Mini review: surveillance of Lyme borreliosis in Southeast Asia and method of diagnosis.

Lyme borreliosis is caused by the Gram-negative spirochetes Borrelia spp., particularly Borrelia burgdorferi sensu lato complex. The disease is transmitted through the bite of the infected black-legged Ixodes tick. Lyme borreliosis extensively occurs in the Northern Hemisphere, mainly in the United States. Lyme borreliosis cases are also detected in Asian countries including Korea, Nepal, China, Taiwan, and Japan. However, there is an inadequate understanding of Lyme borreliosis in the Southeast Asian region. Hence, this review aims to provide a brief update on the prevalence of Lyme borreliosis infection in Southeast Asia based on the latest literature on this issue. Lyme borreliosis has been discovered in human serum in Indonesia, Malaysia, and Singapore. The human serum samples were mainly examined with ELISA test using Borrelia spp. IgG and IgM antigens. Borrelia spp. also has been detected in ticks found on host animals such as Sundamys muelleri and Python in Malaysia, Thailand, and Laos. Polymerase chain reaction (PCR) is used to detect the presence of Borrelia DNAs in the samples. The published studies have demonstrated that Borrelia spp. exists in Southeast Asia and although the incidence is relatively low, it is believed that Lyme disease cases are under-reported.

Evaluation of quantitative point-of-care test for measurement of glucose-6-phosphate dehydrogenase enzyme activity in Malaysia.

INTRODUCTION: The treatment of Plasmodium vivax malaria with 8-aminoquinolines is contraindicated in glucose-6-phosphate dehydrogenase (G6PD) deficient individuals due to the risk of acute haemolytic anaemia. Effective G6PD screening is paramount to avoid adverse drug reactions. This study aimed to evaluate the performance of novel quantitative point-of-care (POC) tests as a new screening method for G6PD deficiency in Malaysia. MATERIALS AND METHODS: A total of 153 neonatal cord blood, 99 peripheral blood of older children aged between 1 month to 12-years old, and 62 peripheral adult blood were screened for G6PD deficiency using two quantitative POC tests, CareStartTM biosensor (Carestart) and CareStartTM Biosensor 1 (S1). The results were compared with OSMMR2000D kit as a reference assay. Two statistical analyses were performed in this study to evaluate the POC test performances, the Spearman's correlation test and the Cohen's kappa method. RESULTS: Both Carestart and S1 tests showed significant positive correlations to OSMMRS000D with r2 = 0.7916 and r2 = 0.7467. Their measurement of agreement showed a kappa (κ) value of 0.805 (p<0.001, 95% CI), and 0.795 (p<0.001, 95% CI), respectively. Analysis of the area under the Receiver Operating Curve (ROC) at 60% cut-off illustrated that the Carestart had 90.2% sensitivity, 98.9% specificity, 98.3% positive predictive value (PPV), and 93.8% negative predictive value (NPV). The corresponding values for the S1 were 95.2%, 100%, 100%, and 96.8%, respectively. CONCLUSION: This study showed that the Carestart and S1 biosensors have high-performance reliability for screening of G6PD deficiency, which can guide safe prescriptions of anti-malaria medications and hence, eradication of Plasmodium vivax malaria.

Evaluation of focal choroidal excavation in the macula using swept-source optical coherence tomography.

PURPOSE: To evaluate imaging findings of patients with focal choroidal excavation (FCE) in the macula using swept-source optical coherence tomography (SS-OCT) and correlate it clinically. METHODS: Prospective observational case series. Eleven consecutive patients (12 eyes) with FCE were described. Data on demographics and clinical presentation were collected and imaging findings (including color photography, fundus autofluorescence imaging, fluorescein angiography, indocyanine green angiography, spectral-domain optical coherence tomography, and SS-OCT) were analyzed. RESULTS: The primary diagnosis was epiretinal membrane (two eyes), choroidal neovascularization (one eye), polypoidal choroidal vasculopathy (three eyes), central serous chorioretinopathy (one eye), and dry age-related macular degeneration (two eyes). Eleven out of 12 of the lesions were conforming. One presented with a non-conforming lesion that progressed to a conforming lesion. One eye had multiFCE and two had two overlapping choroidal excavations. Using the SS-OCT, we found the choroid to be thinned out at the area of FCE but sclera remained normal. The choroidal tissue beneath the FCE was abnormal, with high internal reflectivity and poor visualization of choroidal vessels. There was loss of contour of the outer choroidal boundary that appeared to be pulled inward by this abnormal choroidal tissue. A suprachoroidal space was noted beneath this choroidal tissue and the choroidal-scleral interface was smooth. Repeat SS-OCT 6 months after presentation showed the area of excavation to be stable in size. CONCLUSION: FCE can be associated with epiretinal membrane, central serous chorioretinopathy, and age-related macular degeneration. The choroid was thinned out in the area of FCE.

Comparison of spectral domain and swept-source optical coherence tomography in pathological myopia.

PURPOSE: To compare optical coherence tomography (OCT) images obtained with swept-source OCT (SS-OCT) and spectral domain OCT (SD-OCT) in pathological myopia. METHODS: This is a comparative observational cases series. Five patients with pathological myopia underwent SD-OCT and SS-OCT imaging. SS-OCT was performed using a prototype system (Topcon Medical Systems). SD-OCT was performed using enhanced depth imaging on the Heidelberg Spectralis OCT. The closest corresponding scans from the central subfield were compared. RESULTS: Eight eyes of five patients with pathological myopia were included (mean spherical equivalent: -16.00 ± 4.70 D). Overall, SS-OCT better visualized retino-choroidal structures. The choroid, inner segment (IS)/outer segment (OS) line, and external limiting membrane (ELM) were clearly seen in a higher proportion of SS-OCT than SD-OCT scans, (P<0.01 for all) whereas visualization of the sclera and retinal pigment epithelium (RPE) were similar. SS-OCT demonstrated foveoschisis in four eyes, with one of these not visible on SD-OCT. The wider SS-OCT scan revealed additional pathology not visible using SD-OCT along the staphyloma walls in 4/8 images. These included incomplete posterior vitreous detachment in one eye and peripheral retinoschisis in 3/8 eyes. Vitreoschisis was visible in 3/8 SS-OCT images but not in the SD-OCT images. CONCLUSION: SS-OCT is useful for imaging the posterior staphyloma of pathological myopia, providing greater detail than SD-OCT.

Identification of quantitative trait loci for blast resistance in BC2F3 and BC2F5 advanced backcross families of rice.

Advanced backcross families derived from Oryza sativa cv MR219/O. rufipogon IRGC105491 were utilized for identification of quantitative trait loci (QTL) for blast resistance using simple sequence repeat markers. Two hundred and sixty-one BC(2)F(3) families were used to construct a linkage map, using 87 markers, which covered 2375.2 cM of 12 rice chromosomes, with a mean density of 27.3 cM. The families were evaluated in a greenhouse for resistance to blast disease caused by pathotypes P7.2 and P5.0 of Magnaporthe oryzae. Five QTLs (qBL5.1, qBL5.2, qBL6.1, qBL8.1, and qBL10.1) for pathotype P5.0 and four QTLs (qBL5.3, qBL5.4, qBL7.1, and qBL8.2) for pathotype P7.2 were identified using the BC(2)F(3) families. Another linkage map was also constructed based on 31 BC(2)F(5) families, using 63 SSR markers, which covered 474.9 cM of 9 rice chromosomes, with a mean density of 8.01 cM. Five suggestive QTLs (qBL11.2, qBL11.3, qBL12.1, qBL12.2, qBL12.3) and one putative QTL (qBL2.1) were identified for pathotype P7.2. Also, seven suggestive QTLs (qBL1.1, qBL2.2, qBL4.1, qBL4.2, qBL5.3, qBL8.3, and qBL11.1) were detected for pathotype P5.0. We conclude that there is a non-race-specific resistance spectrum of O. rufipogon against M. oryzae pathotypes.

Dynamics of progestogenic activity in serum following administration of Ligusticum chuanxiong.

Many women are using botanical alternatives for menopausal hormone replacement therapy (HRT) because current progestins, compounds with progesterone activity, have adverse risk profiles. However the development of phyto-progestins for HRT is hampered by the absence of basic pharmacokinetic/pharmacodynamic (PK/PD) data due to the lack of methods to capture summated effects of the numerous compounds that contribute to bioactivity in vivo. In this study, we explored the utility of progesterone receptor (PR)-driven bioassays to track changes in serum progestogenic activity following administration of traditional Chinese medicinal herb, Ligusticum chuanxiong, with potent progestogenic activity. Sensitive and specific (>300-fold) increases in progestogenic activity were observed when HeLa cells transfected with PR and a PR-driven promoter were exposed to the progestogenic drug, medroxy-progesterone acetate (MPA), suggesting the utility of the bioassay to measure progestogenic effects for PK/PD studies. Progestogens were administered to male Sprague-Dawley rats and serum extracted for measurement of progestogenic activity. Effect-time studies indicate that injection of MPA and L. chuanxiong extract raised area-under-curve of progestogenic activity in sera by 8.2-fold (p<0.001) and 4.5-fold (p<0.01) respectively, compared to sera from rats administered vehicle only. Administration of MPA and L. chuanxiong extract by the oral route resulted in a 5.4 (p<0.001) and 2.3-fold (p=0.07) increase respectively. Our data suggest that PR-responsive reporter gene bioassays can measure bioavailability of compounds, known and unknown, of complex botanicals for hormone replacement therapy. L. chuanxiong extracts exert progestogenic activity in vivo, and may have utility for progesterone-replacement therapy.

Dimeric progestins from rhizomes of Ligusticum chuanxiong.

Five dimeric phthalides were isolated from rhizomes of Ligusticum chuanxiong and their structures deduced based on spectral data. All compounds and their parent extracts were assessed for progesterone-like activity using a progesterone receptor driven reporter-gene bioassay. Among all the compounds, riligustilide, displayed weak progesterone-like activity (EC50 approximately 81 microM), whereas, (3Z')-(3a'R,6'R,3R,6R,7R)-3,8-dihydro-6.6',7.3a'-diligustilide (Mr: 382, EC50 approximately 90 nM), was found to be a potent and specific activator of the progesterone receptor. Levistolide A, although having a very similar plenary structure, was inactive indicating the importance of stereochemistry of chiral centers and flexibility of butylidene side chain for progestogenic activity. These bioactive phthalides and their parent extracts (EC50 approximately 8 microg/ml) may have utility for treatment of conditions requiring progesterone action.

Choroidal expansion as a mechanism for acute primary angle closure: an investigation into the change of biometric parameters in the first 2 weeks.

BACKGROUND/AIM: Choroidal expansion with anterior movement of the lens was recently proposed as a mechanism for acute primary angle closure (APAC). The aim of this study was to compare the biometric parameters, central anterior chamber depth, limbal chamber depth, lens thickness, and lens position, within 24 hours of presentation and 2 weeks later in eyes with APAC. METHODS: This was a prospective observational case series of 41 subjects with APAC. Subjects who presented with APAC were treated with medical therapy followed by laser iridotomy (LI) in both eyes once the acute attack was broken. Ocular biometry was performed in affected and fellow eyes before LI (baseline) and then 2 weeks later. Optical pachymetry was used to measure central anterior chamber depth (ACD) and the limbal chamber depth (LCD) was graded at the slit lamp. A-scan ultrasound was used to measure lens thickness (LT) and axial length (AL). Lens position (LP) was defined as ACD +(1/2)LT. RESULTS: The majority of subjects were Chinese (83%) and female (61%), and the mean age was 60.4 (SD 10.3) years. In affected eyes, the ACD was 1.81 (0.29) mm before and 1.80 (0.28) mm 2 weeks after LI (p = 0.63), while in fellow eyes, the ACD was 1.83 (0.29) mm and 1.81 (0.38) mm, respectively (p = 0.21). There was no significant change in lens position, relative lens position, or axial length in both affected and fellow eyes over the 2 weeks. CONCLUSIONS: There was no change observed in central anterior chamber depth, lens thickness, or lens position at the time of the acute attack compared to 2 weeks later in both APAC affected and fellow eyes. The findings do not support the hypothesis of lens movement due to choroidal expansion in APAC.

Vitamin A intake and the risk of hip fracture in postmenopausal women: the Iowa Women's Health Study.

Excessive intake of vitamin A is postulated to have a detrimental effect on bone by inducing osteoporosis. This may lead to an increased risk of fracture, particularly in persons who are already at risk of osteoporosis. However, few studies have specifically examined the association of vitamin A intake through diet and supplement use, with fractures in a cohort of older, community-dwelling women. We prospectively followed a cohort of 34,703 postmenopausal women from the Iowa Women's Health Study to determine if high levels of vitamin A and retinol intake through food and supplement use were associated with an increased risk of hip or all fractures. A semiquantitative food frequency questionnaire was used to obtain the participants' baseline vitamin A and retinol intake. Participants were followed for a mean duration of 9.5 years for incident self-reported hip and nonhip fractures. After multivariate adjustment, it was revealed that users of supplements containing vitamin A had a 1.18-fold increased risk of incident hip fracture (n = 525) compared with nonusers (95% CI, 0.99 to 1.41), but there was no evidence of an increased risk of all fractures (n = 6,502) among supplement users. There was also no evidence of a dose-response relationship in hip fracture risk with increasing amounts of vitamin A or retinol from supplements. Furthermore, our results showed no association between vitamin A or retinol intake from food and supplements, or food only, and the risk of hip or all fractures. In conclusion, we found little evidence of an increased risk of hip or all fractures with higher intakes of vitamin A or retinol among a cohort of older, postmenopausal women.

Medical paternalism serves the patient best.

It seems obvious that in a post-modern, constructivist world where meaning and value systems are often subjective and relative, any absolutist view is likely to be questionable. This is more so if it relates to ethics, the foundations, interpretation and application of which have been and continue to be much debated. So, in addressing the proposition, my efforts were directed at identifying a position that would mediate polarity. I examined the contention that the doctor, because he is better informed, may claim greater acuity and powers of judgment, and its defences against the charge of interfering with individual liberty and autonomy through various arguments such as the harm principle, the welfare, the principle of legal moralism and the appeal to uncertainty. While there is some validity to the arguments proposed, absolute paternalism would seem incompatible with respect for individual rights. How satisfactory, then, is the paradigm shift from paternalism to the independent choice model where the doctor presents neutral statistics as little biased as possible by his own views and judgments and leaves the decision making entirely to the patient or his/her relatives. This clearly had its limitations too. As with much of human experience, the answer would seem to rest in mediating the happy mean. Recognising a distinction between autonomy (self-determination) and independence (total freedom of choice without any interference) allows for a model of qualified independence or "enhanced autonomy" (Quill & Brody, 1996). This is predicated on doctor-patient dialogue, exchange of ideas/views, negotiation of differences, and sharing power and influence for the common purpose of serving the patient's best interest. This model would seem to be a responsible and effective approach to management of clinical dilemmas, as well as one that in its pluralistic approach is consistent with fundamental moral and philosophic propositions. It is by no means flawless, but in an imperfect world, there can be no perfect solution; constant negotiation with the realities--however uncomfortable--is an inescapable fact of life. Actions are right in proportion as they tend to promote happiness: wrong as they tend to produce the reverse of happiness. (J S Mil, Utilitarianism) On that supposition, I submit that guided paternalism is arguably what serves the patient best.

Androgen receptor polymorphisms and mutations in male infertility.

Normal spermatogenesis depends on a sequential cascade of genetic events triggered by factors encoded by sex chromosomes. To determine the contribution of genetic aberrations to male infertility, the X-linked androgen receptor (AR) gene was examined for mutations and polymorphisms in a large cohort of infertile men. Genetic screening of over 400 patients and controls showed that defects in the AR gene lead to the production of dysfunctional receptor protein in up to 10% of males with abnormally low sperm production and male infertility. The dozens of mutations and polymorphisms uncovered were associated with subtly reduced intrinsic AR activity, and are of two main categories: polymorphic changes in length of a trinucleotide CAG tract in the N-terminal transactivation domain, and missense mutations in the C-terminal ligand-binding domain. These polymorphisms and mutations are associated with reduced AR function due to defective intermolecular protein-protein interactions with coactivator molecules. Genetic screening for AR mutations and polymorphism should be offered to severely oligospermic and azoospermic patients. These traits can be transmitted to progeny, and counseling can be offered to affected families. Clarification of the molecular mechanisms of pathogenesis has led to rational hormonal therapy.

In vivo metabolism of the antitumor imidazoacridinone C1311 in the mouse and in vitro comparison with humans.

C1311 has emerged as the lead compound from a novel group of anticancer agents, the imidazoacridinones, and will be entering clinical trials shortly. Previous murine pharmacokinetic studies have shown C1311 to be rapidly and extensively distributed into tissues including tumor. This study has identified two major metabolites of C1311 and describes their pharmacokinetics in mice. M1 is a glucuronide of the parent compound with high concentrations in both plasma and liver. Calculated area under the plasma concentration versus time curve values were 6-fold and 2-fold greater, respectively, than C1311. Based on these studies, we propose M2 to be a nonfluorescent oxidation product because electrospray ionization-mass spectroscopy/mass spectroscopy analysis gave a molecular ion at m/z 367, 16 U greater than the parent compound. It formed rapidly in liver preparations in vitro, both murine and human, by a cytosolic process in the presence of NADPH and in vivo was detected in liver tissues at concentrations equivalent to those of C1311 but was not detectable in plasma. Preliminary in vitro toxicity studies showed M2 to be as potent as C1311 against MAC15A tumor cells. Over the first 24 h, 39% of the administered dose is eliminated via the bile (28%) mostly as C1311 or the kidneys (11%) as the glucuronide (M1). This study has given valuable information as to the likely metabolic pathway to occur in humans, and the cytotoxic metabolite M2 may play a role in the antitumor activity or toxicity of C1311 in the clinic.

Diagnosis of ligament rupture of the ankle joint. Physical examination, arthrography, stress radiography and sonography compared in 160 patients after inversion trauma.

We prospectively enrolled 160 consecutive patients with inversion trauma of the ankle in a diagnostic protocol that included physical examination within 2 days and at 5 days after trauma, arthrography, stress radiography, and ultrasonography. 135 patients had pathological lateral ligament laxity on the later physical examination or lateral ligament rupture diagnosed on arthrography and they were operated on 122 of these patients had ligament ruptures. At clinical follow-up after a minimum of half a year, all of the patients who were not operated on had stable joints without signs of previous ligament ruptures. Delayed physical examination at 5 days after the injury led to the highest overall sensitivity (96%) and specificity (84%) for the detection of a ligament rupture. Additional diagnostic procedures, at a considerable cost, yielded little additional information.

Physical examination is sufficient for the diagnosis of sprained ankles.

We studied the merits of physical examination after inversion injury of the ankle in 160 consecutive patients. They had an explanatory operation if they had a positive arthrogram and/or positive signs on a delayed physical examination. To determine the interobserver variation in delayed physical examination, five different examiners were asked to give independent assessment of the injury. Those with limited clinical experience produced more accurate results when physical examination was performed at five days after the injury, rather than within 48 hours. The specificity and sensitivity of delayed physical examination for the presence or absence of a lesion of an ankle ligament were found to be 84% and 96%, respectively. The interobserver agreement for the delayed physical examination of the ankle was good (kappa values 0.5, 0.6, 0.6 and 1.0). Delayed physical examination gives information of diagnostic quality which is equal to that of arthrography, and causes little discomfort to the patient.

Degenerative joint disease in female ballet dancers.

The relationship between long-term ballet dancing and eventual arthrosis of the hip, ankle, subtalar, and first metatarsophalangeal joint was examined in 19 former professional female dancers, aged 50 to 70 years. The dancers were compared with pair-matched controls. All 38 women underwent medical history taking, clinical examination, and roentgenography of the joints studied. The roentgenographs were independently judged by two investigators and grouped according to a modified classification of Hermodsson. We found a statistically significant increase in roentgenologic arthrosis of the ankle, subtalar, and first metatarsophalangeal joints in the ballet group compared with the control group. There was no significant difference regarding degenerative changes of the hip joint. However, subjects in the dance group who had evidence of degenerative changes on roentgenographs had no clinical complaints. There was a statistically significant increase in hallux valgus deformity in the ballet group (P < 0.05). The dancers also showed a statistically significant increase in flexion, external rotation, and abduction of the hip joint, dorsal flexion of the first metatarsophalangeal joint, and inversion and eversion of subtalar joint. But the control group had statistically significant increased plantar flexion of the first metatarsophalangeal joint. The most important cause of the statistically significant increase of arthrosis of the ankle and first metatarsophalangeal joints must be explained by repetitive microtrauma.

A prospective randomized study of the copper 7, Multiload Cu 250 and copper 220C IUDS in Singapore.

PIP: A randomized prospective trail was conducted to assess the comparative complication rates of the 7Cu200 and 2 newer copper bearing IUDs -- the TCu220C and the MLCu250 -- in Singapore. Recruitment for this 2-year trail began in 1976. These results represent the Singapore component of a 3-center (Singapore, Medan, Kuala Lumpur) trial, conducted in conjunction with the International Development Research Center in Ottawa, Canada. The 600 patients recruited between April 1976 and November 1978 were allocated randomly to 1 of the 3 IUDs using a series of presealed envelopes. All volunteers were healthy and ranged in age from 19-35 years. They were of proven fertility and exposed to the risk of pregnancy. There were no significant differences in the age, parity, race, or immediate past contraceptive use in the 3 groups. Insertions were performed at least 8 weeks postpartum (or 4 weeks postabortion) by 1 of 20 different physicians. Followup appointments were scheduled for 6 weeks and 3, 6, 12, and 24 months. Data was recorded for all unscheduled visits, and when necessary, letters, telephone calls, and home visits were used to trace defaulters. 98 (49%) 7C8200 users completed the study compared with the 116 (58%) for both the TCu220C and the MLCu250 users. 4% of the patients were lost to followup, and 1% were withdrawn by the investigators. There were significant differences in the pregnancy rates between the 3 devices. Pregnancy was more common with the 7Cu200 than with the TCu220C and MLCu250. Expulsion was significantly less frequent with the MLCu250 when compared with the 7Cu200 and the TCu220C. There were significant differences in both use-related and total termination rates between the 3 IUDs, but no one IUD was significantly better than either of the other 2 devices.^ieng

Post-abortion insertion of MLCu 250 and MLCu 375--a comparative trial.

This randomized prospective trial compared the use effectiveness and side effects of the MLCu 250 and MLCu 375 inserted immediately post-abortion. Five-hundred-and-forty-nine patients were followed-up over a two-year period involving 9890 woman-months of use with a loss to follow-up rate of only 5.1%. Both IUDs gave good protection against pregnancy (gross rates at 24 months, 1.8 and 2.1). There were no significant differences between the two devices in pregnancies or other termination events.

Combined team management of diabetes mellitus in pregnancy.

225 women with diabetes in pregnancy were managed by a team of obstetricians, physicians (endocrinologists) and paediatricians from the National University of Singapore. A protocol of management was formulated and followed. The incidence of 1.1% or 1 in 90 pregnancies was found, with significantly higher incidence in Indians and lower in Malays. There were 37 established diabetics and 188 diagnosed during pregnancy. Of these (188), 74 were gestational diabetics. All the women were treated with Insulin and Diet or Diet alone. 177 (79%) were treated with Insulin and Diet. Blood sugar profiles were done for monitoring diabetic control. 72.8% of the women were between para 0 and 1 and 85.2% between the ages of 20 and 34. 72.5% of the women delivered at 38 weeks gestation or later. 48.9% went into spontaneous labour, 32.4% were induced and 18.7% had elective caesarean section. 62.2% of the women had labour of less than 12 hours. The overall caesarean section rate was 41.7%. There were 3 stillbirths and 2 neonatal deaths. The perinatal mortality rate was 2.2%. Thirteen babies had congenital malformations (5.8%). 77.8% of the babies had Apgar score of 7 or more at 5 minutes after delivery. 79.1% of the babies weighed between 2.5 kgm and 3.9 kgm. Pre-eclamptic toxaemia was the commonest complication in pregnancy followed by Urinary Tract Infection and Polyhydramnios. Postpartum complications in the mother were confined to 14 women (6.2%), and wound infection or breakdown was the commonest cause.

A randomized comparative trial of the Lippes Loop D, Gravigard and TCu 220C IUDs.

This randomized prospective trial compared the use-effectiveness and pregnancy rates in 3 IUDs following immediate postabortal insertion in 199 women over 3107 months of use. At 24 months the Gravgard (Cu 7) was not significantly different from either of the other 2 devices. However, the Lippes Loop D when compared with the TCu 220C had a higher expulsion rate (P less than 0.05) and a higher use-related termination rate (P less than 0.001). Further details of accidental pregnancies, removal for incomplete abortion or pelvic inflammatory disease and within 48 hours after insertion are presented.