The relationship of proliferating cell density at the invasive tumour front with prognostic and risk factors in human oral squamous cell carcinoma

BACKGROUND: We hypothesise that the density of proliferating cells at the invasive tumour front (ITF) has a positive relationship with prognostic and risk factors in human oral squamous cell carcinoma (SCC). METHODS: Tissues from 47 human oral SCC specimens were collected and stained with a monoclonal antibody directed against the Ki-67 antigen using a horseradish peroxidase based two-step immunostaining method. Counting was performed on two parallel sections at the ITF using an image analyser. The Ki-67 labelling index (LI) was determined by measuring the number of nuclei/mm(2) of epithelium. RESULTS: Our results show that the density of proliferating cells is related to clinical staging, with advanced stage of disease having a significantly higher Ki-67 LI compared with early stage of disease (2111 +/- 905 vs. 1908 +/- 913; P = 0.03). Importantly, this study shows that tumours that have metastasised have a significantly higher Ki-67 LI than tumours where distant metastasis was not detected (3257 +/- 650 vs. 1966 +/- 881; P < 0.0001). CONCLUSIONS: Cell proliferation, as measured by the Ki-67 LI at the ITF, has a positive relationship with clinical staging, tumour thickness, smoking status of the patient and alcohol consumption. Further, we suggest that a multicenter study with a large cohort of patients is indicated to fully elucidate whether cell proliferation at the ITF is directly related to patient survival.     

Cervical esophago-esophageal anastomosis.

We describe our results with cervical esophagoesophageal anastomosis. This approach has been used with success in 4 patients. It has the advantage of avoiding esophagectomy in patients with benign disease and allows restoration of esophageal continuity in patients having limited options for esophageal replacement.     

Oesophageal dissection after thrombolytic treatment for myocardial infarction.

A 62 year old woman admitted with a history suggesting acute myocardial infarction had thrombolytic treatment with anisoylated plasminogen-streptokinase activator complex, which resulted in submucosal haemorrhage in the oesophagus; this caused dissection of the wall of the oesophagus and complete dysphagia. The haematoma resolved spontaneously, leaving behind a diverticulum, with reduced peristalsis and delayed emptying but no obstruction.     

Gd-DOTA as a gastrointestinal contrast agent for gastric emptying measurements with MRI

Current MR meal markers may interfere with gastric motility and secretion restricting the use of MRI in the measurement of gastric physiology. We therefore evaluated Gd-DOTA as a liquid phase marker, in vitro by determining dissociation, and adherence to the solids, and in vivo by simultaneous MRI (0.35 T scanner, multiple T₁-weighted sections of the upper abdomen) and double indicator (perfusion marker PEG 4000, meal marker ^99mTc-DTPA) measurements of emptying and secretion, following ingestion of 500 ml 10% glucose. In vitro Gd-DOTA was stable at a pH > 2 with < 2% dissociation at 24 h during incubation with HCI. Dissociation during incubation with HCI was linearly dependent on H⁺ concentration (0.77 < pH < 2.02). Less Gd-DOTA was absorbed onto the solid phase than ^99mTc-DTPA (25% cf 36%). in vivo Gd-DOTA marked gastric contents provided strong positive contrast. Similar emptying curves were observed with both MRI and double-indicator techniques (r = 0.987, P < 0.001). Gd-DOTA has the potential to be a useful liquid phase contrast agent in MR studies on gastric function.     

Brain cyclosporin A levels are determined by ontogenic regulation of mdr1a expression.

Cyclosporin A (CyA) toxicity is a common occurrence in pediatric organ transplant patients. We hypothesized that reduced mdr1a expression in newborn and developing mice would affect CyA accumulation within organs and/or toxicity. For functional studies, CyA was administered (5 mg kg(-1) i.p.) to 1-, 12-, and 19-day, and adult male and female mdr1a+/+ and mdr1a-/- mice. Peak blood CyA was lower in 1-, 12-, and 19-day-old (1000 ng ml(-1)) versus adult (1500 ng ml(-1)) mice but was similar in mdr1a+/+ and mdr1a-/- mice. Kidney mdr1a expression (measured by quantitative polymerase chain reaction) increased 2.5-fold in 19-day-old male and female mice and increased another 4-fold in adult females compared with adult males. Liver mdr1a expression increased 6-fold by day 12 compared with neonatal mice. Thereafter, maintenance of hepatic mdr1a expression in females and a reduction to neonatal levels in males was observed. Kidney/blood (8- to 9-fold) and liver/blood (12- to 15-fold) CyA levels were highest on days 12 and 19 and were not dependent on maturational changes in mdr1a mRNA levels. Adults had higher brain expression of mdr1a mRNA (3-fold), a corresponding 5-fold increase in immunodetectable P-glycoprotein, and 80% lower brain accumulation of CyA compared with 1-day-old mice. Conversely, in mdr1a-null mice, brain/blood CyA was similar in newborn and adult mice. A similar pattern was observed for the brain accumulation of the mdr1a substrate 3H-digoxin. We conclude that the risk for central nervous system drug toxicity could be higher in neonates or young children as a consequence of underdeveloped P-glycoprotein.     

Cognitive symptoms and correlates of physical disability in individuals with multiple sclerosis.

There are inconsistencies in the literature regarding the prevalence of cognitive impairment among individuals with multiple sclerosis (MS). The purpose of this study was to examine perceived cognitive impairment in secondary progressive and relapsing-remitting multiple sclerosis (MS) and to examine the relationship between level of disability, age, and number of years with MS and self-reported cognitive symptoms. The sample consisted of 447 individuals (96 participants with secondary progressive MS and 351 participants with MS) who responded to mailed data collection instruments. The Performance Scales, a self-report measure of disability in eight domains of function, and a sociodemographic data sheet were analyzedfor this study. Of individuals with secondary progressive MS, 83% reported cognitive symptoms, while 82% of individuals with relapsing-remitting MS reported cognitive symptoms. Individuals with secondary progressive MS were reportedly experiencing a significantly greater level of total disability. A statistically significant, strong, positive relationship was found between cognitive symptoms and fatigue for those with secondary progressive MS and those with relapsing-remitting MS. Statistically significant, moderate, positive relationships were also found between cognitive symptoms in those with secondary progressive MS and those with relapsing-remitting MS, and sensory symptoms, vision, hand function, bladder/bowel symptoms, and spasticity. A statistically significant, weak, positive relationship was found between cognitive symptoms and mobility in individuals with relapsing-remitting MS. There was no relationship between cognitive symptoms and mobility in those with secondary progressive MS. Cognitive symptoms were not significantly related to age in those with secondary progressive MS or those with relapsing-remitting MS. In addition, cognitive symptoms were not significantly related to the number of years with MS in individuals with secondary progressive MS or those with relapsing-remitting MS. The perception of cognitive deficits in individuals with MS was found in this study to be even more prevalent than previously reported. Because cognitive deficits occur at all stages of MS, early identification and treatment is essential. Healthcare providers must aggressively screen for cognitive impairment and rehabilitate individuals with MS who exhibit symptoms.