Paramyxovirus-like inclusions in two cases of pycnodysostosis

We describe the biochemical and histological features of two related patients with pycnodysostosis. Examination of bone biopsies taken from both patients showed the presence of large nonfunctional osteoclasts which contained paramyxovirus-like inclusions similar in size and arrangement to those found in Paget's disease of bone. No radiographic, histologic or biochemical evidence for Paget's disease was found in either patient. The presence of osteoclast inclusions may not be specific for Paget's disease, therefore, and could be the result rather than the cause of abnormal osteoclast metabolism.     

Canadian Consensus Recommendations for the Optimal Use of Enfuvirtide in HIV/AIDS Patients.

BACKGROUND AND OBJECTIVES: An eight-member group consisting of Canadian infectious disease and immunology specialists and a family physician with significant experience in HIV management was convened to update existing recommendations, specifically intended for use by Canadian HIV-treating physicians, on the appropriate use of enfuvirtide in HIV/AIDS patients with resistance to other antiretroviral drugs. METHODS: Evidence from the literature and expert opinions of the group members formed the basis of the guidelines. Comments on the draft guidelines were obtained from other physicians across Canada with HIV expertise. The final guidelines represent the group's consensus agreement. RESULTS AND CONCLUSIONS: The recommendations were developed to guide physicians in optimal practices in patient selection for enfuvirtide treatment and subsequent patient management. The issues considered include positive predictors of response to enfuvirtide, stage of disease, optimization of the background regimen, early indicators of enfuvirtide response, and patient education and support.     

Fluid movement in the lumen of the rat epididymis: effect of vasectomy and subsequent vasovasostomy

Intraluminal fluid movement rate was measured in four regions of the rat epididymis. The fastest flow occurred in the proximal caput epididymis (18.5 +/- 3.7 mm/hour) and the slowest in the distal cauda (2.5 +/- 0.5 mm/hour). Vasectomy significantly reduced caput fluid flow rates unless a sperm granuloma was present at the vasectomy site. Thirty days after vasovasostomy, caput fluid movement remained reduced in animals unless a granuloma was present. Failures of this or other aspects of epididymal biology to return to normal after vasovasostomy could play a role in the frequent infertility which persists after the operation.     

Quantitative MRI volume changes in late onset schizophrenia and Alzheimer''s disease compared to normal controls

Volumes of medial and lateral temporal lobe structures were assessed using magnetic resonance imaging (MRI) in 11 patients with late-life onset schizophrenia (LOS), 18 normal elderly controls and 12 patients with moderate cognitive impairment due to Alzheimer's disease (AD) who had no non-cognitive symptoms. While both patient groups has smaller volumes of several medial temporal regions (e.g. entorhinal cortex, left hippocampus), schizophrenics had significantly smaller anterior superior temporal gyri (STG) than normal controls, but AD patients did not. We have previously demonstrated anterior STG volume to be reduced in early life onset schizophrenia.     

Clinical and genetic changes in a case of a Cushing''s carcinoma

A 30-year-old presented In 1984 with a clinically nonfunctional tumour which subsequently developed Into a metastatic corticotrophlnoma from which he died despite surgery In 1984,1986 and 1991 and external radiotherapy In 1986. Molecular genetic analysis of tumour and metastatic tissue revealed loss of heterozygosity at loci on the autosomes 1p, 3p, 10q26,11q13 and 22q12. Tissue taken at surgery In 1986 also revealed positive cytoplasmic Immunostalning for p53 protein. No such staining was evident in tissue taken at first surgery in 1984. Further analysis of Invasive pituitary adenomas may reveal loci associated with such behaviour, enabling better prediction of subsequent clinical outcome than is possible using standard histological techniques, and delivery of early, aggressive treatment to those tumours which show molecular markers associated with a poor prognosis.     

LYSOSOMAL IRON ACCUMULATION AND TUBULAR DAMAGE IN RAT PUROMYCIN NEPHROSIS AND AGEING

1. Energy dispersive X-ray spectrometry was used to examine the relationship between proteinuria and increased urinary iron excretion, and structural and functional damage in puromycin nephrosis. 2. After 11–12 days rats treated with puromycin (10 mg/100g, i.v.i.) had greater proteinuria (211.6 ± 35.7 mg/day, mean ± s.e.m.) and urinary iron excretion (15.4 ± 2.2 μg/day) than salinetreated controls (14.5 ± 1.4 mg/day and 1.1 ± 0.2 μg/day, respectively, both P<0.001). 3. On day 13, mean lysosomal iron concentration of proximal tubular cells (306.6 ± 64.5 vs 11.9 ± 8.6 mg%, P<0.001), and proximal tubular cell damage assessed semi-quantitively (1.17 ± 0.10 vs 0.62 ± 0.10, P<0.001) were higher and creatinine clearance (0.15 ± 0.01 vs 0.29 ± 0.02 mL/min perg kidney weight, P<0.001) lower than in control rats. 4. At days 35, 60 and 360 there were no differences in any of the measured parameters between rats treated with puromycin or saline, and in both groups proteinuria, tissue damage and lysosomal iron concentration increased with time. 5. Lysosomal iron accumulation was the only independent predictor of both functional and structural damage. 6. In conclusion, the apparent association between proteinuria and tubulo-interstitial damage in puromycin nephrosis, and with ageing, is best explained by factors associated with accumulation of iron within lysosomes of proximal tubule cells.     

Hypercalcemic hyperparathyroidism and hypophosphatemic osteomalacia complicating neurofibromatosis

Summary Neurofibromatosis is sometimes complicated by impaired renal tubular reabsorption of phosphate, hypophosphatemia, and osteomalacia. Hyperparathyroidism has also been reported in patients with neurofibromatosis. When hypercalcemia and elevated levels of parathyroid hormone are found in osteomalacia, however, it may be difficult to determine if the hyperparathyroidism was primary or tertiary. We describe a patient with neurofibromatosis, hypercalcemic hyperparathyroidism, hypophosphatemic osteomalacia, vitamin D deficiency, and clear-cell hyperplasia of all four parathyroid glands. Serial biomechanical, bone biopsy, and densitometric studies confirmed that treatment with ergocalciferol, calcium, and phosphate supplements significantly improved the osteomalacia but caused increased parathyroid overactivity. After subtotal parathyroidectomy, the parathyroid hormone concentration became normal and the bone mineral content increased at the spine and hip, but inappropriate phosphaturia persisted. The findings indicate that hyperparathyroidism, osteomalacia, and vitamin D deficiency adversely affect each other.     

Management of venous stasis ulcer: long-term follow-up

In this study 112 patients (122 lower limbs) who had chronic venous stasis ulceration refractory to conservative management were treated surgically. Subfascial ligation was performed on 118 limbs and the long saphenous vein was removed in 4. Complications consisted of postoperative thrombophlebitis (2%), wound infection (2%) and wound infection with ulcer necrosis (1.5%). These all responded to conservative management. Follow-up (mean 7.9 years, median 11 years) showed a good or excellent result in 82% of cases, with healing of the ulcer and no ulcer recurrence despite significant noncompliance with support stockings. This paper is a long-term follow-up study of a surgical procedure for chronic venous stasis ulcers. The authors believe that the 82% good and excellent results may indicate that surgical intervention for refractory venous ulcers is a worthwhile procedure, providing potentially satisfactory long-term results.     

Hypoxia and anaemia in head and neck squamous cell carcinoma – mechanisms of therapy failure and provision of new therapeutic targets

? Head and neck squamous cell carcinoma (HNSCC) represents the sixth most common tumour worldwide. ? Tumour hypoxia and anaemia are both independent prognostic indicators of disease free and overall survival in solid tumours, including HNSCC. ? Hypoxia promotes tumour progression through the hypoxia inducible factor 1 pathway (HIF‐1), upregulating factors that control angiogenesis, glycoloysis, pH regulation, erythropoiesis and apoptosis. ? Oxygen delivery to tumours is influenced by the oxygen carrying capacity of the blood, and therefore anaemia may promote tumour hypoxia. ? Targeting the HIF‐1 pathway and anaemia represent potential therapeutic targets in HNSCC and other solid tumours.