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Biomedical subjects

D Hardy

Publications and source records attributed to D Hardy.

At least 19 recordsLinked to original sources

Malignancy in a vestibular schwannoma. Report of a case with central neurofibromatosis, treated by both stereotactic radiosurgery and surgical excision, with a review of the literature.

Malignant change in schwannoma is rare. Malignant change in a vestibular schwannoma (acoustic neuroma) is even more rare. This paper presents a case of rapidly growing vestibular schwannoma first treated by radiosurgery whose histopathology after surgical excision 42 months later showed malignant changes. Up to now, eight cases of malignancy in eighth nerve tumours have been reported, four of which, including the present case, had previously been treated with radiosurgery and four cases that had not received radiation. Thus, it would seem, the overall incidence is extremely low. Nevertheless, extreme vigilance and careful reporting continues to be necessary.

Adult↗

Identification and characterization of a family of Rab11-interacting proteins.

Rab11a is a small GTP-binding protein enriched in the pericentriolar plasma membrane recycling systems. We hypothesized that Rab11a-binding proteins exist as downstream effectors of its action. Here we define a family of four Rab11-interacting proteins: Rab11-Family Interacting Protein 1 (Rab11-FIP1), Rab11-Family Interacting Protein 2 (Rab11-FIP2), Rab11-Family Interacting Protein 3 (Rab11-FIP3), and pp75/Rip11. All four interacting proteins associated with wild type Rab11a and dominant active Rab11a (Rab11aS20V) as well as Rab11b and Rab25. Rab11-FIP2 also interacted with dominant negative Rab11a (Rab11aS25N) and the tail of myosin Vb. The binding of Rab11-FIP1, Rab11-FIP2, and Rab11-FIP3 to Rab11a was dependent upon a conserved carboxyl-terminal amphipathic alpha-helix. Rab11-FIP1, Rab11-FIP2, and pp75/Rip11 colocalized with Rab11a in plasma membrane recycling systems in both non-polarized HeLa cells and polarized Madin-Darby canine kidney cells. GFP-Rab11-FIP3 also colocalized with Rab11a in HeLa cells. Rab11-FIP1, Rab11-FIP2, and pp75/Rip11 also coenriched with Rab11a and H(+)K(+)-ATPase on parietal cell tubulovesicles, and Rab11-FIP1 and Rab11-FIP2 translocated with Rab11a and the H(+)K(+)-ATPase upon stimulating parietal cells with histamine. The results suggest that the function of Rab11a in plasma membrane recycling systems is dependent upon a compendium of protein effectors.

Amino Acid Sequence↗

A self-assessment program for multidisciplinary mental health teams.

OBJECTIVE: The authors describe a self-assessment training program for multidisciplinary mental health teams that was developed in a public multihospital system, the process of implementing the training at a state psychiatric hospital, and a measurement instrument, the Scale for Leadership Assessment and Team Evaluation (SLATE), which they have used for self-assessment of multidisciplinary teams and which is currently being studied. They assessed whether changes in team self-assessments could be seen after the training program. METHODS: A total of 102 mental health professionals from 12 inpatient units representing the disciplines of psychiatry, psychology, nursing, social work, and occupational and activity therapy completed the SLATE before and after participation in a training program that consisted primarily of team self-assessment in the context of treatment planning sessions. The training program included structured feedback, didactics, consultation, and videotaping of sessions. Aggregate data were used to compare mean item scores for the SLATE overall and for its four subscales (team, psychiatrist, participation, and treatment plan) at baseline and after the training. RESULTS: Scores increased significantly for the overall SLATE and for all four subscales, indicating improved team functioning in the areas addressed. The increase in mean score was greatest for the subscale that assessed the leadership of the psychiatrist. CONCLUSIONS: Treatment planning sessions can be used successfully by multidisciplinary mental health teams to examine team functioning in various areas in a self-assessment model. Participation in a training program that included videotaping of sessions, consultation, and structured attention to team functioning was associated with improved ratings of team functioning.

Case Management↗

A comparison of routine and rapid microwave tissue processing in a surgical pathology laboratory. Quality of histologic sections and advantages of microwave processing.

Rapid processing of histopathologic material is becoming increasingly desirable to fulfill the needs of clinicians treating acutely ill patients. Traditional techniques for rapid processing of paraffin-embedded tissues require 4 to 5 hours, delaying treatment for some critically ill patients and requiring additional shifts of technologists in the laboratory. Microwave processing further shortens this time, allowing even more rapid histopathologic diagnosis. Few data exist comparing quality of microwave-processed tissue with that processed by more traditional techniques. We randomly selected 158 paired specimens from 111 patients. One member of the pair was processed routinely overnight, while the other was processed by the rapid microwave technique. The slides then were compared for quality of histologic preparation in a blinded fashion by 2 pathologists. Eight routinely processed specimens were judged as suboptimal, while 6 microwave-processed specimens were judged as suboptimal and 1 was considered unsatisfactory for evaluation. In the remaining cases, the material obtained by the 2 techniques was considered of identical quality. Microwave processing considerably shortens the preparation time for permanent histologic sections without a demonstrable decrease in section quality or "readability."

Female↗

[Shock absorption by intermediate hip prostheses].

PURPOSE OF THE STUDY: The bipolar prosthesis was developed in an attempt to alleviate acetabular wear of conventional metallic endoprostheses. The prosthesis was designed to achieve low-friction metal-on-polyethylene inner bearing motion while decreasing shear stress across the acetabular cartilage. Although good clinical results were obtained, the principle of a persistent inner mobility was contested and some authors have assigned the delay of cartilage erosion to the shock absorption capacity of the polyethylene. The present study was focused on assessing the vibration and shock damping effect of metal monoblock and bipolar head prostheses. MATERIAL AND METHODS: The transmission of the shock wave through these two types of prostheses was studied in vitro. The two heads were first tested in a rigid environment to eliminate all external parasite frequencies. The impact excitation was applied with a hammer connected to an oscillometer. A second accelerometer was connected to the prosthesis stem. Shock wave transmission was analyzed. Secondly, the head was tested with a system vibrating in the same order of frequencies as the skeleton, with and without pre-constraint. The frequency response functions were analyzed. RESULTS: For the metallic prosthesis, the frequency of vibration recorded on the femoral stems was in a large frequency range from 0 Hz to 10 KHz. For the bipolar prosthesis, all the high frequencies of the shock wave were eliminated and only shock wave frequencies from 0 to 500 Hz were recorded. In an environmental system vibrating below 100 Hz, the metallic head did not express high frequencies of vibration. The coefficient of shock absorption was not significantly different for the two heads. DISCUSSION: In the first rigid environment, the metallic head did not filter the high frequency components of the shock wave and the bipolar head tended to eliminate high frequency components due to the flattening effect of the impulse load by the polymer. But, the lower leg is not a rigid structure and the musculo-skeletal system vibrates in frequencies below 100 Hz. In similar conditions, the increased shock-absorbing effect of the polyethylene is far more difficult to observe. For the metallic prosthesis, the recorded frequency of vibration also belongs to a small domain of frequency, from 0 Hz to 100 Hz. The range of frequency is similar for the two types of prostheses. CONCLUSION: Even though polyethylene is characterized by a more pronounced damping capacity than metallic materials, in experimental conditions simulating the vibratory characteristics of the human body, the introduction of a high-density polyethylene liner does not afford any additional shock-absorbing effect compared with a metallic head. It cannot explain cartilaginous sparing.

Equipment Failure Analysis↗

Biomechanical evaluation of Hackethal's intramedullary bundle pin fixation of humeral neck fractures.

Humeral neck fractures can be stabilized using a bundle of intramedullary pins as described by Hackethal. In order to decrease the risk of pin migration, packing of the medullary cavity with as many pins as possible is sometimes recommended, but others believe that stability can be decreased by destruction of cancellous bone in the humeral head by a large bundle of pins. A surgical neck fracture was created with a saw in 30 frozen cadaveric humeri. Bone quality was evaluated by radiography and densitometry. Fractures were stabilized using Hackethal's technique of retrograde intramedullary pinning with varying numbers of 2.5-mm diameter pins; increasing torsion or bending moments of force were then applied to the bones studied. Stability was found to improve with an increasing number of pins and with higher humeral head density. Based upon these findings, the use of a large number of pins is recommended to reduce the risk of pin migration. Up to eight pins, the risk of destruction of cancellous bone in the humeral head appears very low.

Biomechanical Phenomena↗

System-Wide Action Team (SWAT)--a new level of collaboration.

A multidisciplinary System-Wide Action Team was coordinated by nursing leadership in response to increasing patient census and acuity. The primary objectives of the team were to develop mechanisms that would expedite patient's admissions and discharges, communicate key messages to all concerned staff, support each other, and communicate announcements about topics or urgent issues that relate to managing the hospital. The team has implemented improvement initiatives around diagnostic testing and scheduling, expediting the admission process, reducing discharge delays, and staffing to hospital census demands.

Cooperative Behavior↗

Phase 1 trial of a single dose of recombinant human interleukin-12 in human immunodeficiency virus-infected patients with 100-500 CD4 cells/microL.

A phase 1 dose-escalation trial of a single subcutaneous dose of recombinant human (rh) interleukin (IL)-12 was conducted in medically stable human immunodeficiency virus (HIV)-infected patients with 100-500/microL absolute CD4(+) T lymphocytes. Subjects at each dose level were randomly assigned (3:1) to receive rhIL-12 or placebo. Among the 47 subjects enrolled, rhIL-12 was well tolerated at doses of 3-300 ng/kg, but 4 of 5 subjects who received rhIL-12 at 1000 ng/kg had severe adverse events. Dose-related increases in serum interferon-gamma occurred after rhIL-12 administration at doses > or =30 ng/kg. There was no effect of rhIL-12 on plasma HIV RNA or absolute CD4(+) T cell counts. However, dose-related increases in absolute CD8(+) T and NK cells were observed in subjects assigned to rhIL-12 doses of 30-300 ng/kg. Single rhIL-12 doses of 30-300 ng/kg were well tolerated and had biologic activity that could potentially be of benefit in the treatment of HIV disease or its complications.

Adult↗

Comparative in vitro activities of ciprofloxacin, gemifloxacin, grepafloxacin, moxifloxacin, ofloxacin, sparfloxacin, trovafloxacin, and other antimicrobial agents against bloodstream isolates of gram-positive cocci.

The in vitro activity of gemifloxacin against 316 bloodstream isolates of staphylococci, pneumococci, and enterococci was compared with the activities of six fluoroquinolones and three other antimicrobial agents. Of the antimicrobial agents tested, gemifloxacin was the most potent against penicillin-intermediate and -resistant pneumococci, methicillin-susceptible and -resistant Staphylococcus epidermidis isolates, and coagulase-negative staphylococci.

Anti-Bacterial Agents↗

Clinical and pathological findings of a newly recognized disease of elephants caused by endotheliotropic herpesviruses.

The unique clinical and pathological findings in nine Asian (Elephas maximus) and two African (Loxodonta africana) elephants from North American Zoos with a highly fatal disease caused by novel endotheliotropic herpesviruses are described. Identification of the viruses by molecular techniques and some epidemiological aspects of the disease were previously reported. Consensus primer polymerase chain reaction (PCR) combined with sequencing yielded molecular evidence that confirmed the presence of two novel but related herpesviruses associated with the disease, one in Asian elephants and the second in African elephants. Disease onset was acute, with lethargy, edema of the head and thoracic limbs, oral ulceration and cyanosis of the tongue followed by death of most animals in 1 to 7 days. Pertinent laboratory findings in two of three clinically evaluated animals included lymphocytopenia and thrombocytopenia. Two affected young Asian elephants recovered after a 3 to 4 wk course of therapy with the anti-herpesvirus drug famciclovir. Necropsy findings in the fatal cases included pericardial effusion and extensive petechial hemorrhages in the heart and throughout the peritoneal cavity, hepatomegaly, cyanosis of the tongue, intestinal hemorrhage, and ulceration. Histologically, there were extensive microhemorrhages and edema throughout the myocardium and mild, subacute myocarditis. Similar hemorrhagic lesions with inflammation were evident in the tongue, liver, and large intestine. Lesions in these target organs were accompanied by amphophilic to basophilic intranuclear viral inclusion bodies in capillary endothelial cells. Transmission electron microscopy of the endothelial inclusion bodies revealed 80 to 92 nm diameter viral capsids consistent with herpesvirus morphology. The short course of the herpesvirus infections, with sudden deaths in all but the two surviving elephants, was ascribed to acute cardiac failure attributed to herpesvirus-induced capillary injury with extensive myocardial hemorrhage and edema.

2-Aminopurine↗

Safety and antiretroviral effects of combined didanosine and stavudine therapy in HIV-infected individuals with CD4 counts of 200 to 500 cells/mm3.

The safety and antiretroviral effects of didanosine and stavudine in combination were evaluated in 86 people infected with HIV with CD4 counts between 200 and 500 cells/mm3 who had received <7 days of prior nucleoside analogue antiretroviral treatment. Patients were randomized to receive blinded treatments with one of five weight-adjusted, twice-daily regimens of didanosine and stavudine (100 + 10 mg, 100 + 20 mg, 100 + 40 mg, 200 + 20 mg, and 200 + 40 mg) for up to 1 year. Dosages were adjusted appropriately for patients weighing <60 kg and reduced in response to adverse effects. No clear dose-related differences among treatment groups were detected with regard to suppression of plasma HIV RNA level or reduction in infectious titers in peripheral blood mononuclear cells (PBMCs), improvement in CD4 count, or adverse effects. However, trends toward greater decreases in viral load and increases in CD4 count were detected when treatment groups containing the full recommended dosage of one or both agents (high-dose subgroup; arms 3, 4, and 5) were compared with the groups receiving lower dosages. At 28 weeks the mean log 10 HIV RNA decrease was 1.12 (n = 52) and at 52 weeks it was 0.97 (n = 32). Combination therapy was well tolerated, with no apparent dose-related adverse effects. Peripheral neuropathy occurred in 2 of 86 (2.3%) of patients. Didanosine and stavudine together appear to be a good nucleoside analogue foundation for aggressive triple- or quadruple-drug therapy. Full therapeutic doses of each of these two agents should be used to achieve optimal suppression of HIV replication.

Adult↗

Tertiary contacts of helix V in the lactose permease determined by site-directed chemical cross-linking in situ.

The six N-terminal transmembrane helices (N6) and the six C-terminal transmembrane helices (C6) in lactose permease, each containing a single Cys residue, were coexpressed, and cross-linking was studied. The proximity of paired Cys residues in helices V and VII, VIII, or X was studied by thiol-specific chemical cross-linking. The results demonstrate that Cys residues in the periplasmic half of helix V cross-link with Cys residues in the periplasmic half of helix VII. In contrast, no cross-linking is evident with paired Cys residues in the cytoplasmic halves of helices V and VII. Moreover, Cys residues on one entire face of helix V cross-link with Cys residues on one face of helix VIII. Finally, paired Cys residues at the cytoplasmic ends of helices V and X cross-link, but no cross-linking is observed when paired Cys residues are placed at the periplasmic ends of the two helices. Taken together, the results indicate that the periplasmic halves of helices V and VII are in close proximity and that the two helices tilt away from one another toward the cytoplasmic side of the membrane. Furthermore, helices V and VIII are in close proximity throughout their lengths and do not tilt appreciably with respect to one another, and helices V and X are in close proximity at the cytoplasmic but not at the periplasmic face of the membrane.

Amino Acid Substitution↗

Novel endotheliotropic herpesviruses fatal for Asian and African elephants.

A highly fatal hemorrhagic disease has been identified in 10 young Asian and African elephants at North American zoos. In the affected animals there was ultrastructural evidence for herpesvirus-like particles in endothelial cells of the heart, liver, and tongue. Consensus primer polymerase chain reaction combined with sequencing yielded molecular evidence that confirmed the presence of two novel but related herpesviruses associated with the disease, one in Asian elephants and another in African elephants. Otherwise healthy African elephants with external herpetic lesions yielded herpesvirus sequences identical to that found in Asian elephants with endothelial disease. This finding suggests that the Asian elephant deaths were caused by cross-species infection with a herpesvirus that is naturally latent in, but normally not lethal to, African elephants. A reciprocal relationship may exist for the African elephant disease.

Africa↗

Site-directed chemical cross-linking demonstrates that helix IV is close to helices VII and XI in the lactose permease.

The N-terminal six transmenbrane helices (N6) and the C-terminal six transmembrane helices (C6) of the lactose permease, each containing a single-Cys residue, were coexpressed, and proximity was studied. Paired Cys residues in helices IV (positions 114, 116, 119, 122, 125, or 129) and VII (227, 231, 232, 234, 235, 238, 239, 242, 243, 245, or 246) or XI (350, 353, 354, 357, 361, or 364) were tested for cross-linking in the presence of two rigid homobifunctional thiol-specific cross-linkers, N,N'-o-phenylenedimaleimide (o-PDM; 6 A) and N,N'-p-phenylenedimaleimide (p-PDM; 10 A). Cys residues in the middle of helix IV (position 119 or 122) cross-link to Cys residues in the middle of helix VII (position 238, 239, 242, or 243). In contrast, no cross-linking is evident with paired Cys residues at either end of helix IV (position 114, 116, 125, or 129) or helix VII (position 227, 231, 232, 234, 235, 245, or 246). On the other hand, Cys residues in the cytoplasmic half of helix IV (position 125 or 129) cross-link with Cys residues in the cytoplasmic half of helix XI (position 350, 353, or 354), while paired Cys residues at the periplasmic ends of the two helices do not cross-link. The results indicate that helices IV and VII cross in a scissors-like manner with the cytoplasmic end of helix IV tilting toward helix XI.

Amino Acid Sequence↗