Proliferating cell nuclear antigen expression and the progression of cervical intraepithelial neoplasia

Cell proliferation is an important biological aspect of a tumor cell population which can affect clinical outcome. In addition to other well established clinical and histopathological prognostic criteria? cell kinetic data have significant predictive value. This study evaluates the proliferative activity of benign, premalignant and malignant cervical tissue by analyzing the expression of the proliferating cell nuclear antigen (PCNA). PCNA is a 36 kD nuclear protein associated with the cell cycle and is directly involved in DNA synthesis during cell proliferation. A total of 122 subjects were included in the study. This included 30 benign tissue samples, 30 low grade lesions (CIN 1), 30 high grade lesions (CIN 2/3) and 32 invasive squamous carcinomas. There was significant difference in PCNA index between benign and high grade lesions as well as benign and invasive cancer. The percentage of PCNA positive cells were significantly higher in invasive carcinoma when compared with non malignant lesions. Moreover, there was also good correlation between increasing histological abnormality and PCNA expression. These results suggest that cell proliferation index as detected by PCNA expression may be useful in the evaluation of alterations in cell kinetics of various grades of cervical lesions. Such data could also possibly help explain the biological behaviour of these lesions and be useful in planning of radiotherapy for invasive cervical cancer.     

A study of dose distribution patterns from cobalt-60 and Varian Clinac-4 beams.

Dose distribution patterns of 4 MV x-rays from a Varian Clinac 4 linear accelerator are compared with those from a 60Co teletherapy machine. Field flatteners of lead and depleted uranium were used. Dose distribution maps display the off-axis high dose or "horns" with lead filters and circular dose distribution patterns. The uranium field flattener clearly "clipped the horns" and eliminated circular dose distribution patterns with larger fields.     

Number and size-spectra of myelinated nerve fibers of human premolars

Summary The primary objective of this study was to determine the number and size of myelinated nerve fibers at the subcervical, midroot and juxta-apical levels of human premolars. Sixty-seven healthy premolars extracted from adolescents were utilized. Root-discs were prepared from the three sites and processed for light and electron microscopy. The myelinated nerve fibers were counted from semithin sections using a sampling microscope. The measurements were taken from composite electron micrographs using an electronic image processing unit. A total of 1883 myelinated axons from seven mandibular second premolars was gauged. The 67 teeth had an average of 312±149 myelinated nerve fibers at the juxta-apical level (range 18 to 728). The contra- and ipsilateral differences in means among the four groups of premolars were not significant (P>0.05). The number of nerves increased significantly (P<0.05) toward midroot and subcervical (P<0.001) levels in all groups. The average neural diameter was 3.51.0 m at the juxta-apical level, and the between-teeth difference in mean was found to be significant (P<0.01). There was no decline (P>0.05) in the diameter of myelinated nerve fibers toward midroot and subcervical levels.     

Poloxamer gel as vehicle for transdermal iontophoretic delivery of arginine vasopressin: evaluation of in vivo performance in rats

The present study describes the formulation and evaluation for pharmacokinetic and pharmacodynamic activity of arginine vasopressin (AVP), a nanopeptide with antidiuretic activity on being delivered by transdermal iontophoresis. Poloxamer 407 was used to form stable gels that did not reduce the release of AVP. The release rate from the gel followed Higuchi kinetics indicating that the dominant mechanism of release is diffusion. Iontophoresis alone and in combination with chemical enhancers was used to augment the transdermal permeation of AVP. The results of both pharmacokinetic and pharmacodynamic studies emphasize the dimension of 'rapid onset' achieved by iontophoresis. The correlation between pharmacokinetic data and pharmacodynamic activity was only qualitative. Histopathological studies revealed that skin toxicity caused by either iontophoresis or chemical enhancers when used alone could be reduced by using a combination of both the techniques in tandem.     

Effect of iontophoresis and fatty acids on permeation of Arginine Vasopressin through rat skin

The aim of this study was to assess the effects of fatty acids and iontophoretic mode of penetration enhancement on transdermal delivery of Arginine Vasopressin (AVP). Sprague-Dawley (SD) rat skin was pretreated with fatty acids (e.g. 5% w/v, lauric acid, oleic acid, and linoleic acid in ethanol:water (EtOH:W, 2:1 system) for 2h and iontophoresis in vitro, separately or together. The results indicate that all fatty acids studied increased (P<0.05) the flux of AVP in comparison to control (not pretreated with enhancer) and their effectiveness in flux enhancement was comparable. Further, oleic acid in combination with iontophoresis significantly increased the permeation of AVP both in comparison to pretreatment with fatty acids and iontophoresis alone. However, iontophoresis did not further increase the permeation of AVP through linoleic acid pretreated skin. Fourier transform infrared (FT-IR) spectroscopic studies revealed that EtOH:W (2:1) system is not effective in lipid extraction. The shift to higher wavenumbers of the symmetric and asymmetric stretching peaks at 2850 and 2920cm(-1) revealed that at the concentration used, oleic acid and linoleic acid caused fluidization of stratum corneum (SC) lipids. This study provides direct evidence that oleic acid in EtOH:W (2:1) system causes disruption of the SC lipid lamellae and that a combination of oleic acid with iontophoresis further enhances the effects of oleic acid in a synergistic manner.     

Gemcitabine and ISIS-2503 for patients with locally advanced or metastatic pancreatic adenocarcinoma: a North Central Cancer Treatment Group phase II trial.

PURPOSE: Gemcitabine remains the standard therapy for metastatic pancreatic adenocarcinoma (ACA), but has limited activity. ISIS-2503 is an antisense compound directed against H-ras with preclinical activity against pancreatic ACA in tumor models. The combination of ISIS-2503 and gemcitabine has been evaluated in a prior phase I study. METHODS: Patients with metastatic or locally advanced pancreatic ACA not amenable to surgery or local radiation received gemcitabine 1,000 mg/m(2) intravenously over 30 minutes on days 1 and 8 and ISIS-2503 6 mg/kg/d as a continuous intravenous infusion over 14 days of an every-3-weeks cycle. Responses were monitored by radiologic imaging every 6 weeks. RESULTS: Forty-eight eligible patients were enrolled, 43 with metastatic disease. Median follow-up was 12.6 months (range, 2.2 to 16.8 months) for living patients. A median of four cycles of treatment was given (range, 1 to 18 cycles). All patients were assessable for response and toxicity. The 6-month survival percentage was 57.5% (95% CI, 44.9% to 73.5%) and the median survival was 6.6 months. The response rate was 10.4% (one complete response, four partial responses). Clinically significant toxicity was limited except for one fatal pulmonary embolism. CONCLUSION: This study shows a promising response rate to the combination of gemcitabine and ISIS-2503 in patients with pancreatic ACA. The observed 6-month survival rate in these patients met our protocol-defined criteria for success. This regimen is tolerable, but is of unclear benefit. Additional studies evaluating the role of gemcitabine and ISIS-2503 in the treatment of pancreatic ACA should be considered.     

Delayed presentation of congenital diaphragmatic hernia in association with group B streptococcus infection in a preterm Omani neonate

We present an interesting case of a preterm Omani newborn that had delayed onset of congenital diaphragmatic hernia in association with group B streptococcus infection. The association and the pathogenesis are supported by literature review. The message to follow is that any neonate with prolonged course of streptococcal pneumonia, with unusual course, should be investigated for presence of congenital diaphragmatic hernia.     

Screening for complement deficiency in bacterial meningitis

Seventy-seven children with bacterial meningitis were screened for complement deficiency. Both the classical and the alternate pathways were normal in 75 patients. Transiently reduced total haemolytic activity of the classical pathway was documented in a boy with meningococcal meningitis. Total haemolytic activity of both the classical and the alternate pathways were reduced in another patient with pneumococcal meningitis: individual complement components determination indicated predominant activation of the alternate pathway.