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Biomedical subjects

R Sharp

Publications and source records attributed to R Sharp.

At least 37 records · Page 2Linked to original sources
PubMed1996

Titanium plate fixation: a review of implant failures.

Titanium plates and screws have become widely used for the fixation of fractures and osteotomies. We began using them in 1992; however, several early hardware failure prompted a retrospective review of the occurrence of this complication. A 2-year time period was reviewed at two institutions with comparison of hardware failure rates using titanium and stainless steel implants. At one institution, 51 fractures or osteotomies of the long bones were fixed by the senior author using titanium implants between July 1992 and July 1994. One hundred one similar cases were treated over the same period by the same surgeon using stainless steel implants. The outcome is known for 48 of the cases performed with titanium and for 80 of the cases performed with stainless steel. There were five postoperative implant failures using titanium and one using stainless steel. Metallurgical analysis of one set of broken implants retrieved during a revision surgery showed no manufacturing defects. At the second institution, 21 titanium and 138 stainless steel platings were performed over 2 years. There were four titanium implant failures in four patients and one stainless steel implant failure. Our experience suggests that these implants should be used with care, particularly in high-demand settings such as nonunion or noncompliance, and that further research needs to be conducted to establish appropriate clinical indications for their usage.

Adolescent↗
PubMed1996

The efficacy of intrathecal injection of sufentanil using a microspinal catheter for labor analgesia.

Intrathecal sufentanil can provide labor analgesia. We investigated the efficacy of multiple injections and the maternal and neonatal effects of intrathecal sufentanil during labor. Seventeen healthy women in active labor received multiple injections of intrathecal sufentanil of 5 micrograms each through microspinal catheters. Overall maternal satisfaction of analgesia was quantified using 10 cm visual analogue scales and side effects were evaluated. Neonatal outcome was also determined. Onset of analgesia was less than 5 min after the first injection and lasted approximately 148 min. Tolerance developed for the successive injections. The mean onset times were 12.9 and 20.1 min and the durations were 76.6 and 33.9 min for the second and third injections, respectively (P < 0.05). Failure to obtain analgesia developed in all patients after the forth injection. No motor blockade was observed in any of the patients. Mild or moderate pruritus developed in 88% of the patients. Mean systolic blood pressure decreased by a maximum of 11.3% at 30 min and up to 90 min (P < 0.05) after the first injection; three patients required ephedrine treatment. No significant hemodynamic changes were observed after subsequent injections. Five patients experienced transient decrease in sensation. Neonatal status, as evaluated by Apgar scores, Neurological Adaptive Capacity Scores (NACS), fetal heart rate (FHR), and umbilical cord acid-base status, were within normal limits. Results from our study suggest that multiple small doses of sufentanil administered intrathecally provided satisfactory analgesia for parturients with short duration of labor since acute tolerance developed with multiple injections. High incidence of mild or moderate pruritus was observed during the study. Close attention should be given to hemodynamically unstable patients when this technique is applied.

Adult↗
PubMed1996

A freshwater anaerobe coupling acetate oxidation to tetrachloroethylene dehalogenation.

Strain TT4B has been isolated from anaerobic sediments known to be contaminated with a variety of organic solvents. It is a gram-negative, rod-shaped bacterium and grew anaerobically with acetate as the electron donor and tetrachloroethylene as the electron acceptor in a mineral medium. cis-Dichloroethylene was the halogenated product. This strain did not grow fermentatively and used only acetate or pyruvate as electron donors. Tetrachloroethylene and trichloroethylene were used as electron acceptors, as were ferric nitriloacetate and fumarate. Nitrogen and sulfur oxyanions were not able to substitute as the electron acceptor for this organism. Modest growth occurred in a two-phase system with 1 ml of hexadecane containing 50 to 200 mM tetrachloroethylene (aqueous concentrations, 25 to 100 microM) and 10 ml of anaerobic mineral solution with Na2S as the reducing agent. Growth was completely inhibited at tetrachloroethylene levels above 100 microM.

Acetic Acid↗
PubMed1996

Effect of leucine metabolite beta-hydroxy-beta-methylbutyrate on muscle metabolism during resistance-exercise training.

The effects of dietary supplementation with the leucine metabolite beta-hydroxy-beta-methylbutyrate (HMB) were studied in two experiments. In study 1, subjects (n = 41) were randomized among three levels of HMB supplementation (0, 1.5 or 3.0 g HMB/day) and two protein levels (normal, 117 g/day, or high, 175 g/day) and weight lifted for 1.5 h 3 days/wk for 3 wk. In study 2, subjects (n = 28) were fed either 0 or 3.0 g HMB/day and weight lifted for 2-3 h 6 days/wk for 7 wk. In study 1, HMB significantly decreased the exercise-induced rise in muscle proteolysis as measured by urine 3-methylhistidine during the first 2 wk of exercise (linear decrease, P < 0.04). Plasma creatine phosphokinase was also decreased with HMB supplementation (week 3, linear decrease, P < 0.05). Weight lifted was increased by HMB supplementation when compared with the unsupplemented subjects during each week of the study (linear increase, P < 0.02). In study 2, fat-free mass was significantly increased in HMB-supplemented subjects compared with the unsupplemented group at 2 and 4-6 wk of the study (P < 0.05). In conclusion, supplementation with either 1.5 or 3 g HMB/day can partly prevent exercise-induced proteolysis and/or muscle damage and result in larger gains in muscle function associated with resistance training.

Adult↗
PubMed1996

Laboratory studies of the effect of Pall extracorporeal leucocyte filters LG6 and AV6 on patients undergoing coronary bypass grafts.

A total of 14 patients with ischaemic heart disease undergoing coronary artery bypass grafts were studied for the effect of AV6 control filter and LG6 neutrophil filter, used in the extracorporeal circulation, on different laboratory parameters. There was no statistical difference between the effects of AV6 and LG6 filters on total white cells, neutrophils, monocytes, lymphocytes, platelets or haemoglobin. The expression of neutrophil activation antigens identified with a panel of monoclonal antibodies demonstrated that for the LG6 filter the leucocyte tyrosine phosphate CD45Ro fell during the procedure, whilst there were no significant changes in any of the other neutrophil antigens. The AV6 filter did not significantly diminish the expression of any of the neutrophil antigens. An indirect measure of superoxide production using Dihydrorhodamine 123 identified that the more activated cells appeared to be depleted across the LG6 filter which was not evident with the AV6 filter. These studies indicate that the LG6 is not capable of significantly depleting the neutrophil load generated during extracorporeal circulation but may be capable of selectively removing the more activated forms.

Aged↗
PubMed1996

Hepatocyte growth factor/scatter factor overexpression induces growth, abnormal development, and tumor formation in transgenic mouse livers.

To investigate the in vivo role of hepatocyte growth factor/scatter factor (HGF/SF) in liver function, we generated transgenic mice using a mouse HGF/SF cDNA under the control of the mouse metallothionein gene promoter and 5'/3' flanking sequences. In adult HGF/SF transgenic mice, liver weight as a percentage of total body weight was at least twice that of wild-type mice. Comparison of transgenic and control liver morphology revealed dramatic heterogeneity in the size and appearance of hepatocytes as a distinctive feature of HGF/SF overexpression. Transgenic livers exhibited a significant increase in the number of small hepatocytes with a 2N DNA content, accounting for the observed increase in liver mass. The DNA labeling index of hepatocytes increased 11-fold at 4 weeks of age, when liver enlargement first became apparent, and was still elevated about 5-fold in adult HGF/SF transgenic mice. Moreover, hepatocytes isolated by perfusion of transgenic livers doubled every 2 days in culture, whereas little or no growth was observed with isolated control hepatocytes. The mechanistic basis of hepatocyte proliferation was elucidated as the chronic activation of the c-met proto-oncogene product. Met and substrates such as phosphatidylinositol 3-kinase, Src homology and collagen-like, pp60c-src, focal adhesion kinase p125FAK, and paxillin were associated with tyrosine-phosphorylated complexes in a hepatocyte cell line established from the transgenic liver. This proliferative stimulus triggered the formation of hepatocellular adenomas and/or carcinomas in most transgenic mice > or = 1.5 years of age. Finally, the rate of transgenic mouse liver regeneration was increased 3-fold over control livers following partial hepatectomy.

Adaptor Proteins, Signal Transducing↗
PubMed1995

Regulation of terminal differentiation of zymogenic cells by transforming growth factor alpha in transgenic mice.

BACKGROUND/AIMS: Transforming growth factor (TGF) alpha affects the growth of gastric mucosa. Its overexpression alters the mucosa. The aim of this study was to test the possibility that it regulates differentiation of gland cells. METHODS: Transgenic mice that overexpress TGF-alpha were used to detect its effect on zymogenic (chief) cells in the stomach. To test for a general regulatory role of TGF-alpha in differentiation of zymogen-producing cells, salivary glands from transgenic mice were studied. RESULTS: In these mice, messenger RNA for pepsinogen C is present in the stomach at normal levels during the neonatal period and then decreases markedly. Zymogenic cells are present in the stomach during the neonatal period but are missing in transgenic adults. The bases of gastric glands, normally rich in zymogenic cells, are occupied by undifferentiated cells and mucous neck cells, the precursors of zymogenic cells. Zymogen granules in submandibular glands of transgenic female mice are reduced in number. Zymogen granule-containing cells in the parotid gland undergo redifferentiation to form tubular complexes, collections of ductularlike structures like those formed in the transgenic pancreas. CONCLUSIONS: TGF-alpha is a major participant in the regulation of terminal differentiation of zymogenic cells in the stomach and salivary glands.

Animals↗
PubMed1995

Determinants of HIV risk among men who have homosexual sex and inject drugs.

Men with histories of both homosexual contact and injecting drug use (IDU) are at increased risk of HIV infection over men who have only one such risk. Despite this, their special needs and circumstances have been neglected by AIDS prevention programmes. A survey of a wide spectrum of homosexual male IDUs was carried out in Melbourne and Sydney in 1993 to inform the development of specific policy and programmes for HIV prevention in these subcultures. Of 169 men, self-reported HIV prevalence was 27%. Decreasing compliance with safe sex guidelines (as measured by numbers of casual partners, participation in anal intercourse and use of condoms) was associated with HIV seropositivity, increased age, and increased participation in sex work; having a regular male partner was not protective against unsafe sexual behaviour, no matter the length of the relationship. A substantial proportion (15%) reported inconsistent condom use during anal sex with more than two partners in the preceding month: they were slightly more likely to be engaging in sex work, less 'stable' and more likely to be HIV infected. Sexual risk was not strongly associated with unsafe injecting, which was in general safe. Men who both have homosexual sex and inject drugs are groups at high risk of HIV, more from unsafe sex than from shared injecting equipment; men who believed themselves to be HIV infected were continuing to have sex in such a way that would allow transmission. These are clearly groups in need of priority targeted interventions.

Adolescent↗
PubMed1995

Studies of the effect of Pall leucocyte filters LG6 and AV6 in an in vitro simulated extracorporeal circulatory system.

Neutrophil activation is thought to play a major role in the inflammatory response seen in reperfusion injury and similar clinical situations, i.e. extracorporeal circulation. Impairment of neutrophil function or reduction of total numbers of neutrophils using a leucocyte filter may be beneficial in reducing the adverse clinical effects. In this study we have investigated the effect of the Pall LG6 and control AV6 filters during simulated in vitro cardiopulmonary bypass (CPB). Various parameters were evaluated including neutrophils, total leucocytes, monocytes, lymphocytes and platelets, expression of antigens on neutrophils using a panel of leucocyte-associated monoclonal antibodies CD13, 14, 15, 45Ro, 67, 11a, 11b and L selectin. The effects of leucocyte stimulation with phorbol myristate acetate (PMA) and a leucocyte bolus from a patient with chronic myeloid leukaemia (CML) were also investigated. We have demonstrated that the LG6 significantly reduces leucocytes, in particular neutrophils, with a modest reduction of lymphocytes, platelets and haematocrit, whereas the AV6 had no effect on leukocytes or neutrophils in the test system. In addition the LG6 was associated with a reduction in expression of all leucocyte antigens by approximately 20%; however there was no appreciable alteration of any of the antigens with AV6. Leucocyte stimulation with PMA resulted in a dramatic decrease of all cellular elements and an extra leucocyte load (using CML leucocytes) was not effectively filtered by the LG6 filter. These studies identify the capacity of the LG6 as compared with the AV6 to deplete activated neutrophils in an in vitro simulated cardiopulmonary bypass circuit.

Blood Component Removal↗
PubMed1995

Transforming growth factor alpha disrupts the normal program of cellular differentiation in the gastric mucosa of transgenic mice.

Transforming growth factor alpha (TGF alpha) evokes diverse responses in transgenic mouse tissues in which it is over-expressed, including the gastric mucosa, which experiences aberrant growth and a coincident repression of hydrochloric acid production. Here we show that ectopically expressed TGF alpha induces an age-dependent cellular reorganization of the transgenic stomach, in which the surface mucous cell population in the gastric pit is greatly expanded at the expense of cells in the glandular base. Immunohistochemical analysis of BrdU incorporation into DNA demonstrated that although mature surface mucous cells were not proliferating, DNA synthesis was enhanced by approximately 67% in the glandular base and isthmus, where progenitor cells reside. RNA blot and in situ hybridization were employed to determine temporal and spatial expression patterns of specific markers representing a variety of exocrine and endocrine gastric cell types. Mature parietal and chief cells were specifically depleted from the glandular mucosa, as judged by a 6- to 7-fold decrease in the expression of genes encoding H+,K(+)-ATPase, which is required for acid secretion, and pepsinogen C, respectively. The reduction of these markers coincided in time with the activation of TGF alpha transgene expression in the neonatal stomach. The rate of cell death in the glandular region was not overtly different. Significantly, the loss of parietal and chief cells occurred without a concomitant loss of their respective cellular precursors. In contrast to exocrine cells, D and G endocrine cells were much less severely affected, based on analysis of somatostatin and gastrin expression. Analysis of these dynamic changes indicates that TGF alpha can induce selective alterations in terminal differentiation and proliferation in the gastric mucosa, and suggests that TGF alpha plays an important physiological role in the normal regulation of epithelial cell renewal.

Animals↗
PubMed1995

Transforming growth factor-alpha promotes mammary tumorigenesis through selective survival and growth of secretory epithelial cells.

Transforming growth factor (TGF)-alpha stimulates the growth and development of mammary epithelial cells and is implicated in the pathogenesis of human breast cancer. In this report we evaluate the consequences of overexpressing TGF-alpha in the mammary gland of transgenic mice and examine associated cellular mechanisms. When operating on a FVB/N genetic background (line MT100), TGF-alpha induced the stochastic development of mammary adenomas and adenocarcinomas f secretory epithelial origin in 64% of multiparous females. In contrast, tumors were exceedingly rare in virgin MT100 females, MT100 males, and multiparous FVB/N females. In MT100 females multiple foci of hyperplastic secretory lesions preceded the development of frank tumors; these initial lesions appeared during the involution period after the first lactation. Serial transplantation of these hyperplasias indicated an absence of proliferative immortality. Nevertheless, they gave rise to tumors at a low frequency and after a prolonged latency in virgin hosts; in multiparous hosts, tumors developed earlier and at a high incidence. The TGF-alpha transgene was highly expressed in hyperplasias and tumors but not in virgin and nonlesion-bearing tissue, suggesting that TGF-alpha overexpression provides a selective growth advantage. TGF-alpha also induced at lactation a 6.4-fold increase in DNA synthesis in MT100 epithelial cells, many of which were binucleated. MT100 mammary tissue experienced an obvious delay in involution, resulting in the postlactational survival of a significant population of unregressed secretory epithelial cells. In contrast, another line of transgenic mice on a CD-1 genetic background (MT42), in which TGF-alpha overexpression induced liver but not mammary tumors, failed to demonstrate postlactational epithelial cell survival. These data show that TGF-alpha promotes mammary tumorigenesis in multiparous MT100 mice by stimulating secretory epithelial cell proliferation during lactation and prolonging survival during involution. These points support the notion that TGF-alpha can act as a mitogen and also as a differentiation factor in mammary epithelium.

Adenocarcinoma↗
PubMed1995

Incisional hernias: incidence following abdominal aortic aneurysm repair.

It is thought there is an increased incidence of incisional herniation after the repair of an abdominal aortic aneurysm. We sought to assess this premise by reviewing 281 patients who had undergone abdominal aortic aneurysm repair over the preceding eight years at Concord Hospital. Incisional hernias were found in fourteen patients. This made up 5% of the total group having surgery (281 patients) or 6% of those surviving 12 months or more after operation (231 patients). Of these 231 patients, seven had transverse incision hernias (6.7% of all those with transverse incisions), and seven had vertical incision hernias (5.4% of all those with vertical incisions). Six of the fourteen patients with a hernia had needed an urgent repair of an abdominal aortic aneurysm. We conclude from this study, that there is no evidence of an increased incidence of incisional hernias associated with aneurysmal disease itself. Rather, the factors causing such hernias are common to all laparotomies for major disease in sick, elderly patients, in the absence of intra-abdominal sepsis.

Aged↗
PubMed1994

Deletion and transposon mutagenesis and sequence analysis of the pRO1600 OriR region found in the broad-host-range plasmids of the pQF series.

The nucleotide sequence of the replicative origin (OriR) region of the small cryptic broad-host-range plasmid, pRO1600, which forms the basis of a number of useful cloning vectors has been determined. In addition it has been subjected to Tn5 mutagenesis, deletion analysis, and subcloning in order to define the regions essential for replication in Pseudomonas aeruginosa. The sequence (1894 bp) contains a fragment derived from transposon Tn1. The OriR region is structurally related to other replication (Rep) protein-dependent origins in that it has an A-T-rich region upstream of four 17-bp direct repeats (iterons) which presumably function in initiator protein binding. The sequence also contains a DNA-A-binding site and an open reading frame which could encode a basic (pI 10.6) 25,343-Da Rep protein with homology to RepA from the Neisseria gonorrhoeae beta-lactamase plasmid pFA3. The possible evolutionary origin of this plasmid in P. aeruginosa (RP1) is discussed.

Amino Acid Sequence↗
PubMed1994

Unmodified and recombinant strains of Lactobacillus plantarum are rapidly lost from the rumen by protozoal predation.

A genetically-manipulated strain of Lactobacillus plantarum and the unmodified parent strain were introduced into the rumen of sheep at an initial inoculum level of 1 x 10(7) cfu ml-1 of rumen fluid. There were no significant differences between the viable counts of the two inoculants throughout a 24 h sampling period. The rates of loss were 0.36 and 0.29 h-1 (proportion of colony-forming units lost, measured over the first 2 h) for the parent strain and recombinant strain respectively, and within 24 h of inoculation neither of the strains were detectable in rumen fluid. Further experiments in vitro revealed that the inoculants persisted in sterile rumen fluid with a loss rate of 0.044 and 0.057 h-1 for the parent strain and the recombinant strain respectively. Incubations with rumen fluid alone, protozoa-free rumen fluid and protozoa-enriched rumen fluid revealed that protozoal predation was the most significant factor in the loss of the introduced population. The loss rates from protozoa-free rumen fluid were not significantly different (P < 0.05) from those observed in sterile rumen fluid.

Animals↗
PubMed1993

Collaboration between growth factors and diverse chemical carcinogens in hepatocarcinogenesis of transforming growth factor alpha transgenic mice.

Transforming growth factor alpha (TGF-alpha) has been shown to induce liver tumors within 1 year in transgenic male mice in which this potent mitogen is overexpressed. To determine more precisely how TGF-alpha participates in multistep tumorigenesis of the liver, genotoxic (diethylnitrosamine or dimethylnitrosamine) and nongenotoxic (phenobarbital) chemical carcinogens were administered independently to TGF-alpha transgenic mice [line MT42 on a Crl:CD-1(ICR)BR background]. TGF-alpha overexpression dramatically accelerated carcinogen-induced hepatocarcinogenesis in MT42 males but not females. Interestingly, all three chemical agents were found to enhance strongly both hepatic tumor formation and progression in TGF-alpha transgenic male mice. In this study 100%, 90%, and 78% of transgenic males exposed to diethylnitrosamine, dimethylnitrosamine or phenobarbital, respectively, developed tumors between 24 and 32 weeks of age. Moreover, approximately 70% of tumor-bearing transgenic mice from each treatment group had hepatocellular carcinomas; no malignant lesions were found in any carcinogen-treated or untreated nontransgenic mice or in untreated MT42 mice at this age. These results demonstrate that chemical agents as diverse as nitrosamines and phenobarbital act as cocarcinogens with TGF-alpha in the livers of these transgenic mice, indicating that TGF-alpha possesses the unique ability to complement both initiation and promotion in hepatocarcinogenesis. Furthermore, because carcinogen-induced malignant conversion was restricted to transgenic mice, constitutive TGF-alpha overexpression may promote liver tumor progression as well.

Animals↗
PubMed1993

Treatment of spasmodic torticollis with intradural selective rhizotomies.

To determine the effects of ventral cervical and selective spinal accessory nerve rhizotomy on spasmodic torticollis, 58 patients who had undergone surgery between 1979 and 1987 were reviewed retrospectively. At the time of surgery, each nerve rootlet was electrically stimulated to determine its effect on the nuchal musculature prior to sectioning. Forty-nine patients (85%) had a marked improvement in their condition, with 33 (57%) attaining an excellent result and 16 (28%) noting significant improvement. Patients complained of abnormal head posture, nuchal muscle spasms, and pain prior to surgery. Muscle spasms were completely relieved in 42 patients (72%) and markedly reduced in 10 (17%). Of the 47 patients with preoperative pain, 30 (64%) were free of their pain and eight (17%) noted that the pain was reduced in intensity and frequency. Thirty-four patients (59%) reported that their resting head posture was restored to a neutral position. The likelihood that a patient's head posture returned to normal was inversely proportional to the preoperative duration of the spasmodic torticollis. Twenty-six patients (45%) suffered mild transient difficulty with swallowing solid foods in the immediate postoperative period. In most cases these minor difficulties abated in the months following surgery.

Accessory Nerve↗
PubMed1992

Molecular and genetic analysis of liver oncogenesis in transforming growth factor alpha transgenic mice.

Overexpression of a transforming growth factor alpha (TGF-alpha) transgene induced the development of liver tumors in 69 of 93 (74%) adult male mice. To identify factors associated with oncogenesis, liver tumors from transgenic animals were characterized at the molecular level. TGF-alpha RNA transcripts were elevated in 17 of 25 (68%) liver tumors, relative to adjacent nontumorous tissue. Expression of the endogenous c-myc and insulin-like growth factor II genes was enhanced in 7 of 19 (37%) and 12 of 16 (75%) tumors, respectively. In contrast, epidermal growth factor receptor RNA levels were unchanged or reduced in all liver tumors, and mutations were not detected in either the Ha-ras or Ki-ras genes. The occurrence of liver tumors in castrated TGF-alpha transgenic mice was reduced about 7-fold, while in ovariectomized transgenic animals the incidence was increased about 6-fold. The progeny of a cross between CD1-derived TGF-alpha transgenic (MT42) and C57BL/6 mice exhibited no reduction in tumor burden (83%); however, the incidence of tumor formation in MT42 x FVB/N offspring was substantially lower (19%). We conclude that in these transgenic mice TGF-alpha promotes tumor formation and appears to play a major role in tumor progression. Moreover, other factors that may collaborate in TGF-alpha-induced hepatocarcinogenesis include c-myc, insulin-like growth factor II, sex hormones, and the genetic background upon which the transgene operates.

Animals↗