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Biomedical subjects

O M Williams

Publications and source records attributed to O M Williams.

8 recordsLinked to original sources

Novel method for detection, typing, and quantification of human papillomaviruses in clinical samples.

We report the development of a novel detection and typing methodology for human papillomaviruses (HPV) based on real-time PCR with the self-probing fluorescent primers known as Scorpions. This technique is quick, simple, specific, sensitive, and capable of estimating viral load per cell. We report the results of over 100 typing reactions performed on cell lines, biopsies, and cervical cytobrush samples which, when compared to the current reference HPV detection and typing technique, present a kappa value of 0.89. We further report preliminary data suggesting a relationship between viral load per cell and grade of cervical disease.

Cervix Uteri↗

Non-hepatic hyperammonaemia: an important, potentially reversible cause of encephalopathy.

The clinical syndrome of encephalopathy is most often encountered in the context of decompensated liver disease and the diagnosis is usually clear cut. Non-hepatic causes of encephalopathy are rarer and tend to present to a wide range of medical specialties with variable and episodic symptoms. Delay can result in the development of potentially life threatening complications, such as seizures and coma. Early recognition is vital. A history of similar episodes or clinical risk factors and early assessment of blood ammonia levels help establish the diagnosis. In addition to adequate supportive care, investigation of the underlying cause of the hyperammonaemia is essential and its reversal, where possible, will often result in complete recovery. Detection of an unborn error of metabolism should lead to the initiation of appropriate maintenance therapy and genetic counselling.

Adult↗

Vitamin D receptor gene polymorphisms and susceptibility to Mycobacterium malmoense pulmonary disease.

Polymerase chain reaction using sequence-specific primers was utilized to ascertain the prevalence of 3 polymorphisms of the vitamin D receptor (VDR) gene (FokI F/f, ApaI A/a, and TaqI T/t) in 56 patients with Mycobacterium malmoense pulmonary disease. When compared with 101 controls, M. malmoense patients displayed an increased prevalence of Apa1 A (P=.03; Fisher's exact test), TaqI t (P=.04), and the At VDR haplotype (P=.04), and they displayed a decreased prevalence of FokI f (P=.04). Only 4 (7%) of 56 patients (vs. 29 [28%] of 101 controls) were both positive for FokI f and negative for At (P=.001). This indicates that polymorphisms in the VDR (or in closely linked genes) modulate the susceptibility to M. malmoense and that susceptibility involves multiple genetic and environmental factors.

Disease Susceptibility↗

Pituitary apoplexy following metastasis of bronchogenic adenocarcinoma to a prolactinoma.

A 42-year-old house wife presented with worsening headaches over 6 months in the absence of visual symptoms or symptoms suggestive of focal neurology. She was a life-long smoker. Systems review was unremarkable apart from secondary amenorrhoea and galactorrhoea of 6 months duration. Her serum prolactin was found to be 620 mU/l (60-400), FT4 12.6 nmol/l (9.8-23.1), TSH 1.38 mU/l (0.35-5.5), oestradiol < 73 pmol/l, LH and FSH of 4.4 and 12.6 mIU/l, respectively. She was on bromocriptine. A presumptive diagnosis of pneumonia, based on pyrexia and CXR findings, was made and she was started on IV antibiotics. Two days later she developed meningism and deterioration of conscious level. (Lumbar puncture results: no organisms, 312 neutrophils and 164 lymphocytes). CT scan revealed a 2.5-cm pituitary adenoma, with suprasellar extension. A repeat hormonal profile revealed FSH 1.4, LH < 0.3 mU/l, oestradiol < 73 pmol/l, prolactin 488 mU/l (60-400), and low random cortisol at 29 nmol/l. T1-weighted MRI revealed a large pituitary mass with evidence of haemorrhage. The patient subsequently underwent a transsphenoidal exploration with resection of the pituitary lesion. Whilst awaiting the histopathology results, CT of chest revealed a 1. 5-cm diameter rounded well defined density in the right lower lobe associated with hilar, pre- and right para-tracheal lymphadenopathy. The histopathology of the pituitary lesion, obtained piecemeal, revealed fragments of fibrous tissue infiltrated by sheets of acidophilic prolactin-positive cells, in keeping with a prolactinoma. In addition, other fragments with blood clot included highly atypical epithelial cells with mitotic figures. These were negative for prolactin but showed HMFG-and CEA-positivity, excluding them from a pituitary lineage. Transbronchial biopsy revealed moderately differentiated adenocarcinoma, with evidence of lymphatic spread. The overall conclusion was of bronchogenic adenocarcinoma, metastasizing to a prolactinoma and complicated by apoplexy.

Adult↗

Isolated hyperthermic limb perfusion chemotherapy in Merkel cell tumour: a case report.

Merkel cell carcinoma of the skin is a rare malignant tumour first described in 1972 by Toker. The optimal management of this disease has not been clearly defined, especially that of advanced locoregional disease. Surgery, radiotherapy and chemotherapy have been advocated separately or in combination, with less-than-optimal results. Localized high-dose chemotherapy has never been tried, although it would seem to be the logical step forward.

Aged↗

Presence of a dysfunctional form of CD59 on a CD59+ subclone of the U937 cell line.

U937 cells are known to be relatively sensitive to C-mediated killing and have been reported to show variable expression of CD59. We have obtained stable CD59+ and CD59- sublines of the U937 cell line. Expression of other C-regulatory proteins, decay-accelerating factor (DAF), MCP and CR1, was similar on both cell lines. Although the sublines were morphologically similar and expressed similar amounts of most surface antigens, qualitative difference in expression of CD13 and CD64 and a quantitative difference in CD15 expression was observed. Sensitivity to C-mediated killing of the cell lines was measured using classical pathway activation. Both cell lines appeared to be equally sensitive to C-mediated killing. Monoclonal antibodies against CD59, which neutralize CD59 and enhance killing of most cell lines (including K562, HL60 and Molt4), did not enhance the killing of the CD59- cells but, surprisingly, also did not enhance killing of the CD59+ U937 subline. CD59 was expressed on the U937 subline at similar levels to that on HL60 and K562 cells, was glycosylphosphatidylinositol (GPI) anchored and could be immunoprecipitated from cell extracts. However, unlike these other cell lines, U937 cell extracts were negative in a Western blot using a variety of anti-CD59 antibodies even when ultrasensitive detection methods were used. These results indicate that the CD59+ U937 cell expresses a form of CD59 which is dysfunctional and structurally abnormal.

Animals↗