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Biomedical subjects

J P Dowling

Publications and source records attributed to J P Dowling.

At least 19 recordsLinked to original sources

Transforming growth factor-beta1 and tumor growth factor-beta-inducible gene-H3 in nonrenal transplant cyclosporine nephropathy.

Cyclosporine nephropathy (CyAN) is a major limiting factor in the otherwise successful widespread use of cyclosporine in solid organ transplant. Transforming growth factor-beta1 (TGF-beta1) has been implicated as an important fibrogenic cytokine in the development of this disease. TGF-beta-inducible gene-H3 (beta(ig)-H3) is a TGF-beta1- induced gene product, which acts as a marker for biologically active TGF-beta1. This study reports TGF-beta1 gene expression and beta(ig)-H3 tissue distribution in non-renal allograft CyAN. Renal tissue from nine patients who had developed CyAN after successful heart or heart-lung transplantation and from four kidneys removed for tumour were analyzed for TGF-beta1 gene expression beta(ig)-H3 protein with reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry, respectively. TGF-beta1 gene expression was increased in CyAN compared to nephrectomy (P<0.0001). Beta(ig)-H3 protein expression was identified in distal convoluted tubular epithelium and parietal glomerular epithelium in CyAN, and not in nephrectomy samples. Expression of TGF-beta1 mRNA was significantly higher in renal tissue from patients not receiving angiotensin converting enzyme inhibitor (ACEI) therapy for hypertension (P<0.05). These findings support the hypothesis that TGF-beta1 is an important cytokine in the development of CyAN, independent of its role in chronic rejection in renal allografts.

Adult↗

Primary T-cell-rich B-cell lymphoma in the kidney presenting with acute renal failure and a second malignancy.

Infiltration of the kidney is commonly found in lymphoma, but acute renal failure arising from bilateral renal infiltration is uncommon. Primary renal lymphoma may occur and is usually of B-cell lineage. It is rare for patients with lymphoma to develop acute renal failure as their initial clinical presentation. Recently, an association between primary renal lymphoma and a second primary malignancy has been reported. We describe the first case of a renal T-cell-rich B-cell lymphoma presenting as acute renal failure, which was associated with a second primary pulmonary malignancy.

Acute Kidney Injury↗

Prominence of cell-mediated immunity effectors in "pauci-immune" glomerulonephritis.

The majority of patients with rapidly progressive crescentic glomerulonephritis show histologic features of extensive necrosis and focal and segmental proliferation with fibrin production, but little or absent Ig deposition in the glomerulus. This subcategory of the disease, labeled "pauci-immune" glomerulonephritis, has recently been shown to be associated with the presence of antineutrophil cytoplasmic antibody in the patient's circulation (but not within the glomerulus). The absence of the effectors of humoral immunity at the site of renal injury led to this investigation of the contribution of cell-mediated immunity to the glomerular injury in this form of glomerulonephritis. In 15 patients presenting acutely with pauci-immune glomerulonephritis, CD3-positive T cells (3.7+/-2.5 [mean +/- SD] cells per glomerular cross section, [c/gcs]), CD45RO-positive T cells (2.7+/-1.9 c/cgs), macrophages (7.3+/-6.1 c/gcs), fibrin (3+), and endothelial-associated tissue factor were demonstrated to be prominent in glomeruli. These mediators were absent in a group of 12 patients with thin basement membrane disease and only occasionally observed in a group of eight patients with "humorally mediated"(noncrescentic) glomerulonephritis. Thus, in pauci-immune glomerulonephritis, there is the development of significant cell-mediated immunity with activated T cells, macrophages, tissue factor, and fibrin at the site of glomerular injury, suggesting that this glomerular disease is most likely a manifestation of T cell-directed cognate immune injury.

Adult↗

Granulomatous glomerulonephritis in intravenous drug users: a report of three cases in oxycodone addicts.

Various well-documented renal lesions are associated with intravenous drug use; however, intraglomerular mesangial granulomas have not been previously described. We report three patients who developed an unusual granulomatous glomerulonephritis and interstitial nephritis after intravenous injection of oxycodone, derived from suppositories. Granulomas were seen in an intraglomerular mesangial and also interstitial location. In both sites, the granulomas were associated with filamentous material, presumably derived from a component of the suppositories. This material was periodic acid-Schiff-positive, but negative with Congo red and silver stains. Ultrastructurally, the filamentous material was seen within the mesangial granulomas and also in a subendothelial location, suggesting derivation from the circulation with subsequent transport across the basement membrane and accumulation in the mesangium, where a granulomatous reaction was elicited. All patients developed a degree of renal failure; two of the patients require hemodialysis 20 and 30 months after presentation.

Adult↗

Acute glomerulonephritis associated with acute Q fever: case report and review of the renal complications of Coxiella burnetii infection.

We report a case of acute glomerulonephritis associated with acute Q fever. An abattoir worker with a nonspecific febrile illness and pneumonia and abnormal liver function test results developed hematuria, proteinuria, and acute renal failure that resolved with appropriate antimicrobial therapy. Renal biopsy demonstrated diffuse proliferative and exudative glomerulonephritis. Serological tests confirmed recent infection with Coxiella burnetii, with a fourfold rise in the titer of phase II antibody, positive phase II IgM antibody, and negative phase I antibody. Other known causes of glomerulonephritis were excluded. Most reports of renal complications of C. burnetii infection describe glomerulonephritis associated with endocarditis due to chronic Q fever. Renal involvement in patients with acute C. burnetii infection has been rarely described. Glomerulonephritis should be recognized as a complication of acute C. burnetii infection and endocarditis due to chronic Q fever.

Acute Disease↗

Characteristics of familial and non-familial melanoma in Australia.

Between 6 and 14% of malignant melanomas have been reported to occur in a familial pattern. In this study 785 melanoma patients from the Victorian Melanoma Service and the private practice of a dermatologist were assessed for the total number of melanocytic naevi, the number of dysplastic naevi and other clinical characteristics categorized according to whether there was a family history of melanoma. It was found that the presence of 100 or more naevi, six or more dysplastic naevi and blue eyes in a patient with melanoma were significantly associated with a family history of melanoma. Patients with two or more family members with melanoma were significantly more likely to develop melanoma at a younger age and to develop multiple melanomas. This study concludes that large numbers of melanocytic naevi and dysplastic naevi in melanoma patients are useful characteristics in practice to identify patients at risk of familial occurrence of melanoma. Family members of these patients should receive a medical assessment for their pigmented lesions.

Adult↗

Spitz naevi misdiagnosed histologically as melanoma: prevalence and clinical profile.

A Spitz naevus is a benign melanocytic tumour that may histologically resemble a malignant melanoma. Data was retrospectively gathered from patients who attended the Victorian Melanoma Service to determine the prevalence of Spitz naevi pathologically misdiagnosed as melanoma. Assessment of the clinical characteristics of these patients was also performed and compared to those with correctly diagnosed melanoma. It was found that 6.5% of all melanomas referred were in fact Spitz naevi and that Spitz naevi represented the majority of pathologically misdiagnosed melanomas. The Spitz naevi were more likely to be on the lower extremities and were no average, considerably smaller than the melanomas. Patients with Spitz naevi were more likely to be younger, female, have fewer dysplastic naevi and have brown eyes. One hundred per cent of the Spitz naevi were brought to the attention of the initial doctor by the patient compared to 72% of the melanomas. This study concludes that Spitz naevi that are pathologically misdiagnosed as melanomas retain the clinical characteristics of other Spitz naevi and that greater clinicopathological communication may reduce the frequency of diagnostic error.

Chi-Square Distribution↗

Vasculitis and thrombotic thrombocytopenic purpura in a patient with limited scleroderma.

Inflammatory vasculopathy and thrombotic thrombocytopenic purpura (TTP) are rare complications of scleroderma. We report a 54-year-old woman with limited cutaneous scleroderma who developed medium size and small vessel vasculitis. Inflammatory changes of medium size muscular arteries presented as ovarian vasculitis and mononeuritis multiplex, while arteriolar involvement presented as TTP with associated central nervous system involvement. In addition, possible noninflammatory involvement of small muscular arteries was expressed as Raynaud's phenomenon.

Female↗

Melanoma botryoides: a distinctive myxoid pattern of sino-nasal malignant melanoma.

Two primary sino-nasal melanomas are presented which were characterized by their botryoid growth pattern and myxoid stroma. These polypoid tumours contained small amounts of melanin and only focal areas of epithelioid cells. An in situ component was present in both of the tumours. Malignant melanoma should be considered when confronted by a myxoid tumour (with or without melanin) in the sino-nasal region. These tumours are widely infiltrative, and there is no evidence to suggest that they will behave any differently from conventional, non-botryoid, non-myxoid sino-nasal melanomas.

Aged↗

A unique presentation of multicentric reticulohistiocytosis in pregnancy.

We describe a patient with multicentric reticulohistiocytosis who presented, during the second trimester of pregnancy, with symmetric polyarthritis, marked erythematous, pulsatile synovial swelling of the distal interphalangeal joints of both hands, and widespread telangiectasias. She did not have the typical skin manifestations of multicentric reticulohistiocytosis. The erythema and pulsatility of the synovial swellings of the distal interphalangeal joints resolved after delivery, but she continued to have widespread active synovitis, which did not resolve until treatment with low-dose oral methotrexate was instituted.

Adult↗

Systemic giant cell arteritis and cerebellar infarction.

BACKGROUND AND PURPOSE: Systemic giant cell arteritis causing cerebellar infarction due to intracranial arteritis of the anterior inferior cerebellar artery has not been previously reported. We report this infrequent occurrence and discuss the differential diagnosis. CASE DESCRIPTION: An 85-year-old woman was admitted with a 2-week history of episodic ataxia, unilateral headaches, and vomiting. She had a history of atrial fibrillation and breast carcinoma. Her mental state was initially normal, and there were right-sided cerebellar signs. An ejection systolic murmur was heard, and peripheral pulses were palpable. A postmortem examination revealed cerebellar infarction due to giant cell arteritis of the anterior inferior cerebellar artery and basilar arteries. Systemic giant cell arteritis was also present. CONCLUSIONS: Giant cell arteritis is a systemic disorder that can infrequently involve intracranial vessels, including the basilar, vertebral, and anterior cerebellar arteries. Cerebellar infarction secondary to the arteritis may occur. The distribution and size of intracranial vessel involvement is distinct from isolated cranial angiitis.

Aged↗

Leiomyosarcoma of the thyroid: immunohistochemical and ultrastructural study.

A primary leiomyosarcoma of the thyroid was seen in a 54 yr old female. The patient had a solitary, cold nodule with no abnormalities of thyroid function tests. Histologically it was composed of characteristic interlacing fascicles of spindle cells which, electron microscopically, showed thin myofilaments with focal dense bodies. Immunohistochemistry showed a strong reaction with vimentin, smooth muscle actin and desmin. No epithelial differentiation was noted immunohistochemically or ultrastructurally. No tumor recurrence was detected 15 mths after surgery. It is postulated that the smooth muscle differentiation had arisen by metaplastic change or de-differentiation with re-differentiation of anaplastic thyroid carcinoma.

Cytoskeletal Proteins↗