Quorum-sensing system in Acinetobacter baumannii: a potential target for new drug development.

Acinetobacter baumannii causes several nosocomial infections and poses major threat when it is multidrug resistant. Even pan drug-resistant strains have been reported in some countries. The intensive care unit (ICU) mortality rate ranged from 45.6% to 60.9% and it is as high as 84.3% when ventilator-associated pneumonia was caused by XDR (extensively drug resistant) A. baumannii. Acinetobacter baumannii constituted 9.4% of all Gram-negative organisms throughout the hospital and 22.6% in the ICUs according to a study carried out in an Indian hospital. One of the major factors contributing to drug resistance in A. baumannii infections is biofilm development. Quorum sensing (QS) facilitates biofilm formation and therefore the search for 'quorum quenchers' has increased recently. Such compounds are expected to inhibit biofilm formation and hence reduce/prevent development of drug resistance in the bacteria. Some of these compounds also target synthesis of some virulence factors (VF). Several candidate drugs have been identified and are at various stages of drug development. Since quorum quenching, inhibition of biofilm formation and inhibition of VF synthesis do not pose any threat to the DNA replication and cell division of the bacteria, chances of resistance development to such compounds is presumably rare. Thus, these compounds ideally qualify as adjunct therapeutics and could be administered along with an antibiotic to reduce chances of resistance development and also to increase the effectiveness of antimicrobial therapy. This review describes the state-of-art in QS process in Gram-negative bacteria in general and in A. baumannii in particular. This article elaborates the nature of QS mediators, their characteristics, and the methods for their detection and quantification. Various potential sites in the QS pathway have been highlighted as drug targets and the candidate quorum quenchers which inhibit the mediator's synthesis or function are enlisted.

A structural, epidemiological & genetic overview of Klebsiella pneumoniae carbapenemases (KPCs).

Klebsiella pneumoniae carbapenemases (KPCs) are plasmid encoded carbapenem hydrolyzing enzymes which have the potential to spread widely through gene transfer. The instability of upstream region of blaKPC accelerates emergence of different isoforms. Routine antibiotic susceptibility testing failed to detect KPC producers and some commercial kits have been launched for early identification of KPC producers. Notable among the drugs under development against KPC are mostly derivatives of polymixin; ß-lactamase inhibitor NXL104 with combination of oxyimino cephalosporin as well as with ceftazidime; a novel tricyclic carbapenem, LK-157, potentially useful against class A and class C enzymes; BLI-489-a bicyclic penem derivative; PTK-0796, a tetracycline derivative and ACHN-490. Combination therapy might be preferable to control KPC infections in immediate future. Clinicians are likely to opt for unconventional combinations of antibiotics to treat KPC infections because of unavailability of alternative agents. The KPCs have become endemic in many countries but there is no optimal treatment recommendation available for bacteria expressing KPCs. Reports of outbreaks involving KPCs have focused mainly on laboratory identification, empirical treatment outcomes and molecular epidemiology. This review includes information on the emergence of KPC variants, limitations of phenotyping methods, available molecular methods for identification of the KPC variants and treatment options highlighting the drugs under development.

Biomarkers for the management of pre-eclampsia in pregnant women.

Pre-eclampsia (PE) is a pregnancy related disorder characterized by hypertension and proteinuria noticeable after 20 wk of gestation. It is a leading cause of maternal and foetal mortality and morbidity worldwide. The aetiology of the disease is unknown, but recent studies have revealed that this disorder appears to originate in placenta and is characterized by widespread maternal endothelial dysfunction. Till date, delivery of placenta is the only cure for the disease. So, there is a need for the identification of highly specific and sensitive biochemical markers that would allow early identification of patients at risk and thus help in providing proper prenatal care. Several promising biomarkers have been proposed, alone or in combination, that may help in predicting women who are likely to develop PE. Maternal serum concentrations of these biomarkers either increase or decrease in PE during gestation. This review focuses on the various biomarkers available and their utility in predicting pre-eclampsia.

Infantile rhabdomyofibrosarcoma: a distinct variant or a missing link between fibrosarcoma and rhabdomyosarcoma?

Infantile rhabdomyofibrosarcoma (IRMFS) is a rare soft tissue tumour affecting infants and young children. It occupies an intermediate position between infantile fibrosarcoma and spindle cell rhabdomyosarcoma in its clinical presentation, behaviour, morphology, immunohistochemical and ultrastructural features. This case is reported here to reiterate its occurrence as tumour with distinct morphological immunohistochemical and clinical behavioral patterns.

Lymph node infarction--a rare complication associated with disseminated intra vascular coagulation in a case of dengue fever.

BACKGROUND: Lymph node infarction is known to occur in association with many non-neoplastic and neoplastic conditions however its occurrence in association with DIC is not reported hitherto in the literature. CASE PRESENTATION: We describe an unusual case of lymph node infarction in a twenty seven year old male following disseminated intravascular coagulation (DIC) in a case of dengue fever. Multiple sections of the infarcted and the surrounding non-infarcted lymph nodes failed to reveal any predisposing condition. How ever the parahilar vessels showed thrombotic occlusion, which must have been responsible for the infarction. CONCLUSION: Global infarction of the lymph node may mask the underlying pathology. Any malignancy especially lymphoma may coexist or follow lymph node infarction, therefore the patient needs constant surveillance.

Melatonin: an antioxidant protects against cyclosporine-induced nephrotoxicity.

BACKGROUND: Cyclosporine (CsA) causes a dose-related decrease in renal function in experimental animals. Different mediators for CsA nephrotoxicity have been suggested; oxygen free radicals are one of them. In experimental model of Wistar rats, the role of antioxidant melatonin (Mel), the main product of pineal secretion, was investigated in CsA nephrotoxicity. METHODS: Male Wistar rats were divided into four groups: saline control, 50 mg/kg CsA, 500 microg/kg Mel, and CsA + Mel. At the end of 14th day of treatment, blood urea, creatinine, malondialdehyde, and creatinine and lithium clearance were estimated. Histopathological examination of kidney from all the groups was performed. RESULTS: CsA caused marked elevation in blood urea, serum creatinine, and plasma malondialdehyde and a decrease in creatinine and lithium clearance. Mel significantly antagonized CsA-induced renal impairment. Microcalcification in corticomedullary junction seen with CsA was prevented by Mel. CONCLUSION: These results indicate that Mel, through its antioxidant properties, provides protection against CsA-induced nephrotoxicity.

Endobronchial metastasis from giant cell tumor of bone.

A young woman presented with cough, dyspnea on exertion, and weight loss. A chest roentgenogram revealed collapse of the left lung. On doing fiberoptic bronchoscopy, a growth was found in the left main bronchus. Cytologic examination and sections from cell block revealed that it was a metastatic growth from a giant cell tumor (GCT) of the bone. To the best of our knowledge, this is the first report of endobronchial metastasis from a GCT of the bone.

Carvedilol: a beta blocker with antioxidant property protects against gentamicin-induced nephrotoxicity in rats.

Gentamicin is an antibiotic effective against gram negative infections, whose clinical use is limited by its nephrotoxicity. Since the pathogenesis of gentamicin-induced nephrotoxicity involves oxygen free radicals, the antioxidant carvedilol may protect against gentamicin-induced renal toxicity. We therefore tested this hypothesis using a rat model of gentamicin nephrotoxicity. Carvedilol (2 mg/kg) was administered intraperitoneally 3 days before and 8 days concurrently with gentamicin (80 mg/kg BW). Estimations of urine creatinine, glucose, blood urea, serum creatinine, plasma and kidney tissue malondialdehyde (MDA) were carried out, after the last dose of gentamicin. Kidneys were also examined for morphological changes. Gentamicin caused marked nephrotoxicity as evidenced by increase in blood urea, serum creatinine and decreased in creatinine clearance. Blood urea and serum creatinine was increased by 883% and 480% respectively with gentamicin compared to control. Carvedilol protected the rats from gentamicin induced nephrotoxicity. Rise in blood urea, serum creatinine and decrease in creatinine clearance was significantly prevented by carvedilol. There was 190% and 377% rise in plasma and kidney tissue MDA with gentamicin. Carvedilol prevented the gentamicin induced rise in both plasma and kidney tissue MDA. Kidney from gentamicin treated rats, histologically showed necrosis and desquamation of tubular epithelial cells in renal cortex, whereas it was very much comparable to control with carvedilol. In conclusion, carvedilol with its antioxidant property protected the rats from gentamicin-induced nephrotoxicity.

Surgical pathology of mitral valves--the Indian scene.

Of the 75 cardiac valves excised at surgery over a 2 year period, 54 were mitral valves. Using simple morphological criteria along with clinical data, the valves were assigned to 2 major groups, rheumatic and non-rheumatic. The group with rheumatic disease accounted for 90% of cases. Mitral stenosis, incompetence and combined stenosis with incompetence were encountered with equal frequency (38, 38 and 24%). Mitral insufficiency of rheumatic etiology, no longer considered to be a major problem in the west, continues to be frequent in India. An increased incidence of mitral regurgitation in young females is an important feature noticed in this series.

Penetrating keratoplasty in xeroderma pigmentosum. Case reports and review of the literature.

Xeroderma pigmentosum is an uncommon inherited disorder characterized by hypersensitivity to ultraviolet radiation, with defective repair of DNA damage caused by short-wavelength radiation. Corneal complications of this disorder may require penetrating keratoplasty for visual rehabilitation. Surgery is rarely undertaken in these eyes due to multiple associated problems involving the ocular surface and the lids. We report three cases of successful penetrating keratoplasty in xeroderma pigmentosum and review nine cases reported earlier. Successful grafts were achieved in all 12 eyes initially. Persistent superficial punctate keratopathy was observed in one eye and graft rejection episodes in five eyes. However, graft failure occurred due to an untreated rejection episode in only one eye. Another eye was treated by exenteration for recurrent ocular malignancies. This report highlights the encouraging results of penetrating keratoplasty in carefully selected patients of xeroderma pigmentosum with corneal pathology.

Clinicohistopathological findings of gelatinous droplike corneal dystrophy among Asians.

We describe the findings in nine Asian-Indian patients with gelatinous droplike corneal dystrophy (GDCD). Most patients showed initial signs of bilateral decreased vision and photophobia at an early age. The siblings were affected in four cases, and parental consanguinity was recorded in seven cases. We classified the disease into three forms based on clinicopathologic findings. Clinically, the mild form of the disease was evidence by central subepithelial, whitish-yellow, nodular lesions that corresponded to the subepithelial nodular deposits seen histologically. In the moderate form, the lesions coalesced, forming central, diffuse subepithelial lesions with superficial vascularization. On histology, the amyloid deposits assumed a sheetlike distribution in the subepithelial regions and in the superficial stroma. Aggregates of chronic inflammatory cells and stromal neovascularization were seen in the adjacent stroma. The severe form presented as diffuse, whitish opacification of the cornea with extensive neovascularization and scarring. Histologically this form was characterized by a visible plaque of vascularized scar tissue that partly replaced the stroma and enveloped the amyloid deposits. Frequent, early recurrence of the disease was noted in the grafts. This study provides a detailed clinicopathologic description of GDCD from the Indian subcontinent. We also discuss previously unreported findings from the most advanced stage of the disease.

Intraosseous schwannoma of the cervical spine associated with skeletal fluorosis.

Intraosseous Schwannoma of the cervical spine is very rare. Its association with skeletal fluorosis is also extremely rare. A case of successfully treated intraosseous neurofibroma of the cervical spine associated with skeletal fluorosis causing tetraparesis is reported. The clinical features, diagnostic aspects and the management is described and the literature is reviewed.

Posterior mediastinal paravertebral hydatid cyst presenting as spinal compression. A case report.

A primary posterior mediastinal hydatic cyst presenting with spinal compression syndrome is rare. We describe the case of a 35-year-old lady with a posterior mediastinal hydatid cyst who presented with progressive paraplegia. Excision of cyst was followed by systemic Albendazole therapy. She showed neurological recovery without recurrence till now. The role of Albendazole in preventing recurrence has been stressed and the relevant literature has been reviewed.

Extramedullary glioma of the cervicodorsal spinal cord--a case report.

Extramedullary gliomas are rare and usually have an intramedullary component. A case of extramedullary astrocytoma without intramedullary mass in an adolescent girl has been reported.

The spectrum of glomerular diseases in the kingdom of bahrain: an epidemiological study based on renal biopsy interpretation.

Glomerular diseases continue to be the leading cause of end-stage renal disease globally. Hence it is important to recognize the glomerular disease pattern in any given geographical area to understand the pathobiology in the region as well as the incidence and progression of the disorder. A total of 498 renal biopsies were performed on patients with proteinuria, hematuria, and mild to moderate renal impairment during a period of 13 years (between January 1990 and December 2002) at a tertiary care hospital. Primary glomerular disease accounted for two-thirds of the glomerular diseases, which was 44.8% of all renal biopsies. The most common histological lesion was minimal change disease (30%). Focal segmental glomerulosclerosis was the second most common lesion (23.8%) followed by membranoproliferative glomerulonephritis (14.3%). Secondary glomerular disease included 33.6% of glomerular diseases with 22.7% with lupus nephritis as the commonest lesion (38.9%) followed by diabetic nephropathy (31.9%) and hypertension (20.4%). Tubulointerstitial diseases accounted for 13.1% of all renal biopsies, whereas transplant diseases were noted in 12.2%. The miscellaneous group including inadequate biopsies, which constituted 7.2% of all the tissues. The results of this analysis were compared with surveys from other parts of the world.

Diagnostic dilemma of an intramedullary vascular malformation. A case report.

A young man was seen at a neurologic center for a slowly progressive myelopathy involving the lower limbs in 1983. After examination and investigations, a diagnosis of chronic tuberculous spinal arachnoiditis was made and the patient was administered antituberculous treatment. However, his condition continued to deteriorate. He was reviewed at another center in 1985, where a diagnosis of demyelinating disorder was made, for which he was treated. However, this also did not help, and he was diagnosed as having a nonspecific spinal arachnoiditis at yet another center in 1988. His condition continued to worsen, and after ten years of symptoms, when magnetic resonance imaging (MRI) was done, an intramedullary cystic lesion opposite D-12 vertebrae was seen, which on histopathology was proved to be a vascular malformation. After excision of the lesion his neurologic status has been slowly improving. The conditions that a malformation could mimic, misleading a clinician, and the role of MRI in clinching the diagnosis are highlighted.

Diagnostic utility of fine-needle sampling without aspiration: a prospective study.

Fine-needle sampling without aspiration (FNS) was done in 100 consecutive patients with 109 palpable masses. Its efficiency in obtaining adequate material is compared with conventional fine-needle aspiration cytology (FNAC) and found to be 80% with either method. FNS shows a diagnostic accuracy that correlates well with FNAC and histopathology. Malignant lesions are sampled more easily. Anatomic site has no influence on the yield. Most of the negative cases are small swellings, less than 1.5 cm in diameter. It is more cost effective than FNAC. Trauma to the tissues and the resultant artifacts are less. It is relatively painless and can safely be applied to many areas, including some sensitive sites.

Amyloidosis of the iris.

A case of ocular lepromatous leprosy with secondary amyloidosis of the iris is reported.

Splenic hemangiomatosis with osseous involvement.

A rare case of splenic hemangiomatosis with bone involvement in the upper extremity is presented. The findings on ultrasonography and CT scan abdomen were suggestive of splenic hemangiomatosis. X-ray of left forearm showed findings characteristic of osseous hemangiomatosis, which was subsequently confirmed on histology.

Conjunctival and corneal peroxidases in vitamin A deficiency.

Xerophthalmia is a commonly encountered nutritional disorder that affects the growing population of the world. Conjunctival and corneal epithelial cells contain peroxidase enzyme. In experimentally induced Vitamin A deficiency conjunctival and corneal peroxidases are markedly lowered indicating direct or indirect relation of Vitamin A to epithelial functional integrity.