Search PubMed⌕ Search

Biomedical subjects

R L Meyer

Publications and source records attributed to R L Meyer.

At least 37 records · Page 2Linked to original sources

The prevalence and causes of chronic diarrhea in patients with celiac sprue treated with a gluten-free diet.

BACKGROUND & AIMS: The majority of patients with celiac sprue experience diarrhea before diagnosis. There have been no studies of the prevalence or causes of chronic diarrhea in these patients after treatment with a gluten-free diet. METHODS: Seventy-eight patients with celiac sprue (59 women and 19 men) treated with a gluten-free diet for at least 12 months were surveyed about their bowel habits. Those with chronic diarrhea, defined as passage of loose stools three or more times per week for 6 months, underwent an extensive diagnostic evaluation to determine its cause. RESULTS: Sixty-two of the 78 patients (79%) experienced diarrhea before treatment, and 13 (17%) had chronic diarrhea (of lesser severity) after treatment. The causes of diarrhea in 11 patients consenting to this study were microscopic colitis, steatorrhea secondary to exocrine pancreatic insufficiency, dietary lactose or fructose malabsorption, anal sphincter dysfunction causing fecal incontinence, and the irritable bowel syndrome. Only 1 patient had antigliadin antibodies detected in serum or small intestinal villous atrophy. CONCLUSIONS: After treatment of celiac sprue with a gluten-free diet, chronic diarrhea persists in a substantial percentage of patients. Although ongoing gluten ingestion is one possible cause, other causes may be more frequent. Therefore, diagnostic investigation of diarrhea in celiac sprue after treatment seems warranted.

Adult↗

Heterotrimeric G protein activation rapidly inhibits outgrowth of optic axons from adult and embryonic mouse, and goldfish retinal explants.

Axons in the adult mammalian CNS normally do not regenerate following axotomy even though they retain the capacity for growth under certain experimental conditions. Although this implies that the regeneration of adult axons is under regulative control, very little is known about the signaling pathways "responsible" for this regulation. This study examines the possibility that a G protein signaling system exists in adult mouse optic fibers and that it functions to regulate axonal outgrowth. To induce the growth of optic fibers, retinas from adult mouse were placed in organotypic culture under serum free conditions and allowed to regenerate onto a laminin substrate. Heterotrimeric G proteins were stimulated by adding mastoparan (MST) to the medium while monitoring growing fibers with time lapse microscopy. Mastoparan treatment produced rapid growth cone collapse and axonal retraction which persisted while MST was present. Prior addition of pertussis toxin (PTX), which irreversibly inactivates the G proteins, G(o) and G (i),completely blocked the effect of MST, confirming that MST was acting through the PTX sensitive G proteins. Selective activation of G proteins in the growth cone by local application of MST with a micropipet was equally effective. For comparison, equivalent experiments were performed on embryonic day 15 retinal explants and on retinal explants from adult goldfish, which normally regenerate in vivo. MST similarly inhibited these axons and this effect was blocked by PTX. However, embryonic fibers were less reliably affected compared to goldfish or adult mouse, suggesting a developmentally regulated sensitivity. The presence of G-proteins in the mouse axons was further tested immunohistochemically using antibodies against G(o)/G(i). Positive staining was detected in the growth cones and shaft of adult and embryonic mouse optic fibers. These findings demonstrate that G protein activation inhibits axonal outgrowth and suggest that there may be a G protein signaling pathway that normally regulates this outgrowth. However, since this pathway appears to exist in both axons that can regenerate and those that normally do not, the presence of PTX-sensitive G proteins alone cannot account for regenerative failure. Regenerative failure may instead be explained as the selective or increased activation of this pathway in the adult mammalian CNS.

Animals↗

Measurement of dimeric inhibin in porcine serum: evidence for low concentrations and existence of binding proteins.

An immunoradiometric assay and serum extraction procedure were developed to measure dimeric inhibin in porcine serum with minimal interference by putative inhibin-binding proteins. Assay sensitivity was 50 pg/tube, and it incorporated antibodies against the N-terminal region of inhibin's alpha-subunit, alpha-(1-25)-Ab, and against the C-terminal region of inhibin's beta A-subunit. To determine whether inhibin-binding proteins were present in porcine serum, serum was incubated with [125I]-recombinant human (rh)-inhibin and then chromatographed by gel filtration. Radioiodinated rh-inhibin was associated with protein(s) > 600 kDa. Radioiodinated rh-inhibin also was incubated with alpha 2-macroglobulin, an inhibin-binding protein in human and rat serum. Elution profiles were similar for serum and alpha 2-macroglobulin. Serum- and alpha 2-macroglobulin-[125I]rh-inhibin complexes dissociated upon exposure to 8 M urea. Porcine serum was treated with urea, after which inhibin was isolated and concentrated. The recovery of rh-inhibin added to starting serum was 28%. Concentrations of endogenous dimeric inhibin were < 28 pg/ml in serum collected from sows at random stages of the estrous cycle and were < 21 pg/ml in serum collected from sows 2 d postweaning. Results demonstrate that 1) concentrations of dimeric inhibin are low in porcine serum, and 2) an inhibin-binding protein(s), consistent with alpha 2-macroglobulin, is present in porcine serum.

Animals↗

Effects of passive immunization against inhibin-peptide on secretion of follicle-stimulating hormone and ovulation rate in ewes carrying the Booroola fecundity gene.

Objectives of the study were to determine whether 1) inhibin negative feedback regulation of FSH secretion is diminished in ewes carrying a copy of the Booroola fecundity (FecB) gene and 2) differential FSH secretion is obligatory for expression of gene-specific differences in ovulation rate (OR). The approach was to compare FSH and ovulatory responses to passive immunoneutralization of inhibin in ewes with and without a copy of the FecB gene. Twenty-eight 2- to 3-yr-old ewes were assigned within genotype to antibody (alpha-IF-Ab) or control groups. Genotypes consisted of 3/4 Rambouillet x 1/4 Booroola ewes with one copy of the FecB gene (FecB+; 57 kg) and 3/4 Rambouillet x 1/4 Booroola ewes without the FecB gene (++; 59 kg). Estrus was synchronized during the breeding season using progesterone-releasing pessaries (CIDR-G). Pessaries were removed at 0 h. A single injection of alpha-IF-Ab or control solution was given at -48 h. Alpha-IF-Ab had been developed against a synthetic inhibin fragment matching the N-terminal region of ovine inhibin's alpha subunit. For injection, alpha-IF-Ab had been precipitated from ovine immune sera and concentrated. Blood samples were collected at 6-h intervals from -48 to 48 h, and laparoscopy was performed 14 days after CIDR-G withdrawal. All ewes exhibited estrus and ovulated. Genotype and alpha-IF-Ab treatment were without effect on intervals to estrus. Both factors affected OR (p < or = 0.001). Mean OR in control ++ and FecB+ ewes were 1.6 and 2.7, respectively; mean OR in alpha-IF-Ab-treated ++ and FecB+ ewes were 2.5 and 4.6, respectively. Following injection of alpha-IF-Ab, FSH concentrations increased within 6 h, peaked 12-18 h later, and then declined. Magnitude of FSH increases was similar in ++ and FecB+ ewes (70% and 85% over control values, respectively). Results demonstrate that 1) inhibin negative feedback regulation of FSH secretion is not a site of FecB gene action and 2) the mechanism by which the FecB gene increases OR does not necessarily involve increased FSH secretion during the period of preovulatory follicular development.

Animals↗

Spontaneous bursting and long-lived local correlation in normal and denervated tectum of goldfish.

The formation of fine retinotopic order by growing optic fibers in the goldfish is thought to be mediated by the correlated firing of optic fibers from neighboring retinal ganglion cells. Although the activity of the tectal cells must also be important for this activity-dependent refinement, few studies have analyzed the pattern and local correlation of the intrinsic activity of tectal neurons and the effect of denervation on this activity. To address this issue, spontaneous (nonoptic driven) activity was analyzed and cross-correlograms were computed between individual tectal neurons using single and double electrode extracellular recordings. Recordings were made in normally innervated tectum in which the contribution of optic activity was eliminated by short-term intraocular blockade with tetrodotoxin and in denervated tecta in which the optic nerve had been severed several weeks prior. Several observations were relevant to activity-dependent refinement: First, coupling between neighboring tectal cells is weak. Second, the time duration for local correlation is relatively long, as long as 200 ms. Third, tectal neurons exhibit spontaneous bursting. Fourth, denervation increased the level of spontaneous activity in the tectum. The increased spontaneous activity and bursting following denervation implies that tectal neurons are more excitable when optic fibers are beginning to reinnervate the tectum. This could make it possible for optic fibers to drive tectal neurons at a time when their input to individual neurons is severely weakened by a lack of spatial convergence. The weak coupling between tectal cells and the consequent long-time constant for correlated activity implies a constraint on the duration of correlated retinal activity that is used for activity-dependent refinement. Since optic fibers likely need to detect the postsynaptic activity of a local group of tectal neurons, rather than that of a single neuron, the long tectal time constant means that retinal activity need not be correlated with precision much better than 200 ms because the postsynaptic circuitry cannot generate shorter correlations.

Animals↗

Effects of passive immunization of ewes against an inhibin-peptide on gonadotropin levels, ovulation rate, and prolificacy.

The experimental objectives were to determine whether injection of semi-purified (sp; ammonium sulfate-precipitated) and highly purified (hp; immunoaffinity-purified) ovine antibody (Ab) against an inhibin-peptide fragment (alpha-IF) before the preovulatory period would 1) stimulate FSH secretion in a dose-response manner, 2) induce an increase in ovulation rate, and 3) affect pregnancy rate and prolificacy (lambs born alive per ewe lambing). During the early breeding season, estrus was synchronized in 30 2-yr-old crossbred ewes through use of progesterone-releasing pessaries (CIDR-G). Two doses (330 and 660 laboratory reference preparation [RP-2] kU) of sp- and hp-alpha-IF-Ab were injected i.m. 48 h before CIDR-G removal (6 ewes per group). Six other ewes received control solution. Plasma alpha-IF-Ab titers peaked at 12 h postinjection. Plasma FSH levels were higher (p < 0.02) in alpha-IF-Ab-treated ewes than in control ewes from 12 to 24 h postimmunization. Magnitudes of FSH increases were similar in ewes administered sp- and hp-alpha-IF-Ab and were greater (p < 0.05) in ewes receiving 660 than in those receiving 330 RP-2 kU. Compared to control values, the higher alpha-IF-Ab dose increased FSH levels by 44 +/- 5% and the lower dose increased the levels by 22 +/- 3%. Plasma LH levels were similar among passively immunized and control sheep. Ovulation rate was increased (p < 0.0005) by alpha-IF-Ab treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Passive immunization of ewes against an inhibin-like peptide increases follicle-stimulating hormone concentrations, ovulation rate, and prolificacy in spring-mated ewes.

The objective of this experiment was to determine whether passive immunization against a synthetic inhibin-like peptide (alpha-IF) increases FSH secretion and reproductive performance of ewes bred in the spring. Crossbred ewes were assigned to three treatment groups of 10 ewes each. Progesterone-releasing pessaries (CIDR-G) were inserted and left in place for 12 d. The CIDR-G were removed on April 7 (0 h), and three rams were introduced. A single 1.8-mL i.m. injection containing 0, 315-, or 630-reference preparation-2 (RP-2) kU semipurified alpha-IF-antibody (Ab) was given at -48 h. Antibody solution was prepared by ammonium sulfate precipitation and concentration of ovine immune sera that had been generated against alpha-IF-human-alpha-globulin. After the alpha-IF-Ab injection, plasma alpha-IF-Ab titers and FSH concentrations increased within 6 h, peaked 12 to 24 h later, and then decreased. At 12 h after injection, FSH concentrations were increased (P = .05) 28 and 42% over control values in ewes injected with 315- and 630-RP-2 kU alpha-IF-Ab, respectively. All ewes expressed estrus and ovulated, except one control that did not ovulate. Ovulation rate (OR) was increased (P < .0001) by alpha-IF-Ab treatment. Mean OR was 1.0 in control ewes, 1.7 in ewes given 315-RP-2 kU, and 2.5 in ewes injected with 630-RP-2 kU. Fertility (ewes lambing/ewes exposed) from breeding at the induced-synchronized estrus tended (P = .09) to be greater for ewes injected with 630-RP-2 kU alpha-IF-Ab.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Normal activity-dependent refinement in a compressed retinotectal projection in goldfish.

When the optic nerve in a goldfish is crushed, regenerating fibers can reform a normal retinotopic projection. Two processes are thought to generate this retinotopic order. One is an activity-independent process, presumed to be some form of substrate-directed growth, which generates rough retinotopy as seen in the early formed projection. The other is an activity-dependent process that generates fine retinotopy during a protracted period of refinement. This projection also displays two other behaviors. One is retinotopic plasticity, in which optic fibers can compensate for retinal or tectal ablations by expanding or compressing into the available tectal space while preserving retinotopic order. These plasticities can dramatically alter the scale of the projection. The other behavior is the formation of fixed synaptic sites in tectum. Optic fibers make a characteristic number of synaptic connections in tectum, which is not changed by increasing the number of invading optic fibers. This has been interpreted to mean that fibers compete for limited synaptic sites. How the two processes that generate order, substrate-directed growth, and activity-dependent refinement might each be affected by the expression of retinotopic plasticity and altered synaptic competition is largely unknown. In particular, it is not known how fine retinotopic order (activity-dependent refinement) might be affected by altering the scale of the projection. Would optic fibers from neighboring ganglion cells converge into the same-sized area of tectum, or would they expand or compress in proportion to the altered scale of the overall map? To explore this issue, the posterior half of tectum of goldfish was removed, and the optic nerve was crushed, thereby forcing regenerating fibers to form a compressed retinotopic projection onto the anterior half of tectum. Under these conditions, optic fibers are also forced to compete for half the normal number of synaptic sites. The effect on retinotopy was monitored at various times during regeneration by making a small spot injection of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) into nasal retina corresponding to fibers that would normally terminate in the missing posterior half of tectum. To distinguish between activity-dependent and activity-independent processes, retinal impulse activity was blocked in some animals by repeated intraocular injections of tetrodotoxin. The initial projection was found to be unaffected by impulse activity. Regardless of activity, nasal fibers failed initially to grow to the most posterior available regions, but instead were dispersed across much of the "incorrect" anterior half of tectum at 30 days.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Imaging of individual normal and regenerating optic fibers in the brain of living adult goldfish.

Retinal arbors in the tectum of living adult goldfish were imaged to determine whether the structural remodelling and refinement that occurs during development continues in adulthood. Individual optic fibers were labelled by making small injections of the lipophilic fluorescent dye DiI into ventral retina and viewing the exposed tectum through a fluorescence microscope equipped with a cooled CCD camera. Arbors were imaged in the living fish every 30-60 minutes for up to 7 hours. Normal adult goldfish showed no evidence of arbor remodelling during this period, though dynamic movements of varicosities present along axon segments were observed. For comparison, regenerating optic fibers were similarly imaged in fish that had undergone optic nerve crush 2-6 weeks previously. In these fish, dynamic structural changes were seen, including branch remodelling, extension and retraction of growth cones, and movement of varicosities.

Animals↗

Differential effect of serum on laminin-dependent outgrowth of embryonic and adult mouse optic axons in vitro.

Laminin is an extracellular matrix molecule which promotes neurite outgrowth from a variety of neurons in culture. However, the reported effectiveness of laminin on neurite outgrowth from retinal ganglion cells in rat and that from chick have been contradictory. In chick, embryonic retinal ganglion cells show strong laminin-dependent neurite outgrowth which is lost during development. In contrast, in rat, laminin promotes neurite outgrowth from adult, but not embryonic retinal ganglion cells. We have reexamined the response of adult and embryonic mouse retinal ganglion cells to laminin in culture. We found, first, that both adult and embryonic retinal neurites respond to laminin with neurite outgrowth in serum-free medium. Second, we found that the addition of serum to the medium greatly inhibits the outgrowth of neurites from embryonic, but not adult, retinal explants. This inhibition appears specific for neurite outgrowth involving laminin receptors, since embryonic explants showed extensive neurite outgrowth in the presence of serum when astrocytes were used as a substrate. These developmental differences in the effect of serum on laminin-dependent neurite outgrowth may indicate maturational changes in surface molecules on optic fibers related to regenerative failure in the adult CNS.

Aging↗

Injury induced expression of growth-associated protein-43 in adult mouse retinal ganglion cells in vitro.

In optic fibers, as in most axons of the central nervous system, the axonal growth-associated protein, GAP-43, is abundant during development but absent in adults. Since optic fibers can be induced to regenerate in culture, we examined whether this was associated with an increased expression of GAP-43 in adult mouse optic fibers that were regenerating from organotypic retinal explants on to laminin substrates. We found that simply placing adult mouse retina in culture under serum-free conditions was sufficient to induce GAP-43, which was detectable after about four to five days in vitro, coincident with the initiation of neurite outgrowth. In explants taken from animals in which the optic nerve was crushed in the orbit eight days prior to culturing, GAP-43 was observed within one day, as was neurite outgrowth. This priming effect was also seen in vivo as an increased level of GAP-43 reactivity in retinal ganglion cells and optic fibers in histological sections taken eight days after nerve crush. Reactivity in the adult fibers in culture was comparable to that observed in optic neurites growing from embryonic retinal explants and could be maintained for at least four weeks in culture. In the adult neurites, especially with longer times in culture, GAP-43 tended to be concentrated into varicosities that were often found in terminal-like arbors that formed in culture. Placing adult retina in culture under serum-free conditions in sufficient to induce re-expression of GAP-43 for an indefinite period of time. This suggests that GAP-43 expression and the propensity for growth in vivo may be repressed by a factor that is absent in vitro.

Aging↗

Activity-dependent retinotopic refinement in a low-density retinotectal projection in the goldfish: evidence favoring synaptic cooperation over competition.

During optic nerve regeneration in goldfish, the label from a small retinal spot injection of WGA-HRP has been previously reported to be initially widely dispersed in the tectum and subsequently to condense into a small patch in the retinotopically appropriate location of tectum. This refinement involves two separate processes: one is activity independent and generates gross retinotopy; the other is activity dependent and mediates the formation of fine retinotopy. Since the number of synapses remains constant during this refinement, one or both of these processes may involve some form of competition for a limited number of synaptic sites. To clarify the role of synaptic competition, we created a low-density retinotectal projection in goldfish by deflecting about 20% of the optic fibers from one tectum into the opposite tectum, which was denervated of all other optic fibers. Under this condition, it was previously shown that less than half the normal density of synapses is formed. If competition for synaptic sites is a requirement of refinement, refinement should be prevented or significantly hindered. To monitor refinement during regeneration, 2 nl spot injections of WGA-HRP were made into the retina at various times after deflection. To distinguish between activity-dependent and activity-independent refinement, retinal impulse activity was blocked in some fish with repeated injections of TTX into the eye for the duration of the experiment. It was found that considerable activity-independent refinement occurred under continuous TTX blockade although the fibers remained more dispersed than in previous TTX studies when normal numbers of fibers were present. Surprisingly, in fish with normal impulse activity, the degree of activity-dependent refinement was almost normal. Labeled fibers condensed into a small area roughly comparable in size to that observed when the full complement of fibers was regenerating into tectum. These results suggest that competition for limited synaptic sites is not essential for activity-dependent refinement, which may, instead, be mediated by a cooperative process that actively promotes convergence. The findings further suggest that if synaptic competition plays a role in this system, it is in regulating activity-independent mechanisms that determine the large-scale distribution of fibers within tectum.

Animals↗

[The refinement of retinotectal projection on tectal whole mount during the regeneration of the goldfish optic nerve labeled with DiI anterogradely].

The refinement of retinotectal projection during the regeneration of the goldfish optic nerve was studied with microinjection of the lipophilic dye DiI (1,1-dioctadecyl-3,-3,-3',-3',-tetramethylindo-carbocyanine perchlorate) into the dorsal retina to label a few of retinal ganglion cells, which could be transported anterogradely to their terminal arbors on the tectum. The regenerated optic nerve fibers on the tectal whole mount were examined at various time intervals (from 7 to 365 days) following an optic nerve crush. At the early regeneration stage (2 to 8 weeks postcrush), the regenerated optic fibers travelled in abnormal paths through both appropriate ventral and inappropriate dorsal hemitecta, but the majority of the fibers (about 60% to 70%) were found in the appropriate ventral hemitectum. At the late regeneration stage (2 months afterward postcrush), after refinement of regenerated optic fibers, the retinotectal projection was reestablished preciously as in the normal fish. Present study shows that the refinement of the retinotectal projection manifests in three major changes: 1) The disappearance of the regenerated optic fibers at the inappropriate tectal positions; 2) The disappearance of the side branches on the optic fiber shaft; 3) The formation of overlapping terminal arbors by the optic fibers that arrived at the retinotopic target. These results suggest that there may be two kinds of factors in the tectum: One is a common guiding factor which distributes over all the tectum and guides the regenerated optic fibers growing into the tectum at early regeneration; another is a position-specific neurotrophic factor which guides the regenerated optic fibers arriving at the retinotopic target at late regeneration.

Animals↗

Distribution of microtubule-associated proteins (MAPs) in adult and embryonic mouse retinal explants: presence of the embryonic map, MAP5/1B, in regenerating adult retinal axons.

Microtubule-associated proteins (MAPs) are developmentally regulated proteins involved in microtubule polymerization and stabilization. We have asked whether MAPs in regenerating adult mouse retinal ganglion cell axons recapitulate the pattern of MAPs seen during development. Adult and Embryonic Day 15 (E15) mouse retinal segments were explanted onto laminin-coated coverslips and allowed to extend neurites in serum-free medium. Using a variety of monoclonal antibodies (Mabs), we stained adult and E15 explant cultures for early (MAP5) and late (MAP1, MAP2, MAP2a+b, tau) MAPs. Optic neurites growing from E15 explants were strongly immunoreactive for MAP5. Labeling was absent for MAP1 and MAP2a+b. Mabs to MAP2 and tau lightly stained axons and cell bodies, probably due to MAP2c and juvenile tau which are found in developing neurons. In adult explant cultures, both perikarya and axons were immunoreactive for MAP1. MAP2 and MAP2a+b labeled perikarya and fibers within the explant, and tau stained axons on the substrate. MAP5 immunoreactivity was intense in the adult explant cultures, labeling axons extending over the substrate and perikarya and dendrites in the explant in a pattern similar to that seen in E15 explants. In summary, adult retinal explants maintain their adult complement of MAPs, in showing high levels of MAP1, tau immunoreactivity restricted to neurites on the substrate, and MAP2 segregated into neurites and perikarya within the explant. The exception is MAP5 for which the pattern of immunoreactivity is similar in adult and E15 retinal explants.

Animals↗

The heavy neurofilament protein is expressed in regenerating adult but not embryonic mammalian optic fibers in vitro.

Axonal neurofilaments are composed of light (NF-L), medium (NF-M), and heavy (NF-H) subunits which are sequentially expressed during axonal development. In retina, NF-L and NF-M appear prenatally, followed postnatally by NF-H which occurs at about the time axons are reaching their target tissue. Phosphorylation of the NF-H protein occurs after it has first appeared in the axon. Phosphorylated NF-H is also downregulated in regenerating peripheral nerves. These observations lead to the hypothesis that NF-H stabilizes axons, thereby inhibiting their ability to grow. We have previously shown that adult mouse retinal ganglion cells (RGCs) can extend neurites in vitro and that these neurites reexpress the developmental protein GAP-43. Here we ask whether the expression of neurofilament proteins in the growing adult RGC axons involves the recapitulation of development. Adult mice which had a priming lesion of the optic nerve and Embryonic Day 15 mouse retinas were explanted onto laminin substrates and grown in culture. After 2-4 days the growing neurites were stained with a battery of monoclonal antibodies against differentially phosphorylated versions of the neurofilament subunits. Both adult and embryonic neurites were highly immunoreactive for NF-L and NF-M. Only the adult neurites stained with antibodies against phosphorylated NF-H. There was no immunoreactivity in the embryonic explants. This indicates that regrowing adult RGC axons maintain their adult cytoskeletal properties and can nevertheless regenerate.

Aging↗

Activity and excitatory amino acid receptors.

1. In lower vertebrates, optic fibers form a highly ordered retinotopic projection to the contralateral midbrain. 2. The formation of fine retinotopy during development or regeneration requires patterned impulse activity in optic fibers. 3. The transmitter used by optic fibers is probably glutamate. 4. Blockade of NMDA receptors prevents the formation of fine retinotopy. 5. The available evidence leaves open several different interpretations for these NMDA effects.

Animals↗

Hypertrophic cardiomyopathy: medical, surgical, and nursing management.

Hypertrophic cardiomyopathy (HCM) has been intriguing health care professionals for years. It is a disease of the cardiac muscle characterized by hypertrophy with or without left ventricular outflow tract obstruction. It affects people of all ages and is commonly associated with sudden death. The clinical presentation and treatment of HCM varies widely with the individual and therefore offers the cardiovascular nurse a unique challenge. This article assists the nurse in providing care to these patients by reviewing the cause and prognosis, pathophysiology, clinical manifestations, surgical and medical therapy, and the nursing care following surgical intervention for HCM.

Cardiac Surgical Procedures↗

The effect of TTX-activity blockade and total darkness on the formation of retinotopy in the goldfish retinotectal projection.

In the normal goldfish, neighboring retinal ganglion cells terminate in one small tectal locus to produce the precise retinotopy characteristic of this projection. This can be directly demonstrated by labeling neighboring ganglion cells with small "spot" injections of WGA-HRP, which yield a single small patch of product at the retinotopically appropriate part of the tectum. When the optic nerve is crushed, label from these spot injections was previously found to be widely dispersed during the early phase of regeneration. With time, label subsequently condensed, typically into several discrete patches reminiscent of ocular dominance columns. In this study, we tested whether the formation of these patches required impulse activity by injecting tetrodotoxin (TTX) into the eye during regeneration. We found that impulse blockade completely inhibited the formation of discrete patches while permitting considerable condensation of the label. This implies that these patches are generated by activity but that some map "refinement" utilized cellular processes that are activity independent. This activity-independent condensation progressed at a noticeably slower rate than the equivalent condensation seen with activity, thus suggesting that activity normally participates as a "helper factor," even though it is not strictly required. Since the formation of discrete patches during regeneration provides a sensitive measure of activity-dependent refinement, this was used to further address two controversial questions concerning the role of impulse activity. One is whether there is a chronologically defined critical period for activity-dependent refinement. This was tested by blocking impulse activity for 2 to 4 months, much longer than the activity-dependent refinement is thought to last, and then permitting activity to resume. We found that multiple patches were formed following this period of late activity, thus indicating that synaptic plasticity extends for several months beyond the supposed critical period. The other question was whether spontaneous retinal activity was sufficient for activity-dependent ordering. To test this, fish were kept in constant darkness during optic nerve crush and labelled with retinal spot injections at various times during regeneration. Condensation of label with the final formation of multiple patches formed at about the same time as fish with normal visual experience. This implies that the amount and extent of correlation of spontaneous activity in retina is adequate for driving activity-dependent refinement.

Animals↗