The impact of delayed diagnosis on the outcomes of oral cancer patients: a retrospective cohort study.

The contemporary literature is discordant regarding the role of delayed diagnosis in the prognosis of patients with oral cancer. This study examined data on a previously reported cohort of 101 patients with oral squamous cell carcinoma diagnosed at a single institution between 2008 and 2010. The time interval between symptom onset and initial histological diagnosis (diagnostic delay) was recorded for each patient, as were demographic data and cancer features such as T stage, nodal status, and smoking status. The mean follow-up period was 4 years 10 months. The mean diagnostic delay was 4 months, mean overall survival was 5years 6 months, and mean disease-specific survival was 4 years 9 months. No significant correlation was found between diagnostic delay and overall survival, disease-specific survival, or recurrence rates. Patients with node-positive disease were more likely to be diagnosed earlier, whereas women and non-smokers were more likely to have a delayed diagnosis. Inherent tumour biology is likely an important prognostic factor separate to diagnostic delay. Public education efforts should focus on symptom recognition and encourage early presentation for investigation of oral lesions, particularly for females and non-smokers, so that more aggressive tumours can be treated sooner to give the best chance at survival.

Spindle Cell Lipoma in an End-Stage Renal Allograft: Case Report.

BACKGROUND: Spindle cell lipoma is an uncommon variant of lipoma and usually occurs as a solitary, subcutaneous, and well circumscribed lesion in the posterior neck, shoulders, and back of older men. Primary renal lipomas are rarely reported. Spindle cell lipoma in the kidney has not been previously described in the literature. CASE REPORT: A 60-year-old Chinese man suffered graft failure 10 years after living related donor kidney transplantation. During cancer surveillance, he was found to have a mass in the renal allograft, which increased in size and was suspicious for renal cell carcinoma on computerized tomographic scan. The patient underwent renal graft explantation. Grossly, the kidney was atrophic, containing a 6.5 cm yellowish solid lesion without hemorrhage and necrosis in the renal sinus fat. Microscopically, the lesion was composed of variably sized adipocytes and cellular areas of bland spindle cells with no cytologic atypia. There were prominent slender blood vessels within the lesion, along with focal myxoid change as well as scattered mast cells and inflammatory cells. Lipoblasts were not identified. The spindle cells were positive for CD34 and negative for Melan-A, HMB45, S100, and SMA. Pax-2 stain was nonspecific. MDM2 amplification by means of fluorescence in situ hybridization (FISH) and overexpression by immunohistochemistry were negative. The Ki-67 proliferation index was <1%. Interphase FISH revealed loss of 13q and 16q in the tumor. CONCLUSIONS: Renal spindle cell lipoma is a rare benign tumor. Angiomyolipoma and well differentiated liposarcoma are the main differential diagnoses. Immunohistochemistry and cytogenetic techniques are helpful in differentiating it from malignant entities.

High rates of susceptibility to ceftazidime among globally prevalent CTX-M-producing Escherichia coli: potential clinical implications of the revised CLSI interpretive criteria.

The CTX-M family of extended-spectrum ß-lactamases (ESBLs) is a significant global public health threat. The prevalence of specific bla (CTX-M) genes varies geographically, but bla (CTX-M-15) and bla (CTX-M-14) dominate in most countries. We applied the latest Clinical Laboratory Standards Institute (CLSI) interpretive criteria (M100-S20) to a diverse collection of ESBL-producing Escherichia coli strains obtained from clinical specimens in our laboratory. Whereas under previous CLSI recommendations all isolates in this strain collection would have been reported as ceftazidime-resistant, under the new recommendations, approximately 11% of CTX-M-15-producing E. coli and 93% of CTX-M-14-producing E. coli respectively tested as ceftazidime-susceptible. We also found that, whilst many CTX-M-14-producers had minimum inhibitory concentrations (MICs) less than the breakpoint of 4 mg/L, the MIC distribution for these strains was higher than that of wild-type E. coli, with one CTX-M-14-producing isolate having an MIC of >64 mg/L. Although the new CLSI recommendations imply that ceftazidime can be safely used to treat serious infections due to CTX-M-producing E. coli, clinical outcome data are lacking. Consequently, the widespread use of ceftazidime in this setting could have profound clinical implications.

Multiple sites of exposure in an outbreak of ornithosis in workers at a poultry abattoir and farm.

Cases of ornithosis amongst workers on a rural duck abattoir and farm were notified from late 2003 to health authorities in Victoria, Australia. In May 2004 we conducted a serological survey to identify the extent of exposure to Chlamydophila psittaci amongst workers and a case control study to identify high-risk work areas for ornithosis-related pneumonia. Some workers in all occupational groups showed serological evidence of exposure, while those with pneumonia were more likely to have worked in the slaughtering area of the abattoir (adjusted odds ratio 16.7, 95% confidence interval 1.3-207). High exposure to blood and feathers from recently killed birds is likely to represent an occupational hazard to workers, but pneumonia did occur in workers without these exposures. We recommended respiratory protection for all abattoir workers and improvements to airflow and reduction of environmental contamination in high-risk work areas to prevent further cases.

Risperidone in the treatment of first episode psychosis.

OBJECTIVE: To evaluate the efficacy and safety of risperidone in Singapore patients with first-episode psychosis in an eight-week open label prospective study. METHOD: Previously untreated male and female patients aged 18 - 65 with DSM IV schizophreniform disorder or DSM IV schizophrenia for no longer than 12 months were recruited from Woodbridge Hospital and Geylang Psychiatric Outpatient Clinic. Patients were treated with risperidone for 56 days. Outcome was assessed with the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impression scale (CGI). Safety was assessed by monitoring of vital signs and by comparing the frequency of adverse events (AEs) before and after treatment. RESULTS: 24 patients with a mean age of 33.29+/-9.12 years and a mean duration of illness of 166.5+/-111.4 days (median 180 days) were included. The mean risperidone dosage was 2.7 mg +/- 1.0 at day 56. Mean PANSS total scores reduced by 50.21% from 88.29+/-21.55 at baseline to 43.96+/-7.5 at endpoint (p < 0.001). The responder rate (> or = 20% reduction in the total PANSS score) was 87.5%. 13 patients (54.2%) exhibited a 50% or greater reduction in total PANSS score. Except for item G5 (mannerisms and posturing) all single PANSS items were reduced significantly. The CGI scores of all patients improved at endpoint. No serious adverse events were reported. CONCLUSIONS: Overall the therapy of first-episode psychosis patients with risperidone was effective and safe.

The characterization of beta adrenoceptor subtypes in the rat amygdala and hippocampus.

(-)-[125I]Iodocyanopindolol [-]ICYP), is a ligand with high specific activity and nearly equal affinity for beta 1 and beta 2 adrenoceptors in a variety of tissues. Unfortunately, (-)ICYP also has affinity for 5HT1B serotonin receptors. To get an accurate estimate of beta adrenoceptors in the rat amygdala and hippocampus, (-)ICYP binding studies were done with membranes from these limbic structures in the presence of 10 microM serotonin to prevent the binding of (-)ICYP to serotonin receptors. Under these conditions. (-)ICYP binding to amygdaloid and hippocampus membrane preparations is saturable and reversible. Scatchard analyses revealed in both regions a single class of binding sites with an equilibrium dissociation constant (KD) of 18.5 pM for the amygdala and 19.6 pM for the hippocampus. The hippocampus has a significantly lower density of binding sites (Bmax) than amygdala (51.6 vs 62.3 fmol/mg membrane protein, p less than .05). The two brain regions do not differ with respect to kinetic reactions in that both show comparable slow association and dissociation rates. However, the dissociation reactions do reveal two affinity states for the binding sites in both areas. Detailed competition analyses with beta adrenoceptor subtype selective drugs (ICI-89406 and ICI-118551) show that in both regions about 70% of the beta adrenoceptor population is of the beta 1 subtype with the remainder being beta 2 subtype.

Differential effects of olfactory bulbectomy on beta-adrenoceptors in rat amygdala, hippocampus and cerebral cortex.

Rats were bilaterally olfactory bulbectomized. At 15 days post-lesion, olfactory bulbectomized (OB) rats exhibited significant deficits in the acquisition of passive avoidance learning compared to sham lesioned rats. beta-Adrenoceptor binding in the amygdala, hippocampus and cerebral cortex was assayed with (-)-[125I]iodocyanopindolol (ICYP). Scatchard analyses revealed no difference between OB and sham rats in maximal binding density (Bmax) in any of the three tissues. However, in the OB rats, the affinity of the beta-adrenoceptor for the ligand was significantly increased in the amygdala and hippocampus but not in the cortex. Bulbectomy did not affect the ratio of beta 1- to beta 2-adrenoceptor subtypes in the three brain tissues. In amygdala and hippocampus but not cerebral cortex, bulbectomy resulted in an increase in the proportion and the affinity of the high-affinity beta-adrenoceptor binding sites for isoproterenol. The affinity of the low-affinity sites in the hippocampus was also increased in the OB rats. The results suggest that olfactory bulbectomy causes supersensitivity of the amygdaloid and hippocampal beta-adrenoceptor by increasing the degree of coupling of the receptor with the stimulatory guanine nucleotide binding protein (Gs protein).

Beta-adrenoceptor and post-receptor components show different rates of desensitization to desipramine.

Both 3-day and 15-day desipramine treatments (10 mg/kg, once daily) significantly reduced beta 1- but not beta 2-adrenoceptor and isoproterenol-stimulated adenylyl cyclase activities in rat cortical, hippocampal and amygdaloid membrane preparations. In contrast, 15-day but not 3-day desipramine treatment resulted in a significant reduction in NaF-, GppNHp- and forskolin-stimulated adenylyl cyclase activity. The results suggest that post-beta-adrenoceptor component desensitization occurs more slowly than receptor downregulation in response to desipramine.

Characterization of rat cerebral cortical beta adrenoceptor subtypes using (-)-[125I]-iodocyanopindolol.

(-)-[125I]-Iodocyanopindolol [-)ICYP), used to characterize beta adrenoceptors on membrane preparations from rat cerebral cortex, was shown to have affinity for both beta adrenoceptors and serotonin receptors. Therefore, 10 microM serotonin was added to the assays to prevent (-)ICYP binding to serotonin receptors. Under these conditions, (-)ICYP binding to the cortical membrane preparation was reversible and saturable, and the association reaction was very slow. The dissociation reaction was also very slow, and revealed two affinity states corresponding to a high and a low affinity state. Scatchard analysis showed a single class of binding sites with an equilibrium dissociation constant (KD) of 20.7 pM, and a maximal density of binding sites (Bmax) of 95.1 fmol/mg membrane protein. Displacement binding analyses revealed a potency series of (-) isoproterenol greater than (-) epinephrine equal to (-) norepinephrine, suggesting a predominance of the beta 1 adrenoceptor subtype. Detailed competition ligand binding studies with the selective beta 1 adrenoceptor antagonist ICI-89406 and the selective beta 2 adrenoceptor antagonist ICI-118551, showed that about 70% of the beta adrenoceptor population in the rat cortex is of the beta 1 subtype with the remainder being of the beta 2 subtype. We conclude that since (-)ICYP binds to both beta adrenoceptors and serotonin receptors, it is important to prevent the binding of (-)ICYP to serotonin receptors by adding a suppressing ligand like excess cold serotonin when assaying beta adrenoceptors. We have presented the first such characterization of rat cerebral cortical beta adrenoceptors with (-)ICYP in this study.