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Biomedical subjects

H Pinar

Publications and source records attributed to H Pinar.

At least 19 recordsLinked to original sources

Inhibins and activins in human fetal abnormalities.

To date, the only routine clinical application of inhibin or activin measurement in testing for fetal abnormalities has been the use of inhibin A in prenatal screening for trisomy 21 (Down syndrome). Second trimester maternal serum levels of inhibin A are, on average, two-fold higher in Down syndrome than in unaffected pregnancies. Although the biology of altered second trimester maternal serum analyte levels in Down syndrome pregnancy cannot yet be explained, it seems that fetal products tend to be decreased, while placental products tend to be increased. This pattern holds true for inhibin A because maternal serum levels appear to be derived from placental rather than fetal sources. Therefore, the measurement of inhibins and activins in maternal fluids, although clinically useful and relatively easy to obtain, may not be helpful in studying their role in human fetal development. Studies in transgenic mice indicate a role for activin, follistatin, and activin receptor type IIA in development of the palate and craniofacial region. Cleft palate is a common birth defect and is associated with serious feeding and respiratory complications in newborns. We have begun to investigate the potential role of activin in human craniofacial development by examining the spatial and temporal expression of inhibin/activin subunits, follistatin and the activin receptors in the fetal palate. Palate tissues were collected at autopsy from fetuses ranging in gestational age from 9 to 42 weeks, and 8 week embryonic tissues were also examined. Tissues were either stored in paraffin for immunocytochemistry or were frozen for RT-PCR examination of the expression of inhibin/activin proteins or mRNAs, respectively. To date, betaA subunit, follistatin, and activin receptor, but not alpha and betaB subunit, mRNAs are present in palate tissues and inhibin/activin betaA immunoreactivity has been consistently observed in developing bone. Expression of the activin A subunit and its receptors in the human fetal palate are consistent with a developmental role. Studies are ongoing to determine whether altered activin biosynthesis is associated with cleft palate. Future studies of fetal tissues may help to elucidate other roles for the TGF-beta family in human development.

Activins↗

Aromatase p450 expression in a feminizing adrenal adenoma presenting as isosexual precocious puberty.

A 7-yr-old girl presented with isosexual precocious puberty secondary to a feminizing adrenal adenoma. The adrenal tumor was found to express aromatase messenger ribonucleic acid. Enzyme kinetic studies revealed a high level of aromatase activity in the adrenal tumor, with a K(m) of 45 nmol/L and a maximum velocity of 25.6 pmol/mg.h. Aromatase activity was approximately 500-fold higher in the tumor than in adjacent normal adrenal tissue. Although histopathological examination of the tumor was most consistent with a benign adenoma, the aromatase transcripts present in the tumor corresponded to those previously associated with malignant as well as benign tumors. We consider the pattern of aromatase expression sufficient to warrant continued follow-up for tumor recurrence. Our case demonstrates that isosexual precocious puberty secondary to a feminizing adrenal tumor can be due to estrogen synthesis from the tumor itself rather than peripheral aromatization as had been previously theorized.

Adenoma↗

Outcome of very low birth weight infants with histopathologic chorioamnionitis.

OBJECTIVE: To determine neonatal outcome at 7 months of corrected age in very low birth weight (VLBW) infants with placental chorioamnionitis. METHODS: We conducted a cohort study of 287 VLBW infants delivered as a result of preterm premature rupture of membranes (PROM) or preterm labor. Control subjects (n = 123) had placentas with absent umbilical cord inflammation and absent or low-grade membrane inflammation. Case subjects (n = 164) had moderate membrane inflammation or any umbilical cord inflammation. Neonatal and 7-month outcomes were compared. A power analysis showed that 98 total subjects were needed to reject the two-sided null hypothesis with a difference in mean Bayley index scores of at least 8. RESULTS: Infants in the study group had significantly more preterm PROM, antenatal antibiotics, lower birth weight, lower gestational age, longer duration of ruptured membranes, and clinical chorioamnionitis. Intraventricular hemorrhage occurred more commonly in infants with placentas demonstrating chorioamnionitis (relative risk = 1.6, 95% confidence interval 1.1, 2.4, P =.013). One hundred sixty-seven (69%) of the 243 surviving infants had 7-month follow-up. There was no difference between cases and controls in mean Bayley mental developmental index (93 compared with 90, P =.25), psychomotor developmental index (89 compared with 90, P =.68), or in the number of infants that were developmentally delayed. CONCLUSION: Despite a higher frequency of intraventricular hemorrhage, no difference in developmental scores was detected at 7 months of corrected age in VLBW infants with histologic chorioamnionitis.

Adult↗

Influence of chorioamnionitis on developmental outcome in very low birth weight infants.

OBJECTIVE: To determine the effect of exposure to chorioamnionitis on developmental outcome in very low birth weight (VLBW) infants. METHODS: Five hundred four maternal charts (97% of all VLBW infants delivered from 1990 to 1994) were reviewed. A historical cohort study of the 330 infants delivered secondary to preterm premature rupture of membranes or preterm labor was performed. Case subjects (71) were delivered of mothers with chorioamnionitis by clinical criteria; control subjects (259) were delivered of mothers without chorioamnionitis. Bayley index scores at 7 months' corrected age and special care nursery outcomes were compared. One hundred seventy-three subjects were necessary to reject the two-sided null hypothesis with 80% power with a difference in mean Bayley index scores of at least 8. RESULTS: Neonatal sepsis (8.5% compared with 1.9%; odds ratio [OR] = 4.7, 95% confidence interval [CI] 1.4, 15.9, P = .015) and a low 5-minute Apgar (72% compared with 55%; OR = 2.1, CI 1.2, 3.8, P = .012) occurred more frequently in the chorioamnionitis group. One hundred eighty-seven (68%) of 273 surviving neonates had follow-up. Cases and controls were similar in mean Bayley mental developmental index (91.2 compared with 91.8, P = .84), Bayley psychomotor developmental index (89.8 compared with 89.1, P = .82), and number of infants developmentally delayed. Duration of exposure to chorioamnionitis did not affect neonatal outcome. CONCLUSION: Despite higher rates of sepsis and low Apgar scores, no difference in outcome at 7 months of corrected age was detected in VLBW infants exposed to chorioamnionitis. Contemporary neonatal management may reduce the adverse effects of this exposure.

Adult↗

The distal fascicle of the anterior inferior tibio-fibular ligament as a cause of anterolateral ankle impingement: results of arthroscopic resection.

We arthroscopically resected the impinged distal fascicle of the anterior inferior tibiofibular ligament (AIT-FL) in 21 patients (mean age 31 (11-68) years, 14 women) with chronic ankle pain after an ankle sprain. Clinical tests revealed moderate laxity in 2 and severe laxity in another 2, the remaining 17 ankles showing only mild laxity. During arthroscopy, an impinging distal fascicle of the AITFL was found in all cases. Following anterolateral synovectomy, the fascicle was excised. At the follow-up after mean 3 (2-4) years, good-to-excellent results were obtained in 17 patients. 19 patients were satisfied with the procedure and 17 patients returned to their previous level of activity. 2 patients who had mild laxity were graded as poor because of neuromas of the terminal branches of the superficial peroneal nerve. These patients became asymptomatic after an injection of steroids.

Adolescent↗

Expression of the RNA component of telomerase in Wilms tumor and nephrogenic rest recapitulates renal embryogenesis.

Telomerase is a ribonucleoprotein enzyme associated with cellular immortality and has been detected in the vast majority of adult tumors. Wilms tumor is a histologically diverse embryonal malignancy of childhood, and the histological features of Wilms tumor and its precursor lesion, the nephrogenic rest, recapitulate the components of normal renal embryogenesis. Both the epithelial and the stromal components of Wilms tumor arise by differentiation of primitive mesodermal blastema. We compared expression of the RNA component of human telomerase (hTR) in normal developing kidneys, Wilms tumors, and nephrogenic rests and correlated expression of hTR with cell proliferation. Using a radioactive in situ hybridization method, we examined archival material from 17 Wilms tumors (including nine with nephrogenic rests), four therapeutically aborted embryos (37 to 56 days), three fetuses on whom autopsies had been performed, and one neonate for expression of hTR. Proliferative index was measured by immunohistochemical staining for MIB1. In the embryonic kidney, Wilms tumors, and nephrogenic rests, the patterns of hTR expression were similar: expression was usually maximal within the immature epithelial elements followed by the poorly differentiated blastema, but was weak or absent in the immature stroma. Mature tubules, glomeruli, and stroma were negative for hTR expression, as were differentiated heterologous elements present in post-therapy Wilms tumors. There was only a partial relationship between proliferative index and hTR expression. In the embryonic kidney, Wilms tumors, and nephrogenic rests, blastema had the highest proliferative index, whereas the indices were significantly lower in the immature epithelium and stroma. The proliferative index in mature and heterologous elements was low or zero. Thus, the pattern of hTR expression in Wilms tumor and its precursor lesion recapitulates embryogenesis precisely and may represent that aspect of the persistent fetal phenotype which predisposes to the development of malignancy.

Child, Preschool↗

Dislocating anterior horn of the medial meniscus.

Dislocating anterior horn of the medial meniscus was found in 15 knees of 13 patients during arthroscopic examinations done between 1992 and 1995. All of them were available for follow-up evaluation (4 by telephone). There were 11 men and 2 women (average age, 28 years; range, 17 to 49 years). Nine knees had a history of trauma. Only 1 knee had had trauma in two bilateral cases. Duration of symptoms was an average of 3.3 years (range, 3 months to 10 years). The knees were stable clinically. Arthroscopy revealed associated lesions in 13 knees; hypertrophic medial plicae, meniscal, chondral and anterior cruciate ligament (ACL) lesions predominated. Three knees had unusually hypertrophic ligamentum mucosum. Eleven of 13 knees had more than one associated lesions. Only 2 knees (2 patients) had isolated dislocating anterior horn of the medial meniscus. Only the associated lesions were treated (except for ACL lesions) and dislocating anterior horns of the medial menisci were left alone. Follow-up averaged 21 months (7 to 40 months). At follow-up, 11 knees were graded as excellent, 3 as good, and 1 as fair according to the Lysholm scale. Eight knees had minor symptoms and 6 were asymptomatic; no improvement was noted in 1 knee. Overall, 12 patients (14 knees) were satisfied with their treatment. Dislocating anterior horn of the medial meniscus is a normal anatomic variant with little or no clinical significance. When seen during arthroscopy, a significant lesion should be looked for. It is an incidental finding and should be left alone.

Adolescent↗

Expression of the RNA component of telomerase during human development and differentiation.

We used a radioactive in situ method to study expression of the RNA component of human telomerase (hTR) during normal human development and differentiation using archival tissues. In embryonic tissues, the highest and most uniform expression was present in undifferentiated neuroepithelium. Expression was stronger in immature epithelium than in accompanying immature mesenchyme. Differentiation of most tissues was accompanied by decreased or absent expression. Except for testis and adrenal, the adult pattern of expression was present by the 10th postnatal week. In adult tissues, high expression was present in the testis (primary spermatocytes and Sertoli cells), moderate expression was present in lymphoid follicles (germinal centers), and weak expression was present in epithelia (regenerative cells) but was absent in the nervous system and mesenchymal derived tissues. Expression in adult tissues was predominantly limited to dividing cells, although certain differentiated postmitotic cells expressed the hTR. Our studies demonstrate the complex interrelationship of hTR expression with human development, differentiation, and cell division.

Adolescent↗

Bone bruises detected by magnetic resonance imaging following lateral ankle sprains.

Although bone bruises have been well described in the knee joint, little is known about their presence in the ankle joint. The present study attempted to document the association of bone bruises with lateral ankle sprains. Magnetic resonance (MR) images were obtained from 60 consecutive patients with lateral ankle sprains between April 1994 and June 1995. There were 29 men and 31 women, aged on average 25 years (range 12-68 years). All of the patients presented within 3 weeks of the sprain. MRI examinations were done within 3 weeks of the injury in 15, after 3-6 weeks in 21, and after 6-8 weeks in 24 cases. There were 28 first-time sprains, while 32 patients had suffered one or more sprains before the most recent one. Plain radiographs showed no evidence of osseous abnormality. Following the conventional MRI examination, magnetic resonance arthrography (MRA) was done by injecting 2 mM of gadolinium diethylene triamine penta-acetic acid (DTPA) into the joint under fluoroscopic control, and the same images were obtained again to search for ligamentous lesions. A total of 11 bone bruises were detected in 10 ankles. In this group of patients, there were 5 men and 5 women aged on average 27 years (range 12-50 years). Four MRI examinations were done within 3 weeks, while six were done 3-6 weeks after the injury. One ankle which had suffered one previous sprain and complete ruptures of anterior talofibular ligament (ATFL) and calcaneofibular ligament (CFL) had two lesions (talus and navicula). In another recurrent case with complete ATFL and CFL ruptures, the lesion was found in the calcaneus. The remaining eight lesions were in the talus in eight ankles. The ligamentous lesions in these ankles included three complete ATFL and CFL ruptures, and four isolated ATFL ruptures; in one ankle there were no ligamentous lesions. The location of talar bruises was medial in six and lateral in three ankles. The incidence of bone bruises associated with isolated ATFL lesions was 16% (4/25). With combined ATFL and CFL lesions the incidence was 50% (5/10). The incidence of ankles with bone bruises and first-time and recurrent sprains was 7% (2/28) and 25% (8/32), respectively. The occurrence of bone bruises should be kept in mind following ankle sprains. Their clinical significance in the long term remains to be determined.

Adolescent↗

Intra-articular hemangioma of the knee with meniscal and bony attachment.

A hemangioma in the knee joint of a 37-year-old woman was diagnosed by magnetic resonance imaging. The case presented with pain and a tender localized swelling lateral to the patellar tendon. Arthroscopy verified the diagnosis but did not allow visualization of the full extent of the tumor. After arthroscopic subtotal excision of the associated hypertrophic medial plica, a miniarthrotomy was done. The tumor was attached to the periphery of the anterior horn of the lateral meniscus, to the anterior tibial plateau, and to the fat pad. It seemed to take its origin from the venous plexus just below the anterior lip of the central tibial plateau. The patient was asymptomatic 9 months after surgery. In hemangiomas not amenable to arthroscopic surgery, open excision through miniarthrotomy ensures complete removal without prolonging recovery.

Adult↗

Ischemia-reperfusion injury in the intestines of newborn pigs.

Although the pathogenesis of necrotizing enterocolitis remains uncertain, ischemia appears to be an important contributing factor to the development of this disorder. Reperfusion plays a major role in ischemia-related injury, and oxygen free radicals produced during reperfusion most likely contribute to the injury. These oxidants can be generated during prostanoid metabolism, which increases during reperfusion of ischemic gut in adult subjects. The present study was designed to: 1) examine the effects of superior mesenteric artery occlusion, e.g. ischemia and reperfusion in vivo on the development of histopathologic intestinal injury; 2) determine whether products of arachidonic acid metabolism, e.g. prostanoids are increased during reperfusion of ischemic gut; and 3) determine whether oxygen free radical scavengers attenuate the injury in newborn pigs. Chronically catheterized placebo-pretreated newborn pigs exposed to ischemia-reperfusion, placebo-pretreated nonischemic control pigs, and polyethylene glycol-superoxide dismutase (SOD) plus polyethylene glycol-catalase (CAT)-pretreated, ischemic pigs were studied by examining changes in intestinal circulation, oxygenation, prostanoids, and tissue injury. In the placebo-pretreated pigs, intestinal blood flow decreased to very low levels during superior mesenteric artery occlusion. During reperfusion, blood flow increased, but remained below baseline. After ischemia, oxygen uptake returned to values that were similar to baseline. Intestinal efflux of the vasodilator 6-keto-prostaglandin F1alpha was evident (p < 0.05 versus no or zero efflux) during early reperfusion. Histopathologic scoring of terminal ileal samples showed significant mucosal necrosis, surface epithelial disruption, lamina propria congestion and hemorrhage, submucosal hemorrhage, edema, and increases in cells compared with the placebo-pretreated nonischemic pigs. In the SOD plus CAT-pretreated ischemic pigs, changes in intestinal blood flow, oxygen uptake, 6-keto-prostaglandin F1alpha efflux, and the pattern of the ileal tissue injury did not differ significantly from the placebo-pretreated ischemic pigs. In summary, superior mesenteric artery occlusion for 1 h and reperfusion for 2 h resulted in severe intestinal ischemia, early postocclusive limited increases in intestinal perfusion and oxygen uptake, efflux of vasodilating prostanoids during early reperfusion, and signs of ischemic tissue injury in the placebo- and SOD plus CAT-pretreated pigs. This study demonstrates that, after superior mesenteric artery occlusion and reperfusion, severe intestinal tissue injury is detected in vivo, prostanoid efflux increases, and SOD plus CAT given just before occlusion does not attenuate the extent of injury in newborn pigs.

Animals↗

Traumatic prepatellar neuroma: an unusual cause of anterior knee pain.

Although the patellar (infrapatellar) branch of the saphenous nerve is vulnerable to direct trauma, traumatic prepatellar neuroma has rarely been reported in the literature. It should be considered in the differential diagnosis of disorders causing anterior knee pain. Point tenderness, a palpable fusiform nodule and a positive Tinel's sign are the diagnostic features. Simple excision is curative.

Adult↗

Intraarticular fibroma of the tendon sheath of the knee.

Fibroma of the tendon sheath is an uncommon soft-tissue tumor. Intraarticular localization has not been previously reported. The patient presented with unexplained recurrent swelling of the knee not associated with recent trauma. The soft-tissue tumor was identified by magnetic resonance imaging. Arthroscopy confirmed the diagnosis. Arthrotomy was performed because of the large size of the lesion.

Adult↗

Kinematic and dynamic axial computed tomography of the patello-femoral joint in patients with anterior knee pain.

Thirty-eight knees of 26 patients with anterior knee pain (12 bilateral) were included in the study. There were 22 women and 4 men, and their average age was 29 years. Axial computed tomography (CT) examination of both knees were done at 0 degrees, 10 degrees, 20 degrees, 30 degrees, 40 degrees and 60 degrees of flexion with and without muscle contraction. Images were always taken at the mid-patellar level. Patellar tilt angle (PTA), congruence angle (CA) and sulcus angle (SA) were measured at each knee position. Normal values were also obtained from 14 healthy volunteers (28 knees). Thus, the types of patello-femoral incongruence were determined at each knee position: 1, tilt + lateralisation (TL: 12 knees); 2, lateralisation (L: 4 knees); 3, medialisation (M: 5 knees); 4, lateral to medial instability (LM: 1 knee); 5, tilt (T: 1 knee). Fifteen knees were classified as normal. When the groups were analysed separately, in the TL group the T or L component would have been missed in nine cases if the images were taken only at 30 degrees or only in the first 30 degrees of flexion. In the L group two patellae were reduced at 30 degrees. In three knees in the M group, medialisation began at 10 degrees, 20 degrees and 30 degrees. One patella was reduced at 40 degrees. In the LM case, the patella was lateralised at 0 degrees, 10 degrees, 20 degrees and medialised at 30 degrees and 40 degrees. In the T case, the patella was tilted only at 20 degrees, 40 degrees and 60 degrees.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Kinematic and dynamic axial computerized tomography of the normal patellofemoral joint.

Fourteen normal volunteers with no history suggesting previous or current knee pathology underwent axial computed tomographic examination of the patellofemoral joint. There were 11 men and 3 women, whose ages ranged from 10 to 46 years (average 25 years). Axial images were obtained at 0 degrees, 10 degrees, 20 degrees, 30 degrees, 40 degrees, and 60 degrees flexion both with and without contraction of the thigh muscles. Thus, 12 images were obtained for each individual. The CT scanner was focused at the midpatellar level prior to each image. Three measurements were made on 24 knees for each individual: congruence angle (CA), patellar tilt angle (PTA), and sulcus angle (SA). PTA increased slightly from 0 degrees to 20 degrees, and decreased slightly with more flexion (not significant, NS). The lower limit of PTA was usually 9 degrees-10 degrees; it was not lower than 7 degrees in any knee position. Muscle contraction increased PTA slightly at each degree of flexion (NS). Mean CA was +18.3 degrees (SD 20.8 degrees) at 0 degrees, which means that normal individuals may have CAs as high as +39 degrees at full extension. There was a gradual decrease in CAs with knee flexion. The mean values became negative between 20 degrees and 60 degrees flexion. Contraction of the thigh muscles caused lateralisation of the patella except at 30 degrees and 40 degrees flexion. This lateral pull was statistically significant at full extension (P < 0.01) and at 10 degrees flexion (P < 0.05). The SA decreased gradually as the flexion of the knee increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗