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Biomedical subjects

J Perry

Publications and source records attributed to J Perry.

At least 37 records · Page 2Linked to original sources
PubMed2001

Prolactin, growth hormone, and epidermal growth factor activate Stat5 in different compartments of mammary tissue and exert different and overlapping developmental effects.

Prolactin (Prl)-induced phosphorylation of Stat (signal transducer and activator of transcription) 5 is considered a key event in functional mammary development and differentiation. We now demonstrate that not only Prl, but also growth hormone (GH) and epidermal growth factor (EGF), can activate Stat5 in mammary tissue. We investigated the roles of these hormones in mammary development using mice in which the respective receptors had been inactivated. Although Prl receptor (PrlR)-null mice are infertile, we were able to maintain pregnancies in a few mice by treatment with progesterone. Mammary tissue in these mice was severely underdeveloped and exhibited limited differentiation as assessed by the phosphorylation status of Stat5 and the expression of milk protein genes. PrlR +/- mice showed impaired mammary development and alveolar differentiation during pregnancy, which corresponded with reduced phosphorylation levels of Stat5a and 5b, and impaired expression of milk protein genes. Development of the glands in these mice was arrested at around day 13 of pregnancy. While Prl activated Stat5 only in the epithelium, GH and EGF activated Stat5 preferentially in the stroma. To assess the relevance of the GH receptor (GHR) in the mammary gland, we transplanted GHR-null epithelium into cleared fat pads of wild-type mice. These experiments demonstrated that the GHR in the epithelium is not required for functional mammary development. Similarly, the EGFR in the epithelium is not required for alveolar development. In contrast, epithelial PrlR is required for mammary development and milk protein gene expression during pregnancy. Although GH is not required for alveolar development, we were able to demonstrate its lactogenic function in cultured mammary epithelium from PrlR-null mice. However, ductal development in GHR-null mice was impaired, supporting the notion that GH signals through the stromal compartment. Our findings demonstrate that GH, Prl, and EGF activate Stat5 in separate compartments, which in turn reflects their specific roles in ductal and alveolar development and differentiation.

Animals↗
PubMed2001

The effect of level of spinal cord injury on shoulder joint kinetics during manual wheelchair propulsion.

OBJECTIVE: The effects of spinal cord injury level on shoulder kinetics during manual wheelchair propulsion were studied. DESIGN: Single session data collection in a laboratory environment. METHODS: Male subjects were divided into four groups: low level paraplegia (n=17), high level paraplegia (n=19), C7 tetraplegia (C7, n=16) and C6 tetraplegia (C6, n=17). Measurements were recorded using a six-camera VICON motion analysis system, a strain gauge instrumented wheel, and wheelchair ergometer. Shoulder joint forces and moments were calculated using the inverse dynamics approach. RESULTS: Mean self-selected propulsion velocity was higher in the paraplegic (low paraplegia=90.7 m/min; high paraplegia=83.4 m/min) than tetraplegic (C7=66.5 m/min; C6=47.0 m/min) groups. After covarying for velocity, no significant differences in shoulder joint moments were identified. However, superior push force in subjects with tetraplegia (C7=21.4 N; C6=9.3 N) was significantly higher than in those with high paraplegia (7.3 N), after covarying velocity. CONCLUSIONS: The superior push force in the tetraplegic groups coupled with weakness of thoraco-humeral depressors increases susceptibility of the subacromial structures to compression. RELEVANCE: Increased vertical force at the shoulder joint, coupled with reduced shoulder depressor strength, may contribute to shoulder problems in subjects with tetraplegia. Wheelchair design modifications, combined with strength and endurance retention, should be considered to prevent shoulder pain development.

Adult↗
PubMed2001

Reconstruction of stenotic or occluded iliofemoral veins and inferior vena cava using intravascular stents: re-establishing access for future cardiac catheterization and cardiac surgery.

OBJECTIVES: The study evaluated the safety and efficacy of stent reconstruction of stenotic/occluded iliofemoral veins (IFV) and inferior vena cava (IVC). BACKGROUND: Patients with congenital heart defects and stenotic or occluded IFV/IVC may encounter femoral venous access problems during future cardiac surgeries or catheterizations. METHODS: Twenty-four patients (median age 4.9 years) underwent implantation of 85 stents in 22 IFV and 6 IVC. Fifteen vessels were severely stenotic and 13 were completely occluded. Although guide wires were easily passed across the stenotic vessels, occluded vessels required puncture through the thrombosed sites using a stiff wire or transseptal needle. Once traversed, the occluded site was dilated serially prior to stent implantation. RESULTS: Following stent placement, the mean vessel diameter increased from 0.9 +/- 1.6 to 7.4 +/- 2.6 mm (p < 0.05). Twenty-one of 28 vessels had long segment stenosis/occlusion requiring two to seven overlapping stents. Repeat catheterizations were performed in seven patients (9 stented vessels) at mean follow-up of 1.6 years. Seven vessels remained patent with mean diameter of 6.4 +/- 2.0 mm. Two vessels were occluded, but they were easily recanalized and redilated. Echocardiographic follow-up in two patients with IVC stents demonstrated wide patency. In four additional patients, a stented vessel was utilized for vascular access during subsequent cardiac surgery (n = 3) and endomyocardial biopsy (n = 1). Therefore, 13 of 15 stented vessels (87%) remained patent at follow-up thus far. CONCLUSIONS: Stenotic/obstructed IFV and IVC may be reconstructed using stents to re-establish venous access to the heart for future cardiac catheterization and/or surgeries.

Angioplasty, Balloon↗
PubMed2001

Screening for herpesvirus genomes in common acute lymphoblastic leukemia.

There is epidemiological evidence that infection may play a role in the etiology of childhood leukemia in particular common B cell precursor acute lymphoblastic leukemia. A panel of 20 leukemic samples (panel 1) was examined for the presence of four lymphotropic herpesviruses using conventional molecular techniques. A second independent panel of 27 leukemic samples (panel 2), along with 28 control peripheral blood samples from children with other forms of cancer, was tested for the presence of the same four viruses using sensitive real-time quantitative PCR. While herpesvirus genomes were detected, they were present at very low levels; detection rates and levels were similar in the leukemic and control panels. In addition we surveyed 18 leukemic samples (five from panel 1, six from panel 2 and a further seven samples not previously analyzed) using a degenerate PCR assay capable of detecting the genomes of known herpesviruses plus putative new members of the family. No novel herpesvirus genomes were detected suggesting that a herpesvirus is unlikely to be etiologically involved as a transforming agent in common acute lymphoblastic leukemia.

Adolescent↗
PubMed2001

Validity and reliability of the FACT-G scale for use in the older person with cancer.

This project was designed to evaluate the Functional Assessment of Cancer Therapy General Scale (FACT-G) for use in the older patient with cancer. Subjects were administered the MOS Short Form Health Survey (SF-36) and the FACT-G scale. Subscale and total scores were compared using the Pearson product correlation test. FACT-G total and subscores were compared with the mixed aged cancer patient normative group of Cella et al. (1993). Good correlations were found between total and subscores of the SF-36 and the FACT-G in all areas except vitality. The mean total FACT-G score was 82.2 +/- 16.2 SD for the patients with cancer, and 92.3 +/- 11.8 SD for community-dwelling elderly (CDE). The FACT-G was able to discriminate between patients that received cancer care and CDE (p < 0.002). Subjects who scored higher on the FACT-G were found to have higher Eastern Cooperative Oncology Group Performance Status (PS). Subjects with a PS of 0 had a mean total FACT-G score of 87.9 +/- 14.4 SD. Subjects with a PS of 3 had a mean score of 59.0 +/- 23.2 SD. The FACT-G is a valid and reliable instrument for use in the older patient with cancer. The FACT-G is not an age-biased instrument.

Aged↗
PubMed2001

A short pseudoautosomal region in laboratory mice.

The pseudoautosomal region (PAR) of mammalian sex chromosomes is a small region of sequence identity that is the site of an obligatory pairing and recombination event between the X and Y chromosomes during male meiosis. During female meiosis, X chromosomes can pair and recombine along their entire length; recombination in the PAR is therefore approximately 10x greater in male meiosis compared with female meiosis. A consequence of the presence of the PAR in two copies in males and females is that genes in the region escape the process of X-inactivation. Although the structure and gene content of the human PAR at Xq/Yq is well understood, the mouse PAR, which appears to be of independent evolutionary origin, is poorly characterized. Here we describe a yeast artificial chromosome (YAC) contig covering the distal part of the mouse X chromosome, which we have used to define the pseudoautosomal boundary, that is, the point of divergence of X-specific and X-Y-identical sequences. In addition, we have investigated the size of the mouse PAR by integrating a unique restriction endonuclease recognition site just proximal to the pseudoautosomal boundary by homologous recombination. Restriction digestion of this modified DNA and pulsed field gel electrophoresis reveal that the PAR in these cells is approximately 700 kb. Thus, the mouse PAR, although small in size, has retained essential sex chromosome pairing functions despite its rapid rate of evolution.

Animals↗
PubMed2001

Evaluation of a weekend respite program for persons with Alzheimer disease.

The documented under-use of respite programs in the face of unmet family caregiver needs is puzzling. The purpose of this study was to explore family caregivers' experience with a pilot respite program of weekend care for persons with Alzheimer disease (AD) or a related dementia. The goal-free evaluation approach captured the responses of 18 family caregivers to a pilot program developed by a community nursing organization. A content analysis of the caregiver interviews identified 3 categories: caregiver self-care, relief for the caregiver, and safety and comfort of the family member. The results suggest a link between the family caregiver achieving respite and the safety and comfort of the family member. The caregivers' perspective regarding the costs and benefits of respite influences the frequency with which they use the program. Research implications are discussed.

Adult↗
PubMed2001

One nurse's fight.

The CDC estimates that there are almost 400,000 needlestick injuries annually among hospital-based healthcare workers. Up to 4% develop acute hepatitis C. But nothing brings home the reality of the disease like this nurse's story.

Blood Banks↗
PubMed2000

The use of a force-controlled dynamic knee simulator to quantify the mechanical performance of total knee replacement designs during functional activity.

The experimental evaluation of any total knee replacement (TKR) design should include the pre-implantation quantification of its mechanical performance during tests that simulate the common activities of daily living. To date, few dynamic TKR simulation studies have been conducted before implantation. Once in vivo, the accurate and reproducible assessment of TKR design mechanics is exceedingly difficult, with the secondary variables of the patient and the surgical technique hindering research. The current study utilizes a 6-degree-of-freedom force-controlled knee simulator to quantify the effect of TKR design alone on TKR mechanics during a simulated walking cycle. Results show that all eight TKR designs tested elicited statistically different measures of tibial/femoral kinematics, simulated soft tissue loading, and implant geometric restraint loading during an identical simulated gait cycle, and that these differences were a direct result of TKR design alone. Maximum ranges of tibial kinematics over the eight designs tested were from 0.8mm anterior to 6.4mm posterior tibial displacement, and 14.1 degrees internal to 6.0 degrees external tibial rotation during the walking cycle. Soft tissue and implant reaction forces ranged from 106 and 222N anteriorly to 19 and 127N posteriorly, and from 1.6 and 1.8Nm internally to 3.5 and 5.9Nm externally, respectively. These measures provide valuable experimental insight into the effect of TKR design alone on simulated in vivo TKR kinematics, bone interface loading and soft tissue loading. Future studies utilizing this methodology should investigate the effect of experimentally controlled variations in surgical and patient factors on TKR performance during simulated dynamic activity.

Biomechanical Phenomena↗
PubMed2000

NCIC-CTG phase II study of gemcitabine in patients with malignant glioma (IND.94).

PURPOSE: We conducted a phase II multicentre study of gemcitabine in patients with anaplastic astrocytoma and glioblastoma multiforme at first relapse. PATIENTS AND METHODS: Patients with anaplastic astrocytoma or glioblastoma multiforme receiving a stable dose of steroids and ECOG performance status < or = 3 were eligible for this study at the time of first relapse. One adjuvant chemotherapy regimen was permissible. Patients received gemcitabine 1000 mg/m2 i.v. weekly x 3, repeated on a four-weekly cycle. RESULTS: Of 20 patients enrolled, 15 were evaluable for response, 19 for non-hematological toxicity and 18 for hematological toxicity. Seven patients had anaplastic astrocytoma (AA) and twelve glioblastoma multiforme (GBM). Age ranged from 28-71 years (median 50). Fifteen patients discontinued therapy due to disease progression. The median number of cycles administered was 1 (range 1-11); only two patients received more than three cycles. Hematologic toxicity was acceptable and no grade 4 toxicity was seen. One patient developed Pneumocystis pneumonia and eventual pulmonary embolism; one died of gastric hemorrhage related to steroid therapy. No objective responses were seen. Nine patients had stable disease (median duration 2.7 months, range 0.9-11.2). CONCLUSIONS: Gemcitabine given in this dose and schedule seems well tolerated but is not active in patients with recurrent high-grade gliomas.

Adult↗
PubMed2000

A randomized phase 2 study of PBPC mobilization by stem cell factor and filgrastim in heavily pretreated patients with Hodgkin's disease or non-Hodgkin's lymphoma.

This randomized, controlled study compared the ability to mobilize and collect an optimal target yield of 5 x 10(6) CD34+ cells/kg using stem cell factor (SCF; 20 microg/kg/day) plus filgrastim (G-CSF; 10 microg/kg/day) vs filgrastim alone (10 microg/kg/day) in 102 patients diagnosed with non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD), who were prospectively defined as being heavily pretreated. Leukapheresis began on day 5 of cytokine administration and continued daily until the target yield was reached, or until a maximum of five leukaphereses had been performed. Compared with the filgrastim-alone group (n = 54), the SCF plus filgrastim group (n = 48) showed an increase in the proportion of patients reaching the target yield within five leukaphereses (44% vs 17%, P = 0.002); reduction in the number of leukaphereses required to reach the target yield (P = 0.003); reduction in the proportion of patients failing to reach a minimum yield of 1 x 10(6) CD34+ cells/kg to proceed to transplant (16% vs 26%, P = NS); increase in the median yield of CD34+ cells per leukapheresis (0.73 x 10(6)/kg vs 0.48 x 10(6)/kg, P = 0.04); and an increase in the median total CD34+ cells collected within five leukaphereses (3.6 x 10(6)/kg vs 2.4 x 10(6)/kg, P = 0.05). All patients receiving SCF were premedicated (antihistamines and albuterol), and treatment was generally well tolerated. Five patients experienced severe mast cell-mediated reactions, none of which were life-threatening. In this study of heavily pretreated lymphoma patients, SCF plus filgrastim was more effective than filgrastim alone for mobilizing PBPC for harvesting and transplantation after high-dose chemotherapy.

Adult↗