Non-Contractile Cells with Thin Processes Resembling Interstitial Cells of Cajal Found in the Wall of Guinea-Pig Mesenteric Arteries

Arterial interstitial cells of Cajal (ICC)-like cells (AIL cells) with a multipolar, irregular, elongated shape and with numerous thin (often less than 1 μm), sometimes branching, processes with lengths up to ≈60 μm were isolated enzymatically from 1st to 7th order branches of guinea-pig mesenteric artery. Some of the processes of AIL cells were growing (average speed ≈0.15 μm min⁻¹) and their growth was blocked by 10 μ M latrunculin B, an inhibitor of actin polymerisation. Staining with BODIPY phalloidin, a fluorescent dye selective for F-actin, showed the presence of F-actin in the processes of AIL cells. Voltage clamp of single AIL cells revealed an inward current that was four times more dense than in myocytes and was abolished by 10 μ M nicardipine, and an outward current carried exclusively by potassium ions that was reduced by 1 m M 4-aminopyridine and/or 100 n M iberiotoxin but unaffected by 10 n M dendrotoxin-K. Imaging of intracellular ionised calcium with fluo-4 using a laser scanning confocal microscope showed local or global calcium transients lasting several seconds in ≈28 % of AIL cells. When membrane current was recorded simultaneously, the calcium transients were found to correspond to long-lasting transient outward currents, which occurred at potentials positive to −40 mV. Unlike myocytes, AIL cells did not contract in response to 1 m M caffeine or 5 μ M noradrenaline, although they responded with a [Ca²⁺]_i increase. The segments of intact arteries did not stain for c-kit, a marker of ICCs. Single AIL cells stained positive for vimentin, desmin and smooth muscle myosin. The presence of ICC-like cells is demonstrated for the first time in the media of resistance arteries.     

The pathogenicity of long versus short fibre samples of amosite asbestos administered to rats by inhalation and intraperitoneal injection.

For many years it has been accepted that fibre dimensions are the most important factor in the development of asbestos related disease with long fibres being more dangerous than short for all types of asbestos. This information has been derived from in vitro experiments and injection or implantation experiments since the kilogramme quantities of specially prepared dusts that are necessary for long term inhalation have not been available. The present study has taken advantage of the availability of a sample of amosite produced so that almost all fibres were less than 5 micron in length. The effects of this dust were compared to dust prepared from raw amosite that contained a very high proportion of long fibres. Previous data from studies with UICC amosite, which was intermediate in length, were also available for comparison. At the end of 12 months of dust inhalation, significantly more short fibre amosite was present in the lung tissue compared to the long but while the long fibre dust caused the development of widespread pulmonary fibrosis, no fibrosis at all was found in animals treated with short fibre. One third of animals treated with long fibre dust developed pulmonary tumours or mesotheliomas but no pulmonary neoplasms were found in animals treated with short fibre dust. Following intraperitoneal injection, the long fibre amosite produced mesotheliomas in 95% of animals with a mean induction period of approximately 500 days. With short fibre dust, only a single mesothelioma developed after 837 days. In previous inhalation studies with UICC amosite, relatively little pulmonary fibrosis had developed and only two benign pulmonary tumours. This would suggest that to produce a significant carcinogenic response in rat lung tissue amosite fibres must be longer than those in the UICC preparation. Following the injection of UICC amosite, however, mesotheliomas developed in the same proportion of animals and with the same mean induction period as with long fibre dust. From this it would appear that while very short fibres exhibit little carcinogenicity to either lung or mesothelial tissues, mesotheliomas can be produced by dust preparations consisting of shorter fibres than are needed to produce tumours.     

Learning disability and epilepsy in an epidemiological sample of individuals with tuberous sclerosis complex

BACKGROUND: Intellectual impairments are a recognized feature of tuberous sclerosis complex (TSC), but the frequency and degree of intellectual impairments has not been systematically studied in large epidemiological samples using standardized measures. As such, the form of the IQ distribution (uni- or bi-modal) has not been established and the relationship between IQ and other features (e.g. epilepsy history) is poorly delineated. To address these shortcomings, we assessed the intellectual abilities of a large epidemiological sample of individuals with TSC, drawn from the 'Wessex' area of SW England and compared them with the abilities of their unaffected siblings. METHOD: Standardized tests were used to estimate the abilities of 108 (56 males, 52 females, median age = 25, range = 4-75) individuals with TSC and 29 unaffected siblings (14 males, 15 females, median age = 18, range = 6-55). Seizure history was obtained from informants and medical records. RESULTS: Estimated IQ was bi-modally distributed: 55.5% had an IQ in the normal range; 14% had mild to severe impairments: and 30.5% had profound disability (IQ < 21). Forty-four per cent of the individuals with TSC had an IQ < 70. In the subset of normally intelligent individuals with TSC, IQ was normally distributed with a mean of 93.6. This mean was significantly lower than the mean IQ of unaffected siblings (IQ = 105.6). All individuals with learning disability had a history of seizures that usually commenced before 12 months of age and that often presented as infantile spasms. Multivariate analyses indicated that a history of seizures as well as a history of infantile spasms was predictive of the degree of intellectual impairment. CONCLUSIONS: Intellectual abilities were bi-modally distributed in a representative sample of individuals with TSC. The likelihood of impairment was associated with a history of seizures, particularly infantile spasms. The genetic and brain basis of these findings requires further investigation.     

Short-term therapy for recurrent abortion using intravenous immunoglobulins: results of a double-blind placebo-controlled Italian study

It is still unclear whether i.v. immunoglobulins (Ig) can facilitate the reproductive prognosis of women who have suffered recurrent pregnancy loss. We report the results of a multicentre placebo- controlled study on the effect of Ig administration on pregnancy outcome in 46 women who had suffered at least three recurrent miscarriages. All were screened to exclude chromosomal or Mullerian abnormalities, the presence of antinuclear antibodies, lupus anticoagulant (LA) or elevated titres of anticardiolipin antibodies which may have revealed an underlying autoimmune problem. To avoid a selection bias towards ongoing pregnancies, i.v. Ig or placebo were administered between weeks 5 and 7 of gestation for 2 consecutive days as soon as each woman knew she was pregnant and before embryonic heart activity could be detected. A further infusion was administered at week 8 when ultrasonography confirmed an ongoing embryonic development. In all, 68% of the women who received Ig went to term versus 79% of those who received a placebo (not significant), with no significant differences in the pregnancy course or the perinatal outcome. These results suggest either that women with recurrent miscarriages who have no recognized cause of pregnancy loss have a good reproductive prognosis without any treatment or that the emotional care associated with the administration of a placebo can indirectly facilitate the progression of pregnancy.      

Cognitive deficits in normally intelligent patients with tuberous sclerosis

Webb, Thomson, and Osborne [1991: Arch Dis Child 66:1375-1377] reported on the pattern of cerebral lesions found in an epidemiological sample of patients with tuberous sclerosis (TS) and clinically judged to be of normal intellect. Varying numbers of tubers and subependymal nodules were found, but clinically there appeared to be few associated neuropsychological impairments. Our objectives in this study were to conduct a detailed neuropsychological assessment to determine whether these patients were indeed free of cognitive deficits. We report the results of a detailed neuropsychological assessment in this sample and a matched comparison group. Although of average intelligence, most TS individuals had a significant cognitive deficit of one sort or another, and in a number of cases the pattern of cognitive impairments matched that seen in other neurological disorders. Additionally, the overall rate of cognitive deficits was significantly greater than in the controls. We conclude that normally intelligent individuals with TS are prone to specific cognitive difficulties. Further research will be required to clarify the nature of the links between the brain abnormalities and type of neuropsychological dysfunction. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:642-646, 1999.     

Incidence and demographic correlates of eating disorder symptoms in a pregnant population.

OBJECTIVE: To obtain a picture of eating disorder symptoms in a population of pregnant women. METHOD: Five hundred thirty women attending antenatal follow-up clinics at a large London district general hospital during a 4-week period were surveyed. The Eating Attitudes Test (EAT), the Edinburgh Postnatal Depression Scale (EPDS), and a demographic questionnaire were administered. Unadjusted relative risks and their 95% confidence intervals were calculated for a series of prognostic factors. RESULTS: 4.9% of women scored above the recommended threshold on the EAT in pregnancy. Eating disorder symptomatology was found to be associated with younger age, previous symptomatology, lower educational attainment, poorer housing, employment status, and previous miscarriage. DISCUSSION: The meaning and potential implications of high levels of eating disorder symptomatology in a pregnant population are discussed in the light of the physiological and psychological effects of eating disorders on both pregnancy outcome and infant development.     

Spontaneous rupture of the liver

A patient with systemic lupus erythematosus developed an acute surgical abdomen secondary to spontaneous rupture of the liver and died. Postmortem examination revealed an arteritis of the liver, pancreas, adrenal gland, skeletal muscle, and spleen. It appeared that an arteritis of the liver produced areas of infarction that ruptured and caused the clinical findings.     

An analysis of sestamibi-positive versus -negative patients with primary hyperparathyroidism.

We performed this study to evaluate two patient groups with primary hyperparathyroidism depending on whether their abnormal gland(s) could be preoperatively imaged with sestamibi. Patients with primary hyperparathyroidism evaluated by preoperative sestamibi examination from January 1999 to June 2000 were divided into two groups depending on the ability of sestamibi to localize their disease. Records were reviewed to determine pre- and postoperative biochemical data, weight of the excised glands, and total operating room time. When the sestamibi imaging was positive a minimally invasive parathyroidectomy was performed; however, when sestamibi scanning was negative patients underwent a formal bilateral neck exploration. All 40 patients in the sestamibi-positive group and 17 of 18 patients in the sestamibi-negative group were cured of their primary hyperparathyroidism as a result of surgery. Sestamibi scanning with a minimally invasive parathyroidectomy shortens operating room time and is most effective when adenomas are large. The results of this study suggest that strategies to preoperatively increase the activity of adenomas may improve the sensitivity of sestamibi scan localization of parathyroid adenomas.