Depression among chronic pain patients at Hospital Tengku Ampuan Rahimah, Klang.

INTRODUCTION: Despite the high prevalence rates of depression amongst chronic pain patients reported globally, the condition is often under-recognised and under-treated. Depression frequently complicates the effective management of pain and is associated with poor quality of life. This study aimed to explore the incidence of depression and its' associated factors in a sample of chronic pain patients in Malaysia. MATERIALS AND METHODS: This descriptive cross-sectional study was conducted amongst clinically diagnosed chronic pain patients from the pain management clinic of Hospital Tengku Ampuan Rahimah over a period of seven months. Socio-demographics and clinical data were obtained from patients' interview and medical records. The validated Depression Anxiety Stress Scale-21 (DASS-21) was used for screening and Mini International Neuropsychiatric Interview (MINI) was used to establish the depression diagnoses among the patients. Numeric pain intensity scale was used to assess the severity of pain. RESULTS: Eighty-three patients with a mean age of 50.4±12.50 years participated in this study. The majority of the patients were females (56.6%), married (85.5%) and being employed (49.4%). The percentage of depression was 37.4%. Depression was significantly associated with severity of pain (p<0.001) and the duration of pain (p <0.05). CONCLUSION: Almost one third of chronic pain patients in this study have depression. Depression was significantly associated with the severity and duration of pain. Depression should be regularly screened among patient with chronic pain.

A novel small molecule hydroxamate preferentially inhibits HDAC6 activity and tumour growth.

BACKGROUND: This study investigates whether a histone deacetylase subtype 6 (HDAC6) inhibitor could be used in the treatment of solid tumours. METHODS: We evaluated the effect of a novel inhibitor, C1A, on HDAC6 biochemical activity and cell growth. We further examined potential of early noninvasive imaging of cell proliferation by [(18)F]fluorothymidine positron emission tomography ([(18)F]FLT-PET) to detect therapy response. RESULTS: C1A induced sustained acetylation of HDAC6 substrates, α-tubulin and HSP90, compared with current clinically approved HDAC inhibitor SAHA. C1A induced apoptosis and inhibited proliferation of a panel of human tumour cell lines from different origins in the low micromolar range. Systemic administration of the drug inhibited the growth of colon tumours in vivo by 78%. The drug showed restricted activity on gene expression with <0.065% of genes modulated during 24 h of treatment. C1A treatment reduced tumour [(18)F]FLT uptake by 1.7-fold at 48 h, suggesting that molecular imaging could provide value in future studies of this compound. CONCLUSION: C1A preferentially inhibits HDAC6 and modulates HDAC6 downstream targets leading to growth inhibition of a diverse set of cancer cell lines. This property together with the favourable pharmacokinetics and efficacy in vivo makes it a candidate for further pre-clinical and clinical development.

Kamlet-taft and Catalan studies of some novel Y-shaped imidazole derivatives.

Some novel Y-shaped imidazole derivatives were developed and characterized by NMR and mass spectral techniques. The photophysical properties of these imidazole derivatives were studied in several solvents. The Kamlet-Taft and Catalan's solvent scales were found to be the most suitable for describing the solvatochromic shifts of the absorption and fluorescence emission. The adjusted coefficient representing the electron releasing ability or basicity of the solvent, C(ß) or C(SB) has a negative value, suggesting that the absorption and fluorescence bands shift to lower energies with the increasing electron-donating ability of the solvent. This effect can be interpreted in terms of the stabilization of the resonance structures of the chromophore. The observed lower fluorescence quantum yield may be due to an increase in the non-radiative deactivation rate constant. This is attributed to the loss of planarity in the excited state provided by the non co-planarity of the cinnamaldehyde ring attached to C(2) atom of the imidazole ring. Such a geometrical change in the excited state leads to an important Stokes shift, reducing the reabsorption and reemission effects in the detected emission in highly concentrated solutions.

1,2-Diphenyl-1H-imidazo[4,5-f][1,10]phenanthroline.

In the title compound, C(25)H(16)N(4), the fused ring system is essentially planar [maximum deviation = 0.1012 (15) Å]. The imidazole ring makes dihedral angles of 77.41 (8) and 56.26 (8)° with the phenyl rings attached to nitro-gen and carbon, respectively. The dihedral angle between the two phenyl rings is 65.50 (8)°. Weak C-H⋯π inter-actions are found in the crystal structure.

2-(4-Fluoro-phen-yl)-1-phenyl-1H-imidazo[4,5-f][1,10]phenanthroline monohydrate.

In the title compound, C(25)H(15)FN(4)·H(2)O, the fused ring system is essentially planar [maximum deviation of 0.0822 (14) Å]. The imidazole ring makes dihedral angles of 76.83 (7) and 32.22 (7)° with the phenyl group attached to nitro-gen and the fluoro-benzene group to carbon, respectively. The dihedral angle between the two phenyl rings is 72.13 (7)°. Inter-molecular O-H⋯N, O-H⋯F, C-H⋯F, C-H⋯O and C-H⋯N hydrogen bonds are found in the crystal structure.

Health-seeking behaviour of new smear-positive TB patients under a DOTS programme in Tamil Nadu, India, 2003.

BACKGROUND: Although case detection is above 70% in Tamil Nadu after DOTS implementation, an assessment of the timeliness of patient diagnosis and treatment is still needed. OBJECTIVE: To study the health-seeking behaviour of new smear-positive pulmonary tuberculosis (PTB) patients treated at government facilities. METHODS: New smear-positive patients diagnosed and treated between January and March 2003 in government facilities of randomly selected blocks in Tamil Nadu were interviewed using a semi-structured interview schedule. RESULTS: Of 601 patients interviewed, 65% contacted a provider within 28 days. The first contact was governmental for 47% and non-governmental for 53%. Median total, patient and provider delays were respectively 62, 28 and 28 days; provider delay was 9 days with government and 50 with private provider. In multivariate analysis, patient delay was significantly associated with smoking (P < 0.001) and mode of travel (P < 0.01), and provider delay with first consultation with a private provider (P < 0.001) and distance > 5 km from the health facility (P < 0.01). Twenty-five per cent of patients took more than two actions before diagnosis. CONCLUSION: Community awareness of TB needs to be increased. Greater private sector involvement in the Revised National Tuberculosis Control Programme is essential to reduce provider delay. Referral and sputum transportation to the diagnostic facility should be given priority.

Initial drug susceptibility profile of M. tuberculosis among patients under TB programme in South India.

SETTING: Pulmonary tuberculosis (PTB) patients enrolled for treatment at government health facilities in a sub-district of Thiruvallur district, Tamil Nadu, India. OBJECTIVES: To determine the drug susceptibility profile among PTB patients admitted to treatment according to the Revised National Tuberculosis Control Programme (RNTCP). METHODOLOGY: From May 1999 to December 2003, two additional sputum samples were collected from all patients at the start of anti-tuberculosis treatment under DOTS and were transported to a central laboratory for Mycobacterium tuberculosis culture and drug susceptibility testing (DST). RESULTS: DST results were available for 1603 new sputum smear-positive patients; 85% of patients had organisms fully susceptible to streptomycin (S), isoniazid (H) and rifampicin (R), 10.4% any resistance to H and 1.7% to HR. Of 443 patients with history of previous anti-tuberculosis treatment, 59% had organisms susceptible to S, H and R, 37% had any resistance to H and 11.7% to HR. CONCLUSION: The DST profile showed that the vast majority of patients have drug-susceptible organisms, and that currently recommended regimens under the RNTCP would be effective in the treatment of TB.

Application of lot sampling of sputum AFB smears for the assessment of microscopy centres.

SETTING: Designated microscopy centres (DMC) and additional microscopy centres (AMC) performing sputum acid-fast bacilli (AFB) microscopy, the District TB Centre (DTC) and a reference laboratory (RL). OBJECTIVES: To ascertain the feasibility of adopting lot sampling of AFB smears and to assess the performance of MCs employing Senior Tuberculosis Laboratory Supervisors (STLS) with no knowledge about the principles of quality assurance of AFB microscopy and RL-based laboratory technicians with training on quality assurance for blinded checking of AFB smears. METHODS: Slides from MCs were transported to the DTC and the RL; 20 smears per month per MC were selected systematically; 1547 slides from DMCs and 726 from AMCs were checked, respectively, by STLSs at the DTC and by RL laboratory technicians. Discrepancies were resolved by referee. RESULTS: The discrepancy between MC laboratory technicians and STLSs at the DTC was 4.7%, compared to 1% at the RL. The STLSs and RL-based laboratory technicians had 70 and 2 errors, respectively. CONCLUSIONS: Lot sampling of AFB smears is feasible under field conditions. Assessment of MCs was more valid with RL-based technicians trained in principles of quality assurance of sputum AFB microscopy than with STLSs with no such training and working in the field.

Storage of heat-fixed unstained sputum AFB smears for panel testing in a tuberculosis unit in South India.

To evaluate the suitability for panel testing of heat-fixed unstained sputum AFB smears stored for up to 10 months, panels of slides were prepared at the national laboratory and stored under ambient conditions. Every month, three slides were utilised for panel testing in each of 12 microscopy centres; 70 smears were checked in a blinded fashion after 10 months. Reading errors occurred in 15/360 slides used in panel testing and in 4/70 slides used in blinded checking. The quality and grading of heat-fixed unstained smears were unaffected for up to 10 months and were found suitable for panel testing.

Comparison of cough of 2 and 3 weeks to improve detection of smear-positive tuberculosis cases among out-patients in India.

SETTING: Governmental health facilities in six districts of India. OBJECTIVE: To estimate the prevalence of cough and to compare the detection of smear-positive tuberculosis (TB) among out-patients with cough of > or =2 or > or =3 weeks. DESIGN: Trained health workers questioned each out-patient for presence of cough. Those with cough > or =2 weeks underwent sputum microscopy. RESULTS: Of 55561 out-patients interviewed, 2210 (4%) had cough > or =2 weeks, of whom 267 had sputum-positive TB, compared to 182/1370 with cough > or =3 weeks. The 31% who did not spontaneously complain of cough were less likely to be sputum-positive than those who did (45/680 [7%] vs. 222/1530 [15%], P < 0.001), but they accounted for 45/267 smear-positive cases. Using cough > or =2 weeks as the screening criterion, the estimated number of smears performed per day at each primary and secondary health care facility was respectively 8 and 19, compared to 5 and 12 using cough > or =3 weeks. CONCLUSION: The detection of smear-positive TB cases can be substantially improved by actively eliciting history of cough from all out-patients, and by changing the screening criterion for performing sputum microscopy among out-patients from cough > or =3 weeks to > or =2 weeks. Before implementing this change nationally, its programmatic feasibility should be assessed.

Gender disparities in tuberculosis: report from a rural DOTS programme in south India.

SETTING: Tiruvallur District, south India. OBJECTIVES: To examine gender differences in tuberculosis among adults aged >14 years with respect to infection and disease prevalence, health care service access, care seeking behaviour, diagnostic delay, convenience of directly observed treatment (DOT), stigma and treatment adherence. METHODS: Data were collected from 1) community survey, 2) self-referred out-patients seeking care at governmental primary health institutions (PHIs), 3) tuberculosis suspects referred for sputum microscopy at PHIs, and 4) tuberculosis patients notified under DOTS. Community survey results were compared with those for patients notified at PHIs. RESULTS: In the community, 66% of males and 57% of females had tuberculosis infection. The prevalence of smear-positive tuberculosis was 568 and 87/100,000, respectively, among males and females. Fewer males than females attended PHIs (68 men for every 100 women). Females constituted 13% of all smear-positive patients detected in the community survey, and 20% of those detected at PHIs (P < 0.05). The probability of notification decreased significantly with age among both males and females. Significantly more females than males felt inhibited discussing their illness with family (21% vs. 14%) and needed to be accompanied for DOT (11% vs. 6%). Males had twice the risk of treatment default than females (19% vs. 8%; P < 0.01). CONCLUSIONS: Despite facing greater stigma and inconvenience, women were more likely than men to access health services, be notified under DOTS and adhere to treatment. Men and elderly patients need additional support to access diagnostic and DOT services.

Computational studies of 1,2-disubstituted benzimidazole derivatives.

Some 1,2-disubstituted benzimidazole derivatives (1-6) have been synthesized and characterized by mass, (1)H, (13)C NMR and elemental analysis. XRD analysis was carried out for 1-(4-methylbenzyl)-2-p-tolyl-1H-benzo[d]imidazole. Calculated bond lengths, bond angles and thus dihedral angles are found to be slightly higher than that of X-ray diffraction values of its experimental data. The charge distribution has been calculated from the atomic charges by non-linear optical (NLO) and natural bond orbital (NBO) analyses have been calculated by ab initio method. Since the synthesized 1,2-disubstituted benzimidazole derivatives have the largest µ(g)ß(0) value and can be used as potential NLO materials. Analysis of the molecular electrostatic potential (MEP) energy surface exploited the region for non-covalent interactions in the molecule. Atom in molecule analysis (AIM) was carried out to show the presence of bond critical points (BCPs).

Physiochemical properties of organic nonlinear optical crystal from combined experimental and theoretical studies.

2-(4-fluorophenyl)-1-(4-methoxyphenyl)-4,5-dimethyl-1H-imidazole (fpmpdi) was synthesised and its structure was characterized by 1H, 13C, mass, elemental analysis and X-ray techniques. It belongs to monoclinic crystal system having the lattice dimensions of monoclinic with point group, P21/c; a=8.5132 (1) Å, b=9.5128 (2) Å, c=19.2610 (3) Å, ß=96.798 (2). Since (fpmpdi) is highly sensitive to different external stimulations such as UV irradiation, heat, increasing pressure and changing the environmental pH causing color change and so they can be used as a "multi-way" optically switchable material. A prominent fluorescence enhancement was found in the presence of transition metal ions such as Hg2+, Pb2+ and Cu2+ and this was suggested to result from the suppression of radiationless transitions from the n-π* state in the chemosensors. The optimized geometrical parameters obtained by DFT calculation is in good agreement with single crystal XRD data. The Mulliken, NBO charge analysis and the HOMO-LUMO energies were also calculated. The molecular electrostatic potential surface (MEP) and first static hyperpolarisability have also been employed theoretically which reveal that the fpmpdi have non-linear optical (NLO) behavior with non-zero values. Ground and excited states DFT calculations were carried out in order to find out dipole moment and energy.

Lot quality assurance sampling of sputum acid-fast bacillus smears for assessing sputum smear microscopy centers.

Assessment of 12 microscopy centers in a tuberculosis unit by blinded checking of eight sputum smears selected by using a lot quality assurance sampling (LQAS) method and by unblinded checking of all positive and five negative slides, among the slides examined in a month in a microscopy centre, revealed that the LQAS method can be implemented in the field to monitor the performance of acid-fast bacillus microscopy centers in national tuberculosis control programs.

Health seeking behaviour of tuberculosis patients--role of the private practitioner.

India accounts for nearly 30% of the global tuberculosis burden. The goal of the Revised National TB Control Programme (RNTCP) is to cure at least 85% of new smear positive cases of TB and detect at least 75% of such patients. There are many reasons for patient delaying seeking healthcare. A Private Practitioner plays a major role in combating the disease but unfortunately the doctor-delay is more than patient-delay. Still patients seem to prefer Private Practitioners and they are often the first point of contact for a significant number of patients with TB.