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Biomedical subjects

T Helliwell

Publications and source records attributed to T Helliwell.

At least 19 recordsLinked to original sources

Ultrasound-guided fine needle aspiration cytology in the diagnosis and management of thyroid nodules.

OBJECTIVE: To examine the accuracy of fine needle aspiration cytology (FNAC) in the diagnosis of thyroid nodules and compare the inadequacy rates for ultrasound-guided and freehand FNAC. METHODS: A retrospective study of 434 patients with thyroid nodules who underwent diagnostic FNAC over a 2-year period. Cytological diagnoses have been compared with the histological assessment of resection specimens in 69 cases. RESULTS: The inadequacy rate was significantly lower from ultrasound guided FNAC (24/373 cases, 6.4%) than from freehand FNAC (8/61 cases, 13.1%) (P = 0.043). Seventy-six percentage of patients had a non-neoplastic cytological diagnosis and, after multidisciplinary review, the patients were reassured and assigned to clinical follow-up. Sixty-seven patients had a resection for cytological appearances consistent with non-neoplastic disease (n = 34), suspicious of follicular neoplasia (n = 23), or suspicious of malignancy (n = 10), and two patients had resections following inadequate cytology with ultrasound appearances suspicious of a neoplasm. The overall accuracy of FNAC analysis for malignancy was 97.0%, with sensitivity 83.3%, specificity 98.0%, positive predictive value 71.4% and negative predictive value 98.4%. The overall accuracy of FNAC analysis for the prediction of neoplasia was 97.5%, with sensitivity 80.5%, specificity 97.8%, positive predictive value 89.2% and negative predictive value 95.9%. Difficulties in cytological diagnosis were associated with lymphoid infiltrates and with degenerative changes in follicular adenomas. CONCLUSION: Ultrasound-guided FNAC has a significantly lower yield of inadequate aspirates than palpable FNAC. The ability of FNAC to predict neoplasia in 89% patients and to exclude neoplasia in 95.9% patients makes an important contribution to the multidisciplinary assessment of patients.

Adolescent↗

The spectrum of pathology in central core disease.

Central core disease is a congenital myopathy with muscle weakness defined pathologically by the presence of extensive areas in muscle fibres that are devoid of oxidative enzyme activity. The gene responsible has been shown to be the ryanodine receptor 1 on chromosome 19q13 and mutations have now been identified in several patients. Some cases with the morphological defect remain molecularly undefined, particularly those studied before molecular studies were available. We have studied three families with congenital onset, each with a dominantly inherited mutation in a C-terminal exon of the ryanodine receptor 1. They illustrate the spectrum of pathology that can be observed in patients with the myopathic features of central core disease. We show that extensive fibrosis and fat may be present, type 1 fibre uniformity may occur in the absence of cores; cores may be central or peripheral, single or multiple; and that an appearance of multiple focal minicores might cause a diagnostic pathological dilemma. In addition, we show the value of immunocytochemistry in identifying cores, in particular the use of antibodies to desmin and gamma-filamin.

Adult↗

Rheumatoid nodule of the nasal septum.

Necrotizing granulomatous nodules are a common feature in patients with rheumatoid disease, affecting 20 per cent of seropositive patients. Although most commonly found subcutaneously at points of pressure, these nodules may occur in the connective tissues elsewhere in the body. In the upper aerodigestive tract, nodules have been described in diverse locations, but commonly in the trachea, larynx and the ear. We present the first reported case of a rheumatoid nodule affecting the nasal septum.

Aged↗

Differing expression of bax and bcl-3 may influence the different cure rates in mouth and orophayrngeal cancer

AIM: To determine the reason for the differing cure rates of cancers between the mouth and oropharynx. MATERIALS AND METHODS: To achieve our aim we carried out immunohistochemistry on paraffin-embedded tissue from 31 oral and 38 oropharyngeal squamous carcinomas using the streptavidin-biotin/HRP method. RESULTS: The results from this study revealed the mean percentage of bax and bcl-2 expression was higher in the oropharyngeal samples (56.34% and 97.36%, respectively) than in the oral samples (6.6% and 82.38%, respectively). In the oral carcinomas bcl-2 was expressed in a higher percentage of cells than bax, and a high proportion of cases were bcl-2 positive in the absence of significant bax expression. In contrast the oropharyngeal cases showed a high percentage of cells expresssing both bcl-2 and bax. CONCLUSION: The predominance of anti-apoptotic bcl-2 over the pro-apoptotic bax may result in a survival advantage of the cells of oral carcinomas over the cells of the oropharynx. Tumours of the oral cavity have been found to be clinically more radioresistant than those of the oropharynx. These findings may have implications for radiotherapy treatment since the cells of oral carcinomas may already have a survival advantage and the carcinomas may be less likely to respond to treatment.

Journal Article↗

Skeletal muscle involvement in falciparum malaria: biochemical and ultrastructural study.

Biochemical evidence of skeletal muscle damage is common in malaria, but rhabdomyolysis appears to be rare. To investigate the relationship between serum creatine kinase and myoglobin levels, muscle histology, and renal function in Plasmodium falciparum infections, we studied 13 patients with uncomplicated malaria, 13 with severe noncerebral malaria, and 10 with cerebral malaria. A muscle biopsy specimen was obtained from each patient for light microscopy and electron microscopy. Mean serum creatine kinase concentrations +/- SD were raised but similar for the three groups (258 +/- 277, 149 +/- 158, and 203 +/- 197 U/L, respectively; P = .5). The mean serum myoglobin level +/- SD was highest in cerebral malaria (457 +/- 246 vs. 170 +/- 150 and 209 +/- 125 ng/mL in uncomplicated and severe malaria, respectively; P < .01) and correlated with the mean serum creatinine level (r = .39 for 36 patients; P = .02). The number of intravascular parasites, proportion of mature forms, and glycogen depletion were highest in biopsy specimens from patients with cerebral malaria. Myonecrosis was not observed. Muscle appears to be an important site for P. falciparum sequestration, which could contribute to metabolic and renal complications.

Adult↗

Serial changes in serum vitamin K1, triglyceride, cholesterol, osteocalcin and 25-hydroxyvitamin D3 in patients after hip replacement for fractured neck of femur or osteoarthritis.

Serum vitamin K1 concentrations were measured at presentation (just before surgery) and then at weekly intervals for 3 weeks in two groups of elderly patients requiring either hemiarthroplasty for fractured neck of femur (FON, n = 13) or total hip replacement for osteoarthritis of the hip (OA, n = 16). In comparison with healthy elderly volunteers (n = 25), serum vitamin K1 concentrations were significantly lower in both groups at presentation, and fell significantly within 24 h after surgery to concentrations approaching non-detectable, subsequently returning to pre-operative values within 3 weeks. Serum vitamin K1 tended to be lower in the fracture group both before and after operation, although calculation of a vitamin K1-triglyceride ratio reduced the apparent difference as triglyceride concentrations were lower in the fracture group. Osteocalcin concentrations were similar and fell significantly after operation in both groups, returning to pre-operative levels within 7 days. No differences in the two forms of osteocalcin (carboxylated and undercarboxylated) were observed either before or after operation in either group. 25-Hydroxyvitamin D3 concentrations were not significantly different between the two groups at any time. Vitamin K1 status may be lower than desirable in certain groups of the elderly population, and supplementation should be considered as prophylactic therapy.

Aged↗

Congenital peripheral neuropathy presenting as apnoea and respiratory insufficiency.

A seven-week-old girl presented with recurrent apnoeic episodes and respiratory insufficiency. The child was hypotonic, weak, areflexic and had a paradoxical movement of the right hemidiaphragm. Cranial nerve and sphincter function was normal; there was no fasciculation. Nerve conduction studies showed a severe axonal sensory and motor peripheral neuropathy. Biopsy of the sural nerve revealed marked axonal atrophy. The infant is now over two years of age, is ventilator-dependent and has clinical and electrophysiological evidence of further progression of one of the earliest reported presentations of a congenital peripheral neuropathy.

Apnea↗

Muscle histopathology and physiology in chronic fatigue syndrome.

Chronic fatigue syndrome (CFS) is characterized by fatigue at rest which is made worse by exercise. Previous biopsy studies on small numbers of CFS patients have shown a range of morphological changes to which have been attributed fatigue and myalgia. We have now studied 108 patients with CFS or muscle pain and 22 normal volunteers by light and electron microscopy. There was no consistent correlation between symptoms and changes in fibre type prevalence, fibre size, degenerative or regenerative features, glycogen depletion, or mitochondrial abnormalities. Physiological contractile properties of quadriceps (maximal isometric force generation, frequency: force characteristics and relaxation rate) were also examined before and for up to 48 hours after a symptom-limited incremental cycle ergometer exercise test in 12 CFS patients and 12 normal volunteers. Voluntary and stimulated force characteristics were normal at rest and during recovery. Exercise duration was similar in the two groups although CFS patients had higher perceived exertion scores in relation to heart rate during exercise, indicating a reduced effort sensation threshold. On physiological and pathological grounds it is clear that CFS is not a myopathy. Psychological/psychiatric factors appear to be of greater importance in this condition.

Adolescent↗

Resistance to recombinant human erythropoietin due to aluminium overload and its reversal by low dose desferrioxamine therapy.

Seventeen severely anaemic and transfusion-dependent haemodialysis patients with a haemoglobin less than 7 g/dl were treated with recombinant human erythropoietin (r-Hu-EPO). Aluminium toxicity was diagnosed by a positive desferrioxamine (DFO) test and bone biopsy. Seven out of eight patients without aluminium toxicity responded to r-Hu-EPO therapy. Similarly all patients with aluminium toxicity (n = 4) but pre-treated with standard dose of DFO prior to r-Hu-EPO therapy responded but none of the patients with untreated aluminium toxicity (n = 5) responded to r-Hu-EPO therapy. In order to achieve adequate response in these patients, r-Hu-EPO and DFO had to be given in combination. The dose of desferrioxamine used to reverse r-Hu-EPO resistance was less and also used for a short time. We therefore confirm r-Hu-EPO resistance owing to aluminium overload and report its successful and safe reversal with low dose DFO therapy.

Aluminum↗

Pyrophosphate in synovial fluid and urine and its relationship to urinary risk factors for stone disease.

Inorganic pyrophosphate (PPi) measurement in urine and synovial fluid has been established using the PPi-dependent phosphorylation of fructose-6-phosphate and subsequent reduction of dihydroxyacetone phosphate by NADH. The assay is linear up to 200 mumol/L, easy to perform and gives results comparable to more complex methods. Daily urinary output of PPi was independently related to both age (P = 0.0014) and sex (P = 0.0002). Men had higher values than women and older individuals excreted greater amounts. Male stone formers, younger than 45 years, had lower values than age matched male controls (P = 0.012). Younger female stone formers also tended to have lower values. In stone formers' urine significant and independent correlations were found of PPi excretion with urine volume (P = 0.004) and with phosphate excretion (P = 0.008). Oxalate excretion and that of other urine constituents and the degree of supersaturation with common stone-forming salts were not correlated with PPi. PPi excretion was markedly elevated in the urine of two patients with hypophosphatasia. The PPi concentration in synovial fluid from painful, swollen knee joints was elevated, but unrelated to the presence or absence of PPi or urate crystals.

Adolescent↗

Low-dose desferrioxamine test for the diagnosis of aluminium-related bone disease in patients on regular haemodialysis.

Bone biopsy in an invasive method of diagnosing aluminium related bone disease (ABD). Toxic side-effects have been reported with the currently used 'high-dose Desferrioxamine (DFO) tests.' A low-dose DFO test was evaluated for the diagnosis of ABD in 28 symptomatic patients (13 male) on regular haemodialysis treatment. DFO 0.5 g diluted in 100 ml of 0.9% sodium chloride was given intravenously during the first 2 h of dialysis. Aluminium estimation before (t1) and 48 h after DFO challenge (t2) were made by DC plasma emission spectrometry. Following the DFO test bone biopsy was performed and the specimen stained for aluminium using soluchrome zurine. The DFO test was considered positive if the t2 concentration was 150 micrograms/l or treble the amount of t1. Nineteen patients (8 male) fell into this group and all except two had ABD. Of the nine remaining patients (5 male) who had a negative DFO test none had ABD. We conclude that ABD can be diagnosed safely in the majority of patients using a low-dose DFO test, thereby avoiding toxic side-effects.

Adult↗

Use of lectin histochemistry in pancreatic cancer.

Lectin peroxidase histochemical analysis was carried out on pancreatic tissue from patients with pancreatic carcinoma and chronic pancreatitis and from subjects with normal pancreas to find a tumour specific pattern of lectin binding that would aid histological and cytological diagnosis. There were striking differences between the lectin binding characteristics of the different cell types in the normal pancreas. Acinar cells were uniformly positive for binding with wheat germ agglutinin and soy bean agglutinin while islet cells were usually negative for these lectins. Ulex europaeus I lectin however, was found not to be specific for endothelium, showing positivity also for acinar and ductal tissue. Griffonia simplicifolia II lectin was found to be highly specific for ductal epithelium, and because of this was tested in a hamster pancreatic cancer model where it was not specific for ductal epithelium, reflecting differing carbohydrate expression in the hamster pancreas. Pancreatic carcinomas and chronic pancreatitis bound all five lectins without any qualitative distinction from each other or from normal pancreatic tissue, but there was increased intensity of peanut agglutinin binding to secreted mucins in pancreatic carcinoma, which may be of potential use in radiolabelled lectin scanning.

Animals↗