Can Paediatric Femoral Fracture Hip Spica Application be Done in the Outpatient Setting?

INTRODUCTION: Hip spica casting is a standard treatment for children with femur fractures. This study compares the outcomes of spica cast application, in terms of quality of fracture reduction and hospital charges when performed in operating theatre versus outpatient clinics at a local institution. MATERIALS AND METHODS: A total of 93 paediatric patients, aged between 2 months to 8 years, who underwent spica casting for an isolated femur fracture between January 2008 and March 2019, were identified retrospectively. They were separated into inpatient or outpatient cohort based on the location of spica cast application. Five patients with metaphyseal fractures and four with un-displaced fractures were excluded. There were 13 and 71 patients in the outpatient and inpatient cohort respectively who underwent spica casting for their diaphyseal and displaced femur fractures. Variables between cohorts were compared. RESULTS: There were no significant differences in gender, fracture pattern, and mechanism of injury between cohorts. Spica casting as inpatients delayed the time from assessment to casting (23.55 ± 29.67h vs. 6.75 ± 4.27h, p<0.05), increased average hospital stay (41.2 ± 31.1h vs. 19.2 ± 15.0h, p<0.05) and average hospital charges (US$1857.14 vs US$775.49, p<0.05). Excluding the un-displaced fractures, there were no significant differences in the period of cast immobilisation and median follow-up length. Both cohorts had a similar proportion of unacceptable reduction and revision casting rate. CONCLUSION: Both cohorts presented similar spica casting outcomes of fracture reduction and follow-up period. With spica cast application in operating theatre reporting higher hospital charges and prolonged hospital stay, the outpatient clinic should always be considered for hip spica application.

Detection of QTc interval prolongation using jacket telemetry in conscious non-human primates: comparison with implanted telemetry.

BACKGROUND AND PURPOSE: During repeat-dose toxicity studies, ECGs are collected from chemically or physically-restrained animals over a short timeframe. This is problematic due to cardiovascular changes caused by manual restraint stress and anesthesia, and limited ECG sampling. These factors confound data interpretation, but may be overcome by using a non-invasive jacket-based ECG collection (JET). The current study investigated whether a jacketed external telemetry system could detect changes in cardiac intervals and heart rate in non-human primates (NHPs), previously implanted with a PCT transmitter. EXPERIMENTAL APPROACH: Twelve male cynomolgus monkeys were treated weekly with vehicle or sotalol (8, 16, 32 mg kg⁻¹) p.o. ECGs were collected continuously for 24 hours, following treatment, over 4 weeks. A satellite group of six NHPs was used for sotalol toxicokinetics. KEY RESULTS: Sotalol attained Cmax values 1-3 hours after dosing, and exhibited dose-proportional exposure. In jacketed NHPs, sotalol dose-dependently increased QT/QTc intervals, prolonged PR interval, and reduced heart rate. Significant QTc prolongation of 27, 54 and 76 msec was detected by JET after 8, 16, and 32 mg kg⁻¹ sotalol, respectively, compared with time-matched vehicle-treated animals. Overall, JET-derived PR, QT, QTc intervals, QRS duration, and heart rate correlated well with those derived from PCT. CONCLUSIONS AND IMPLICATIONS: The current findings clearly support the use of JET to quantify cardiac interval and rhythm changes, capable of detecting QTc prolongation caused by sotalol. JET may be a preferred method compared to restraint-based ECG because high-density ECG sampling can be collected in unstressed conscious monkeys, over several weeks.

A single nucleotide polymorphism in the E-cadherin gene promoter alters transcriptional activities.

E-cadherin plays a critical role in many aspects of cell adhesion, epithelial development, and the establishment and maintenance of epithelial polarity. The loss of the adhesive function of E-cadherin is a critical step in the promotion of epithelial cells to a more malignant phenotype. We identified a C/A single nucleotide polymorphism at -160 from the transcriptional start site of the E-cadherin gene promoter. Transient transfection experiments showed that the A allele of this polymorphism decreased the transcriptional efficiency by 68% compared with the C allele (P<0.001). Electrophoretic mobility shift and footprinting assays revealed that the C allele had a stronger transcriptional factor binding strength than the A allele. These results indicate that the -160 C/A polymorphism has a direct effect on E-cadherin gene transcriptional regulation. This allelic variation may be a potential genetic marker that can help identify those individuals at higher risk for invasive/metastatic diseases.

Frequent methylation of estrogen receptor in prostate cancer: correlation with tumor progression.

Prior studies have shown that the estrogen receptor (ER) gene is down-regulated in prostate cancer, but the mechanism of its inactivation is not known. We hypothesize that inactivation of the ER gene in prostate cancer is through promoter methylation. To test this hypothesis, we investigated the methylation status of the ER gene in prostate cancer cell lines, prostate cancer, and benign prostatic hyperplasia (BPH) tissues samples using the bisulfite genomic sequencing method. Our results show that the ER gene promoter was methylated in 100% (six of six) of the prostate cancer cell lines tested and all were accompanied by loss of ER mRNA expression. Treatment of these cell lines with demethylating agent 5-aza-2'-deoxycytidine restored ER mRNA expression in all of the ER-negative cell lines. In addition, elevated expression of DNA methyltransferase mRNA was found in all of the prostate cancer cell lines. Of the prostate tissue samples analyzed, 60% (6 of 10) in the BPH samples, 80% (8 of 10) in the low-grade cancer samples (grades I and II), and 95% (20 of 21) in the high-grade cancer samples (grades III-V) exhibited promoter methylation of the ER gene. The overall methylation levels in the cancer samples were higher than that in the BPH samples. The differences between the high-grade cancer samples and BPH samples were significant at all CpG sites. Only at three CpG sites were the differences significant between the low-grade cancer samples and BPH samples. This study presents the first evidence that ER gene is transcriptionally inactivated by DNA methylation in prostate cancer. Our data suggest that ER may be involved in the pathogenesis of prostate cancer, as well as BPH.

[Distinct structural bases of the immunoregulatory and central analgesic effects of IFNalpha].

Interferon-alpha (IFNalpha), a cytokine, is also an analgesic molecule. There is significant cross reactivity between IFNalpha and anti-opioid sera, suggesting a strong antigenic relatedness between human IFNalpha molecules and opioid peptides. Different structural basis of the immunoactivity and analgesic effect of IFNalpha can be demonstrated by different reactivities of the two reactions towards different mutants of IFNalpha obtained by using the site-directed mutagenesis. When the 129th Tyr residue of human IFNalpha was mutated to Ser, the immunoactivity of the mutant almost disappeared, while the strong analgesic activity still persisted, which could be blocked by naloxone. These results indicate that there exist distinct domains in the IFNalpha molecule, which mediate immune and analgesic effects differentially, and that the receptor mechanism underlying immune and analgesic effects of IFNalpha may be different.

Differential gene expression of growth factors in young and old rat penile tissues is associated with erectile dysfunction.

The molecular mechanisms of erectile dysfunction with aging are unclear. Recent studies have suggested that growth factors may play a role in the etiology of erectile dysfunction. This present study was designed to test the hypothesis that gene expression of various growth factors such as TGF alpha, TGF beta 1, TGF beta 2, TGF beta 3, IGF and NGF modulate with aging in rat penile tissues. For this purpose, total RNA was extracted from young and old rat penile tissues and the gene expression for these growth factors was determined by differential reverse-transcriptase-polymerase chain reaction (RT-PCR) using specific oligonucleotide primers. mRNA levels of growth factors were quantified by using beta-actin as an internal standard. The results of these experiments suggest that: (1) young and old rat penile tissues expressed mRNA transcripts for TGF alpha, TGF beta 1, TGF beta 2, TGF beta 3, IGF and NGF; (2) TGF beta 1 gene expression was significantly increased in old rat penile tissues as compared to young; (3) mRNA transcripts for NGF and TGF beta 3 were significantly lower in old rat penile tissues as compared to young; and (4) TGF alpha, TGF beta 2 and IGF mRNA expression did not change in young and old rat penile tissues. These results suggest that the differential gene expression for various growth factors in young and old rat penile tissues may be important in understanding the pathophysiology of erectile dysfunction associated with aging.

Effects of diabetes on nitric oxide synthase and growth factor genes and protein expression in an animal model.

Erectile dysfunction occurs frequently in humans with diabetes mellitus; the molecular basis of this phenomenon is not known. We investigated the effects of diabetes on penile erection, nitric oxide synthase and growth factors expression in an animal model. Forty male rats were divided into two groups: the experimental group (n = 30) received intraperitoneal injection of Streptozotocin (STZ) dissolved in citrate buffer to induce diabetes; ten age-matched control rats received injection of citrate buffer vehicle only. Before euthanization at eight weeks, erectile function was assessed by electrostimulation of the cavernous nerves. NADPH diaphorase staining was used to identify NOS and immunostaining technique was used to identify nNOS in the penile nerve fibers. RT-PCR was used to identify mRNA expression of nNOS, eNOS, iNOS, ER-beta, ER-alpha, NGF, IGF-I, TGF-beta 1, and AR. Western blot was used to identify nNOS, IGF-I, NGF, and TFG-beta protein expressions. In the diabetic group, there was: (1) a significant decrease in NOS containing nerve fibers in the dorsal and intracavernosal nerves; (2) a significant lower maximal intracavernosal pressure. RT-PCR showed down-regulation of nNOS (large form), iNOS and ER-beta mRNA expression, Immunoblot showed down-regulation of nNOS protein expression and nNOS immunostaining showed less positive staining in the dorsal and intracavernous nerves in the diabetic group. These molecular changes may provide the basis for further studies to explore the association between diabetes and impotence.

An animal model of Peyronie's-like condition associated with an increase of transforming growth factor beta mRNA and protein expression.

PURPOSE: Transforming growth factor beta (TGF-beta) is involved in numerous vital processes including tissue fibrosis. Our objective was to study the role of TGF-beta in the induction of a Peyronie's-like condition and to produce an animal model for the further study of Peyronie's disease. MATERIALS AND METHODS: Twenty-four adult male Sprague-Dawley rats were divided into two groups. Different concentrations of cytomodulin, a synthetic heptopeptide with TGF-beta-like activity, were injected into the tunica of each rat from the first group (n = 18). Rats in the second group (n = 6) received saline injections as a control. The tunical tissues were taken after 3 days, 2 weeks, and 6 weeks and were examined using Hart and Trichrome stains. In the same tissue samples, TGF-beta mRNA and protein expression were studied. RESULTS: Histological alterations were observed in 15 out of 18 cytomodulin-injected rats, especially in tissue examined after 6 weeks. The most prominent changes were chronic cellular infiltration, focal and diffuse elastosis, thickening, disorganization and clumping of the collagen bundles. Results from immunoblot revealed remarkable TGF-beta1 protein expression in all the cytomodulin-injected rats only after 2 and 6 weeks. No remarkable TGF-beta2 or TGF-beta3 protein expression was observed. TGF-beta1 mRNA expression in the cytomodulin-injected rats was noticed in rats injected with higher concentrations after 3 days, while it was expressed in all rats after 2 weeks. There was no expression in the control group after either 3 days or 2 weeks. CONCLUSIONS: Cytomodulin can induce Peyronie's-like condition in the rat penis, which may explain the role of TGF-beta in the pathogenesis of Peyronie's disease.

[Character and UV spectral identification of deer's heart].

In this paper, the fresh and dried hearts of Cervus nippon and C. elaphus are identified on character, fluorescence and UV spectra. The alcohol extract of the blood of the deer's hearts has mininum absorption at UV 310 nm.

Chromosome 3p24-26 and 3p22-12 loss in human prostatic adenocarcinoma.

Identification of loss of heterozygosity on specific genetic loci is crucial for understanding the pathogenesis of prostate cancer at the molecular level. This is especially important because the deleted regions may contain putative tumor suppressor genes. Chromosome 3p loss appears to be frequently associated with various epithelial cancers. To our knowledge, there is no report on loss of heterozygosity (LOH) of chromosome 3 in human prostate cancer. The present study was designed to investigate the LOH on chromosome 3p in microdissected samples of delineated regions of normal and invasive carcinoma areas of prostatic epithelium from the same tumor sections. For this purpose, DNA was extracted from microdissected normal and tumor cells of 38 prostate cancers, amplified by PCR and analyzed for LOH on chromosome 3p using 6 different polymorphic DNA markers (D3S1560, THRB, D3S647, D3S1298, D3S1228 and D3S1296). Our results suggest that LOH was identified in 34 of 38 cases (89%) with at least one marker. Twelve of 30 informative cases showed LOH at D3S1560; 18 of 22 informative cases showed loss at THRB; 20 of 38 informative cases showed deletion at D3S647; 16 of 38 informative cases showed loss at D3S1298; 12 of 34 informative cases showed LOH at D3S1228; and 6 of 34 informative cases showed LOH at D3S1296 regions. Our results suggest that the LOH is on the 3p24-26 and 3p22-12 regions of the short arm of chromosome 3, indicating 2 discrete areas of deletion on chromosome 3p. The deletion at 3p24-26 and 3p22-12 was not related to the stage or grade of the tumor.

Differential gene expression of transforming growth factors alpha and beta, epidermal growth factor, keratinocyte growth factor, and their receptors in fetal and adult human prostatic tissues and cancer cell lines.

OBJECTIVES: Recent studies have shown that growth factors may play a role in the etiology of benign prostatic hyperplasia (BPH) and prostatic carcinoma. Several growth factors have been reported to be expressed by prostatic tissues, but these growth factors have never been examined in human fetal prostate and compared with adult prostates and cancer cell lines. The present study was designed to investigate the messenger ribonucleic acid (mRNA) expression of transforming growth factor (TGF)-alpha, TGF-beta 1, TGF-beta 2, TGF- beta 3, keratinocyte growth factor (KGF), epidermal growth factor (EGF), EGF receptor (EGF-R), and KGF receptor (KGF-R) in human fetal and adult prostatic tissues and cancer cell lines by reverse-transcriptase-polymerase chain reaction-(RT-PCR) using specific oligonucleotide primers. METHODS: Total RNA was extracted from human fetal and adult prostates (BPH tissues) and cancer cell lines. The gene expression of these growth factors and their receptors was determined by RT-PCR using specific oligonucleotide primers. RESULTS: The results of these experiments suggest that: (1) human fetal prostate expressed mRNA transcripts for TGF-alpha, TGF-beta 1, TGF-beta 2, TGF-beta 3, and EGF. However, KGF, KGF-R, and EGF-R mRNA were not expressed by human fetal prostate; (2) human adult prostate (BPH tissues) showed mRNA transcripts for all growth factors and their receptors except KGF-R; (3) human BPH-1 cell lines expressed mRNA transcripts for TGF-alpha, TGF-beta 1, TGF-beta 2, TGF-beta 3, EGF, and KGF-R, but not for EGF-R and KGF growth factors; (4) human primary prostate cancer cell line (ND-1) showed mRNA transcripts for all growth factors except EGF and KGF; and (5) human prostate cancer cell lines (LNCaP, DU-145, PC-3) expressed mRNA transcripts for all growth factors except KGF, which was absent in all cell lines. However, KGF-R mRNA was absent in the PC-3 prostate cancer cell line. CONCLUSIONS: These results suggest that the differential gene expression for various growth factors and their receptors in human fetal and adult prostatic tissues and cancer cell lines may be important in understanding the role of these factors in the pathophysiology of prostatic diseases.

P53 tumour-suppressor gene mutations are mainly localised on exon 7 in human primary and metastatic prostate cancer.

Mutations in the p53 tumour-suppressor gene are among the most common genetic alterations in human cancers. In the present study we analysed the mutations in the p53 tumor-suppressor gene in 25 primary and 20 metastatic human prostate cancer specimens. DNA extracted from the paraffin-embedded sections was amplified by hot-start polymerase chain reaction, and p53 gene mutations in the conserved mid-region (exons 4-9) were examined using single-strand conformation polymorphism (SSCP) analysis and immunohistochemistry. In the present study, we used a novel hot-start PCR-SSCP technique using DNA Taq polymerase antibody, which eliminates primer-dimers and non-specific products. Because of this new technique, the results of PCR-SSCP showed very high resolution. Polymerase chain reaction products were sequenced directly for point mutations for the p53 gene. Mutations were found in 2 out of 25 primary prostate cancers (8%) and 4 out of 20 metastatic cancers (20%). Mutations were observed exclusively in exon 7 and not in exons 4, 5, 6, 8 or 9. Nuclear accumulation of p53 protein, determined by immunohistochemistry, correlated with the degree of metastasis in prostatic cancer.

[Comparative study of protein polymorphism in the gray Ukrainian breed]. / Sravnitel'noe issledovanie belkovogo polimorfizma seroi ukrainskoi porody.

The electrophoresis of blood serum proteins in polyacrylamide gel has been used to analyze genetic variability of Grey Ukrainian and Hungarian Grey breeds of cattle. The differences in allelic frequency between the breeds and populations of Grey Ukrainian cattle are found. In cattle, post-transferrin-3, new polymorphic protein, controlled by two co-dominant alleles is detected.

[Absorption of ceftizoxime from peritoneal dialysate and its pharmacokinetics in chronic kidney failure patients].

The pharmacokinetics of ceftizoxime (Cef) and its diffusivity across the peritoneal membrane were studied in 10 chronic kidney failure patients undergoing continuous ambulatory peritoneal dialysis. Cef was determined by HPLC. The results showed that the disposition of Cef could be described with a 2-compartment open model after 1 g intravenous infusion. VD = 20 +/- 5 L, AUC = 1237 +/- 327 micrograms.ml-1.h. T1/2 beta = 16.9 +/- 4.5 h, which was much longer than that of patients with normal renal function. Therefore, the regulation of dose regimen was necessary when treating patients with renal failure. Cef was partly eliminated by peritoneal dialysis with the ClD of 2.9 +/- 1.0 ml.min-1. The bidirectional exchange of Cef was seen between blood and dialysate. It is more suitable to describe the diffusive characteristics of Cef from dialysate (or blood) into blood (or dialysate) with a zero order constant rate model. The absorption percentage of Cef after 0.5 g instilled with peritoneal dialysate was 90.4 +/- 7.0%.

Recurrent oncocytoma of the ethmoid sinus with orbital invasion.

A patient is presented with recurrent oncocytic tumor that arose from the lateral nasal wall and posterior ethmoid sinus and then invaded the orbit. The diagnosis of an oncocytic lesion was made from the masses of intracellular mitochondria noted on electron microscopy. The malignant character of the tumor was evident from its local aggressiveness. In agreement with earlier authors, we believe that oncocytic tumors of the nose and paranasal sinuses should be classified as low-grade malignancies.

Meniere's disease at the University of Iowa: 1973 to 1980.

The goals of treatment in Meniere's disease are hearing preservation and control of vertigo. Controversy abounds with regard to the most expeditious and efficacious means of attaining these goals. Low-salt diet, diuretic therapy, endolymphatic-mastoid shunt, and middle cranial fossa vestibular neurectomy are all modes of treatment employed for Meniere's disease at the University of Iowa. This review of our experience from 1973 to 1980 summarizes the efficacy of each therapeutic option.

Otitis media.

Dysfunction of the eustachian tube is the underlying problem in all types of otitis media. Systemic antibiotics and careful follow-up are the treatment of choice for acute suppurative otitis media, whereas topical antibiotics with saline irrigation are used in patients with a chronic condition. Myringotomy and tube insertion may be required in patients with secretory otitis media that does not undergo spontaneous resolution.