Antenatal and postnatal factors associated with neonatal death in the Indian subcontinent: a multilevel analysis.

OBJECTIVES: This study aimed to identify significant antenatal and postnatal factors associated with neonatal death at 2-7 days and at 2-28 days in the Indian subcontinent. Results from this study may help guide strategies to improve antenatal and postnatal care services and reduce neonatal mortality. STUDY DESIGN: Nationally representative recent Demographic and Health Survey data sets from five countries, including Bangladesh, India, Pakistan, Maldives and Nepal, were used. METHODS: Survey-weighted univariate distributions were used for study population characteristics and bivariate distributions, along with the chi-squared test for unadjusted associations. Finally, multilevel logistic regression models were performed to determine the association of antenatal care (ANC) and postnatal care (PNC) factors with neonatal deaths. RESULTS: Among 200,499 live births, the highest neonatal death rate was observed in Pakistan, followed by Bangladesh, whereas the lowest rate was in Nepal. After adjusting for sociodemographic and maternal control variables, the multilevel analysis showed a significantly lower likelihood of neonatal death at 2-7 days and 2-28 days with ANC visits <12 weeks' gestation, at least four ANC visits during pregnancy, PNC visits within the first week after birth and breastfeeding. Delivery at home by a skilled birth attendant compared to unskilled birth attendant was significantly associated with lower neonatal death at 2-7 days. Multifoetal gestation was significantly associated with higher neonatal death at 2-7 days and at 2-28 days. CONCLUSIONS: The findings suggest that strengthening ANC and PNC services will improve newborn health in the Indian subcontinent and decrease neonatal mortality.

A splenic 'cyst': histology confirmed splenic sarcoma.

Primary malignant fibrous histiocytoma, now classified as pleomorphic undifferentiated sarcoma, is the most common soft-tissue sarcoma in adult life. Primary splenic pleomorphic undifferentiated sarcoma is extremely rare and aggressive, and is associated with a poor prognosis; only 14 cases of splenic pleomorphic undifferentiated sarcoma have been documented in the English literature. We discuss a case of a 56-year-old woman with iron-deficiency anaemia, early satiety and left upper-quadrant pain, who was preoperatively diagnosed with a large splenic cyst following thorough investigation. This was excised in an elective procedure. Unfortunately, histology confirmed splenic pleomorphic undifferentiated sarcoma. Following a review and summary of the literature, we discuss key differentials between splenic cysts and splenic pleomorphic undifferentiated sarcoma. This case highlights that iron-deficiency anaemia is unusual in splenic cysts and more sinister causes must be considered.

Early and Late Alkali Igneous Pulses and a High-3He Plume Origin for the Deccan Flood Basalts.

Several alkalic igneous complexes of nephelinite-carbonatite affinities occur in extensional zones around a region of high heat flow and positive gravity anomaly within the continental flood basalt (CFB) province of Deccan, India. Biotites from two of the complexes yield (40)Ar/(39)Ar dates of 68.53 +/- 0.16 and 68.57 +/- 0.08 million years. Biotite from a third complex, which intrudes the flood basalts, yields an (40)Ar/(39)Ar date of 64.96 +/- 0.1 1 million years. The complexes thus represent early and late magmatism with respect to the main pulse of CFB volcanism 65 million years ago. Rocks from the older complexes show a (3)He/(4)He ratio of 14.0 times the air ratio, an initial (87)Sr/(86)Sr ratio of 0.70483, and other geochemical characteristics similar to ocean island basalts; the later alkalic pulse shows isotopic evidence of crustal contamination. The data document 3.5 million years of incubation of a primitive, high-(3)He mantle plume before the rapid eruption of the Deccan CFB.

Hybrid thermoreversible gels from covalent polymers and organogels.

This paper reports on experiments intended for investigating the feasibility of preparing hybrid thermoreversible gels from covalent polymers and noncovalent self-assembling pi-conjugated molecules. The formation and the degree of dispersion of these hybrid gels have been studied with polystyrenes of various tacticities and oligo(p-phenylenevinylene) molecules (OPV) in different nonpolar organic solvents. Detailed investigations of the systems have been carried out by DSC, SAXS, and AFM. It is shown that no liquid-liquid phase separation is involved, indicating that the systems are highly compatible, and that the growth of one type of gel does not interfere with the other. These studies reveal that the resultant hybrid gels are composed of the intermingled fibrillar architectures of both gels.

Quality of life after liver resection for hepatobiliary malignancies.

BACKGROUND: Few prospective longitudinal studies have used a validated quality of life (QOL) instrument in patients undergoing liver resection for hepatobiliary malignancy. METHODS: Patients undergoing liver resection for hepatobiliary tumours in a 1-year period were enrolled. The cancer-specific European Organization for Research and Treatment of Cancer core questionnaire (EORTC QLQ-C30) was completed before operation, and at 6, 12 and 36-48 months after surgery. QOL over time was analysed in relation to several clinical factors. RESULTS: A total of 103 patients were enrolled. Patient compliance was at least 75 per cent at all stages. Most functional scales and the global QOL scale showed a non-significant trend towards deterioration at 6 months and a return to preoperative level at 12 months. Physical functioning and dyspnoea deteriorated significantly at 6 months (P = 0.020 and P = 0.004 respectively) and did not recover by 12 months (P = 0.002 and P < 0.001 respectively). Pain and fatigue showed clinically significant deterioration over 12 months, which was not statistically significant. Survivors without recurrence at 36-48 months showed better QOL than those with recurrent disease. CONCLUSION: Major liver resection is associated with acceptable QOL outcomes, and QOL continues to improve in the long term in those without recurrence.

Enhancement of transcriptional activity of T7 RNA polymerase by guanidine hydrochloride.

T7 RNA polymerase shows an increase in processive transcription in the presence of low concentrations of guanidine hydrochloride (GdnCl) upto 60 mM, which is not observed when the enzyme is treated with urea. Higher concentrations of the denaturant lead to a progressive loss in the processive transcriptional activity of the enzyme. We have attempted to explain the above phenomenon in terms of the structural change in the enzyme. Fluorescence and CD studies suggest that the tertiary structure of the native enzyme undergoes an alteration upon addition of low concentration of guanidine hydrochloride. This is also indicated from the decreased susceptibility of the enzyme to limited proteolysis by trypsin.

Involvement of colchicine binding site of tubulin in the polymerisation process.

Role of lysine residues in the colchicine binding site and in the assembly-disassembly process was examined. It was observed that at 4 degrees C (pH 7.5-8, 8 +/- 1) lysine residues and the N-terminal methionine residue of tubulin were all buried within the molecule. Evidence indicates that epsilon-amino groups of lysine residues of tubulin are shared by both the colchicine binding site and the polymerisation process.

Interaction of synthetic analogs of distamycin with DNA. Role of the conjugated N-methylpyrrole system in specificity of binding.

Interaction of two synthetic analogs of distamycin (Dst), PPA and PAP, containing a saturated beta-alanine moiety replacing one N-methylpyrrole ring, with different polynucleotides and natural DNAs were studied using UV and CD spectroscopy. The results indicate that, similar to Dst, these analogs bind to DNA via the minor groove with a specificity towards AT-base pairs. It may be proposed that pyrrole chromophores in Dst probably do not play a role in the AT-base selectivity exhibited by Dst.

Synthesis of a photoaffinity taxol analogue and its use in labeling tubulin.

A photoaffinity analogue of taxol, N-([3,5-3H]-4-azidobenzoyl)-N-debenzoyltaxol (7), was synthesized and used to photolabel microtubules. Approximately 20% of the noncovalently bound analogue becomes covalently bound upon irradiation at 300 nm. Incorporated label was stable to a 50% ethanol solution and sodium dodecyl sulfate. About 80% of the incorporated label was found in the beta-subunit and 20% in the alpha-subunit. Incorporation did not occur into unpolymerized tubulin, consistent with the fact that taxol binds only to polymerized tubulin, and was decreased by the presence of taxol. Little or no nonspecific labeling occurs. This analogue is currently being used to identify taxol binding site(s) on tubulin.

Fab fragments of digoxin-specific antibodies used to reverse ventricular fibrillation induced by digoxin ingestion in a child.

Digitalis poisoning is a rare problem in children, but it may be life threatening. A case of massive overdose of digoxin in a 2 1/2-year-old boy that produced prolonged ventricular fibrillation refractory to conventional therapy is reported. After two hours the boy was given digoxin-specific Fab fragments of antibody in sufficient quantity to bind his estimated dose of 10 mg. By completion of the treatment minutes later, normal rhythm and circulation were restored. The serum free digoxin level before antibody administration was greater than 100 ng/ml, and it rapidly fell to undetectable levels after antibody was given. Digoxin bound to the antibody had a clearance half-life of approximately 48 hours. The child had no apparent neurologic damage and his intellectual function was normal on discharge. He had a transient hematuria and a residual incomplete right bundle branch block. Administration of purified Fab fragments of digoxin-specific antibodies can be life saving in children with digitalis poisoning, and prolonged cardiopulmonary resuscitation in children is justified when the cause of cardiac arrest is potentially reversible.

Interaction of the antitumor antibiotic chromomycin A3 with glutathione, a sulfhydryl agent, and the effect upon its DNA binding properties.

Chromomycin A3 (CHR), an anticancer antibiotic, blocks macromolecular synthesis via reversible interaction with DNA only in the presence of divalent cations like Mg2+. In the absence of DNA, the antibiotic forms a dimer: Mg2+ complex [(CHR)2Mg2+]. It is the DNA-binding ligand. The antibiotic has potential reactive centers that could interact with GSH, the most abundant non-protein thiol in eukaryotic cells and a putative cofactor involved in the activation of many antibiotics in vivo. To understand the mode of action of CHR in vivo, we studied the interactions of CHR and the (CHR)2Mg2+ complex with GSH and the association of the resultant complexes with DNA by means of absorption, fluorescence, and circular dichroism spectroscopy. The novel finding was that GSH interacts non-covalently with CHR without a chemical modification of the antibiotic. The interaction was reversible in nature. The results are reported in two parts: the interaction of CHR with GSH in the absence and presence of Mg2+, and the effect of this interaction on the DNA-binding properties of the antibiotic. CHR forms a single type of complex with GSH. In contrast, (CHR)2Mg2+ forms two different types of complexes with GSH: a low GSH complex at approximately 12 mM GSH and a high GSH complex at > or = 16 mM GSH. Binding and thermodynamic parameters for the reversible association of the complexes with DNA demonstrated that they bind differently to the same DNA. The thermodynamic parameters indicate that the presence of GSH alters the mode of binding of the (CHR)2Mg2+ complex with DNA. The (CHR)2Mg2+ complex binds to DNA via an entropy-driven process, whereas in the presence of GSH the association is enthalpy-driven. The significance of these results in the understanding of the molecular basis of action of the antibiotic is discussed.

Conformational changes of E. coli RNA polymerase during transcription initiation.

Escherichia coli RNA polymerase-promoter complex undergoes a multistep process to initiate transcription. We have employed fluorescence spectroscopic approaches to detect the conformational states of the enzyme during this multistep process. A fluorescence assay based on the measurement of fluorescence of free and promoter-bound enzyme as a function of temperature within the range of 4 to 37 degrees C showed that, starting with initial 'closed complex', there are conformationally two distinct intermediate states of the polymerase till it attains the final form required for transcription initiation. The equilibrium from closed complex (RPc) to open complex (RPo) consists of at least the following two intermediate complexes: [formula: see text] Higher order structure of RNAP in each of these complexes was probed by means of measurement of accessibilities of the tryptophan fluorophores to the acrylamide. In the next part of the study, TbGTP, a fluorescent substrate, has been used to probe the state of active site in the enzyme for the complexes RPc, RPi1, RPi2 and RPo, respectively. From the comparison of changes in the parameters such as, fluorescence polarization anisotropy of TbGTP and its accessibility to the neutral quencher, acrylamide, in free and promoter-bound enzyme, we have further substantiated the first part of our results. Together these results suggest that formations of RPc and RPi1 do not involve radical conformational changes in the enzyme, while the enzyme undergoes major change in conformation in the steps RPil-->RPi2 and RPi2-->RPo. The strong tryptophan promoter cloned in plasmid pDR720 was chosen as a model promoter in these studies.

Role of Mg2+ in the interaction of anticancer antibiotic, chromomycin A3 with DNA: does neutral antibiotic bind DNA in absence of the metal ion?

Antitumor antibiotic, Chromomycin A3 (CHR), inhibits DNA replication and transcription via reversible interaction with double stranded DNA with GC-base specificity. The interaction, at and above physiological pH, requires the presence of bivalent metal ions, such as Mg2+. Anionic antibiotic does not bind DNA in the absence of Mg2+. In this paper we have examined the structural potential of neutral CHR at pH 5.2 to bind DNA in the absence of Mg2+. We have demonstrated the ability of the neutral antibiotic to bind DNA by means of different spectroscopic techniques and evaluated the necessary thermodynamic parameters for elucidation of the molecular basis of recognition. The results are compared with the scenario when Mg2+ is present in the system, because the ultimate aim of these studies is to elucidate the role of Mg2+ in CHR-DNA recognition. Neutral CHR binds to Mg2+ with lesser affinity than its anionic form. Spectroscopic features of the drug and its Mg2+ complex indicate self association of the antibiotic in the absence and presence of Mg2+. GC-base specificity of the drug and its Mg2+ complex are retained at pH 5.2, though the modes of recognition of DNA by the two ligands are different. Minor groove width of DNA plays a role in the accommodation of the ligand(s) during the GC base specific recognition while positive charge of Mg2+ in CHR:Mg2+ complex further facilitates the association. Relatively lower affinity of the neutral drug and its Mg2+ complex for DNA can be ascribed to the self association of these ligands in the absence of DNA.

Reactivity of 3-HBA-6-hydroxylase with diethylpyrocarbonate and N-bromosuccinimide: effect of chemical modifications on kinetic and spectral properties of the enzyme.

The rapid inactivation of 3-HBA-6-hydroxylase by 100 microM diethylpyrocarbonate or 40 microM N-bromosuccinimide and protection offered by the substrate, 3-hydroxybenzoate, against these chemical modifications implicate the involvement of histidine and tryptophan in the catalytic activity of the enzyme. Inactivation of the enzyme by diethylpyrocarbonate followed pseudo-first-order kinetics, and an "n" value of 1.3 was obtained. Inactivation of the enzyme by N-bromosuccinimide was instantaneous and failed to follow pseudo-first-order kinetics. Distinct and incremental changes in the UV absorption, emission fluorescence, and near UV-CD spectra of the enzyme upon its titration with increasing concentrations of diethylpyrocarbonate or N-bromosuccinimide may be ascribed to modification and/or changes in the microenvironment of aromatic amino acid residue(s) such as tryptophan in the enzyme.

Interaction of 3-hydroxybenzoate with 3-hydroxybenzoate-6-hydroxylase.

The gradual quenching of the emission fluorescence of 3-HBA in the visible region upon titration with 3-HBA-6-hydroxylase and distinct changes in the near-UV circular dichroic spectrum of the enzyme in the presence of substrate suggest the formation of a stable enzyme-substrate complex. The binding of aromatic substrate 3-hydroxybenzoate to 3-hydroxybenzoate-6-hydroxylase occurs without gross changes in the backbone structure of the enzyme. The binding strength of the ES complex is partially reduced upon chemical modification of arginine, histidine, or tryptophan residues of enzyme, probably implicating their concerted action in the binding of substrate to enzyme. Partial inactivation of enzyme and diminished stability of the ES complex in response to treatment with 1 M urea could be ascribed to localized effects of the denaturant.

Interaction between antitumor antibiotic chromomycin A3 and Mg2+. I. Evidence for the formation of two types of chromomycin A3-Mg2+ complexes.

Chromomycin A3 (CHRA3) is an antitumor antibiotic which binds to Mg2+. In the present communication, we show, by means of equilibrium spectroscopic studies (such as absorption, fluorescence and circular dichroism), that two types of CHRA3-Mg2+ complexes (of 1:1 and 1.9:1 stoichiometries in terms of CHRA3:Mg2+, respectively) are formed depending on the concentrations of CHRA3 and Mg2+. The rate constant and activation energy for the formation of two complexes are different, thereby reinforcing the proposition that they are different molecular species. This observation is novel and significant in order to understand the anticancer property of the drug. It also provides explanation for earlier observations that site, affinity parameters and mode of interaction of the drug with DNA in the presence of Mg2+ depend on the relative concentration of Mg2+.

fMLP receptor stimulated activation of macrophage: its effect on killing of intracellular Leishmania donovani.

The fMLP receptor of peritoneal macrophages stimulated by fMLP grafted liposomes as ligand, was analysed and compared with respective controls for its ability to promote killing of intracellular Leishmania parasites. fMLP grafted liposomes show greater efficacy in killing intracellular L. donovani (MHOM/IN/1983/AG83) parasites in a time dependent manner than free fMLP. fMLP grafted liposomes also release more active oxygen intermediates and reactive nitrogen intermediates (O2-, H2O2, NO) than free fMLP. The key enzymes PKC and PTK for the respiratory burst and nitric oxide generation were found to be important in this fMLP receptor mediated signaling process as the enzyme specific inhibitors viz. staurosporine, genistein and AG126 suppressed the leishmanicidal effect of fMLP grafted liposomes. The above findings suggest that the fMLP receptor of macrophages activates PKC and PTK mediated signalling that is responsible for the intracellular parasite killing.

Myocardial infarction with topical cocaine anesthesia for nasal surgery.

Cocaine, the active alkaloid in coca leaf, is widely used as local anesthetic for otolaryngologic procedures. Our patient suffered an acute nontransmural myocardial infarction following clinical use of cocaine as topical anesthesia for nasal surgery, the first such case to be documented, to our knowledge. Although evidence documenting its cardiovascular toxicity is listed in contemporary pharmacologic literature, clinical cardiac injury has been reported to date only with the recreational use of cocaine. Authentic documentation of drug composition when received through the intervention of illicit vendors is always difficult. The literature is reviewed, justifying the use of cocaine as the most popular topical anesthetic in otolaryngologic practice. However, we hope that awareness of this possible complication will create a resurgence of research interest in topical cocaine anesthesia.

One-stage "front" and "back" correction for rigid cervical kyphosis. A safer technique of correction for a rare case of adult-onset Still's disease.

This report describes a new safe technique for surgical correction of rigid cervical kyphosis, in a very rare case of adult-onset Still's disease. It differs from all the previously mentioned reports of similar corrective osteotomies, the essential difference being a combined anterior (front) and posterior (back) approach performed at one stage (under a single anesthesia). The "front" is a release procedure of an open-wedge variety, and the "back" is a closed-wedge type of osteotomy. Such a double procedure ensures a slow and controlled correction at the preoperatively determined level, rather than a snapshot, rapid, and often a violent correction, which may occur at an undesired level. This osteotomy is performed under general anesthesia after an endotracheal intubation by a special "guided" maneuver. This new technique, the authors believe, is only a more comfortable option for the surgeon, but also a safer alternative for the patient.