Improved Corneal Pilocarpine Permeability with O,O′-(l,4-Xylylene) Bispilocarpic Acid Ester Double Prodrugs

0,0-(l,4-Xylylene) bispilocarpic acid esters are pilocarpine pro-drugs containing two pilocarpic acid monoesters linked with one pro-moiety. Each mole of prodrug forms two pilocarpine moles in the presence of esterases. Corneal uptake and permeability of various bispilocarpic acid diesters were investigated in vitro using isolated albino rabbit corneas. The permeability coefficient of pilocarpine was 2.8 × 10 ^–6 cm/sec, whereas for bispilocarpic acid diesters, despite their large molecular weights (between 638 and 722), permeability coefficients were 6.5–20.2 × 10 ^–6 cm/sec. Only pilocarpine, and no intact prodrug, was observed at the endothelial side. Corneal uptake was increased with increasing lipophilicity, but a parabolic relationship between the logarithm of the apparent partition coefficient (1-octanol–pH 7.4 phosphate buffer) (log PC) and the corneal permeability was noticed. Corneal permeability and the rate of enzymatic hydrolysis of the compounds correlated well. The corneal permeability of pilocarpine given as lipophilic bispilocarpic acid diester (log PC 3) prodrugs seems to be controlled by the formation of pilocarpine in the corneal epithelium rather than by the absorption of prodrugs into the epithelium or their epithelium–stroma transport rate.     

Growth of asthmatic children is slower during than before treatment with inhaled glucocorticoids

Reports on the influence of inhaled glucocorticoids on growth have been controversial. We studied the growth of prepubertal asthmatic children prior to and during glucocorticoid therapy. We collected retrospectively the notes of 201 asthmatic children aged 1–11 years receiving inhaled beclomethasone dipropionate or budesonide. We calculated their height and height velocity standard deviation scores (HSDS and HVSDS, respectively) before the treatment and up to 5 years during the treatment and compared those with the growth of healthy peers. The dose of the medication was calculated and the severity of asthma was assessed. The asthmatic children grew similarly to their healthy peers before treatment with inhaled glucocorticoids: the mean HSDS was +0.02 and the mean HVSDS +0.01 for boys and -0.16 and +0.13 for girls, respectively. Growth retardation took place soon after the start of the treatment, the most profound decrease in the growth velocity (the change in the mean HVSDS from +0.05 to -0.88) occurring during the first year of treatment. The growth-retarding effect of inhaled glucocorticoids was not dose dependent. In the covariance analysis the increasing severity of asthma had a significant interaction with repeated measurements, showing more growth retardation along with more severe asthma, especially during long-term treatment. Asthma per se does not impair growth, but inhaled glucocorticoids may do so. Careful monitoring of the growth of all asthmatic children receiving inhaled glucocorticoids is necessary because the growth-retarding effect of the medication is not dose dependent. Individual sensitivity might explain the differences seen in the growth patterns of children receiving inhaled glucocorticoids.     

Pre-operative serum level of tumour-associated trypsin inhibitor and residual turnour size as prognostic indicators in Stage III epithelial ovarian cancer

Objective To evaluate the use of the pre-operative tumour-associated trypsin inhibitor (TATI) level and residual tumour size at primary surgery as a prognostic indicators for patients with Stage III epithelial ovarian cancer.
Design Retrospective cohort study.
Setting Department of Obstetrics and Gynaecology, University Hospital, Helsinki, Finland.
Participants Ninety-eight women with Stage III ovarian cancer.
Methods TATI was measured by radioimmunoassay from serum samples obtained within one week before surgery. A cutoff value of 22 μg/L was used. Multivariate analysis included pre-operative TATI level, age, histologic grade and histologic type. Mantel-Cox test was used for calculating statistical significance of differences in survival between groups.
Main outcome measures Cumulative five-year survival, pre-operative serum TATI level and residual tumour size.
Results Surgery was optimal (residual tumour size ≤ 2 cm) in 55 patients and suboptimal (residual tumour size > 2 cm) in 43. Pre-operative TATI level ≤ 22 μg/L predicted better prognosis both in patients with optimal and suboptimal surgery compared with patients with pre-operative TATI level > 22 μ/L. Patients with optimal surgery and a pre-operative TATI > 22 μg/L had a twofold relative risk of death compared with those with a pre-operative TATI ≤ 22 μg/L. The cumulative survival was less than three years for patients with suboptimal surgery and pre-operative TATI > 22 μg/L.
Conclusions Pre-operative serum TATI in combination with residual tumour size may be useful in stratifying patients with Stage III ovarian cancer into different categories in randomised treatment trials.     

Detection of severe acute pancreatitis by contrast-enhanced magnetic resonance imaging

The aim of the study was to assess the ability of MRI to differentiate between the two forms of severity of acute pancreatitis (AP), which is important for the detection of patients who require intensive monitoring and therapy. The second objective was to evaluate whether the distinction would be possible regardless of the MRI equipment. Magnetic resonance imaging was performed before and after intravenous administration of a gadolinium (Gd) chelate at 1.0 T using the breath-hold multislice rapid gradient-echo turbo fast low-angle shot (FLASH) sequence in 14 patients, and at 1.5 T with the 2D FLASH(50) sequence with fat saturation in 18 patients with acute pancreatitis early in the course of the disease. The patients were classified according to the Atlanta classification system as having the mild (MAP) or severe (SAP) form of the disease. At 1.0 T with use of a body coil, contrast-enhanced MRI failed to distinguish mild from severe pancreatitis. At 1.5 T with a phased-array body coil, the signal intensities of the patients with SAP were statistically significantly lower than those of the MAP group. Our initial clinical experience suggests that MRI with a sufficient magnetic field gradient strength may be useful for separating the two forms of acute pancreatitis in their early phases. Received: 19 January 1999; Revised: 28 May 1999; Accepted: 22 July 1999     

Chlamydial antibodies and risk of prostate cancer.

OBJECTIVE: We assessed the risk of prostate cancer by exposure to Chlamydia trachomatis. METHOD: Seven hundred thirty eight cases of prostate cancer and 2,271 matched controls were identified from three serum sample banks in Finland, Norway, and Sweden by linkage to the population based cancer registries. RESULTS: A statistically significant inverse association (odds ratio, 0.69; 95% confidence interval, 0.51-0.94) was found. It was consistent by different serotypes and there was a consistent dose-response relationship. CONCLUSION: C. trachomatis infection is not likely to increase the risk of prostate cancer. Whether the inverse relationship is true or due to difficulties in measuring the true exposure in prostatic tissue by serology, confounders or other sources of error remain open.     

Testing for high‐risk HPV in cervical and tonsillar paraffin‐embedded tissue using a cartridge‐based assay

This study evaluates the suitability of Xpert HPV (Cepheid, Sunnyvale, CA, USA) test for cervical and tonsillar formalin‐fixed paraffin‐embedded (FFPE) tissue samples as compared to the tests currently used in diagnostics. Cervical biopsies and liquid cytology (LC) samples were collected from 48 women attending colposcopy. Biopsies were processed for histology and tested for hrHPV using Xpert HPV. LC samples were tested using Xpert and Hybrid Capture 2 (HC2; Qiagen, Hilden, Germany) tests. Also 29 archived tonsillar carcinoma samples were tested using Xpert, and the results were compared with histology and immunohistochemical p16INK4a (p16) staining. Among valid cervical LC samples 46.8% were hrHPV positive using Xpert test and 55.3% with HC2. The sensitivity of Xpert was 84.6% as compared to HC2, and overall test concordance was 91.5%. Test concordance between valid Xpert results from biopsies and LC samples was 84.6%. Among valid tonsillar samples 70.4% were hrHPV positive, and concordance of 96.3% was found between Xpert and p16 staining. To conclude, Xpert HPV test cartridge provides a convenient platform to test individual samples, including FFPE samples. Further studies are needed to establish whether test sensitivity is sufficient to reliably differentiate between hrHPV positive and hrHPV negative head and neck carcinomas.     

Effect of sampling site on fatty acid composition of human breast adipose tissue

The effect of sampling site and proximity of malignant tumor on the relative fatty acid composition of human breast adipose tissue was studied in 10 cases of breast cancer. The four anatomic quadrants of breast did not statistically significantly differ from each other in relation to any of the 30 fatty acids studied. Proximity of the malignant tumor did not affect the relative fatty acid composition of fat when compared with more distant sampling sites. Representative samples of breast adipose tissue for fatty acid composition analysis can be obtained from tissue adjacent to the tumor.     

Determinants for preventive oral health care need among community‐dwelling older people: a population‐based study

The aim was to study the determinants of preventive oral health care need among community‐dwelling old people. The study population consisted of 165 participants, a subpopulation in the Geriatric Multidisciplinary Strategy for Good Care of Elderly People (GeMS) study. Fifty‐five percent of the edentate participants with full dentures and 82% of the dentate had a need for preventive oral health care. In the total study population, the need for preventive care was associated with co‐morbidity (measured by means of the Modified Functional Co‐morbidity Index) odds ratios (OR) 1.2 (confidence intervals [CI] 1.0–1.5), being pre‐frail or frail, OR 2.5 (CI 1.2–5.1), presence of natural teeth, OR 4.8 (CI 2.2–10.4), and among dentate participants, the use of a removable partial denture, OR 12.8 (CI 1.4–114.4). Primary care clinicians should be aware of the high need for preventive care and the importance of nonoral conditions as determinants of preventive oral health care need.