Mortality in red squirrels (Sciurus vulgaris) associated with exudative dermatitis.

Red squirrels (Sciurus vulgaris) found dead or dying on the Isle of Wight and the island of Jersey were suffering from exudative, ulcerative dermatitis and superficial staphylococcal pyoderma. The principal gross lesions were on the lips, eyelids and feet and showed similarities to those of squirrelpox. The histopathological lesions were also similar and, although there was no ballooning degeneration of epidermal cells, intracytoplasmic inclusions resembling those seen in poxvirus infections were present. Examination of lesions by electron microscopy failed to identify any virions, and PCR analysis for squirrelpox virus proved negative. The skin lesions also resembled those of mange, but although numerous mites were present in the fur these were mostly Dermacarus sciurinus with small numbers of Metalistrophorus pagenstecheri. The occurrence of these species on red squirrels in Britain is confirmed, but neither is pathogenic and they were not considered to have been involved in the pathogenesis of the dermatitis, the primary cause of which was not established.

Mechanical testing of the wire clamping characteristics of the Fixclip internal fixation system.

Stainless steel wires (Kirschner's wires) have been used for over 60 years to fix internally a wide range of osteotomies and fractures in bones. Fixclips (Corifix, Cirencester, UK) shaped like winged washers have been used to clamp pairs of K wires of diameters ranging from 0.8 to 3.0 mm to standard orthopaedic screws and to fix bones internally in more than 400 patients. The system has proved to be biologically and mechanically very effective. This paper describes the design and some biomechanical test results of the Fixclip. Preliminary strength tests conducted using a Hounsfield Tensometer show that the pull-out force, reflecting the grip of the clip on the wire, is dependent on the wire size and, throughout the clinically relevant range, increases linearly with increasing screw torque. Changing the surface finish of the clip did not confer any advantage over the existing polished clip in terms of grip strength.

Longitudinal study of effects of alcohol use and/or personal exercise on high density lipoprotein cholesterol in aging humans.

Self-controlled alcohol use and/or personal physical exercise is generally believed to be advantageous in extending good health in aging humans. We investigated whether data collected over 31 years in the same subjects (369 men, 75 women) in our Longitudinal Aging Study of humans (1969-2000) showed strong relationship between alcohol and/or physical exercise with High Density Lipoprotein Cholesterol (HDLC). Women s HDLC interactions among age, diet, alcohol use and/or exercise were not found to be statistically significant in our study. Men, however, showed a strong positive statistical significance (p

FixclipsTM - biological internal fixator for upper femoral osteotomies in cerebral palsy.

We describe the technique and results of 63 proximal femoral osteotomies in 39 cerebral palsy patients performed with the Fixclip (Corifix, Cirencester, UK) internal fixator system. Post-operative splintage was determined by soft tissue requirements and not to protect the femoral osteotomy. Three patients needed revision surgery for readjustment of the device and two patients had superficial infections. All osteotomies except one healed by 12-16 weeks. There were no mal-unions, or avascular necrosis. One patient had a non-union that united after revision surgery. The Fixclip system is modular and easily adjustable. The fixation, sitting just off the bone, is less disturbing to the periosteal blood supply and lateralises the fixation, like a wave plate, to load both the medial and lateral femoral cortices on weight-bearing. Compared to the other available fixation implants, Fixclips are biologically and mechanically very effective and well suited in cerebral palsy patients where rigid fixation with a plate can cause extensive loss of bone mass. (Hip International 2002; 12: 314-9).

Randomized, placebo-controlled, double-blind clinical trial of sertraline in the treatment of depression complicating Alzheimer's disease: initial results from the Depression in Alzheimer's Disease study.

OBJECTIVE: This study evaluated the efficacy and safety of sertraline in the treatment of major depression in 22 outpatients with Alzheimer's disease. METHOD: Twelve of the 22 patients were given sertraline and 10 were given placebo by random group assignment for 12 weeks. Response to treatment was measured by using the Cornell Scale for Depression in Dementia. The patients were also assessed with the Hamilton Depression Rating Scale, the activities of daily living subscale of the Psychogeriatric Dependency Rating Scales, and the Mini-Mental State. RESULTS: After 12 weeks of double-blind, placebo-controlled treatment, nine of the patients given sertraline and two of those given placebo were at least partial responders. Patients given sertraline had significantly greater mean declines from baseline in Cornell Scale for Depression in Dementia scores; the bulk of antidepressant response occurred by the third week of treatment. CONCLUSIONS: Sertraline is superior to placebo in reducing depression in patients with Alzheimer's disease who also suffer from major depression.

Extended use of the k wire and the orthopaedic screw: the fixclip project.

The results of the first 280 fixations with the Fixclip systems are reported. The intended advantages of increased fixation accuracy and versatility have been realised. Two hundred and fifty four fixations have been followed-up to union; there have been three deep infections, two persistent non-unions, and 12 fixation failures requiring revision. A range of sizes has allowed use of the system with screws from the small and basic fragment sets with wires from 1.2 to 3 mm diameter. Its use in the management of paediatric conditions, intra-articular fractures, fractures in osteoporotic bone and as a blade plate substitute are illustrated. Its potential as a biologically and mechanically effective means of bone fixation is discussed.

The crystal structure of bacillus cereus phosphonoacetaldehyde hydrolase: insight into catalysis of phosphorus bond cleavage and catalytic diversification within the HAD enzyme superfamily.

Phosphonoacetaldehyde hydrolase (phosphonatase) catalyzes the hydrolysis of phosphonoacetaldehyde to acetaldehyde and phosphate using Mg(II) as cofactor. The reaction proceeds via a novel bicovalent catalytic mechanism in which an active-site nucleophile abstracts the phosphoryl group from the Schiff-base intermediate formed from Lys53 and phosphonoacetaldehyde. In this study, the X-ray crystal structure of the Bacillus cereus phosphonatase homodimer complexed with the phosphate (product) analogue tungstate (K(i) = 50 microM) and the Mg(II) cofactor was determined to 3.0 A resolution with an R(cryst) = 0.248 and R(free) = 0.284. Each monomer is made up of an alpha/beta core domain consisting of a centrally located six-stranded parallel beta-sheet surrounded by six alpha-helices. Two flexible, solvated linkers connect to a small cap domain (residues 21-99) that consists of an antiparallel, five-helix bundle. The subunit-subunit interface, formed by the symmetrical packing of the two alpha8 helices from the respective core domains, is stabilized through the hydrophobic effect derived from the desolvation of paired Met171, Trp164, Tyr162, Tyr167, and Tyr176 side chains. The active site is located at the domain-domain interface of each subunit. The Schiff base forming Lys53 is positioned on the cap domain while tungstate and Mg(II) are bound to the core domain. Mg(II) ligands include two oxygens of the tungstate ligand, one oxygen of the carboxylates of Asp12 and Asp186, the backbone carbonyl oxygen of Ala14, and a water that forms a hydrogen bond with the carboxylate of Asp190 and Thr187. The guanidinium group of Arg160 binds tungstate and the proposed nucleophile Asp12, which is suitably positioned for in-line attack at the tungsten atom. The side chains of the core domain residue Tyr128 and the cap domain residues Cys22 and Lys53 are located nearby. The identity of Asp12 as the active-site nucleophile was further evidenced by the observed removal of catalytic activity resulting from Asp12Ala substitution. The similarity of backbone folds observed in phosphonatase and the 2-haloacid dehalogenase of the HAD enzyme superfamily indicated common ancestry. Superposition of the two structures revealed a conserved active-site scaffold having distinct catalytic stations. Analysis of the usage of polar amino acid residues at these stations by the dehalogenases, phosphonatases, phosphatases, and phosphomutases of the HAD superfamily suggests possible ways in which the active site of an ancient enzyme ancestor might have been diversified for catalysis of C-X, P-C, and P-O bond cleavage reactions.

Delusions and hallucinations in Alzheimer's disease: prevalence and clinical correlates.

OBJECTIVES: The purpose of this study was to examine the frequency of delusions and hallucinations in patients with Alzheimer's disease (AD) and to investigate factors associated with each or the combination of the two. DESIGN: This was a cross-sectional, case-control study. SETTING: Neuropsychiatry and Memory Group, The Johns Hopkins University, USA. PARTICIPANTS: Three hundred and forty-two community-residing patients with probable AD according to NINCDS/ADRDA criteria were included in the study. MEASURES: Patients were assessed clinically for the presence of psychotic symptoms using the DSM-IV glossary definitions. The patients were also rated on standardized measures of cognitive impairment, depression, extrapyramidal symptoms, functional impairment and general health. RESULTS: Seventy-five (22%) AD patients had delusions only, nine (3%) had hallucinations only and 30 (9%) had both delusions and hallucinations. Hallucinations were associated with less education, African-American race, more severe dementia, longer duration of illness, falls and use of anxiolytics. Delusions were associated with older age, depression, aggression, poor general health and use of antihypertensives. Patients with both delusions and hallucinations were similar to the patients with delusions only. CONCLUSIONS: This study confirms the high prevalence of psychotic symptoms in AD patients encountered in clinical practice and suggests that individual psychotic symptoms have different associations.

Crystallization and preliminary crystallographic analysis of phosphonoacetaldehyde hydrolase.

Phosphonoacetaldehyde hydrolase, a C-P bond-cleaving enzyme which utilizes an unusual bicovalent catalytic strategy, has been crystallized by the hanging-drop vapor-diffusion method using PEG 4000 as the precipitant. The crystals belong to the monoclinic system and belong to space group C2, with unit-cell parameters a = 210.5, b = 45.5, c = 64.7 A, beta = 105.0 degrees. The asymmetric unit contains a dimer related by a non-crystallographic dyad. In addition to a 2.7 A native data set, the following data sets have been collected: a 2.4 A data set from crystals complexed with the intermediate analog vinyl sulfonate, a 3.0 A three-wavelength MAD data set from crystals complexed with the product analog WO(4)(2-), as well as several heavy-atom data sets to 3.0 A or better, of which only three have proven useful for MIR calculations. Examination of the native Patterson map revealed NCS that made previously uninterpretable derivative data useful. Independent phase sets were first calculated and refined for the MAD and MIR experiments separately and were then combined. The combined phase set was further improved by solvent flattening, histogram matching and NCS averaging. Interpretation of the resulting electron-density map is currently under way.

Two new species of larval mites (Acari: Trombidioidea: Microtrombidiidae and Johnstonianidae) parasitising Culicoides impunctatus, the highland midge (Insecta: Ceratopogonidae), in Scotland.

The larval stage of the trombidioid mites Parafeiderium stuarti n. sp. (family Microtrombidiidae Thor, 1935) and Centrotrombidium blackwellae n. sp. (family Johnstonianidae Newell, 1957) are described. Both species were found parasitising Culicoides impunctatus Goetghebuer, the highland midge (Diptera: Ceratopogonidae), in Scotland. A revised diagnosis for Parafeiderium Vercammen-Grandjean & Cochrane, 1974 and a key to the world species of larval Centrotrombidium Kramer, 1896 are given.

Isolation of Mycoplasma species from a patient with seal finger.

The etiologic agent of seal finger (speck finger) is unknown. Seal finger occurs after a seal bite, and the symptoms include acute pain, swelling, discharge, and, in some cases, there is joint involvement. The discovery of Mycoplasma species in epidemics of seal disease prompted attempts to link seal finger to mycoplasma. Mycoplasma species were isolated in cultures of a specimen from the finger of an aquarium trainer who was bitten by a seal and of a specimen from the front teeth of the biting seal. The two Mycoplasma isolates were identical biochemically; they were serum-dependent and hydrolyzed arginine. The isolates were susceptible to tetracycline but resistant to erythromycin. By growth inhibition and immunofluorescent antibody tests, both strains were identified as Mycoplasma phocacerebrale, a mycoplasma isolated in an epidemic of seal disease occurring in the Baltic Sea. The patient's infection was treated successfully with tetracycline. To our knowledge, this is the first case in which a mycoplasma has been associated with seal finger.

Curriculum revision: reaching faculty consensus through the Nominal Group Technique.

A fundamental concept to initiate change in the curriculum revision process is to overcome resistance to change and the boundaries of self-interest. Curriculum change cannot occur without an "unfreezing" of faculty values and interests. The Nominal Group Technique (NGT) was used to facilitate faculty identification of areas needing change in the undergraduate nursing curriculum. The process led to the generation of numerous independent ideas in which all faculty participated. The revised curriculum which resulted from the NGT process has had full and enthusiastic support of the faculty.

Treatment of experimental Staphylococcus epidermidis endophthalmitis with oral trovafloxacin.

PURPOSE: To investigate the ocular pharmacokinetics and efficacy of oral trovafloxacin, a novel fluoroquinolone antibiotic, in Staphylococcus epidermidis endophthalmitis. METHODS: Albino rabbits (n = 20) were infected with an intravitreal inoculum of S epidermidis (1.0 x 10(8) colony-forming units [CFU/0.1 ml) and 24 hours later received a single oral dose of trovafloxacin (250 mg/kg). Serum and intraocular samples from infected and control (noninfected) eyes were obtained up to 24 hours after antibiotic administration for measurement of trovafloxacin levels. A second group of rabbits (n = 72) was infected intraocularly and randomized 24 hours later to oral trovafloxacin (250 mg/kg twice a day) for 6 days or no treatment (control). Treatment efficacy was assessed by vitreous culture, clinical examination, and histopathology. RESULTS: Following a single dose of trovafloxacin, maximal vitreous levels were achieved at 8 hours in infected eyes, with a penetration ratio of 36%. Vitreous levels were greater than 15 times the minimum inhibitory concentration of the strain employed. In animals with established endophthalmitis, treated eyes were sterilized after 5 days (P = .0495) compared with control eyes, which autosterilized at 14 days. Clinical and histologic examination revealed significant amelioration of anterior segment inflammation in treated eyes, although severe destruction of posterior segment structures occurred in both groups after 6 days of therapy. CONCLUSIONS: These data support trovafloxacin as a potential oral agent for treatment or prophylaxis of S epidermidis endophthalmitis, although retinal alterations that occur over the period required for vitreous sterilization suggest that it will not replace intravitreal therapy in established endophthalmitis.

Insights into the mechanism of catalysis by the P-C bond-cleaving enzyme phosphonoacetaldehyde hydrolase derived from gene sequence analysis and mutagenesis.

Phosphonoacetaldehyde hydrolase (phosphonatase) catalyzes the hydrolysis of phosphonoacetaldehyde to acetaldehyde and inorganic phosphate. In this study, the genes encoding phosphonatase in Bacillus cereus and in Salmonella typhimurium were cloned for high-level expression in Escherichia coli. The kinetic properties of the purified, recombinant phosphonatases were determined. The Schiff base mechanism known to operate in the B. cereus enzyme was verified for the S. typhimurium enzyme by phosphonoacetaldehyde-sodium borohydride-induced inactivation and by site-directed mutagenesis of the catalytic lysine 53. The protein sequence inferred from the B. cereus phosphonatase gene was determined, and this sequence was used along with that from the S. typhimurium phosphonatase gene sequence to search the primary sequence databases for possible structural homologues. We found that phosphonatase belongs to a novel family of hydrolases which appear to use a highly conserved active site aspartate residue in covalent catalysis. On the basis of this finding and the known stereochemical course of phosphonatase-catalyzed hydrolysis at phosphorus (retention), we propose a mechanism which involves Schiff base formation with lysine 53 followed by phosphoryl transfer to aspartate (at position 11 in the S. typhimurium enzyme and position 12 in the B. cereusphosphonatase) and last hydrolysis at the imine C(1) and acyl phosphate phosphorus.

Distribution of Borrelia burgdorferi s.l. spirochaete DNA in British ticks (Argasidae and Ixodidae) since the 19th century, assessed by PCR.

The distribution of Borrelia burgdorferi sensu lato, the Lyme borreliosis agent, was surveyed in British ticks in the collection of the Natural History Museum, London. Alcohol-preserved specimens of eight species of ticks known to attack humans were studied: Ixodes ricinus, I. hexagonus, I. uriae, I. trianguliceps, Dermacentor reticulatus, Haemaphysalis punctata, Rhipicephalus sanguineus and Argas vespertilionis. The sample comprised all life stages and originated from a wide range of host species, collection dates (1896-1994) and geographical localities in England, Scotland and Wales. Borrelia burgdorferi s.l. DNA, detected by a polymerase chain reaction that targeted the outer surface protein A gene, was found in all eight species. The overall proportion of PCR-positive specimens ranged from 7.8% for I. hexagonus (mostly from mustelids and hedgehogs) to 98.3% for I. uriae (mostly from seabirds). Borrelia burgdorferi s.l. DNA was found for the first time in the bat parasite A. vespertilionis (85.3%). The spirochaete is newly recorded in British populations of I. trianguliceps (97.4%, mostly from voles, mice and shrews), D. reticulatus (12.5% from dog and man) and R. sanguineus (30% from dogs and human dwellings). Of the four tick species with larvae available for testing, examples of I. ricinus, I. uriae and A. vespertilionis were PCR positive, as were significantly more nymphs than adults of I. ricinus, I. hexagonus and A. vespertilionis. Analyses showed that B. burgdorferi s.l. has been consistently present in British tick populations since at least 1897. Ticks positive for B. burgdorferi s.l. DNA were collected in all months of the year, throughout Britain, and were found on a wide range of mammal and bird species. PCR positivity does not prove vector or reservoir competence, but the use of archived material has demonstrated an extensive range of host-tick relationships involving B. burgdorferi s.l. in Britain for > 100 years.

Blebitis, early endophthalmitis, and late endophthalmitis after glaucoma-filtering surgery.

PURPOSE: The differentiating characteristics in blebitis and early and late endophthalmitis after glaucoma filtration surgery are reviewed. METHODS: All admission records and operative reports, as well as available office notes, on patients with blebitis or bleb-associated endophthalmitis admitted to a large referral eye center from 1985 to 1995 were reviewed retrospectively. RESULTS: Ten cases of blebitis and 33 cases of bleb-associated endophthalmitis were identified. One patient with blebitis progressed to culture-positive endophthalmitis. Of the 33 cases of bleb-associated endophthalmitis, there were 6 cases of early endophthalmitis (before postoperative week 6) and 27 cases of late endophthalmitis. In early endophthalmitis, Staphylococcus epidermidis was isolated on vitreous culture in 4 (67%) of 6 cases, whereas in late endophthalmitis, this organism was isolated in only 1 (4%) of 27 cases. In the 27 late cases, Streptococcus species and gram-negative organisms comprised 48% of isolates; of 33 cases of endophthalmitis, 15 (45%) demonstrated no growth on vitreous culture. Patients with endophthalmitis fared more poorly than those with blebitis in terms of visual outcome. CONCLUSIONS: Because blebitis may be prodromal to endophthalmitis, aggressive antimicrobial therapy, perhaps with oral quinolones, is warranted. In addition, patients with blebitis should be observed closely to identify extension into the vitreous cavity so that intravitreous antibiotics can be administered in a timely fashion. Finally, clinicians should not extrapolate the results of the Endophthalmitis Vitrectomy Study to the postfiltration surgery endophthalmitis given the differing pathogenesis and unique spectrum of organisms.

Observations on the mite fauna associated with adult Stomoxys calcitrans in the U.K.

Adult females of the blood-sucking muscid Stomoxys calcitrans sampled between June and September 1993 from a cattle farm (n = 839) and from a pig farm (n = 542) in North-West England were examined for mites. Twelve species of mites from ten families and three orders were identified as follows. In the Prostigmata, Eryenetes sp., Family Ereynetidae and Pediculaster mesembrinae, Family Pygmephoridae. In the Astigmata, Procalvolia zacheri Family Saproglyphidae, Acarus farris, Family Acaridae, Bonomoia sphaerocerae and Myianoetus sp., Family Anoetidae. In the Mesostigmata, Macrocheles muscaedomesticae and Macrocheles subbadius Family Macrochelidae, Digamasellus sp., Family Digamasellidae, Halolaelaps sp., Family Halolaelapidae. Prodinychus sp., Family Uropodoidea and Thinoseius sp., Family Eviphididae. Mean infestation rates at the two sites (all mite species) for the entire sampling period were 31.6 +/- 13.9% and 19.8 +/- 3.6% respectively. 51% of synbovine flies sampled in July were infested with mites. Mean numbers of flies infested in August at both farms were significantly lower compared to other months. The presence of tritonymphs of Ereynetes sp. on S. calcitrans demonstrates for the first time that this life cycle stage is naturally associated with insects in the field. All mites were recovered from the ventral thorax and abdomen, and two or more species commonly infested individual flies. Associations of mites with their dipteran hosts are described and discussed.

Implication of pneumolysin as a virulence factor in Streptococcus pneumoniae endophthalmitis.

PURPOSE: To determine if pneumolysin, a multifunctional cytotoxin produced by Streptococcus pneumoniae, may be a virulence determinant in the pathogenesis of pneumococcal endophthalmitis. METHODS: Lewis rats (n = 20) were injected intravitreally with purified recombinant pneumolysin at the following doses; 3.9 hemolytic units (HU), 39 HU, 390 HU, 3.9 x 10(3) HU, and 3.9 x 10(4) HU. After 24 hours, eyes were examined clinically and enucleated for histopathologic examination to elucidate the dose-response relationship. To determine the temporal progression of the disease model, a second group of rats (n = 8) were injected intravitreally with 390 HU of pneumolysin. At 6 and 48 hours, eyes were examined clinically and enucleated for histopathology. RESULTS: Eyes injected with pneumolysin demonstrated increasing anterior and posterior segment inflammation in response to increasing doses of administered toxin. The onset of inflammation and tissue damage occurred rapidly, and was maximal at 24 to 48 hours. The clinical and histopathologic changes observed mimicked those of S. pneumoniae endophthalmitis. Histopathologic analysis demonstrated rapid onset of iridocyclitis and vitritis with polymorphonuclear leukocyte influx, inner retinal necrosis, and retinal detachment. Retinal pigment epithelial necrosis and choroiditis were noted at the highest doses administered. Inflamed eyes were shown to be sterile. CONCLUSIONS: Pneumolysin injected intravitreally induces many of the clinical and histopathologic features of pneumococcal endophthalmitis, and may play an important role in the inflammation and tissue damage that occurs in pneumococcal endophthalmitis.