Management of congenital glaucoma.
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Adrenergic beta-Antagonists↗
Biomedical subjects
S Freedman
Publications and source records attributed to S Freedman.
A prospective study of heart rate response following trauma and the subsequent development of posttraumatic stress disorder.
BACKGROUND: Physiological arousal during traumatic events may trigger the neurobiological processes that lead to posttraumatic stress disorder (PTSD). This study prospectively examined the relationship between heart rate and blood pressure recorded immediately following a traumatic event and the subsequent development of PTSD. METHODS: Eighty-six trauma survivors who presented at the emergency department of a general hospital were followed up for 4 months. Heart rate and blood pressure were recorded on arrival at the emergency department. Heart rate, anxiety, depression, and PTSD symptoms were assessed 1 week, 1 month, and 4 months later. The clinician-administered PTSD scale defined PTSD status at 4 months. RESULTS: twenty subjects (23%) met PTSD diagnostic criteria at the 4-month assessment (PTSD group), and 66 (77%) did not (non-PTSD group). Subjects who developed PTSD had higher heart rates at the emergency department (95.5+/-13.9 vs 83.3+/-10.9 beats per minute, t=4.4, P<.001) and 1 week later (77.8+/-11.9 vs 72.0+/-9.5 beats per minute, t=2.25, P<.03), but not after 1 and 4 months. The groups did not differ in initial blood pressure measurement. Repeated-measures analysis of variance (ANOVA) for heart rate showed a significant group effect (P<.02), time effect (P<.001), and group x time interaction (P<.001). The time effect and group x time interaction remained significant when adjusted for sex, age, trauma severity, immediate response, and dissociation during the traumatic event. CONCLUSION: Elevated heart rate shortly after trauma is associated with the later development of PTSD.
Adult↗
Prospective study of posttraumatic stress disorder and depression following trauma.
OBJECTIVE: The purpose of this study was to prospectively evaluate the onset, overlap, and course of posttraumatic stress disorder (PTSD) and major depression following traumatic events. METHOD: The occurrence of PTSD and major depression and the intensity of related symptoms were assessed in 211 trauma survivors recruited from a general hospital's emergency room. Psychometrics and structured clinical interview (the Structured Clinical Interview for DSM-III-R and the Clinician-Administered PTSD Scale) were administered 1 week, 1 month, and 4 months after the traumatic event. Heart rate was assessed upon arrival at the emergency room for subjects with physical injury. Twenty-three subjects with PTSD and 35 matched comparison subjects were followed for 1 year. RESULTS: Major depression and PTSD occurred early on after trauma; patients with these diagnoses had similar recovery rates: 63 survivors (29.9%) met criteria for PTSD at 1 month, and 37 (17.5%) had PTSD at 4 months. Forty subjects (19.0%) met criteria for major depression at 1 month, and 30 (14.2%) had major depression at 4 months. Comorbid depression occurred in 44.5% of PTSD patients at 1 month and in 43.2% at 4 months. Comorbidity was associated with greater symptom severity and lower levels of functioning. Survivors with PTSD had higher heart rate levels at the emergency room and reported more intrusive symptoms, exaggerated startle, and peritraumatic dissociation than those with major depression. Prior depression was associated with a higher prevalence of major depression and with more reported symptoms. CONCLUSIONS: Major depression and PTSD are independent sequelae of traumatic events, have similar prognoses, and interact to increase distress and dysfunction. Both should be targeted by early treatment interventions and by neurobiological research.
Accidents, Home↗
Combined gastric and ileocecal toxicity (serpiginous ulcers) after oral kayexalate in sorbital therapy.
Kayexalate (Roxane Labs, Columbus, OH) in sorbitol is commonly administered by the oral and rectal route for the treatment of hyperkalemia in patients with renal failure. It is believed to have minimal toxicity because it functions as a cation exchanger and is not absorbed. We herein report on a patient who developed identical serpiginous ulcers in the stomach and the terminal ileum after the use of Kayexalate. We believe that this drug could have significant gastrointestinal toxicity in specific patient groups and suggest tentative guidelines, both for the identification of such patients and for the safer use of Kayexalate in these circumstances.
Administration, Oral↗
Immuno and functional characterization of CFTR in submandibular and pancreatic acinar and duct cells.
Cystic fibrosis results from defective Cl- channel activity mediated by the cystic fibrosis transmembrane conductance regulator (CFTR) gene product. In the gastrointestinal tract this is manifested in abnormal salivary secretion and pancreatic insufficiency. This is generally attributed to defective Cl- transport by the ductal system of the glands. We provide the first immunocytochemical and functional evidence for expression of CFTR protein and Cl- current in rat and mouse submandibular gland (SMG) and pancreatic acinar cells, a site proximal to the ductal system of these secretory glands. Monoclonal and polyclonal antibodies recognizing COOH-terminal epitopes of CFTR show that duct and acinar cells from the two glands express CFTR in the luminal membrane. Specificity of the polyclonal antibody was verified by absence of staining in duct and acinar cells of the SMG of cf-/cf- and delta F/delta F mice. Identification of CFTR in acinar cells was aided by demonstrating coexpression of CFTR and type 3 inositol 1,4,5-trisphosphate receptors in the luminal pole of acini and absence of type 3 inositol 1,4,5-trisphosphate receptors in ducts. Electrophysiological characterization in single SMG duct and acinar cells shows the presence of a protein kinase A-activated, voltage- and time-independent, ohmic Cl- current and absence of repolarization-dependent tail currents, all of which are kinetic properties of the CFTR-dependent Cl- channel. In addition, the channel was activated by the nonhydrolyzable ATP analog 5'-adenylylimidodiphosphate and the benzimidazalone NS-004. Channels activated by all activators were inhibited by glibenclamide and a known inhibitory antiserum [anti-CFTR-(505-511)]. Combined immunologic, functional, and pharmacological evidence allows us to conclude that acinar cells of the SMG and pancreas express functional CFTR-dependent Cl- channels. Because this site is proximal to the duct, modification of activity of this channel in acinar cells is likely to contribute to abnormal salivary secretion and pancreatic insufficiency typical of cystic fibrosis.
Animals↗
Predicting PTSD in trauma survivors: prospective evaluation of self-report and clinician-administered instruments.
BACKGROUND: This study examined the ability of commonly used questionnaires and a structured clinical interview to predict PTSD in recent trauma survivors. METHOD: Horowitz's Impact of Event Scale (IES), Speilberger's State Anxiety (SANX) and the Peri Traumatic Dissociation Questionnaire (PDEQ) were administered one week post-trauma to 239 traumatised individuals recruited from a general hospital emergency room. The IES, the SANX, the civilian version of the Mississippi Scale for Combat Related PTSD (MISS), and the Clinician Administered PTSD Scale (CAPS) were administered one month and four months post-trauma. Receiver operator characteristic (ROC) analysis was used with these data. RESULTS: All questionnaires were better than chance at predicting PTSD. The so-called PTSD questionnaires (IES and MISS) were not better than the more general ones. No difference in predictive value was found when questionnaires were carried out one week or one month after a trauma. Recovery was better predicted than PTSD, and the CAPS was better than the questionnaires. DISCUSSION: The use of psychometrics and clinical interviews to predict PTSD should be guided by clinical relevance and by the availability of resources.
Adolescent↗
Children's health care use in the Healthy Kids Program.
BACKGROUND: In 1990, the Florida Legislature established the Florida Healthy Kids Corporation to implement the concept of school enrollment-based health insurance coverage for children. The county school districts are used as a grouping mechanism to negotiate health insurance policies. The Florida Healthy Kids Corporation negotiates contracts with health maintenance organizations (HMOs) to assume financial risk and to provide health care services at each program site. In 1994, there were five sites with four different participating HMOs. Assessing quality of care is particularly important when contracting with HMOs because of the perception that financial and utilization review arrangements may restrict the enrollees' access to needed health care. One essential component of health care quality is the extent to which health care services are used in a manner consistent with the expected pattern of use for the population of enrolled children. The purpose of this study is to compare children's health care use across five different Florida Healthy Kids Program sites. Specifically, we compare the enrollees' actual health care use across HMO settings and program sites to the expected health care use based on the enrollees' case-mix. METHODS: Each HMO provided child-specific health care use data including Physician's Current Procedural Terminology codes and International Classification of Diseases, 9th Revision codes. We used the Ambulatory Care Groups (ACGs) software to compare the children's actual health care use to the expected health care use at each site adjusted for case-mix. Several steps were then taken to determine if the children were receiving the anticipated number of health care visits based on their diagnoses. First, we divided the average number of encounters at each site by the group average across all of the sites, without adjusting for the case-mix of the enrollees. We then divided the average number of visits at each site by the expected number of visits based on the case-mix adjustment. A value of 1.00 means that the actual use and the expected use are identical. Values below 1 indicate underuse and values over 1 indicate overuse of health care services. Statistical comparisons of the actual versus expected average health care use across the five sites were performed by deriving the appropriate chi2 statistics. RESULTS: A census of all children (N = 14 688) enrolled in the Florida Healthy Kids Program at each of the sites for 6 months or longer were included in the analysis. The average number of health care encounters across all sites for a 12-month time period was 2.98 +/- 4.6 visits. After adjusting for the case-mix of the enrollees in each site using the ACG software, several of the five sites differed from one in a statistically significant way. However, these statistical assessments must be tempered with assessing the practical magnitude of the observed differences. CONCLUSIONS: The number of public and private efforts to insure children who are not eligible for Medicaid and whose parents cannot purchase private insurance has grown dramatically. These programs are vital for ensuring financial access to care for uninsured children. However, it is essential that such programs are not viewed as merely cost containment efforts. Assessing the degree to which children receive the health care services they need across multiple delivery settings is an essential yet challenging component of quality assurance. Generally, our analysis indicates that children in the Florida Healthy Kids Program are receiving the amount of health care expected based on their health care needs; which is one component of a high-quality health care program.
Child↗
Internal sclerostomy with a mechanical trephine versus the neodymium:YAG laser in dogs.
BACKGROUND AND OBJECTIVES: To experimentally compare and contrast the internal sclerostomy produced using a mechanical trephine with that made by an Nd:YAG laser, and to evaluate the healing patterns, efficacy, and technical advantages of each method. MATERIALS AND METHODS: Four healthy dogs with normal eyes were used in this study. The left eye of each dog had an internal sclerostomy performed with an automated mechanical trephine. The right eye of each dog had an internal sclerostomy performed with an Nd:YAG laser. Postoperatively, the intraocular pressure of each eye was measured at regular intervals. The dogs were euthanized successively at 1, 2, 3, and 4 weeks postoperatively, and the morphology of the surgical sites was studied. RESULTS: The Nd:YAG laser was easier to manipulate and technically less demanding than the mechanical trephine. However, the Nd:YAG laser induced more prominent corneal edema and conjunctival hyperemia compared with the automated trephine. Morphology of the tissue response showed tissue necrosis and greater inflammation with the Nd:YAG laser than with the automated trephine. CONCLUSIONS: These two techniques demonstrate differences in technical demands and tissue response. Both are characterized by minimal reactive fibrosis of the episcleral and Tenon's capsule fibroblast.
Animals↗
Biological profile of L-745,870, a selective antagonist with high affinity for the dopamine D4 receptor.
L-745,870,(3-([4-(4-chlorophenyl)piperazin-1-yl]methyl)-1H- pyrollo[2,3-b] pyridine, was identified as a selective dopamine D4 receptor antagonist with excellent oral bioavailability and brain penetration. L-745,870 displaced specific binding of 0.2 nM [3H] spiperone to cloned human dopamine D4 receptors with a binding affinity (Ki) of 0. 43 nM which was 5- and 20-fold higher than that of the standard antipsychotics haloperidol and clozapine, respectively. L-745,870 exhibited high selectivity for the dopamine D4 receptor (>2000 fold) compared to other dopamine receptor subtypes and had moderate affinity for 5HT2, sigma and alpha adrenergic receptors(IC50 < 300 nM). In vitro, L-745,870 (0.1-1 microM) exhibited D4 receptor antagonist activity, reversing dopamine (1 microM) mediated 1) inhibition of adenylate cyclase in hD4HEK and hD4CHO cells; 2) stimulation of [35S] GTPgammaS binding and 3) stimulation of extracellular acidification rate, but did not exhibit any significant intrinsic activity in these assays. Although standard antipsychotics increase dopamine metabolism or plasma prolactin levels in rodents, L-745,870 (</=30 mg/kg p.o.) had no effect in these assays. The lack of a suitable in vivo assay for D4 receptor activation prompted the use of in vivo surrogate marker assays which confirmed that doses of 5-60 microg/kg L-745,870 would be sufficient to occupy 50% D4 receptors in the brain. These results show that dopamine D4 receptor antagonism in the brain does not result in the same neurochemical consequences (increased dopamine metabolism or hyperprolactinemia) observed with typical neuroleptics.
Animals↗
Identification of K-ras mutations: from microscope to endoscope.
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Adenocarcinoma↗
Antagonism of the effects of (+)-PD 128907 on midbrain dopamine neurones in rat brain slices by a selective D2 receptor antagonist L-741,626.
1. The ability of PD 128907 to activate dopamine receptors in the ventral tegmental area, substantia nigra pars compacta, and striatum was investigated by use of in vitro electrophysiological recording and fast cyclic voltammetry. The affinity of a novel D2 selective antagonist L-741,626 for receptors activated by this agonist was measured to determine if its effects were mediated by D2 or D3 receptors. 2. The active (+) enantiomer of PD 128907 bound with high affinity and selectivity to rat D3 dopamine receptors. The Ki values for (+)-PD 128907 were 620 nM at D2, 1 nM at D3 and 720 nM at D4 receptors. 3. (+)-PD 128907 inhibited cell firing in both the ventral tegmental area and substantia nigra pars compacta with EC50 values of 33 nM (pEC50 = 7.48 +/- 0.10, n = 10) and 38 nM (pEC50 = 7.42 +/- 0.15, n = 5), respectively. No effects of (+)-PD 128907 (100 nM) were observed on glutamate or GABA-mediated synaptic potentials elicited by focal bipolar stimulation. 4. L-741,626 antagonized these effects of (+)-PD 128907 in a concentration-dependent and surmountable manner with an affinity, determined from Schild analysis, of 20 nM (pKB = 7.71 +/- 0.14) in the ventral tegmental area and 11 nM (pKB = 7.95 +/- 0.18) in the substantia nigra pars compacta. 5. (+)-PD 128907 also inhibited dopamine release in the caudate-putamen with an EC50 of 66 nM (n = 5). The affinity of L-741,626 for these nerve terminal autoreceptors (pKB = 7.71 +/- 0.06; = 20 nM) was identical to that observed on midbrain dopamine neurones. 6. These data demonstrate that the D3 receptor ligand (+)-PD 128907 is a potent agonist on rat midbrain dopamine neurones. However, its lack of regional selectivity, and the high affinity of the selective D2 receptor antagonist L-741,626 for receptors activated by (+)-PD 128907, was more consistent with an action on D2 autoreceptors rather than upon a D3 dopamine receptor subtype.
Animals↗
Corneal coloboma, aphakia and retinal neovascularization with anterior segment dysgenesis (Peters' anomaly).
An infant with bilateral Peters' Anomaly, with corneal opacification in the right eye and an opacification with an axial defect in the left also had an associated hydrocephalus and cardiac anomalies that proved fatal; histopathology of the right eye showed retinal neovascularization in addition to findings consistent with a diagnosis of Peters' Anomaly; in the left eye, pathologic findings were suggestive of a corneal coloboma associated with aphakia.
Abnormalities, Multiple↗
Cognitive-behavioural treatment of shoplifting in a depressed female.
This paper describes the successful treatment of a depressed shoplifter, using cognitive therapy combined with exposure, an approach not previously described in the literature for this problem. Definitions of shoplifting behaviour are discussed, and other treatment methods examined.
Adult↗
The School Enrollment-Based Health Insurance program: socioeconomic factors in enrollees' use of health services.
OBJECTIVES: The School Enrollment-Based Health Insurance program is designed to reduce financial barriers to children's health care use. This study sought to determine if any socioeconomic measures differed between enrollees with at least one health care encounter and those with no encounters. METHODS: Logistic regression was used to assess the impact of various predictors on the odds that a child would use health care services. RESULTS: Children receiving free insurance premiums were less likely to use health care than those receiving partial subsidy. African-American and Hispanic children were less likely than Whites to use health care. Age, sex, and months enrolled also influenced the likelihood of health care use. CONCLUSIONS: Financial and non-financial factors must be considered when developing children's health care programs.
Child↗
How to recognise myasthenia gravis.
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Adult↗
Infant with mos45,x/46,XY/47,XYY/48,XYYY: genetic and clinical findings.
We describe an infant with mos45,X/46,XY/47,XYY/48,XYYY who presented with ambiguous genitalia. Her phenotype was also remarkable for minor ear and eye anomalies and coarctation of the aorta with bicuspid aortic valve. Laparoscopy revealed bilateral Fallopian tubes and a left infantile testis with epididymis. Chromosomal analyses of blood, skin, aorta, right Fallopian tube, and left gonadal tissue showed mos45,X/46,XY/47,XYY/48,XYYY. The 46,XY cell line was identified with routine trypsin-Giemsa banding only in cultured cells from an aortic biopsy. Fluorescence in-situ hybridization (FISH) was utilized to identify the presence of 46,XY cells in other tissues. The clinical manifestations of this patient are discussed and compared with those of similar cases of Y chromosome aneuploidy. To our knowledge, this is the first report of a patient with this unusual karyotype.
Aneuploidy↗
Amphotericin B-induced dilated cardiomyopathy.
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Adult↗