The effect of the steroid sulfatase inhibitor (p-O-sulfamoyl)-tetradecanoyl tyramine (DU-14) on learning and memory in rats with selective lesion of septal-hippocampal cholinergic tract.

Dehydroepiandrosterone sulfate (DHEAS), is an excitatory neurosteroid synthesized within the CNS that modulates brain function. Effects associated with augmented DHEAS include learning and memory enhancement. Inhibitors of the steroid sulfatase enzyme increase brain DHEAS levels and can also facilitate learning and memory. This study investigated the effect of steroid sulfatase inhibition on learning and memory in rats with selective cholinergic lesion of the septo-hippocampal tract using passive avoidance and delayed matching to position T-maze (DMP) paradigms. The selective cholinergic immunotoxin 192 IgG-saporin (SAP) was infused into the medial septum of animals and then tested using a step-through passive avoidance paradigm or DMP paradigm. Peripheral administration of the steroid sulfatase inhibitor, DU-14, increased step-through latency following footshock in rats with SAP lesion compared to both vehicle treated control and lesioned animals (p<0.05). However, in the DMP task, steroid sulfatase inhibition impaired acquisition in lesioned rats while having no effect on intact animals. These results suggest that steroid sulfatase inhibition facilitates memory associated with contextual fear, but impairs acquisition of spatial memory tasks in rats with selective lesion of the septo-hippocampal tract.

Plasmodium chabaudi adami: use of the B-cell-deficient mouse to define possible mechanisms modulating parasitemia of chronic malaria.

Our previous observation that B-cell-deficient JH-/- mice utilize T cell-dependent immunity to suppress acute Plasmodium chabaudi adami-induced malaria but then develop chronic low-level parasitemia prompted this study of control mechanisms for chronic parasitemia. When we infected JH-/- mice with blood-stage parasites, chronic parasitemia exacerbated after the 6th month and persisted for up to 17 months. This exacerbation of parasitemia could not be attributed to host aging because the time-course of acute infection in naïve aged mice was nearly identical to that seen in young mice. Nor could exacerbated parasitemia be attributed to mutation in the parasite genome resulting in increased virulence; when subinoculated into naïve JH-/- mice, parasites from chronically infected JH-/- mice with exacerbated parasitemia produced acute stage parasitemia profiles in most recipients comparable to those seen in JH-/- mice upon infection with the original stabilate material. Of the pro-inflammatory cytokines measured, including IFNgamma, TNFalpha, IL-12p70, and MCP-1beta, none were significantly different in the sera of mice with exacerbated parasitemia compared to uninfected controls. Levels of IL-6 were significantly (P=0.002) less in the sera of mice with exacerbated parasitemia. Serum levels of the anti-inflammatory cytokine, TGFbeta, were significantly depressed in chronically infected JH-/- mice compared to uninfected controls. In contrast, IL-10 levels were markedly increased. These findings suggest that the cytokine balance may be disturbed during chronic malaria, thereby impacting on mechanisms that modulate levels of parasitemia.

Design and rationale of the ARBITER trial (Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol)--a randomized trial comparing the effects of atorvastatin and pravastatin on carotid artery intima-media thickness.

BACKGROUND: As a class, statins are remarkably effective in reducing low-density lipoprotein (LDL) cholesterol, and several of these drugs have now been shown to reduce coronary heart disease morbidity and mortality. However, several important controversies in the use of statins remain to be answered by clinical trials. For example, it is controversial whether marked cholesterol reduction to levels below 100 mg/dL would further reduce the incidence of coronary heart disease. Furthermore, concerns about differences among statins for nonlipid effects has raised the concern that the assumption of a class effect is premature until head-to-head clinical trials are completed. METHODS: Arterial Biology for the Investigation for the Treatment Effects of Reducing Cholesterol (ARBITER) is a single-center, randomized, active-controlled study comparing the efficacy of high-dose atorvastatin (80 mg/d) and pravastatin (40 mg/d) in patients being treated for either the primary or secondary prevention of coronary heart disease. This trial will enroll up to 200 patients for the primary end point of the mean change in intima-media thickness of the common carotid artery. This effect will be evaluated over a treatment duration of 12 months. Secondary end points include the effects of statin therapy on inflammatory and hemostatic markers (C-reactive protein and fibrinogen). CONCLUSION: ARBITER will provide important data on the role of marked LDL reduction and the "class effect" theory of statin therapy in cardiovascular medicine.

Arthrogryposis multiplex congenita.

Arthrogryposis multiplex congenita (AMC) is a term that is used to describe the presence of multiple joint contractures at birth. AMC can be seen singularly or in conjunction with other abnormalities. Historically, the term arthrogryposis was used as a disease diagnosis, but it is now clear that AMC is not a disease entity but a syndrome, involving a manifestation of many fetal and neonatal disorders of the neuromuscular system. Its etiology is multifocal, and there is a wide variation in the degree to which muscles and joints are affected. Early identification and implementation of a plan of therapy are essential. The purpose of this article is to provide an overview of the AMC 'syndrome, specifically, clinical features, etiology, diagnosis, therapeutic interventions, family support, and outcomes.

[A new trichromic safranin stain for the detection of Cryptosporidium parvum, Cyclospora cayetanensis, species of Microsporidia and Isospora belli in fecal material]. / Una nueva coloración safranina tricrómica para la detección de Cryptosporidium parvum, Cyclospora cayetanensis, especies de Microsporidia e Isospora belli en materia fecal.

Cryptosporidium parvum, Isospora belli, Cyclospora cayetanensis and Microsporidia are frequent pathogens in the immunodeficient host, which may cause multiple infections. The above mentioned parasites are found in feces by the application of different specific tintorial techniques. The objective of this work was the development of a stain for the simultaneous detection of these parasites, reducing costs as well as the time taken to make the diagnosis. The safranin-trichrome stain is simple, chip and its results are similar to those of specific tints. All microorganisms are easy to detect and besides being perfectly distinguishable from fungi and faecal elements.

[In vivo selectivity of nonsteroidal anti-inflammatory drugs on COX-1-COX-2 and gastrointestinal ulcers, in rats]. / Selectividad "in vivo" de daines COX-1-COX-2 y úlceras gastrointestinales, en ratas.

UNLABELLED: This work was aimed to study COX-1 and COX-2 selectivity in 16 non-steroidal anti-inflammatory drugs (NSAIDs), at ulcerogenic doses in 2 experimental models: 1) provided subcutaneously (sc), after solid food(SF), (antrum ulcers and intestinal erosions); and 2) orally (O) (fundic and intestinal erosions). METHODS: 17 groups of female Wistar rats (n = 7 each group), weighing 200 g, 36 h fasting with water ad libitum, were submitted to the following experiments: 1. SF (Cargill chow) during 1 h, and then sc: 1.1 ml saline; 2. diclofenac (Di); 3. indomethacine (Indo); 4. Ketorolac (Ke); 5. meloxicam (Mel); 6. Pyroxicam (P); 7. tenoxicam (T). The dose for the aforementioned drugs was 60 mg/kg; 8. aceclofenac (Ace); 9. 200 mg/kg nimesulide (Ni); 10. mefenamic acid (Mac); 11. aspirin (A); 12. etodolac (E); 13. ibuprophen (Ibu); 14. nabumetone (Na); 15. naproxene (Nap); 16. ketoprophen (Ket); 17. paracetamol (Pa), 500 mg/kg. II. The drugs where administered by orogastric tubing to the same groups of fasting animals. After 24 h the animals were killed by ether overdose. Laparotomy was performed and the stomach and the small intestine was removed. The percentage of antum ulcer, and fundic and intestinal erosion (mm2) was tabulated by planimetry. Blood and histological samples were obtained. RESULTS: The NSAIDs Indo, Ibu, Ke, Ket, P and Te yielded an antrum ulcer area: 5-29% and intestinal erosion, 101-395 mm2, similar to Indo (p > 0.50). In contrast there were neither ulcers nor intestinal erosions with Mac, A, Di, E and Nap (p > 0.50). While there were absence of ulcers with Ace, Me, Na, Ni and Pa and slight intestinal erosion (0-23 mm2; p < 0.01). II. There were differences in the following oral (NAIDs: Ace, Me, NA, Ni and Pa, yielding 0-5% fundic erosion and 0-22 mm2 intestinal erosion (p < 0.001). The other NSADs yielded 33-90% fundic erosion and 116-550 mm2 intestinal erosion, similarly to Indo (p > 0.50). HISTOLOGY: Leukocyte infiltrate in the gastrointestinal mucosa with all the NSADs, except Ibu and Pa. There was also neutrophilia (5000-20,000), but not with Ibu and Pa (700-1200). CONCLUSIONS: COX-2-COX-1 selectivity was demonstrated "in vivo" in aceclofenac, meloxicam, nabumetone, nimesulide and paracetamol.

Acute hospital admission systems: problems experienced by general practitioners.

This study was undertaken to examine the existing system of access for general practitioners in arranging acute admissions to three general hospitals in the Southern Health Board (SHB) area. One hundred and twenty eight patients were admitted to the three hospitals over a one week period. General practitioners were surveyed on the process of admission for each patient. Response rate was 118/128 (92.2%). Hospital A had 53 admissions, Hospital B had 41 admissions and Hospital C had 24 admissions. In total, 30/118 (25.4%) admissions took over one hour to arrange, of these 23 (76.7%) were admitted to Hospital A, 4 (13.3%) were admitted to Hospital B and 3 (10.0%) were admitted to Hospital C. The admission sister was responsible for confirming the route of admission in 102 (86.4%) of cases. In Hospital A, 23/53 (43.4%) patients were referred to Accident and Emergency (A&E) for assessment prior to admission, 4/41 (9.8%) were referred in Hospital B, and 2/24 (8.3%) in Hospital C. In the light of current findings, possible alternatives to the current acute admissions system are discussed.

Selectividad "in vivo" de daines cox-1 - cox-2 y ulceras gastrointestinales, en ratas / In vivo selectivity of nonsteroidal anti-inflammatory drugs on COX-1 - COX-2 and gastrointestinal ulcers, in rats

En ratas Wistar "in vivo", se evaluó la selectividad COX-2 - COX-1 de 16 DAINEs, dados en dois ulcerógenas, en dos modelos experimentales: A) Ayuno 36 horas, comida sólida 1 hora y AINE sc, donde indometacina (inhibidor selectivo COX-1) produce úlceras en antro gástrico y erosines en intestino delgado y B) Ayuno 36 horas y DAINEs dados por vía oral. Se estudiaron: indometacina, aceclofenac, ácido mefenámico, aspirina, diclofenac, etodolac, ibuprofeno, ketoprofeno, ketorolac, meloxicam, nabumetona, naproxeno, nimesulida, paracetamol, piroxicam y tenoxicam. Se concluyó que los AINEs con menor daño gastrointestinal y prevalentes inhibidores COX-2 fueron: aceclofenac, meloxicam, nabumetona, nimesulida y paracetamol.

Selectividad "in vivo" de daines cox-1 - cox-2 y ulceras gastrointestinales, en ratas / In vivo selectivity of nonsteroidal anti-inflammatory drugs on COX-1 - COX-2 and gastrointestinal ulcers, in rats

En ratas Wistar "in vivo", se evaluó la selectividad COX-2 - COX-1 de 16 DAINEs, dados en dois ulcerógenas, en dos modelos experimentales: A) Ayuno 36 horas, comida sólida 1 hora y AINE sc, donde indometacina (inhibidor selectivo COX-1) produce úlceras en antro gástrico y erosines en intestino delgado y B) Ayuno 36 horas y DAINEs dados por vía oral. Se estudiaron: indometacina, aceclofenac, ácido mefenámico, aspirina, diclofenac, etodolac, ibuprofeno, ketoprofeno, ketorolac, meloxicam, nabumetona, naproxeno, nimesulida, paracetamol, piroxicam y tenoxicam. Se concluyó que los AINEs con menor daño gastrointestinal y prevalentes inhibidores COX-2 fueron: aceclofenac, meloxicam, nabumetona, nimesulida y paracetamol. (AU)

A simple, inexpensive applicator for irradiation of localized areas of the vagina with intracavitary brachytherapy.

PURPOSE: To describe the construction of a simple, inexpensive applicator for irradiation of localized areas of the vagina with intracavitary brachytherapy. METHODS AND MATERIALS: It was desirable to avoid an interstitial implant in an elderly patient with a stage T2 vaginal cancer. The final phase of radiation therapy was delivered with a custom made intracavitary cylinder that allowed the high-dose area to be limited to the portion of the vagina at high risk for residual disease. The applicator was fabricated from a clear cast acrylic (Lucite) rod with dimensions 3.5 cm diameter x 5.0 cm long. The applicator contained 11 parallel grooves, each 1.8 mm deep x 2.2 mm wide, machined along the surface of the cylinder parallel its long axis at 1.0 cm increments. Plastic needles (15 gauge) were inserted into the grooves along the surface of the acrylic cylinder and held in place with heat shrink tubing. The applicator was easily inserted and positioned without anesthesia. Standard low dose rate 192Ir ribbons were inserted into the plastic needles after positioning the applicator in the vagina. RESULTS: Construction of this applicator system requires a few weeks notice and approximately $150. Fabrication of the grooved cylinder is a routine task for a workshop with a milling machine. A step-by-step description of how to construct and use the applicator is provided along with the telephone numbers of commercial vendors to call to order all necessary materials. CONCLUSION: This article describes a simple, inexpensive method for constructing a customized vaginal applicator that can be used to treat a limited area of the vagina with intracavitary brachytherapy.

Neurocognitive assessment in the treatment of incontinence following severe traumatic brain injury.

Although a variety of techniques have been developed for treatment of incontinence, strategies for applying these techniques to adults having significant cognitive impairments or mobility restrictions have not been well described in the literature. This case study describes the rehabilitation of urinary incontinence in a 20-year-old woman through behavioral interventions targeting the cognitive impairments that prevented her from independently managing her own continence needs. The outcome demonstrates the importance of blending cognitive assessment with behavioral intervention techniques in individuals having severe cognitive and mobility impairments following brain injury.

Activity-based resource allocation: a system for predicting nursing costs.

As hospital-based managers are being confronted with changing patterns of reimbursement, ranging from revenue generating to cost management, it is imperative that hospitals know the exact nursing costs associated with the actual care delivered to specific patients. Nursing care has traditionally been bundled into the room rate for patients. This approach is extremely limiting when facilities are negotiating per diem rates and capitated rate contracts. At Braintree Hospital Rehabilitation Network, the nursing department has developed and implemented an activity-based management system to determine the actual cost of nursing care provided to each patient. This approach, which differentiates nursing costs accurately by diagnostic group and by intensity of nursing care, has contributed to the hospital's success in negotiating individual patient contracts with insurers in the managed care environment that increasingly focuses on costs and outcomes. Another result has been to enhance the accuracy of the network's cost accounting system.

[The creation of partnerships: perspectives and possibilities]. / La création de partenariats: perspectives et possibilités.

This article re-examines access to treatment and care in the current context of fiscal restriction and change in locus of care. Taking the position that the development of partnerships with all parties who work in the mental health area is an important process, this article argues that such processes are infrequently discussed. Further, creating a partnered relationship with the person with mental disorder is also neglected. The authors examine mechanisms of relationship change as care moved from large, total-care institutions to general hospitals and finally, to the community. How professionals, individuals with mental disorder and their families have been affected by this change in terms of how alliances are constituted and maintained is discussed. The authors conclude with two case examples which illustrate the reconciliation and non-reconciliation of differing points of view between all partners which likely affected clinical outcomes.

Synthesis and selective monoamine oxidase B-inhibiting properties of 1-methyl-1,2,3,6-tetrahydropyrid-4-yl carbamate derivatives: potential prodrugs of (R)- and (S)-nordeprenyl.

The results of previous studies have established that the monoamine oxidase-catalyzed oxidation of 1-methyl-1,2,3,6-tetrahydropyridyl derivatives bearing heteroatom substituents at C-4 generates 2,3-dihydropyridinium intermediates that undergo spontaneous hydrolysis to release the C-4 substituent and form the amino enone 1-methyl-2,3-dihydro-4-pyridone. We have attempted to adapt this metabolic pathway to the preparation of amine-containing prodrugs that may target the central nervous system which is rich in monoamine oxidase A and B. In this paper we report the synthesis and the in vitro and in vivo metabolic fate of the tetrahydropyridyl carbamate derivatives which are designed to release (S)- and (R)-nordeprenyl. These carbamates are selective monoamine oxidase A substrates. An ex vivo assay has shown that the R-enantiomer is an effective and selective inhibitor of brain mitochondrial monoamine oxidase B.

Synthesis and evaluation of N-(phenylacetyl)trifluoromethanesulfonamides as anticonvulsant agents.

A series of N-(phenylacetyl)trifluoromethanesulfonamides (3a-g) was prepared according to the Topliss scheme in order to determine if aryl substituents would influence anticonvulsant activity. In initial (phase I) screening and quantitative (phase II) evaluation, all seven compounds exhibited significant activity against MES- and scMet-induced seizures. N-(Phenylacetyl)trifluoromethanesulfonamide (3a) was then advanced through five additional testing phases (phases III-VII). Compound 3a displayed good oral bioavailability, low toxicity, and a larger protective index in mice than the prototype drugs, phenytoin, phenobarbital, valproate, and ethosuximide. Additionally, 3a exhibited a longer time to peak effect in all tests and a greater 24-h margin of safety (HD(50)/ED(50)) than the prototypes. Compound 3a blocked picrotoxin-induced seizures but was ineffective against seizures induced by bicuculline or strychnine. In vitro receptor binding studies revealed that 3a did not displace [(3)H]-labeled gamma-aminobutyric acid or [(3)H]-labeled flunitrazepam, and tolerance did not develop during a 5-day chronic administration.

A-ring ortho-disubstituted aporphine derivatives as potential agonists or antagonists at serotonergic 5-HT1A receptors.

(R)- And (S)-11-hydroxy-10-methylaporphine 1 and 2 are, respectively, a potent, highly specific serotonergic (5-HT1A) agonist and antagonist. In an ongoing structure-activity study, racemates of the positional isomers 8-hydroxy-9-methyl- and 8-methyl-9-hydroxyaporphine were prepared by modifications of literature methods and were resolved. The methyl ethers of the target compounds were also evaluated pharmacologically. All of the free phenolic derivatives [(+)- and (-)-8 and 10] were inert in an assay for 5-HT1A receptor activity. All of the methyl ethers [(+)- and (-)-9 and 11] demonstrated quantitatively similar low potency stimulant effect at 5-HT1A receptors. The agonist or antagonist activity exhibited by 1 and 2 reflects the high degree of structural specificity required of aporphine derivatives for action at 5-HT1A receptors.

A controlled investigation of current and premorbid personality: characteristics of Parkinson's disease patients.

It has been suggested that before development of motor symptoms, Parkinson's disease (PD) patients with idiopathic display a specific cluster of personality traits consisting of increased rigidity, conscientiousness, industriousness, orderliness, and cautiousness. The idea of such a distinctive premorbid personality profile remains controversial. This hypothesis was reexamined using a methodology that expands on previous studies. Patients with idiopathic PD, probable Alzheimer's Disease (AD), and medical controls with nonneurological chronic progressive motor disorders were rated by a close relative on the NEO-Personality Inventory (PI) to compare current and premorbid personality profiles. For PD and control subjects, current and past self-ratings were also obtained. Results do not support the postulated distinctive PD personality either premorbidly or following onset of symptoms. Both in terms of the premorbid personality profile and perceived changes in personality post-dating the onset of illness, PD patients are similar to AD patients. Though not differing from medical controls premorbidly, after developing symptoms, PD patients were described as less extroverted; less exploratory and curious; and less organized, goal directed, and disciplined.

Use of laser to extract unwanted pacemaker leads.

Of the total number of pacemakers implanted each year, 6% must eventually be replaced because of infection, lead failure, or other problems. Often however, removal of the pacing leads is precluded by scarring at the tip of the leads. Because abandoned leads can cause serious problems, we initiated the present study to test the feasibility of using a laser to remove such leads. After performing in vitro experiments to establish the laser settings required for severing leads, we implanted 6 leads, from 4 different manufacturers, in 3 dogs. Five weeks later, we passed a laser fiber through each lead to the tip and delivered a 10-watt impulse for 2 seconds, which resulted in the successful removal of all the leads. When the dogs were killed 3 days later, postmortem examination revealed no thromboembolism in the heart or lungs and no myocardial damage. Subsequent experiments in 3 human cadaver hearts-involving leads implanted for 5 years, 2 years, and 2 months-yielded the same satisfactory results as did the canine experiments.

Increased phagocytosis of outer segments in the presence of serum by cultured normal, but not dystrophic, rat retinal pigment epithelium.

Cultured normal rat retinal pigment epithelium (PE) ingested six times more rod outer segments in the presence of 20% fetal bovine serum than in serum-free medium. PE cultured from Royal College of Surgeons (RCS) rats with hereditary retinal dystrophy, known to have a defect in vivo in the phagocytosis of shed outer segment tips, ingested amounts of outer segments comparable to normal PE in serum-free medium but did not show an increase in the presence of serum. In both strains of rat PE phagocytosis of latex spheres was similar in the absence of serum and was six-fold higher in the presence of serum, showing that the RCS phagocytic deficiency for outer segments in vitro is not due to a general defect in the phagocytic capacity of the cell. Increased phagocytosis of outer segments by normal PE was observed in the presence of the high molecular weight fraction of ultrafiltered serum but was not seen with serum that was heated at 93 degrees C or precipitated with 5% trichloroacetic acid. Bovine serum albumin had no effect on phagocytosis. These results are consistent with the idea that the phagocytosis of outer segments by cultured normal rat PE, but not by cultured RCS rat PE, is increased in the presence of a specific protein or other macromolecular component of fetal bovine serum.