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Biomedical subjects

R King

Publications and source records attributed to R King.

At least 73 records · Page 4Linked to original sources

Thin melanomas.

Thin melanoma refers to that grouping of melanomas that statistically have a good prognosis and survival rate. A small but significant percentage of these lesions metastasize and cause mortality. Histologically, these lesions comprise a diverse grouping of tumors of any intraepidermal growth pattern; in the radial or vertical growth phase; or in anatomic level I, II, III, or IV. Additional histologic findings may also be variably present, such as regression, tumor infiltrating lymphocytes, and mitoses. Molecular studies suggest that thin melanomas may have different properties to thicker and metastatic melanomas. The factors governing the ability of thin melanomas to metastasize and cause mortality are not known. Certain histologic and molecular parameters, some of which have been alluded to previously, may provide clues to understanding the parameters governing the aggressive nature of some of these lesions. Further research is required to enhance our understanding of thin melanomas.

Disease Progression↗

Antibodies reactive with Ehrlichia canis, Ehrlichia phagocytophila genogroup antigens and the spotted fever group rickettsial antigens, in free-ranging jackals (Canis aureus syriacus) from Israel.

A seroepidemiological survey was conducted to investigate the prevalence of antibodies reactive with the Ehrlichia canis and Ehrlichia phagocytophila genogroup antigens, and the spotted fever group (SFG) rickettsiae antigens in jackals in Israel (Canis aureus syriacus), to assess the possible role of the jackal in the epidemiology of these diseases. Fifty-three serum samples from jackals were assayed by the indirect immunofluorescence antibody test. Antibodies to E. canis were detected in 35.8% serum samples while 26.4% of the samples tested were positive to Ehrlichia chaffeensis. Twenty-six percent of the jackals tested were seropositive to E. phagocytophila, of which 5.7% were seropositive to E. phagocytophila alone without any seroreactivity to either E. canis or E. chaffeensis. Fifty-five percent of the jackals were seropositive to the SFG-rickettsiae antigens. The results suggest a high exposure rate of jackals in Israel to E. canis. Positive reactivity to E. chaffeensis was considered to be due to antigenic cross-reactions with E. canis. The study demonstrated for the first time the presence of E. phagocytophila antibodies in free-range jackals. The high incidence of antibodies to the SFG-rickettsiae and their relatively high antibody titers was suggestive of either recent or persistent infection. The possibility that jackals may play a role in the transmission of E. canis, E. phagocytophila and the SFG-rickettsiae for human and canine infections is discussed.

Animals↗

Microphthalmia transcription factor. A sensitive and specific melanocyte marker for MelanomaDiagnosis.

Malignant melanomas do not uniformly retain expression of melanocytic gene products-an observation associated with diagnostic dilemmas. Microphthalmia transcription factor (Mitf) is a melanocytic nuclear protein critical for the embryonic development and postnatal viability of melanocytes. It serves as a master regulator in modulating extracellular signals, such as those triggered by alpha-MSH and c-Kit ligand. Because of its central role in melanocyte survival and to assess its potential use as a histopathological marker for melanoma, Mitf expression was examined in histologically confirmed human melanoma specimens. Western blot analysis of melanoma cell lines revealed consistent expression of two Mitf protein isoforms differing by MAP kinase-mediated phosphorylation. In a series of 76 consecutive human melanoma surgical specimens, 100% stained positively for Mitf with a nuclear pattern of reactivity. In a side-by-side comparison, Mitf staining was positive in melanomas that failed to stain for either HMB-45 or S-100, the most common currently used melanoma markers. Of 60 non-melanoma tumors, none displayed nuclear Mitf staining and two displayed cytoplasmic staining. Although Mitf does not distinguish benign from malignant melanocytic lesions, for invasive neoplasms it appears to be a highly sensitive and specific histopathological melanocyte marker for melanoma.

Animals↗

Cat scratch disease: posterior segment manifestations.

OBJECTIVE: To evaluate the posterior segment findings seen in ocular cat scratch disease. DESIGN: Retrospective case series. PARTICIPANTS: There were 24 patients (35 eyes) with choroidal, retinal, or optic disc manifestations of Bartonella infection evaluated at the authors' institutions over a 6-year period. MAIN OUTCOME MEASURES: Clinical and photographic records were reviewed for evidence of disc edema, macular star, foci of retinitis or choroiditis, choroidal masses, optic nerve masses, vascular-occlusive events, or other findings. RESULTS: Discrete white retinal or choroidal lesions, 50 to 3000 microm in diameter, were the most common posterior segment findings in this series of patients (83% of eyes, 83% of patients). Optic disc swelling was the second most common finding (46% of eyes, 63% of patients) followed by a macular star (43% of eyes, 63% of patients). Vascular-occlusive events were also seen (14% of eyes, 21% of patients), and the site of occlusion was found to be intimately associated with the aforementioned retinal lesions. Final visual acuity was 20/25 or better in 26 (74%) of 35 eyes and was similar in both treated and untreated patients. CONCLUSION: Isolated foci of retinitis or choroiditis were the most common ocular manifestation of cat scratch disease in the authors' patient population, but an array of posterior segment findings may occur.

Adolescent↗

In vivo demonstration of noninvasive thermal surgery of the liver and kidney using an ultrasonic phased array.

A 256-element, continuous-wave ultrasonic phased array has been used to thermally coagulate deep-seated liver and kidney tissue. The array elements were formed on a 1-3 piezocomposite bowl with a 10-cm radius of curvature and 12-cm diameter. The 0.65 x 0.65 cm2 projection elements were driven at 1.1 MHz by a custom-built amplifier system. A series of in vivo porcine experiments demonstrated the ability to coagulate liver and kidney tissue using the large-scale phased array. The temperature response of the treatment was guided and monitored using magnetic resonance (MR) images. Focal lesion volumes greater than 0.5 cm3 in kidney and 2 cm3 in liver were formed from a single 20-s sonication.

Animals↗

Long-term changes in intraocular pressure after clear corneal phacoemulsification: normal patients versus glaucoma suspect and glaucoma patients.

PURPOSE: To compare the effects of clear corneal phacoemulsification on intraocular pressure (IOP) in patients without glaucoma, glaucoma suspects, and patients with glaucoma. SETTING: Urban, multisubspecialty private practice. METHODS: A retrospective analysis of patients who had clear corneal phacoemulsification with a minimum of 12 months follow-up was performed. The patients were divided into 3 groups: no glaucoma (NG), glaucoma suspects (GS), and glaucoma (GG). None had a history of prior surgery. Glaucoma suspects included patients with elevated IOPs, abnormal discs, pseudoexfoliation syndrome, or pigment dispersion syndrome on no medications and with no field defects. Glaucoma patients had received only medical treatment. Two-tailed, homoscedastic t tests were used for statistical analysis. RESULTS: There were 143 patients (164 eyes) in the NG group, 65 (75) in the GS group, and 61 (71) in the GG group. The mean preoperative IOP was 16.42 mm Hg +/- 2.77 (SD), 17.59 +/- 4.15 mm Hg, and 16.97 +/- 4.86 mm Hg in the 3 groups, respectively. At 1 year, the mean IOP was lower in all groups: 14.37 +/- 2.97 mm Hg, 15.68 +/- 3.38 mm Hg, and 15.86 +/- 4.00 mm Hg, respectively. The change was statistically significant in the NG and GS groups. Glaucoma patients showed a statistically significant reduction in the number of glaucoma medications postoperatively. CONCLUSION: Clear corneal phacoemulsification was associated with a statistically significant long-term reduction in IOP.

Aged↗

Alzheimer's disease: correlation of the suppression of beta-amyloid peptide secretion from cultured cells with inhibition of the chymotrypsin-like activity of the proteasome.

Peptide aldehyde inhibitors of the chymotrypsin-like activity of the proteasome (CLIP) such as N-acetyl-Leu-Leu-Nle-H (or ALLN) have been shown previously to inhibit the secretion of beta-amyloid peptide (A beta) from cells. To evaluate more fully the role of the proteasome in this process, we have tested the effects on A beta formation of a much wider range of peptide-based inhibitors of CLIP than published previously. The inhibitors tested included several peptide boronates, some of which proved to be the most potent peptide-based inhibitors of beta-amyloid production reported so far. We found that the ability of the peptide aldehyde and boronate inhibitors to suppress A beta formation from cells correlated extremely well with their potency as CLIP inhibitors. Thus, we conclude that the proteasome may be involved either directly or indirectly in A beta formation.

Aldehydes↗

Marrow transplantation from unrelated donors for patients with severe aplastic anemia who have failed immunosuppressive therapy.

Allogeneic marrow transplantation offers curative therapy for patients with aplastic anemia. We analyzed retrospective results in 141 patients with severe aplastic anemia who received transplants between 1988 and 1995 from an unrelated volunteer donor identified through the National Marrow Donor Program (NMDP). All patients had failed one or more courses of immunosuppressive therapy. Of the patients, 121 (86%) received a radiation-containing conditioning regimen, and 20 (14%) were given chemotherapy only. Based on serologic human leukocyte antigen (HLA) typing (class I and II), 105 patients (74%) received HLA-matched marrow, and 36 (26%) received marrow mismatched for at least one HLA-A, -B, or -DR antigen. Allele-level (molecular) typing for HLA-DRB1 was available in 108 donor-recipient pairs; 77 patients received DRB -matched and 31 DRB1-mismatched transplants. All but 13% of patients were given a cyclosporine-containing regimen for graft-vs.-host disease (GVHD) prophylaxis, and 45 patients (32%) received marrow that was T cell-depleted. Among 131 evaluable patients, 116 (89%) achieved sustained engraftment and 15 (11%) did not. Among patients with engraftment, acute GVHD of grades II-IV developed in 60 patients (52%) and extensive chronic GVHD in 24 patients at risk (31%). Currently, 51 patients (36%) are surviving at 11-94 months (median 36) after transplantation. All but five have Karnofsky scores > or =80. Patients who received a serologically matched transplant fared somewhat better than did patients given a serologically mismatched transplant p = 0.03). Patients with donors matched by both serology and allele-level DRB1 typing had significantly better survival than DRB1-mismatched patients with 56 vs. 15% surviving at 3 years p = 0.001). Outcome in patients transplanted within 3 years of diagnosis was superior to that among patients transplanted with greater delay. Major causes of death were graft failure, GVHD, and infections. These data suggest that unrelated marrow transplantation offers successful therapy for a proportion of patients who have failed immunosuppressive therapy.

Adolescent↗

Evaluating herbal medicine for the management of Herpes zoster in human immunodeficiency virus-infected patients in Kampala, Uganda.

OBJECTIVE: This study was carried out to evaluate the potential effectiveness of herbal treatments used for herpes zoster (HZ) by a great number of people living with acquired immunodeficiency syndrome (PLWAs) in Uganda. SETTING: Kampala, Uganda. Clinics of indigenous traditional healers, at the Department of Medicine of Mulago Hospital, Makerere University, and at The AIDS Support Organization (TASO) Clinic, providing primary care to people living with HIV and AIDS. DESIGN, PATIENTS, AND PARTICIPANTS: Nonrandomized, nonplacebo controlled, observational study in two phases. Inclusion criteria included HIV seropositivity and a recent HZ attack. In phase 1, 52 patients were enrolled, treated, and followed for up to 3 months at three healers' clinics, and compared to 52 TASO Clinic controls receiving ambulatory care. Phase 2 was similar in design to phase 1, but lasted longer (6-month follow-up) and involved 154 hospital outpatients treated with herbal medicine and 55 TASO controls. In both phases, healer patients were given herbal treatment according to healers' prescriptions, while controls received either symptomatic treatment or acyclovir. RESULTS: Healer patients and controls experienced similar rates of resolution of their HZ attacks. Fewer healer patients than controls experienced superinfection in phase 1 (18% versus 42%, p < 0.02) and fewer healer patients showed keloid formation in either phase. This difference was not statistically significant. In both phases, zoster-associated pain resolved substantially faster among healer patients with a higher degree of significance in phase 2 where the progression of pain over time could be seen because of the longer follow-up (phase 1: maximum p value (pmax) < pmax < 0.02 at 1 month, pmax < 0.005 at 2 months, pmax < 0.0001 at 3 months). CONCLUSION: Herbal treatment is an important local and affordable primary care alternative for the management of HZ in HIV-infected patients in Uganda and similar settings.

Adolescent↗

Metastatic malignant melanoma resembling malignant peripheral nerve sheath tumor: report of 16 cases.

We report 16 cases of metastatic malignant melanoma presenting clinically as lymphadenopathy or a soft-tissue mass and histologically resembling malignant peripheral nerve sheath tumor (MPNST). In two cases, the metastatic malignant melanoma was preceded by a primary cutaneous malignant melanoma; in four cases, it presented synchronously with such a tumor; and in 10 cases, there was no evidence of a previous or concomitant malignant skin lesion. Histologically, the tumors were characterized by a malignant-appearing spindle cell proliferation arranged in fascicles, often accompanied by a peritheliomatous growth pattern, alternating hypercellular and hypocellular areas, numerous mitoses, and foci of necrosis. In nine cases, there was residual lymph node tissue. In none of the cases was there evidence of an anatomic connection with a nerve, a coexistent neurofibroma, or the stigmata of neurofibromatosis. Fourteen of the cases showed strong and generally diffuse immunoreactivity for S-100 protein, and five cases showed positivity for HMB-45. Four of eight patients with follow-up information died of the disease. Tumors with a microscopic appearance compatible with MPNST but showing strong diffuse S-100 protein staining and featuring remnants of lymph node may represent metastatic malignant melanomas and should elicit a search for a previous or concomitant tumor in the skin and other sites. The similarities these tumors share with MPNST are probably related to their common neuroectodermal histogenesis.

Adolescent↗

Can routine information systems be used to monitor serious disability?

OBJECTIVE: To determine whether reliable birth cohort prevalence rates of disabling conditions in early childhood can be obtained from child health information systems. DESIGN: Comparison of two sources of information on motor and sensory disabilities: from child health information systems held by health authorities, and a population register that uses multiple sources of ascertainment. SETTING: The counties of Oxfordshire, Buckinghamshire, and Northamptonshire. PARTICIPANTS: Children born to residents of the three counties between 1984 and 1989. RESULTS: Eight hundred and twenty children (6.0/1000 live births) were identified from the child health system as having one or more of the conditions, and 580 (4.2/1000 live births) were identified from the population register; however, only 284 children were identified by both sources. CONCLUSIONS: It is currently impossible to monitor trends in the prevalence rate of disabling disorders in childhood using the child health information systems. Agreement about ways of collecting, recording, and collating information on disability would be a useful step towards realising the full potential of these systems.

Cerebral Palsy↗

Atrial septal defects in Florida panthers.

Ostium secundum atrial septal defects (ASDs) were observed in six (3 M, 3 F) of 33 (20 M, 13 F) (18%) Florida panthers (Puma concolor coryi) necropsied by veterinary pathologists between 1985 and 1998. A seventh ASD was found in a female panther necropsied in the field and is included in the pathological description but not the prevalence of ASDs in Florida panthers. One panther (FP205) with severe ASD also had tricuspid valve dysplasia (TVD). Atrial septal defects and/or TVD are believed to have caused or contributed to the deaths of three (9%) Florida panthers in this study. Mean diameter +/- SD of ASDs was 9.0 +/- 4.7 mm (range 3 to 15 mm). Gross pathological changes attributed to ASDs/TVD in severely affected panthers (ASD > or = 10 mm) (n = 4) included mild right ventricular dilatation (n = 3) and hypertrophy (n = 2), mild to severe right atrial dilatation (n = 2), and acute pulmonary edema (n = 3). Panthers with mild ASDs (ASD < or = 5 mm) (n = 3) had no other detectable gross pathological changes associated with the ASDs. Histological examination of lungs of three panthers with severe ASDs revealed mild to moderate dilatation with fibrosis and smooth muscle atrophy of the tunica media of medium to large caliber arteries (n = 2), interstitial and/or pleural fibrosis (n = 2), perivascular fibrosis (n = 1), and acute to chronic edema (n = 3). Twenty-six necropsied panthers were examined one or more times while living; medical records were retrospectively evaluated. Antemortem radiographic, electrocardiographic, and echocardiographic examinations were performed on two panthers with severe ASDs (FP20 and FP205). Thoracic radiographic abnormalities in both included right heart enlargement, and in FP205 (severe ASD and TVD), mild pulmonary overperfusion. Electrocardiographic examination of FP205 revealed a right ventricular hypertrophy pattern, while FP205 had a normal electrocardiogram. Echocardiographic examination of FP20 revealed marked right atrial dilatation; a bubble contrast study indicated regurgitation across the tricuspid valve. Echocardiographic abnormalities in FP20 included right atrial and ventricular lilatation, atrial septal drop-out, and severe tricuspid regurgitation; non-selective angiography revealed significant left to right shunting across the ASD. All panthers with severe ASDs ausculted (n = 3) had systolic right or left-sided grade I-V/VI murmurs loudest at the heart base. All male panthers with ASDs (n = 3) (100%) and 9 of 17 (53%) male panthers without ASDs in this study were cryptorchid.

Animals↗

Volunteers as adjunct researchers in a cancer prevention trial: the American Cancer Society Colon Polyp Prevention Study.

BACKGROUND: In April 1991, the Virginia Division of the American Cancer Society (ACS) initiated the feasibility phase of the Colon Polyp Prevention Study (CPPS) to determine whether a high fiber supplement would decrease new adenomatous colorectal polyp occurrence. The feasibility phase had two specific objectives: 1) to evaluate accrual and compliance to the designed protocol and 2) to evaluate and demonstrate the effectiveness of volunteers as research assistants. The CPPS is an innovative project in which trained volunteers play a significant role in the research process. METHODS: In the CPPS, volunteer adjunct researchers (VARs) were trained to perform individual dietary data collection and intervention and other general study monitoring functions. VARs were trained, certified, and monitored in the performance of their assigned tasks by ACS staff and expert consultants. RESULTS: A total of 119 volunteers were trained as VARs, 74 of whom were certified and matched to a study participant. Between 1991-1995, only six VARs left the study. After active accrual of participants to the study ceased in 1995, 38 VARs (50% of the certified VARs) continued to monitor the active study participants. All VARs were consistently able to conduct the functions for which they were trained. CONCLUSIONS: In spite of expected volunteer attrition rates, a core of 38 dedicated VARs were matched to 72 participants and demonstrated the ability to perform selected data collecting activities on a consistent and efficient basis. The use of trained volunteers has allowed the CPPS to function in its feasibility phase at personnel cost considerably less than that of other similar cancer prevention trials.

American Cancer Society↗

Diverse paths: the elderly British in Tuscany.

"This paper investigates the life, migration and retirement experiences of elderly British residents of Tuscany and its adjacent districts.... Many pathways have led the elderly British to Tuscany; only a minority have simply migrated from the UK on retirement.... Key themes explored include class background, reasons for migration to Tuscany, previous connections to Italy, post-retirement behaviour, integration and future plans. The findings challenge some commonly-held ¿expectations' about the nature of retirement migration."

Acculturation↗

International retirement migration in Europe.

"This paper presents a review and prospectus of international retirement migration (IRM), dealing mainly with European evidence but also referring to some analogous trends in North America. The paper is in three main parts. It first makes the case for regarding IRM as a significant aspect of population geography and of migration studies; in certain areas of Mediterranean Europe, IRM also has effects on regional economic geography. The second section of the paper discusses some of the early findings from a comparative study of British elderly residents in Tuscany, Malta, the Costa del Sol and the Algarve.... The final part of the article offers further reflections on why IRM is important--for the individual migrants themselves, for the host communities, and for public policy."

Adult↗