Patient satisfaction with the care provided at a gynaecology oncology clinic.
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Journal Article↗
Biomedical subjects
J R Smith
Publications and source records attributed to J R Smith.
Linkage analyses at the chromosome 1 loci 1q24-25 (HPC1), 1q42.2-43 (PCAP), and 1p36 (CAPB) in families with hereditary prostate cancer.
Recent studies suggest that hereditary prostate cancer (PRCA) is a complex disease, involving multiple susceptibility genes and variable phenotypic expression. Through linkage analysis, potential prostate cancer susceptibility loci have been mapped to 3 regions on chromosome 1. To investigate the reported linkage to these regions, we conducted linkage studies on 144 PRCA families by using microsatellite markers in regions 1q24-25 (HPC1) and 1q42.2-43 (PCAP). We also examined the 1p36 (CAPB) region in 13 PRCA families with at least one case of brain cancer. No significant evidence of linkage to the HPC1 or PCAP region was found when the entire data set was analyzed. However, weak evidence for linkage to HPC1 was observed in the subset of families with male-to-male transmission (n=102; maximum multipoint nonparametric linkage [NPL] 1.99, P=.03). Weak evidence for linkage with heterogeneity within this subset was also observed (HLOD 1.21, P=.02), with approximately 20% of families linked. Although not statistically significant, suggestive evidence for linkage to PCAP was observed for the families (n=21) that met the three criteria of male-to-male transmission, average age of diagnosis <66 years, and >/=5 affected individuals (maximum multipoint NPL 1.45, P=.08). There was no evidence for linkage to CAPB in the brain cancer-prostate cancer subset. These results strengthen the argument that prostate cancer is a heterogeneous disease and that multiple genetic and environmental factors may be important for its etiology.
Aged↗
Fibroid embolisation: a technique not without significant complications.
Uterine artery embolisation is a new minimally invasive technique used for the treatment of fibroids. Twenty-one women underwent bilateral uterine artery embolisation at our unit, and we assessed the efficacy, morbidity and patient satisfaction with the procedure. Mixed outcomes were found. Reduction in fibroid volume measured by magnetic resonance imaging was impressive, and the majority of women felt their symptoms had improved. One woman achieved a full term pregnancy following the procedure. However, the procedure involved a significant inpatient stay, analgesia requirement, and a slower recovery time than anticipated. One woman died following overwhelming sepsis occurring 10 days after the procedure. Further studies are required to assess the role this technique may play in the management of uterine fibroids.
Adult↗
Apoptosis is a prominent feature of acute anterior uveitis in the Fischer 344 rat.
AIMS: To examine the hypothesis that apoptosis of infiltrating cells contributes to spontaneous resolution of uveitis in clinically relevant rodent models. METHODS: Experimental melanin induced uveitis (EMIU) was induced in Fischer 344 rats by immunisation with 250 microg bovine ocular melanin. Endotoxin induced uveitis (EIU) was induced by injection of 200 microg Escherichia coli lipopolysaccharide. Formalin fixed, paraffin embedded ocular cross sections were stained by terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate biotin nick end labelling (TUNEL) to identify apoptotic cells. Indirect immunoperoxidase staining of paraformaldehyde lysine periodate fixed tissue cross sections was used to demonstrate expression of inducible nitric oxide synthase (iNOS). RESULTS: TUNEL positive mononuclear cells were observed in the anterior uvea during both EMIU and EIU at all selected time points. However, whereas the majority of mononuclear cells appeared apoptotic from the outset of disease, neutrophils were notably TUNEL negative at all time points examined. Many infiltrating neutrophils expressed iNOS. CONCLUSION: Apoptosis occurs early in the course of rat EMIU and EIU, and may contribute to resolution of these diseases. In general, infiltrating mononuclear cells die rapidly, while neutrophils survive, producing inducible nitric oxide synthase which may contribute to disease pathogenesis.
Acute Disease↗
Uterine fibroleiomyoma: MR imaging appearances before and after embolization of uterine arteries.
PURPOSE: To evaluate the magnetic resonance (MR) imaging appearances of uterine fibroleiomyoma before and after embolization and to determine whether there are preembolization MR imaging characteristics that are predictive of a successful outcome. MATERIALS AND METHODS: MR imaging was performed in 18 patients (32 fibroleiomyomas) before and at 2 and 6 months after embolization of the uterine arteries. On each occasion, fibroleiomyoma signal intensity and gadolinium enhancement characteristics were assessed in comparison with those of myometrium on T1-weighted and gadolinium-enhanced images or with those of skeletal muscle on T2-weighted images. Fibroleiomyoma volume was measured by using the ellipsoid formula. RESULTS: The mean fibroleiomyoma volume before embolization was 340 cm3 (range, 15-1,383 cm3). The mean reduction in fibroleiomyoma volume was 43% at 2 months and 59% at 6 months. Before embolization, high signal intensity on T1-weighted images was predictive of a poor response (P = .008), and high signal intensity on T2-weighted images was predictive of a good response (P = .007). The degree of gadolinium enhancement was not correlated with fibroleiomyoma volume reduction (P = .46). CONCLUSION: MR imaging was useful for evaluation of changes in fibroleiomyoma volume after uterine arterial embolization. MR imaging characteristics of fibroleiomyomas before embolization can help predict subsequent response to treatment.
Adult↗
Proton magnetic resonance spectroscopic observations of epilepsia partialis continua in children.
We performed magnetic resonance spectroscopy in three pediatric patients (two boys and one girl, ages 11 to 17 years) with epilepsia partialis continua. Single-voxel proton magnetic resonance spectroscopy was performed on each patient. Data were acquired from voxels of 4 or 8 cm3 from the affected hemisphere and from contralateral homologous regions. The spectral peaks of several metabolites (N-acetyl-aspartate, choline, creatine, and lactate) were measured. Neuropathologic findings revealed Rasmussen's syndrome in two children and gliosis in one. We observed increased lactate-to-creatine ratios and reduced N-acetyl-aspartate-to-creatine ratios in the affected hemispheres in all three children with epilepsia partialis continua. These data support previous reports. The largest increase in the lactate-to-creatine ratio was detected in a patient with Rasmussen's syndrome and ongoing epilepsia partialis continua at the time of measurement. The other two patients had an increase in the lactate-to-creatine ratio and a decrease in the N-acetyl-aspartate-to-creatine ratio in the affected area. The increased lactate-to-creatine ratio was associated with recurrent focal seizures from different underlying pathologies.
Adolescent↗
Gamma knife radiosurgery as a primary treatment for prolactinomas.
OBJECT: The purpose of this study was to estimate the efficacy of gamma knife radiosurgery (GKS) in controlling tumor growth and endocrinopathy associated with prolactinomas. METHODS: Between 1993 and 1997, 164 of 469 patients with pituitary adenomas treated by GKS harbored prolactinomas. The dose to the tumor margin ranged from 9 to 35 Gy (mean 31.2 Gy), and the visual pathways were exposed to a dose of less than 10 Gy. The mean tumor diameter was 13.4 mm. The mean follow-up time for 128 cases was 33.2 months (range 6-72 months). Tumor control was observed in all but two patients who underwent surgery 18 and 36 months, respectively, after GKS. Clinical cure was achieved in 67 cases. Clinical improvement was noted with a decrease in the hyperprolactinemia after GKS. Nonetheless, in 31 (29%) of 108 patients who were followed for more than 2 years no improvement in serum prolactin levels was demonstrated, although this could be normalized by bromocriptine administration after treatment. Nine infertile women became pregnant 2 to 13 months after GKS and all gave birth to normal children. There was no visual deterioration related to GKS. Five women experienced premature menopause. In these patients there was subtotal disappearance of the tumor and an empty sella developed. CONCLUSIONS: Gamma knife radiosurgery as a primary treatment for prolactinomas can be safe and effective both for controlling tumor growth and for normalization of prolactin hypersecretion. A higher margin dose (> or = 30 Gy) seemed to be associated with a better clinical outcome. Gamma knife radiosurgery may make prolactinomas more sensitive to the bromocriptine.
Humans↗
The effects of growth hormone and insulin-like growth factor on the proliferation rate and morphology of RAW 264.7 macrophages.
UNLABELLED: It is well documented that growth hormone (GH) functions to regulate both cell growth and cell number and is considered the master hormone because it affects almost every cell of the body. Growth hormone stimulates the liver to secrete insulin-like growth factor (IGF-1), which is also capable of binding insulin as well as insulin-like binding receptors on the cell surface. It is possible that GH cellular effects are mediated by IGF-1 rather than GH itself. In this study, RAW 264.7 cells were challenged with a high dose of GH (48 ng/microliter), a low of dose GH (4.8 ng/microliter), a high dose of IGF-1 (26 ng/microliter) or low doses of IGF-1 (6.3 ng/microliter) for 24, 48, 72, and 96 hours. Cell number, cell protein concentration, cell damage, and cellular morphology were measured at each time point and compared to untreated RAW 264.7 cells. The results show significant increases in cell number for cells treated with low doses of GH and IGF-1 at 24 hour phase. Cell proliferative effects were also observed at 48 hours in IGF-1 treated cells. Cellular damage (MDA levels) was not statistically significant for any treated group for the entire duration of the experiment. Most notable differences were observed in cellular morphology for both IGF-1 and GH treated cells. IGF-1 resulted in condensation of the nuclear material as early as 24 hours after treatment. IN CONCLUSION: (1) RAW 264.7 responded to both IGF-1 and GH equally (viability and proliferation), and (2) morphological changes were observed in all cells treated with both hormones compared to control group. This study indicates that GH hormone could induce its effect directly or indirectly through IGF-1.
Animals↗
Further evolution of hepatitis C treatment: individualized therapy.
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Antiviral Agents↗
Magnetoencephalography in neocortical epilepsy.
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Epilepsy↗
Effects of vitamin A deficiency on rat liver alcohol dehydrogenase expression and alcohol elimination rate in rats.
BACKGROUND: Vitamin A has been suggested to regulate the expression of liver alcohol dehydrogenase (ADH) in humans. There are few studies on the ability of retinoic acid to affect ADH expression in vivo and none on its effects on alcohol metabolic rate. METHODS: Male Sprague Dawley rats were used for isolation of hepatocytes or were rendered vitamin A deficient by feeding a deficient diet for 7 weeks. ADH, retinoic acid receptor beta, and retinoid X receptor alpha protein levels were analyzed by Western blotting. Alcohol elimination rate was determined by following blood alcohol levels after administering a 1.5 g/kg dose of ethanol intraperitoneally. RESULTS: Retinoic acid had no effect on ADH protein in cultured hepatocytes. In the vitamin A deficient rats, retinol was not detectable in serum or liver at the time animals were killed. ADH and retinoid X receptor alpha protein levels were unchanged in the deficient group compared with a vitamin A sufficient control group, whereas retinoic acid receptor beta levels increased 40%. The deficient rats had a reduced volume of distribution of alcohol, but this largely was accounted for by their smaller body size. The alcohol elimination rates were lower in the deficient animals, but this was accounted for by reduced body and liver weights. CONCLUSIONS: Severe vitamin A deficiency did not alter liver ADH protein expression or rates of alcohol elimination when expressed per gram of body or liver weight.
Alcohol Dehydrogenase↗
Toward new therapies for ocular inflammation.
While the use of this type of therapy and its application are far from immediate clinical application, the theory to support this approach is plausible. Most forms of anti-inflammatory therapy employed for ocular inflammatory diseases including iritis, scleritis, and chorioretinitis are derived from the success of these therapies for other organ systems. Just as ophthalmologists have the unique opportunity to visualize the hallmarks of the immune response, so do ophthalmologists have the unique opportunity to test this therapeutic approach which we speculate could offer improved efficacy and specificity over current modalities. Technological advances have helped to create an exciting era in ophthalmology. We believe that this technology can eventually be applied to the treatment of inflammatory diseases involving other body systems, as well as those primarily involving the eye.
Animals↗
Acute retinal necrosis syndrome complicating chickenpox.
Chickenpox may be complicated by ocular involvement. In these patents, acute retinal necrosis usually forms a relatively mild course. Systemic antiviral treatment during the acute phase of the disease is recommended. Rarely, retinal detachment may develop, resulting in blindness. It is strongly recommended that patients with chickenpox who develop visual symptoms should be referred for an ophthalmological opinion early.
Acyclovir↗
Trimethyltin reduces ATP levels and MTT reduction in the LRM55 rat astrocytoma cell line.
The LRM55 rat astrocytoma cell line was used to study the time and concentration effects of trimethyltin (TMT) exposure on intracellular adenosine triphosphate (ATP) levels, formazan production from (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), and lactate dehydrogenase (LDH) release. TMT concentrations of > or =50 microM produced a delayed increase in extracellular LDH from approximately 20% at 24 h to almost 70%, at 72 h. Twenty-four hours before cell lysis was detectable ATP levels decreased to less than 30% and formazan production declined to 70% (50 microM), 31% (100 microM), and 21% (200 microM) of control values. Concentrations of TMT (5 and 10 microM) that produced little or no LDH release also decreased ATP levels (62 and 49% of control, respectively) and formazan production (63 and 52% of control, respectively) by 48 h. These data support the hypothesis that TMT exposure interferes with energy production and that this event likely contributes to the delayed cell death seen in this cell line. Moreover, the declines in ATP and formazan production can occur at subtoxic concentrations in LRM55 cells.
Adenosine Triphosphate↗
Complex mechanisms underlying impaired activation of Cdk4 and Cdk2 in replicative senescence: roles of p16, p21, and cyclin D1.
Numerous changes in gene expression are known to occur during replicative senescence, including changes in genes involved in the cell cycle control. In the present study, we have found a severe impairment in the activation of Cdk2 and Cdk4 in response to mitogens in senescent human fibroblasts and determined the molecular basis for this. Although Cdk4 protein was constitutively expressed in senescent cells at the same level as in early-passage young cells, it was found to be complexed with a distinct set of Cdk inhibitors. Cdk4 derived from early passage quiescent cells was effectively activated by incubation with cyclin D1 and Cdk-activating kinase (CAK) in vitro, whereas Cdk4 from senescent cells was not. Cdk2 protein was dramatically decreased in senescent cells and complexed primarily with cyclin D1 and p21. This cyclin D1-bound Cdk2 was not activated by CAK either in vivo or in vitro, implicating cyclin D1 as an inhibitor of Cdk2 activation. Thus, one of the underlying molecular events involved in replicative senescence is the impaired activation of Cdk4 and Cdk2 due to increased binding of p16 to Cdk4 and increased association of Cdk2 with cyclin D1 and p21.
Blood Proteins↗
Prenatal sonographic diagnosis of hypochondroplasia in a high-risk fetus.
Hypochondroplasia (HCH) is caused by mutations in the fibroblast growth factor receptor type 3 (FGFR 3). Prenatal diagnosis of HCH based exclusively on the sonographic measurements of the fetal skeleton is difficult and has not been reported. We describe a newborn infant with HCH who was born to a mother with achondroplasia (ACH) and a father with HCH. Serial sonographic measurements were recorded from 16 weeks of gestation. All measurements remained normal up to 22 weeks of gestation. At 25 weeks of gestation, the long bones began to appear shorter than expected for gestational age, while the head measurements (biparietal diameter and head circumference) remained normal. The measurements were sufficiently different to distinguish from findings in normal and achondroplastic fetuses. Our findings suggest that it is possible to distinguish the normal fetus from a fetus affected with HCH and to distinguish HCH and ACH from each other based on the sonographic measurements alone. To our knowledge, this is the first report of longitudinal sonographic measurements of HCH in the second and third trimesters.
Achondroplasia↗
Achondroplasia-hypochondroplasia complex in a newborn infant.
We describe the case of an 8-month-old girl with achondroplasia-hypochondroplasia complex. The diagnosis was suggested antenatally when obstetrical ultrasonography at 27 weeks of gestation showed short limbs, small chest, and macrocephaly. The father has achondroplasia due to the common G1138A (G380R) mutation in the fibroblast growth factor receptor 3 (FGFR3) gene, while the mother has hypochondroplasia due to the C1620G (N450K) mutation in the FGFR3 gene. Neither had had genetic counseling or molecular testing prior to the pregnancy. Antenatal ultrasound study at 29 weeks of gestation showed a large head, very short limbs, and a small chest; the findings were more severe than in achondroplasia or hypochondroplasia alone. The patient was born by cesarean section at 37 weeks of gestation and had rhizomelic shortness of limbs with excess skin creases, large head, and small chest, diagnostic of achondroplasia. Radiographs showed shortness of the long bones and flaring of the metaphyses. She had mild hypoplasia of lungs. Molecular testing showed both the G1138A and the C1620G mutations in FGFR3, confirming the diagnosis of achondroplasia-hypochondroplasia complex. At 8 months, she has disproportionate shortness of the long bones and a large head with frontal bossing and a depressed nasal bridge. Her chest remains small, and she is on home oxygen at times of respiratory stress. She has a large gibbus. She is delayed in her motor development and has significant head lag. To our knowledge, there is only one previously published report of achondroplasia-hypochondroplasia complex.
Abnormalities, Multiple↗
Evaluation of sperm washing as a potential method of reducing HIV transmission in HIV-discordant couples wishing to have children.
OBJECTIVE: A number of discordant couples, in whom the man is HIV positive and the woman is HIV negative, wish to have children. To conceive they must abandon protected sex, posing a risk of HIV transmission to the woman and so to the child. In such circumstances purification of spermatozoa ('sperm-washing') to inseminate the woman artificially has been proposed as a method of reducing the risk of transmission. Here we evaluate whether this does represent a true risk reduction. METHODS: Semen samples from HIV-positive patients were separated into spermatozoa, non-sperm cells (NSCs) and plasma fractions. The amount of viral RNA present in each fraction was measured and compared with the level in the peripheral blood. Each fraction was also assessed for the presence of proviral DNA. The ability of spermatozoa to be infected was assessed by evaluating for the presence of HIV receptors, i.e. CD4, CCR5 and CXCR4 on the surface of the sperm, by flow cytometry. RESULTS: A poor correlation was found between the levels of HIV in blood and semen. Within the semen the virus was restricted to the plasma and/or NSCs. All spermatozoa were negative for viral RNA or proviral DNA. Spermatozoa did not express significant levels of CD4, CCR5 or CXCR4, suggesting that they are unlikely to be major targets for HIV infection. CONCLUSIONS: These data suggest that spermatozoa are not major targets of HIV infection. Purifying spermatozoa reduced the level of HIV RNA and proviral DNA to below the detection limit of the assays irrespective of the amount of virus present in the unfractionated semen. On the basis of these data we would recommend 'sperm-washing' followed by insemination as a safer alternative to natural conception for HIV-discordant couples wishing to have children.
DNA, Viral↗