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Biomedical subjects

P Flaherty

Publications and source records attributed to P Flaherty.

13 recordsLinked to original sources

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.

Aging↗

[In vivo selectivity of nonsteroidal anti-inflammatory drugs on COX-1-COX-2 and gastrointestinal ulcers, in rats].

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.

Animals↗

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.

Aged↗

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.

Journal Article↗

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.

Animals↗

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.

Age Factors↗

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.

Journal Article↗

Organization of a type I keratin gene. Evidence for evolution of intermediate filaments from a common ancestral gene.

The genomic structure of the mouse 59-kDa keratin gene, a Type I intermediate filament (IF) gene is presented. A comparison of the organization of this gene with that of the human 67-kDa keratin, a Type II IF gene, and hamster vimentin, a Type III IF gene, suggests a common evolutionary origin for Type I, II, and III IF genes. Most introns in these three types of IF genes occur at similar positions within the region encoding sequences predicted to form coiled-coils, but do not delineate structural subdomains. Interestingly though, most of the introns interrupt at or near the beginning of the characteristic 7-residue (heptad) repeat of sequences which form the coiled-coil. These data suggest that the three types of IF genes arose from a common ancestor which may have been assembled from smaller units containing multiple heptad repeats. Subsequent duplication events may then have formed the three known alpha-helical types and each of their various members.

Animals↗

What is the optimum A-V interval in D.D.D. pacing?

One of the programmable parameters in recent pacemakers is atrio-ventricular interval. To find out the optimum A-V interval studies were done in 14 patients. Multigated radionuclide scans were used to measure the left ventricular function, at a resting heart rate of 70/minute. Seven patients had poor left ventricles (ejection fraction less than 50%). Left ventricular ejection fraction, relative cardiac output and end diastolic counts were highest at 250 M. Sec. interval compared to 150. Ejection rates and end systolic counts were not related to A-V interval. Relative cardiac output was 27% higher in poor ventricles at 250 delay than 150. This observation was not significant in normal hearts. Optimum P-R interval is 250 M. Sec. for maximum left ventricular function.

Aged↗

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.

Cost Allocation↗

[A new trichromic safranin stain for the detection of Cryptosporidium parvum, Cyclospora cayetanensis, species of Microsporidia and Isospora belli in fecal material].

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.

AIDS-Related Opportunistic Infections↗

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.

Data Collection↗