Molecular characterization of CTX-Mβ-lactamases among Klebsiella pneumoniae isolated from patients at Tehran hospitals

Purpose: Plasmid-encoded CTX-M-group of extended-spectrum β-lactamases (ESBLs) represent a significant and rapidly emerging problem in most part of the world. The aim of the present study was to describe the prevalence of CTX-M producing Klebsiella pneumoniae at Tehran hospitals. Materials and Methods: Clinical isolates of K. pneumoniae (n=250) were collected from 10 hospitals of Tehran. Susceptibility to antimicrobial agents, MIC of cefotaxime and ESBLs production of collected isolates were detected. All ESBL-producing isolates were screened for bla_CTX-M genes using PCR and DNA sequencing. Molecular typing of bla_CTX-M harboring isolates was performed by Pulsed–field gel electrophoresis assay. Results: Of 250 K. pneumoniae clinical isolates, 102 isolates revealed ESBLs – phenotype. PCR assay and sequencing detected bla_CTX-M genes in 71.5% (n= 73) of ESBL-producing isolates. The prevalence of CTX-M -I and CTX-M-III clusters among these isolates was 35.61% (n=26) and 21.9 % (n=16) respectively. Coexistence of CTX-M -I and CTX-M-III clusters was found among 42.5% (n= 31) of isolates. Of 102 isolates that were positive in the phenotypic confirmatory test (PCT), 29 isolates (28.4%) did not produce any amplicons in PCR for bla_CTX-M gene. The results of PCR for CTX-M -II and CTX-M-IV clusters were also negative. Analysis of the 31 CTX-M producing K. pneumoniae isolates by PFGE typing showed 26 distinct patterns. Conclusions: The bla_CTX-M genes are widespread among Iranian isolates of K. pneumoniae. PFGE demonstrated the high diversity of K. pneumoniae harboring bla_CTX-M in our study.     

Discovery of Imidazopyridines as Potent Inhibitors of Indoleamine 2,3-Dioxygenase 1 for Cancer Immunotherapy

Indoleamine 2,3-dioxygenase 1 (IDO1) has been identified as a target for small-molecule immunotherapy for the treatment of a variety of cancers including renal cell carcinoma and metastatic melanoma. This work focuses on the identification of IDO1 inhibitors containing replacements or isosteres for the amide found in BMS-986205, an amide-containing, IDO1-selective inhibitor currently in phase III clinical trials. Detailed subsequently are efforts to identify a structurally differentiated IDO1 inhibitor via the pursuit of a variety of heterocyclic isosteres, leading to the discovery of highly potent, imidazopyridine-containing IDO1 inhibitors.     

Involvement of hypothalamic pituitary adrenal axis on the effects of nifedipine in the development of morphine tolerance in rats

It has been shown that nifedipine, as a calcium channel blocker, can attenuate the development of tolerance to the antinociceptive effect of morphine; however, the role of HPA axis on this action has not been elucidated. We examined the effect of nifedipine on morphine analgesic tolerance in intact and adrenalectomized (ADX) rats and on HPA activity induced by morphine. Adult male rats were rendered tolerant to morphine by daily injection of morphine (15 mg/kg i.p.) for 8 days. To determine the effect of nifedipine on the development of morphine tolerance, nifedipine (1, 2 and 5 mg/kg i.p.) was injected concomitant with morphine. The tail-flick test was used to assess the nociceptive threshold, before and 30 min after morphine administration in days 1, 3, 5 and 8. Our results showed that despite the demonstration of tolerance in both ADX and sham operated rats, nifedipine in ADX rats prevented morphine tolerance development at a lower dose (2 mg/kg) than in sham operated rats, however corticosterone replacement prevented nifedipine effect in ADX rats. Acute administration of morphine produced significant increase in plasma corticosterone level, and with repeated injection, a tolerance to this neurosecretory effect was developed. Nifedipine (5 mg/kg) attenuated the acute effect of morphine, but could not block its neurosecretory tolerance.     

Computer-aided dermoscopy for diagnosis of melanoma

Background

Recently, it has been observed that Video Display Terminals (VDTs) usage for long periods can cause some dermatological manifestations on the face. An analytical cross-sectional study was designed in order to determine this relationship.

Methods

In this study, 600 office workers were chosen randomly from an organization in Tehran (Iran). The subjects were then divided into two groups based on their exposure to VDTs. 306 workers were considered exposure negative (non VDT user) who worked less than 7 hours a week with VDTs. The remainders 294 were exposure-positive, who worked 7 hours or more with VDTs. The frequency of dermatologic manifestations was compared in these two groups.

Results

In the exposure-positive and exposure-negative groups, the frequency of these dermatologic manifestations were 27 and 5 respectively. After statistical analysis, a P.value of < 0.05 was obtained indicating a statistically significant difference between these two groups for dermatological manifestations.

Conclusion

According to our study, there is a relationship between dermatologic manifestations on the face and exposure to VDTs.     

Meningiomas of the posterior petrous bone: functional outcome after microsurgery

OBJECT: The aim of this study was to analyze a subgroup of patients harboring cerebellopontine angle meningiomas originating from the posterior petrous bone in regard to clinical presentation, surgical anatomy, complications, and long-term functional postoperative results. METHODS: Data in a series of 51 patients with meningiomas of the posterior petrous bone who had undergone microsurgical treatment at the authors' institution between 1989 and 2002 were retrospectively reviewed. The patient population consisted of 46 women and five men with a mean age of 53 years (range 22-70 years). The main symptom on first admission was impaired hearing in 41%, dizziness in 20%, and tinnitus in 18% of the patients. Results of physical examination and audiological testing revealed hypacusis in 65% of patients, cerebellar ataxia in 31%, and impairment of the fifth cranial nerve in 26%. All patients underwent surgical treatment via a lateral suboccipital approach. Intraoperatively, the tumor was found to be attached to the postmeatal dura in 37%, the premeatal dura in 27.5%, the suprameatal dura in 19.6%, the inframeatal dura in 7.8%, and centered on the porus acusticus in 5.9% of cases. Tumor extension into the internal acoustic meatus was present in seven patients. Tumor resection was categorized as Grade I in 14 patients, Grade II in 29, Grade III in six, and Grade IV in two patients, according to the Simpson classification system. The site of displacement of the cranial nerves was predictable in up to 84% of patients, depending on the dural origin of the tumor as depicted on preoperative magnetic resonance (MR) imaging studies. Postoperatively, a new and permanent facial paresis was observed in five patients (9.8%). In 38 patients in whom both pre- and postoperative audiological data were available, hearing function deteriorated after surgery in 18.4% and improved in 7.9%. Clinical and MR imaging postsurgical data from a mean period of 5.8 years (range 13 months-13 years) were available in all patients. Forty-four patients (86%) resumed normal daily activity. Tumor recurrence was observed in two patients (3.9%), and both underwent a second surgery. CONCLUSIONS: Preoperative detailed analysis of MR imaging data gives the surgeon a clue about the dislocation of critical neurovascular structures, particularly the cranial nerves. Nonetheless, the exact relationship of the cranial nerves to the tumor (dislocation, adherence, infiltration, and splaying of nerves) can only be fully appreciated during surgery.     

Intra-operative characterization of gliomas by near-infrared spectroscopy: possible association with prognosis

Summary ?Background. Growth and expansion of gliomas are highly dependent on vascular neogenesis. An association of microvascular density and tumour energy metabolism is assumed in most human gliomas. The purpose of this investigation was to characterize a series of gliomas by intra-operative near-infrared spectroscopy (NIRS), and to elucidate the relationship between microvascular blood volume (BV), oxygen saturation (SaO₂), histology and patient survival. Method. The study included 13 patients with gliomas, in whom complete tumour resection according to postoperative magnetic resonance imaging criteria was achieved. Intra-operatively, one low grade astrocytoma, five anaplastic astrocytomas and seven glioblastomas with the ipsilateral cortex were investigated by NIRS revealing capillary BV (total haemoglobin) and SaO₂. Intratumoural BV (tBV) and SaO₂ (tSaO₂) were additionally used in relation to histology and survival. Findings. The mean tBV of the astrocytomas was 4.96 mg/ml compared to 18.40 mg/ml in the glioblastoma group. Mean tSaO₂ was 36% in the astrocytoma group and 52% in the glioblastomas, respectively. Both tBV and tSaO₂ were significantly higher (p<0.01) in the glioblastoma group. Median survival time was shortest for patients with glioblastoma (12.5 months), with tBV >10/mg/ml (10 months), and tSaO₂ >50% (10 months). Longest median survival times were observed in the astrocytoma group (32.5 months), in patients with Tbv <10/mg/ml (30 months), and tSaO₂ <50% (27.5 months). The differences were highly significant (p<0.01). Interpretation. Intra-operative characterization of gliomas by NIRS is feasible. High tBV represents extensive angiogenetic activity of the tumour, whereas high tSaO₂ may be result of non-oxidative glucose metabolism with less oxygen extraction from the capillary bed of the tumour. However, the extent of tBV and tSaO₂ are both of possible prognostic value thus resulting in additional information about the tumour. Published online June 11, 2003     

The Effect of Sleep Deprivation on Cardiac Function and Tolerance to Ischemia-Reperfusion Injury in Male Rats

Background

Sleep deprivation (SD) is strongly associated with elevated risk for cardiovascular disease.

Objective

To determine the effect of SD on basal hemodynamic functions and tolerance to myocardial ischemia-reperfusion (IR) injury in male rats.

Method

SD was induced by using the flowerpot method for 4 days. Isolated hearts were perfused with Langendorff setup, and the following parameters were measured at baseline and after IR: left ventricular developed pressure (LVDP); heart rate (HR); and the maximum rate of increase and decrease of left ventricular pressure (±dp/dt). Heart NOx level, infarct size and coronary flow CK-MB and LDH were measured after IR. Systolic blood pressure (SBP) was measured at start and end of study.

Results

In the SD group, the baseline levels of LVDP (19%), +dp/dt (18%), and -dp/dt (21%) were significantly (p < 0.05) lower, and HR (32%) was significantly higher compared to the controls. After ischemia, hearts from SD group displayed a significant increase in HR together with a low hemodynamic function recovery compared to the controls. In the SD group, NOx level in heart, coronary flow CK-MB and LDH and infarct size significantly increased after IR; also SD rats had higher SBP after 4 days.

Conclusion

Hearts from SD rats had lower basal cardiac function and less tolerance to IR injury, which may be linked to an increase in NO production following IR.