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Biomedical subjects

R L Anderson

Publications and source records attributed to R L Anderson.

At least 19 recordsLinked to original sources

ST7-mediated suppression of tumorigenicity of prostate cancer cells is characterized by remodeling of the extracellular matrix.

Multiple lines of evidence have provided compelling evidence for the existence of a tumor suppressor gene (TSG) on chromosome 7q31.1. ST7 may be the target of this genetic instability but its designation as a TSG is controversial. In this study, we show that, functionally, ST7 behaves as a tumor suppressor in human cancer. ST7 suppressed growth of PC-3 prostate cancer cells inoculated subcutaneously into severe combined immunodeficient mice, and increased the latency of tumor detection from 13 days in control tumors to 23 days. Re-expression of ST7 was also associated with suppression of colony formation under anchorage-independent conditions in MDA-MB-231 breast cancer cells and ST7 mRNA expression was downregulated in 44% of primary breast cancers. Expression profiling of PC-3 cells revealed that ST7 predominantly induces changes in genes involved in re-modeling the extracellular matrix such as SPARC, IGFBP5 and several matrix metalloproteinases. These data indicate that ST7 may mediate tumor suppression through modification of the tumor microenvironment.

Base Sequence↗

Presynaptic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors modulate release of inhibitory amino acids in rat spinal cord dorsal horn.

Local inhibition within the spinal cord dorsal horn is mediated by the neurotransmitters GABA and glycine and strongly influences nociceptive and temperature signaling. Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are expressed by inhibitory interneurons and have been shown to modulate GABA release in other regions of the CNS. In the spinal cord, there is morphological evidence for presynaptic AMPA receptor subunits in GABAergic dorsal horn neurons, but functional data are lacking. To determine if AMPA receptors are indeed functional at presynaptic terminals of inhibitory neurons, we recorded evoked and miniature inhibitory postsynaptic currents (mIPSPs) in the superficial dorsal horn of the rat spinal cord. We show that AMPA receptor activation enhances spontaneous release of inhibitory amino acids in the presence of tetrodotoxin onto both lamina II neurons and NK1 receptor-expressing (NK1R+) lamina I neurons. This effect is sensitive to the concentration of extracellular Ca2+, yet is not fully blocked in most neurons in the presence of Cd2+, suggesting possible Ca2+ entry through AMPA receptors. Postsynaptic Ca2+ elevation is not required for these changes. AMPA-induced increases in mIPSP frequency are also seen in more mature dorsal horn neurons, indicating that these receptors may play a role in nociceptive processing in the adult. In addition, we have observed AMPA-induced depression of evoked release of GABA and glycine onto lamina I NK1R+ neurons. Taken together these data support a role for presynaptic AMPA receptors in modulating release of GABA and glycine in the superficial dorsal horn. Because inhibition in the dorsal horn is important for controlling pain signaling, presynaptic AMPA receptors acting to modulate the inhibitory inputs onto dorsal horn neurons would be expected to impact upon pain signaling in the spinal cord dorsal horn.

Age Factors↗

Unmet need for recommended preventive health services among clients of California syringe exchange programs: implications for quality improvement.

BACKGROUND: Comprehensive preventive services are recommended for injection drug users (IDU), including screening tests, vaccinations, risk reduction counseling, and sterile syringes. Syringe exchange programs (SEP) may facilitate receipt of preventive services by IDUs, but whether SEP clients receive recommended preventive care is not known. We examined use of recommended preventive services by clients of 23 SEPs throughout California. METHODS: Five hundred and sixty SEP clients were recruited from 23 SEPs throughout California between March and September 2003. Receipt of 10 recommended preventive services and source of care (SEP versus non-SEP providers) was ascertained from client interviews. RESULTS: On average, SEP clients received only 13% of recommended preventive services and 49% of clients received none of the recommended services. Of services that were received, 76% were received from SEPs. In multivariate analysis, use of drug treatment and more frequent SEP visits were associated with receipt of recommended preventive services by clients. CONCLUSIONS: SEPs are often the only source of preventive care for their IDU clients. Still, SEP clients fail to receive most recommended preventive services. Interventions to increase use of preventive services and improve the quality of preventive care received by IDUs, such as increased access to drug treatment and SEPs, are needed.

California↗

Characterizing blood pressure control in individuals with Type 2 diabetes: the relationship between clinic and self-monitored blood pressure.

AIMS: To determine the relationship between blood pressure (BP) measurement in the clinic and self-monitored blood pressure (SMBP); and to evaluate the accuracy of self-reported data in patients with Type 2 diabetes treated intensively for hypertension. METHODS: Seventy subjects had baseline and 1-week follow-up clinic BP measured using an Omron 907 automated device. During a contemporaneous 14-day period these subjects measured their BP at least four times each day using an Omron IC semiautomatic portable monitor which, unknown to them, contained an onboard memory capable of storing BP with corresponding time and date. RESULTS: There was no significant difference between mean clinic and mean self-monitored BP. Correlations between clinic BP and SMBP were r=0.61 (P<0.0001) for systolic BP and r=0.69 (P<0.0001) for diastolic BP. Clinic BP classified 56 subjects as uncontrolled hypertension (BP > or = 130/80 mmHg, adjusted for diabetes) and 14 subjects as controlled hypertension. Using World Health Organization-International Society of Hypertension criteria for SMBP (> or = 125/75 mmHg), 55 cases of clinic classified uncontrolled hypertension were confirmed, resulting in 98% sensitivity. Clinic and SMBP agreed in one case of controlled hypertension, resulting in 7% specificity. For all subjects, the median percent of values exceeding SMBP criteria for controlled hypertension was systolic 92% and diastolic 70%. Self-reporting precision averaged 89+/-10% (range 45-100%); under-reporting was 25+/-16% (ranging from 0 to 56%) and over-reporting was 12+/-15% (ranging from 0 to 46%). The overall logbook mean was not significantly different from the downloaded data from the Omron IC(R) monitors. CONCLUSIONS: SMBP was able to identify 13 patients with uncontrolled hypertension who, by clinic BP measurement, had been classified as controlled.

Adult↗

Genes involved in breast cancer metastasis to bone.

Metastasis to bone occurs frequently in advanced breast cancer and is accompanied by debilitating skeletal complications. Current treatments are palliative and new therapies that specifically prevent the spread of breast cancer to bone are urgently required. While our understanding of interactions between breast cancer cells and bone cells has greatly improved, we still know little about the molecular determinants that regulate specific homing of breast cancer cells to the bone. In this review, we focus on genes that have been implicated in migration and adhesion of breast cancer cells to bone, as well as genes that promote tumor cell proliferation in the bone microenvironment. In addition, the review discusses new technologies, including better animal models, that will further assist with the identification of the molecular determinants of bone metastasis and will guide the development of new therapies.

Animals↗

A systematic review of the quality of homeopathic clinical trials.

BACKGROUND: While a number of reviews of homeopathic clinical trials have been done, all have used methods dependent on allopathic diagnostic classifications foreign to homeopathic practice. In addition, no review has used established and validated quality criteria allowing direct comparison of the allopathic and homeopathic literature. METHODS: In a systematic review, we compared the quality of clinical-trial research in homeopathy to a sample of research on conventional therapies using a validated and system-neutral approach. All clinical trials on homeopathic treatments with parallel treatment groups published between 1945-1995 in English were selected. All were evaluated with an established set of 33 validity criteria previously validated on a broad range of health interventions across differing medical systems. Criteria covered statistical conclusion, internal, construct and external validity. Reliability of criteria application is greater than 0.95. RESULTS: 59 studies met the inclusion criteria. Of these, 79% were from peer-reviewed journals, 29% used a placebo control, 51% used random assignment, and 86% failed to consider potentially confounding variables. The main validity problems were in measurement where 96% did not report the proportion of subjects screened, and 64% did not report attrition rate. 17% of subjects dropped out in studies where this was reported. There was practically no replication of or overlap in the conditions studied and most studies were relatively small and done at a single-site. Compared to research on conventional therapies the overall quality of studies in homeopathy was worse and only slightly improved in more recent years. CONCLUSIONS: Clinical homeopathic research is clearly in its infancy with most studies using poor sampling and measurement techniques, few subjects, single sites and no replication. Many of these problems are correctable even within a "holistic" paradigm given sufficient research expertise, support and methods.

Clinical Trials as Topic↗

Neuropeptide Y immunoreactivity in cutaneous sympathetic and sensory neurons during development of the guinea pig.

Different levels of the cutaneous vasculature are innervated selectively by subpopulations of sympathetic neurons distinguished by the presence or absence of immunoreactivity (-IR) for neuropeptide Y (NPY). This study used multiple-labelling immunohistochemistry to examine the appearance of NPY-IR in neurons innervating cutaneous vessels in the ear pinna of embryonic, fetal, and neonatal guinea pigs. NPY-immunoreactive axons were detected in the ear bud at embryonic day 25. However, these axons lacked IR for tyrosine hydroxylase (TH) and often ran in bundles with substance P (SP)-immunoreactive axons close to the epidermis. Many neuronal somata in the cervical dorsal root ganglia (DRG) at late embryonic stages contained NPY-IR with or without SP-IR, but no NPY-IR was detected in DRG or subepidermal axons by late fetal stages. IR for calcitonin gene-related peptide increased in DRG neurons from midfetal to late fetal stages, after the decrease in NPY-IR. Populations of TH-IR neurons with or without NPY-IR were present in the superior cervical ganglion (SCG) from midembryonic stages. TH-immunoreactive axons were not detected in the ear pinna until midfetal stages, when axons with TH-IR and NPY-IR innervated proximal arteries and TH-immunoreactive axons without NPY-IR innervated distal vessels. Vasoactive intestinal peptide-IR was detected transiently in most fetal SCG neurons with TH-IR and NPY-IR but was not detected in cutaneous axons. These results demonstrate that selective expression of NPY by subpopulations of sympathetic neurons occurs prior to innervation of their targets. This suggests that target contact is not required to establish appropriate patterns of expression of peptide neurotransmitters by cutaneous sympathetic neurons.

Aging↗

Nitric oxide synthase II gene disruption: implications for tumor growth and vascular endothelial growth factor production.

The expression of a primary initiator of tumor angiogenic responses, vascular endothelial growth factor (VEGF), may be induced by nitric oxide (NO) in carcinoma cells. However, the net impact of NO on carcinogenesis remains unclear, because manipulation of NO levels has been shown to either stimulate or inhibit tumor growth. We have investigated the relationship between inducible NO synthase (NOS II), VEGF expression, and growth of B16-F1 melanoma over 14 days in wild-type (NOS II+/+) mice and in those in which the gene for NOS II has been deleted (NOS II-/-). B16-F1 tumor growth was measured as wet weight of the excised tissue. Tumor NOS II and VEGF localization were evaluated by immunohistochemistry, and VEGF mRNA levels were measured by Northern blot analysis. In NOS II+/+ mice inoculated with B16-F1 melanoma cells, macroscopic tumors were always observed at 14 days; however, 22% of NOS II-/- mice had no detectable tumor mass. Immunoreactive NOS II was detected in tumor cells of tumors grown in NOS II+/+ but not in NOS II-/- mice. Although immunoreactive VEGF was detected in the granules of tumor-associated mast cells from both NOS II+/+ and NOS II-/- mice, VEGF mRNA expression in tumors from NOS II-/- was half that in NOS II+/+ mice. Neither NOS II inhibition, exogenous NO, nor peroxynitrite influenced DNA synthesis in culture B16-F1 melanoma cells. The NO donor did not alter either VEGF mRNA levels or degranulation in cultures of the mast cell line RBL-2H3, but peroxynitrite increased both VEGF mRNA expression and degranulation. We conclude that host expression of NOS II contributes to induction of NOS II in the tumor and to melanoma growth in vivo, possibly by regulating the amount and availability of VEGF.

Animals↗

Neurochemical differentiation of functionally distinct populations of autonomic neurons.

The coeliac ganglion of guinea pigs displays a unique topographical arrangement of neurochemically and functionally distinct populations of sympathetic neurons. The authors used multiple-labeling immunohistochemistry to investigate the neurochemical differentiation of these neurons during embryonic and fetal development. Sympathoadrenal precursors, located on either side of the abdominal aorta, were intensely immunoreactive for tyrosine hydroxylase (TH-IR), neurofilament, and the human natural killer 1 antibody at midembryonic stages (Carnegie stages 16-19). During late embryonic stages (stages 20-23), a single bilobed ganglion had formed. At this time, neuropeptide Y immunoreactivity (NPY-IR) was widely expressed in sympathetic neurons (with moderate TH-IR) and chromaffin cells (with intense TH-IR). The onset of somatostatin (Som-IR) expression followed that of NPY-IR and was restricted to sympathetic neurons. However, at late embryonic stages, most TH-IR neurons with Som-IR also expressed NPY-IR (a combination of peptides not found in the mature coeliac ganglion). Between late embryonic stages and the end of the early fetal period, there was a significant increase in the proportion of neurons in lateral regions that had both NPY-IR and TH-IR. At the same time, there was an increase in the proportion of neurons in medial regions that had both Som-IR and TH-IR. Neurons expressing both Som-IR and TH-IR were rarely observed in lateral regions of the coeliac ganglion. Thus, a clear topography within the coeliac ganglion is established during late embryonic and early fetal stages of development and reflects that found in the mature animal by the end of the early fetal period.

Adrenal Glands↗

A new groove director for simplified nasolacrimal intubation.

Silicone intubation is commonly performed to maintain patency of the lacrimal drainage system. We describe a new lacrimal groove director, designed to simplify retrieval of the metal Crawford probe with minimal trauma to the nasal mucosa. This instrument can also be used to infracture or medialize the inferior turbinate in both pediatric and adult populations during nasolacrimal duct intubation or external or endoscopic dacryocystorhinostomy.

Dacryocystorhinostomy↗

Needs-based planning for persons with serious mental illness residing in intermediate care facilities.

This study examined the association of clinical status to mental health service use among persons with mental illness living in residential care. Two hundred residents with a chart diagnosis of schizophrenia were randomly selected from four intermediate care facilities. The severity of psychiatric illness-community mental health (SPI-CMH) scale was used to assess clinical status and symptom severity according to three dimensions: symptoms and functioning, risk behaviors, and complication to illness. Lower levels of severity of psychiatric illness were associated with participation in workshops, family contact, and admitting to mental health problems. Results suggest that residents of the intermediate care facilities have clinical needs consistent with habilitation and rehabilitation services. While residents infrequently engage in high-risk behavior such as suicide and violence, they have considerable living skills and vocational needs. Future research should consider the relationship over time of mental health service utilization, severity of psychiatric illness, and psychosocial factors.

Adult↗

Management of eyelid anomalies associated with Blepharo-cheilo-dontic syndrome.

PURPOSE: To describe the previously unreported management of the eyelid anomalies associated with blepharocheilo-dontic syndrome. Blepharo-cheilo-dontic syndrome is a syndrome of congenital cleft lip/palate, oligodontia, euryblepharon, eyelid ectropion, and lagophthalmos. METHODS: Case report. A 3-month-old male presented with bilateral upper and lower eyelid ectropion with eyelid retraction, marked euryblepharon, severe lagophthalmos, and a right side cleft lip/palate. Lateral tarsal strips, lower eyelid retractor disinsertion, myocutaneous advancement of the cheek and eyelids, and lateral tarsorrhaphy were performed. RESULTS: Correction of the ectropion, eyelid retraction, euryblepharon, and marked improvement in his lagophthalmos were achieved postoperatively. No recurrence of the ectropion or euryblepharon has been noted after 6 months of follow-up. CONCLUSION: Appropriate reconstructive surgery of the eyelids reduces the morbidity associated with the eyelid anomalies and provides an excellent cosmetic result for patients with blepharo-cheilo-dontic syndrome.

Cleft Lip↗

Orbicularis myectomy with levator advancement in Schwartz-Jampel syndrome.

PURPOSE: Schwartz-Jampel syndrome is a disorder of continuous myotonia causing blepharospasm, acquired ptosis, and blepharophimosis. We report the management of the associated eyelid anomalies with orbicularis oculi myectomy, levator aponeurosis resection, and lateral canthopexy. METHODS: Interventional case reports. Two patients with Schwartz-Jampel syndrome presented with blepharospasm, acquired ptosis, and blepharophimosis. Orbicularis myectomy, levator aponeurosis resection, and lateral canthopexy were performed to relieve the blepharospasm and to correct the ptosis and blepharophimosis. RESULTS: Significant functional and cosmetic improvements were achieved by increasing the palpebral fissure height and length while greatly decreasing the blepharospasm of the patients. No recurrence of the blepharospasm or eyelid anomalies has been noted after 1 and 15 years of follow-up, respectively. CONCLUSION: The blepharospasm and eyelid alterations caused by Schwartz-Jampel syndrome should be treated to provide functional and cosmetic improvements. Our technique of myectomy, levator resection, and lateral canthopexy provides an excellent, long-lasting result.

Blepharophimosis↗

The prediction of mental health service use in residential care.

The purpose of this study was to characterize the clinical and psychosocial factors of residents living in psychiatric nursing homes, assess residents' levels of mental health service utilization, and examine the factors that predict the utilization of mental health services. Data were collected from 200 randomly selected residents with schizophrenia living in four intermediate care facilities. Fewer than 60% of residents received mental health services beyond medication and nearly one-half of the residents were readmitted to the hospital in the course of a year. Family contact and involvement in activities were associated with mental health service utilization. Hospital readmission was predicted, not by substance use, but rather by not using substances. There is a growing need among service providers to better identify relevant factors that are important in treatment planning and service delivery. Attention to these issues may impact treatment provision and outcomes for persons with schizophrenia and their families.

Activities of Daily Living↗

Systemic corticosteroid use in orbital lymphangioma.

PURPOSE: To describe the clinical results of systemic corticosteroid use in a series of patients with orbital lymphangioma. METHODS: Four patients (two adults and two children) were treated with corticosteroids using intravenous, oral, or both routes for 2 days to a month. Corticosteroids were used with and without other therapies for symptomatic exacerbations. RESULTS: The adults showed more improvement with pain than with swelling, whereas the children had improvement with both the signs and symptoms. There were no complications in any patient. CONCLUSIONS: Systemic corticosteroids are a useful therapeutic option for patients with orbital lymphangioma and can be used as an adjuvant treatment to surgery and other modalities. Resolution of symptoms with corticosteroids was expedited compared with the natural history of the disease in the patients studied.

Administration, Oral↗

Solitary fibrous tumor of the orbit in a child.

PURPOSE: Solitary fibrous tumor is a rare spindle-cell tumor that usually is seen in the pleura. The orbit is one of the most common extrapleural sites. It is frequently misdiagnosed as hemangiopericytoma and is seen in older patients. We present the youngest case of this tumor, which was apparent in family photographs by age 10 and removed at age 15. The first reported echography findings are presented. METHODS: Case report and literature review. RESULTS: Solitary fibrous tumor was diagnosed by microscopy and immunohistochemical study that showed cells reactive with vimentin and CD34. CONCLUSIONS: Solitary fibrous tumor of the orbit has been diagnosed with increasing frequency in recent years as the result of improved methods of pathologic examination. It is important to be aware of this tumor and recognize that it must be included in the differential diagnosis of highly vascular spindle-cell tumors even in young children.

Adolescent↗

Predicting level of mental health care among children served in a delivery system in a rural state.

The purpose of this study was to establish benchmark data to assist in identifying factors associated with mental health service needs and level of care for children living in a rural state. Clinical and psycho-social needs and strengths were assessed using retrospective chart review for all children and adolescents (n=150) with symptoms or a diagnosis of reactive attachment disorder who presented to a comprehensive treatment facility between January 1997 and December 1999. Logistic regression was used to predict factors associated with inpatient admission (n=15) vs. community-based care (n=135). Significant individual contributors to the prediction of inpatient care were more limited clinical/psycho-social strengths, history of inpatient use and history of sexual abuse. Although 80 percent of children admitted to inpatient care had a history of hospitalization, two-thirds had no history of receiving community-based services and presented to current treatment with a two-year or longer history of symptoms. Approximately two-thirds of children admitted to inpatient care had a history of sexual abuse; however, one-third of these children had no history of mental health service use and presented to current treatment with a two-year or longer history of symptoms. Findings raise concerns about current efforts in public health education, community awareness and health prevention and early intervention programs for children with mental/behavioral health challenges and children and families at risk for abuse and/or neglect living in rural areas.

Adolescent↗