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Biomedical subjects

C Beyer

Publications and source records attributed to C Beyer.

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

Caudal epidural injections with sarapin or steroids in chronic low back pain.

Epidural steroid injections are the most commonly used procedures to manage chronic low back pain in interventional pain management settings. Approaches available to access the epidural space in the lumbosacral spine include the interlaminar, transforaminal, and caudal. The overall effectiveness of epidural steroid injections has been highly variable. This study included 65 patients who underwent diagnostic facet joint nerve blocks utilizing comparative local anesthetic blocks and were shown to be negative for facet joint pain and other problems such as sacroiliac joint pain before enrollment into the study. They were randomly selected from 105 patients negative for facet joint pain allocated into three groups, with Group I consisting of 15 patients comprising a convenience control sample treated conservatively; Group II, consisting of 22 patients treated with caudal epidural with local anesthetic and Sarapin(R); and Group III, consisting of 33 patients treated with caudal epidural with a mixture of local anesthetic, and betamethasone. The study period lasted for 3 years. Results showed that there was significant improvement in patients receiving caudal epidural injections, with a decrease in pain associated with improved physical, functional and mental status; and decreased narcotic intake combined with return to work. The study showed that at 1 month 96% of the patients evaluated showed significant improvement, which declined to 56% at 3 months and 16% at 6 months, with administration of 1 to 3 injections. Cumulative relief with 1 to 12 injections was noted in 96% of the patients at 1 month, 95% at 3 months, 85% at 6 months, and 67% at 1 year. The study also showed cost effectiveness of this treatment, with a cost of $ 2550 for 1-year improvement of quality of life . In conclusion, caudal epidural injections with steroids or Sarapin are an effective modality of treatment in managing chronic, persistent low back pain that fails to respond to conservative modalities of treatments and is also negative for facet joint pain. The treatment is not only effective clinically but also is cost effective.

Journal Article↗
PubMed2001

Effectiveness of percutaneous adhesiolysis with hypertonic saline neurolysis in refractory spinal stenosis.

The increasing proportion of elderly patients, coupled with increasing longevity, causes the problem of lumbosacral pain secondary to spinal stenosis of the lumbar spine to be an important issue. Symptoms of spinal stenosis are caused by entrapment and compression of intraspinal vascular and nervous structures; which may lead to inactivity, loss of productivity, and potential loss of independence, particularly in the elderly. Surgical decompression is considered as the natural treatment. However, the results of surgical treatments have been mixed. Results of conservative treatment are also not encouraging. While the effectiveness of caudal epidural blocks for lumbar canal stenosis was positive, the effectiveness of interlaminar epidural steroid injections showed no beneficial effects on symptomatology of spinal stenosis. Percutaneous epidural adhesiolysis with hypertonic saline neurolysis has been studied in patients with refractory low back pain secondary to post lumbar laminectomy syndrome, as well as spinal stenosis. The specific role of adhesiolysis and hypertonic saline neurolysis in the management of refractory low back and lower extremity pain secondary to spinal stenosis has not been studied. This retrospective evaluation included 18 patients derived from a total sample of 239 patients undergoing adhesiolysis and hypertonic saline neurolysis over a period of 3 years. The results showed significant improvement with reduction of pain; with improvement of physical health, mental health, and functional status. Improvement in psychological status was also noted, with decrease in narcotic intake. Epidural adhesiolysis with hypertonic saline neurolysis is a safe and probably effective modality of treatment in managing symptomatic moderate to severe lumbar spinal canal stenosis.

Journal Article↗
PubMed2000

Temporal loss of Nef-epitope CTL recognition following macaque lipopeptide immunization and SIV challenge.

To address the subtle interactions between antiviral cytotoxic T-cell (CTL) immune responses and the evolution of viral quasispecies variants in vivo, we performed a longitudinal study in a simian immunodeficiency virus (SIV)-infected rhesus macaque that had a long experimental SIV infection before developing simian AIDS. Before being infected with SIV, this animal was immunized with a mixture of seven lipopeptides derived from SIV Nef and Gag proteins and showed a bispecific antiviral CTL response directed toward Nef 169-178 and 211-225 peptides. After SIV infection, CTL activity against the Nef 169-178 epitope was no longer detectable, as assessed from peripheral blood mononuclear cells stimulated by autologous SIV. CTL activity against the 211-225 epitope was lost after 3 months, and an additional CTL response to the amino acids 112-119 Nef epitope emerged. Analysis of the Nef proviral sequence revealed the presence of immune escape variants first in the 211-225 epitope and much later in the 112-119 epitope. In contrast, epitope 169-178 showed only two mutations among all viral sequencing performed. We conclude that in this macaque, bispecific CTL exerted a strong selective pressure and escape virus mutants finally emerged. We identified CTL recognizing a conserved Nef epitope 112-119 (SYKLAIDM), essential for viral replication, which could be associated with a prolonged AIDS-free period. These results stress the importance of the induction of broader multispecific CTLs directed against highly conserved and functional T-cell epitopes by vaccination, with the aim of keeping HIV infection in check.

Amino Acid Sequence↗
PubMed2000

Developmental regulation of glutamic acid decarboxylase mRNA expression and splicing in the rat striatum by dopamine.

Dopamine (DA) promotes the morphological differentiation of striatal GABAergic neurons through D(1) receptor activation and cAMP/PKA signaling. In this study, we investigated the developmental role of DA on the expression of the two GAD(65/67) genes and the alternative splicing of GAD(67) transcripts in the rat striatum. In vivo, embryonic and adult GAD(67) splice variants and GAD(65) transcripts increased until E17 and E19, respectively. Thereafter, the embryonic GAD(67) isoform disappeared, whereas GAD(65) mRNA levels remained unchanged postnatally. The hypothesis that the prenatal ingrowth and functional maturation of nigrostriatal afferents may be responsible for these developmental events through DA-dependent signaling pathways was tested in E17 rat striatal cultures. Treatment with DA and D(1) but not D(2) agonists decreased the ratio of embryonic to adult GAD(67) mRNAs and increased GAD(65) mRNA levels as well as GABA synthesis rates. Our findings demonstrate a distinct developmental switch in the regulation of GAD(65) expression and GAD(67) splicing in the rat striatum which clearly depends upon D(1) receptor but not D(2) signaling. The dopaminergic input thus appears to control the functional differentiation of GABAergic neurons not only by upregulation of expression of the two GAD genes but also by regulating GAD(67) splicing.

Aging↗
PubMed2000

Coitus-induced activation of c-fos and gonadotropin-releasing hormone in hypothalamic neurons in female rabbits.

Copulation induces hypothalamic release of neuropeptides and catecholamines, especially gonadotropin-releasing hormone (GnRH) and norepinephrine, in female rabbits. The forebrain distribution of GnRH cells and the cellular events responsible for the coitally induced GnRH surge have not been identified. We characterized the expression of c-fos mRNA before (0 min) and up to 60 min after coitus in forebrain tissues of mated and nonmated females and compared these findings with those in which single- and double-labeled GnRH/Fos protein cells were identified by immunocytochemistry (ICC). Enhanced expression of fos-mRNA occurred 30 min after coitus, especially in the anteroventral periventricular nucleus (AVPV), the encapsulated portion of the bed nucleus of the stria terminalis (BNSTe) and the ventrolateral hypothalamus (VLH); this increased fos-mRNA activity remained elevated at 60 min in the AVPV and VLH, and was reflected by Fos protein expression 90 min postcoitus. Both ICC Fos-labeled and ICC GnRH-labeled cells were widely distributed throughout the forebrain with postcoital increased double-labeling in the preoptic-septal areas, the anterior-medial hypothalamus and the VLH. The increased number of dual-labeled and unchanged number of single-labeled GnRH cells after coitus suggest some GnRH neurons were non-detected before coitus. Many dual-labeled neurons were adjacent to Fos-labeled cells, suggesting enhanced interneuronal input to GnRH cells after coitus. Collectively, the results suggest that coitus activates hypothalamic GnRH neurons via several loci that include the AVPV, BNSTe and VLH. The distinct anatomical location of the AVPV, BNSTe and VLH further suggests that coital signals may reach the hypothalamus via separate neural pathways that are likely developed within the brainstem.

Animals↗
PubMed2000

Generation of CD8+ T cell-generated suppressor factor and beta-chemokines by targeted iliac lymph node immunization in rhesus monkeys challenged with SHIV-89.6P by the rectal route.

The targeted lymph node (TLN) immunization strategy was investigated in macaques, in order to determine the efficacy in generating secretory, systemic, and cellular immune responses, CD8+ T cell-generated suppressor factors, and beta-chemokines. TLN immunization of the rectal and genital mucosa-associated iliac lymph nodes (TILNs) was compared with axillary TLN immunization (TAxLN) using HIV-1 MN/LAI gp140env and SIV p27gag in alum. Significantly higher immune responses, as well as CD8+ T cell-generated anti-SIV factors and the beta-chemokines RANTES, MIP-1alpha, and MIP-1beta, were elicited by iliac as compared with axillary TLN immunization. The immune responses induced by TLN immunization were examined for their capacity to prevent rectal mucosal infection by the pathogenic dual-tropic SHIV-89.6P. Despite significant secretory, serum, cellular, and beta-chemokine responses, the macaques were infected by SHIV-89.6P. Whether the lack of protection was associated with the antigenic unrelatedness of SHIV-89.6P to the immunizing HIV-1 MN/LAI gp140 or to the virus utilizing CXCR4 to a much greater extent than CCR5, remains to be determined.

Animals↗
PubMed2000

Implication of the C-terminal domain of nef protein in the reversion to pathogenicity of attenuated SIVmacBK28-41 in macaques.

We have analyzed the nef gene sequences amplified from 12 macaques presenting various patterns of infection with SIVmacBK28-41, a clone derived from attenuated SIVmacBK28. We have observed seven mutation hot spots at positions 56, 75, 432, 588, 680, 699, and 779. The major alteration was a thymidine insertion at position 699, leading to a frameshift in the SIVmacBK28-41 nef gene and changing the last 15 amino acids of Nef into a 31-amino-acid-long C-terminal domain nearly identical to that encoded by pathogenic SIVmac239 and SIVmac251. The insertion was found at early time points in proviruses obtained from rapid progressor macaques, after 2 years postinfection in progressors, and rarely or only after 4 years postinfection in nonprogressors. Fixation of the other mutations occurred only after insertion of thymidine 699. Phylogenetic analysis demonstrated that the nef genes isolated from progressors evolved from the allele present in SIVmacBK28-41 to alleles present in SIVmac239 or SIVmac251, whereas nef sequences from nonprogressors stayed clustered with that of the inoculated molecular clone. These data stress the importance of the C-terminal extremity of the Nef protein of SIVmac239 or SIVmac251 in viral pathogenesis.

Amino Acid Sequence↗
PubMed2000

Estrogenic stimulation of neurite growth in midbrain dopaminergic neurons depends on cAMP/protein kinase A signalling.

Previous work from this laboratory indicates that the differentiation of mouse midbrain dopaminergic neurons is influenced by estrogen. These effects may be transmitted either through classical nuclear receptors or via "nongenomic" mechanisms, including the interaction with hypothetical membrane receptors coupled to distinct intracellular signalling pathways. The latter mechanism seems to be of particular interest for the observed interactions of estrogen with developing dopaminergic neurons, insofar as estrogen has been shown to increase intracellular calcium levels within seconds. This study focuses on signal transduction cascades that might be activated by estrogen during differentiation of dopaminergic cells. Treatment with 17beta-estradiol or a membrane-impermeable estrogen-BSA construct (E-BSA) increased neurite growth and arborization of dopaminergic neurons. This effect was inhibited by antagonists of cAMP/ protein kinase A (PKA) and calcium signalling pathways but not by the estrogen receptor antagonist ICI. In addition, estrogen exposure stimulated the phosphorylation of CREB in midbrain dopaminergic cells as studied by quantitative double-labelling immunocytochemistry and gel shift assay. Again, this effect was antagonized only by the simultaneous treatment with inhibitors of the cAMP/PKA or calcium pathways and not by ICI pretreatment. These data together with our previous findings demonstrate that estrogen can interact with membrane binding sites on dopaminergic neurons, thereby stimulating the cAMP/PKA/phosphorylated cAMP-responsive element binding protein (CREB) signalling cascade, most likely through the activation of calcium-dependent kinases. In conclusion, rapid "nongenomic" estrogen signalling represents another mechanism, in addition to the activation of classical nuclear estrogen receptors, that is capable of influencing neuronal differentiation in the mammalian brain.

Animals↗
PubMed2000

Ontogenetic expression and sex differences of aromatase and estrogen receptor-alpha/beta mRNA in the mouse hippocampus.

Estrogen plays an important role during brain development interfering with the maturation of distinct neural systems and, in particular, with the sexual differentiation of brain structures and function. Similar to other brain regions, estrogen is known to influence neuronal differentiation and plasticity in the hippocampus. The present study is concerned with the developmental expression of mRNAs for the estrogen-synthesizing enzyme aromatase and the two known nuclear estrogen receptors (alpha/beta) in the male and female mouse hippocampus. Using semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) analysis, we found that aromatase as well as estrogen receptors (alpha/beta) are already expressed prenatally in the hippocampus of both sexes. Aromatase expression increased during the first two postnatal weeks and decreased, thereafter, to lower levels in adults. Sex differences in aromatase expression were observed postnatally with higher levels in males. Estrogen receptor-alpha/beta mRNAs did not fluctuate obviously throughout pre- and postnatal development but revealed a distinct sex-specific pattern at the end of the first postnatal week. Again, higher expression was detected in males. These findings clearly demonstrate the capacity of estrogen formation and the presence of both estrogen receptor subtypes in the developing hippocampus. Sex differences in aromatase mRNA levels paralleled the sex-specific pattern of estrogen receptor expression. Thus, our data support the idea that the developing hippocampus is a target for estrogen action and estrogen receptor-mediated sexual differentiation.

Animals↗
PubMed2000

Pharmacological evidence that prolactin acts from late gestation to promote maternal behaviour in rabbits.

We investigated the role of prolactin and suckling stimulation in the expression of maternal behaviour of primiparous rabbits. Bromocriptine (1 mg/kg/day), given to intact mothers across postpartum days 1-5, decreased serum concentrations of prolactin to undetectable levels, reduced crouching, and increased time inside the nest. Failure of maternal nest-building, provoked by bromocriptine injections from pregnancy day 26 to parturition or to postpartum day 5, correlated with a stronger reduction in crouching and an increased time inside the nest, measures of disturbed maternal behaviour, on postpartum days 3 and 5. Preventing suckling by thelectomy did not prevent prolactin release but reduced crouching incidence and increased the time spent inside the nest on postpartum days 3 and 5. Bromocriptine, injected in thelectomized mothers across postpartum days 1-5, further reduced the incidence of crouching and increased the time spent inside the nest on postpartum days 3 and 5. We conclude that prolactin acting prepartum facilitates maternal behaviour initiation in rabbits and, together with pup stimulation, maintains this behaviour across lactation.

Animals↗
PubMed2000

The effect of neuraxial steroids on weight and bone mass density: a prospective evaluation.

The deleterious effects of corticosteroids utilized in neural blockade are a commonly discussed and contentious issue. Corticosteroids are considered to have widespread effects on almost all body systems, with suppression of the release of corticotropin (ACTH) from the pituitary suppressing the secretion of endogenous corticosteroids, thus producing a secondary adrenocortical insufficiency. Even though a multitude of complications of neuraxial steroids have been popularized, the more practical complications of corticosteroid administration are twofold - those resulting from withdrawal and those resulting from continued use of large doses. These mainly include suppression of the pituitary-adrenal axis, weight gain, osteopenia, osteoporosis, and a variety of other minor complications. This prospective evaluation was undertaken to evaluate the effect of corticosteroids and the dose relationship on weight gain, bone-mass density (BMD), and other deleterious effects of steroids. The study population consisted of 204 patients; however, complete data were available on only 123 patients. These patients were divided into two groups, with group I receiving neural blockade without any steroids, and, Group II consisting of patients receiving neuraxial steroids. The results of serial determination of weight and BMD showed no significant change at any interval or at the end of 1 year in all 123 patients with or without steroid administration. In addition, this study also showed some improvement in BMD, as well as weight reduction indicating improvement in functional status. It is concluded that low-dose administration of neuraxial steroids is safe in patients suffering with chronic pain who have failed to respond to conservative modalities of treatment with a favorable risk-benefit ratio. This study also showed no deleterious effect on weight or BMD.

Journal Article↗
PubMed1999

Expression of estrogen receptor-alpha and beta mRNA in the developing and adult mouse striatum.

Estrogen not only modulates nigrostriatal function but also developmental processes in the striatum. Recently, we have demonstrated the presence of the estrogen-synthesizing enzyme aromatase in the developing mouse striatum. This study is concerned with the expression of estrogen receptor-alpha/beta (ER) mRNA in the developing and adult mouse striatum by semiquantitative reverse transcription-polymerase chain reaction. Expression of both ER subtypes occurred already prenatally and further increased until birth. Early postnatally, ER-alpha/beta levels remained high but decreased to lower levels in adults. No sex difference in ER expression was observed. These data together with our previous findings demonstrate the simultaneous expression of both ER subtypes and aromatase in the mouse striatum. It is concluded that estrogen signalling through both nuclear receptors plays a potential role for striatal differentiation.

Animals↗
PubMed1999

Ontogenetic expression and splicing of estrogen receptor-alpha and beta mRNA in the rat midbrain.

Several studies have shown that estrogen is important for the differentiation of midbrain dopaminergic neurons. This is supported by the previous demonstration of estrogen synthesis in the perinatal ventral midbrain. The present study attempts to characterize the expression pattern of nuclear estrogen receptors (ER-alpha/beta) mRNAs in the ventral rat midbrain during development. By applying primers specific for the hormone-binding domain, ER-alpha mRNA was detected from embryonic day (E) 14 until postnatal day (P) 20, whereas considerable levels of ER-beta mRNA were found from P3 to P20. In contrast, primers spanning the DNA-binding domain demonstrated the presence of transcripts for ER-alpha as well as ER-beta after birth. These findings indicate that both ERs are expressed in the developing midbrain. The presence of ER-alpha transcripts devoid of the DNA-binding region is discussed in the context of 'non-genomic' estrogen signaling possibly by membrane receptors.

Animals↗
PubMed1999

The development of brain sex differences: a multisignaling process.

In order to account for the development of sex differences in the brain, we took, as an integrative model, the vomeronasal pathway, which is involved in the control of reproductive physiology and behavior. The fact that brain sex differences take place in complex neural networks will help to develop a motivational theory of sex differences in reproductive behaviors. We also address the classic genomic actions in which three agents (the hormone, the intracellular receptor, and the transcription function) play an important role in brain differentiation, but we also point out refinements that such a theory requires if we want to account of the existence of two morphological patterns of sex differences in the brain, one in which males show greater morphological measures (neuron numbers and/or volume) than females and the opposite. Moreover, we also consider very important processes closely related to neuronal afferent input and membrane excitability for the developing of sex differences. Neurotransmission associated to metabotropic and ionotropic receptors, neurotrophic factors, neuroactive steroids that alter membrane excitability, cross-talk (and/or by-pass) phenomena, and second messenger pathways appear to be involved in the development of brain sex differences. The sexual differentiation of the brain and reproductive behavior is regarded as a cellular multisignaling process.

Animals↗
PubMed1999

Indomethacin inhibits lordosis induced by ring A-reduced progestins: possible role of 3alpha-oxoreduction in progestin-facilitated lordosis.

Progestins with a delta-4-3-keto configuration bind to the progestin receptor (PR) and facilitate estrous behavior in estrogen-primed rats. Some ring A-reduced progestins [5alpha-dihydroprogesterone (alphaDHP), allopregnanolone, and epipregnanolone] are more potent estrus-inducing agents than progesterone when iv injected despite their lower affinity for the PR. Yet the estrus-inducing action of such progestins is reduced by the antiprogestin RU486, suggesting that binding to the PR is required for this effect. Because allo- and epi-pregnanolone are oxidized to alpha- and betaDHP, respectively, by 3alpha-hydroxysteroid oxo-reductase (3alphaHSOR), part of their estrus-inducing action may occur through the binding of such DHPs to the PR. Conversely, because 3alphaHSOR reduces alpha- and betaDHP to allo- or epi-pregnanolone, both of which exert membrane effects, the estrus-inducing effect of DHPs may involve actions independent of the PR. To test these possibilities we assessed the effect of indomethacin, a blocker of 3alphaHSOR, on the estrus-inducing action of such progestins. Because indomethacin also inhibits cyclooxygenases, we selected a dose and treatment schedule that does not interfere with prostaglandin-mediated brain processes (e.g., LHRH release). Indomethacin did not significantly modify the effect of progesterone or megestrol acetate on lordosis. Yet, it significantly reduced the action of all ring A-reduced progestins. Results suggest that: (a) oxidation is essential for lordosis facilitation by 3alpha-pregnanolones and (b) reduction of 3-keto progestins generates 3alpha-hydroxy metabolites which synergize with processes triggered by occupation of the PR by 3-keto progestins. The possible participation in this response of other events influenced by indomethacin (e.g., prostaglandin or melatonin synthesis) is discussed.

3-Hydroxysteroid Dehydrogenases↗
PubMed1999

Estrogen and the developing mammalian brain.

In recent years, the knowledge of how estrogen interferes with mammalian brain functions and development has broadened substantially. In the adult brain, estrogen is not only involved in the neuroendocrine feedback regulation at the hypothalamic and pituitary level but also in the control of motor and cognitive functions. More recently, estrogen was found to act as a protective factor for neurodegenerative disorders such as Parkinson's and Alzheimer's disease. In contrast to these regulatory and protective functions, estrogen plays a different role during neuronal development. After the demonstration that the estrogen-synthesizing enzyme aromatase and both nuclear estrogen receptors are expressed in many brain areas during ontogeny, it was soon realized that estrogen modulates neuronal differentiation, notably by influencing cell migration, survival and death, and synaptic plasticity of neurons. These effects were initially seen in the classical target area for estrogen, the hypothalamus, but successive studies revealed the neurotrophic potential of estrogen also in other brain regions. The focus of this review will be to summarize estrogen formation and the role of estrogen during mammalian brain development. Moreover, cellular mechanisms involved in these neurotrophic effects will be discussed, giving special emphasis to "nongenomic" estrogen signaling and cross-coupling of estrogen signaling with those of growth factors.

Animals↗
PubMed1999

An illustration of the clinical relevance of detecting human antimouse antibody interference by affinity chromatography.

Elevated Cancer antigen 125 (CA 125) serum concentrations (up to 221 kU/1) were measured in a 39 year old woman with a positive family history of breast cancer. The serum determinations were performed with the automated Immulite OM-MA chemiluminescent enzyme immunoassay system (Diagnostic Products). Laparoscopic evaluation of the ovaries did not reveal any abnormalities. CA 125 measurements in the same patient using the automated IMx immunoassay system (Abbott) demonstrated normal serum levels. Using a previously reported chromatography procedure IgG type human antimouse antibody activity was found to be present in the serum samples explaining the falsely elevated levels. To prevent this interference the manufacturer modified the assay system by replacing the monoclonal M11 detection antibody with a rabbit polyclonal antibody. Using the modified OM-MA CA 125 assay results were comparable with the IMx values.

Adult↗