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Biomedical subjects

P Jarrett

Publications and source records attributed to P Jarrett.

At least 19 recordsLinked to original sources

Subcutaneous panniculitic T-cell lymphoma and cytophagic histiocytic panniculitis.

A 43-year-old Maori man presented with a 1 month history of malaise, weight loss, anorexia, arthralgia, recurrent fever and tender erythematous subcutaneous skin lesions. Histological examination of an incisional biopsy of a lesion revealed a lobular panniculitis with an inflammatory infiltrate of atypical lymphocytes and evidence of cytophagocytosis consistent with a diagnosis of subcutaneous T-cell lymphoma. The systemic symptoms and skin lesions resolved spontaneously within 3 weeks, only to recur 2 months later, requiring treatment with oral prednisolone. T-cell gene rearrangement studies demonstrated a monoclonal T-cell receptor (gamma-chain) gene rearrangement, further supporting the diagnosis of subcutaneous panniculitic T-cell lymphoma. Treatment with chemotherapy (cyclophosphamide, doxorubicin, vincristine and prednisone) led to remission of symptoms. Four months after completing chemotherapy, the patient remained asymptomatic with a few indurated subcutaneous plaques on the chest. Biopsy of these areas revealed lobular panniculitis, lymphocytic infiltrate without cytological atypia, abundant lipophages and fibrosis and sclerosis consistent with a healing response. He remains well 24 months following chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

Sequence analysis of insecticidal genes from Xenorhabdus nematophilus PMFI296.

Three strains of Xenorhabdus nematophilus showed insecticidal activity when fed to Pieris brassicae (cabbage white butterfly) larvae. From one of these strains (X. nematophilus PMFI296) a cosmid genome library was prepared in Escherichia coli and screened for oral insecticidal activity. Two overlapping cosmid clones were shown to encode insecticidal proteins, which had activity when expressed in E. coli (50% lethal concentration [LC(50)] of 2 to 6 microg of total protein/g of diet). The complete sequence of one cosmid (cHRIM1) was obtained. On cHRIM1, five genes (xptA1, -A2, -B1, -C1, and -D1) showed homology with up to 49% identity to insecticidal toxins identified in Photorhabdus luminescens, and also a smaller gene (chi) showed homology to a putative chitinase gene (38% identity). Transposon mutagenesis of the cosmid insert indicated that the genes xptA2, xptD1, and chi were not important for the expression of insecticidal activity toward P. brassicae. One gene (xptA1) was found to be central for the expression of activity, and the genes xptB1 and xptC1 were needed for full activity. The location of these genes together on the chromosome and therefore present on a single cosmid insert probably accounted for the detection of insecticidal activity in this E. coli clone. Although multiple genes may be needed for full activity, E. coli cells expressing the xptA1 gene from the bacteriophage lambda P(L) promoter were shown to have insecticidal activity (LC(50) of 112 microg of total protein/g of diet). This is contrary to the toxin genes identified in P. luminescens, which were not insecticidal when expressed individually in E. coli. High-level gene expression and the use of a sensitive insect may have aided in the detection of insecticidal activity in the E. coli clone expressing xptA1. The location of these toxin genes and the chitinase gene and the presence of mobile elements (insertion sequence) and tRNA genes on cHRIM1 indicates that this region of DNA represents a pathogenicity island on the genome of X. nematophilus PMFI296.

Animals↗

Role of proteolysis in determining potency of Bacillus thuringiensis Cry1Ac delta-endotoxin.

Bacillus thuringiensis protein delta-endotoxins are toxic to a variety of different insect species. Larvicidal potency depends on the completion of a number of steps in the mode of action of the toxin. Here, we investigated the role of proteolytic processing in determining the potency of the B. thuringiensis Cry1Ac delta-endotoxin towards Pieris brassicae (family: Pieridae) and Mamestra brassicae (family: Noctuidae). In bioassays, Cry1Ac was over 2,000 times more active against P. brassicae than against M. brassicae larvae. Using gut juice purified from both insects, we processed Cry1Ac to soluble forms that had the same N terminus and the same apparent molecular weight. However, extended proteolysis of Cry1Ac in vitro with proteases from both insects resulted in the formation of an insoluble aggregate. With proteases from P. brassicae, the Cry1Ac-susceptible insect, Cry1Ac was processed to an insoluble product with a molecular mass of approximately 56 kDa, whereas proteases from M. brassicae, the non-susceptible insect, generated products with molecular masses of approximately 58, approximately 40, and approximately 20 kDa. N-terminal sequencing of the insoluble products revealed that both insects cleaved Cry1Ac within domain I, but M. brassicae proteases also cleaved the toxin at Arg423 in domain II. A similar pattern of processing was observed in vivo. When Arg423 was replaced with Gln or Ser, the resulting mutant toxins resisted degradation by M. brassicae proteases. However, this mutation had little effect on toxicity to M. brassicae. Differential processing of membrane-bound Cry1Ac was also observed in qualitative binding experiments performed with brush border membrane vesicles from the two insects and in midguts isolated from toxin-treated insects.

Amino Acid Sequence↗

The risk of dementia and death after delirium.

BACKGROUND: delirium is common and is associated with many adverse short-term consequences. OBJECTIVES: to examine the relationship between an episode of delirium and subsequent dementia and death over 3 years. DESIGN: prospective cohort study. SETTING: patients (n = 203) were aged 65 years or older at baseline and survivors of the index admission. METHODS: Using a standard assessment of cognitive function, we followed 38 inpatients diagnosed with delirium (22 with delirium and dementia, 16 with delirium only) and 148 patients with no delirium or dementia, for a median of 32.5 months. Follow-up was by personal interviews, supplemented by standardized clinical examinations. We calculated the incidence and odds of dementia and the incidence and hazard ratio for death, with adjustment for potential confounders. RESULTS: The incidence of dementia was 5.6% per year over 3 years for those without delirium and 18.1% per year for those with delirium. The unadjusted relative risk of dementia for those with delirium was 3.23 (95% confidence interval 1.86-5.63). The adjusted relative risk of death also increased (1.80; 1.11-2.92), while the median survival time was significantly shorter in those with (510 days; 433-587) than in those without delirium (1122 days; 922-1322). CONCLUSION: delirium appears to be an important marker of risk for dementia and death, even in older people without prior cognitive or functional impairment.

Aged↗

Scabies presenting as a necrotizing vasculitis in the presence of lupus anticoagulant.

A 75-year-old man presented with a progressive eruption of 6 weeks' duration. Purpura and focal areas of cutaneous infarction were present on the legs. There were scabies burrows on the wrists and hands, and a mite was extracted. Histology of a skin biopsy showed a necrotizing leucocytoclastic vasculitis. Circulating lupus anticoagulant was detected. Treatment consisted of topical 5% permethrin cream and systemic steroids.

Aged↗

Necrotizing fasciitis complicating disseminated cutaneous herpes zoster.

The association of necrotizing fasciitis, often due to group A streptococcus and primary varicella (chicken pox), is unusual but recognized in children. The association in adults is rare but one report in the literature describes a previously healthy man with the two disorders. We now describe a case of disseminated cutaneous herpes zoster complicated by subacute necrotizing fasciitis in an elderly woman taking low dose methotrexate and prednisone for rheumatoid arthritis. Staphylococcus aureus was isolated. Localized debridement and split skin grafting were required.

Aged↗

The clinical spectrum of necrotising fasciitis. A review of 15 cases.

BACKGROUND: Necrotising fasciitis represents a spectrum of disease which ranges from fulminant through acute to subacute varieties. While fulminating necrotising fasciitis is a well recognised entity the subacute variety is not. AIM: To assess six years' experience of necrotising fasciitis at Waikato Hospital. METHOD: Cases of necrotising fasciitis were identified from discharge statistics for the period 1990-1995. Records were reviewed for clinical features, predisposing factors, microbiology, histology, treatment and outcome. RESULTS: Fifteen cases were identified of which ten were female. The average age was 55 years (range of 15-92 years). One patient presented with fulminant, eight with acute and six with subacute necrotising fasciitis. Significant blister formation was noted in eight cases. Risk factors were identified in 14 patients including trauma, renal impairment, diabetes mellitus, and various drugs including diclofenac (four patients), naproxen (one patient) and prednisone (two patients). Group A beta haemolytic streptococcus (GABHS) was identified in ten cases. Swab or tissue cultures had the highest yield for isolating the organism. Blood cultures grew GABHS in only three of 12 cases. Eight patients (53%) died. Of the survivors all but one patient required debridement and skin grafting. CONCLUSIONS: Necrotising fasciitis is a clinical spectrum of disease. It affects a wide age group and can have associated morbidities. It is often a fatal disease. Early recognition, high dose antibiotics and surgical debridement are important in the management of the entire spectrum of necrotising fasciitis.

Adolescent↗

Mycobacterium kansasii infection in a patient presenting with porphyria cutanea tarda.

Mycobacterium kansasii, an atypical mycobacterium, is an uncommon cause of cutaneous and joint disease in immunocompetent patients. We report an unusual case of infection with this organism in a patient who initially presented with porphyria cutanea tarda (PCT), and who was noted also to have a crusted ulcer over the middle phalanx and swelling of the proximal interphalangeal joint of the right middle finger. The cutaneous ulcer healed with minocycline, but the joint disease required a combination of rifampicin and ethambutol before a therapeutic response was obtained.

Arthritis, Infectious↗

Increasing the recognition of delirium in elderly patients.

OBJECTIVE: To determine if an educational intervention aimed at house staff will increase knowledge about and recognition of delirium. DESIGN: Before/after study, with blinding of participants to the intent of the study. SETTING: University hospital in Halifax, Nova Scotia. PATIENTS: One hundred eighty-seven control patients, seen as consecutive admissions of elderly patients (65 + years) to the General Medicine services of the Victoria General Hospital prior to the educational intervention, and 247 patients seen thereafter. INTERVENTION: Educational intervention at grand rounds, housestaff rounds, sign-in rounds, and bedside teaching. MEASUREMENTS: Recognition of delirium in the admitting history or progress notes, Confusion Assessment Method (CAM) as recorded by nurses, diagnosis of delirium by independent study physicians using DSM-IIIR criteria and the Trzepacz Delirium Symptom Rating Scale. RESULTS: Prior to the intervention, delirium or acute confusion was diagnosed in 3% of patients; after the intervention, delirium or acute confusion was diagnosed in 9% of patients (P < 0.01). Other abnormalities in mental state were noted in 8.5% of admissions prior to the intervention, and 15.6% of admissions after the intervention. After the intervention there was a significant difference in the proportion of patients in whom a mental status questionnaire had been carried out and in whom there was formal comment on various aspects of the mental state. The nursing CAM had a sensitivity of 0.68 and a specificity of 0.97. CONCLUSIONS: A simple educational intervention aimed at house staff appears to be effective in changing house staff behavior. Improved recognition of delirium may lead to better patient outcomes.

Aged↗