Profile of Patients Admitted in Maternal Intensive Care Unit at BPKIHS, a Tertiary Hospital in Eastern Nepal.

BACKGROUND: Maternal death is a tragic event. It can be reduced by prompt recognition of critical illness in pregnancy and earlier initiation of intensive care. The physiological changes of pregnancy and the presence of a fetus complicates the assessment and management of critically ill obstetric patients. The objective of this study was to analyse the basic contributing factors for maternal intensive care unit admission and the maternal outcome. METHODS: This was a prospective study conducted in the department of Obstetrics and Gynaecology at B.P. Koirala Institute of Health Sciences, a tertiary hospital in eastern Nepal, for one year duration from January-December 2012. Data like age, diagnosis at admission, intervention, indication for admission, duration of stay and outcome were analysed. RESULTS: One hundred and ninety two patients were admitted in one year. Among them 177 were obstetrics related admission and 15 were non obstetrics. Out of 177 patients, 21(11.8%) were antenatal, 123(69.4%) were postnatal and 33(18.6%) had early pregnancy complications. The mean age in years was 25.67±7.169. One hundred and seventy one patients (96.6%) were unbooked and only 6(3.3%) were booked. Among the postnatal patients, 83(67.4%) had delivered at BPKIHS, 24(19.5%) at other health centres and 16 (13%) at home. Antepartum eclampsia was the commonest diagnosis. Out of 192 patients, 148(78.12%) were improved, 24(12.5%) had expired, 15(7.8%) went against medical advice and 5(1.6%) were referred. The median duration of MICU stay in days (IQR) was 2(1-4). CONCLUSIONS: An intensive care unit often offers the opportunity to improve the patient care.

Induction of Labor Using Misoprostol With or Without Mifepristone in Intrauterine Death.

INTRODUCTION: Rapid expulsion of fetus in intrauterine fetal death is usually requested without any medical grounds for it. So an efficient, safe method for induction of labor is required. The objective of this study is to determine if pre-treatment with mifepristone followed by induction of labor with misoprostol in late intrauterine fetal death is more efficacious. METHODS: We conducted a randomized controlled trial in 100 patients in B.P.Koirala Institute of Health Sciences, Nepal from June 2011 to May 2013. Group A women received single oral dose of 200 mg mifepristone, followed by induction with vaginal misoprostol after 24 hours. Group B women were induced only with vaginal misoprostol. In each group, five doses of misoprostol was used four hourly. If first cycle was unsuccessful, after break of 12 hour, second course of misoprostol was started. The primary outcome was a measure of induction to delivery time and vaginal delivery within 24 hours. Secondary outcome was to measure need of oxytocin and complications. RESULTS: Maternal age, parity and period of gestation were comparable between groups. Number of misoprostol dose needed in group A was significantly less than group B. Mann Whitney U test showed, women in group A had significantly earlier onset of labor, however total induction to delivery interval was not significant. In group A, 85.7% delivered within 24 hours of first dose of misoprostol while in group B 70% delivered within 24 hours (p=0.07). More women in Group B required oxytocin. CONCLUSIONS: Pretreatment with mifepristone before induction of labor following late intrauterine fetal death is an effective and safe regimen. It appears to shorten the duration of induction to onset of labor.

Pandemic influenza A (H1N1) 2009 outbreak investigation in Nepal.

BACKGROUND: The World Health Organization, on 24 April 2009, announced a Public Health emergency of international concern caused by a new influenza virus Pandemic Influenza A 2009. The objective of this study was to analyze the basic epidemiology and distribution of Pandemic Influenza A 2009 in order to understand the course of Pandemic Influenza A 2009 in Nepal. METHODS: The analyses were based upon all confirmed and probable cases that consulted Avian Influenza Control Project and National Public Health Laboratory during 29 April 2009 to 21 September 2010. RESULTS: Out of total 739 suspected samples collected, Pandemic Influenza A 2009 was detected in 210 cases in different districts of Nepal. The majority of cases were from the urban settlement of Kathmandu valley, Chitwan and Kaski and among age group 11-30 years. The clinical attack rate for Influenza like illness (ILI) was 28.48%. There was no significant difference between the clinical presentation of ILI and confirmed cases of Pandemic Influenza A 2009. CONCLUSIONS: This study presented the investigation of outbreak that helped to inform the course of epidemic in affected population and therefore urge for public health interventions.

Screening of Nepalese crude drugs traditionally used to treat hyperpigmentation: in vitro tyrosinase inhibition.

South-East Asian population is daily exposed to strong sunlight. As a result, the majority of population will have darker, ethnic skin. Moreover, many people suffer from dark spots, hyperpigmentation, which is considered to be a skin disorder and causes psychological disturbance. To treat dark spots, most of the population will still rely on traditionally used crude drugs, knowledge about which is transferred from generation to generation. Fifty-two crude drugs were selected based on the survey performed among local healers and beauticians of different ethnic origin. These crude drugs were screened for mushroom tyrosinase inhibitory activity, as tyrosinase inhibitors are becoming increasingly important as cosmetic and medicinal products, primarily to control hyperpigmentation. Among the tested crude drugs, methanolic extracts of Glycyrrhiza glabra, Morus alba, Syzygium aromaticum, Citrus aurantifolia, Cypreae moneta, Punica granatum and Citrus aurantium, at the final concentration of 50 microg mL(-1), showed mushroom tyrosinase inhibitory activity of 78.9%, 71.0%, 69.4%, 59.0%, 56.0%, 53.4 and 51.9%, respectively, with 91.4% inhibitory activity of kojic acid taken as positive control. To our knowledge, this is the first report that extracts of Cypreae moneta shell and Syzygium aromaticum flowering bud have tyrosinase inhibitory activity. These potent extracts were further evaluated at different concentration. The final concentration of the extracts in reaction mixtures was 50, 25 and 5 microg mL(-1) for the initial concentration of 1000, 500 and 100 microg mL(-1), respectively. They showed concentration-dependent inhibition of mushroom tyrosinase. Those extracts expressing relatively weak tyrosinase inhibitory activity may act through different inhibition pathway which is not based on tyrosinase activity. Further evaluation of the most potent tyrosinase inhibitors in in vivo conditions would be recommended.

Microalbuminuria among type-2 diabetes mellitus patients in Pokhara, Nepal.

Microalbuminuria is considered to be an early stage of diabetic nephropathy as well as a marker of cardiovascular disease. The aim of this study was to see the prevalence of microalbuminuria in type 2 diabetic patients and assess its association with cardiovascular risk factors among them. A total of 143 type 2 diabetic patients with the mean age of 56.06 +/- 1.08 years were analysed. The prevalence of microalbuminuria and overt proteinuria was 45.5% and 11.2%, respectively. Prevalence of microalbuminuria in female was marginally higher than in male (p > 0.05). Subjects with microalbuminuria had significantly higher blood pressure (p < 0.001) and duration of diabetes (p < 0.05) compared with normoalbuminuric subjects. High density lipoprotein was found to be significantly lower (p < 0.05) in subjects with microalbuminuria whereas fasting blood sugar, triglyceride, total cholesterol and very low density lipoprotein were marginally higher in microalbuminuric than in normoalbuminuric subjects (p > 0.05). High prevalence of microalbuminuria in diabetic patients and its positive association with blood pressure and altered lipid profile suggests that screening for microalbuminuria is essential for intervention and prevent further complications like end stage renal disease and cardiovascular diseases.

An integrated treatment approach: a case report for dentinogenesis imperfecta type II.

Dentinogenesis imperfecta type II or hereditary opalscent dentin is one of the most common autosomal dominant anomaly of dentin that occurs in both sex affecting approximately 1:8000 persons. Clinically this disorder is characterized by variable blue gray to yellow brown teeth, with fracture of enamel and excessive wear. The treatment strategy is focused towards protecting teeth from further wear and tear and total oral rehabilitation of patient with paramount importance to aesthetics, obtaining an appropriate vertical dimension and providing soft tissue support which will help to return the facial profile to a more normal appearance. A multidisciplinary treatment planning is required for treatment of these individuals.

Tonsillar microbial flora: a comparison of infected and non-infected tonsils.

OBJECTIVE: The main objective of this study was to find out the most common organism affecting the tonsils in recurrent tonsillitis. METHODOLOGY: This was a prospective study consisting of total number of 50 patients, conducted in the ENT department of Dhulikhel Hospital, KUTH, Dhulikhel, Nepal. The study period was one year and three months (March 2004 to April 2005). RESULTS: Total numbers of 50 patients were selected, of which 32 were of acute tonsillitis and 18 were taken as control. Among these males were 32 and females were 18. The age group was from 3 years to 64 years. Throat swabs of patients were taken by aseptic method and were sent to the laboratory immediately. Among the infected tonsils the most common organism was Streptococcus viridans followed by Streptococcus pneumoniae and Moraxella catarrhalis. The third most common was Beta haemolytic streptococci whereas Micrococcus was not isolated in any of the infected samples. Likewise in non-infected tonsils, the most common organism isolated was again Streptococcus viridans followed by Micrococcus and Diptheroids. In these specimen no Beta haemolytic streptococci was isolated from the control group. CONCLUSION: Thus, the study is able to put forward the fact that most common organism affecting the tonsils in infected as well as non- infected state is Streptococcus viridans. Where as Beta haemolytic streptococci was not found in non-infected tonsils, likewise Micrococcus was not found in infected tonsils.

Retrieval of a separated file using Masserann technique: a case report.

The separated instrument particularly a broken file leads to metallic obstruction, in the root canal and blocks thorough cleaning and shaping procedure. When attempts of bypassing such a fragment go in vain, it should be retrieved by mechanical devices. Masserann Kit is one such device for orthograde removal of intracanal metallic obstructions. This clinical case demonstrates usage of Masserann technique in successful retrieval of a separated file which was tightly binding in the apical 3rd root canal dentin of maxillary left lateral incisor.

Anatomical variation of maxillary sinus mimicking a periapical cyst: a case report.

Maxillary sinus can pose diagnostic dilemma radiographically because of its anatomical variation which can mimic a periapical pathosis. This case report deals with one such diagnostic problem, where a maxillary sinus was interpreted in an intraoral periapical radiograph as a periapical cyst. With the advances in imaging techniques, the use of an Ultrasound imaging together with application of Colour Power Doppler helped in revealing the contents of the radiolucent area and come up with an accurate diagnosis. Thus a thorough knowledge about the normal anatomy and its variations and proper diagnostic aids are essential in the diagnosis of periapical pathology.

Clinical profile of typhoid patients.

OBJECTIVE: The present study was undertaken to determine the clinical profile of typhoid fever in hospitalised patients. DESIGN: Prospective cross-sectional study. SETTING: Kathmandu Medical College and Teaching Hospital. METHOD: Total of thirty patients above fifteen years of age who had clinical features strongly suggestive of typhoid fever and on blood culture found to be positive for Salmonella typhi were analysed for clinical features. RESULT: Among total of thirty cases, there were 17 (57%) males and 13 (43%) females. 86% of cases of typhoid fever clustered around 15-30 years of age. Predominant symptoms were fever (100%), headache (90%), abdominal Pain (37%) and constipation (33%). Common clinical signs were splenomegaly (37%), relative bradycardia (27%) and hepatomegaly (17%). None of the patients presented with complications. CONCLUSION: The clinical profile of typhoid fever in our study revealed not much difference from that of other studies on typhoid fever. Rose spots were not noticed and we did not find a single case of complication of typhoid fever. Probably early initiation of antibiotics prevented the complications.

Inhibition of itch-scratch response by fruits of Cnidium monnieri in mice.

We previously screened the anti-itching activities of 33 herbal medicines in substance P (SP)-induced itching model mice. One of the most potent antipruritogenic extracts, the methanol extract of fruits of Cnidium monnieri (Cnidii Fructus) was studied further. The chloroform-soluble fraction of the methanol extract markedly inhibited SP-induced scratching. Among 10 subfractions of the chloroform-soluble fraction, the CS-3 fraction had the most potent inhibitory effect on scratching. Each of 3 subfractions of CS-3 showed significant anti-scratching activities. However, inhibitory potencies were not different among the three and weaker than that of CS-3 itself at a same dose. These 3 subfractions of CS-3 mainly contained xanthotoxin, isopimpinellin, bergapten, imperatorin and osthol. Single administration of osthol did not inhibit SP-induced scratching, and imperatorin very weakly subsided scratching. These results suggest that the strong antipruritic action was focused on the CS-3 fraction of the C. monnieri methanol extract, and it might result from the combined effects of these coumarin derivatives, or by undetermined minor compounds.

Antiapoptotic effects of propolis extract and propol on human macrophages exposed to minimally modified low density lipoprotein.

An aqueous extract of propolis and the phenolic component of propolis, propol, were assayed for antioxidative and antiapoptotic properties. Both additions inhibited Cu(2+)-initiated low density lipoprotein (LDL) oxidation as characterized by a reduction of the lag time, reduced the increase of relative electrophoretic mobility during oxidation and markedly diminished apoptosis of human macrophages exposed to minimally modified (mmLDL). Moreover, aqueous propolis extract and propol blocked the mmLDL-induced decrease of glutathione (GSH) and the activation of the transcription factor NF-kappa B in these cells. The potent phenolic antioxidant propol thus expands the capability of cells to neutralize oxidative stress and to prevent apoptosis and is therefore suggested to significantly contribute to the antiinflammatory and antioxidative effects of propolis.

Coumarins from the fruits of Cnidium monnieri.

Two novel biscoumarins, cnidimonal (1) and cnidimarin (2), and two new coumarin derivatives, 5-formylxanthotoxol (3) and 2'-deoxymeranzin hydrate (4), were isolated from a traditional Chinese crude drug, the fruits of Cnidium monnieri, together with 15 known compounds. Among the known compounds, five of the minor compounds were isolated for the first time from this plant. The structures of 1-4 were determined with the use of spectroscopic methods.

Inhibitory effect of tetrahydroswertianolin on tumor necrosis factor-alpha-dependent hepatic apoptosis in mice.

We investigated the effect of tetrahydroswertianolin (THS), a hepatoprotective agent from Swertia japonica, on tumor necrosis factor-alpha (TNF-alpha)-dependent hepatic apoptosis induced by D-galactosamine (D-GalN) (700 mg/kg, i.p.) and lipopolysaccharide (LPS) (10 microg/kg, i.p.) in mice. Apoptotic symptoms were observed at the initial stage of liver damage. By 5 hr after intoxication, hepatic DNA fragmentation had risen to 2123%, with the value in untreated mice set at 100%, without a significant elevation of serum alanine transaminase (ALT) activity. There was a parallel increase in hepatocytes undergoing chromatin condensation and apoptotic body formation. By 8 hr after intoxication, serum ALT activity had risen to 3707 U/L. Pretreatment with THS (50 mg/kg, p.o.) at 18 and 2 hr before intoxication significantly reduced DNA fragmentation to 821% of that in untreated mice and prevented the emergence of chromatin condensation and apoptotic body formation. A significant and dose-dependent reduction in serum ALT activity at 8 hr also was observed with THS pretreatment. These effects of THS were different from those observed from pretreatment with glycyrrhizin (GCR), which is a clinically used hepatoprotective agent with membrane-stabilizing activity. GCR pretreatment (100 mg/kg, p.o.) did not inhibit hepatic DNA fragmentation (1588% of untreated mice), although this compound significantly protected against serum ALT elevation (1463 U/L). These data suggest that an inhibitory effect on the progression of hepatic apoptosis prior to liver injury may be involved in the hepatoprotective mechanisms of THS, whereas it appears that GCR affects the processes after apoptosis. In a separate experiment, we found that the concentration of serum TNF-alpha rose to 2016 pg/mL at 1 hr after intoxication of mice with D-GalN and LPS, but this increase was suppressed by THS pretreatment (10, 50, or 200 mg/kg, p.o.) to 716, 454, or 406 pg/mL, respectively. Further study with a reverse transcriptase-polymerase chain reaction method showed that THS blocked TNF-alpha production at the transcriptional level. Because TNF-alpha is a critical mediator to elicit apoptosis in this model, the property of suppressing TNF-alpha production may be of prime importance for THS inhibition of hepatic apoptosis.

Anti-herpes simplex virus activity of moronic acid purified from Rhus javanica in vitro and in vivo.

Rhus javanica, a medicinal herb, has been shown to exhibit oral therapeutic anti-herpes simplex virus (HSV) activity in mice. We purified two major anti-HSV compounds, moronic acid and betulonic acid, from the herbal extract by extraction with ethyl acetate at pH 10 followed by chromatographic separations and examined their anti-HSV activity in vitro and in vivo. Moronic acid was quantitatively a major anti-HSV compound in the ethyl acetate-soluble fraction. The effective concentrations for 50% plaque reduction of moronic acid and betulonic acid for wild-type HSV type 1 (HSV-1) were 3.9 and 2.6 microgram/ml, respectively. The therapeutic index of moronic acid (10.3-16.3) was larger than that of betulonic acid (6.2). Susceptibility of acyclovir-phosphonoacetic acid-resistant HSV-1, thymidine kinase-deficient HSV-1, and wild-type HSV type 2 to moronic acid was similar to that of the wild-type HSV-1. When this compound was administered orally to mice infected cutaneously with HSV-1 three times daily, it significantly retarded the development of skin lesions and/or prolonged the mean survival times of infected mice without toxicity compared with the control. Moronic acid suppressed virus yields in the brain more efficiently than those in the skin. This was consistent with the prolongation of mean survival times. Thus, moronic acid was purified as a major anti-HSV compound from the herbal extract of Rhus javanica. Mode of the anti-HSV activity was different from that of ACV. Moronic acid showed oral therapeutic efficacy in HSV-infected mice and possessed novel anti-HSV activity that was consistent with that of the extract.

Inhibitory effect of diarylheptanoids on nitric oxide production in activated murine macrophages.

Thirteen novel diarylheptanoids bearing a chalcone or a flavanone moiety (1-13), a new curcumin derivative, 1,2-dihydrobis(de-O-methyl)curcumin (14), and two known flavonoids (15 and 16) isolated from the seeds of Alpinia blepharocalyx K. Schum. were tested for their inhibitory effects on nitric oxide (NO) production in lipopolysaccaride (LPS)-activated murine macrophages J774.1 in vitro. All the tested compounds inhibited NO production in a concentration-dependent manner (IC50=36-568 microM). Among the compounds examined, blepharocalyxin B (13) was the most potent inhibitor of NO production (IC50=36 microM). Analysis of the structure activity relationship among these novel diarylheptanoids led to the conclusion that the position of attachment of a chalcone or a flavanone to a diarylheptanoid does not affect their inhibitory potency although their presence in association causes a substantial enhancement of the inhibitory activity. Moreover, a conjugated double bond in a chalcone moiety potentiated the inhibitory activity. On the other hand, hexamethoxydeoxycalyxin A (17) and pentamethoxycalyxin B (18), a methylated product of calyxin A (1) and an epimeric mixture of calyxin B, showed greatly reduced activity suggesting that phenolic hydroxyl groups are involved in the inhibitory activity.

Comparative study of seventeen Salvia plants: aldose reductase inhibitory activity of water and MeOH extracts and liquid chromatography-mass spectrometry (LC-MS) analysis of water extracts.

The dry root and rhizome of Salvia miltiorhiza (Lamiaceae) are used as a crude drug Danshen, while those of S. deserta (Xinjiang-Danshen) are mixed in Danshen at Xinjiang province when the former is in short supply. The water and MeOH extracts of S. deserta showed strong aldose reductase (AR) inhibitory activity, and their active constituents were determined to be polar compounds different from "tanshinones" of S. miltiorhiza, i.e., lithospermic acid B (1), salvianolic acid K (2), salviaflaside (3), and rosmarinic acid (4) (IC50, 2.63-3.91 microM). We also examined the AR inhibitory activity of water and MeOH extracts of seventeen Salvia plants, including ten species of Danshen resources (S. bowleyana, S. deserta, S. miltiorhiza, S. miltiorhiza var. miltiorhiza f. alba, S. paramiltiorhiza, S. paramiltiorhiza f. purpureo-rubra, S. przewalskii, S. przewalskii var. mandarinorum, S. sinica f. purpurea, S. trijuga), and their water extracts were also analyzed by liquid chromatography-mass spectrometry (LC-MS). The results indicated that there were four types with regard to the AR inhibitory activity and three types with regard to the amount of 1. Ten species used as Danshen resources showed good correlation between the AR inhibitory activity and the morphological classification. However, the intensities of their AR inhibitory activity varied, and they contained 1 in varying amounts. These facts suggested that the ten species were not the same, and thus their use as a Danshen resource should be based on their activity and/or active constituents.

Calyxin H, Epicalyxin H, and Blepharocalyxins A and B, Novel Diarylheptanoids from the Seeds of Alpinia blepharocalyx

Four unprecedented diarylheptanoids-calyxin H (1) and epicalyxin H (2), possessing a diarylheptanoid unit and a chalcone moiety, and blepharocalyxins A (3) and B (4), possessing two diarylheptanoid units and a chalcone moiety-were isolated from the seeds of Alpiniablepharocalyx. The structures of 1-4, including absolute stereochemistry, were elucidated by spectroscopic means and after a consideration of their biogenesis.

Purification and characterization of eugeniin as an anti-herpesvirus compound from Geum japonicum and Syzygium aromaticum.

The hot-water extract of Geum japonicum has been shown to exhibit prophylactic and therapeutic anti-herpes simplex virus (HSV) activity in murine infection models. Eugeniin was purified as an anti-HSV compound from the extract and also was isolated from another herbal extract (Syzygium aromaticum) that had exhibited anti-HSV activity in mice. Thus the anti-HSV action of eugeniin was characterized. The effective concentration (5.0 microg/ml) for 50% plaque reduction of eugeniin for wild HSV type 1 (HSV-1) on Vero cells was 13.9-fold lower than its 50% cytotoxic concentration determined by a yield-reduction assay. Eugeniin also inhibited the growth of acyclovir-phosphonoacetic acid-resistant HSV-1, thymidine kinase-deficient HSV-1 and wild HSV type 2. Eugeniin as well as phosphonoacetic acid inhibited viral DNA and late viral protein syntheses in their infected Vero cells, but not cellular protein synthesis at its inhibitory concentrations. Purified HSV-1 DNA polymerase activity was inhibited by eugeniin noncompetitively with respect to dTTP. Its apparent Ki value for euginiin was 8.2- and 5. 8-fold lower than the Ki values of purified human DNA polymerases alpha and beta, respectively. Thus one of the major target sites of inhibitory action of eugeniin is viral DNA synthesis; the inhibitory action for viral DNA polymerase activity was novel compared with anti-HSV nucleoside analogs.