Effects of prostaglandin E and F receptor agonists in vivo on luteal function in ewes.

Loss of progesterone secretion at the end of the estrous cycle is via uterine PGF(2alpha) secretion; however, uterine PGF(2alpha) is not decreased during early pregnancy in ewes to prevent luteolysis. Instead the embryo imparts resistance to PGF(2alpha)-induced luteolysis, which is via the 2-fold increase in prostaglandins E(1) and E(2) (PGE(1), PGE(2); PGE) in the endometrium during early pregnancy. Chronic intrauterine infusion of PGE(1) or PGE(2) prevents spontaneous or an estradiol-17beta, IUD, or PGF(2alpha)-induced luteolysis. Four PGE receptor subtypes (EP(1), EP(2), EP(3), and EP(4)) and an FP receptor specific for PGF(2alpha) have been identified. The objective of this experiment was to determine the effects of EP(1), EP(2), EP(3), or FP receptor agonists in vivo on luteal mRNA for LH receptors, occupied and unoccupied LH receptors, and circulating progesterone in ewes. Ewes received a single treatment of 17-phenyl-tri-Nor-PGE(2) (EP(1), EP(3)), butaprost (EP(2)), 19-(R)-OH-PGE(2) (EP(2)), sulprostone (EP(1), EP(3)), or PGF(2alpha) (FP) receptor agonists into the interstitial tissue of the ovarian vascular pedicle adjacent to the luteal-containing ovary. 17-Phenlyl-tri-Nor-PGE(2) had no effect (P> or =0.05) on any parameter analyzed. Butaprost and 19-(R)-OH-PGE(2) increased (P< or =0.05) mRNA for LH receptors, occupied and unoccupied LH receptors, and circulating progesterone. Both sulprostone and PGF(2alpha) decreased (P< or =0.05) mRNA for LH receptors, occupied and unoccupied LH receptors, and circulating progesterone. It is concluded that both EP(3) and FP receptors may be involved in luteolysis. In addition, EP(2) receptors may mediate prevention of luteolysis via regulation of luteal mRNA for LH receptors to prevent loss of occupied and unoccupied LH receptors and therefore to sustaining luteal function.

Prostaglandin E1 (PGE1), but not prostaglandin E2 (PGE2), alters luteal and endometrial luteinizing hormone (LH) occupied and unoccupied LH receptors and mRNA for LH receptors in ovine luteal tissue to prevent luteolysis.

Loss of luteal progesterone secretion at the end of the ovine estrous cycle is via uterine PGF(2)alpha secretion. However, uterine PGF(2)alpha secretion is not decreased during early pregnancy in ewes. Instead, the embryo imparts a resistance to PGF(2)alpha. Prostaglandins E (PGE; PGE(1)+PGE(2)) are increased in endometrium and uterine venous blood during early pregnancy in ewes to prevent luteolysis. Chronic intrauterine infusion of PGE(1) or PGE(2) prevents spontaneous or IUD, estradiol-17beta, or PGF(2)alpha-induced premature luteolysis in nonbred ewes. The objective was to determine whether chronic intrauterine infusion of PGE(1) or PGE(2) affected mRNA for LH receptors, occupied and unoccupied receptors for LH in luteal and caruncular endometrium, and luteal function. Ewes received Vehicle, PGE(1), or PGE(2) every 4h from days 10 to 16 of the estrous cycle via a cathether installed in the uterine lumen ipsilateral to the luteal-containing ovary. Jugular venous blood was collected daily for analysis of progesterone and uterine venous blood was collected on day-16 for analysis of PGF(2)alpha and PGE. Corpora lutea and caruncular endometrium were collected from day-10 preluteolytic control ewes and day-16 ewes treated with Vehicle, PGE(1) or PGE(2) for analysis of the mRNA for LH receptors and occupied and unoccupied receptors for LH. Luteal weights on day-16 in ewes treated with PGE(1) or PGE(2) and day-10 control ewes were similar (P>or=0.05), but were greater (PPGE(2)>Vehicle-treated ewes. Concentrations of PGF(2)alpha and PGE in uterine venous plasma on day-16 were similar (P>or=0.05) in the three treatment groups. Luteal mRNA for LH receptors and unoccupied and occupied LH receptors were similar (P>or=0.05) in day-10 control ewes and day-16 ewes treated with PGE(2) and were lower (P

Dosage compensation proteins targeted to X chromosomes by a determinant of hermaphrodite fate.

In many organisms, master control genes coordinately regulate sex-specific aspects of development. SDC-2 was shown to induce hermaphrodite sexual differentiation and activate X chromosome dosage compensation in Caenorhabditis elegans. To control these distinct processes, SDC-2 acts as a strong gene-specific repressor and a weaker chromosome-wide repressor. To initiate hermaphrodite development, SDC-2 associates with the promoter of the male sex-determining gene her-1 to repress its transcription. To activate dosage compensation, SDC-2 triggers assembly of a specialized protein complex exclusively on hermaphrodite X chromosomes to reduce gene expression by half. SDC-2 can localize to X chromosomes without other components of the dosage compensation complex, suggesting that SDC-2 targets dosage compensation machinery to X chromosomes.

The 1987 whittier narrows earthquake in the los angeles metropolitan area, california.

The Whittier Narrows earthquake sequence (local magnitude, M(L) = 5.9), which caused over $358-million damage, indicates that assessments of earthquake hazards in the Los Angeles metropolitan area may be underestimated. The sequence ruptured a previously unidentified thrust fault that may be part of a large system of thrust faults that extends across the entire east-west length of the northern margin of the Los Angeles basin. Peak horizontal accelerations from the main shock, which were measured at ground level and in structures, were as high as 0.6g (where g is the acceleration of gravity at sea level) within 50 kilometers of the epicenter. The distribution of the modified Mercalli intensity VII reflects a broad north-south elongated zone of damage that is approximately centered on the main shock epicenter.

Spectrum of movement disorders in professional welders.

OBJECTIVE: To examine the clinical presentation of movement disorder in patients who reported a history of welding. METHODS: A retrospective chart review during a three-year period was performed on all movement disorders and patients who had been welders were identified. The clinical presentation of these patients was categorized by the movement disorder at the time of the initial neurological evaluation and by the therapy response. A comparison group was created by randomly selecting four non-welders for each welder. RESULTS: Among 1126 charts reviewed, eleven patients presented with a welder history. Parkinsonism was a common presentation in both groups: three of the eleven welders (27%) and five of the forty-one controls (12%). Dystonia was also common with 27% and 20%, respectively. Using the chi-squared analysis, the prevalence rates for both parkinsonism and dystonia were similar to controls. All of the welder patients with parkinsonism responded to dopaminomimetic therapy. Six of the eleven welders had elevated manganese levels in either blood or urine. CONCLUSIONS: Welders who present with a movement disorder such as parkinsonism or dystonia, have the prevalence rates for these disorders similar to the non-welder population (Fig. 2, Ref. 15).

Comparative response of rams and bulls to long-term treatment with gonadotropin-releasing hormone analogs.

The objective was to compare the relative response between rams and bulls in characteristics of LH, FSH and testosterone (T) secretion, during and after long-term treatment with GnRH analogs. Animals were treated with GnRH agonist, GnRH antagonist, or vehicle (Control) for 28 days. Serial blood samples were collected on day 21 of treatment, and at several intervals after treatment. Injections of natural sequence GnRH were used to evaluate the capacity of the pituitary to release gonadotropins during and after treatment. Treatment with GnRH agonist increased basal LH and T concentrations in both rams and bulls, with a greater relative increase in bulls. Endogenous LH pulses and LH release after administration of GnRH were suppressed during treatment with GnRH agonist. Treatment with GnRH antagonist decreased mean hormone concentrations, LH and T pulse frequency, and the release of LH and T after exogenous GnRH, with greater relative effects in bulls. Rams previously treated with antagonist had a greater release of LH after administration of GnRH compared with control rams, while rams previously treated with agonist showed a reduced LH response. Bulls previously treated with agonist had reduced FSH concentrations and LH pulse amplitudes compared with control bulls while bulls previously treated with antagonist had greater T concentrations and pulse frequency. The present study was the first direct comparison between domestic species of the response in males to treatment with GnRH analogs. The findings demonstrated that differences do occur between rams and bulls in LH, FSH and testosterone secretion during and after treatment. Also, the consequences of treatment with either GnRH analog can persist for a considerable time after discontinuation of treatment.

Long-term outcome of bulimia nervosa.

BACKGROUND: Since bulimia nervosa's introduction to the psychiatric nomenclature in 1979, data concerning long-term outcome have been largely unavailable. METHODS: Women with the diagnosis of bulimia nervosa between 1981 and 1987 who participated in 1 of 2 studies were located and invited to participate in follow-up assessments. RESULTS: More than 80% of the women from these studies participated in follow-up assessments and the results represent findings for 173 women. More than 10 years following presentation (mean+/-SD length of follow-up, 11.5+/-1.9 years), 11% of this sample met full criteria for bulimia nervosa, and 0.6% met full criteria for anorexia nervosa. An additional 18.5% met criteria for eating disorder not otherwise specified, and 69.90% of this sample were either in full or in partial remission. For predictive factors, only the duration of the disorder at presentation and history of substance use problems demonstrated prognostic significance. Baseline treatment condition was not associated with remission of disordered eating symptoms by the follow-up assessment. CONCLUSIONS: The findings suggest that the number of women who continue to meet full criteria for bulimia nervosa declines as the duration of follow-up increases; approximately 30%, however, continued to engage in recurrent binge eating or purging behaviors (incidence rate, 0.026 cases per person-years). A history of substance use problems and a longer duration of the disorder at presentation predicted worse outcome.

Functional magnetic resonance imaging of symptom provocation in obsessive-compulsive disorder.

BACKGROUND: The new technique of functional magnetic resonance imaging was used to investigate the mediating neuroanatomy of obsessive-compulsive disorder symptoms. METHODS: Ten patients with obsessive-compulsive disorder and 5 normal subjects were studied via functional magnetic resonance imaging during control and provoked conditions. Data analysis entailed parametric and nonparametric statistical mapping. RESULTS: Statistical maps (nonparametric; P < 10(-3)) showed activation for 70% or more of patients with obsessive-compulsive disorder in medial orbitofrontal, lateral frontal, anterior temporal, anterior cingulate, and insular cortex, as well as caudate, lenticulate, and amygdala. No normal subjects exhibited activation in any brain region. CONCLUSIONS: Results of functional magnetic resonance imaging were consistent with past studies of obsessive-compulsive disorder that used other functional neuroimaging modalities. However, paralimbic and limbic activations were more prominent in the present study.

Electroencephalography should not be routine in the evaluation of syncope in adults.

We reviewed the reports of all electroencephalograms obtained at the Nashville (Tenn) Veterans Administration Hospital from September 1987 to August 1989. Seventy-three patients were referred for evaluation of syncope or near syncope. Of these 73 patients, 10 (13.7%) had abnormal findings. Twenty-six patients were referred for other complaints similar to syncope (ie, blackouts, loss of consciousness, falling out, passing out, and fainting). Of these 26 patients, five (19.2%) had abnormal findings. We reviewed the medical records of the patients with abnormal findings and found that the final diagnosis or treatment of the syncope was affected by electroencephalogram in only one patient. These findings suggest that routine electroencephalography is not of significant value in the evaluation of syncope in adults.

Perturbation of experimental ultraviolet light-induced erythema by passive transfer of serum from subacute cutaneous lupus erythematosus patients.

Several lines of investigation have implicated anti-Ro/SS-A antibody in the pathogenesis of photosensitive forms of cutaneous lupus erythematosus such as neonatal lupus erythematosus and subacute cutaneous lupus erythematosus. To further explore this possibility, we have developed a quantitative, experimental system for examining the effect of passively transferring anti-Ro/SS-A antibody-containing and antibody-deficient subacute cutaneous lupus erythematosus patient sera on one aspect of cutaneous photoreactivity, UV-induced erythema. Laser-Doppler velocimetry was used to quantitate the microvascular flow rates in normal control, disease control (rheumatoid arthritis, discoid lupus erythematosus), and subacute cutaneous lupus erythematosus serum-injected guinea pig skin test sites before and after combined ultraviolet B and A radiation from a solar simulator. Results, expressed as change in milli-electron voltage (perturbed milli-electron volts after irradiation minus baseline milli-electron volts before irradiation), revealed that subacute cutaneous lupus erythematosus serum injections consistently resulted in greater UV-induced microvascular flow rates than those elicited by normal or disease control serum injections. Anti-Ro/SS-A containing subacute cutaneous lupus erythematosus sera produced the greatest flow rates observed in this study. Earlier studies have suggested that the pathogenesis of lupus photosensitivity is very likely multifactorial. Our current data suggest that anti-Ro/SS-A autoantibody or other closely related humoral elements should also be considered among the factors which might contribute to this clinical phenomenon.

Predictive validity of bulimia nervosa as a diagnostic category.

OBJECTIVE: The authors sought to investigate the predictive validity of bulimia nervosa as a diagnostic category. METHOD: More than 10 years after they appeared as patients with bulimia nervosa, 177 women (participation rate=79.7%) completed follow-up assessments. RESULTS: Among the women with a current eating pathology, most engaged in recurrent binge eating and purging. Anorexia nervosa and binge eating disorder were relatively uncommon. Eating disorder outcome was significantly related to the presence of mood, substance use, and impulse control disorders but not to the presence of anxiety disorders. CONCLUSIONS: These results support the validity of bulimia nervosa as a diagnostic category that is distinct from anorexia nervosa. Furthermore, these results suggest that bulimic symptoms are associated with disorders involving distress and disinhibition.

Microcircuitry of cat visual cortex: classification of neurons in layer IV of area 17, and identification of the patterns of lateral geniculate input.

Neurons in the cerebral cortex have been classified primarily by their differences in axonal and dendritic branching patterns observed in material impregnated by the Golgi method. Although these morphological differences are widely believed to reflect differences in connectivity, very little is actually known about the patterns of synaptic input to different cell types. We have obtained such information for 32 adjacent neurons in layer IVab of cat cortical area 17 by reconstructing them from electron micrographs of 150 serial sections. Synaptic terminals from the lateral geniculate nucleus were labeled in this material by anterograde degeneration and their distribution, as well as that of normal terminals containing flat or round vesicles, was recorded. The neurons were divided into seven classes based on differences in size, shape, dendritic branching pattern and synaptic input. Class I cells were pyramidal with apical and basilar dendrites, dendritic spines, exclusively flat-vesicle terminals on the somas (11/100 micron2), and geniculate terminals on the basilar dendrites. Class II cells were large stellates (20 micron diameter) with dark cytoplasm and numerous flat-vesicle and round-vesicle terminals on the somas (48/100 micron2). Geniculate terminals contacted the cell bodies and primary, secondary, and tertiary dendrites. The Class III cell was stellate with varicose dendrites, a sparse distribution of flat-vesicle terminals (8/100 micron2) on the soma, and both geniculate and round-vesicle terminals on the dendrites. Class IV cells had radially elongated somas with sharply tapered apical and basilar dendrites bearing spines. There was a medium distribution of flat-vesicles terminals (17/100 mu2), to the somas while geniculate terminals were restricted to the secondary dendrites. Class V cells were multipolar with flat-vesicle terminals on the somas (11/100 micron2) and a few geniculate terminals on the dendrites. Class VI cells were mostly small (as small as 7 micron diameter), with a sparse distribution on the somas of both flat-vesicle terminals (7/100 micron2). Two cells had geniculate terminals on their somas. Class VII cells had sharply tapered apical and basilar dendrites, both flat-vesicle and round-vesicle terminals on the somas (14/100 micron2), and no geniculate input. The results make clear that the neurons in layer IVab are quite heterogeneous, not merely in their intrinsic morphology, but also in their patterns of connectivity. The geniculate input is not funneled to a single type of neuron but diverges widely, contacting at least six different cell types, and may form on each a pattern that is characteristic for the type. The reconstruction approach, in providing a detailed identification of the synaptic patterns on substantial numbers of adjacent cells, should make it possible to address directly certain unanswered questions about cortical circuitry...

Neurons in cat lateral geniculate nucleus that concentrate exogenous [3H]-gamma-aminobutyric acid (GABA).

About one-quarter of the neurons in the A-laminae of the cat lateral geniculate selectively accumulate exogenous [3H]-gamma-aminobutyric acid (GABA), its analog, [3H]-2,4-diaminobutyric acid (DABA), and the GABA agonist, [3H] muscimol. These neurons are small (12-18 micrometers diameter) and lack a laminar body, which suggests that they correspond to the class III cell identified in Golgi material. GABA and DABA are also accumulated by F-terminals which are post-synaptic to retinal terminals and presynaptic to relay cell dendrites. It is suggested that GABA may be the transmitter for these small neurons which appear to mediate by means of local circuits a feed-forward inhibition onto the relay cells.

Dendritic arbors and dendritic excrescences of abnormally positioned neurons in area CA3c of mice carrying the mutation "hippocampal lamination defect".

BALB/cJ and BALB/cByJ mice are homozygous for the autosomal gene "hippocampal lamination defect" (provisional gene symbol: Hld) which produces an abnormality in the lamination of the pyramidal cell layer of area CA3c of the hippocampus such that early-generated neurons are superficial and late-generated neurons are deep. Other inbred strains of mice are wild-type (+/+) at the Hld locus and do not have this inversion in cell position in area CA3c. The Golgi method was used to analyze the dendritic arbors of the abnormally positioned pyramidal cells and to compare the distribution of dendritic excrescences (i.e., the termination sites of the mossy fibers) in +/+ and Hld/Hld mice. It was found that in +/+ mice the late-generated pyramidal cells (whose cell bodies are positioned just below the suprapyramidal mossy fiber layer) have one set of dendritic excrescences on their apical dendrites as they extend through the suprapyramidal mossy fiber layer and a second set on their basal dendrites as they pass through the infrapyramidal mossy fiber layer. In contrast, in Hld/Hld mice the late-generated pyramidal cells (whose cell bodies are abnormally positioned just below the intrapyramidal mossy fiber layer) have two sets of dendritic excrescences on their apical dendrites, as they pass through the intrapyramidal and suprapyramidal mossy fiber layers, and none on their basal dendrites. In addition, in the vicinity of the apparent point of contact of the intrapyramidal mossy fibers, the apical dendrites of some of the abnormally positioned pyramidal cells have several fine-caliber branches.(ABSTRACT TRUNCATED AT 250 WORDS)

Ultrastructure of synapses from the A-laminae of the lateral geniculate nucleus in layer IV of the cat striate cortex.

The morphology of synapses in layer IV of the cat striate cortex was studied by electron microscope (EM) autoradiography of serial sections following injection of tritiated amino acids into the lateral geniculate nucleus. Of the terminals in the neuropil, 22% had 2 or more silver grains in 10 successive sections and were labeled at 8-80 times the background level. These terminals were considered to be specifically labeled and to be derived from the lateral geniculate. Two forms of geniculate synapse were observed. One had medium-size, round vesicles and a modest postsynaptic asymmetry (RA); the other had smaller, pleomorphic vesicles and hardly any postsynaptic opacity; that is, it appeared symmetrical (PS). The geniculate RA terminals were presynaptic to dendritic spines, fine processes, and cell bodies; the geniculate PS terminals were presynaptic to dendrites and cell bodies but not to spines. The possible sources of geniculate PS terminals are discussed.

Pattern of lateral geniculate synapses on neuron somata in layer IV of the cat striate cortex.

The distribution of geniculate synapses on neuron cell bodies in layers IVab and IVc of cat area 17 was studied. Electron microscope autoradiography was used to identify geniculate terminals that were labeled by anterograde transport of radioactivity injected into the A-laminae of the lateral geniculate nucleus. Thirty-eight cell bodies (19 in layer IVab and 19 in layer IVc) were examined in a series of 138 consecutive sections. Two pyramidal somas were studied and had no geniculate contacts. All of the other somas studied were nonpyramidal, and of these, 85% received geniculate contacts. The proportion of somas receiving somatic geniculate input differed in layers IVab and IVc. In layer IVab, 70% of the nonpyramidal somas received geniculate contacts; in IVc, 100%. Such high percentages indicate that geniculate afferents synapse with more types of layer IV neuron than the aspinous neurons that synthesize gamma-aminobutyric acid (GABA) (Freund et al., '85b). The pattern of input to somas was so diverse that it was impossible to form groups of neurons based on only this criterion. We wondered if it would be possible to form groups of neurons based on a range of characteristics among which would be pattern of synaptic input. To this end, pyramidal neurons and neurons that contained a cytoplasmic laminated body (CLB) (Winfield, '79; Einstein et al., '84) were treated as two separate classes. We found fair agreement among the features of these neurons within their own classes, with the CLB-cells in layer IVab and IVc forming separate groups. Among the remaining neurons there was too little agreement within the range of features to enable us to treat them in this manner. Geniculate somatic contacts in both sublayers were of 2 forms, those with round vesicles and asymmetric thickenings (RA) and those with pleomorphic vesicles and symmetric thickenings (PS) (Einstein et al., '87). The distribution of these forms varied: some cells received contacts exclusively from one form or the other; other cells received contacts from both. On one cell that bore 33 somatic geniculate terminals, 61% were RA and 39% were PS. Such substantial numbers of geniculate contacts located near the site of impulse initiation are likely to contribute significantly to the receptive field properties of this neuron, and the possible effects are discussed.

Four types of neuron in layer IVab of cat cortical area 17 accumulate 3H-GABA.

Roughly 10% of the neurons in layer IVab of cat area 17 accumulate exogenous 3H-gamma-aminobutyric acid (GABA) but how many types of neuron comprise this population was unknown. We characterized these neurons by partial reconstruction of their somas from serial electron microscope autoradiograms and distinguished four types. GABA 1 was large (greater than 16.5 micron) and dark with a dense distribution of synaptic terminals, substantial geniculate input to the soma, and a moderate accumulation of GABA. GABA 2 was small (less than 13 micron) and pale, also with a dense distribution of terminals but without evidence of somatic geniculate input, and a moderate accumulation of GABA. GABA 3 was radially fusiform (20 micron X 8 micron) with varicose dendrites, a sparse distribution of synaptic terminals, and a heavy accumulation of GABA. GABA 4 was medium in size (15 micron) with a moderate distribution of synaptic terminals and a heavy accumulation of GABA. Reasons are presented for believing that each of these four categories of GABA-accumulating neuron represents a fundamental cell type.

Dystonia and unique muscle features. A 23-year follow-up and correction of diagnosis in two brothers.

OBJECTIVE: To provide follow-up information and a corrected diagnosis on two brothers who were primarily described in the ARCHIVES in 1971 as having had a genetic dystonia with unusual muscle biopsy features. MEASURES: Clinical observation of response to treatment and muscle histologic findings. RESULTS: These brothers are an unusual example of dopa-responsive dystonia that was present since birth. The muscle histopathologic features were caused by an abnormal cerebral influence on the developing motor unit and were not a primary abnormality. A repeated muscle biopsy performed 1 year after treatment continued to show the same pattern of fiber-type abnormalities. CONCLUSIONS: Dopa-responsive dystonia can be present from birth or early infancy. The response to levodopa is excellent even after a delay in treatment of more than 20 years. Intrauterine dystonia can cause a predominance of small type 2 fibers. A trial of levodopa/carbidopa is indicated in all patients with a childhood-onset dystonia or gait disturbance.

Ropinirole for the treatment of early Parkinson disease: a 12-month experience. Ropinirole Study Group.

OBJECTIVE: To evaluate ropinirole hydrochloride as dopaminergic monotherapy in patients with early Parkinson disease. DESIGN: A 6-month extension of a double-blind, placebo-controlled study. SETTING: Ambulatory care at 22 different sites in the United States. PATIENTS: Patients who successfully completed the initial 6-month study could enter the 6-month extension study (ropinirole, n = 70; placebo, n = 77). INTERVENTION: Use of ropinirole or placebo therapy. MAIN OUTCOME MEASURES: The efficacy variables were the number of patients who successfully completed the 12-month study and did not require supplemental levodopa, the number of patients requiring supplemental levodopa, and the proportion of patients having an insufficient therapeutic response. RESULTS: Significantly fewer ropinirole-treated patients met criteria for insufficient therapeutic response (23 [19.8%] of 116) or required the initiation of levodopa therapy (22 [19%] of 116) compared with placebo-treated patients (60 [48%] of 125 patients for insufficient therapeutic response; 57 [45.6%] of 125 patients for additional levodopa). Significantly more ropinirole-treated patients (51 [44.0%] of 116) successfully completed the 12-month study and did not require supplemental levodopa compared with placebo-treated patients (28 [22.4%] of 125). The incidence of adverse experiences and patient withdrawals was low. CONCLUSION: Ropinirole was effective and well tolerated as monotherapy for 12 months in patients with early Parkinson disease.

Recent advances in the treatment of orthostatic hypotension.

Orthostatic hypotension is a fall in blood pressure on standing that causes symptoms of dizziness, visual changes, and discomfort in the head and neck. The goal of treatment is the improvement of the patient's functional capacity, rather than a target blood pressure. For treatment to be successful, it must be individualized. Non-pharmalogic interventions include carefully managed exercise, scheduled activities, and monitoring of the environmental temperature. Agents such as fludrocortisone, midodrine, and epoetin alfa offer successful pharmacologic interventions. Although these measures ease the symptoms of orthostatic hypotension, current approaches neither reverse nor stabilize the disease process in autonomic disorders.