A 103 year old patient was admitted with pain in the right iliac fossa. There was no response to conservative treatment. Subsequent laparatomy showed the presence of a perforated ulcer in the pyloric region. The condition improved gradually after the surgical management.
In a prospective study of fifty consecutive outpatients (30 men and 20 women) attending the Behaviour Therapy Clinic at a general hospital, the commonest conditions were obsessive compulsive disorders (n = 16), phobic disorders (n = 11) and generalised anxiety disorders (n = 9). Three-quarters of the referrals were from psychiatrists and family physicians. The patients received between 2 to 10 sessions of behaviour treatment; most had 4 to 6 sessions with a mean of 4.7, SD 1.82. The commonest behavioural techniques administered were exposure therapy with response prevention and relaxation therapy. Initially, treatment was therapist-aided, but subsequently self-help was encouraged with regular reviews of the patient's homework. After one month, 42 patients (84%) were assessed to have improved somewhat, with 20 (40%) showing moderate improvement. After three months, 41 (82%) continued to improve, with 33 (66%) showing moderate to great improvement. Nine patients were considered to have failed in therapy-six defaulted and three were non-responders. The reasons for defaulting treatment were unwillingness to bear with the discomfort involved in exposure therapy, lack of motivation or returning to own hometown in Malaysia. Sixteen patients (n = 32%) were treated solely with behavioural techniques while the rest had a combination of behaviour therapy and drugs, especially anxiolytics and antidepressants. However, at the end of treatment, the dosages of most medications were reduced or else discontinued completely.
Study site: Behavior therapy clinic at a general hospital
Using a novel library of 5637 expressed sequence tags (ESTs) from the brain tissue of the Asian seabass (Lates calcarifer), we first characterized the brain transcriptome for this economically important species. The ESTs generated from the brain of L. calcarifer yielded 2410 unique transcripts (UTs) which comprise of 982 consensi and 1428 singletons. Based on database similarity, 1005 UTs (41.7%) can be assigned putative functions and were grouped into 12 functional categories related to the brain function. Amongst others, we have identified genes that are putatively involved in energy metabolism, ion pumps and channels, synapse related genes, neurotransmitter and its receptors, stress induced genes and hormone related genes. Subsequently we selected a putative preprocGnRH-II precursor for further characterization. The complete cDNA sequence of the gene obtained was found to code for an 85-amino acid polypeptide that significantly matched preprocGnRH-II precursor sequences from other vertebrates, and possesses structural characteristics that are similar to that of other species, consisting of a signal peptide (23 residues), a GnRH decapeptide (10 residues), an amidation/proteolytic-processing signal (glycine-lysine-argine) and a GnRH associated peptide (GAP) (49 residues). Phylogenetic analysis showed that this putative L. calcarifer preprocGnRH-II sequence is a member of the subcohort Euteleostei and divergent from the sequences of the subcohort Otocephalan. These findings provide compelling evidence that the putative L. calcarifer preprocGnRH-II precursor obtained in this study is orthologous to that of other vertebrates. The functional prediction of this preprocGnRH-II precursor sequence through in silico analyses emphasizes the effectiveness of the EST approach in gene identification in L. calcarifer.
This study investigates the feasibility of processed human amnion (HAM) as a substrate for chondrogenic differentiation of mesenchymal stem cells (MSCs). HAM preparations processed by air drying (AD) and freeze drying (FD) underwent histological examination and MSC seeding in chondrogenic medium for 15 days. Monolayer cultures were used as control for chondrogenic differentiation and HAMs without cell seeding were used as negative control. Qualitative observations were made using scanning electron microscopy analysis and quantitative analyses were based on the sulfated glycosaminoglycans (GAG) assays performed on day 1 and day 15. Histological examination of HAM substrates before seeding revealed a smooth surface in AD substrates, while the FD substrates exhibited a porous surface. Cell attachment to AD and FD substrates on day 15 was qualitatively comparable. GAG were significantly highly expressed in cells seeded on FD HAM substrates. This study indicates that processed HAM is a potentially valuable material as a cell-carrier for MSC differentiation.
Introduction: Compliance with medical nutrition therapy is important to improve patient outcomes. The purpose of this study was to determine dietary compliance and its association with glycemic control among outpatients with poorly controlled type 2 diabetes mellitus (T2DM) in Hospital Universiti Sains Malaysia (HUSM).
Methods: In this cross-sectional study, patients who had a glycosylated hemoglobin (HbA1c) level of at least 6.5%, after attending a diet counseling session at the Outpatient Dietetic Clinic, HUSM, were enrolled. Out of 150 diabetic patients reviewed between 2006 and 2008, 61 adults (32 men and 29 women) agreed to participate in this study. A questionnaire-based interview was used to collect socio-demographic, clinical and diabetes self-care data. The patient’s dietary compliance rate was determined by the Summary of Diabetes Self-Care Activities (SDSCA) measure. Anthropometric and biological measurements were also taken.
Results: Only 16.4% of the respondents adhered to the dietary regimen provided by dietitians. Among the 7 dietary self-care behaviours, item number 6 (eat lots of food high in dietary fibre such as vegetable or oats) had the highest compliant rate (54.1%); whereas item number 3 (eat five or more servings of
fruits and vegetables per day) had the lowest compliant rate (23.0%). There was a significant association between gender (p=0.037) and fasting blood sugar (FBS) (p=0.007) with the compliance status. Conclusion: Dietary non-compliance is still common among T2DM patients. Dietitians need to improve their skills and use more effective intervention approaches in providing dietary counseling to patients.
Keywords: Dietary compliance, diet counseling, type 2 diabetes mellitus
Rhinoscleroma is a chronic, slowly progressive, inflammatory disease of the upper respiratory tract. It is associated with Klebsiella rhinoscleromatis infection. We present the clinical and pathological features of four patients diagnosed with rhinoscleroma at the National Skin Centre, Singapore between 1997 and 2010. All four patients presented with only cutaneous involvement, and the diagnosis was clinched via histological examination. The patients were treated with a combination of antibiotics. Two patients who were on follow-up at the time of this writing responded positively to the antibiotic treatment, while two were lost to follow-up. Rhinoscleroma is a diagnostic challenge, as it is an uncommon disease in Singapore and Malaysia. We highlight this condition to raise awareness of the disease in order to aid in early diagnosis of patients. Without treatment, this condition can result in significant complications, including involvement of the lower airways. Early diagnosis and appropriate treatment help to reduce morbidity.
The use of growth differentiation factor 5 (GDF-5) in damaged tendons has been shown to improve tendon repair. It has been hypothesized that further improvements may be achieved when GDF-5 is used to promote cell proliferation and induce tenogenic differentiation in human bone marrow-derived mesenchymal stem cells (hMSCs). However, the optimal conditions required to produce these effects on hMSCs have not been demonstrated in previous studies. A study to determine cell proliferation and tenogenic differentiation in hMSCs exposed to different concentrations of GDF-5 (0, 5, 25, 50, 100 and 500 ng/ml) was thus conducted. No significant changes were observed in the cell proliferation rate in hMSCs treated at different concentrations of GDF-5. GDF-5 appeared to induce tenogenic differentiation at 100 ng/ml, as reflected by (1) a significant increase in total collagen expression, similar to that of the primary native human tenocyte culture; (2) a significant upregulation in candidate tenogenic marker gene expression, i.e. scleraxis, tenascin-C and type-I collagen; (3) the ratio of type-I collagen to type-III collagen expression was elevated to levels similar to that of human tenocyte cultures, and (4) a significant downregulation of the non-tenogenic marker genes runt-related transcription factor 2 and sex determining region Y (SRY)-box 9 at day 7 of GDF-5 induction, further excluding hMSC differentiation into other lineages. In conclusion, GDF-5 does not alter the proliferation rates of hMSCs, but, instead, induces an optimal tenogenic differentiation response at 100 ng/ml.
Mesenchymal stem cells (MSCs) are recognized by their plastic adherent ability, fibroblastic-like appearance, expression of specific surface protein markers, and are defined by their ability to undergo multi-lineage differentiation. Although rabbit bone marrow-derived MSCs (rbMSCs) have been used extensively in previous studies especially in translational research, these cells have neither been defined morphologically and ultrastructurally, nor been compared with their counterparts in humans in their multi-lineage differentiation ability. A study was therefore conducted to define the morphology, surface marker proteins, ultrastructure and multi-lineage differentiation ability of rbMSCs. Herein, the primary rbMSC cultures of three adult New Zealand white rabbits (at least 4 months old) were used for three independent experiments. rbMSCs were isolated using the gradient-centrifugation method, an established technique for human MSCs (hMSCs) isolation. Cells were characterized by phase contrast microscopy observation, transmission electron microscopy analysis, reverse transcriptase-polymerase chain reaction (PCR) analysis, immunocytochemistry staining, flow cytometry, alamarBlue(®) assay, histological staining and quantitative (q)PCR analysis. The isolated plastic adherent cells were in fibroblastic spindle-shape and possessed eccentric, irregular-shaped nuclei as well as rich inner cytoplasmic zones similar to that of hMSCs. The rbMSCs expressed CD29, CD44, CD73, CD81, CD90 and CD166, but were negative (or dim positive) for CD34, CD45, CD117 and HLD-DR. Despite having similar morphology and phenotypic expression, rbMSCs possessed significantly larger cell size but had a lower proliferation rate as compared with hMSCs. Using established protocols to differentiate hMSCs, rbMSCs underwent osteogenic, adipogenic and chondrogenic differentiation. Interestingly, differentiated rbMSCs demonstrated higher levels of osteogenic (Runx2) and chondrogenic (Sox9) gene expressions than that of hMSCs (P 0.05). rbMSCs possess similar morphological characteristics to hMSCs, but have a higher potential for osteogenic and chondrogenic differentiation, despite having a lower cell proliferation rate than hMSCs. The characteristics reported here may be used as a comprehensive set of criteria to define or characterize rbMSCs.
To investigate the capability and diagnostic accuracy of diffusion-weighted imaging (DWI) in differentiating benign from malignant breast lesions using 3 T magnetic resonance imaging (MRI).
Evidence for C-H···π(CuCl···HNCS) interactions, i.e. C-H···π(quasi-chelate ring) where a six-membered quasi-chelate ring is closed by an N-H···Cl hydrogen bond, is presented based on crystal structure analyses of (Ph3P)2Cu[ROC(=S)N(H)Ph]Cl. Similar intramolecular interactions are identified in related literature structures. Calculations suggest that the energy of attraction provided by such interactions approximates 3.5 kcal mol(-1).
Topical chemotherapy is the application of cancer drugs directly onto the skin, which has become a standard treatment for basal cell carcinoma. Due to the promising results in the treatment of skin cancer, topical chemotherapy has recently been applied to breast cancer patients because some breast cancer tissues are only superficial. Hydroxytyrosol, a phenolic compound from olives that is present in high amounts in Hidrox(®) olive extract, has been shown to have a protective effect on normal cells and selective antitumor activities on cancerous cells. The aims of the present study were to develop an alginate bilayer film containing Hidrox(®) and to investigate its potential use as a topical chemotherapeutic agent. Alginate films were characterized for swelling and for physical, thermal, rheological, and mechanical properties. Drug content uniformity and in vitro drug release tests were also investigated. The alginate bilayer films containing Hidrox(®), HB2, showed controlled release of hydroxytyrosol at a flux of 0.094±0.009 mg/cm(2)/h. The results of the cytotoxic assay showed that the HB2 films were dose-dependent and could significantly reduce the growth of breast cancer cells (MCF-7) at 150 μg/mL for a cell viability of 29.34±4.64%. In conclusion, an alginate bilayer film containing Hidrox(®) can be a potential alternative for topical chemotherapeutic agent for skin and breast cancer treatment.
Carbamzepine (CBZ) was encapsulated in a parenteral oil-in-water nanoemulsion, in an attempt to improve its bioavailability. The particle size, polydispersity index and zeta potential were measured using dynamic light scattering. Other parameters such as pH, osmolality, viscosity, drug loading efficiency and entrapment efficiency were also recorded. Transmission electron microscopy revealed that emulsion droplets were almost spherical in shape and in the nano-range. The in vitro release profile was best characterized by Higuchi's equation. The parenteral nanoemulsion of CBZ showed significantly higher AUC0→5, AUC0→∞, AUMC0→5, AUMC0→∞, Cmax and lower clearance than that of CBZ solution in plasma. Additionally, parenteral nanoemulsion of CBZ showed significantly higher AUC0→∞, AUMC0→∞ and Cmaxthan that of CBZ solution in brain. The parenteral nanoemulsion of CBZ could therefore use as a carrier, worth exploring further for brain targeting.
To date, the molecular signalling mechanisms which regulate growth factors-induced MSCs tenogenic differentiation remain largely unknown. Therefore, a study to determine the global gene expression profile of tenogenic differentiation in human bone marrow stromal cells (hMSCs) using growth differentiation factor 5 (GDF5) was conducted. Microarray analyses were conducted on hMSCs cultures supplemented with 100 ng/ml of GDF5 and compared to undifferentiated hMSCs and adult tenocytes. Results of QuantiGene® Plex assay support the use and interpretation of the inferred gene expression profiles and pathways information. From the 27,216 genes assessed, 873 genes (3.21% of the overall human transcriptome) were significantly altered during the tenogenic differentiation process (corrected p<0.05). The genes identified as potentially associated with tenogenic differentiation were ARHGAP29, CCL2, integrin alpha 8 and neurofilament medium polypeptides. These genes, were mainly associated with cytoskeleton reorganization (stress fibers formation) signaling. Pathway analysis demonstrated the potential molecular pathways involved in tenogenic differentiation were: cytoskeleton reorganization related i.e. keratin filament signaling and activin A signaling; cell adhesion related i.e. chemokine and adhesion signaling; and extracellular matrix related i.e. arachidonic acid production signaling. Further investigation using atomic force microscopy and confocal laser scanning microscopy demonstrated apparent cytoskeleton reorganization in GDF5-induced hMSCs suggesting that cytoskeleton reorganization signaling is an important event involved in tenogenic differentiation. Besides, a reduced nucleostemin expression observed suggested a lower cell proliferation rate in hMSCs undergoing tenogenic differentiation. Understanding and elucidating the tenogenic differentiation signalling pathways are important for future optimization of tenogenic hMSCs for functional tendon cell-based therapy and tissue engineering.
OBJECTIVE: To evaluate the usefulness of extended-interval gentamicin dosing practiced in neonatal intensive care unit (NICU) and special care nursery (SCN) of a Malaysian hospital.
METHODS: Cross-sectional observational study with pharmacokinetic analysis of all patients aged ≤28 days who received gentamicin treatment in NICU/SCN. Subjects received dosing according to a regimen modified from an Australian-based pediatric guideline. During a study period of 3 months, subjects were evaluated for gestational age, body weight, serum creatinine concentration, gentamicin dose/interval, serum peak and trough concentrations, and pharmacokinetic parameters. Descriptive percentages were used to determine the overall dosing accuracy, while analysis of variance (ANOVA) was conducted to compare the accuracy rates among different gestational ages. Pharmacokinetic profile among different gestational age and body weight groups were compared by using ANOVA.
RESULTS: Of the 113 subjects included, 82.3% (n = 93) achieved therapeutic concentrations at the first drug-monitoring assessment. There was no significant difference found between the percentage of term neonates who achieved therapeutic concentrations and the premature group (87.1% vs. 74.4%), p = 0.085. A total of 112 subjects (99.1%) achieved desired therapeutic trough concentration of <2 mg/L. Mean gentamicin peak concentration was 8.52 mg/L (95% confidence interval [Cl], 8.13-8.90 mg/L) and trough concentration was 0.54 mg/L (95% CI, 0.48-0.60 mg/L). Mean volume of distribution, half-life, and elimination rate were 0.65 L/kg (95% CI, 0.62-0.68 L/kg), 6.96 hours (95% CI, 6.52-7.40 hours), and 0.11 hour(-1) (95% CI, 0.10-0.11 hour(-1)), respectively.
CONCLUSION: The larger percentage of subjects attaining therapeutic range with extended-interval gentamicin dosing suggests that this regimen is appropriate and can be safely used among Malaysian neonates.
KEYWORDS: aminoglycosides; extended-interval; gentamicin; neonate; pharmacokinetics
The title compound, [Au(C8H7ClNOS)(C18H15P)], is a monoclinic (P21/n, Z' = 1; form β) polymorph of the previously reported triclinic form (P-1, Z' = 1; form α) [Tadbuppa & Tiekink (2010 ▸). Acta Cryst. E66, m664]. The mol-ecular structures of both forms feature an almost linear gold(I) coordination geometry [P-Au-S = 175.62 (5)° in the title polymorph], being coordinated by thiol-ate S and phosphane P atoms, a Z conformation about the C=N bond and an intra-molecular Au⋯O contact. The major conformational difference relates to the relative orientations of the residues about the Au-S bond: the P-Au-S-C torsion angles are -8.4 (7) and 106.2 (7)° in forms α and β, respectively. The mol-ecular packing of form β features centrosymmetric aggregates sustained by aryl-C-H⋯O inter-actions, which are connected into a three-dimensional network by aryl-C-H⋯π contacts. The Hirshfeld analysis of forms α and β shows many similarities with the notable exception of the influence of C-H⋯O inter-actions in form β.
In the solid state, the title compound, C12H16BrNO5 [systematic name: 4-bromo-2-((1E)-{[1,3-dihy-droxy-2-(hy-droxy-meth-yl)propan-2-yl]iminium-yl}meth-yl)-6-meth-oxy-benzen-1-olate], C12H16BrNO5, is found in the keto-amine tautomeric form, with an intra-molecular iminium-N-H⋯O(phenolate) hydrogen bond and an E conformation about the C=N bond. Both gauche (two) and anti relationships are found for the methyl-hydroxy groups. In the crystal, a supra-molecular layer in the bc plane is formed via hy-droxy-O-H⋯O(hy-droxy) and charge-assisted hy-droxy-O-H⋯O(phenolate) hydrogen-bonding inter-actions; various C-H⋯O inter-actions provide additional cohesion to the layers, which stack along the a axis with no directional inter-actions between them. A Hirshfeld surface analysis confirms the lack of specific inter-actions in the inter-layer region.
The Yb(III) atom in the title complex, [Yb(C27H24Cl3N4O3)] [systematic name: (2,2',2''-{(nitrilo)-tris-[ethane-2,1-di-yl(nitrilo)-methylyl-idene]}tris-(4-chloro-phenolato)ytterbium(III)], is coordinated by a trinegative, hepta-dentate ligand and exists within an N4O3 donor set, which defines a capped octa-hedral geometry whereby the amine N atom caps the triangular face defined by the three imine N atoms. The packing features supra-molecular layers that stack along the a axis, sustained by a combination of aryl-C-H⋯O, imine-C-H⋯O, methyl-ene-C-H⋯π(ar-yl) and end-on C-Cl⋯π(ar-yl) inter-actions. A Hirshfeld surface analysis points to the major contributions of C⋯H/ H⋯C and Cl⋯H/H⋯Cl inter-actions (along with H⋯H) to the overall surface but the Cl⋯H contacts are at distances greater than the sum of their van der Waals radii.
The title compound, [Au(C9H10NOS)(C18H15P)], features a near linear P-Au-S arrangement defined by phosphane P and thiol-ate S atoms with the minor distortion from the ideal [P-Au-S is 177.61 (2)°] being traced in part to the close intra-molecular approach of an O atom [Au⋯O = 3.040 (2) Å]. The packing features supra-molecular layers lying parallel to (011) sustained by a combination of C-H⋯π and π-π [inter-centroid distance = 3.8033 (17) Å] inter-actions. The mol-ecular structure and packing are compared with those determined for a previously reported hemi-methanol solvate [Kuan et al. (2008 ▸). CrystEngComm, 10, 548-564]. Relatively minor differences are noted in the conformations of the rings in the Au-containing mol-ecules. A Hirshfeld surface analysis confirms the similarity in the packing with the most notable differences relating to the formation of C-H⋯S contacts between the constituents of the solvate.
The title compound, [Cu(C5H5NO2S2)(C18H15P)2]·CHCl3, features a tetra-hedrally coordinated CuI atom within a P2S2 donor set defined by two phosphane P atoms and by two S atoms derived from a symmetrically coordinating di-thio-carbamate ligand. Both intra- and inter-molecular hy-droxy-O-H⋯O(hydroxy) hydrogen bonding is observed: the former closes an eight-membered {⋯HOC2NC2O} ring, whereas the latter connects centrosymmetrically related mol-ecules into dimeric aggregates via eight-membered {⋯H-O⋯H-O}2 synthons. The complex mol-ecules are arranged to form channels along the c axis in which reside the chloro-form mol-ecules, being connected by Cl⋯π(arene) and short S⋯Cl [3.3488 (9) Å] inter-actions. The inter-molecular inter-actions have been investigated further by Hirshfeld surface analysis, which shows the conventional hydrogen bonding to be very localized with the main contributors to the surface, at nearly 60%, being H⋯H contacts. Solution NMR studies indicate that whilst the same basic mol-ecular structure is retained in solution, the tri-phenyl-phosphane ligands are highly labile, exchanging rapidly with free Ph3P at room temperature.
The title compound, [Re(C3H6NS2)(C2H3N)(CO)3], features an octa-hedrally coordinated Re(I) atom within a C3NS2 donor set defined by three carbonyl ligands in a facial arrangement, an aceto-nitrile N atom and two S atoms derived from a symmetrically coordinating di-thio-carbamate ligand. In the crystal, di-thio-carbamate-methyl-H⋯O(carbon-yl) inter-actions lead to supra-molecular chains along [36-1]; both di-thio-carbamate S atoms participate in intra-molecular methyl-H⋯S inter-actions. Further but weaker aceto-nitrile-C-H⋯O(carbonyl) inter-actions assemble mol-ecules in the ab plane. The nature of the supra-molecular assembly was also probed by a Hirshfeld surface analysis. Despite their weak nature, the C-H⋯O contacts are predominant on the Hirshfeld surface and, indeed, on those of related [Re(CO)3(C3H6NS2)L] structures.