Dihydropyrimidine dehydrogenase deficiency as a cause of fatal 5-Fluorouracil toxicity

5-Fluorouracil (5-FU), in combination with other cytotoxic drugs, is commonly used to treat a variety of cancers. Dihydropyrimidine dehydrogenase (DPD) catalyzes the first catabolic step of the 5-FU degradation pathway, converting 80% of 5-FU to its inactive metabolite. Approximately 0.3% of the population demonstrate complete DPD deficiency, translating to extreme toxicity of 5-FU. Here we present a case of a patient who had a fatal outcome after treatment with 5-FU who was found to have an unknown DPD deficiency discovered at autopsy.

Minimum infectious dose for chikungunya virus in Aedes aegypti and Ae. albopictus mosquitoes / Dosis infecciosa mínima del virus del chikungunya en los mosquitos Aedes aegypti y Ae. albopictus

ABSTRACT Understanding the ability of the chikungunya virus (CHIKV) to be transmitted by Aedes vectors in the Americas is critical for assessing epidemiological risk. One element that must be considered is the minimum infectious dose of virus that can lead to transmission following the extrinsic incubation period. This study aimed to determine the minimum infection rate for the two Aedes species studied. The results revealed that doses as low as 3.9 log10 plaque-forming units per mL (pfu/mL) of an Asian genotype CHIKV strain can lead to transmission by Ae. albopictus, and doses of at least 5.3 log10 pfu/mL from the same strain are needed for transmission from Ae. aegypti. These low infecting doses suggest that infected individuals may be infectious for almost the entire period of their viremia, and therefore, to prevent further cases, measures should be taken to prevent them from getting bitten by mosquitoes during this period.(AU)

RESUMEN Comprender la capacidad del virus del chikungunya (CHIKV) de ser transmitido por los vectores del género Aedes en la Región de las Américas es fundamental para evaluar el riesgo epidemiológico. Un elemento que debe tenerse en cuenta es la dosis infecciosa mínima de virus que posibilita la transmisión después del período de incubación extrínseco. El objetivo de este estudio ha sido determinar la tasa de infección mínima para las dos especies del género Aedes estudiadas. Los resultados indican que bastan dosis de tan solo 3,9 log10 unidades formadoras de placas por mililitro (ufp/ml) de una cepa de CHIKV del genotipo asiático para que se produzca la transmisión por Ae. albopictus, en tanto que para la transmisión por Ae. aegypti se necesitan dosis de al menos 5,3 log10 ufp/ml de la misma cepa. Estas dosis bajas indican que las personas infectadas podrían conservar el potencial infeccioso prácticamente durante todo el período de viremia y, por consiguiente, a fin de prevenir más casos, habría que tomar medidas para impedir que reciban picaduras de mosquitos durante ese período.(AU)

A hypomorphic Cbx3 allele causes prenatal growth restriction and perinatal energy homeostasis defects.

Mammals have three HP1 protein isotypes HP1β (CBX1), HP1γ (CBX3) and HP1α (CBX5) that are encoded by the corresponding genes Cbx1, Cbx3 and Cbx5. Recent work has shown that reduction of CBX3 protein in homozygotes for a hypomorphic allele (Cbx3hypo) causes a severe postnatal mortality with around 99% of the homozygotes dying before weaning. It is not known what the causes of the postnatal mortality are. Here we show that Cbx3hypo/hypo conceptuses are significantly reduced in size and the placentas exhibit a haplo-insufficiency. Late gestation Cbx3hypo/hypo placentas have reduced mRNA transcripts for genes involved in growth regulation, amino acid and glucose transport. Blood vessels within the Cbx3hypo/hypo placental labyrinth are narrower than wild-type. Newborn Cbx3hypo/hypo pups are hypoglycemic, the livers are depleted of glycogen reserves and there is almost complete loss of stored lipid in brown adipose tissue (BAT). There is a 10-fold reduction in expression of the BAT-specific Ucp1 gene, whose product is responsible for nonshivering themogenesis. We suggest that it is the small size of the Cbx3hypo/hypo neonates, a likely consequence of placental growth and transport defects, combined with a possible inability to thermoregulate that causes the severe postnatal mortality.

Primary apocrine adenocarcinoma of scrotum suspected as urothelial carcinoma metastasis: a clinical and pathological dilemma

A 78-year-old man presented with an enlarging, tender mass in the scrotum separate to the testes. This was on the background of radical cystoprostatectomy, urethrectomy, and ileal conduit formation for high-grade urothelial carcinoma of the bladder invading submucosa 3 years prior. Examination revealed a 4 × 5 cm lesion, which was hard, fixed to the overlying skin and nodular to palpation. Ultrasound confirmed a solid mass in the scrotum extending into the perineum. Computerized tomography of the chest, abdomen, and pelvis revealed enlargement of inguinal lymph nodes but no other metastases. Complete resection of the scrotal lesion and selective removal of regional lymph nodes was performed. Rather than a cutaneous scrotal metastasis from the bladder urothelial carcinoma, histological examination suggested a primary apocrine adenocarcinoma of the scrotum. This case report explores the clinical and pathological features associated with both of these unusual differential diagnoses

Predicting body composition in college students using the womersley and durnin body mass index equation

When assessing fitness levels, body composition is usually measured. The purpose of this study was to determine the overall efficacy of a body mass index [BM I] equation for predicting body composition with respect to college aged participants. Body composition was measured using dual-energy x-ray absorptiometry [DXA] and was estimated using the Womersley and Durnin BMI prediction equation. There was no significant [P=0.8] percent body fatt [%BF] difference between the BMI prediction equation and DXA [BMI Predicted=25 [10] [min=6; max=52] %PFvs DXA=25 [6] [min=10; max=45] %BF]. In addition, a significant correlation was found between the two approaches [r=0.79l, P=0.001]. However. both the standard error of estimate [6.32%BF] and total error [6.63 %BF] were outside acceptable ranges for prediction equations. The Womersley and Durnin equation for estimating %BF was not found to be a good estimate. Therefore, although the BMI predicted %BF has been previously found to predict skinfold estimated %BF, it does not appear valid in estimating %BF from DXA

estimation of the fat free mass index in athletes

The purpose of this investigation was to compare a practical measurement of fat free mass index [FFMI] from bioelectrical impedance analysis [BIA] to the dual energy X-ray absorptiometry [DEXA] value in collegiate athletes. Thirty-three male baseball players and 16 female gymnasts volunteered to participate in this study during their respective pre-season. Subjects visited the laboratory once and had their measurements taken in the following order: weight, height, DEXA, and Omron HBF-500. The BIA device investigated was not a valid estimate of FFMI when compared to the DEXA. The TE was 0.93 kg/ m[2] for males and 0.78 kg/ m[2] for females. There were also significant mean differences between the BIA prediction and the DEXA value for males [BIA=20.6 kg/m[2] vs. DEXA=21.1 kg/m[2], P=0.007] and females [BIA=16.2 kg/m[2] vs. DEXA=17.5 kg/m[2], P=0.001]. The BIA device investigated in this study did not provide a valid estimate of FFMI in male and female collegiate athletes. Although there was a general tendency for the BIA to underestimate FFMI compared to DEXA, 98% of the estimates were within plus or minus 2 kg/ m[2]. Therefore, while slightly biased, BIA may provide a reasonable [+/- 2 kg/ m[2]] estimate of nutritional status for practitioners who are unable able to afford more expensive equipment

Subtrochanteric Fracture In A Chinese Woman With Pagets Disease Of Bone And On Long Term Bisphosphonate Therapy: Could It Be An Insufficiency Fracture?

Pagets disease is common in Western countries but is very rare in Chinese populations. Although bisphosphonate has been widely used to treat symptomatic Pagets disease, prolonged use may be associated with insufficiency fracture. We highlight this rare case of Pagets disease in a Chinese lady who presented with an insufficiency fracture following long term use of bisphosphonate.