Ramus Condyle Unit Reconstruction Using Vertical Ramus Osteotomy in Temporomandibular Joint Ankylosis.

INTRODUCTION: Treatment of bony Temporomandibular Joint (TMJ) Ankylosis includes release of the ankylosis and creation of a gap with or without insertion of interposing material and complete reconstruction of the joint using e.g. costochondral, autogenous coronoid/ankylosed mass, sternoclavicular, clavicular bone grafts etc. As these are non-pedicled grafts, there is eventual resorption with subsequent decrease in height of the ramus, facial asymmetry, deviated mouth opening and reankylosis. The authors have applied the method of vertical ramus osteotomy (VRO) on the posterior border of the mandibular ramus for reconstruction of the ramus condyle unit (RCU) as a pedicled graft along with Myofascial Temporalis Interposition for the correction of TMJ Ankylosis. MATERIALS AND METHODS: Ten patients of TMJ Ankylosis were included in this study. All ten patients were treated using VRO for the RCU reconstruction with posterior border of mandibular ramus after Gap Arthroplasty. Temporalis myofascial flap was used as an interpositional material in all patients. Patients were followed from 20 to 30 months (mean 24 months). RESULTS: As a result of successful procedure the post-operative maximal mouth opening of 32-45 mm (mean 37 mm) was achieved. No patient experienced pain and infection at surgical site. None of the patients had graft rejection and reankylosis at follow-up. CONCLUSION: The results showed that VRO on the posterior border of the mandibular ramus seems to be an alternative and promising method for RCU reconstruction in patients with TMJ Ankylosis.

Effect of dentin powder on setting time of mineral trioxide aggregate: an in vitro study.

AIM: Mineral trioxide aggregate (MTA) is a biomaterial with numerous clinical applications in the field of endodontics. The properties of this material come closest to the requirements of an ideal endodontic repair material. Delayed setting time though may limit the use of MTA in endodontic procedures. Many chemical based additives have influenced the setting time of MTA. The aim of this paper was to evaluate the effect of a natural additive in the form of human dentin powder on setting properties of ProRoot MTA (Dentsply/Tulsa Dental, Tulsa, OK). METHODS: Thirty extracted human teeth were taken to obtain fine dentin powder. The methodology used to obtain dentin powder for the present study was same as performed by Haapsalo et al. The specimens were divided into two groups. The samples were placed in standardized stainless steel ring moulds. The setting time of MTA alone and in equal proportions with dentin powder as an additive was evaluated using Vicats apparatus. RESULTS: MTA mixed with dentin powder showed faster setting time (70 minutes) in comparison to MTA without dentin powder (120 minutes) (P<0.5). CONCLUSION: Although MTA is an ideal retrograde material with increased efficacy due to reduced setting on addition of dentin powder. A combination of MTA with dentin powder might be a viable option in procedures where fast setting of the MTA is critical.

Copeptin as a marker for arginine-vasopressin/antidiuretic hormone secretion in the diagnosis of paraneoplastic syndrome of inappropriate ADH secretion.

Direct measurement of arginine-vasopressin/antidiuretic hormone (AVP/ADH) concentrations is not included in the standard diagnostic procedures for paraneoplastic syndrome of inappropriate ADH secretion (SIADH). Here, we evaluate the potential of copeptin measurement as a surrogate marker of AVP/ADH secretion for the direct diagnosis of suspected SIADH in cancer patients. Forty-six unselected cancer patients with serum sodium concentrations permanently below 135 mmol/L were included in this study. We compared standard diagnostic criteria for SIADH to the measurement of plasma copeptin in relation to osmolality. Normative data for comparison were constructed from 24 healthy controls studied under basal conditions, experimental dehydration, and hypotonic hypervolemia as well as from 222 hospital patients with no suspicion of an altered ADH regulation. Log transformation of copeptin revealed a linear relationship to plasma osmolality in the controls (R = 0.495, p < 0.001). Compared to these normative data, copeptin levels in most cancer patients were inappropriately high for plasma osmolality and were not significantly correlated. These results, suggestive for paraneoplastic SIADH, could be confirmed by conventional diagnostic procedures for SIADH. Current strategies to diagnose SIADH are difficult to perform under outpatients conditions. Our approach allows screening from a single plasma sample for true paraneoplastic ADH oversecretion and thus rapid selection for a specific therapy with an AVP receptor antagonist.

Role of peroxynitrite-modified H2A histone in the induction and progression of rheumatoid arthritis.

OBJECTIVE: Rheumatoid arthritis (RA) is an autoimmune disease of complex aetiology and pathogenesis. In recent years it has become evident that apoptotically modified histones exert a central role in the induction of autoimmunity, for example in systemic lupus erythematosus (SLE) and RA. Because nitric oxide (NO)-related species have been found in inflamed joints of arthritis patients, we investigated whether nitrotyrosine is present in sera of RA patients, and whether peroxynitrite-modified H2A histone is likely to be involved in the induction and progression of RA. METHODS: Commercially available H2A histone was modified in vitro by peroxynitrite. The RA patients were divided into three groups on the basis of CRP, nitrite, total protein and IgG level. Sera of RA patients with high-titre rheumatoid factor (RF) were analysed for autoantibodies against native DNA and native and peroxynitrite-modified H2A histone. Binding characteristics and specificity of the autoantibodies were analysed by direct binding, inhibition enzyme-linked immunosorbent assay (ELISA), and band shift assay. RESULTS: Sera from control subjects contained almost negligible amounts of 3-nitrotyrosine (3-NT); lower levels were found in group 1 RA patients in comparison to group 2 and group 3 patients, where the level of nitrotyrosine was progressively higher. Enzyme immunoassay data showed preferential binding of RA autoantibodies to peroxynitrite-modified H2A histone in comparison with native H2A histone or native DNA. The results suggest that peroxynitrite modification of self-antigen(s) can generate neoepitopes capable of inducing RA characteristic autoantibodies. CONCLUSION: The preferential binding of peroxynitrite-modified histones by autoantibodies derived from RA sera indicates a role for oxidatively modified and nitrated proteins in the initiation/progression of RA.

Licorice - or more?

A 57 yr old man presented to endocrinology clinic with a six year history of poorly controlled hypertension which was treated with Metoprolol 200 mg/day and Enalapril 20 mg/day. He was asymptomatic but incidentally hypokalaemia was detected while having cholecystectomy, two years prior to his clinic appointment. He had never been on diuretics or laxatives. He was started on potassium supplements (120 mmol/d) and advised to increase dietary potassium by the surgical team. A detailed personal history revealed ingestion of 300-500 g licorice per day. Physical examination was unremarkable apart from increased blood pressure of 180/105 mmHg. Following the initial visit, his serum electrolyes (K+3.7 mmol/l) were normal with potassium supplementation and as were morning cortisol, ACTH, 11-deoxycortisol and plasma metanephrines. 17 OH-P, DHEAS and androstenedione were normal but testosterone was low. Morning ambulant aldosterone was slightly increased at 801 pmol/L and renin activity was undetectable. Urinary 24 h aldosterone excretion was significantly increased at 162 ng/24 h with normal cortisol and catecholamine excretion. Four weeks following advice to stop licorice, serum potassium decreased to 3.4 mmol/L despite continuous supplementation. Morning plasma aldosterone increased to 1 449 pmol/ml, renin activity remained undetectable but 24 h urine aldosterone excretion increased to 434 ng/24 h with a reduction in urinary cortisol excretion. Interestingly 17 OH-P and androstenedione levels, although within the reference range, were slightly higher compared to the levels whilst on licorice. Testosterone level had significantly increased to be within normal range. Abdominal imaging with US and MRI showed a 2.7 cmx2.2 cmx1.7 cm left adrenal mass. He underwent laparoscopic left adrenalectomy and histology confirmed aldosterone producing adrenal adenoma. Post-operatively his aldosterone and serum potassium levels normalized and he became normotensive without any antihypertensive medication.

Following brain trauma, copeptin, a stable peptide derived from the AVP precusor, does not reflect osmoregulation but correlates with injury severity.

The incidence of water and electrolyte disturbances following traumatic brain injury (TBI) is considerable and has been attributed to a dysregulation of the hypothalamic peptide arginine-vasopressin (AVP). Copeptin, the C-terminal part of the AVP prohormone, reflects AVP activity. In 71 TBI patients we measured copeptin in serum by a sandwich immunoassay. Injury severity was assessed by Glasgow Coma Score (GCS) and computed tomography, and recovery by Glasgow Outcome Score (GOS). Neuroendocrine and osmoregulation regulation were examined on day 0, 3 and 7, and 24 months post-injury. Copeptin was highest on admission (40.0 +/- 72.3 pmol/l), stabilized on day 3 and 7 (21.2 +/- 18.3 resp. 20.3 +/- 17.1 pmol/l), and normalized at follow-up (4.2 +/- 1.7 pmol/l). On admission, there was a correlation between serum sodium and urine excretion (p = 0.003), but the correlation got lost on day 3 and 7. Copeptin did not reflect the individual 24 h urine excretion or serum sodium levels indicating an uncoupling of copeptin/AVP release and renal water excretion. High copeptin level on day 3 were correlated with a low GCS (p < 0.001), midline shift (p = 0.019), intracerebral hemorrhage (p = 0.026), SAPS score (p = 0.001), as well as with a low GOS (p = 0.031). Copeptin was significantly decreased following skullbase fracture (p = 0.016).Our data reveal a loss of hypothalamic osmoregulation following TBI. The measurement of Copeptin/AVP release reveals a significant predictive function for the severity of TBI.

Impact of peroxynitrite modification on structure and immunogenicity of H2A histone.

Peroxynitrite is an extremely reactive entity and has in vivo existence. Its interaction with biomolecules may cause oxidation and nitration. In this study, commercially available H2A histone was exposed to peroxynitrite generated in vitro. The peroxynitrite-mediated structural changes in histone were studied by ultraviolet & fluorescence spectroscopy, high performance liquid chromatography, anilinonaphthalene-8-sulfonic acid binding and polyacrylamide gel electrophoresis. Analysis of results revealed that carbonyl, nitrotyrosine and dityrosine contents were significantly increased in peroxynitrite-modified H2A compared with native H2A. Rabbits challenged with peroxynitrite-modified H2A induced high titre antibodies. The immunogenicity of peroxynitrite-modified H2A was directly proportional to protein nitrotyrosine content and induced antibodies showed specificity for the immunogen and good cross-reaction with nitrated epitopes of other modified proteins. Formation of high molecular weight immune complex with retarded mobility further supports the specificity of induced anti-100 mum peroxynitrite-modified H2A antibodies for the immunogen. It may be concluded that induction of anti-H2A histone antibodies could be due to protection of peroxynitrite-modified histone from proteolytic breakdown and its subsequent recognition by immunoregulatory cells as foreign molecule.

Role of nitric oxide modified DNA in the etiopathogenesis of systemic lupus erythematosus.

The role of the nitric oxide (NO) radical in systemic lupus erythematosus (SLE) pathogenesis has been investigated in the present study. The binding characteristics of SLE autoantibodies with native calf thymus DNA, native and NO-modified plasmid DNA were assessed. Binding characteristics and specificity of antibodies were analysed by direct binding and inhibition ELISA, gel retardation assay and quantitative precipitin titration. The data shows preferential binding of SLE autoantibodies to NO-modified plasmid DNA (NO-DNA) in comparison with native plasmid DNA. Inhibition ELISA reiterates the direct binding results. Gel retardation assay further substantiated the enhanced recognition of NO-DNA by anti-DNA autoantibodies. The binding affinity of modified and native plasmid DNA with one of the SLE IgGs was calculated, using the Langmuir plot. The apparent association constant for NO-plasmid DNA was found to be highest, followed by native calf thymus DNA and native plasmid DNA. The results suggest that the NO radical modification of plasmid DNA causes perturbations, resulting in the generation of neo-epitopes, and making it a potential immunogen. The DNA modified with the NO radical may be one of the factors for the induction of circulating SLE anti-DNA autoantibodies.

Antigen binding characteristics of antibodies induced against nitric oxide modified plasmid DNA.

Nitric oxide (NO) generated by the reduction of sodium nitrite with sodium dithionite caused damage to plasmid Bluescript DNA leading to strand breaks and base modifications. The NO-plasmid DNA was highly immunogenic in rabbits. The antibody activity was inhibited to the extent of 86% with the immunogen as inhibitor, indicating the induction of immunogen specific antibodies. However, delineating the antigenic specificity of anti-NO-plasmid DNA antibodies by competition ELISA, multiple cross-reactivity was observed. The antibodies recognised B-, A- and allied conformations. The visual detection of immune complex formation with native and NO-plasmid DNA reiterated preferential binding with modified plasmid DNA. DNA modified by nitric oxide presents unique epitopes which may be one of the factors in antigen-driven autoimmune response in systemic lupus erythematosus.

Evaluation of antiallergic activity (type I hypersensitivity) of Inula racemosa in rats.

Alcoholic extract of root of Inula racemosa, was studied for its antiallergic effect in experimental models of type I hypersensitivity, viz. egg albumin induced passive cutaneous anaphylaxis (PCA) and mast cell degranulation in albino rats. The alcoholic extract was prepared by the process of continuous heat extraction. LD50 of this extract was found to be 2100 +/- 60 mg/kg, i.p. Assessment of protection against egg albumin induced passive cutaneous anaphylaxix by different doses of Inula racemosa was done by giving drug intraperitoneally or orally for seven days or once only. Mast cell degranulation studies were done by using compound 48/80 as degranulation agent with same dosage schedule. Inula racemosa (i.p. as well as p.o.) showed significant protection against egg albumin induced PCA. Protection against compound 48/80 induced mast cell degranulation by alcoholic extract of Inula racemosa (single dose) was similar to that of disodium cromoglycate. The seven days drug treatment schedule showed greater protection than disodium cromoglycate intraperitoneally. The results suggest that Inula racemosa possesses potent antiallergic properties in rats.

Neonatal mydriasis due to effects of atropine used for maternal Tik-20 poisoning.

A neonate was born to a mother who had consumed an organophosphorus(OPC) compound with suicidal intent. The mother was administered atropine and this caused mydriasis in the neonate without any other pharmacological effects. There was no evidence of placental dysfunction. There are no case reports of OPC consumed in pregnancy and its effect on neonates or of effects of massive doses of atropine in the mother and its effects on the fetus or the newborn.

Bacteriological profile of neonatal septicemia cases (for the year 1990-91).

Blood culture reports were studied in 1266 cases of clinically suspected neonatal septicemia, to determine the bacteriological profile and antibiotic sensitivity pattern of the cultured isolates. Blood culture was positive in 24.88% of cases. Gram negative septicemia was encountered in 87.1% of these neonates. Klebsiella and Enterobacter species were the predominant pathogens amongst Gram negative organisms. Of Gram positive isolates, Staphylococcus aureus was the predominant isolate (79.0%). Salmonella species was isolated in 2.4% of these cases.

Substituted quinazolones as potent anticonvulsants and enzyme inhibitors.

A series of 6,8-disubstituted 3-[5- [[2-hydroxy-3-[(substituted phenyl)amino]propyl]thio]-1,3,4-thiadizol-2-yl] 2-methyl-4(3)- quinazolinones were synthesized whose structures were confirmed by elemental analyses, IR, NMR and mass spectral studies. All these compounds were evaluated in vivo for anticonvulsant and analgesic activities and in vitro for monoamine oxidase and succinate dehydrogenase enzyme inhibitory activities using rat brain homogenate as a source of enzyme at final concentration of 1 x 10(-4) mol/l. ALD50 values indicated their relatively nontoxic nature.

Role of dopaminergic system in opioid-induced cardiovascular responses in dogs.

A study was carried out to determine the involvement of dopaminergic system in opioid-induced cardiovascular responses in the dogs. The study population consisted of 32 mongrel dogs of either sexes. The results show that morphine given in small dose (2 mg/kg I.V.) causes significant fall in blood pressure. The results also show that there is involvement of dopaminergic system in opioid-induced vasomotor responses in dogs. Partial blockade of the parenterally induced hypotensive response of morphine by haloperidol given centrally induced hypotensive responses of morphine by haloperidol given centrally in doses, which are too low to be effective by the peripheral route, strongly favours the involvement of central dopaminergic system in the morphine-induced hypotensive responses. The results also show that the hypotensive response of morphine was almost completely blocked after naloxone pretreatment by central route.

Hygiene, health education and collaborative health practices in Nepal.

PIP: Health education in Nepal, according to the Long Term Health Plan (1975- 1990) emphasizes an integrated, intersectorial approach, committed to providing minimum health care to the maximum number of people. Nepal has about 16 million people, 90% of them rural, growing at over 2.7% yearly, with a rising growth rate, a 12.2% infant mortality rate, a 50% child mortality rate, and life expectancies of 46 for men and 42.5 for women. 2 health projects based on community volunteers are described: the urban Bhaktapur Development Project and the rural Jumla Project. The Bhaktapur Project employs Community Health Leaders, Village Health Workers, and Panchayat Based Health Workers to provide basic health care and health education, emphasizing prevention. These workers visit households daily, and teach sanitation, latrine construction, water supply development, first aid, detect deficiency diseases, and refer people to clinics. The Jumla Project supplies a densely populated but inaccessible mountainous region where food supplies have to be airlifted, the per capita income averages $140, firewood must be brought from may kilometers away, and local streams are used for drinking water, livestock, bathing and latrines. In the 1st 2 years of the project, 11 pit latrines and 2 gravity fed water systems were constructed. Now latrines are being built all over the region with materials supplied by the International Human Assistance Programme.^ieng

Role of endogenous opioids and histamine in morphine induced emesis.

The role of opioid and histaminergic system in morphine induced emesis was investigated in dogs. Morphine (25 micrograms, icv) consistently evoked emesis with an average latency of 195 +/- 29 sec which was fully accounted for by an action on the chemoreceptor trigger zone (CTZ) as its ablation rendered animals refractory to vomiting. Intraventricular pretreatment with opioid antagonist naloxone, histamine H1 antagonist mepyramine and H2 antagonists metiamide and cimetidine afforded protection to icv morphine emesis. The CSF histamine concentration was significantly raised 5 min after icv morphine administration. The results suggest that both endogenous opioid and histamine are involved in morphine emesis. Naloxone in high doses (1600 micrograms, icv) elicited emesis which was not blocked by CTZ ablation confirming our earlier report.