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1.  A Virtual Surgical Environment for Rehearsal of Tympanomastoidectomy 
This article presents a virtual surgical environment whose purpose is to assist the surgeon in preparation for individual cases. The system constructs interactive anatomical models from patient-specific, multi-modal preoperative image data, and incorporates new methods for visually and haptically rendering the volumetric data. Evaluation of the system’s ability to replicate temporal bone dissections for tympanomastoidectomy, using intraoperative video of the same patients as guides, showed strong correlations between virtual and intraoperative anatomy. The result is a portable and cost-effective tool that may prove highly beneficial for the purposes of surgical planning and rehearsal.
PMCID: PMC3434876  PMID: 21335772
Surgical simulation; surgical rehearsal; haptic rendering; volume rendering; patient-specifc models; temporal bone surgery
2.  Acquired Epidermodysplasia Verruciformis Due to Multiple and Unusual HPV Infection Among Vertically-Infected, HIV-Positive Adolescents in Zimbabwe 
We have characterized the EV-like dermatosis of acquired HIV in 4 adolescents. Multiple HPV types were isolated in skin tissue samples, including β-HPV, but also high levels of HPV 1 and 2. ARV did not improve the EV eruption.
Background. We have previously described the presentation of epidermodysplasia verruciformis (EV)–like eruptions in almost a quarter of hospitalized adolescents with vertically-acquired human immunodeficiency virus (HIV) infection in Harare, Zimbabwe, a region with a high prevalence of HIV infection.
Methods. We performed a clinical case note review and skin biopsy from affected sites in 4 HIV-infected adolescents with EV-like lesions in Harare. Biopsies were processed for histology and for human papillomavirus (HPV) typing.
Results. All patients had long-standing skin lesions that pre-dated the diagnosis of HIV by several years. The histology of skin biopsies from all patients was consistent with EV. In each biopsy, EV-associated β-HPV type 5 was identified (additionally, type 19 was found in 1 biopsy). Cutaneous wart–associated HPV types 1 and 2 were detected in all biopsies, together with genital lesion–associated HPV types 6, 16, and 52, (as well as ≥3 other genital lesion–associated HPV types). Despite immune reconstitution with combination antiretroviral therapy (cART), there was no improvement in EV-like lesions in any patient.
Conclusions. EV is a disfiguring and potentially stigmatizing condition among this patient group and is difficult to treat; cART appears to have no impact on the progression of skin disease. Among adolescents with longstanding HIV-induced immunosuppression and with high levels of sun exposure, close dermatological surveillance for potential skin malignancy is required.
doi:10.1093/cid/cis118
PMCID: PMC3334361  PMID: 22474219
4.  Myeloma associated amyloidosis presenting as subacute liver failure 
Postgraduate Medical Journal  2006;82(969):e13.
Multiple myeloma related amyloidosis is rare and its presentation with subacute liver failure (SALF) has not been reported. A case is described of a 46 year old woman presenting with a six week history of nausea, abdominal pain, and jaundice. Routine tests failed to establish a cause. Computed tomography showed a small volume liver consistent with SALF. Emergency liver transplantation was not undertaken because of the suspicion of underlying malignancy. At necropsy, liver biopsy showed amyloid deposition and bone marrow biopsy showed multiple myeloma. Thus, amyloidosis should be added to the list of potential causes of SALF.
doi:10.1136/pgmj.2006.044883
PMCID: PMC2563768  PMID: 16822912
amyloidosis; multiple myeloma; acute liver failure; proteinuria
5.  Angiogenesis in chronically ischaemic human heart following percutaneous myocardial revascularisation 
Heart  2002;87(3):281-283.
PMCID: PMC1767021  PMID: 11847177
angiogenesis; percutaneous myocardial revascularisation; vascular endothelial growth factor
10.  Cyclophosphamide, methotrexate and infusional 5-fluorouracil (infusional CMF) in metastatic breast cancer. 
British Journal of Cancer  1998;77(11):1950-1956.
Bolus 5-fluorouracil (5-FU) is a phase-specific drug with a short plasma half-life that is used in combination with bolus cyclophosphamide and methotrexate in the treatment of breast cancer. The efficacy of 5-FU can be improved by continuous intravenous infusion using portable infusion pumps (infusional 5-FU). Infusional 5-FU, 200 mg m(-2) day(-1), in combination with standard doses of bolus cyclophosphamide and methotrexate, was evaluated in a phase I/II dose-finding study. The cyclophosphamide and methotrexate were administered in 28-day cycles as follows: cohort 1, cyclophosphamide 600 mg m(-2), days 1 and 8, and methotrexate 40 mg m(-2), day 1; cohort 2, cyclophosphamide 400 mg m(-2), days 1 and 8, and methotrexate 40 mg m(-2), day 1; cohort 3, cyclophosphamide 480 mg (m-2), days 1 and 8, and methotrexate 40 mg m(-2), day 1; cohort 4, cyclophosphamide 480 mg m(-2), days 1 and 8, and methotrexate 40 mg m(-2), days 1 and 8. Median overall survival was 10 months (range 3-21 months). Objective tumour responses were seen in 9 of 25 patients (36%, 95% CI 18-58%), including 3 of 13 patients (23%) previously treated for metastatic disease. Cohorts 1 and 4 proved to be too toxic, with five of six patients in cohort 1 and three of four in cohort 4 developing grade III/IV neutropenia. The dose intensity of cyclophosphamide achieved was as follows: cohort 1, 82%; cohort 2, 86%; cohort 3, 97%; cohort 4, 90%. Infusional 5-FU can be administered safely and is effective in combination with cyclophosphamide 480 mg m(-2), days 1 and 8, and methotrexate 40 mg m(-2), day 1, in the treatment of metastatic breast cancer.
PMCID: PMC2150339  PMID: 9667673
12.  Immunohistochemical analysis of CDw52 antigen expression in non-Hodgkin's lymphomas. 
Journal of Clinical Pathology  1994;47(4):313-317.
AIM--To determine the antigen expression of CDw52 using Campath-1 antibodies in a series of non-Hodgkin's lymphomas (NHLs). METHODS--Tissue sections of lymphoma were stained immunohistochemically using rat Campath-1G and humanised Campath-1H with avidin-biotin-peroxidase complex techniques. Fifty-two fresh frozen lymphomas and a further 26 paraffin wax embedded sections were studied. RESULTS--Thirty-seven out of 41 B cell lymphomas were positive with Campath-1H in frozen sections (low grade, 24 of 24; high grade, 13 of 17) as were three out of five T cell lymphomas. Reed-Sternberg cells in six cases of Hodgkin's disease did not react. Eleven out of 16 high grade B cell lymphomas also stained positively with Campath-1G in paraffin wax sections as did five out of 10 T cell lymphomas. CONCLUSIONS--The Campath-1 antibodies showed that CDw52 antigen expression was present in all cases of low grade B cell NHL examined. Immunohistochemical staining in high grade B cell NHL and in T cell NHL was variable. These findings may be relevant to patient selection when considering treatment with Campath-1 antibodies.
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PMCID: PMC501933  PMID: 8027367
15.  Biochemical and muscle studies in patients with acute onset post-viral fatigue syndrome. 
Journal of Clinical Pathology  1993;46(8):722-726.
AIMS--To investigate in detail various biochemical and pathophysiological indices of muscle pathology in acute onset post-viral fatigue syndrome (PVFS). METHODS--Twenty three patients with PVFS (of mean duration 4.6 years) were subjected to needle biopsy for histomorphometry and total RNA contents. Plasma analysis included serology and creatine kinase activities. Indices of whole body mass were also measured--namely, whole body potassium content and plasma carnosinase activities. RESULTS--About 80% of the patients had serology indicative of persistent enteroviral infection as determined by VP1 antigen assay. Only about 10% of that same group of patients had serological indications of current enterovirus infection by IgM assay; a separate subset of 10% showed antibody changes suggestive of reactivation of Epstein-Barr virus. Quantitative morphometric analysis of skeletal muscle fibres indicated that the quadriceps muscle was normal or displayed only minor abnormalities in 22 patients. The Quetelet's Index (body mass index) and whole-body potassium values (index of lean body mass) were not affected in PVFS. The mean plasma carnosinase and creatinine kinase activities were also generally normal in these patients. The mean muscle RNA composition--mg RNA/mg DNA--was significantly reduced in acute onset PVFS by about 15%. The protein:DNA ratio was not significantly affected. CONCLUSIONS--Patients with acute onset PVFS, therefore, lose muscle protein synthetic potential, but not muscle bulk. Histopathology is consistent with these observations. These perturbations may contribute to the apparent feature of perceived muscle weakness associated with the persistent viral infection in the muscle themselves.
PMCID: PMC501456  PMID: 7691895
17.  Skin biopsies in general practice. 
PMCID: PMC1239206  PMID: 7612326
18.  Osmotic diarrhoea and skeletal muscle protein synthesis in vivo. 
Gut  1996;38(1):40-46.
The pathogenic nature of the wasting seen in diarrhoea is unknown. This study measured protein synthesis in an established model of diarrhoea using lactose for seven days. Comparisons were also made with data obtained from rats fed an identical diet in which lactose was replaced by isocaloric glucose ad libitum (that is, the control diet). To account for diarrhoea induced anorexia, a third group of rats were included, which were fed identical amounts of the control diet as the rats with diarrhoea inducing diet. Comparisons of the diarrhoea induced group with rats fed the control diet ad libitum showed that diarrhoea caused a significant reduction in body weights. Type I and type II muscles showed significant reductions in protein, RNA, and DNA contents, as well as a fall in the derived parameters, RNA/DNA, protein/DNA, and RNA/protein. Fractional rates of protein synthesis (ks) were also reduced. However, synthesis rates of type I and II muscles relative to RNA (kRNA) were unchanged in these muscles in diarrhoea induced rats compared with ad libitum fed controls. In the jejunum there was an increase in the RNA/DNA ratio, and reductions in ks and kRNA. Comparisons were also made between rats with diarrhoea and rats pair fed the control diet. There were no changes in total muscle protein, RNA or DNA contents. This suggests that an important feature of body wasting in diarrhoea is the element of anorexia, which induces severe metabolic changes. The comparison between rats with diarrhoea and the pair fed group showed that histological features of the plantaris were not overtly changed, though diarrhoea caused significant reductions in RNA/DNA, protein/DNA, ks, and kRNA. Similar changes were seen for the soleus; though the reduction in ks failed to attain statistical significance. In the jejunum a comparison of diarrhoea induced rats with pair fed controls, showed increases in the ratios of RNA/DNA and protein/DNA.
PMCID: PMC1382977  PMID: 8566857
19.  Bryostatin 1, a novel antineoplastic agent and protein kinase C activator, induces human myalgia and muscle metabolic defects: a 31P magnetic resonance spectroscopic study. 
British Journal of Cancer  1995;72(4):998-1003.
Bryostatin 1, a novel antineoplastic agent and protein kinase C (PKC) activator, has been found to induce myalgia (muscle pain) 48 h after administration in clinical trials. This is the dose-limiting toxicity and has restricted the duration of therapy in phase I trials. To investigate the mechanisms and try to increase toleration of the drug, we studied calf muscle metabolism of 14 patients at rest and during exercise and subsequent recovery using 31P magnetic resonance spectroscopy (MRS) before and 4 h, 48-72 h and 1-2 weeks following bryostatin therapy. In resting muscle there was a significant (P < 0.001) increase in the phosphodiester/adenosine 5'-triphosphate (PDE/ATP) ratio 48 h post bryostatin and in patients with myalgia compared with pre-bryostatin control studies. Following exercise, patients with myalgia showed significantly slower phosphocreatine (PCr) and ADP recovery half-time (P < or = 0.05) suggesting impaired mitochondrial (oxidative) energy production, possibly due to a direct effect on the mitochondria or secondary to reduced blood flow. The apparent proton efflux rate following exercise was significantly reduced 4 h after bryostatin (P < or = 0.05), suggesting reduced blood flow. The rate of post-exercise reoxygenation was studied in four patients by near-infrared spectroscopy 4 h post bryostatin. In three of these the rate was reduced, consistent with reduced muscle blood flow. Bryostatin 1 appeared to cause a long-lasting impairment of oxidative metabolism and proton washout from muscle, consistent with a vasoconstrictive action. Thus these studies provide evidence for two mechanisms of the dose-limiting toxicity for bryostatin. Prospective studies on the use of vasodilators to improve the tolerance of the drug should be carried out.
PMCID: PMC2034030  PMID: 7547256
22.  Malignant fibrous histiocytoma. 
Postgraduate Medical Journal  1989;65(770):872-874.
PMCID: PMC2429559  PMID: 2559404
24.  Bilateral adrenal lymphoma presenting as Addison's disease. 
Postgraduate Medical Journal  1989;65(767):684-686.
We describe an unusual case of non-Hodgkin's lymphoma of the adrenals which presented as Addison's disease. Examination of tissue taken by computed tomography guided biopsy revealed a high grade B cell centroblastic lymphoma. The patient was treated with chemotherapy but died from invasive aspergillosis. Autopsy confirmed bilateral adrenal involvement by lymphoma.
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PMCID: PMC2429187  PMID: 2608603
25.  Primary central nervous malignant melanoma in the bathing trunk naevus syndrome. 
Postgraduate Medical Journal  1989;65(764):387-389.
The gross and microscopic features of an unusual case of neurocutaneous melanosis are described. This is an example of the rare association between a primary central nervous system malignant melanoma and a giant congenital melanocytic naevus of 'bathing trunk' distribution.
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PMCID: PMC2429329  PMID: 2608580

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