A real-world experience of a prescribing policy for SGLT2-inhibitors in HFrEF in a Malaysian public tertiary cardiac centre.

A prescribing policy for SGLT2-inhibitors was implemented in a local public tertiary cardiology centre in Sabah to improve access for heart failure (HF) patients. The study evaluated 169 HF patients with reduced ejection fraction (HFrEF) who met the policy criteria. After starting SGLT2- inhibitors, a significant proportion of patients experienced decreased NTproBNP levels, indicating a positive response. HF hospitalisation rates within 1 year were lower compared to the previous year. No adverse events were reported, suggesting that the treatment is safe. Findings demonstrates the benefits of implementing prescribing policies to enhance treatment accessibility and generate valuable real-world data at the local healthcare level..

Vertical InGaN light-emitting diode with a retained patterned sapphire layer.

We present an efficient vertical InGaN light-emitting diode (LED) in which the proposed vertical LEDs were fabricated with patterned sapphire substrates (PSS) using thinning techniques. After the thinning of sapphire substrate, selective dry etching process was performed on the remainder sapphire layer to expose the n-GaN contact layer instead of removing the sapphire substrate using the laser lift-off technique. These processes feature the LEDs with a sapphire-face-up structure and vertical conduction property. The PSS was adopted as a growth substrate to mitigate the light-guided effect, and thereby increase the light-extraction efficiency. Compared with conventional lateral GaN LEDs grown on PSS, the proposed vertical LEDs exhibit a higher light output power and less power degradation at a high driving current. This could be attributed to the fact that the vertical LEDs behave in a manner similar to flip-chip GaN/sapphire LEDs with excellent heat conduction.

Vertical InGaN light-emitting diode with a retained patterned sapphire layer.

We present an efficient vertical InGaN light-emitting diode (LED) in which the proposed vertical LEDs were fabricated with patterned sapphire substrates (PSS) using thinning techniques. After the thinning of sapphire substrate, selective dry etching process was performed on the remainder sapphire layer to expose the n-GaN contact layer instead of removing the sapphire substrate using the laser lift-off technique. These processes feature the LEDs with a sapphire-face-up structure and vertical conduction property. The PSS was adopted as a growth substrate to mitigate the light-guided effect, and thereby increase the light-extraction efficiency. Compared with conventional lateral GaN LEDs grown on PSS, the proposed vertical LEDs exhibit a higher light output power and less power degradation at a high driving current. This could be attributed to the fact that the vertical LEDs behave in a manner similar to flip-chip GaN/sapphire LEDs with excellent heat conduction.

Factors affecting mortality in Hong Kong patients with upper limb necrotising fasciitis.

OBJECTIVE: To identify predictive factors for mortality of patients with upper limb necrotising fasciitis. DESIGN: Retrospective study. SETTING: Six hospitals in Hong Kong. PATIENTS: Clinical records of 29 patients treated in the hospitals were traced and analysed. MAIN OUTCOME MEASURES: Possible predictive factors for mortality as evaluated by application of Fisher's test. RESULTS: Overall mortality was 28%. Digital infections conferred a lower mortality, but progressive necrosis necessitated amputation. Vibrio vulnificus was the commonest organism identified in association with marine injury and in patients with cirrhosis. Prognostic indicators with decreasing significance include deranged renal and liver function, thrombocytopaenia, proximal involvement (elbow or above) initially, and presence of hypotension upon admission. CONCLUSION: With a P value of less than 0.05, deranged renal and liver function, thrombocytopaenia, initial proximal involvement, and hypotension on admission were predictors of mortality in necrotising fasciitis affecting the upper limbs. The ALERTS (Abnormal Liver function, Extent of infection, Renal impairment, Thrombocytopenia, and Shock) score with a cutoff of 3 appeared to predict mortality.

Stonefish envenomation with acute carpal tunnel syndrome.

Stonefish envenomation is a common marine sting. Although stonefish injuries are commonly sustained during maritime activities, this local delicacy can also be considered a regional occupational hazard for chefs. The availability and consumption of stonefish in local restaurants has increased the risk of acute carpal tunnel syndrome after a stonefish injury. This case report describes acute carpal tunnel syndrome following stonefish envenomation. An excellent recovery was achieved after surgical decompression of the carpal tunnel syndrome. Standard management of stonefish injuries should therefore take into account the possibility that this orthopaedic emergency may complicate the injury.

Posterior lumbar apophyseal ring fractures in adolescents: a report of four cases.

Posterior lumbar apophyseal ring fractures are rare in adolescents. We report 4 such cases in Chinese adolescents. Two of the patients had a slipped capital femoral epiphysis; 3 of them were overweight/obese. All presented with low back pain and radicular pain. Apophyseal fractures of the upper lumbar spine usually involve the lower end plate, whereas those of the lumbar sacral spine usually involve the upper end plate. The radiological features and pathophysiology are discussed. Two of the patients were treated with laminotomy and diskectomy after conservative treatment failed. All patients had complete resolution of their neurological deficits at a mean follow-up of 2 years. Despite its benign nature, long-term follow-up is necessary to define the natural course and prognosis of the disease. A high index of suspicion is needed to diagnose these fractures in adolescents.

Hypofractionated CyberKnife stereotactic radiosurgery for acoustic neuromas with and without association to neurofibromatosis Type 2.

CyberKnife stereotactic radiosurgery (CKSRS) has been proved effective in treating intra-cranial lesions. To treat acoustic neuroma (AN) patients with or without neurofibromatosis Type 2 (NF2) associations, the functional preservation of hearing, trigeminal nerve, and facial nerve are important. Twenty-one patients were treated with hypofractionated CKSRS. Fourteen non-NF2 and seven NF2 patients were enrolled. Cranial nerve function, audiograms, and magnetic resonance images (MRI) were monitored. Mean follow-up was 15 month. Tumors with volumes ranging from 0.13 to 24.8 cm3 (mean 5.4 cm3) were irradiated with the marginal dose 1800-2000 cGy/3 fractions. Tumors were treated with an 80 to 89% isodose line (mean 83%) and mean 97.9% tumor coverage. Two patients experienced hearing deterioration (16.7%) in the non-NF2 group, and 3 patients (50%) in the NF2 group. No facial or trigeminal dysfunction, brain stem toxicity, or cerebellar edema occurred. Tumor regression was seen in 9 patients (43%) and stable in 12 patients (57%). 100% tumor control rate was achieved. Hypofractionated CKSRS was not only effective in tumor control but also excellent in hearing preservation for non-NF2 AN. But for NF2 patients, although the tumor control was remarkable, hearing preservation was modest as in non-NF2 patients.

A review on adolescent childbearing in Taiwan: its characteristics, outcomes and risks.

In Taiwan, the age-specific fertility rate for adolescent girls aged 15-19 years has remained at 14-18/1,000 births during the past two decades, which is the highest among developed countries in Asia. There was a surprisingly high age-specific fertility rate for married women aged 15-19 years at 726 per 1,000 in 1994, much higher than that of the United States. Adolescent childbearing causes many adverse outcomes including unwanted and unstable marriage, repeated childbearing during adolescence, and increased risks of having low birth weight and preterm births and neonatal mortality. Studies in Taiwan showed that adolescent childbearing is associated with their poor knowledge but open attitude and behaviour on sexuality, the inadequate contraceptive services for the adolescents in need, some risk-taking behaviors, family dysfunction and low socioeconomic status of the adolescents' families. About two-thirds of the fathers of infants born to adolescent girls were adults, even old adults with a low education level Effective strategies for adolescent childbearing prevention range from sex education, the direct provision of contraceptive supplies, and to life options programmes, especially for the adolescents with high risk of adolescent pregnancy. Reducing the incidence of adolescent childbearing by active use of contraception is more important and practical than prohibiting adolescent sexual activity.

Microstructure and corrosion behavior of porous coatings on titanium alloy by vacuum-brazed method.

The microstructural evolution and electrochemical characteristics of brazed porous-coated Ti-6Al-4V alloy were analyzed and compared with respect to the conventionally 1300 degrees C sintering method. The titanium filler metal of low-melting-point (934 degrees C) Ti-15Cu-15Ni was used to braze commercially pure (CP) titanium beads onto the substrate of Ti-6Al-4V alloy at 970 degrees C for 2 and 8 h. Optical microscopy, scanning and transmission electron microscopy, and X-ray diffractometry (XRD) were used to characterize the microstructure and phase of the brazed metal; also, the potentiostat was used for corrosion study. Experimental results indicate that the bead/substrate contact interface of the 970 degrees C brazed specimens show larger contact area and higher radius curvature in comparison with 1300 degrees C sintering method. The microstructure of brazed specimens shows the Widmanstätten structure in the brazed zone and equiaxed alpha plus intergranular beta in the Ti-6Al-4V substrate. The intermetallic Ti2Ni phase existing in the prior filler metal diminishes, while the Ti2Cu phase can be identified for the substrate at 970 for 2 h, but the latter phase decrease with time. In Hank's solution at 37 degrees C, the corrosion rates of the 1300 degrees C sintering and the 970 degrees C brazed samples are similar at corrosion potential (E(corr)) in potentiodynamic test, and the value of E(corr) for the brazed sample is noble to the sintering samples. The current densities of the brazed specimens do not exceed 100 microA/cm2 at 3.5 V (SCE). These results suggest that the vacuum-brazed method exhibits the potentiality to manufacture the porous-coated specimens for biomedical application.

Thumb polydactyly: clinical outcome after reconstruction.

PURPOSE: To evaluate clinical and cosmetic outcomes of reconstruction in thumb polydactyly and prognostic value of the Wassel classification. METHODS: Between 1993 and 2000 inclusive, out of the patients with thumb polydactyly (involving 80 thumbs) operated on, 34 patients (36 thumbs) were available for review and underwent clinical and radiological assessment. Outcomes in terms of the Tada score and complications were recorded. RESULTS: The mean age of patients at the time of operation was 2.8 (range, 0.6-47) years. The mean follow-up period was 5 (range, 2.4-10) years. According to the Wassel classification, 12 were type-II thumb polydactyly, 3 type-III, 11 type-IV, 6 type-V, one type-VI, and 3 type-VII. There was no perioperative mortality or wound infection. More than 88% of the patients were satisfied or very satisfied with functional and cosmetic outcomes. Postoperative complications such as scar hypertrophy, pulp atrophy, joint deformity, and instability were common but minor. Ridge nail deformity after the Bilhaut Cloquet procedure was amenable to secondary corrective procedures. All types of operated thumb polydactyly achieved similar mean Tada scores (14.7- 16.6 out of 20). The Wassel classification category, age, and surgical procedures were found to have no prognostic value with regard to the Tada score and presence of complications. CONCLUSION: Surgery on thumb polydactyly is rewarding. The Wassel classification category can be used as a guide for treatment, although it fails to predict the occurrence of postoperative complications or Tada scores. Our patients' results can serve as guidelines of expected outcomes after reconstructive procedures in different sub-types of thumb polydactyly.

Breakage of intramedullary femoral guide rod during total knee arthroplasty: a case report.

We report a rare complication during primary total knee arthroplasty. An intramedullary femoral guide rod was broken during insertion. The broken part jammed into the isthmus of the femur. An initial attempt to push the broken rod via the proximal femur by a guide wire to the distal femur was unsuccessful because the broken rod was lodged in the isthmus. Ultimately, the isthmus was opened using a flexible 9-mm end-cutting reamer, and the broken rod was pushed down to the distal femoral entry site in an antegrade fashion under image intensification. Selecting a more medial entry site on the intercondylar notch with a smaller valgus cutting angle and using a shorter guide rod can avoid such a breakage.

Application of xenogeneic anti-canine distemper virus antibodies in treatment of canine distemper puppies.

OBJECTIVE: The clinical feasibility of passive immunotherapy has not been demonstrated in dogs naturally infected with canine distemper. In this study, porcine anti-canine distemper virus IgG and F(ab')2 antibody fragments were used to treat infected puppies. METHODS: A total of 41 naturally infected puppies (age Äsix months) exhibiting severe respiratory signs, but lacking neurological signs, were enrolled in the study. Twenty-five puppies were treated with a combination of IgG or F(ab')2 antibody fragments (Group 1) and supportive therapy and 16 puppies received routine supportive care only (Group 2). RESULTS: The survival rate of dogs in Group 1 (19/25; 76%) was significantly higher than that in Group 2 (5/16; 31·3%) (P<0·05). During the therapy, 8 of the 25 dogs (32%) in Group 1 developed neurological signs versus 12 of the 16 dogs (75%) in Group 2 (P<0·05). Adverse reactions were limited to elevated body temperature in dogs that received IgG antibodies. CLINICAL SIGNIFICANCE: Porcine anti-canine distemper virus antibodies improved survival in puppies affected with canine distemper with minimal adverse effects. Therefore, this therapy could be considered for treatment of endangered animal species infected with canine distemper virus.

Oxidized low density lipoprotein induces apoptosis via generation of reactive oxygen species in vascular smooth muscle cells.

OBJECTIVE: Death of vascular smooth muscle cell (VSMC) induced by oxidized LDL (oxLDL) can occur by both necrosis and apoptosis which may contribute to plaque instability and rupture. Reactive oxygen species (ROS) induces apoptosis in VSMC and is involved in oxLDL action, we tested the hypothesis here that a coupling exists between ROS generation and apoptosis of oxLDL-treated VSMC. METHODS: Cultured VSMC from rat aorta were treated with oxLDL, apoptosis and necrosis were distinguished by using FITC-annexin V label and propidium iodide stain, analyzed by flow cytometry. ROS generation of VSMCs was detected by the fluorescence intensity of DCF. Apoptosis was also determined by cleavage of procaspase-3. RESULTS: OxLDL induced apoptosis (3 h) in a dose-dependent manner and reached maximum (with near-basal necrosis) at a concentration of 300 microg/ml. At this and lower (100 microg/ml) concentration, oxLDL, but not native LDL, stimulated ROS production rapidly (< or =5 min) and ROS level remained elevated for at least 45 min. Catalase and deferoxamine reduced both oxLDL-induced apoptosis and ROS generation. Superoxide dismutase and benzoic acid neither reduced the oxLDL-induced ROS generation nor inhibited apoptosis. Since oxLDL-induced ROS generation were inhibited by nordihydroguaiaretic acid and rotenone, lipoxygenase and mitochondrial pathways could be involved. In addition, catalase, deferoxamine, and N-acetylcysteine inhibited oxLDL-induced cleavage of procaspase-3 as well. CONCLUSIONS: ROS generation and apoptosis are tightly coupled in oxLDL-treated VSMCs. Antioxidants that reduced ROS level inhibited apoptosis, those that did not reduce ROS level were ineffective. Both mitochondrial and lipoxygenase activities may be involved.

Crocalbin: a new calcium-binding protein that is also a binding protein for crotoxin, a neurotoxic phospholipase A2.

Utilizing Marathon-ready cDNA library and a gene-specific primer corresponding to a partial amino acid sequence determined previously, the complete nucleotide sequence for the cDNA of crocalbin, which binds crotoxin (a phospholipase A2) and Ca2+, was obtained by polymerase chain reaction. The open reading frame of the cDNA encodes a novel polypeptide of 315 amino acid residues, including a signal sequence of 19 residues. This protein contains six potential Ca(2+)-binding domains, one N-glycosylation site, and a large amount of acidic amino acid residues. The ability to bind Ca2+ has been ascertained by calcium overlay experiment. Evidenced by sequence similarity in addition, it is concluded that crocalbin is a new member of the reticulocalbin family of calcium-binding proteins.

3,3-Diphenyl-3-(2-alkyl-1,3,4-oxadiazol-5-yl)propylcycloalkylamines, a novel series of antidiarrheal agents.

A series of 4-amino-2,2-diarylbutyronitriles (3) prepared for testing as inhibitors of gastrointestinal propulsive activity did not show any enhancement over such existing agents as diphenoxylate and loperamide. However, conversion of the nitrile group to a 2-methyl-1,3,4-oxadiazol-5-yl function led to compounds 5g and 5j, statistically equipotent to diphenoxylate and loperamide in the mouse and showing a very low order of analgesic activity. Structural modifications determined that the best separation of antipropulsive and analgesic effects was obtained when the amino group was bicyclic and the oxadiazole ring had a 2-methyl substituent. The most potent compounds were and analogues of diphenoxylate and loperamide where the oxadiazole ring was present, but these compounds had marked analgesic activity.

Substituted 2-[(2-benzimidazolylsulfinyl)methyl]anilines as potential inhibitors of H+/K+ ATPase.

A series of substituted 2-[(2-benzimidazolylsulfinyl)methyl]anilines were synthesized as potential inhibitors of the acid secretory enzyme H+/K+ ATPase. Substitutions on the aniline nitrogen atom resulted in potent enzyme inhibition in vitro but weak activity in gastric fistula dogs. Electron-donating substituents on the aniline ring enhanced in vitro and in vivo potency relative to the unsubstituted analogue. The potency showed a correlation to the calculated pKa of the aniline nitrogen atom. Substitutions on the aniline and benzimidazole rings did not further enhance potency. Di- and trisubstituted aniline derivatives were potent inhibitors of the enzyme system. The preferred combination of substituents were a methoxy group on the benzimidazole ring and a single alkyl group on the aniline ring. One such compound, 76, was an effective inhibitor of acid secretion in the dog and was selected for further pharmacological study.

Binding proteins on synaptic membranes for crotoxin and taipoxin, two phospholipases A2 with neurotoxicity.

Crotoxin and taipoxin are both neurotoxic phospholipases A2 capable of affecting the presynaptic activity to bring about ultimate blockade of synaptic transmission. The enzymatic activity has generally been considered to be necessary but not sufficient for the blockade. Since many phospholipases A2 with comparable or even higher enzymatic activity are not toxic, it has been postulated that the difference lies in the affinity of binding to the presynaptic membrane. In confirmation of this proposition, we and others have previously shown that iodinated crotoxin and taipoxin bind specifically with high affinity to the isolated synaptic membrane fraction from guinea-pig brain, whereas specific binding is not detected with the nontoxic pancreatic phospholipase A2. Experiments based on photoaffinity labeling and simple chemical cross-linking techniques have led to the identification of three polypeptides preferentially present in neuronal membranes as (subunits of) the binding protein(s) for crotoxin and/or taipoxin. Some, but not all, other toxic phospholipases A2 also appear to be ligands for the three polypeptides. We now report studies on partial purification of these polypeptides using affinity chromatography and other techniques. In order to learn the normal physiological roles played by the toxin-binding proteins, the phospholipase-independent effects of the toxins on the synaptosomes have been sought. We have found that under Ca(2+)-free condition, taipoxin or crotoxin inhibits with IC50 of 20-1000 nM the Na(+)-dependent uptake of norepinephrine, dopamine and serotonin by the synaptosomes. In contrast, choline uptake is not affected.(ABSTRACT TRUNCATED AT 250 WORDS)

17Beta-estradiol inhibits oxidized low density lipoprotein-induced generation of reactive oxygen species in endothelial cells.

Increase of intracellular reactive oxygen species (ROS) has been proposed to cause endothelial injury, and oxidized LDL (oxLDL) actions are associated with an early increase of ROS. Estrogen protects vascular cells partly via its antioxidant effects and by preventing lipid peroxidation. However, whether it can inhibit oxLDL-induced stimulation of ROS generation in endothelial cells is unknown. We utilized the fluorescent dye (DCFH-DA) to measure ROS generation and compared the stimulant effect of tert-butylhydroperoxide (TBH) and oxLDL in human umbilical vein endothelial cells (HUVECs). We found that TBH, H2O2, and oxLDL rapidly stimulated ROS generation, and in a dose-dependent manner with TBH. A concentration of estrogen effective in preventing lipid peroxidation was employed either by pretreatment of cells 18 h prior to or by direct co-incubation (30 min) with HUVEC and oxLDL. Estrogen (54 microM) pretreatment significantly suppressed both TBH- and oxLDL- induced stimulation of ROS generation. Both 1 and 54 microM concentration of estrogen could directly inhibit oxLDL-induced ROS production in HUVECs. Thus, either 18 h pretreatment or 30 min co-incubation with estrogen reduced stimulated ROS generation, suggesting that both cellular and direct actions of estrogen may be involved.

Trace determination of methanol in water-ethanol solution by derivatization and high-performance liquid chromatography.

A simple and sensitive high-performance liquid chromatographic method has been established for the determination of methanol in water-ethanol solution. The method is based on the transfer of the methoxide anion, which is formed from methanol under strong alkaline treatment in aqueous solution, by benzalkonium chloride into the dichloromethane organic phase for derivatization with 3-bromomethyl-7-methoxy-1,4-benzoxazin-2-one. The derivative obtained was separated on a LiChrospher diol column with n-hexane-dichloromethane (9:1, v/v) as the mobile phase. Several parameters affecting the partition/derivatization of methanol were investigated. The linear range for the determination of methanol was 2-20 mumol/ml; the detection limit (signal-to-noise ratio = 5; sample size, 10 microliters) of methanol was about 0.10 mumol/ml (R.S.D. = 16%, n = 3). The method has been satisfactorily applied to the assay of methanol in spiked commercial liquors.

Inhibitory effect of estrogen on vascular contraction from male rats of different ages.

Both age and sex influence vascular contractile functions and play significant roles in cardiovascular regulation. Recent research has focused on the action of sex steroids on blood vessels and characterized both endothelium-dependent as well as-independent effects in agonists-induced contractile response. However, to study the combined influences of age and sex steroids present a complicated situation. In the current investigation, we studied the role of both these physiological factors in an in vitro approach. We found that high concentrations of estrogen (E2, 17 beta-estradiol) significantly inhibited contractile response induced by KCI in endothelium-denuded aorta derived from both young (24 wk) and aged (53 wk) male rats. The contractile responses in aorta from aged rats were significantly less than that from young adults in the absence or presence of E2 indicating that the vascular effect of E2 could be demonstrated in both young and aged male rats. Taken together, our data suggest that E2's action on endothelium-independent, KCI-induced contractile response in vitro could serve as a simple model system to examine the interaction of aging process and gender difference on vascular functions.