grafts.

Aged↗

The vascular and nerve supply of the human meniscus.

Twenty-three fresh, cadaver knees were studied to evaluate details of the vascular and nerve supply of the menisci in humans. Vascularity was investigated using dye and latex injections, and the nerve supply was studied microscopically using a variety of special stains. Vessels arise mainly from medial and lateral inferior and middle geniculate arteries. Radial branches from a perimeniscal plexus enter the meniscus at intervals, with a richer supply to the anterior and posterior horns. Vessels supplying the body are limited to the peripheral one-third, except in the fetus. There is an avascular area adjacent to the popliteus tendon. The perimeniscal tissue is richly innervated. Most nerves are associated with vessels. Smaller nerves and axons run radially in convoluted patterns. Single axons course through the perimeniscal tissue, and many nerves are seen in the interstitial tissue of the outer one-third of the meniscus and in the anterior and posterior horns. The inner two-thirds has no nerve fibers.

Aged↗

The iliopsoas muscle pedicle bone graft: an experimental study of femoral head vascularity after subcapital fractures and hip dislocations.

Distal iliopsoas muscle pedicle bone graft was investigated in dogs to determine whether a collateral blood supply to the femoral head can develop after displaced femoral neck fractures and dislocation of the hip joint. Microangiography performed in cadavers showed good vascularity of the muscle pedicle graft and similar studies in dogs showed that when transferred to the anterior femoral neck, the iliopsoas muscle pedicle graft healed with an ingrowth of vessels across the graft site. Microangiographic and histologic studies in dogs showed that the procedure could maintain the vascularity and viability of the grafted femoral head. Consequently, an iliopsoas muscle pedicle bone graft can provide a vascular supply to a compromised femoral head and may be applied in both the prevention and treatment of avascular necrosis of the injured femoral head.

Angiography↗

Effect of the high femoral osteotomy upon the vascularity and blood supply of the hip joint.

This investigation was done to study the effects of high femoral osteotomy upon the vascularity and blood supply of the hip and to further our knowledge of its physiologic basis. We have used established methods of study, including bone scans, microangiography, isotope clearance and perosseous venography, and based upon the results of these studies, we have reached certain conclusions. First, high femoral osteotomy increases the blood flow and vascularity in the hip joint, the femoral head and neck and the great trochanter. Second, bone scanning techniques using 99mTc labeled diphosphonate have shown increased uptake in the femoral head and neck after high femoral osteotomy. The localization was done using a Digital Gamma III computer, and the activity on the osteotomy side at two weeks was 3.5 times as great as on the control side. By 16 weeks postoperatively, there was still two times as much activity on the osteotomy side. Third, microangiography showed increased vascularity both at the osteotomy site and in the femoral head and neck and the greater trochanter on that side. Such an increase in vascularity first became evident two weeks after osteotomy and persisted during the four month period studied. Fourth, the results of the 99mTc diphosphonate clearance study showed a 25 per cent increase in femoral head blood flow on the operative side. Fifth, perosseous venography of the femoral head and neck showed a marked increase in venous drainage through the osteotomy site in the immediate postosteotomy stage.

Animals↗

Circulatory and vascular changes in the hip following innominate osteotomy: an experimental study.

The circulatory and vascular changes in the hip following Salter-type innominate osteotomy were studied in 35 dogs to determine the effects of innominate osteotomy on the blood supply of the hip joint. Microangiography, bone scanning, and isotope clearance were employed four months after the innominate osteotomy. Microangiography showed increased vascularity at the osteotomy site, in the ipsilateral side acetabulum, and in the femoral head in 65% of the dogs. Bone scanning with 99mTc diphosphonate showed increased activity at the osteotomy site, in the acetabulum, and in the femoral head and neck in 75% of the dogs. The 99mTc diphosphonate clearance studies showed that the blood supply to the femoral head was increased by almost 30% after innominate osteotomy in 50% of the dogs studied. These observations indicate that innominate osteotomy could increase the vascularity and blood supply of the hip by increasing the collateral circulation in the process of healing of the osteotomy. The physiologic basis of the joint to innominate osteotomy constitutes a rational basis for recommending the operation for the treatment of selected cases of congenital hip dislocation, Legg-Perthes disease of the femoral head, and degenerative osteoarthritis of the hip with or without acetabular dysplasia.

Acetabulum↗

Circulatory and vascular changes in the hip following traumatic hip dislocation.

An experimental study of the extraosseous and intraosseous vascular and circulatory changes following traumatic hip dislocation in dogs and rabbits is reported. The observations were made by dissection, angiography and histology following posterior dislocation and reduction at varying intervals. Traumatic dislocation of the hip causes extraosseous circulatory disturbance in the hip resulting in intraosseous circulatory deficiency in the femoral head. The sites of the vascular lesions are the extraosseous branches of the femoral circumflex arteries and their extraosseous branches of the epiphyseal and metaphyseal arteries and the retinacular artery of the circulus vasculosus articularis. The types of the vascular damage are irreversible tear of the minority of vessels along the ruptured capsule and teres ligament, and the compression, traction and spasm of the majority of intact vessels which are reversible by early reduction. In prolonged dislocation the circulatory disturbance persists or worsens due to additional pathological changes such as posttraumatic inflammatory changes, fixed deformity in the dislocated position, thrombosis, fibrosis and occlusion of vessels which may eventually cause an ischemic necrosis of the femoral head. Early reduction within several hours after dislocation restores nearly normal regional anatomy and relieves vessels from compression, traction or spasm and restores extra and intraosseous circulation. It also prevents or minimizes thrombosis, fibrosis and occlusion of vessels and avascular necrosis of the femoral head.

Animals↗

J. Edouard Samson Address: the autonomic nerve supply of bone. An experimental study of the intraosseous adrenergic nervi vasorum in the rabbit.

The anatomy of the autonomic sympathetic vasomotor nerve supply of bone was studied in rabbits by methods of histochemistry, and fluorescent and electron microscopy. Our observations show that the intraosseous vessels are richly supplied by adrenergic nerves. The large primary nerves are located on or about the surface of the vessel; the medium sized secondary nerves spiral around the long axis of vessels lying more deeply in the tunica adventitia; and the fine tertiary nerves form a rich plexus at the outer area of the tunica media. The tertiary nerves have various structures which probably contain neurotransmitter substance--that is, noradrenaline--and function as neuro-vasomuscular synapses. The sympathetic nerve supply of bone originates from the appropriate ganglion, and in the case of the tibial diaphysis it descends through the sciatic nerve and thereafter mainly through the medial popliteal nerve and enters the bone alongside the nutrient artery.

Adrenergic Fibers↗