First case report of paragonimiasis in a Malaysian man.

Paragonimiasis is an infection caused by Paragonimus, a lung fluke and is acquired by eating raw or undercooked crustaceans containing the infective metacercariae. Herein, we report a case of paragonimiasis in a Malaysian man who presented with incidental findings from chest radiographs. Examination of his biopsied lung tissue and sputum specimen revealed Paragonimus sp. eggs, whereas stool examination showed the presence of Giardia cysts. Patient was succesfully treated with praziquantel and metronidazole respectively.

Efficacy of C.E.R.A. in Routine Clinical Practice for Correction of Anaemia and Maintenance of the Haemoglobin Levels in CKD Patients not on Dialysis.

INTRODUCTION: C.E.R.A. reported effective correction of anaemia and was well tolerated in International studies on CKD patients not on dialysis. OBJECTIVE: The study aimed to describe the management of renal anaemia in CKD patients not on dialysis with C.E.R.A. in routine clinical practice in India. METHODS: This was a prospective, single-arm, open-label, multi-centre, non-interventional, Phase IV study which followed 108 CKD Stage III-IV patients, not on dialysis with Hb < 10 g/dL for correction of anaemia with C.E.R.A. RESULTS: Of the 108 patients with Hb < 10 g/dL at baseline, 83 (90.2%) patients achieved target Hb of 10-12 g/dL and the time taken to achieve correction of anaemia was 9.6 weeks ± 6.13 weeks in the Intent-to-treat population. Haemoglobin concentration increased from 8.59 ± 0.808 g/dL pre-therapy to 10.91 ± 0.634 g/dL post-therapy. The change in mean ± SD Hb value was 2.32 ± 0.174 g/dL. Maintenance of Hb levels within the target range of Hb 10 - 12 g/dL was observed in 78.2% of ITT and 80.8% of the PP population for mean duration of 16.69 weeks. Four patients (3.7%) experienced 5 AEs and 2 patients (1.9%) experienced 3 SAEs in the safety population. As per the treating physician none of the AEs or SAEs was considered related to study drug. There were no deaths reported. CONCLUSIONS: This study demonstrated successful correction of anaemia in Indian patients with C.E.R.A. treatment as well as maintenance of Hb levels within the target range. C.E.R.A. was well tolerated with no new safety concerns specific to the Indian population. The less frequent up to monthly dosing schedule of C.E.R.A. may offer clinicians and patients a simplified regimen of anaemia management as compared to traditional frequently administered (thrice weekly to once weekly) ESAs.

DG-RAR for the treatment of symptomatic grade III and grade IV haemorrhoids: a 12-month multi-centre, prospective observational study.

BACKGROUND: Ultrasound-guided techniques represent a new treatment option in the treatment of haemorrhoids. Doppler-guided haemorrhoidal artery ligation (DG-HAL) proved efficacious in early haemorrhoidal disease, but lacks efficacy for stages III/IV. For these patients, haemorrhoidal artery ligation (HAL) has been combined with a running suture to reduce prolapsing haemorrhoidal tissue (recto-anal repair (RAR)). METHODS: A prospective observational study was conducted in 184 patients with grade III (58 %) or grade IV (42 %) haemorrhoids in seven coloproctological centres. Primary endpoints were the recurrence of symptoms and need of further treatment (medical or surgical). RESULTS: Post-operative complications were seen in 8 % of patients. After a follow-up of 3 months, 91 % of patients were free of symptoms and 91 % of patients were satisfied with the result. After a follow-up of 12 months, 89 % of patients were free of symptoms and 88 % were satisfied with the result. Nineteen per cent of patients received further medical or surgical treatment. CONCLUSIONS: Doppler-guided recto-anal repair (DG-RAR) proves to be an effective treatment option for the treatment of advanced haemorrhoidal disease that shows equal results to other established treatment options.

Phenobarbital, oxazepam and Wyeth 14,643 cause DNA damage as measured by the Comet assay.

Although phenobarbital, oxazepam and Wyeth 14,643 are carcinogens that do not form DNA adducts, they induce mutations in the Big Blue transgenic mouse model. The mutations produced by these compounds were predominantly G-->T and G-->C transversions that we suspect arose from oxidative damage to DNA. To test this, we employed the single cell electrophoresis (Comet) assay that detects alkali-labile lesions in cells sustaining DNA damage. Human myeloid leukemia K562 cells were treated with non-cytotoxic doses of the above compounds for 3 h, then placed on slides containing low melting point agarose. Cells were lysed, exposed to alkaline buffer, electrophoresed and analyzed by microscopy for the existence of DNA damage. Extensive DNA damage, most likely due to the existence of single- and double-strand breaks and apurinic/apyrimidinic (AP) sites, was observed in cells exposed to oxazepam (1 mM) and Wyeth 14,643 (0.5 mM). On the other hand, damage of this sort was not observed in cells exposed to phenobarbital (1 mM). However, the addition of S9 liver extracts to cells exposed in the presence of phenobarbital resulted in significant amounts of DNA damage. We conclude from these studies that two of the three compounds evaluated in this study mediate their mutagenic effects through oxidative stress, but that the mechanism of DNA damage caused by phenobarbital differs from that elicited by oxazepam and Wyeth 14,643.

The human leukocyte antigen HLA DRB3*020/DQA1*0501 haplotype is associated with Graves' disease in African Americans.

Information on genetic susceptibility to Graves' disease in African Americans is limited. We studied DRB1, DQB1, DRB3 subtypes, DQA1*0501, DQA1*0201, and CTLA-4 polymorphisms in 49 African American patients with adult onset Graves' disease and 47 racially-matched controls using PCR-based sequence-specific priming methods. There were no significant differences in DRB1 or DQB1 allelic frequencies or CTLA-4 polymorphisms between patients and controls. However, we found that the frequency of DRB3 was significantly increased in the patients (75.5% vs. 57.4%, P = 0.006, X2 = 3.52), especially for the DRB3*0202 subtype (53.1% vs. 23.4, P = 0.003, X2 = 8.91). In this one respect, the finding was in concordance with our previous observations in Caucasian patients with adult-onset Graves' disease. In addition, whereas the frequency of DQA1*0501 was increased (P = 0.018, X2 = 5.63) in our patients, the haplotype of DRB3/DQA1*0501, or DRB3*0202/DQA1*0501 was found to be more strongly associated (P = 0.008, X2 = 7.0; P = 0.0008, X2 = 11.34, respectively). These data suggest that DRB3*0202, particularly when found with DQA1*0501 in a haplotype is a susceptible gene(s) for Graves' disease in adult African Americans. Considering these data with those in Caucasian patients, our results would suggest that the primary Graves susceptible locus is likely DRB3 and not DRB1.

Analysis of taxol and major taxoids in Himalayan yew, Taxus wallichiana.

A reversed-phase column liquid chromatography method for the analysis of taxol, 10-deacetylbaccatin III, baccatin IV, 1-hydroxybaccatin I, 2-acetoxybrevifoliol, brevifoliol, 2'-deacetoxydecinnamoyltaxinine J and 2'-deacetoxytaxinine J in yew needles has been developed using a Nova-Pak Phenyl column and a binary gradient profile. The various aspects of analysis such as extraction efficiency, detection limits, reproducibility and peak purity were validated using UV-Vis as well as photodiode array detection.

Protective effects of equine herpesvirus-1 (EHV-1) glycoprotein B in a murine model of EHV-1-induced abortion.

In an attempt to determine if pregnant mice could be protected from abortion subsequent to challenge with equine herpesvirus-1 (EHV-1) in the mouse model of EHV-1 disease, female BALB/c mice were inoculated with baculovirus-expressed EHV-1 glycoprotein B (bac-gB), wild-type baculovirus (bac-wt), rabbit kidney (RK-13) or baby hamster kidney (BHK-21) cells. Using an ELISA, antibodies against EHV-1 were detected in the serum of mice following two injections of bac-gB and were enhanced by a third injection, after which low levels of neutralising antibody were also detected. After mating, mice in the bac-gB, bac-wt and RK-immunised groups were infected intranasally with 10(7) pfu of EHV-1 on day 16 of pregnancy. All challenged mice experienced body weight loss post-infection (pi). However, postnatally, the gB-immunised group demonstrated body weight gain which was not seen in the other groups. There were no maternal deaths in the gB-immunised group but 1/6 bac-wt-immunised and 3/6 RK-immunised mice died post-challenge. Litter survival rate was significantly higher (p < 0.001) for the gB-immunised dams (54%) than that of either the bac-wt-(9%) or RK-immunised (0%) dams and the mean body weight of young from the surviving bac-wt-immunised litter was significantly (p = 0.021) lower than either the gB-immunised group or the BHK-immunised unchallenged group at 10 days of age. The virus was not isolated from any foetus from a gB-immunised dam. However, the virus was detected in 9% of foetuses from bac-wt-immunised and 21% of foetuses from RK-immunised dams.

Study of the protective immunity of co-expressed glycoprotein H and L of equine herpesvirus-1 in a murine intranasal infection model.

Equine herpesvirus-1 (EHV-1) glycoproteins H, and L (gH and gL) expressed individually or co-expressed by recombinant baculoviruses were used to immunise BALB/c mice prior to intranasal challenge in a murine model of respiratory infection. Only the co-expressed material (EHV-1 gH/gL) induced neutralising antibody (low levels). The same immunogen also produced the strongest cellular responses. Immunisation with gH/gL and, to a lesser extent, with gH alone was associated with a reduction of virus load in nasal turbinates and olfactory bulbs after challenge infection. Viraemia, detected by polymerase chain reaction, was also reduced. No such protective effects were observed for gL alone. Adoptive transfer of lymphocytes from gH/gL-immunised mice to näive mice subsequently challenged with EHV-1 indicated that both CD4+ and CD8+ cells had a role in protective immunity. Although clearance of EHV-1 from respiratory tissue was not as effective as previously found for glycoproteins D or C, these experiments provide evidence that the co-expression of EHV-1 gL with gH generates a conformational neutralising epitope which is not present in either molecule alone, and suggests that gH/gL antigen may have a better potential as a component of an EHV-1 vaccine than gH alone.

Taxanes from in vitro cultures of the Himalayan yew Taxus wallichiana.

Culture conditions have been standardized for initiation of callus cultures of Himalayan yew (Taxus wallichiana) using young stem and needle explants from mature trees. Cultures were established on a modified Murashige and Skoog's medium supplemented with various levels of auxins (2.4-D, NAA) and cytokinin (kinetin). A medium containing 0.25 mg/l kinetin and 5.0 mg/l 2.4-D was optimal for stem callus growth whereas the presence of 0.25 mg/l kinetin along with 3.0 mg/l NAA in the medium supported optimal needle callus growth. Growth of stem callus was faster than needle callus growth. Supplementation of ascorbic acid (30 mg/l) amongst various anti-phenolic agents tested significantly reduced browning of initiated callus. Two taxanes (2-deacetoxytaxinine 1 and 2'-deacetoxyaustrospicatine) known to occur in stem bark, have also been isolated from undifferentiated tissue of T. wallichiana in equal or higher yields, for the first time.