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Biomedical subjects

G H Millward-Sadler

Publications and source records attributed to G H Millward-Sadler.

At least 19 recordsLinked to original sources
PubMed2001

Pericardial mesothelioma following mantle field radiotherapy.

A 49-year-old female was referred with recurrent pericardial effusion following mantle field radiotherapy for Hodgkin s lymphoma. She underwent video-assisted thoracoscopy and resection of a pericardial window. Intraoperatively she suffered a cardiac arrest and subsequently died in the early postoperative period despite maximal therapy. Pathological examination revealed extensive myocardial fibrosis and multiple nodules of pericardial mesothelioma. The latter has hitherto not been recognised following mediastinal radiation. The cardiac complications of mantle field radiotherapy are discussed.

Fatal Outcome↗
PubMed1996

Invasive cervical cancer in Southampton and South West Hampshire: effect of introducing a comprehensive screening programme.

A study of invasive cervical cancer in Southampton and South West Hampshire is reported, covering three consecutive three year periods during which the screening coverage increased from an estimated 60% to a recorded 87% of eligible women aged 20-64. From the first to the third periods of the study in that age group registrations of fully invasive squamous cell carcinoma (stage lb and above) fell from 64 to 30 (53%), which was largely counteracted by an increase in microinvasive squamous cell carcinoma (linear trend: P<0.0001). In the same age group registrations of adenocarcinoma rose slightly, which resulted from an increase in the number diagnosed at a depth of invasion of less than 3 mm. There were no significant changes in the numbers of stage III and IV cancers or among cancers in women aged 65 and over. A strong inverse association was found between stage of both histological types of cancer and their likelihood of being screen detected rather than symptomatic: 91% of screen detected cancers were diagnosed at stage I compared with 38% of symptomatic cancers. There was a slight downward trend in the incidence of cancer per 100,000 total female population across the three periods of the study with a significant trend towards low stage disease, which is likely to reduce mortality in years to come. The trend towards screen detected cancers and cancers of less than 3 mm depth of invasion is presented as a positive outcome to be expected in early rounds of increasing the screening coverage.

Adenocarcinoma↗
PubMed1995

Chrysiasis revisited: a clinical and pathological study.

Chrysiasis is a distinctive and permanent pigmentation of light-exposed skin resulting from the administration of parenteral gold salts. We report a study of 40 Caucasian patients with rheumatoid arthritis, treated with intramuscular sodium aurothiomalate, of whom 31 had chrysiasis. Visible changes develop above a threshold, equivalent to 20 mg/kg gold content, and their severity depends upon cumulative dose. Focal aggregates of particulate gold are deposited in the reticular and papillary dermis in amounts that correlate with the degree of pigmentation. Characteristically, initially the periorbital region is affected by a mauve discoloration, which intensifies and deepens into a blue/slate-grey colour, while extending to involve the face, neck and upper limbs. Although chrysiasis develops insidiously and patients may be unaware of the changes, positive identification is important in order to avoid misdiagnosis and medical mismanagement, and afford appropriate reassurance. Prevention is difficult, but measures to reduce sunlight exposure may be helpful.

Antirheumatic Agents↗
PubMed1993

T-cell-rich B-cell lymphoma presenting as liver disease.

We describe a series of eight cases of T-cell-rich B-cell lymphoma diagnosed on liver biopsy and collected over a period of 15 years. Of seven cases that were referred from elsewhere, in only one was the correct diagnosis of B-cell lymphoma suggested. Common errors included misdiagnosis as inflammatory disease on histology, and misinterpretation as T-cell lymphoma on immunohistochemistry. However, the cases had a distinct morphological appearance and immunohistochemical profile. They showed a lymphohistiocytic or granulomatous infiltrate, usually centred on portal tracts and containing abundant small T-cells and scanty B-cell blasts. All patients had an atypical clinical presentation which favoured non-neoplastic liver disease. In seven cases liver involvement represented Stage IV disease and in one case disease was confined to the liver consistent with a primary hepatic lymphoma. Despite combination chemotherapy, the prognosis was poor with no patients surviving beyond 15 months from diagnosis. We believe T-cell-rich B-cell lymphoma to be an under-recognized subset of non-Hodgkin's lymphoma that may mimic primary liver disease.

Aged↗
PubMed1992

Assessment of the accuracy of cytology in women referred for colposcopy and biopsy: the results of a 1 year audit.

The results of weekly colposcopy review meetings have been audited for 1 year and cases where there was a discrepancy between the referral cervical smear and the initial colposcopy biopsy have been analysed. New referrals (n = 476) for colposcopy were studied. In the final outcome 80% of 326 women referred for moderate or severe dyskaryosis were found to have cervical intraepithelial neoplasia (CIN) grade II or III or invasive carcinoma. Three women found to have invasive carcinoma had been referred for severely dyskaryotic smears. Twenty women were referred for smears with cell changes suggesting glandular neoplasia: five were found to have adenocarcinoma in situ, whereas eight had CIN and seven had negative biopsies. The results justify the referral policy and demonstrate the need for further investigation when initial colposcopic biopsies are negative.

Adenocarcinoma↗
PubMed1991

Chronic pancreatitis and biliary fibrosis associated with cryptosporidiosis in simian AIDS.

Two Rhesus monkeys infected with simian immunodeficiency virus for 15 and 24 months developed generalized oedema and one became jaundiced. At necropsy, the liver and pancreas were hard and irregular and the gall bladder was thickened. Histopathological examination showed extensive fibrosis of the pancreas, loss of exocrine acini and marked proliferation of ductules. Numerous cryptosporidia were present on the duct epithelium. The liver of both animals had widespread cirrhosis, bile duct proliferation and cholangitis. Cryptosporidia were found in many bile ducts and on the hyperplastic gall bladder epithelium. Lymph nodes and spleen of both animals showed depletion of cortical and paracortical elements characteristic of advanced immunodeficiency virus infection.

Animals↗
PubMed1990

Corticosteroid treatment reduces mast cell numbers in inflammatory bowel disease.

Mast cell degranulation in the gut causes mucus secretion, mucosal edema, and increased gut permeability and may be responsible for some of the symptoms and signs of inflammatory bowel disease. We have used a novel monoclonal antibody (AAI) against tryptase expressed exclusively in the granules of mast cells to enumerate mast cells in rectal biopsies in order to study the effect of inflammatory bowel disease and drug treatment upon rectal mast cell numbers. Rectal mast cell numbers are significantly reduced in inflammatory bowel disease patients taking corticosteroids (mean 4.95 cells/mm2) when compared with control patients (10.1, P less than 0.001) and inflammatory bowel disease patients not taking corticosteroids (9.7, P less than 0.001 Wilcoxon rank sum test). The reduction in mast cell counts was independent of the degree of inflammation or architectural distortion. There was a negative correlation between the dose of corticosteroids and mast cell count (r = 0.53, P less than 0.05 Spearman rank correlation), and the mast cell count was reduced within a few days of treatment and remained low throughout steroid therapy. Mucosal mast cell depletion may be an important mechanism of action of corticosteroids in inflammatory bowel disease.

Adrenal Cortex Hormones↗
PubMed1990

Spontaneous regression of hepatocellular carcinoma.

A 63 year old white woman presented with abdominal discomfort, anorexia, and weight loss. Investigations showed hepatocellular carcinoma with pulmonary metastases. The primary and secondary tumours resolved without specific treatment.

Carcinoma, Hepatocellular↗
PubMed1986

Hepatic regeneration and metabolism after partial hepatectomy in normal rats: effects of insulin therapy.

The effect of insulin therapy on liver regeneration has been studied in normal fed rats 12, 24 and 48 h after partial hepatectomy. Dry weight of regenerating liver increased between 12 and 48 h after partial hepatectomy and was unaffected by insulin therapy. [6-3H] Thymidine uptake peaked at 24-h (24.7 +/- 2.4% of total liver cells) and insulin treatment had no additional effect. At 12-h after partial hepatectomy, hepatic [ATP] was decreased 15%, while [ADP] and [AMP] were increased 47% and 83% respectively compared with sham-operated animals. Partial hepatectomy also caused an increase in hepatic [triglyceride], a decrease in hepatic [glycogen] and an increase in the levels of glucose and several glycolytic intermediates. The hepatic redox ratios, [lactate]:[pyruvate] and [3-hydroxybutyrate]:[acetoacetate], were elevated. Insulin therapy had only minor effects on hepatic adenine nucleotide levels, intermediary metabolite concentrations or intrahepatic redox ratios after partial hepatectomy. These findings suggest a decreased hepatic intracellular energy state in regenerating liver; insulin therapy in normal rats does not influence this metabolic change nor the regenerative response.

Adenine Nucleotides↗
PubMed1986

Hepatic regeneration and metabolism after partial hepatectomy in diabetic rats: effects of insulin therapy.

The effect of insulin deficiency on liver regeneration has been assessed in untreated v. insulin-treated streptozotocin (65 mg kg-1) diabetic rats, 12, 24 and 48 h after partial hepatectomy. Dry weight of regenerating liver increased from 12 to 48 h after partial hepatectomy and insulin treatment caused a further minor increase at 24 h. [6-3H]Thymidine uptake in untreated rats peaked at 24 h (12.5 +/- 3.4% of total cells labelled). Insulin therapy produced a delayed 168% rise in uptake at 48 h. Insulin deficiency alone in sham-operated animals caused a 33% decrease in hepatic [ATP], while [ADP] rose by 43% and [AMP] by 86% at 12 h. Partial hepatectomy produced only minor further abnormalities in untreated animals. Insulin therapy increased hepatic [ATP] and decreased [ADP] and [AMP] 12 h after partial hepatectomy, but [ATP] remained decreased (15%) and [ADP] and [AMP] increased (45% and 73% respectively) compared with insulin-treated sham-operated controls. Metabolite changes observed after partial hepatectomy in untreated animals, including a decrease in hepatic [glycogen] and increases in [triglyceride] and the ratios of [lactate]:[pyruvate] and [3-hydroxybutyrate]:[acetoacetate], were partially reversed by insulin treatment. Insulin deficiency thus impairs regeneration after partial hepatectomy and magnifies the decline in hepatic intracellular energy state and the metabolite changes associated with liver regrowth.

Adenine Nucleotides↗
PubMed1985

Oxygen-derived free radicals promote hepatic injury in the rat.

We have investigated the possible protective effect of superoxide dismutase and allopurinol in a rat model of mild and severe hepatic necrosis produced by Corynebacterium parvum with or without endotoxin. Histology showed a sinusoidal mononuclear cell infiltrate with multiple granulomata but variable degrees of hepatic necrosis. In the severe hepatic injury model there was a reduction in mortality, associated with a decrease in histologic and biochemical evidence of hepatic necrosis, after treatment with superoxide dismutase. This protective effect was not demonstrated with partially heat-inactivated superoxide dismutase. In the mild hepatic injury model similar trends in reduction of serum levels of hepatic enzymes were observed after treatment with both superoxide dismutase and allopurinol. These results indicate that oxygen-derived free radicals may play an important role in the pathogenesis of hepatic injury in the rat.

Alanine Transaminase↗
PubMed1983

Different aetiology of chronic active hepatitis in U.K. and Iraq.

We have compared the clinical, biochemical and immunological features of patients with biopsy-proven chronic active hepatitis from Iraq and from the United Kingdom. Clear-cut differences emerge, which can mostly be attributed to the HBV status, as 91% of patients from Iraq were HBsAg-positive compared to only 6% from the U.K. Most patients from Iraq presented insidiously with established cirrhosis, while those from the U.K. presented more acutely and systemic symptoms were more common. Autoantibodies and associated autoimmune conditions were common in U.K. patients but extremely rare in Iraqis.

Adult↗
PubMed1982

Chronic active hepatitis: the spectrum of disease.

A five-year study of all newly diagnosed cases of chronic active hepatitis (CAH) from a defined population of 404,000, in which the internationally accepted diagnostic criteria were applied, is reported. A putative aetiological agent was identified in all but 14 (23%) of 61 cases. Alcohol (26%) and hepatitis B (20%) were the commonest aetiological factors. The incidence of CAH was 3 per 100,000 per year. Patients were often elderly, mean age 56, with a third aged over 65. A third were symptom-free at diagnosis, and the disease was biochemically or histologically severe in only a few. 9 of 61 (15%) fulfilled the criteria for treatment used in the Mayo Clinic trials. Even after exclusion of those with CAH unresponsive to corticosteroids (i.e., where hepatitis B, drugs, alcohol are involved in the aetiology) and widening of the criteria, only 7 of the remaining 31 (23%) are likely to benefit from corticosteroids. The variety of aetiological agents, spectrum of clinical features, and range of disease severity are very different in an unselected group from those reported from specialised referral centres.

Adrenal Cortex Hormones↗
PubMed1982

Complications in methotrexate treatment of psoriasis with particular reference to liver fibrosis.

All patients taking methotrexate for treatment of psoriasis over the past 5 yr have been reviewed. Thirty-eight patients have had pretreatment liver biopsies and at least 1 repeat liver biopsy. Of the 38, nine (24%) have developed significant liver fibrosis or cirrhosis, and have stopped treatment. The high incidence of fibrosis is attributed to synergism between methotrexate and other hepatotoxic factors, particularly alcohol, the use of a baseline biopsy to identify subsequent changes, and the early detection of fibrosis by sensitive histological techniques.

Adult↗
PubMed1982

Alpha-1-antitrypsin deficiency presenting as a bleeding diathesis in the newborn.

Three cases of alpha-1-antitrypsin deficiency are reported. Each infant presented in the newborn period with a haemorrhagic tendency which responded to vitamin K. Two of them subsequently developed cirrhosis, and Case 2 is one of the few reported cases in infantile cirrhosis associated with the heterozygous protease inhibitor (Pi) SZ phenotype. On the basis of these 3 patients we feel that the exclusion of alpha-1-antitrypsin deficiency by Pi phenotyping should be considered in any baby presenting with a bleeding diathesis, especially in view of the genetic implications of the homozygous Pi ZZ phenotype.

Hemorrhagic Disorders↗