Blood-brain barrier permeability to bilirubin in the rat studied using intracarotid bolus injection and in situ brain perfusion techniques

It has generally been assumed that free unconjugated bilirubin gains access to the brain because of its lipid solubility. However, no measurements of the blood-brain barrier permeability to free bilirubin exist. The aim of these experiments was to determine the blood-brain barrier permeability in the rat to free bilirubin using single-pass (Oldendorf) and in situ perfusion (Takasato) techniques. Studies were performed on adult rats under sodium pentobarbitone anesthesia. [3H]bilirubin IX-alpha-ZZ (sp act 6.2 Ci/mmol) was synthesized by reduction of biliverdin with sodium boro-[3H]hydride. Blood-brain barrier permeability to albumin-bound and free bilirubin was determined using injectates/perfusates containing a molar excess of human serum albumin with or without the addition of the displacing agent sulphadimethoxine. For free bilirubin, the brain uptake index was 28.5 +/- 9.3 (mean +/- SD, n = 18), and the permeability surface area product was 54.84 +/- 36.38 x 10(-4) mL/s/g (mean +/- SD, n = 13). These results demonstrate that the behavior of free bilirubin in vivo in relation to the cerebral microvasculature corresponds to that of a "lipid soluble" molecule.     

Papillary carcinoma of the thyroid associated with sarcoidosis

A case of papillary carcinoma of the thyroid occurring in association with systemic sarcoidosis is reported. Although benign thyroid disorders occurring in conjunction with sarcoidosis have previously been documented, a search of the literature found no report of thyroid carcinoma occurring in association with sarcoidosis. Diagnosis and therapeutic management prove difficult when thyroid carcinoma and sarcoidosis co-exist. Transbronchial biopsy of lung lesions is warranted in staging thyroid carcinoma in order to exclude the possibility of unknown co-existent disease. The management of cervical lymphadenopathy in thyroid carcinoma should not be altered because of the presence of sarcoidosis, and should include a neck dissection.     

A comparative study of transcutaneous electrical nerve stimulation (TENS), entonox, pethidine + promazine and lumbar epidural for pain relief in labor

Analgesic effect, labor outcome, safety and consumer satisfaction were compared in 170 primigravid women; 50 using TENS initially for pain relief, 20 using entonox, 50 pethidine + promazine and 50 lumbar epidural. 88% choosing epidural related it fully effective. 90% using entonox, 96% using TENS and 54% given pethidine + promazine found partial relief. 82% of patients given TENS and 80% given pethidine + promazine required additional analgesia. This was also needed by one of the 20 patients choosing entonox. Women using entonox alone had the shortest labors and women using lumbar epidural, the longest. Operative delivery was significantly more common in women receiving lumbar epidural. No significant inter-group differences were noted in cord pH or Apgar scores. Parturients and midwives both gave high consumer satisfaction ratings to all methods--except for pethidine + promazine, whose use must therefore be questioned. The analgesic efficacy of lumbar epidural outweighs any possible side effects. Entonox appears suited to those able to cope with the earlier part of labor, drug-free. Realization of the potential of TENS requires the design of machines specifically to cope with the quality of the pain of labor.     

Correlation between visual function and visual ability in patients with uveitis

AIM: To investigate the correlation between tests of visual function and perceived visual ability recorded with a quality of life questionnaire for patients with uveitis. METHODS: 132 patients with various types of uveitis were studied. High (monocular and binocular) and low (binocular) contrast logMAR letter acuities were recorded using a Bailey-Lovie chart. Contrast sensitivity (binocular) was determined using a Pelli-Robson chart. Vision related quality of life was assessed using the Vision Specific Quality of Life (VQOL) questionnaire. RESULTS: VQOL declined with reduced performance on the following tests: binocular high contrast visual acuity (p = 0.0011), high contrast visual acuity of the better eye (p = 0.0012), contrast sensitivity (p = 0.005), binocular low contrast visual acuity (p = 0.0065), and high contrast visual acuity of the worse eye (p = 0.015). Stepwise multiple regression analysis revealed binocular high contrast visual acuity (p <0.01) to be the only visual function adequate to predict VQOL. The age of the patient was also significantly associated with perceived visual ability (p <0.001). CONCLUSIONS: Binocular high contrast visual acuity is a good measure of how uveitis patients perform in real life situations. Vision quality of life is worst in younger patients with poor binocular visual acuity.     

Examination of different pointwise linear regression methods for determining visual field progression

PURPOSE: To compare the specificity and sensitivity of several different methods for using pointwise linear regression (PLR) to detect progression (deterioration) in visual fields. METHODS: First, theoretical results were derived to predict which of the considered PLR methods would be the most specific and hence the least sensitive. Then, a "Virtual Eye" simulation model was developed that simulates series of sensitivity readings for a point over time. The model adds normally distributed noise (estimated from published results) to the sensitivity at each point to produce a series of fields to be analyzed using each method. Stable and deteriorating eyes were simulated, with the latter defined to have a noise-free loss of 2 dB/y at a significant cluster of points over the series. RESULTS: The most sensitive method tested was to flag a visual field as progressing if it had a point that exhibited a statistically significant slope (at the 1% level) of at least -1 dB/y in the sensitivity. The most specific was a new "Three-Omitting" method that is being proposed, using two confirmation fields in a novel way. Current methods of using confirmation fields to verify a significant slope incorrectly flagged up to twice as many stable eyes as having progressing fields as did our new method. CONCLUSIONS: Using the new proposed PLR method is recommended in preference to current PLR methods in any applications when a high degree of specificity is the main priority.     

Assessment of bioaccumulation,neuropathology, and neurobehavior following subchronic (90 days) inhalation in Sprague-Dawley rats exposed to manganese phosphate

Methylcyclopentadienyl manganese tricarbonyl (MMT) is an organic manganese (Mn) compound added to unleaded gasoline. It has been suggested that the combustion products of MMT containing Mn, such as manganese phosphate, could cause neurological symptoms similar to Parkinson's disease in humans. The aim of this work was to investigate the exposure-response relationship of bioaccumulation, neuropathology, and neurobehavior following a subchronic inhalation exposure to manganese phosphate in Sprague-Dawley male rats. Rats were exposed 6 h/day, 5 days/week for 13 consecutive weeks at 30, 300, or 3000 microg/m(3) Mn phosphate and compared to controls. Some rats were implanted with chronic EMG electrodes in the gastrocnemius muscle of the hind limb to assess tremor at the end of Mn exposure. Spontaneous motor activity was measured for 36 h using a computerized autotrack system. Rats were then sacrificed by exsanguination and Mn level in different brain tissues and other organs was determined by instrumental neutron activation analysis. Neuronal cell counts were obtained by assessing the sum of five grid areas for the caudate/putamen and the sum of two adjacent areas for the globus pallidus. Increased manganese concentrations were observed in all tissues of the brain and was dose-dependent in olfactory bulb and caudate/putamen. In fact, beginning with the highest level of exposure (3000 microg/m(3)) and ending with the control group, Mn concentrations in the olfactory bulb were 2.47 vs 1.28 vs 0.77 vs 0.64 ppm (P < 0.05) while for the caudate/putamen, Mn concentrations were 1.06 vs 0.73 vs 0.62 vs 0.47 ppm (P < 0.05). The Mn concentrations in lung were also dose-dependent (10.30 vs 1.40 vs 0.42 vs 0.17 ppm; P < 0.05). No statistical difference was observed for loss of neurons in caudate/putamen and globus pallidus. Locomotor activity assessment and tremor assessment did not reveal in neurobehavioral changes between the groups. Our results reinforce the hypothesis that the olfactory bulb and caudate/putamen are the main brain tissues for Mn accumulation after subchronic inhalation exposure.     

Influence of the CB(1) receptor antagonist,AM 251, on the regional haemodynamic effects of WIN-55212-2 or HU 210 in conscious rats

In conscious, freely-moving, male, Sprague-Dawley rats, the regional haemodynamic responses to the synthetic cannabinoids, WIN-55212-2 and HU 210, were compared. The possible involvement of cannabinoid, CB(1)-receptors, or beta(2)-adrenoceptors in the responses to WIN-55212-2 and HU 210 were investigated using the CB(1)-receptor antagonist, AM 251, or the beta(2)-adrenoceptor antagonist, ICI 118551, respectively. Both WIN-55212-2 (150 microg kg(-1)) and HU 210 (100 microg kg(-1)) had pressor, renal, and mesenteric vasoconstrictor and hindquarters vasodilator actions, although the effects of HU 210 were much more sustained than those of WIN-55212-2. Lower doses of the cannabinoids (WIN-55212-2, 50 microg kg(-1), HU 210, 10 microg kg(-1)) had less consistent actions. All the significant cardiovascular effects of WIN-55212-2 and HU 210 were antagonized by pretreatment with AM 251 (3 mg kg(-1)). Furthermore, pretreatment with the beta(2)-adrenoceptor antagonist, ICI 118551, inhibited the hindquarters vasodilator effects of WIN-55212-2 and of HU 210. On the basis of the present findings, and our earlier work, it is suggested that, in conscious rats, the pressor and vasoconstrictor effects of HU 210 and WIN-55212-2 involve cannabinoid-receptor-mediated increases in sympathetic activity. The accompanying hindquarters vasodilator actions of these agonists are cannabinoid receptor-mediated and appear to involve beta(2)-adrenoceptors.