PTF 11kx: a type Ia supernova with a symbiotic nova progenitor.

There is a consensus that type Ia supernovae (SNe Ia) arise from the thermonuclear explosion of white dwarf stars that accrete matter from a binary companion. However, direct observation of SN Ia progenitors is lacking, and the precise nature of the binary companion remains uncertain. A temporal series of high-resolution optical spectra of the SN Ia PTF 11kx reveals a complex circumstellar environment that provides an unprecedentedly detailed view of the progenitor system. Multiple shells of circumstellar material are detected, and the SN ejecta are seen to interact with circumstellar material starting 59 days after the explosion. These features are best described by a symbiotic nova progenitor, similar to RS Ophiuchi.

Hydrogen-poor superluminous stellar explosions.

Supernovae are stellar explosions driven by gravitational or thermonuclear energy that is observed as electromagnetic radiation emitted over weeks or more. In all known supernovae, this radiation comes from internal energy deposited in the outflowing ejecta by one or more of the following processes: radioactive decay of freshly synthesized elements (typically (56)Ni), the explosion shock in the envelope of a supergiant star, and interaction between the debris and slowly moving, hydrogen-rich circumstellar material. Here we report observations of a class of luminous supernovae whose properties cannot be explained by any of these processes. The class includes four new supernovae that we have discovered and two previously unexplained events (SN 2005ap and SCP 06F6) that we can now identify as members of the same class. These supernovae are all about ten times brighter than most type Ia supernova, do not show any trace of hydrogen, emit significant ultraviolet flux for extended periods of time and have late-time decay rates that are inconsistent with radioactivity. Our data require that the observed radiation be emitted by hydrogen-free material distributed over a large radius (∼10(15) centimetres) and expanding at high speeds (>10(4) kilometres per second). These long-lived, ultraviolet-luminous events can be observed out to redshifts z > 4.

An extremely luminous panchromatic outburst from the nucleus of a distant galaxy.

Variable x-ray and γ-ray emission is characteristic of the most extreme physical processes in the universe. We present multiwavelength observations of a unique γ-ray-selected transient detected by the Swift satellite, accompanied by bright emission across the electromagnetic spectrum, and whose properties are unlike any previously observed source. We pinpoint the event to the center of a small, star-forming galaxy at redshift z = 0.3534. Its high-energy emission has lasted much longer than any γ-ray burst, whereas its peak luminosity was ∼100 times higher than bright active galactic nuclei. The association of the outburst with the center of its host galaxy suggests that this phenomenon has its origin in a rare mechanism involving the massive black hole in the nucleus of that galaxy.

A case of cutaneous leukocytoclastic vasculitis associated with gabapentin.

Gabapentin was approved for use in the USA in 1994 as an add-on drug in adults who have partial seizures either alone or with secondary generalised seizures. Its use has been expanded to include treatment for other conditions such as neuropathic pain and paraesthesiae. Gabapentin was prescribed for our patient who had persistent left-sided hemi-paraesthesiae consequential of a previous thalamic infarct. One week after commencement of gabapentin, she developed an adverse reaction in the form of a purpuric rash over bilateral lower limbs. Skin biopsy revealed histological features of cutaneous leukocytoclastic vasculitis. This rash completely resolved with withdrawal of gabapentin and steroidal treatment. This cutaneous adverse reaction to gabapentin has not been reported in the medical literature.

Cholinergic stimulation enhances colonic motor activity, transit, and sensation in humans.

The cholinesterase inhibitor neostigmine indirectly stimulates muscarinic M(1)/M(2)/M(3) receptors, thereby reducing colonic distension in acute colonic pseudo-obstruction. We investigated the dose-response profile for the colonic sensorimotor effects of neostigmine and bethanechol, a direct muscarinic M(2)/M(3) agonist in humans. A barostat-manometric assembly recorded phasic pressures, tone, and pressure-volume relationships (compliance) in the descending colon and rectum of 30 healthy subjects who received intravenous neostigmine (0.25, 0.75, or 1.5 mg; n = 15) or subcutaneous bethanechol (2.5, 5, or 10 mg; n = 15). Sensation to luminal distension was also assessed. Thereafter, the effects of neostigmine and bethanechol on colonic transit (geometric center) were compared with those of saline by scintigraphy in 21 subjects. Both drugs increased colonic phasic pressure activity, reduced rectal compliance, and enhanced urgency during rectal distension. Neostigmine also reduced colonic and rectal balloon volumes, reflecting increased tone by an average of 12% and 25% for the highest dose, respectively. Only neostigmine reduced colonic compliance, accelerated colonic transit [mean geometric center at 90 min 2.5 vs. 1.0 (placebo)], and increased pain perception during colonic distension. We conclude that neostigmine has more prominent colonic motor and sensory effects than bethanechol. Moreover, neostigmine induces coordinated colonic propulsion, perhaps by stimulating muscarinic M(1) receptors in the myenteric plexus.

A randomised trial of amoxycillin versus clarithromycin in combination with omeprazole for eradication of Helicobacter pylori infection in Singapore.

Dual therapy has been reported to produce H.pylori eradication rate of 75-80%. This study is designed to determine the efficacy of omeprazole 20 mg bd in combination with amoxycillin 500 mg tid (Group A), amoxycillin 750 mg tds (Group B) and clarithromycin 500 mg tid (Group C) in Singapore. One hundred and forty-eight patients with H. pylori positive duodenal ulcers between ages of 22 and 69 were enrolled from two centres. There were 48 patients in Group A, 50 patients in Group B and 50 patients in Group C. The medication was given for 14 days. The patients were re-evaluated with an upper GI endoscope 4 weeks after cessation of treatment Successful eradication was defined as H.pylori negative on histology and culture. Based on intention to treat analysis, the eradication rate was 47.8% in Group A, 68% in Group B and 66% in Group C. The difference between GroupA and B were statistically significant (p = 0.04). Based on all patient treated analysis, the eradication rate was 57.5% in Group A, 70.7% in Group B and 75% in Group C. The difference in eradication rates was not statistically significant. Adverse events were reported in 21% of all patients with no difference in the adverse event rate between all groups. The eradication rate achieved with dual therapy in this study was similar to that attained in Western population. Higher dose amoxycillin regime gives a significantly higher eradication than a lower dose amoxycillin.

Crohn's disease in the Singapore Chinese population.

Crohn's disease (CD) is rare in the Chinese population, but lately there seems to be an increasing trend of CD in the Singapore Chinese population. We carried out a retrospective study of all Chinese patients with CD seen from 1987 to 1993 at the Singapore General Hospital. All patients were regularly followed up and treated. Disease activity was defined by the Organisation Mondiale de Gastroenterologie index. We also compared our series with our first series reported in 1987 and a Western series. There were 32 patients (20 men, 12 women) giving a hospital prevalence of 26.7 per 100,000 patients compared with 3.5 per 100,000 patients in 1986. The mean age was 37.1 years (range, 19-80 years). Twelve patients had small intestinal disease, 9 had colonic disease, and 11 had both. The common presenting symptoms were bloody diarrhea (67%), abdominal pain (53%), loss of weight (47%), and fever (34%). Extraintestinal manifestations were rare. Six patients had no relapse during the follow-up period, whereas the remaining 26 patients had an average of two relapses (range, 1-5). These relapses were complicated by fistulas in 8 patients and strictures in 11 patients. Response to steroids and sulfasalazine was good in most patients. Four patients required repeated surgery despite medical treatment. The prevalence of CD appears to be increasing among the Singapore Chinese population. The clinical features are similar to those of the Western population. Most of our patients responded to standard medical therapy, but further follow-up is needed to assess their long-term clinical outcome.

Inhibition of cromolyn-induced phosphorylation of a 78-kDa protein by phorbol esters in rat peritoneal mast cells.

Disodium cromoglycate (cromolyn) is a well documented inhibitor of immunologically-induced histamine release from rat peritoneal mast cells and has been shown to stimulate the phosphorylation of a mast cell protein of apparent molecular mass 78,000 Da (78 kDa), an event which may be involved in terminating secretion. Here we aimed to determine the role of the ubiquitous enzyme, protein kinase C, in the phosphorylating activity of cromolyn by examining the effects of phorbol esters (activators of protein kinase C) on protein phosphorylation in [32P]orthophosphate loaded rat peritoneal mast cells. Protein kinase C-activating phorbol esters such as 12-O-tetradecanoyl phorbol-13-acetate (TPA) and 4beta-phorbol 12,13-dibutyrate (PdBu) were found to potently inhibit cromolyn-induced phosphorylation when added to mast cells simultaneously with cromolyn (IC50 22 and 79 nM respectively). 4Alpha-phorbol 12,13-didecanoate (PdD), a phorbol ester which does not activate protein kinase C, had no effect on cromolyn-induced phosphorylation. Addition of TPA to mast cells previously exposed to cromolyn for 60 sec (i.e. when 78-kDa protein phosphorylation is maximal) also caused a very rapid dephosphorylation of the 78-kDa protein. Phosphorylation of the 78-kDa protein can also be induced by dibutyryl cyclic GMP and this action was similarly inhibited by TPA and PdBu. Cromolyn inhibited secretion induced by anti-IgE, but not by TPA, and thus inhibition of secretion by cromolyn is further correlated to its phosphorylation of the 78-kDa protein. The data suggest that the inhibitory action of cromolyn on mast cell secretion and phosphorylation of the 78-kDa protein are not mediated through a phorbol ester-sensitive protein kinase C, but more likely that such an enzyme could be involved in regulating dephosphorylation of the 78-kDa protein. Further explanations for this novel dephosphorylating activity of phorbol esters are discussed.

Eye diseases in the elderly in Singapore.

OBJECTIVE: The study was conducted to determine the prevalence rates of blindness and visual impairment in those aged 60 years and above in Singapore and to determine the pickup rate of undiagnosed eye diseases through an active screening programme. METHOD: A random frame of 3,000 elderly persons aged 60 years and above was obtained from the Ministry of Home Affairs in Singapore. They were invited by mail to attend eye screening at Hougang Senior Citizens' Health Care Centre. The eye screening was in two parts: the first part by a trained registered nurse or therapy aide and the second part by the ophthalmologist. For each respondent, autorefraction, tonometry, retinal photography and visual field analysis were done. Examination criteria and disease classification were modelled after the Framingham Eye Study. RESULTS: 574 subjects attended the screening, giving a response rate of 22.2%. The prevalence rates for blindness and visual impairment in the elderly screened were 3.0% and 15.2% respectively. The prevalence rates for cataract, age-related macular degeneration, glaucoma and diabetic retinopathy were 78.6%, 27.0%, 5.7% and 5.1% respectively. For every person known to have cataract, 2 were unknown; for every person with age-related macular degeneration, 154 were unknown. None of the 29 persons with diabetic retinopathy was diagnosed previously. CONCLUSION: Almost 1 in 5 of the elderly screened had some degree of visual disability. The rates of visual impairment and blindness were similar to those reported in other studies and indicate a significant burden of visually impairing diseases in the community.

Endoscopic stenting in the management of biliary stones.

INTRODUCTION: Endoscopic sphincterotomy and stenting are established modes of treatment in the management of bile duct stones and cholangitis. It is the first choice of treatment when the patients are elderly and have other medical conditions rendering them unfit for surgery. AIMS: We studied the immediate and long-term outcome of endoscopic stenting in patients who underwent Endoscopic Retrograde Cholangiopancreatography (ERCP) for ductal stones. PATIENTS AND METHODS: From January 1990 to December 1992, 366 patients had ERCP done for biliary stone disease. Fifty-five of these patients received a 10 French biliary stent for the treatment of bile duct stones. Most of these patients (60%) had an advanced age of more than 70 years and 45% had co-existing medical conditions rendering them high risk for surgery. Ninety-one percent had stones greater than 1.2 cm in diameter and 82% had multiple stones. RESULTS: Eighty-nine percent of the patients had relief of jaundice and cholangitis resolved in 96% of the patients after stenting. None required immediate surgery after ERCP. Temporary bile drainage was achieved in 19 patients who went for surgery at a later date when they became more stable. Twenty-nine patients were on long-term follow-up for a mean period of 13 months. Nineteen patients still have their stents in place and remained well. The stents were repeatedly changed in 15 patients after an average duration of 5.5 months. Late complications were cholangitis in 2 patients and stent migration in one patient. There was no related mortality. In 5 patients, the stones have either disappeared spontaneously or become smaller and have been removed at subsequent ERCP. CONCLUSION: Endoscopic stenting is a valuable alternative to surgical bile duct exploration. It can be the definitive mode of treatment for large or multiple bile duct stones in the elderly and patients with multiple medical problems who are unfit for surgery.

Oedipism.

BACKGROUND: Oedipism or self-enucleation is a rare form of self-mutilation, and most often described in acutely psychotic patients, who have religious or sexual delusions. CLINICAL RECORD: A 47-year-old Chinese man with a history of chronic schizophrenia enucleated his own left eye and mutilated his right eye. The reason for his behaviour was unknown. The history and legends surrounding autoenucleation and the medical literature are reviewed. RESULTS: The patient was managed jointly with the psychiatrist. He suffered extensive injury to his right eye, resulting in loss of vision. CONCLUSION: The management of Oedipism requires close cooperation between ophthalmologists and psychiatrists. Precautions must be taken to prevent repeated attempts or other self-mutilatory behaviour.

Blood aflatoxin levels in patients with hepatocellular carcinoma in Singapore.

Aflatoxin (AF), a highly potent hepatocarcinogen, is strongly implicated in the pathogenesis of human hepatocellular carcinoma (HCC). In this study, our aim was to determine if this carcinogen is associated with cases of HCC in Singapore. Blood levels of the naturally-occurring AFs--B1, B2, G1 and G2--were assayed in 56 cases of HCC. AF was detected in only 2/56 (3.6%) cases of HCC, one each of AF-B1 and AF-G1. In contrast, in a similar survey done in Singapore on normal subjects, AF was positive in 64/423 (15.1%) cases. The low frequency of AF detection in our patients suggests that HCC in Singapore is not associated with significant chronic exposure to AF.

Neuronal insulin receptors in Y79 retinoblastoma cells.

Immunoblot analysis of Y79 cell membrane proteins indicated that Y79 insulin receptors (InsRs) alpha subunits had a mass of 115 kDa. Biosynthetic studies revealed a typical transit time for InsR delivery to the Golgi (approximately 2h) and receptor processing. However, neither the proreceptor nor the mature receptor exhibited endoglycosidase H-resistance, consistent with a lack of N-linked glycan processing. Insulin stimulated a rapid and transient tyrosine phosphorylation of receptor beta subunits (95 kDa) and of IRS-1 in intact Y79 cells, whereas in vitro studies with enriched membrane glycoproteins resulted in the autophosphorylation of both InsR (95 kDa) and IGF-1-R (98k Da) beta subunits. These studies provide the first biochemical dissection of InsR structure and function in retinoblastoma cells.

Characterization of vasoactive intestinal peptide receptors in rabbit ciliary processes.

PURPOSE: To demonstrate a potential role for vasoactive intestinal peptide (VIP) in the regulation of ciliary process function, VIP receptors on rabbit ciliary process membranes were identified and characterized in biochemical and immunochemical studies. METHODS: Membranes were isolated from rabbit ciliary processes, and VIP receptors were characterized by competition binding, affinity cross-linking, and N-glycanase digestion. A site-specific polyclonal antibody directed against the NH2-terminal end of the deduced sequence of the recently cloned rat VIP receptor was generated and used to identify the VIP receptor by immunoblot analysis. RESULTS: Membranes isolated from rabbit ciliary processes exhibited a high-affinity VIP binding site (KD approximately 1 nM). Secretin and glucagon, which possess considerable primary sequence homology with VIP, were ineffective in inhibiting 125I-VIP binding to ciliary process membranes. In conjunction with the chemical cross-linking agent disuccinimidyl suberate, 125I-VIP specifically labeled a 63-kd protein in membranes from ciliary processes. This apparent size was confirmed by immunoblot analysis of ciliary body membranes using a site-specific polyclonal antibody that recognizes residues 92 to 104 of the rat VIP receptor. Digestion of the affinity-labeled receptor with N-glycanase generated an N-linked oligosaccharide free core protein of -50 kd. CONCLUSIONS: These findings demonstrate the presence of specific VIP receptors in rabbit ciliary processes. The differences in ligand specificity and structure of the ciliary process VIP receptor, compared to VIP receptors on peripheral tissues, suggest either a specific role(s) for VIP that may be unique to the anterior segment or the existence of VIP receptor isoforms.

Role of ERCP in the management of bile duct lesions post bile duct surgery.

INTRODUCTION: Therapeutic Endoscopic Retrograde Cholangio-Pancreatography (ERCP) is an established mode of treatment for bile duct lesions. AIM: This paper reviews the role of ERCP in the management of bile duct lesions developing after biliary surgery. PATIENTS AND METHODS: Of the 894 ERCPs performed in our department between January 1990 and May 1992, 23 (13 female, 10 male) were for patients with post-operative bile duct lesions. The mean age of these 23 patients was 59 years (range 38-91 years). The previous biliary surgical procedures were conventional cholecystectomy (n = 19), laparoscopic cholecystectomy (n = 3) and a cholecystectomy with choledochojejunostomy. Associated medical conditions of ischaemic heart disease, unstable angina, hypertensive heart disease, chronic obstructive airway disease and hepatitis B cirrhosis were present in 7 of these patients. RESULTS: Ten patients had benign biliary strictures. Endoscopic stenting (with one or 2 stents) was successful in 9. The strictures reopened in 2 patients after a total stenting duration of 12 and 18 months respectively. Four patients had biliary leakages that were successfully treated with stenting. Two patients had spontaneous sealing of biliary leak at 3 and 6 months respectively. Nine patients had retained stones (7 with solitary stone, 2 with multiple stones) that were successfully removed with Dormia basket after sphincterotomy. Complications were few and manageable. CONCLUSIONS: Therapeutic ERCP is safe and effective. It is a useful adjunct in the management of patients with post-operative biliary lesions.

Phenylephrine eye drops in ophthalmic surgery--a clinical study on cardiovascular effects.

Phenylephrine in concentrations of either 2.5% or 10% is widely used as a mydriatic agent in ophthalmic surgery. Its potential cardiovascular effects are seldom recorded as ophthalmic surgery is not usually monitored by an anaesthetist. A prospective randomised double blind study was carried out in 89 consecutive cases of uncomplicated cataract surgery in the presence of an anaesthesiologist ensuring the continuous monitoring of blood pressure, heart rate, electrocardiography and pulse oximetry. All these patients were given a drop of either normal saline, 2.5% or 10% phenylephrine in addition to mydriacyl prior to surgery. Blood pressure readings were found to be significantly higher in non-hypertensive patients receiving phenylephrine at the start of the operation and at five, 10, 15 and 20 minutes intra-operatively and the first three hours post-operatively. Blood pressure readings in hypertensive patients, on the other hand, were also found to increase after phenylephrine administration, though not statistically significant. 10.3% of the 10% phenylephrine group and 3% of the 2.5% phenylephrine group required intraoperative intravenous hypotensive agent to control the blood pressure. There were no arrhythmias or ischaemic changes observed intraoperatively. None of the patients complained of palpitation, headache or chest discomfort. There was no oxygen desaturation observed. We concluded that significant hypertensive effects can arise after phenylephrine eye drop administration. Hence, it should be used cautiously with intraoperative monitoring of the cardiovascular status during cataract surgery.

Characterization of the G-protein linked orphan receptor GPRN1/RDC1.

Site specific antibodies were raised against the second intracellular loop of the G-protein coupled orphan receptor GPRN1 for analysis of receptor protein expression from a number of sources. Immunoblot analyses showed GPRN1 to be a 60 kDa membrane bound glycoprotein. It was found in AR4-2J, PC12 and SK-N-MC cell lines. High amounts of GPRN1 were found in rat stomach, liver, lung, brain, small intestine and pancreas, with lower amounts in spleen and kidney: none was detectable in rat heart. This distribution differs markedly from that of the closely related orphan receptor RDC1. The receptor shows high evolutionary conservation: immunoreactive 60 kDa GPRN1 was detected in membrane glycoprotein fractions from the livers of rat, toad, chick, stingray and shark. It is therefore predicted that GPRN1 and RDC1 represent two tissue specific subtypes of a 60 kDa receptor for a ligand which has likely been highly conserved throughout evolution and which is active upon many organs of the body.

Specific recognition of the human neuroendocrine receptor for vasoactive intestinal peptide by anti-peptide antibodies.

Rabbit polyclonal IgG antibodies were generated to three distinct synthetic peptide substituents of the human neuroendocrine-type 7 transmembrane-domain receptor for vasoactive intestinal peptide (VIP), including a portion of the amino-terminus, first extracellular loop, and carboxyl-terminus. Immunofluorescent staining of both human K293 cell transfectants, expressing recombinant VIP receptors, and HT-29 human intestinal epithelial cells, bearing native VIP receptors, was observed with each of the antibodies and was eliminated specifically after absorption of antibodies with the respective peptide immunogen. Each of the antibodies recognized the same approximately 70-kDa membrane proteins, extracted from both K293 cell transfectants and HT-29 cells, in sodium dodecyl sulfate-polyacrylamide gel electrophoresis blots. Neither IgG nor Fab preparations of the antibodies inhibited VIP binding to cellular receptors at a concentration of 1 microgram/ml, that yielded optimal immunofluorescence, or at 5-300 micrograms/ml. In contrast, 5-200 micrograms/ml of anti-peptide antibodies as IgG, but not Fab, significantly inhibited the increase in concentration of cyclic AMP in HT-29 cells elicited by 1 nM VIP, without affecting the greater increase evoked by 100 nM VIP or alone altering the level of cyclic AMP. Antibodies to several peptide substituents thus bind specifically to VIP receptors in immunoblots and permeabilized cells, and may affect the cellular functions of VIP receptors with sufficient selectivity to reduce transduction of signals, without altering the binding of VIP.

Insulin like growth factor 1 receptor signal transduction to the nucleus.

The mechanism by which IGF-1Rs regulate the growth and maintenance of cells in normal and disease states provides an important setting for studies addressing signal transduction events at the nuclear level. With the identification of c-Jun/AP-1 as a nuclear target of IGF-1 action we are provided with a model system for pursuing the molecular mechanisms triggered by IGF-1 action.