Spectrum of cutaneous granulomatous lesions: A 5-year experience in a tertiary care centre in Sarawak.

INTRODUCTION: Granulomatous skin lesions can have various histopathological features leading to diagnostic confusion. The study aimed to determine the frequency and pattern of different granulomatous skin lesions. MATERIALS AND METHODS: This was a 5-year retrospective study done between April 2017 and March 2022 at Dermatology Department, Sarawak General Hospital. Subjects with a clinicopathological diagnosis of granulomatous diseases were included in the analysis. RESULTS: A total of 1718 skin biopsies were done during the study periods, with 49 (2.8%) confirmed granulomatous skin lesions. Most patients were aged 40-60 with a male predominance of 51%. Most of the skin biopsy samples were taken from the upper limb (36%). In this study, epitheloid granuloma was the commonest subtype (21, 43%) followed by suppurative granuloma (12, 24%), tuberculoid granuloma (8, 16%) and foreign body granuloma (5, 10%). The commonest aetiology of granulomatous skin lesions in our study was infections (30, 61%) followed by foreign body inoculation (8, 16%). Fungal infection was the most common infective cause, followed by cutaneous tuberculosis. CONCLUSION: The major cause of granulomatous dermatoses in developing countries is still infections, fungal and tuberculosis being the leading causes.

Comparison of two different optical coherence tomography angiography devices in detecting healthy versus glaucomatous eyes - an observational cross-sectional study.

BACKGROUND: To understand the differences between two different optical coherence tomography angiography (OCTA) devices in detecting glaucomatous from healthy eyes by comparing their vascular parameters, diagnostic accuracy and test-retest reliability. METHODS: A cross-sectional observational study was performed on healthy and glaucoma subjects, on whom two sets of OCTA images of optic disc and macula were acquired using both AngioVue (Optovue, USA) and Swept Source (Topcon, Japan) OCTA devices during one visit. A novel in-house software was used to calculate the vessel densities. Diagnostic accuracy of the machines in differentiating healthy versus glaucomatous eyes was determined using area under the receiver operating characteristic curve (AUROC) and test-retest repeatability of the machines was also evaluated. RESULTS: A total of 80 healthy and 38 glaucomatous eyes were evaluated. Glaucomatous eyes had reduced mean vessel density compared to healthy controls in all segmented layers of the optic disc and macula using AngioVue (p ≤ 0.001). However, glaucomatous eyes had higher mean vessel density on optic disc scans using Swept Source, with lack of statistically significant difference between healthy and glaucomatous eyes. The AUROC showed better diagnostic accuracy of AngioVue (0.761-1.000) compared to Swept Source (0.113-0.644). The test-retest reliability indices were generally better using AngioVue than Swept Source. CONCLUSIONS: AngioVue showed better diagnostic capability and test-retest reliability compared to Swept Source. Further studies need to be undertaken to evaluate if there is any significant difference between the various machines in diagnosing and monitoring glaucoma.

Recovery of Lactobacillus casei strain Shirota (LcS) from faeces of healthy Singapore adults after intake of fermented milk.

To validate survival of Lactobacillus casei strain Shirota (LcS) during passage through the gastrointestinal tract of healthy Singaporean young adults, 21 participants (18-25 years old) were asked to consume a 100 ml of fermented milk drink containing 1.0×108 cfu/ml of LcS daily for 14 days, and to maintain their dietary habit and life style. During and at the end of the ingestion period, both culture method (identity confirmed by ELISA) and 16s rRNA sequencing results revealed that viable LcS (7.27 and 7.64 log10 cfu/g of faeces at the ingestion period Day 7 and Day 14, respectively) and Lactobacillus could be recovered from the faeces of all the subjects. The viable LcS count from male and female were comparable for each time point. Before consumption (baseline) and 14 days after cessation of consumption of the fermented milk, LcS was not detected in most of the subjects. In this study condition, the composition of the major gut microbiota (>0.1% in relative abundance of genus) and characteristics of defaecation such as stool consistency and frequency of defecation did not change throughout the study before and after ingestion of LcS. LcS was able to survive passage through the gastrointestinal tract of Singapore adults without sustainable colonisation, but the effect of LcS on microbiota modulation, stool consistency and frequency was not observed under this study condition.

An unexpected cause for aplastic anaemia in an elderly woman.

Aplastic anaemia is a rare clinical syndrome associated with diminished or absent precursors in the bone marrow. Acquired aplastic anaemia secondary to human immunodeficiency virus (HIV) is very rare. We present a 71-year-old woman with severe aplastic anaemia secondary to HIV infection, which was after extensive exclusion of other causes. She achieved undetectable viral load after 5 months of combination antiretroviral therapy but remains profoundly pancytopenic, complicated by recurrent infectious and bleeding complications. HIV infection should be considered in patients with pancytopenia.

Aggressive osteoblastoma of the proximal humerus.

A nine-year-old boy presented with increasingly worsening right shoulder pain of 18 months' duration. On physical examination, there was a tender firm swelling over the right upper arm. Radiographs showed a large osteolytic lesion in the proximal humeral diaphysis, with prominent mixed acute-on-chronic periosteal reaction in a lamellar fashion. There was a pathological fracture. The lesion appeared to be radiographically aggressive in nature. Bone scintiscan showed solitary marked uptake. On-table frozen section histopathological examination of the lesion showed an osteoblastic lesion with aggressive features. Completion curettage and high speed burring of the cavity was performed. In view of the patient's young age, which required a biological solution, and potential for local recurrence, that necessitated a radiopaque filler, the lesion was packed with a calcium phosphate cement paste. The final diagnosis was osteoblastoma with aggressive features. The patient remained well on follow-up to date. The filler continues to be remodelled to native tissue and there is no evidence of local recurrence. Osteoblastoma is a relatively rare benign tumour that typically occurs in the posterior elements of the vertebral column. The humerus is a very rare site of disease in the appendicular skeleton, and poses a diagnostic dilemma which implicates the possibility of osteogenic sarcoma.

Generation of radially polarized beam with a segmented spiral varying retarder.

We convert a linearly polarized Gaussian beam into a radially polarized doughnut beam with an eight-segment spirally varying retarder (SVR) at wavelength of 808 nm. The SVR is designed based on the linear birefringence of alpha-barium borate (alpha-BBO) crystal and fabricated using a dry etching process. Radially polarized light of high purity (> 96% at far-field distribution) was generated experimentally using the segmented SVR positioned between two quarter waveplates with orthogonal slow axes. The emergent polarization can be switched between radially and azimuthally polarized cylindrical vector beams with a pair of half-wave plates.

Mimicking optical activity for generating radially polarized light.

We propose a new scheme for generating radially polarized light by mimicking optical activity using linear birefringence. It involves a birefringent spirally varying retarder sandwiched between two orthogonally oriented quarter-wave plates. Using Poincaré sphere representation, we show that the polarization transformation of such a scheme is equivalent to that of a spirally varying optical activity and is capable of generating radially polarized light. We demonstrate the proof-of-concept using y-cut crystalline quartz.

Paediatric PNET: pre-surgical MRI features.

AIM: To describe the preoperative magnetic resonance imaging (MRI) characteristics of primitive neuroectodermal tumours (PNETs), in particular the diffusion-weighted imaging (DWI), MR spectroscopy (MRS) features and cerebrospinal fluid (CSF) tumour dissemination. MATERIAL AND METHODS: Twelve patients with PNETs were reviewed: nine with medulloblastoma and three with supratentorial PNETs (SPNETs). The MRI examination included contrast-enhanced intracranial and spinal MRI, and in some patients, gradient recalled echo, fluid-attenuated inversion recovery (FLAIR), DWI, and MRS. RESULTS: All PNETs were either hypointense or isointense on T1-weighted images. Ten of the 12 tumours were either isointense or hypointense on T2-weighted images, and 11 were isointense on FLAIR images. Patients with SPNETs had large, vascular and haemorrhagic tumours. On DWI, all PNETs were hyperintense and had restricted apparent diffusion coefficient. MRS (two patients with medulloblastoma and one with a SPNET), showed elevated choline, decreased N-acetyl aspartate, and a small taurine peak in all three patients. Intraspinal tumour dissemination, visible as uniform or nodular enhancement coating the conus medullaris, was detected in six of 12 patients, two of whom also had intracranial dissemination. CONCLUSION: PNETs have a characteristic imaging appearance on FLAIR, DWI and MRS, which may help in differentiating these highly cellular neoplasms from other tumours. There is CSF tumour dissemination in a high proportion of patients, and spinal imaging is important for disease staging and to formulate treatment protocols.

Follow-up imaging of the urinary tract in spinal injury patients: is a KUB necessary with every ultrasound?

STUDY DESIGN: Prospective study of 100 consecutive patients. OBJECTIVES: To evaluate the diagnostic usefulness of the urinary tract (KUB) radiograph routinely performed as part of spinal injury patient urinary tract screening with ultrasound (US) and the KUB radiograph. SETTING: Orthopaedic and District General Hospital with spinal injuries unit, UK. METHODS: Prospective study of the urinary tract of 100 consecutive routine follow-up spinal injury patients with KUB (kidneys, ureters, bladder) radiograph and US of the urinary tract. The percentage of the visualised area of kidneys and urinary bladder and relevant abnormal findings were recorded. Relevant patient history was recorded. RESULTS: In all, 80 men 20 women were examined (average age 46 years, average time since injury 11 years). A total of 199 kidneys and 99 urinary bladders were examined. On average, less than 50% of the renal area and about 70-75% of the urinary bladder area were visualised. Five patients had renal stones identified on the KUB radiograph, and of these two were seen on US. There were no stones seen on US only. The patient history was not helpful to identify patients with renal stones. Significant further renal abnormalities were identified with US in 14 patients, and with the KUB radiograph in 0 patients. Significant urinary bladder abnormalities were identified with US in 20 patients, and with the KUB radiograph in 0 patients. CONCLUSION: On average, less than 50% of the kidney area is visualised on the KUB due to overlying bowel markings making the KUB radiograph a poor tool to assess the kidneys. The KUB radiograph and US are poor tools to assess urinary tract stones. In the absence of a therapeutic consequence, the KUB radiograph does not seem justified in the routine follow-up of the urinary tract in spinal injury patients.

Clinics in diagnostic imaging (87). Subcutaneous lipoma.

A 40-year-old man presented with recent increase in size of a painless long-standing soft mass over the right shoulder. Magnetic resonance (MR) imaging showed a lobulated mass located within the subcutaneous layer overlying the deltoid muscle. It was homogeneously T1-hyperintense, T2-hyperintense, and non-enhancing. Signal characteristics were those of a simple lipoma. The diagnosis was confirmed on histopathological examination of the excised specimen. Musculoskeletal lipomas are discussed, with emphasis on their characteristic appearances on various imaging modalities, and illustrated by additional examples.

Analysis of the nu(12) Band of Ethylene-(13)C(2) by High-Resolution FTIR Spectroscopy.

The Fourier transform infrared (FTIR) spectrum of the nu(12) fundamental band of ethylene-(13)C(2) ((13)C(2)H(4)) was recorded with an unapodized resolution of 0.004 cm(-1) in the frequency range from 1380 to 1500 cm(-1). Rovibrational constants for the upper state (nu(12)=1) up to five quartic and three sextic centrifugal distortion terms were derived for the first time by assigning and fitting a total of 1177 infrared transitions using a Watson's A-reduced Hamiltonian in the I(r) representation. The rms deviation of the fit was 0.00045 cm(-1). The ground state rovibrational constants were also determined for the first time by a fit of 738 combination differences from the present infrared measurements, with a rms deviation of 0.00060 cm(-1). The A-type nu(12) band with a band center at 1436.65411+/-0.00005 cm(-1) was found to be relatively free from local frequency perturbations. The inertial defect Delta(12) was found to be 0.24300+/-0.00002 uÅ(2). Copyright 2001 Academic Press.

High resolution FTIR spectrum of the nu1 band of DCOOD.

Accurate spectral information on formic acid has wide application to radioastronomy since it was the first organic acid found in interstellar space. In this work, the infrared absorption spectrum of the nu1 band of deuterated formic acid (DCOOD) has been measured on a Bomem DA3.002 Fourier transform spectrometer in the wavenumber region 2560-2690 cm(-1) with a resolution of 0.004 cm(-1). A total of 292 infrared transitions have been assigned in this hybrid type A and B band centred at 2631.8736 +/- 0.0004 cm(-1). The assigned transitions have been fitted to give a set of eight rovibrational constants for the nu1 = 1 state with a standard deviation of 0.00078 cm(-1).

Clinics in diagnostic imaging (37). Germinoma of the pineal gland.

Tumours occurring in the region of the pineal gland are uncommon in paediatric patients but may manifest with typical signs and symptoms. A 6-year-old boy with precocious puberty caused by a germinoma of the pineal gland detected on skull radiographs and confirmed on MR imaging is reported. The different types of tumours occurring in the region of the pineal gland and their imaging findings are discussed.

The crystal structure of an intact human Max-DNA complex: new insights into mechanisms of transcriptional control.

BACKGROUND: Max belongs to the basic helix-loop-helix leucine zipper (bHLHZ) family of transcription factors. Max is able to form homodimers and heterodimers with other members of this family, which include Mad, Mxi1 and Myc; Myc is an oncoprotein implicated in cell proliferation, differentiation and apoptosis. The homodimers and heterodimers compete for a common DNA target site (the E box) and rearrangement amongst these dimer forms provides a complex system of transcriptional regulation. Max is also regulated by phosphorylation at a site preceding the basic region. We report here the first crystal structure of an intact bHLHZ protein bound to its target site. RESULTS: The X-ray crystal structure of the intact human Max protein homodimer in complex with a 13-mer DNA duplex was determined to 2.8 A resolution and refined to an R factor of 0.213. The C-terminal domains in both chains of the Max dimer are disordered. In contrast to the DNA observed in complex with other bHLH and bHLHZ proteins, the DNA in the Max complex is bent by about 25 degrees, directed towards the protein. Intimate contacts with interdigitating sidechains give rise to the formation of tetramers in the crystal. CONCLUSIONS: The structure confirms the importance of the HLH and leucine zipper motifs in dimerization as well as the mode of E box recognition which was previously analyzed by X-ray crystallography of shortened constructs. The disorder observed in the C-terminal domain suggests that contacts with additional protein components of the transcription machinery are necessary for ordering the secondary structure. The tetramers seen in the crystal are consistent with the tendency of Max and other bHLHZ and HLH proteins to form higher order oligomers in solution and may play a role in DNA looping. The location of the two phosphorylation sites at Ser1 and Ser10 (the latter is the N-cap of the basic helix) suggests how phosphorylation could disrupt DNA binding.

Characterization of thymic involution induced by murine cytomegalovirus infection.

Infection of BALB/c mice with murine cytomegalovirus (MCMV) decreased the numbers of cells recovered from the thymus by 80-90% after 4-7 days, although less than 10 thymocytes per million were productively infected with the virus. A loss of cortical thymocytes was evident in histologic sections and correlated with depletion of CD4+ CD8+ cells. Thymic involution was minimal in C57BL/6 mice. This resistance was not H-2b-associated, as BALB.B (H-2b) mice were severely affected. In CXB recombinant inbred mice, thymic involution and MCMV replication co-segregated with atrophy and infection of the spleen and bone marrow. This suggests common regulation by natural killer (NK)1.1+ cells, consistent with the enhanced thymic involution demonstrated in NK-deficient bg/bg mice. However, CD4- CD8- cells were not depleted, so bone marrow hypoplasia may not be the proximal cause of thymic involution. MCMV infection activated CD4+, CD8+ and CD4+ CD8+ thymocytes, as expression of MEL14, major histocompatibility complex class I (H-2) and Sca-1 antigens increased on these cells. In vitro lymphoproliferation and interleukin (IL)-3 release were enhanced in unseparated and CD4(+)-enriched thymus preparations. Maturation of the thymus population was also evident from the high frequencies of single positive CD4+ and CD8+ cells and the decline in Sca-2 expression. However, unlike peripheral T cells, thymocytes from infected mice did not release IL-2. The results suggest that thymic involution accelerates the transit of cells through the thymus. The possibility that this impairs the elimination of autoreactive T cells within the thymus and promotes the autoimmune manifestations of MCMV disease is discussed.

Modulation of immunocompetence by cyclosporin A, cyclophosphamide or protein malnutrition potentiates murine cytomegalovirus pneumonitis.

Following intranasal infection with murine cytomegalovirus (MCMV), the levels of viral replication in the lungs of susceptible BALB/c mice were enhanced by treatment with cyclophosphamide (CY), or to a greater extent cyclosporin A (CsA) or the Nu/Nu genotype. Focal inflammation was seen 2-4 days after infection in all groups. This was followed by diffuse interstitial pneumonitis which cleared 12-20 days later in the absence of immunosuppression. Although the initial foci of inflammation were less prominent in infected mice treated with CY or CsA, the most severe interstitial pneumonitis was seen 7 days p.i. in mice given CY, whilst CsA-treatment produced focal and disseminated pneumonitis 7-14 days p.i. and Nu/Nu mice exhibited only the focal response. MCMV-infected mice maintained from weaning on a low protein (4% casein) diet also retained higher titres of virus in their lungs than did normally-fed controls, and displayed more prominent focal pneumonitis.

The effects of protein malnutrition on the pathogenesis of murine cytomegalovirus disease.

BALB/c and CBA mice maintained on low (4%) or normal (18%) protein diets for 2 weeks after weaning were infected with a sublethal dose of murine cytomegalovirus, adjusted in proportion to body weight. Viral replication, histopathological changes and humoral responses to the virus were compared between the dietary groups 2-42 days post infection (p.i.). Higher numbers of viral antigen-positive cells and/or more prominent tissue necrosis were noted in the livers, spleens, hearts, adrenal glands, kidneys and bone marrows of infected protein-deficient mice. These mice also showed a delayed onset of leucocytic exudation in their livers and salivary glands, relative to infected mice on the normal diet. Second peaks of viral replication were detected by plaque assays in livers and spleens from protein-deficient mice and in livers from normal mice 12-18 days p.i., but few antigen-positive cells and no tissue necrosis were observed. Virus also persisted at higher titres in the salivary glands from protein-deficient mice. Although cellular immunity may be defective in these mice, humoral IgG and IgM responses to the virus were not inhibited. The influence of genetic factors on the pathogenesis of murine cytomegalovirus disease in protein-deficient mice is discussed.

Improved sperm concentration, motility, and fertilization rates following Ficoll treatment of sperm in a human in vitro fertilization program.

Duplicate sperm samples from the spouses of 54 patients admitted to an in vitro fertilization program were prepared by the swim-up and a simplified procedure using Ficoll. Cellsoft (CRYO Resources, New York, NY) sperm curvilinear velocities (microns/sec) and mean amplitude of lateral head displacement values (microns) equivalent to grade 1 and 2 visual sperm motility were significantly higher for Ficoll as compared with swim-up samples (P less than 0.01). Fertilization rates were significantly higher in the Ficoll as compared with the swim-up group for poor semen samples (grade less than 2: 58% versus 24%; P less than 0.01) and normal semen samples (grade greater than or equal to 2: 85% versus 78%; P less than 0.05). Ficoll sperm separation appears to be an excellent method of yielding increased fertilization rates in in vitro fertilization programs.