Severe hypophosphatemia induced by denosumab in a patient with osteomalacia and tenofovir disoproxil fumarate-related acquired Fanconi syndrome.

Denosumab, a novel agent that inhibits osteoclasts, reduces the risk of fracture in patients with osteoporosis. However, worsening of hypophosphatemia and other symptoms may be induced by denosumab in patients with pre-existing hypophosphatemic osteomalacia. A 58-year-old man with hepatitis B presented with diffuse bone pain and muscle weakness. Denosumab was prescribed by the orthopedist according to documented low bone mass and spine compression fracture. After administering denosumab, the patient's bone pain worsened, and he later developed a right tibia stress fracture. His condition was diagnosed as adult-onset hypophosphatemic osteomalacia complicated by multiple bone fractures, which resulted from Fanconi syndrome with proximal tubulopathy due to tenofovir disoproxil fumarate (TDF) treatment for his hepatitis B. Denosumab use leads to aggressive hypophosphatemic osteomalacia and the complication of stress fractures, because of its effects on bone resorption. Physicians should be aware that in patients with chronic hepatitis B monoinfection who are administered TDF therapy, bone pain or fracture is possible but preventable by timely monitoring of serum phosphate levels. Denosumab should not be used in patients with untreated osteomalacia or vitamin D deficiency, as it may lead not only to hypocalcemia but also to hypophosphatemia in these patients.

T-lymphocyte and glycemic status after vitamin D treatment in type 1 diabetes: A randomized controlled trial with sequential crossover.

BACKGROUND: Type 1 diabetes mellitus (T1D) is mediated by autoaggressive T effector cells with an underlying regulatory T-cell (Treg) defect. Vitamin D deficiency is highly prevalent in T1D, which can aggravate immune dysfunction. High-dose vitamin D treatment may enhance Tregs and improve metabolism in T1D patients. METHODS: In a randomized double-blind placebo-controlled trial with crossover design, patients received either for 3 months cholecalciferol 4000 IU/d followed by 3 months placebo or the sequential alternative. Thirty-nine T1D patients (19 women and 20 men) completed the trial. RESULTS: Primary outcome was a change of Tregs, secondary HbA1C, and insulin demand. Effects were evaluated based on intra-individual changes between treatment and placebo periods for outcome measures. Exploratory analyses included vitamin D system variant genotyping and C-peptide measurements. Median 25(OH)D3 increased to 38.8 ng/ml with males showing a significantly stronger increase (p = .003). T-lymphocyte profiles did not change significantly (p > 2); however, the intra-individual change of Tregs between males and females was different with a significantly stronger increase in men (p = .017), as well as between genotypes of the vitamin D receptor (Apa, Taq, and Bsm: genotypes aa, TT, and bb; p = .004-0.015). Insulin demands declined significantly (p = .003-.039) and HbA1C improved (p < .001). Random C-peptide levels were low but rising (median, 0.125 ng/ml; range, 0.02-0.3) in 6 patients. No toxicity was observed. CONCLUSION: A daily vitamin D dose of 4000 IU for 3 months was well tolerated and enhanced Tregs in males. Glucometabolic control improved in all. Subsequent larger trials need to address ß-cell function and genotyping for individualized vitamin D doses.

Association of endothelin-1 and matrix metallopeptidase-9 with metabolic syndrome in middle-aged and older adults.

BACKGROUND: Metabolic syndrome (MetS) contains a cluster of cardiovascular risk factors. People with MetS are more susceptible to cardiovascular disease, diabetes mellitus, and cancer. Endothelin-1 (ET-1) and matrix metallopeptidase-9 (MMP-9) have been implicated in the development of cardiovascular diseases, diabetes mellitus and cancers. This cross-sectional study aimed to examine the association of ET-1 and MMP-9 with MetS in middle-aged and older Hong Kong Chinese adults. METHODS: 149 adults aged 50 to 92 (n = 75 for non-MetS group and n = 74 for MetS group) were examined. All subjects were screened for MetS according to the diagnostic guideline of the United States National Cholesterol Education Program (NCEP) Expert Panel Adult Treatment Panel (ATP) III criteria. Serum levels of ET-1 and MMP-9 were measured. Independent t test was used to detect differences between non-MetS and MetS groups and between subjects with or without certain metabolic abnormality. The association of the serum concentration of MMP-9 and ET-1 with MetS parameters were examined by Pearson's correlation analysis. RESULTS: Serum level of ET-1 is higher in MetS-positive subjects and in subjects with high blood pressure, elevated fasting blood glucose, and central obesity. The serum concentration of MMP-9 is higher in subjects positively diagnosed with MetS and subjects with high blood pressure, elevated fasting blood glucose, low blood high-density lipoprotein-cholesterol (HDL-C), high blood triglycerides, and central obesity. Correlation analyses revealed that serum concentration of ET-1 is positively correlated to systolic blood pressure, waist circumference, fasting blood glucose, and age whereas it is negatively correlated to HDL-C. MMP-9 is positively correlated to systolic blood pressure, waist circumference, fasting blood glucose, and age whereas it is negatively correlated to HDL-C. CONCLUSION: Serum ET-1 is higher in subjects with hypertension, hyperglycemia, central obesity or MetS. Serum MMP-9 is higher in subjects diagnosed with MetS or having either one of the MetS parameters. Both circulating levels of ET-1 and MMP-9 are correlated to systolic blood pressure, waist circumference, fasting blood glucose, HDL-C, and age. Further research is needed to fully dissect the role of ET-1 and MMP-9 in the development of cancers, diabetes and cardiovascular disease in relation to MetS.

Organization of ribosomal RNA genes from a Loofah witches' broom phytoplasma.

Using the technique of integrative mapping with three vectors carrying chromosomal rDNA sequences, one of two rRNA operons of loofah witches' broom (LfWB) phytoplasma was constructed. This is the first complete rRNA operon of a phytoplasma to be reported. The operon has a context of 5'-16S-23S-5S-3' with a tRNA(Ile) gene in the ITS and tRNA(Val) and tRNA(Asn) genes downstream from the 5S rRNA gene. Although the other operon has not been cloned, the DNA sequence of a PCR-amplified product shows that it has no tRNA(Ile) gene in the ITS region. The complete nucleotide sequences of 16S, 23S, and 5S rDNA are 1538, 2864, and 113 bp, respectively. Five -10-like sequences, but no -35 sequences, were found within a 494-bp leader region. There was a TG dinucleotide two nucleotides upstream from each -10-like sequence. The existence of a TG dinucleotide at this position has been reported to enhance the efficiency of a promoter without a -35 region. The regions immediately flanking the 5' and 3' ends of 16S and 23S rDNA can form long basepaired stems that contain sites for processing by RNase III. No obvious sequence for a rho-dependent or rho-independent termination site was found downstream from the tRNA(Asn) gene. The transcription may stop within a pyrimidine-rich region, as has been reported for several polypeptide-encoding genes and rRNA operons of archaeobacteria. The presence of the tRNA genes downstream from the 5S rRNA gene in the rRNA operon of LfWB phytoplasma further supports the hypothesis that phytoplasmas are phylogenetically closer to acholeplasmas than to mycoplasmas. The phylogenetic relatedness of LfWB phytoplasma to other phytoplasmas is discussed on the basis of the nucleotide sequence of rRNA genes and ITS.

Molecular cloning and characterization of a unique 60 kDa/72 kDa antigen gene encoding enzyme I of the phosphoenolpyruvate: sugar phosphotransferase system (PTS) of Mycoplasma hyopneumoniae.

The recombinant clone expressing a 60 kDa (P60) antigen was isolated from Escherichia coli by screening a lambda EMBL3 genomic library using rabbit produced antiserum against Mycoplasma hyopneumoniae. Sequence analysis revealed that an interrupted (by a UGA codon) open reading frame coding for a 72 kDa protein (P72) may contain the P60 antigen gene. Western blot analysis with an anti-P60 monospecific antibody confirmed the presence of a P72 antigen from the total protein of M. hyopneumoniae, and a 72 kDa protein was also expressed in E. coli after changing the codon (UGA to UGG) by site-directed mutagenesis. BLAST (Basic Local Alignment Search Tool) comparison showed that the amino acid sequences of P72 share approximately 70% homology with the phosphotransferase enzyme I (PTSI) of bacteria and other mycoplasma species. The biological function of the P72 cytosolic protein was further confirmed by complementation using an E. coli ptsI mutant. The bacterial phosphoenolpyruvate-sugar phosphotransferase system (PTS) is known to mediate the uptake and phosphorylation of carbohydrates and to be involved in signal transduction. The immune responses of specific pathogen free (SPF) pigs and farm animals toward this unique antigen were observed. The transcription start positions of the PTSI gene were determined in M. hyopneumoniae and E. coli by primer extension experiments and the promoter site was also predicted.

Molecular cloning and analysis of a HSP (heat shock protein)-like 42 kDa antigen gene of Mycoplasma hyopneumoniae.

The recombinant clone expressing the 42 kDa protein (P42) of Mycoplasma hyopneumoniae in Escherichia coli was analyzed. The 4.4 kb HindIII-Xmal DNA fragment expressing the p42 gene product encodes three ORFs: p42 and p16 in the forwarding strand, p24 in the reverse strand. Sequence comparisons revealed that p42 could be part of a p65 gene, and has 62% identities with Mycoplasma genitalium HSP70 gene and 56% identities with Bacillus subtilis dnaK gene; p16 and p24 genes share 73% and 47% identities with Erysipelothrix rhusiopathiae dnaJ gene and Pseudomonas fluorescens uvrC gene, respectively. Further analysis demonstrated that P42 is indeed a heat shock protein and the monospecific antibodies against P42 can block the growth of Mycoplasma hyopneumoniae.

Mushroom poisoning in children: report of an accident.

There were very few cases of mushroom poisoning every year in Taiwan and yet no fatal incident have been reported. A species named Amanita phalloides had high lethality rate (22-33%). Physicians should be aware of it's toxic property and be able to treat the patient in case of mushroom poisoning. However, mycologist sometimes might not distinguish edible from toxic mushroom so that educating people not to ingest wild mushroom is very important. We present 4 children with gastrointestinal syndrome after ingesting wild mushroom. We also introduce some basic approaches in treating mushroom poisoning in this paper.

The trend of sudden infant death syndrome in Taiwan from 1984 to 1993.

We collected 1984 to 1993's health statistics to calculate the incidence and trend of SIDS in Taiwan. Deaths of SIDS were listed in the International Classification of Diseases (ICD) code 798.0. All infants under 1 year of age died of SIDS were included in our study. We found Taiwan was a low incidence area of SIDS. The incidences of SIDS from 1984 to 1993 were increased from 0.25 to 0.56 per 1000 live births. We also found the SIDS had inclining trend from 1984 to 1993. Whether the reason of inclining trend of SIDS in Taiwan is due to westernization of living style needs further exploration.