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Platelet accumulation in brain microvessels in fatal pediatric cerebral malaria

Grau GE, Mackenzie CD, Carr RA, Redard M, Pizzolato G, Allasia C, et al.

J Infect Dis, 2003 Feb 1;187(3):461-6.
PMID: 12552430

The pathogenesis of fatal cerebral malaria (CM) is not well understood, in part because data from patients in whom a clinical diagnosis was established prior to death are rare. In a murine CM model, platelets accumulate in brain microvasculature, and antiplatelet therapy can improve outcome. We determined whether platelets are also found in cerebral vessels in human CM, and we performed immunohistopathology for platelet-specific glycoprotein, GPIIb-IIIa, on tissue from multiple brain sites in Malawian children whose fatal illness was severe malarial anemia, CM, or nonmalarial encephalopathy. Platelets were observed in 3 locations within microvessels: between malaria pigment and leukocytes, associated with malaria pigment, or alone. The mean surface area of platelet staining and the proportion of vessels showing platelet accumulation were significantly higher in patients with CM than in those without it. Platelet accumulation occurs in the microvasculature of patients with CM and may play a role in the pathogenesis of the disease.

Matched MeSH terms: Anemia
Fulltext Plasmodium knowlesi malaria during pregnancy

Barber BE, Bird E, Wilkes CS, William T, Grigg MJ, Paramaswaran U, et al.

J Infect Dis, 2015 Apr 1;211(7):1104-10.
PMID: 25301955 DOI: 10.1093/infdis/jiu562

BACKGROUND: Plasmodium knowlesi is the commonest cause of malaria in Malaysia, but little is known regarding infection during pregnancy.
METHODS: To investigate comparative risk and consequences of knowlesi malaria during pregnancy, we reviewed (1) Sabah Health Department malaria-notification records created during 2012-2013, (2) prospectively collected data from all females with polymerase chain reaction (PCR)-confirmed malaria who were admitted to a Sabah tertiary care referral hospital during 2011-2014, and (3) malaria microscopy and clinical data recorded at a Sabah tertiary care women and children's hospital during 2010-2014.
RESULTS: During 2012-2013, 774 females with microscopy-diagnosed malaria were notified, including 252 (33%), 172 (20%), 333 (43%), and 17 (2%) with Plasmodium falciparum infection, Plasmodium vivax infection, Plasmodium malariae/Plasmodium knowlesi infection, and mixed infection, respectively. Among females aged 15-45 years, pregnancy was reported in 18 of 124 (14.5%), 9 of 93 (9.7%), and 4 of 151 (2.6%) P. falciparum, P. vivax, and P. malariae/P. knowlesi notifications respectively (P = .002). Three females with knowlesi malaria were confirmed as pregnant: 2 had moderate anemia, and 1 delivered a preterm low-birth-weight infant. There were 17, 7, and 0 pregnant women with falciparum, vivax, and knowlesi malaria, respectively, identified from the 2 referral hospitals.
CONCLUSIONS: Although P. knowlesi is the commonest malaria species among females in Sabah, P. knowlesi infection is relatively rare during pregnancy. It may however be associated with adverse maternal and pregnancy outcomes.
KEYWORDS: Plasmodium knowlesi; malaria; maternal anemia; pregnancy; preterm delivery

Matched MeSH terms: Anemia
Fulltext No evidence that protein truncating variants in BRIP1 are associated with breast cancer risk: implications for gene panel testing

Easton DF, Lesueur F, Decker B, Michailidou K, Li J, Allen J, et al.

J Med Genet, 2016 May;53(5):298-309.
PMID: 26921362 DOI: 10.1136/jmedgenet-2015-103529

BACKGROUND: BRCA1 interacting protein C-terminal helicase 1 (BRIP1) is one of the Fanconi Anaemia Complementation (FANC) group family of DNA repair proteins. Biallelic mutations in BRIP1 are responsible for FANC group J, and previous studies have also suggested that rare protein truncating variants in BRIP1 are associated with an increased risk of breast cancer. These studies have led to inclusion of BRIP1 on targeted sequencing panels for breast cancer risk prediction.
METHODS: We evaluated a truncating variant, p.Arg798Ter (rs137852986), and 10 missense variants of BRIP1, in 48 144 cases and 43 607 controls of European origin, drawn from 41 studies participating in the Breast Cancer Association Consortium (BCAC). Additionally, we sequenced the coding regions of BRIP1 in 13 213 cases and 5242 controls from the UK, 1313 cases and 1123 controls from three population-based studies as part of the Breast Cancer Family Registry, and 1853 familial cases and 2001 controls from Australia.
RESULTS: The rare truncating allele of rs137852986 was observed in 23 cases and 18 controls in Europeans in BCAC (OR 1.09, 95% CI 0.58 to 2.03, p=0.79). Truncating variants were found in the sequencing studies in 34 cases (0.21%) and 19 controls (0.23%) (combined OR 0.90, 95% CI 0.48 to 1.70, p=0.75).
CONCLUSIONS: These results suggest that truncating variants in BRIP1, and in particular p.Arg798Ter, are not associated with a substantial increase in breast cancer risk. Such observations have important implications for the reporting of results from breast cancer screening panels.

Matched MeSH terms: Fanconi Anemia Complementation Group Proteins
Fulltext Case review of sarcoidosis resembling Sjogren's syndrome

Ahmad Y, Shahril NS, Hussein H, Said MS

J Clin Med Res, 2010 Dec 11;2(6):284-8.
PMID: 22043264 DOI: 10.4021/jocmr482w

We would like to report a case of a 29-year-old male patient who presented with multiple lymphadenopathy and vague symptoms of low grade fever, cough, weight loss, rashes, vomiting, dry eyes and dry mouth. Physical examination revealed submandibular lymphadenopathy, vasculitic rashes over both lower limbs, and parotid gland enlargement. Blood investigations showed mild anemia with leukocytosis, predominantly eosinophilia and high erythrocyte sedimentation rate and C-reactive protein. Computed tomography of the neck, thorax and abdomen showed bilateral submandibular, submental adenopathy, mediastinal and para-aortic lymphadenopathy with generalized reticulonodular densities in both lower lobes. There were hepatomegaly and bilateral enlarged kidneys with renal cyst. Histopathological examination from the cervical lymph node later revealed non-caseating granuloma, consistent of sarcoidosis. Patient responded well to prednisolone 50 mg daily with subsequent reduction in the size of cervical lymphadenopathy and parotid swelling.

KEYWORDS: Lymphadenopathy; Granuloma; Sjogren; Sarcoidosis.

Matched MeSH terms: Anemia
Fulltext Pyoderma gangrenosum and cobalamin deficiency in systemic lupus erythematosus: a rare but non fortuitous association

Teoh SC, Sim CY, Chuah SL, Kok V, Teh CL

BMC Rheumatol, 2021 Mar 03;5(1):7.
PMID: 33653418 DOI: 10.1186/s41927-021-00177-4

BACKGROUND: Pyoderma gangrenosum (PG) is an uncommon, idiopathic, ulcerative neutrophilic dermatosis. In many cases, PG is associated with a wide variety of different disorders but SLE in association with PG is relatively uncommon. In this article we present the case of a middle aged patient with PG as the initial clinical presentation of SLE. We also provide a brief review of cobalamin deficiency which occurred in our patient and evidence-based management options.
CASE PRESENTATION: A 35 years old man presented with a 5 month history of debilitating painful lower limb and scrotal ulcers. This was associated with polyarthralgia and morning stiffness involving both hands. He also complained of swallowing difficulties. He had unintentional weight loss of 10 kg and fatigue. Physical examination revealed alopecia, multiple cervical lymphadenopathies, bilateral parotid gland enlargement and atrophic glossitis. There was Raynaud's phenomenon noted over both hands and generalised hyper-pigmented fragile skin. Laboratory results disclosed anaemia, leukopenia, hyponatraemia and hypocortisolism. Detailed anaemic workup revealed low serum ferritin and cobalamin level. The autoimmune screen showed positive ANA, anti SmD1, anti SS-A/Ro 52, anti SSA/Ro 60, anti U1-snRNP with low complement levels. Upper gastrointestinal endoscopy with biopsies confirmed atrophic gastritis and duodenitis. Intrinsic factor antibodies and anti-tissue transglutaminase IgA were all negative. Punch biopsies of the leg ulcer showed neutrophilic dermatosis consistent with pyoderma gangrenosum. Based on the clinical findings and positive immunologic studies, he was diagnosed as systemic lupus erythematosus. His general condition improved substantially with commencement of corticosteroids, immunosuppressants and vitamin supplements.
CONCLUSIONS: We report a case of PG as the first manifestation of SLE which was treated successfully with immunosuppressants and vitamin supplements. Our report highlighted the need to consider connective tissue diseases such as SLE in a patient presenting with PG in order for appropriate treatment to be instituted thereby achieving a good outcome.

Matched MeSH terms: Anemia
Fulltext Nutritional anemia in pregnancy: a study at the maternity hospital, Kuala Lumpur

Tee ES, Kandiah M, Ali J, Kandiah V, Zahari MR, Kuladevan R, et al.

Malays J Reprod Health, 1984 Jun;2(1):32-50.
PMID: 12267519

The study presents recent data on the prevalence and pattern of nutritional anemia in the Maternity Hospital, Kuala Lumpur. A total of 309 pregnant women in their third trimester, of Malay, Chinese and Indian origin from the lower socio-economic strata were randomly selected for the study. Hematological indices (including Hb, PCV, MCHC, and TRBC), serum iron, transferrin saturation and ferritin, serum folate as well as protein and albumin were determined. Based on Hb and PCV values, 30-40 percent of the women could be considered anemic; approximately 50 percent of them presented with unsatisfactory serum iron, transferrin saturation and ferritin values; 60.9 percent had low serum folate levels; and about 30 percent may be considered to be of poor protein nutriture. Anemia in the study population was seen to be related mostly to iron and to a lesser extent, folate deficiency. Hematological, iron, folate and protein status was observed to be the poorest amongst the Indian women, better in the Malay group and generally the best amongst the Chinese women. Birth records of 169 of these women revealed that all of them had live births. Nearly all the infants were delivered by normal vaginal delivery (NVD) The mean gestational age was 38.6 weeks. One of the infants had a birth weight of <2.0 kg; incidence of low birth weight, <2.5 kg, was 8.3 percent. Although there was a trend of deteriorating hematological, iron and protein status of women from the 0, 1 -3 and >=4 parity groups, these differences were not statlstlcally significant.

Matched MeSH terms: Anemia*