Beneficial effects of pulmonary embolism response team establishment in patients with pulmonary embolism in a developing country: a single-center experience.

Objective: The impact of establishing a pulmonary embolism response team (PERT) in patients with pulmonary embolism (PE) has been proven in many developed countries. However, the efficacy of a PERT largely depends on expertise and infrastructure. This study explored the benefit of establishing a PERT in developing countries with limited healthcare resources by comparing the outcomes of patients with acute PE before and after PERT establishment at University Medical Center Ho Chi Minh City in Vietnam. Methods: We conducted a single-center observational study from January 1, 2019, to August 1, 2021. All patients with PE confirmed on computed tomography were included. Patients admitted before PERT establishment were treated by cardiologists alone, while those hospitalized after PERT establishment were managed by the PERT. Results: A total of 130 patients were included (pre-PERT estab-lishment: 51 patients; post-PERT establishment: 79 patients). The demographic characteristics, severity of PE, and clinical and laboratory findings were similar between the two groups. The post-PERT establishment group had a lower incidence rate of major and clinically relevant nonmajor bleeding (11.3% vs. 31.4%, p = 0.005) and required more interventional therapies (16.5% vs. 3.9%, p = 0.046) than did the pre-PERT establishment group. The in-hospital mortality rate decreased in the post-PERT establishment group compared with that in the pre-PERT establishment group (8.9% vs. 21.6%, p = 0.041). Conclusions: Involvement of the PERT in PE management was associated with improved outcomes of patients with PE, including reduced bleeding and mortality rates in a resource-constrained hospital.

Uncovering hypercoagulation status using rotational thromboelastometry in patients with sepsis presented with hypocoagulation based on conventional coagulation tests: an observational study.

OBJECTIVE: Conventional coagulation tests (CCTs) cannot identify hypercoagulation, despite being common in patients with sepsis. Moreover, CCTs overdiagnose hypocoagulation, which increases unnecessary blood transfusion. Therefore, we aimed to use rotational thromboelastometry (ROTEM) to classify the coagulation status of patients with sepsis with abnormal CCTs and to identify the main coagulation components that affect coagulation status. PATIENTS AND METHODS: This study was part of an observational study to investigate ROTEM use in 161 patients with sepsis with the Sepsis-3 criteria. They underwent concurrent CCTs and ROTEM assessments within 24 hours of Intensive Care Unit admission at the University Medical Center, Ho Chi Minh City, from June 2020 to December 2021. This study only extracted data from patients with sepsis with abnormal CCTs, including activated partial thromboplastin time ratio, international normalized ratio (INR), platelet count, and fibrinogen concentration. RESULTS: A total of 158 patients with sepsis with abnormal CCTs had a median age of 69, and 48.7% were women. Of 34 patients with INR ≥1.6, ROTEM identified 11.8% with hypercoagulation and 20.6% with normal coagulation. Of 29 patients with platelet counts <100 (103/mm3), ROTEM identified 3.5% with hypercoagulation and 24.1% with normal coagulation. In the ROTEM-based hypercoagulability group, an increase in maximum clot firmness was observed in 95.1% of cases; also, this group had significantly higher plasma fibrinogen concentrations than other groups (p<0.005). CONCLUSIONS: ROTEM can reveal hypercoagulability in patients with sepsis with hypocoagulation based on CCTs. Hyperfibrinogenemia causes hypercoagulation in patients with sepsis.

Sinus arrest in familial hypokalemic periodic paralysis caused by SCN4A mutation: a case report.

BACKGROUND: Primary hypokalemic periodic paralysis (HypoPP), a rare skeletal muscle channelopathy resulting in episodic muscle weakness or paralysis under hypokalemic conditions, is caused by autosomal-dominant genetic mutations. HypoPP limits physical activity, and cardiac arrhythmias during paralytic attacks have been reported. We describe a rare familial HypoPP case complicated by sinus arrest and syncope requiring urgent temporary pacemaker implantation. CASE REPORT: A 27-year-old Vietnamese man with a family history of periodic paralysis presented with his third attack of muscle weakness triggered by intense football training the previous day. Clinical and laboratory features justified a HypoPP diagnosis. During intravenous potassium replacement, the patient experienced syncopal sinus arrest requiring urgent temporary pacemaker implantation. The patient gradually improved, responding favorably to oral potassium supplements. Genetic testing revealed an Arg1132Gln mutation in the sodium ion channel (SCN4A, chromosome 17: 63947091). At discharge, the patient received expert consultation regarding nonpharmacological preventive strategies, including avoidance of vigorous exercise and carbohydrate-rich diet. CONCLUSIONS: No evidence has established a relationship between hypokalemia and sinus arrest, and no specific treatment exists for familial HypoPP due to SCN4A mutation. Clinician awareness of this rare condition will promote appropriate diagnostic approaches and management strategies for acute paralytic attacks. Treatment should be tailored according to HypoPP phenotypes and genotypes.

Current status of fasciolosis in Vietnam: an update and perspectives.

Vietnam is recognized to be endemic for fasciolosis. However, most of the available publications have not been published in international journals. This review is based on national and international Vietnamese publications and highlights the current status of fasciolosis in Vietnam. It also provides some information available for neighbouring countries. Updated data on responsible species, distribution, transmission and control aspects are summarized. The central region of Vietnam is reported as being highly endemic for fasciolosis, with a high number of human patients (more than 20,000 in 2011). Fasciola gigantica is reported to be the main species in Vietnam. However, hybrids between F. gigantica and F. hepatica were identified. Both humans and animals are infected by the ingestion of raw vegetables and possibly contaminated drinking water. Three lymnaeid snail species (Austropeplea viridis, Radix auricularia and Radix rubiginosa) may act as intermediate hosts of Fasciola spp. However, due to the likely misidentification of snail species and cercariae during the past decade the critical analysis of published data is difficult. A better understanding of transmission aspects of fasciolosis would allow the implementation of preventive measures of this important neglected zoonotic disease.

Mobilizing for the Lilongwe Diabetes Peer Support Programme in Malawi.

Diabetes has become a significant cause of morbidity and mortality in Malawi but there are shortages of drug supply and healthcare providers to support quality care and treatment. Diabetes self-management support is necessary to improve patient outcomes, and peer support has gained acceptance as a solution for improving diabetes self-management. In this programme summary, we describe the components and facilitators essential to implementing a diabetes peer support programme in Lilongwe, Central Malawi. Peer support has the potential to play a key role for the Ministry of Health in the development of the 2011-2026 health sector strategic plan, which addresses diabetes and non-communicable diseases.

Functional patency of autogenous AV fistulas for hemodialysis.

BACKGROUND: Although AV fistulas are the preferred access for hemodialysis and have low complication rates, failure to function remains high and time to first dialysis may be several months. METHODS: Data from a Computerized Patient Record System of patients undergoing AV fistula from October 2000 to March 2006 were reviewed for type of fistula, interval from AV fistula construction to first hemodialysis, patency period, and complication rate. RESULTS: 129 patients were identified who underwent 155 autogenous AV fistula constructions. The average age was 62.1 (range 40-84) years old. 114 radiocephalic and 41 brachiocephalic fistulas were performed. 57 (50%) radiocephalic fistulas allowed successful hemodialysis after an average length of 13+/-5 weeks with a primary patency of 13+/-4 months. 24 (42%) fistulas subsequently thrombosed, 7 (12%) developed fistula stenosis, and 2 (4%) developed steal syndrome. 28 (68%) brachiocephalic fistulas reached successful hemodialysis after 6+/-2 weeks with a primary patency of 16+/-7 months. Eleven (42%) of the brachiocephalic fistulas that reached hemodialysis remained patent while four (15%) thrombosed. Two (8%) brachiocephalic fistulas thrombosed before reaching hemodialysis. There were two incidences (5%) of steal syndrome in the brachiocephalic group with one case being severe leading to tissue loss in the hand. CONCLUSION: Brachiocephalic fistulas were superior to radiocephalic in both time to maturity, primary patency, and functional primary patency. Brachiocephalic fistulas had a higher maturation rate and were less likely to fail once hemodialysis began. Vascular surgeons should develop better patient selection to predict which fistulas will function successfully rather than risk complications of prolonged central catheters.

Cross-sectional study of sexual behaviour and knowledge about HIV among urban, rural, and minority residents in Viet Nam.

OBJECTIVE: A cross-sectional survey was conducted in three districts of Quang Ninh province, Viet Nam, to find out what proportion of the people who lived there engaged in behaviour that put them at risk of becoming infected with HIV, and to measure their knowledge about HIV infection and AIDS. METHODS: The survey was conducted in a rural district, Yen Hung; a mountainous district inhabited primarily by ethnic minority groups, Binh Lieu; and an urban district, Ha Long. Participants aged 15-45 years were randomly selected from the general population to be interviewed. FINDINGS: A total of 630 people from 707 households were interviewed; 8% were not home despite repeated visits and 3% refused to participate. The prevalence of premarital intercourse ranged from 9% to 16% among married men and 4% to 7% among married women. Among single men the proportion who had ever had intercourse ranged from 6% to 16%. Fewer than 3% reported having ever had sex with a sex worker. The median number of extramarital sex partners was 1. Knowledge about HIV/AIDS was high in the urban and rural areas but low in the mountainous area. Being male and being 20-29 years old were associated with having multiple sex partners. CONCLUSION: The low prevalence of individuals reporting that they had had intercourse with sex workers and partners other than their spouse may explain the low rates of HIV infection among the heterosexual population; these rates are in contrast to the high rates of HIV infection found among injecting drug users. The association between having extramarital partners and being a younger man suggests that the tendency to have more sexual partners may increase in the future. If this happens, the potential for HIV to be spread through heterosexual sex will increase.

Up-regulation of macrophage wnt gene expression in adenoma-carcinoma progression of human colorectal cancer.

Defects in the APC-beta-catenin pathway are common in colon cancer. We investigated whether aberrant regulation of upstream ligands stimulating this pathway occur in colon cancer. Using RNAase protection analysis, six out of eight wnt genes were expressed in 14 matched cases of normal, adenomatous and malignant colorectal tissues. Wnt 2 and wnt 5a were significantly up-regulated in the progression from normal through adenoma to carcinoma. Transcripts for wnts 4, 7b, 10b and 13, but not wnt 2 and wnt 5a were detected in several colorectal cell lines. In situ hybridization demonstrated that wnt 2 and wnt 5a transcripts were mainly in the lamina propria/stroma region with labelling predominantly in macrophages. Immunostaining with CD68 confirmed the wnt-expressing cells as macrophages. These results show a major difference in wnt expression in colon cancer compared to colon adenomas and suggest stromal wnt expression may play a role in tumour progression.

cDNA characterization and chromosomal mapping of human golgi SNARE GS27 and GS28 to chromosome 17.

Transport of proteins along the exocytotic pathway is primarily achieved by vesicular intermediates. Two proteins, Golgi SNAREs of 27 kDa, GS27, and of 28 kDa, GS28 (HGMW-approved nomenclature GOSR2 and GOSR1, respectively), are important trafficking membrane proteins between the endoplasmic reticulum and the Golgi and between Golgi subcompartments. Here, we present the human GS27 and GS28 cDNA sequences. They encode predicted proteins of 212 and 250 amino acids, respectively. Chromosomal mapping analyses reveal that human GS27 is located on chromosome 17q21 and GS28 on approximately 17q11. The chromosomal location of GS27 near a locus implicated in familial essential hypertension and its known function in trafficking indicate that it is a potential candidate gene for this disease.

Modeling bronchial circulation with application to soluble gas exchange: description and sensitivity analysis.

The steady-state exchange of inert gases across an in situ canine trachea has recently been shown to be limited equally by diffusion and perfusion over a wide range (0.01-350) of blood solubilities (betablood; ml . ml-1 . atm-1). Hence, we hypothesize that the exchange of ethanol (betablood = 1,756 at 37 degrees C) in the airways depends on the blood flow rate from the bronchial circulation. To test this hypothesis, the dynamics of the bronchial circulation were incorporated into an existing model that describes the simultaneous exchange of heat, water, and a soluble gas in the airways. A detailed sensitivity analysis of key model parameters was performed by using the method of Latin hypercube sampling. The model accurately predicted a previously reported experimental exhalation profile of ethanol (R2 = 0.991) as well as the end-exhalation airstream temperature (34.6 degrees C). The model predicts that 27, 29, and 44% of exhaled ethanol in a single exhalation are derived from the tissues of the mucosa and submucosa, the bronchial circulation, and the tissue exterior to the submucosa (which would include the pulmonary circulation), respectively. Although the concentration of ethanol in the bronchial capillary decreased during inspiration, the three key model outputs (end-exhaled ethanol concentration, the slope of phase III, and end-exhaled temperature) were all statistically insensitive (P > 0.05) to the parameters describing the bronchial circulation. In contrast, the model outputs were all sensitive (P < 0.05) to the thickness of tissue separating the core body conditions from the bronchial smooth muscle. We conclude that both the bronchial circulation and the pulmonary circulation impact soluble gas exchange when the entire conducting airway tree is considered.

High expression of Wnt7b in human superficial bladder cancer vs invasive bladder cancer.

Aberrant Wnt gene expression is involved in the development of breast cancer, but its role in other tumours is unknown. Wnts regulate cadherin function, previously shown to be more commonly deregulated in invasive bladder cancer. This study investigated whether factors upstream of cadherins were aberrantly expressed in superficial bladder cancer. The expression of one transforming (Wnt7b) and one non-transforming (Wnt5a) Wnt gene in four human bladder carcinoma cell lines, and in normal human bladder tissues (n = 8) and bladder cancers (n = 48) were analysed by ribonuclease protection analysis. All cell lines expressed an approximately equal level of Wnt7b mRNA. Wnt5a and Wnt7b mRNAs were both expressed in normal bladder tissues and bladder tumours. The median expression of Wnt7b was fourfold higher in superficial tumours (n = 29) than in normal tissues (n = 8, P = 0.002) and five fold higher than in invasive tumours (n = 17, P = 0.003). There was no significant difference between normal tissues and invasive tumours (P = 0.3). The expression of Wnt5a did not vary significantly between normal tissues and superficial tumours (P = 0.4), normal tissues and invasive tumours (P = 0.3) or superficial tumours and invasive tumours (P = 0.2). The differential expression of Wnt7b suggests a role in the early events of superficial bladder tumorigenesis involving cell adhesion and provides further evidence of different pathways of evolution of superficial and invasive cancer.

Expression of Wnt5a is downregulated by extracellular matrix and mutated c-Ha-ras in the human mammary epithelial cell line MCF-10A.

Wnt genes are involved in tumour growth and regulate cell adhesion. Some (Wnt5a and Wnt7b) are more highly expressed in human breast cancer compared to normal tissues. Wnt5a is involved in the regulation of cell movement in Xenopus and is upregulated in several human cancers. Factors regulating Wnt gene expression in human breast epithelium are poorly understood, but c-erbB2 is amplified in many breast cancers and associated with rapid growth and metastasis, as is high expression of c-Ha-ras. To further understand the regulation of Wnt gene expression, this study investigated the effect of proto-oncogenes c-Ha-ras and c-erbB2, and collagen on Wnt mRNA expression, in a normal spontaneously immortalised human mammary epithelial cell line MCF-10A. Out of nine human Wnt genes investigated, Wnt5a and Wnt7b were expressed in the parental cell line, and neomycin-, c-Ha-ras- and c-erbB2-transfected cell lines. The level of Wnt5a mRNA expression was decreased 40-fold and 3-fold when parental cells were grown on collagen and in collagen, respectively. This downregulation correlated with cell branching. However, Wnt7b was not regulated by collagen. In the presence of activated c-Ha-ras, the level of Wnt5a mRNA expression was markedly decreased (> 200-fold) and cell growth rate was elevated. When treated with p21ras inhibitor, BZA-5B, there was a moderate reversal of Wnt5a mRNA expression (2-fold) with a parallel decrease in cell growth. The data indicate that c-Ha-ras is an upstream inhibitory regulator of Wnt5a, and provide further evidence of an inverse relationship between Wnt5a mRNA expression and cell branching. This demonstrates selectivity of regulation of individual members of the Wnt gene family by the ras pathway. Overexpression of c-erbB2 had no effect on Wnt5a or Wnt7b mRNA expression. Thus, extracellular matrix and ras regulate Wnt5a, providing a mechanism for feedback of morphogenetic movements, which is relevant also to cancer biology.

cDNA cloning of a human dishevelled DVL-3 gene, mapping to 3q27, and expression in human breast and colon carcinomas.

dishevelled (Dsh) is a member of the segment polarity gene family in Drosophila which plays an important role in the early developmental patterning processes. A human homologue of Dsh (DVL-1) has recently been described. Here, we report the cloning of a second human homologue of Dsh (called DVL-3) by cDNA library screening. The human DVL-3 gene encodes a predicted 716 amino acid protein which exhibits 98% amino acid identity with mouse Dvl-3 and 49% with Drosophila Dsh. DVL-3 was mapped to 3q27. The expression of DVL-3 mRNA was detected in 30 human cell lines and 2 primary cell cultures. DVL-3 mRNA was detected in normal human breast tissues (n = 4) and tumours (n = 25). Statistically, there was no difference in DVL-3 mRNA level between normal breast tissues and tumours. In human colorectal samples, DVL-3 was expressed equally in matched normal tissues, polyps and tumours. The data indicates that DVL-3 is widely expressed in human cells and supports the notion of a new developmental gene family for dishevelled which may have a widespread role in signal transduction.

Isolation of a full-length human WNT7A gene implicated in limb development and cell transformation, and mapping to chromosome 3p25.

The Wnt gene family has a role in development as well as tumourigenesis. One mouse member, Wnt7a, is vital for limb development in vivo and also possesses transforming ability in vitro. This study reports the isolation of a full length of human homologue of mouse Wnt7a gene by library screening. Yeast artificial chromosome-fluorescence in situ hybridisation (YAC-FISH) mapped the WNT7A gene to chromosome 3p25. Human WNT7A had an ORF encoding a deduced protein of 349 aa that exhibited 97% and 92% identity to mouse Wnt7a at the aa and nucleic acid levels, respectively. It possessed the 22 conserved cysteine residues and 3 more at the amino terminus, and a putative poly A tail. This is the fifth human WNT gene in which a complete cDNA sequence had been determined.

A novel human Wnt gene, WNT10B, maps to 12q13 and is expressed in human breast carcinomas.

Several members of the Wnt gene family have been shown to cause mammary tumors in mouse. Using degenerate primer polymerase chain reaction (PCR) on human genomic DNA, and specific PCR of cDNA libraries, we have isolated a WNT gene which has not previously been described in human. The gene is the human homologue of mouse Wnt10b, recently shown to be one of the oncogenes cooperating with FGF3 in the development of mouse mammary tumour virus (MMTV) induced mouse mammary carcinomas. The human WNT10B sequence was 88% and 95% identical to the murine gene at nucleotide and amino acid levels, respectively. YAC FISH mapping localises the gene to 12q13, a chromosomal region frequently rearranged in human tumours and also containing the WNT1 gene. In normal and benign proliferations of human breast tissue, WNT10B expression was not detected by ribonuclease protection assays but was found at low levels in RT-PCR experiments. In contrast, using both methods, WNT10B expression was found to be elevated in 3 of 50 primary breast carcinomas. Southern blot analysis of the carcinoma expressing the highest levels of WNT10B showed no amplification or rearrangement of the gene. The WNT10B gene was also expressed in some cancer and non cancerous breast cell lines. These findings suggest that the WNT10B gene may be involved in human breast cancer, and show that there is differential expression of the WNT10B gene in benign and malignant disease.

Expression and hormone regulation of Wnt2, 3, 4, 5a, 7a, 7b and 10b in normal human endometrium and endometrial carcinoma.

Wnt genes are transforming to mouse breast epithelium and are hormonally regulated in vivo. To assess their role in another endocrine-responsive human cancer, the expression of seven Wnt genes (Wnt 2, 3, 4, 5a, 7a, 7b and 10b) in normal human endometrium and endometrial cells, and endometrial carcinoma tissues and cell lines was investigated by ribonuclease protection analysis. Wnt2, 3, 4 and 5a mRNAs but not Wnt7a, 7b or 10b mRNAs were expressed in primary culture of normal endometrial epithelial (NEE) and stromal (NES) cells. In contrast, in four endometrial carcinoma cell lines (RL95-2, HEC-1-A, AN3 CA and Ishikawa), Wnt2 and Wnt3 mRNAs were absent. Wnt4 was expressed in only one out of four cell lines (RL95-2), and Wnt5a was much lower. Wnt7a and Wnt7b mRNAs were expressed in three out of four cell lines (RL95-2, HEC-1-A and Ishikawa). Wnt10b mRNA was expressed in RL95-2 and AN3 CA. In fresh tissues, all Wnt genes apart from Wnt10b were expressed in normal endometrium and endometrial carcinoma. Similar to the cell lines, the level of Wnt4 mRNA expression was significantly higher in the normal endometrium than endometrial carcinoma. Wnt2, 3 and 5a mRNAs were also lower in endometrial carcinoma compared with normal endometrium. There was no difference in the level of Wnt2, 3, 4 and 5a mRNA expression between proliferative phase and secretory phase of the menstrual cycle, or between either menstrual phase and the first trimester of pregnancy. In vitro, progesterone and/or 17beta-oestradiol had no effect on Wnt2, 3, 4, 5a and 7b mRNA expression in NES and all endometrial carcinoma cell lines. The data indicate that all Wnt genes were expressed in vitro, six out of seven Wnt genes (Wnt 2, 3, 4, 5a, 7a and 7b) were expressed endogenously in the human endometrium, their mRNA expression was hormonally independent and Wnt4 gene down-regulation as well as down-regulation of Wnt 2, 3 and 5a may be associated with endometrial carcinoma.

Two nuclear proteins bind to the promoter P3 region of the human parathyroid hormone-related peptide gene.

We have used a 5' regulatory sequence fragment of the human parathyroid hormone-related peptide (PTHrP) gene to identify nuclear DNA-binding proteins (DBP), using South-Western analysis. The PTHrP 549 bp DNA fragment was amplified from a human genomic DNA, and composed of 5' non-coding exon Ic, the intervening intron and 5' non-coding exon II. The DNA fragment bound very specifically to a 70 kDa and a 65 kD protein from the nuclear extract of human hepatocyte, HepG2, and keratinocyte, SVK-14, cell lines. This is the first evidence of a physical binding between nuclear protein and the human PTHrP gene. The 70 kDa and 65 kDa nuclear proteins may have a role in the regulation of human PTHrP gene expression.