Diabetic gastroparesis: clinical features, diagnosis and management.

Diabetic gastroparesis carries a heavy burden on people with diabetes and the healthcare system. It remains underdiagnosed and represents challenges to treat. This article reviews the epidemiology, pathophysiology, clinical features, diagnosis and treatment of diabetic gastroparesis. The disorder is characterized by delayed gastric emptying without evidence of mechanical gastric outflow obstruction. It presents with upper gastrointestinal (GI) symptoms such as nausea, vomiting, early satiety, postprandial fullness, upper abdominal discomfort and or bloating. As the prevalence of diabetes has been growing over the last few decades, we would expect an increased incidence of delayed gastric emptying in poorly controlled diabetes and perhaps in line with the increasing use of medications that act on the GI tract such as incretin-based therapy. The disease results from multiple reversible and irreversible mechanisms. Diagnosing diabetic gastroparesis requires careful history, examination and investigations to exclude other disorders that could mimic its clinical presentation. Treatment involves a wide variety of options starting with optimization of glycaemic control, stopping any offending medications and lifestyle modifications followed by the introduction of medical therapeutics such as prokinetics. Then, surgical interventions are considered in refractory cases.

Vacuum pressure combined with osmosonication as an innovative pre-drying technique for Ghanaian ginger: Evidence from the metabolome and quality characteristics of the dried product.

We assessed the impact of selected pretreatment techniques, thus, vacuum-assisted osmotic dehydration (VOD), vacuum-assisted sonication (VSON) and vacuum-assisted osmosonication (VOS) on the metabolomes and quality characteristics of infrared-dried ginger slices. We found marked metabolome differences between the pretreated ginger samples, evidenced by differential amounts of 6-gingerol and 6-shogaol, total phenolic content (TPC), total flavonoid content (TFC) and antioxidant activities. We also found distinct differences in the drying kinetics and sensory characteristics of the pretreated samples. Generally, VOS pretreatment gave the best outcomes. The VOS-pretreated samples contained the highest contents of the marker compounds, TPC, TFC and gave the best antioxidant activity. The VOS-pretreated samples also recorded the shortest drying time and exhibited the best sensory attributes. Overall, the general order observed was, VOS > VSON > VOD > control for all quality parameters examined. VOS pretreatment of ginger before drying therefore holds a great potential for large-scale industrial application.

HIST1H1E syndrome with type 2 diabetes.

A 20-year-old woman was referred to the diabetes clinic with type 2 diabetes diagnosed at the age of 19. Her body mass index was 31.4 kg/m2, HbA1C was 76 mmol/mol, GAD antibodies were negative with a detectable C-peptide. She had a characteristic facial appearance with widespread eyes, posterior hairline suggesting a facial gestalt and abnormal dentition. She also had hypothyroidism, mild intellectual disability, primary amenorrhoea and patent ductus arteriosus. Karyotyping reported normal 46XX karyotype. Genetic testing revealed a pathogenic variant in the gene encoding the HIST1H1E protein which confirmed her diagnosis of HIST1H1E syndrome. Type 2 diabetes has not been reported in previous cases of HIST1H1E and so this is the first reported case of type 2 diabetes with HIST1H1E syndrome.

Anticoccidial effects of Khaya senegalensis aqueous stem bark extract on broiler chickens experimentally infected with Eimeria species.

Graded concentrations (200, 400 and 800 mg/kg) of the aqueous stem bark extract of Khaya senegalensis was evaluated for its therapeutic efficacy against experimentally induced coccidiosis in broiler chicken. The phytochemical analysis shows the presence of tannins, saponins, cardiac glycosides and steroids. There was significant reduction in oocyst count across the groups in a graded dose manner with 800 mg/kg being the most efficacious dose. There was also weight gain across the treatment groups with immuno-modulatory and erythropoetic activities observed. Also, a significant (p < 0.05) graded dose-dependent reduction in the oocyst count in the treatment groups. A significant (p < 0.05) increase in mean weight gain was also recorded across the experimental groups except the negative control. The haematology also showed a dose-dependent increase in red blood cells, haemoglobin and packed cell volume of the treatment groups. The extract had no significant difference (p > 0.05) on the white blood cells, but a slight decrease in the white blood cells and heterophil counts was observed at 400 mg/kg. Furthermore, the aspartate amino transaminase level showed a significant difference (p < 0.05). Fluctuating levels of other serum biochemical parameters such as total protein, albumin and potassium were observed. No significant difference (p > 0.05) in the sodium concentration was observed. In addition, oxidative stress biomarkers such as catalase significantly increased (p < 0.05) in all the experimental groups in addition to the concomitant increase in reduced gluthathione (GSH) and superoxide dismutase (SOD) levels. Conclusively, the aqueous extract of K. senegalensis was effective in the management of coccidiosis thus supporting its folkloric use.

Drug Rash with Eosinophilia and Systemic Symptoms Syndrome Presenting After the Initiation of Staphylococcus hominis Infectious Endocarditis Treatment: A Case Report and Updated Review of Management Considerations.

We present the case of a 62-year-old Caucasian man who was being treated for mitral valve endocarditis via a six-week course of vancomycin. On Day 32 of the treatment, he developed an erythematous, pruritic, desquamating, and painful rash covering 80% of the total body surface area and intermittent fevers. Laboratory findings included leukocytosis with peripheral blood eosinophilia and elevated erythrocyte sedimentation rate, C-reactive protein, and serum creatinine. Although the patient only completed five weeks of antibiotics, the decision was made to not complete the six-week antibiotic course due to suspicion of vancomycin-induced drug rash with eosinophilia and systemic symptoms (DRESS). The patient was then given 80 mg of intramuscular triamcinolone (Kenalog) and advised to apply topical 0.1% triamcinolone twice per day. At the three-month follow-up, the rash, leukocytosis, eosinophilia, and renal dysfunction had resolved. Clinicians must maintain a high index of suspicion for vancomycin-induced DRESS in patients with rash and eosinophilia for early recognition and treatment. DRESS syndrome treatment typically involves discontinuing the causative drug and promptly administering steroids. However, there is a therapeutic dilemma in administering steroids during the course of an active infection. Therefore, this article serves two purposes. First, this case report highlights our approach towards managing a patient with DRESS and concurrent infectious endocarditis. Second, we include a review of the management considerations when prescribing pulsed steroids so that clinicians have a single source as a practical guide towards reducing the potentially severe systemic sequelae in DRESS syndrome and its associated treatment.

The homeostatic chemokine CCL21 predicts mortality in aortic stenosis patients and modulates left ventricular remodeling.

BACKGROUND: CCL21 acting through CCR7, is termed a homeostatic chemokine. Based on its role in concerting immunological responses and its proposed involvement in tissue remodeling, we hypothesized that this chemokine could play a role in myocardial remodeling during left ventricular (LV) pressure overload. METHODS AND RESULTS: Our main findings were: (i) Serum levels of CCL21 were markedly raised in patients with symptomatic aortic stenosis (AS, n = 136) as compared with healthy controls (n = 20). (ii) A CCL21 level in the highest tertile was independently associated with all-cause mortality in these patients. (iii) Immunostaining suggested the presence of CCR7 on macrophages, endothelial cells and fibroblasts within calcified human aortic valves. (iv). Mice exposed to LV pressure overload showed enhanced myocardial expression of CCL21 and CCR7 mRNA, and increased CCL21 protein levels. (v) CCR7-/- mice subjected to three weeks of LV pressure overload had similar heart weights compared to wild type mice, but increased LV dilatation and reduced wall thickness. CONCLUSIONS: Our studies, combining experiments in clinical and experimental LV pressure overload, suggest that CCL21/CCR7 interactions might be involved in the response to pressure overload secondary to AS.

Molecular and pathological studies in the posterior interosseous nerve of diabetic and non-diabetic patients with carpal tunnel syndrome.

AIMS/HYPOTHESIS: We sought to establish the molecular and pathological changes predisposing diabetic and non-diabetic patients to the development of carpal tunnel syndrome (CTS). METHODS: The posterior interosseous nerve (PIN) was biopsied in 25 diabetic and 19 non-diabetic patients undergoing carpal tunnel decompression for CTS. Detailed morphometric and immunohistological analyses were performed in the nerve biopsy. RESULTS: In diabetic patients median nerve distal motor latency was prolonged (p < 0.05 vs non-diabetic patients), PIN myelinated fibre density (p < 0.05), fibre area (p < 0.0001) and axon area (p < 0.0001) were reduced, the percentage of unassociated Schwann cell profiles (p < 0.0001) and unmyelinated axon density (p < 0.0001) were increased and the axon diameter was reduced (p < 0.0001). Endoneurial capillary basement membrane area was increased (p < 0.0001) in diabetic patients, but endothelial cell number was increased (p < 0.01) and luminal area was reduced (p < 0.05) in non-diabetic patients with CTS. There was no difference in the expression of hypoxia-inducible factor 1α between diabetic and non-diabetic patients with CTS. However, the expression of vascular endothelial growth factor A (VEGF) (p < 0.05) and its receptors VEGFR-1 (p < 0.01) and VEGFR-2 (p < 0.05) was significantly increased in diabetic patients, particularly those with type 1 diabetes, and related to the severity of nerve fibre pathology. CONCLUSIONS/INTERPRETATION: This study demonstrates increased nerve fibre and microvascular pathology in relation to enhanced expression of VEGF and its receptors in a non-compressed nerve in diabetic compared with non-diabetic patients with CTS. It therefore provides a potential molecular and pathological basis for the predisposition of diabetic patients to the development of CTS.

Treatment of idiopathic membranous nephropathy with the herb Astragalus membranaceus.

A 77-year-old woman with nephrotic syndrome secondary to idiopathic membranous nephropathy was treated with angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, cyclosporine A, and mycophenolate mofetil, without response. After more than 2 years of unremitting nephrosis, she began therapy with the herb Astragalus membranaceus, used by traditional Chinese physicians to treat various immune disorders, including glomerulonephritis. After institution of Astragalus at a dose of 15 g/d, there was a marked decrease in proteinuria. Nephrotic syndrome recurred after temporary cessation of Astragalus therapy, with complete remission of nephrosis observed after its reintroduction. The clinical course of this patient suggests that Astragalus may have beneficial effects in patients with idiopathic membranous nephropathy.

Simultaneous transjugular renal biopsy and hemodialysis catheter placement in patients with ARF.

BACKGROUND: Previous studies have evaluated transjugular renal biopsy in patients with contraindications to percutaneous renal biopsy or those undergoing simultaneous renal and hepatic biopsies. We sought to evaluate transjugular renal biopsy in patients with acute renal failure (ARF) or ARF in the presence of chronic renal insufficiency (CRI) who required venous catheter placement for hemodialysis (HD). METHODS: Ten consecutive patients (6 patients, ARF; 4 patients, ARF on CRI) at a single tertiary-care medical center, while undergoing placement of HD access through the internal jugular route, also underwent transjugular renal biopsy using the Quick-Core (Cook, Bloomington, IN) system to delineate the cause of ARF. Transjugular renal biopsy was performed because it was the opinion of the attending nephrologist that a histological diagnosis might alter management. RESULTS: Renal biopsy findings were diabetic nephropathy (3 patients), acute tubular necrosis (ATN; 2 patients), nephrosclerosis (2 patients), immunoglobulin A nephropathy (1 patient), lupus nephritis with focal crescents and ATN (1 patient), and pauci-immune necrotizing glomerulonephritis (1 patient). There were no major complications from the procedures. Among the 6 patients with ARF, management was directly affected in 3 patients (either initiation of appropriate immunosuppressive therapy or withholding of such therapy). In the remaining 3 patients with ARF and in patients with ARF on CRI, performing transjugular renal biopsy at the time of HD access placement obviated additional testing and/or unnecessary therapy. Four patients recovered renal function and HD therapy was discontinued, 2 patients died, and 1 patient was lost to follow-up. CONCLUSION: Simultaneous transjugular renal biopsy/HD catheter placement should be considered in patients with ARF requiring HD therapy for whom knowledge of the renal histological diagnosis may alter patient management.

Genotype and allele frequencies of TPMT, NAT2, GST, SULT1A1 and MDR-1 in the Egyptian population.

AIMS: The goal of this study was to determine the frequencies of important allelic variants in the TPMT, NAT2, GST, SULT1A1 and MDR-1 genes in the Egyptian population and compare them with the frequencies in other ethnic populations. METHODS: Genotyping was carried out in a total of 200 unrelated Egyptian subjects. TPMT*2 was detected using an allele-specific polymerase chain reaction (PCR) assay. TPMT*3C and NAT2 variants (*5,*6 and *7) were detected using an allele-specific real-time PCR assay. Detection of GSTM1 and GSTT1 null alleles was performed simultaneously using a multiplex PCR assay. Finally, a PCR-restriction fragment length polymorphism assay was applied for the determination of TPMT*3A (*3B), SULT1A1*2 and MDR-1 (3435T) variants. RESULTS: Genotyping of TPMT revealed frequencies of 0.003 and 0.013 for TPMT*3A and TPMT*3C, respectively. No TPMT*2 or *3B was detected in the analysed samples. The frequencies of specific NAT2 alleles were 0.215, 0.497, 0.260 and 0.028 for *4 (wild-type), *5 (341C), *6 (590A) and *7 (857A), respectively. GSTM1 and GSTT1 null alleles were detected in 55.5% and 29.5% of the subjects, respectively. SULT1A1*2 was detected at a frequency of 0.135. Finally, the frequencies of the wild-type allele (3435C) and the 3435T variant in the MDR-1 gene were found to be 0.6 and 0.4, respectively. CONCLUSIONS: We found that Egyptians resemble other Caucasians with regard to allelic frequencies of the tested variants of NAT2, GST and MDR-1. By contrast, this Egyptian population more closely resemble Africans with respect to the TPMT*3C allele, and shows a distinctly different frequency with regard to the SULT1A1*2 variant. The predominance of the slow acetylator genotype in the present study (60.50%) could not confirm a previously reported higher frequency of the slow acetylator phenotype in Egyptians (92.00%), indicating the possibility of the presence of other mutations not detectable as T341C, G590A and G857A. The purpose of our future studies is to investigate for new polymorphisms, which could be relatively unique to the Egyptian population.

Genotyping of four genetic polymorphisms in the CYP1A2 gene in the Egyptian population.

AIMS: The goal of this study was to determine the frequencies of CYP1A2*1C, *1D, *1E and *1F variants in the Egyptian population and compare frequencies with other populations. METHODS: Genotyping was performed in a total of 212 unrelated Egyptian subjects using polymerase chain reaction-restriction fragment length polymorphism assay. RESULTS: The frequencies of CYP1A2*1C, *1D, *1E and *1F variants in the Egyptian population were 0.07, 0.40, 0.03 and 0.68, respectively. The Egyptians have a lower frequency of CYP1A2*1C, and CYP1A2*1E than the Japanese (0.07 vs 0.21 and 0.03 vs 0.08, respectively), while the frequencies of CYP1A2*1D and CYP1A2*1F did not differ significantly between the two groups. CYP1A2*1F (0.68) frequency in Egyptians was identical to that observed in Caucasians (0.68 among 236 German individuals). CONCLUSIONS: The present study is the first to describe the frequencies of four known allelic variants of CYP1A2 among the Egyptian population. CYP1A2*1C and *1E occurred at frequencies significantly lower than that in Japanese, while similar frequencies were observed for CYP1A2*1D and *1F. The CYP1A2*1F frequency appeared to be identical to that of Caucasians. This does not exclude the possibility of the presence of new mutations relatively specific to the Egyptian population that have not been identified.