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Biomedical subjects

S Wharton

Publications and source records attributed to S Wharton.

13 recordsLinked to original sources

Extra-cranial metastasis of glioblastoma multiforme presenting as acute parotitis.

We present an unusual case of extracranial metastasis of glioblastoma multiforme (GBM) to the parotid gland and cervical lymph nodes. The patient had previously undergone two craniotomies to debulk a left frontal GBM, followed by radiotherapy. After the second craniotomy, while waiting for chemotherapy, the patient was re-admitted with a short history of a painful swelling of his left parotid gland. The initial diagnosis was infective parotitis; however, as there was no improvement with broad-spectrum antibiotics, CT was undertaken, which revealed a mass in the parotid gland with a necrotic centre and enlarged cervical lymph nodes. Parotid gland biopsy revealed a parotid GBM metastasis. This case illustrates how GBM behaves in an aggressive manner even outside the CNS. A brief review of the literature and of the theories, which might explain the extra-neural metastasis of this tumour is also presented.

Acute Disease↗

Vascular endothelial growth factor and the nervous system.

Vascular endothelial growth factor (VEGF) is an angiogenic factor essential for the formation of new blood vessels during embryogenesis and in many pathological conditions. A new role for VEGF as a neurotrophic factor has recently emerged. In the developing nervous system, VEGF plays a pivotal role not only in vascularization, but also in neuronal proliferation, and the growth of coordinated vascular and neuronal networks. After injury to the nervous system, activation of VEGF and its receptors may restore blood supply and promote neuronal survival and repair. There is a growing body of evidence that VEGF is essential for motor neurone survival, and that aberrant regulation of VEGF may play a role in the degeneration of neurones in diseases such as amyotrophic lateral sclerosis.

Animals↗

An antibody which binds to the membrane-proximal end of influenza virus haemagglutinin (H3 subtype) inhibits the low-pH-induced conformational change and cell-cell fusion but does not neutralize virus.

A monoclonal antibody, LMBH6, was derived from mice which had been sequentially immunized with bromelain-cleaved haemagglutinin (BHA) from influenza virus A/Aichi/2/68, A/Victoria/3/75 and A/Philippines/2/82 (all H3N2). LMBH6 recognizes the haemagglutinin (HA) of all H3N2 influenza A strains tested, which were isolated between 1968 and 1989. HA in the low-pH-induced conformation is not recognized, and cleavage of the HA0 precursor to HA1 and HA2 is needed to obtain efficient binding. Compared to other monoclonal antibodies, binding of LMBH6 to virus and to virus-infected cells is weak, while binding to BHA is comparable. Electron microscopy demonstrates binding to the membrane proximal end of the stem structure. The antibody shows no haemagglutination-inhibition activity, but inhibits polykaryon formation and the low-pH-induced conformational change of BHA. However, LMBH6 cannot prevent infection of MDCK cells but slows the growth of virus when included in a plaque assay overlay.

Animals↗

Adult polyglucosan body disease associated with an extrapyramidal syndrome.

A 50 year old patient is described who presented with parkinsonism, frontal dementia, peripheral neuropathy, neurogenic bladder, and upper motor neuron signs. No improvement in objective measurements of extrapyramidal dysfunction were seen with an incremental apomorphine test or more prolonged oral dopamine challenge. Neurophysiology disclosed changes compatible with a diffuse axonal neuropathy and pathological examination of a length of sural nerve taken at biopsy showed multiple polyglucosan bodies characteristic of adult polyglucosan body disease (APGBD). This case underlines the diverse clinical presentation of this rare neurological disease and the importance of recognising the unusual association of clinical features in making the diagnosis. APGBD should be included in the differential diagnosis of parkinsonism unresponsive to dopaminergic therapy.

Adult↗

Validation of 99Tcm-HMPAO leucocyte scintigraphy in ulcerative colitis by comparison with histology.

Leucocyte scintigraphy offers an alternative to more invasive techniques in the investigation of inflammatory bowel disease. The accuracy of 99Tcm-HMPAO leucocyte scintigraphy has not been assessed by comparison with colonic histology, which was the aim of this study. 15 patients with ulcerative colitis underwent 99Tcm-HMPAO leucocyte scintigraphy (TLS) less than 5 days before colonoscopy. Histological features of mucosal biopsies were compared with total and segmental colonic TLS scores. Segmental and total scintigraphy scores correlated most strongly with histological grades for acute inflammation (r = 0.75, p < 0.001 and r = 0.9, p < 0.001, respectively) and chronic inflammatory cell infiltration in the lamina propria (r = 0.76, p < 0.001 and r = 0.86, p < 0.001, respectively). 99Tcm-HMPAO leucocyte scintigraphy detected acute inflammation in the colon of patients with ulcerative colitis with a sensitivity of 91% and negative predictive value of 80% and localized acute inflammation to a particular colonic segment with a sensitivity of 82%, specificity of 94%, accuracy of 88%, positive predictive value of 94% and negative predictive value of 91%. 99Tcm-HMPAO leucocyte scintigraphy positivity predicts and localizes colonic acute inflammation with a high degree of confidence, but negative scintigraphy does not exclude acute inflammation.

Adult↗

Intravaginal immunization in sheep using a bioadhesive microsphere antigen delivery system.

An enzymatically cleaved glycoprotein fragment (amino acids 28-328: 40 kDa) from influenza virus haemagglutinin (TOPS) was used to assess an intravaginal antigen delivery system, comprising lysophosphatidylcholine (LPC) and degradable starch microspheres (DSM). Three groups of three sheep received intravaginal immunization with TOPS as follows: group 2, TOPS in solution; group 3, TOPS and DSM/LPC as a powder formulation and group 4, TOPS and LPC in solution. A fourth group, group 1, received intramuscular immunization with TOPS adsorbed to aluminium hydroxide gel (Alugel). Intravaginal immunizations were repeated on two consecutive days. Two weeks later, booster doses of the same formulations were administered on two consecutive days to each group. Group 1 sheep were boosted with a single injection, 2 weeks after the single primary immunization. The serum and vaginal wash IgA and IgG antibody responses were compared among the four groups of sheep at days 15, 30 and 45 after the booster immunizations. At day 45, the serum IgG and the vaginal wash IgA antibody responses induced by TOPS and DSM/LPC (group 3), were significantly greater than the responses induced by intravaginal immunization with TOPS (group 2). However, the highest levels of antibodies in serum and vaginal wash samples were induced by intramuscular immunization with TOPS and Alugel (group 1). Intravaginal immunization with TOPS and LPC (group 4) did not result in the induction of enhanced levels of antibodies in serum or vaginal wash samples.

Administration, Intravaginal↗

Bilateral and recurrent obturator hernia.

Obturator hernia is a rare condition which was first described in 1722 by de Ronsil. It occurs most commonly in elderly women who have lost weight and may strangulate in 25-100% of cases. Strangulated obturator hernia has a mortality as high as 10-50%, which is partly due to delay in diagnosis. A patient who developed three obturator hernias is described.

Aged↗

Moderate alcohol consumption during pregnancy and the incidence of fetal malformations: a meta-analysis.

To determine whether there is an association between moderate alcohol consumption in the first trimester of pregnancy and increased risk of fetal malformations, we conducted a literature search using Medline (1966-present), PsycLit (1974-1995), and EMBASE (1988-1995). The following inclusion criteria were used to select the studies to be evaluated: 1) pregnant women; 2) moderate alcohol consumption (> 2 drinks/week to 2 drinks/day); 3) case-control or cohort studies; 4) presence of an abstainer group (0 to 2 drinks/wk); 5) outcome measures include major or minor malformations; 6) papers published in the English language. The exclusion criteria were: 1) studies in which moderate alcohol consumption could not be confirmed; 2) case reports, and editorials. The Methods section of each study was examined independently by two blinded investigators with a third investigator settling any disagreement. The number of malformations in the abstainer and moderate alcohol consuming groups in two by two tables. Out of 24 studies which met the inclusion criteria, only seven had extractable data. The included studies evaluated 130,810 pregnancy outcomes, with 24,007 in the moderate alcohol group and 106,803 in the control group. An overall Mantel-Haenszel odds ratio showed that the relative risk for fetal malformations was 1.01 with 95% confidence limits of 0.94 to 1.08 and a chi-square for homogeneity of 8.26 (p = 0.220). Quality of the studies did not correlate with their showing negative or positive association. Moderate alcohol consumption during the first trimester of pregnancy is not associated with increased risk of fetal malformations.

Abnormalities, Drug-Induced↗