Intra-gastric balloons have been in use as an aide to weight loss. Since its introduction, it has evolved from air filled to saline filled intra-gastric balloons. The SPATZ-ABS is a new adjustable saline filled balloon.
PRESENTATION OF CASE
Three patients have presented to our hospital as emergencies due to complications arising from this balloon. Two of these patients required emergency laparotomy and resection of small bowel due to pressure necrosis effects of the anchoring device. One patient had migration of the device into the duodenum that was removed endoscopically. Of the 2 patients who underwent a laparotomy, one patient did not have any symptoms or signs that correlated with the intra-operative findings.
The anchoring device meant to prevent the intra-gastric balloon from migrating distally has migrated in three patients. To our knowledge, there has been no reported incident of migration of this device. These serious complications pose a risk to patients having these balloons fitted.
There is a need to study our experience with a larger population of patients who have had this device inserted. Its safety needs to be questioned and its design may need to be addressed.
Intra-gastric adjustable balloon system; Anchoring device; Migration; Infarction; Resection
Bacterial toxins possess specific mechanisms of binding and uptake by mammalian cells. Mycoplasma pneumoniae CARDS (Community Acquired Respiratory Distress Syndrome) toxin is a 68 kDa protein, which demonstrates high binding affinity to human surfactant protein-A and exhibits specific biological activities including mono-ADP ribosylation and vacuolization. These properties lead to inflammatory processes in the airway and a range of cytopathologies including ciliostasis, loss of tissue integrity and injury, and cell death. However, the process by which CARDS toxin enters target cells is unknown. In this study, we show that CARDS toxin binds to mammalian cell surfaces and is internalized rapidly in a dose and time-dependent manner using a clathrin-mediated pathway, as indicated by inhibition of toxin internalization by monodansylcadaverine but not by methyl-β-cyclodextrin or filipin. Furthermore, the internalization of CARDS toxin was markedly inhibited in clathrin-depleted cells.
Mycoplasma pneumoniae continues to be a significant cause of community-acquired pneumonia and can manifest as fulminant disease leading to mortality in healthy individuals.
Background. Mycoplasma pneumoniae continues to be a significant cause of community-acquired pneumonia and, on rare occasions, manifests as fulminant disease that leads to mortality, even in healthy individuals.
Methods. We conducted a retrospective study on members of a family who were quarantined by the Centers for Disease Control and Prevention in 2002 for respiratory failure and death of a 15-year-old brother (sibling 1) and a 13-year-old sister (sibling 2). Collected airway, cerebrospinal fluid (CSF), and serum samples from both deceased siblings and serum samples from both parents and the remaining 3 ill siblings (sibling 3–5) were tested using a range of diagnostic assays. Autopsy lung tissue samples from sibling 2 were also assessed using immunohistochemical and immunoelectron microscopic methods.
Results. Autopsy evaluation of sibling 1 revealed cerebral edema consistent with hypoxic ischemic encepatholopathy and pulmonary findings of bronchiolitis obliterans with organizing pneumonia (BOOP). Postmortem lung examination of sibling 2 revealed lymphoplasmacytic bronchiolitis with intraluminal purulent exudate, BOOP, and pulmonary edema. Results of diagnostic assays implicated the household transmission of M. pneumoniae among all 5 siblings and both parents. Further analysis of lung tissue from sibling 2 demonstrated the presence of M. pneumoniae organisms and community-acquired respiratory distress syndrome toxin. M. pneumoniae was cultured directly from sibling 2 autopsy lung tissue.
Conclusion. Evidence is provided that M. pneumoniae was readily transmitted to all members of the household and that the resulting infections led to a spectrum of individual responses with variation in disease progression, including lymphoplasmacytic bronchiolitis, BOOP, and death.
Mice were infected with Mycoplasma pneumoniae and monitored for the synthesis and distribution of the unique adenosine diphosphate–ribosylating and vacuolating Community Acquired Respiratory Distress Syndrome (CARDS) toxin in bronchiolar lavage fluid (BALF) and lung. We noted direct relationships between the concentration of CARDS toxin and numbers of mycoplasma genomes in BALF and the degree of histologic pulmonary inflammation. Immunostaining of lungs revealed extensive colonization by mycoplasmas, including the detection of CARDS toxin in the corresponding inflamed airways. Lung lesion scores were higher during the early stages of infection, decreased gradually by day 14 postinfection, and reached substantially lower values at day 35. Infected mouse immunoglobulin (Ig) M and IgG titers were positive for CARDS toxin as well as for the major adhesin P1 of M. pneumoniae. These data reinforce the proposed pathogenic role of CARDS toxin in M. pneumoniae–mediated pathologies.
Mycoplasma pneumoniae is the smallest self-replicating bacterium with a streamlined genome of 0.81 Mb. Complete genome analysis revealed the presence of multiple copies of four large repetitive elements (designated RepMP1, RepMP2/3, RepMP4 and RepMP5) that are implicated in creating sequence variations among individual strains. Recently, we described RepMP1-associated sequence variations between reference strain M129 and clinical isolate S1 that involved three RepMP1-genes (i.e. mpn130, mpn137 and mpn138). Using PCR and sequencing we analyze 28 additional M. pneumoniae strains and demonstrate the existence of S1-like sequence variants in nine strains and M129-like variants in the remaining nineteen strains. We propose a series of recombination steps that facilitates transition from M129- to S1-like sequence variants. Next we examined the remaining RepMP1-genes and observed no other rearrangements related to the repeat element. The only other detected difference was varying numbers of the 21-nucleotide tandem repeats within mpn127, mpn137, mpn501 and mpn524. Furthermore, typing of strains through analysis of large RepMPs localized within the adhesin P1 operon revealed that sequence divergence involving RepMP1-genes mpn130, mpn137 and mpn138 is strictly type-specific. Once more our analysis confirmed existence of two highly conserved groups of M. pneumoniae strains.
Mycoplasma pneumoniae respiratory infection is a common cause of acute respiratory infection in children and adults. We evaluated the efficacy of increasing dosages of clarithromycin for the optimized therapy of M. pneumoniae respiratory infection in a mouse model.
BALB/c mice were intranasally inoculated once with M. pneumoniae or SP4 broth (control). Groups of mice were treated with increasing dosages of clarithromycin (10, 25 or 75 mg/kg/day) or placebo subcutaneously daily. Groups of mice were evaluated after 1, 2, 3, 6 and 12 days of therapy. Outcome variables included quantitative M. pneumoniae culture, histopathological score of the lungs, bronchoalveolar lavage (BAL) cytokine/chemokine/growth factor concentrations and plethysmography after aerosolized methacholine to assess airway hyperresponsiveness.
Elevated dosages of clarithromycin resulted in greater antimicrobial efficacy with significantly reduced M. pneumoniae quantitative cultures (P < 0.05), as well as greater improvement in markers of disease severity with significantly reduced lung histopathology scores, BAL cytokine concentrations and airway hyperresponsiveness (P < 0.05).
Escalated dosing of clarithromycin resulted in significantly greater therapeutic efficacy in the treatment of experimental M. pneumoniae respiratory infection.
macrolides; cytokines; asthma; pharmacokinetics; pharmacodynamics
Faciomaxillary and oral surgical procedures are frequently done under local anesthesia. Only few techniques are used widely in these areas in spite of the numerous blocks available. Knowledge about these techniques could encourage use of these techniques for the benefit of patients and operators’ comfort. Leaving aside the commonly used intraoral anesthetic technique by faciomaxillary and dental surgeons, focus is given on regional blocks of extraoral route, like maxillary block, mandibular block, superficial cervical plexus block, forehead and scalp block, trigeminal nerve block, sphenopalatine nerve block, and they are discussed with their indications and technical details involved in administering them. Advantages of using the regional blocks over general anesthesia and multiple pricks include reduced dosage and number of needle pricks. Pediatric considerations like prolonged duration of anesthesia and wider area of action for regional blocks warrant that they should be used with caution.
Faciomaxillary; nerve blocks; regional blocks
The mandibular foramen (MF) is an opening on the internal surface of the ramus for divisions of the mandibular vessels and nerve to pass. The aim of this study is to determine the position of the MF from various anatomical landmarks in several dry adult mandibles.
Materials and Methods:
A total of 102 human dry mandibles were examined, of which 93 were of dentulous and 9 were of edentulous. The measurements were taken from the anterior border of the ramus (coronoid notch) to the midportion of the MF and then from the midportion of the MF to the other landmarks such as internal oblique ridge, inferior border, sigmoid notch, and condyle were measured and recorded.
The data were compared using Student's t-test. The MF is positioned at a mean distance of 19 mm (with SD 2.34) from coronoid notch of the anterior border of the ramus. Superio-inferiorly from the condyle to the inferior border MF is situated 5 mm inferior to the midpoint of condyle to the inferior border distance (ramus height).
We conclude that failures in the anesthesia of the inferior alveolar nerve are due to the operator error and not due to the anatomical variation.
Failure of anesthesia; inferior alveolar nerve; mandible foramen
Ruta graveolens L., is a odoriferous herb belonging to the family Rutaceae. It is the source of Rue or Rue oil, called as Sadab or Satab in Hindi. It is distributed throughout the world and cultivated as a medicinal and ornamental herb. The ancient Greeks and Romans, held the plant in high esteem. It is used in Ayurveda, Homoeopathy and Unani. Phytochemical constituents and pharmacological properties were studied in depth. In 14 species of genus Ruta, R. graveolens and R. chalepensis are available in India and also cultivated in gardens. Taxonomical characters to identify the Indian plants are very clear with fringed and or non-fringed petals. However, references to it are confused in the traditional literature. Due to sharing of regional language name, its identity is confused with Euphorbia dracunculoides. Morphological and anatomical characters were described. Pharmacognostic studies with microscopic characters were also published. Upon reviewing the anatomical characters and pharmacognostic characters one finds that it is highly confused and conflicting. The characters described are opposite of each other and authenticity of the market sample of R. graveolens cannot be guaranteed and able to be differentiated from R. chalepensis. Present work is to describe the pharmacognostic characters of R. graveolens to differentiate it from R. chalepensis. It is concluded that morphologically, R. graveolens can be identified with its non-fringed petals and blunted apices of fruit lobes. Whereas, in R. chalepensis petals are fringed or ciliated and apices of the fruit lobes are sharp and projected. Microscopically, in stem of R. graveolens pericyclic fibers have wide lumen. Whereas, in R. chalepensis, it is narrow. The published pharmacognosy reports do not pertain to authentic plant or some of the characteristic features like glandular trichomes are not observed in our samples.
Pharmacognosy; ruta chalepensis; ruta graveolens; rutaceae
Gmelina asiatica Linn (G. parvifolia Roxb.) is a large shrub or a small tree. Roots and aerial parts are used in Ayurvedic medicine and also have ethno-medical uses. Root is reported as adulterant to G. arborea roxb roots. Pharmacognostical characters of root were reported. Owing to the shortage of genuine drug and ever-increasing demands in market, it becomes necessary to search an alternative with equal efficacy without compromising the therapeutic value. Nowadays, it becomes a common practice of using stem. In case of roots phytochemical and pharmacological analysis of stem was reported. However, there is no report on the pharmacognostical characters of stem and to differentiate it from roots. The present report describes the botanical pharmacognostical characters of stem and a note to differentiate it from root. Hollow pith, faint annual rings in cut ends, alternatively arranged macrosclereids and bundle cap fibers, and presence of abundant starch grains and calcium oxalates in pith and in ray cells are the diagnostic microscopic characters of stem. Stem pieces can be differentiated from roots by absence of tylosis.
Botanical pharmacognosy; ethnobotany; Gmelina arborea; Gmelina asiatica; pharmacognosy; root; stem
Community-acquired respiratory distress syndrome toxin (CARDS TX) from M. pneumoniae was cloned, expressed, purified and crystallized. A diffraction data set from a native CARDS TX crystal was obtained at 2.2 Å resolution.
Community-acquired respiratory distress syndrome toxin (CARDS TX) is a 591-amino-acid protein with ADP-ribosyltransferase and vacuolating activities that damages the cells lining the respiratory tracts of patients infected with the bacterial pathogen Mycoplasma pneumoniae. Crystals of CARDS TX were grown in space group C2, with unit-cell parameters a = 191.4, b = 107.4, c = 222.1 Å, β = 90.6°. A complete 2.2 Å data set was obtained from a single CARDS TX crystal.
CARDS TX; community-acquired respiratory distress syndrome; Mycoplasma pneumoniae; ADP-ribosyltransferases; ADP-ribosylation
Basal cell carcinoma accounts for 70–80% of all cutaneous malignancies in the head, face and neck region . This article reports a case of basal cell carcinoma involving the ala of the nose with the excision of the lesion and reconstruction.
Bilobed flap; Ala reconstruction; Nasolabial fold
Histone and protein acetylation catalyzed by p300/CBP transcriptional coactivator regulates a variety of key biological pathways. This study investigates the proposed Theorell-Chance or “hit-and-run” catalytic mechanism of p300/CBP histone acetyltransferase (HAT) using bisubstrate analogs. A range of histone peptide tail peptide-CoA conjugates with different length linkers were synthesized and evaluated as inhibitors of p300 HAT. We show that longer linkers between the histone tail peptide and the CoA substrate moieties appear to allow for dual engagement of the two binding surfaces. Results with D1625R/D1628R double mutant p300 HAT further confirm the requirement for a negatively charged surface on the enzyme to interact with the histone tail.
Alar rim defects are most commonly acquired as a result of trauma, burns, tumor excision or sometimes accompanying craniofacial clefts. However, isolated congenital alar defects are extremely rare occurring in about 1 in 20,000 to 40,000 live births. We are presenting a case report of an isolated congenital cleft of the alar rim. The defect was closed by the use of a rotation advancement full-thickness flap. With this technique, both symmetry and desired thickness of the nostrils were achieved. The skin color and texture of the alar rim were good with minimal scars.
Advancement rotation flap; alar cleft; congenital; nasal deformities
We identified Mpn133 as a Ca2+-dependent cytotoxic nuclease of Mycoplasma pneumoniae. Flow cytometry analysis and immunofluorescence studies revealed the binding and internalization of recombinant Mpn133 (rMpn133) in human airway A549 cells. Amino acid sequence comparisons of Mpn133 with other mycoplasma nucleases demonstrated the presence of a unique glutamic acid, lysine and serine rich region (EKS region; amino acids 72–110). Deletion of this EKS peptide (rMpn133Δ72–110) abrogated its binding and internalization but not its nuclease activity. The function of the EKS region in host cell trafficking and nuclear localization was reinforced by the successful delivery of EKS-conjugated mCherry protein into A549 cells. rMpn133, but not rMpn133Δ72–110, induced apoptosis-like death in A549 cells. This observation suggested a unique role of Mpn133 as an important contributor to M. pneumoniae-associated life cycle events and as a virulence factor in host-associated cytopathologies. In addition, the distinct property of the EKS peptide in delivery of proteins, like mCherry, into target cells opens new avenues to the establishment of novel concepts of drug delivery and therapy.
Mycoplasma pneumoniae; Mpn133; nuclease; apoptosis; lysine rich region
Recently, we identified an ADP-ribosylating and vacuolating cytotoxin in Mycoplasma pneumoniae designated Community Acquired Respiratory Distress Syndrome (CARDS) toxin. In this study we show that vacuoles induced by recombinant CARDS (rCARDS) toxin are acidic and derive from the endocytic pathway as determined by the uptake of neutral red and the fluid-phase marker, Lucifer yellow, respectively. Also, we demonstrate that the formation of rCARDS toxin-associated cytoplasmic vacuoles is inhibited by the vacuolar ATPase inhibitor, bafilomycin A1, and the ionophore, monensin. To examine the ontogeny of these vacuoles, we analyzed the distribution of endosomal and lysosomal membrane markers during vacuole formation and observed the enrichment of the late endosomal GTPase, Rab9, around rCARDS toxin-induced vacuoles. Immunogold-labeled Rab9 and overexpression of green fluorescent-tagged Rab9 further confirmed vacuolar association. The late endosomal- and lysosomal-associated membrane proteins, LAMP1 and LAMP2, also localized to the vacuolar membranes, while the late endosomal protein, Rab7, and early endosomal markers, Rab5 and EEA1, were excluded. HeLa cells expressing dominant-negative (DN) Rab9 exhibited markedly reduced vacuole formation in the presence of rCARDS toxin, in contrast to cells expressing DN-Rab7, highlighting the importance of Rab9 function in rCARDS toxin-induced vacuolation. Our findings reveal the unique Rab9-association with rCARDS toxin-induced vacuoles and its possible relationship to the characteristic histopathology that accompanies M. pneumoniae infection.
Balanophora fungosa Forster & Forster ssp. indica (Arn.) B. Hansen var. indica, (Balanophoraceae) syn. B. indica, is a root parasite found in hills of south India. This plant is included in the list of negative list, which are restricted and prohibited for export. Though it is not an official drug in any of the indigenous systems of medicine in India, it is used in tribal medicines in south India. However, it is found in crude drug markets as substitute/adulterant for the Ayurvedic drug Gajapippali (Scindapsus officinalis). Few phytochemical constituents were reported on this plant. However, there is no pharmacognostical report to authenticate the commercial samples of B. fungosa and to differentiate them from Scindapsus officinalis. This article describes the pharmacognostical characteristics of Balanophora fungosa and diagnostic features to differentiate it from Scindapsus officinalis.
Balanophora fungosa Forster & Forster ssp. Indica (Arn.) B. Hansen var. Indica; B. indica (Arn.) Wallich ex Griffith; Langsdorffia indica Arn.; Balanophoraceae; root parasite; pharmacognosy; ethnobotany; indigenous systems of medicine; Gajapippali; Scindapsus officinalis; adulterant; substitute; Negative list; prohibited plants
In this study, we identified and characterized the enzymatic properties of MG_186, a calcium-dependent Mycoplasma genitalium nuclease. MG_186 displays the hallmarks of nucleases, as indicated by its amino acid sequence similarity to other nucleases. We cloned, UGA corrected, expressed, purified, and demonstrated that recombinant MG_186 (rMG_186) exhibits nuclease activity similar to that of typical sugar-nonspecific endonucleases and exonucleases. Biochemical characterization indicated that Ca2+ alone enhances its activity, which was inhibited by divalent cations, such as Zn2+ and Mn2+. Chelating agents EGTA and EDTA also inhibited nuclease activity. Mycoplasma membrane fractionation and Triton X-114 phase separation showed that MG_186 was a membrane-associated lipoprotein, and electron microscopy revealed its surface membrane location. Incubation of purified human endometrial cell nuclei with rMG_186 resulted in DNA degradation and morphological changes typical of apoptosis. Further, immunofluorescence analysis of rMG_186-treated nuclei indicated that morphological changes were linked to the disintegration of lamin and the internalization of rMG_186. Since M. genitalium has the capacity to invade eukaryotic cells and localize to the perinuclear and nuclear region of parasitized target cells, MG_186 has the potential to provide M. genitalium, which possesses the smallest genome of any self-replicating cell, with the ability to degrade host nucleic acids both as a source of nucleotide precursors for growth and for pathogenic purposes.
The advent of transoral microlaryngoscopic laser surgery is making a significant impact on treatment decisions in the management of early squamous cancers of the larynx and the hypopharynx. It has, to a great extent replaced the conventional open partial laryngectomy procedures. Moreover many cancers of the larynx or the hypopharynx that were earlier being treated with radiation therapy are now resected transorally with the CO2 laser. This article focuses on the progress of transoral laser microsurgery in the management of early larygopharyngeal cancers.
Transoral CO2 laser microsurgery; glottic carcinoma; supraglottic carcinoma; carcinoma hypopharynx
The histone acetyltransferase (HAT) p300/CBP has been shown to undergo autoacetylation on lysines in an apparent regulatory loop that stimulates HAT activity. Here we developed a strategy to introduce acetyl-Lys at up to six known modification sites in p300/CBP HAT using a combination of circular permutation and expressed protein ligation. We show that these semisynthetic, circularly permuted acetylated proteins retain high affinity for an acetyl-CoA substrate analog and that HAT activity correlates positively with degree of acetylation. This study provides novel evidence for control of p300/CBP HAT activity by site-specific autoacetylation and outlines a potentially general strategy to use expressed protein ligation and circular permutation to chemically interrogate internal regions of proteins.
Acute toxic leukoencephalopathy may be caused by endogenous or exogenous toxins. It may reverse clinically if the offending agent is withdrawn or the underlying condition is treated. However, demonstration of reversibility on imaging, especially with diffusion-weighted MRI, has been reported only very recently. We report two such cases.
5-FU; diffusion restriction; leukoencephalopathy; uremia
Mycoplasma penetrans is a urogenital tract pathogen implicated in the deterioration of the immune system in human immunodeficiency virus-infected AIDS patients. Here, we describe a 78-kDa protein from M. penetrans, designated MYPE9110, that exhibits sequence similarity to known ADP-ribosyltransferases (ADPRTs) such as Bordetella pertussis pertussis toxin and Mycoplasma pneumoniae community-acquired respiratory distress syndrome toxin. MYPE9110 possesses key amino acid residues found in all ADPRTs that are essential for ADPRT activity. Several mammalian cell proteins are ADP-ribosylated by MYPE9110, and the full-length recombinant protein exhibits a strong auto-ADP-ribosylating activity. In the absence of target proteins, MYPE9110 demonstrates a NAD-glycohydrolase activity by hydrolyzing NAD. Furthermore, this toxin elicits cytopathology in HeLa cells by inducing cytoplasmic vacuolization in the presence of ammonium chloride. The deletion of the C-terminal region of MYPE9110 significantly diminishes its binding to host cells while still exhibiting an ADPRT activity, suggesting that MYPE9110 is a member of the family of A-B ADPRT toxins.
Mycoplasma pneumoniae and Mycoplasma genitalium are closely related organisms that cause distinct clinical manifestations and possess different tissue predilections despite their high degree of genome homology. We reported earlier that surface-localized M. pneumoniae elongation factor Tu (EF-TuMp) mediates binding to the extracellular matrix component fibronectin (Fn) through the carboxyl region of EF-Tu. In this study, we demonstrate that surface-associated M. genitalium EF-Tu (EF-TuMg), in spite of sharing 96% identity with EF-TuMp, does not bind Fn. We utilized this finding to identify the essential amino acids of EF-TuMp that mediate Fn interactions by generating modified recombinant EF-Tu proteins with amino acid changes corresponding to those of EF-TuMg. Amino acid changes in serine 343, proline 345, and threonine 357 were sufficient to significantly reduce the Fn binding of EF-TuMp. Synthetic peptides corresponding to this region of EF-TuMp (EF-TuMp 340-358) blocked both recombinant EF-TuMp and radiolabeled M. pneumoniae cell binding to Fn. In contrast, EF-TuMg 340-358 peptides exhibited minimal blocking activity, reinforcing the specificity of EF-Tu-Fn interactions as mediators of microbial colonization and tissue tropism.