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Biomedical subjects

F W Hanna

Publications and source records attributed to F W Hanna.

13 recordsLinked to original sources

Pneumococcal necrotizing fasciitis in a patient with Type 2 diabetes.

Necrotizing fasciitis (NF) is a rare and often fatal soft-tissue infection involving the superficial fascial layers of the extremities, abdomen or perineum. Progression to septic shock can occur very rapidly with its associated high morbidity and mortality. NF is usually caused by beta haemolytic streptococci; less often a poly-microbial isolate is the cause. It typically occurs in patients with some degree of immune dysfunction. We present a case of severe pneumococcal necrotizing fasciitis in an obese patient with Type 2 diabetes. There was no history of trauma or evidence of diabetes-related complications. The initial presentation was with features of septic arthritis of the left knee, which subsequently progressed to NF. Differentiation from cellulitis is often difficult in the early stages. Invasive pneumococcal infections are extremely rare, with only a few reported in the literature. Moreover, our case highlights the need to consider other differential diagnoses (and to look out for complications) in patients with diabetes, especially if there is little clinical response to the initial treatment.

Adult↗

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↗

Effect of replacement doses of thyroxine on bone mineral density.

INTRODUCTION: Hyperthyroidism is associated with a reduction in bone mineral density (BMD). Suppressive doses of thyroxine (T4), inducing subclinical hyperthyroidism, have been reported by some investigators to reduce BMD. Little work has been done on replacement doses of T4. AIM: The aim was to investigate the effect of replacement doses of T4 on BMD. STUDY DESIGN: Cross-sectional study of hypothyroid patients on long-term T4 replacement doses, comparing those who had primary hypothyroidism with those who were previously hyperthyroid. PATIENTS: Fifty women on replacement doses of T4 for more than 5 years were recruited. Twenty-five were treated for primary (group 1) and 25 for radioiodine-induced hypothyroidism (group 2). They were well matched for age, menstrual status, smoking history, body mass index (BMI), dose and duration of T4 replacement as well as thyroid status. MEASUREMENTS: BMD was assessed by dual energy X-ray absorptiometry. Free T4 (FT4), FT3 as well as ultrasensitive TSH assays were used to assess thyroid status. RESULTS: The two groups showed no difference in BMD (g/cm2) of the lumbar spine (1.008 vs. 0.957, P = 0.25), femoral neck (0.745 vs. 0.735, P = 0.79) and total hip (0.878 vs. 0.837, P = 0.24). When the two groups were pooled, there was no significant difference between the patients and a reference population with femoral neck and total hip BMD expressed as a standard deviation (Z) score. However, the lumbar spine mean Z score was significantly greater than zero. For each site, there was a negative correlation of BMD with age in at least one group but, in general, BMI, FT4, FT3 and duration of T4 replacement did not correlate with BMD. T4 dose, however, had a consistent positive correlation with BMD in the spine, femoral neck and the hip (P = 0.01, 0.04 and 0.02, respectively) in group 2 but not group 1. CONCLUSION: In this study, there is no evidence for a difference in bone mineral density in patients receiving replacement doses of thyroxine irrespective of the aetiology of their hypothyroidism. The reduced bone mineral density associated with hyperthyroidism appears to be restored, maintained and in some cases possibly improved while on long-term thyroxine replacement post-radioiodine.

Absorptiometry, Photon↗

Regulatory peptides and other neuroendocrine markers in medullary carcinoma of the thyroid.

Medullary thyroid carcinoma (MTC) is an APUDoma (APUD refers to amine precursor uptake and decarboxylation) arising from the parafollicular cells. Diarrhoea has been reported in some 30% of patients, variously attributed to excess production of calcitonin (CT), serotonin (5-HT), vasoactive intestinal peptide (VIP) or other factors. The regulatory factors in MTC were examined employing immunocytochemistry and RIA to tumours and their extracts. The patients were followed up for more than 15 years. CT and calcitonin gene-related peptide were universally expressed in all the tumours. The neuroendocrine markers chromogranin A (and its fragments pancreastatin and WE-14), neurone-specific enolase, protein gene product 9.5 and carcino-embryonic antigen were found in the majority of MTCs and might be useful as immunocytochemical markers. 5-HT, substance P, neurokinin A, glucagon and VIP could not be detected, excluding them as candidates in the diarrhoea of MTC.

Apudoma↗

Expression of a novel receptor for the calcitonin peptide family and a salmon calcitonin-like peptide in the alpha-thyrotropin thyrotroph cell line.

We have previously shown an increased incidence of alpha-subunit-producing thyrotroph tumors after salmon calcitonin (sCT) injection into rats. However, it is not clear whether the effects of CT are direct or indirect. Our hypothesis was that for sCT to act directly, it must have a binding site on thyrotrophs. The alpha TSH cell line was used as a model for thyrotrophs. Receptor binding studies using alpha TSH membranes revealed a high affinity binding site for sCT [IC50 = 0.97 +/- 0.18 nM (n = 4); Kd = 5.45 +/- 0.43 nM (n = 3); binding capacity = 6.6 pmol/mg protein (n = 3)]. Rat CT did not compete with binding at this site. Receptor screening for other CT peptide family members revealed high specific binding for CT gene-related peptide (CGRP; IC50 = 0.25 +/- 0.08 nM; n = 3) and islet amyloid polypeptide (IC50 = 4.36 +/- 1.1 nM; n = 3). This together with the absence of rat CT binding excluded a conventional CT-binding site, and we propose a site similar to the CGRP subtype III receptor described in the rat nucleus accumbens. Guanosine 5'O-(3-thiotriphosphate) (GTP gamma S) (20 microM), reduced [125I]CGRP binding to 38% of maximal, indicating that this site is G-protein coupled. Immunocytochemically, all of the cells displayed intense sCT-like immunoreactivity, which was totally abolished by preabsorption of the antibody with sCT. The presence of this receptor supports the hypothesis that sCT mediates tumorigenesis via a direct pituitary action and, together with the coexistence of a sCT-like peptide in these cells, provides evidence for a possible autocrine role of this peptide in the control of thyrotroph function.

Amyloid↗