Histamine induced contraction of human ciliary muscle cells

In cultured human ciliary muscle cells we previously showed that histamine, via an H1 receptor, stimulates the production of inositol phosphates and mobilization of intracellular calcium. We further investigated in this study whether histamine would cause contraction of human ciliary muscle cells. Photomicrographs were taken of the ciliary muscle cells before and after exposure to histamine. Cross sectional surface area of the cells was quantified using image analysis software. A decrease in cross sectional surface area was interpreted as an indication of cell contraction. The results of this study indicated that histamine (10(-6) M-10(-4) M) caused contraction of human ciliary muscle cells in a concentration-dependent fashion. The effect of histamine was mediated by the H1 receptor subtype since the histamine effect was antagonized by 10(-6) M chlorphentramine (an H1 receptor subtype selective antagonist) but not by 10(-6) M cimetidine (H2 antagonist) or thioperamide (H3 antagonist). The phospholipase C (PLC) inhibitor, U73122 (10(-6) M) and the intracellular calcium store depleting agent thapsigargin (10(-6) M) both prevented the histamine induced contraction, demonstrating that the activation of PLC and the intracellular calcium release were the key steps necessary for contraction. Our data indicate that in ciliary muscle cells, histamine, via an H1 receptor, activates PLC and increases intracellular calcium, which subsequently causes contraction of the cells.     

Measurements of Thermal Kinetic Characteristics of Film Structures

The features of the arrangement of a procedure of measuring thermal kinetic characteristics (specific heats of films and substrates, the substrate thermal conductivity, and the thermal resistance of the film–substrate and substrate–thermostat interfaces) of film structures using a computer are described. An amplifier circuit developed taking into account the technical and procedure requirements of the method is presented. The circuit includes a wide-band dc amplifier with a differential input and a linear amplitude–frequency characteristic in the range of 0 to 2 × 10⁶ Hz combined with a sample-and-hold circuit for controlling the dc component of a pulse signal.     

A clinical, echocardiographic and genetic characterization of a Danish kindred with familial amyloid transthyretin methionine 111 linked cardiomyopathy

AIMS: To identify carriers and non-carriers of the mutant transthyretin methionine 111 linked familial amyloid disease, to detect early signs of the restrictive cardiomyopathy and other clinical manifestations characteristic of this inheritable disease. METHODS AND RESULTS: Out of 125 living family members 99 were available for clinical, echocardiographic and genetic examination. Twenty-five family members were heterozygous carriers of the mutant transthyretin methionine 111 genotype, while 74 were non-carriers. Among the 25 carriers, none had overt clinical signs of heart disease. Eight carriers, all above the age of 35, showed echocardiographic abnormalities suggestive of developing or manifest restrictive cardiomyopathy. Three had biopsy-verified transthyretin-related amyloid cardiomyopathy. None of the 15 carriers in the younger age group exhibited aberrant echocardiographic patterns. Nine carriers had carpal tunnel syndrome as opposed to none of the non-carriers. CONCLUSION: For early detection of familial amyloid cardiomyopathy, echocardiography is the investigation of choice. The first sign is diastolic dysfunction detected as an abnormal relaxation pattern. The appearance of echocardiographic aberrations solely in the older age group suggests that the cardiomyopathy is a late onset disease. Carpal tunnel syndrome appears to be the earliest presenting clinical symptom. A curative treatment seems to be an early liver transplantation.     

Towards cost-effective dialysis therapy in Europe: the need for a multidisciplinary approach

BACKGROUND AND PURPOSE: Although the reliability of the assessment of severe 70% to 99% carotid stenosis by carotid angiography has been proven excellent, this may not necessarily be the case for a more detailed classification of carotid stenoses by 10% categories. METHODS: Angiograms of the carotid arteries were assessed pairwise by three independent, experienced observers. The measurements of the degree of stenosis of both the carotid bifurcation and the internal carotid artery were made according to the European Carotid Surgery Trial method. Kappa statistics were used to assess the agreement beyond chance for severe (70% to 99%) carotid stenosis (kappa 1) and for 10% categories of carotid stenosis (kappa 2). The penalty scores were adjusted by weights for the relative difference in risk (RDR) of stroke in the ipsilateral carotid distribution between the 10% categories (kappa 3). An adjustment of the RDR method was made by assuming that only patients with a severe carotid stenosis would undergo surgery, and the penalty would be 0 if no disagreement would exist about the indication for surgery (kappa 4). An even further adjustment (kappa 5) was made by assuming that assessment of the rate of carotid stenosis by one or both observers would lead to different treatment recommendations in 50% of the cases, and accordingly the penalty for disagreement (RDR) was halved. RESULTS: One hundred twenty-one carotid bifurcations in 65 patients with a transient ischemic attack or nondisabling stroke were assessed. The intraclass correlation between the exact estimates of carotid stenosis was .90 (95% confidence interval, .85 to .92). The mean difference in stenosis between the two raters was 0.8% (95% confidence interval, -2.1% to 3.7%). kappa 1 to kappa 5 equaled 0.80, 0.40, 0.79, 0.91, and 0.92, respectively. CONCLUSIONS: Interobserver agreement for distinct 10% categories of angiographic carotid stenosis is moderate, but when realistic risk- and decision-based weights are used, agreement between experienced observers can be almost perfect.     

Intracapsular hip fractures. Results of management adopting a treatment protocol

The results of the treatment of 166 patients with intracapsular fractures of the femoral neck during a 30-month period are reviewed. A protocol was adopted whereby patients younger than 65 years of age, together with those with undisplaced fractures, were treated with internal fixation, whereas patients older than 85 years of age were treated with primary hemiarthroplasty. The remaining 120 patients, aged 65-85 years, with displaced fractures were carefully evaluated preoperatively using a scoring system of their physiologic status. The more ambulant and independent patients who were medically fit and mentally alert, with good proximal femoral bone stock, who achieved a physiologic status score (PSS) of 20 or more from a maximum of 26, were managed by reduction and internal fixation of their fractures. Those patients with a PSS below 20 were treated with replacement arthroplasty. At a mean of 21 months postfracture, the mortality was 14%, although, among survivors, there was a low incidence of fracture-related complications, with only 5% of the total group requiring reoperation for infection, internal fixation failure, or prosthetic dislocation. The functional outcome was satisfactory in both treatment groups, although the mean scores for regained mobility and final placement more closely approximated the prefracture scores in the patients undergoing internal fixation. The authors conclude that preoperative assessment of the PSS is a useful guide in determining the appropriate treatment for these fractures, and that internal fixation in the 42% of patients aged 65-85 years with a high PSS appears to be well justified.     

Treatment of hyperhomocysteinemia in renal transplant recipients. A randomized, placebo-controlled trial

BACKGROUND: Stable renal transplant recipients have an excess prevalence of hyperhomocysteinemia, which is a risk factor for arteriosclerosis. OBJECTIVE: To determine the effect of treatment with 1) vitamin B6 or 2) folic acid plus vitamin B12 on fasting and post-methionine-loading plasma total homocysteine levels in renal transplant recipients. DESIGN: Block-randomized, placebo-controlled, 2 x 2 factorial study. SETTING: University-affiliated transplantation program. PATIENTS: 29 clinically stable renal transplant recipients. INTERVENTION: Patients were randomly assigned to one of four regimens: placebo (n = 8); vitamin B6, 50 mg/d (n = 7); folic acid, 5 mg/d, and vitamin B12, 0.4 mg/d (n = 7); or vitamin B6, 50 mg/d, folic acid, 5 mg/d, and vitamin B12, 0.4 mg/d (n = 7). MEASUREMENTS: Fasting and 2-hour post-methionine-loading plasma total homocysteine levels. RESULTS: Vitamin B6 treatment resulted in a 22.1% reduction in geometric-mean post-methionine-loading increases in plasma total homocysteine levels (P = 0.042), and folic acid plus vitamin B12 treatment caused a 26.2% reduction in geometric-mean fasting plasma total homocysteine levels (P = 0.027). These results occurred after adjustment for age; sex; and pretreatment levels of total homocysteine, B vitamins, and creatinine. CONCLUSIONS: Vitamin B6 should be added to the combination of folic acid and vitamin B12 for effective reduction of both post-methionine-loading and fasting plasma total homocysteine levels in renal transplant recipients.     

Orbital dermoid cysts: clinicopathologic correlations, classification, and management. The 1997 Josephine E. Schueler Lecture

The dermoid cyst is one of the most common space-occupying orbital lesions, but there has been no large series that details the clinical, pathologic, and therapeutic aspects of this condition. Furthermore, despite the various presentations and types of dermoid cysts, there is no clinically applicable classification of these lesions. We performed a retrospective histopathologic study of 197 consecutive orbital and periorbital dermoid cysts excised at Wills Eye Hospital during a 32-year period, correlated the histopathologic findings with the recorded clinical and radiographic observations, and devised a clinically applicable classification of orbital dermoid cysts. The mean age at excision was 17 years (range, 5 months to 85 years), and the most frequent clinical finding was a painless subcutaneous mass, present in 89% of cases. In 72% of patients, the mass was located in the superotemporal orbital region and produced no abnormalities of vision or intraocular pressure. Computed tomography and magnetic resonance imaging, performed mainly in the more recent cases, disclosed a characteristic round to ovoid cystic lesion with a well-defined lining. Histopathologically, 165 of the cysts (84%) were lined by keratinizing, stratified squamous epithelium. Ten (5%) were lined by nonkeratinizing epithelium resembling conjunctival epithelium. Hair shafts were present in the wall or lumen of the cyst in 195 (99%) of specimens, sebaceous glands in 148 (75%), and sweat glands in 39 (20%); inflammation was present in 75 cases (38%). Based on these personal observations and a review of the literature, a classification of orbital dermoid cysts is proposed that we believe will provide guidance for the ophthalmologist in the management of these lesions.     

Ethical dilemmas associated with hypoplastic left-heart syndrome

This questionnaire-based study elucidates the attitudes of Norwegian paediatricians and child cardiologists towards the surgical treatment of hypoplastic left-heart syndrome. During the last five years, 29 out of 53 Norwegian children have received surgical treatment in the USA or Switzerland. To date, approximately 50% of the children have survived three operations. In the present study, which comprises 26 of the physicians who are most frequently confronted with these children, none expressed that they were opposed to surgical treatment. Five of the 26 physicians stated that surgery should be obligatory, while 15 felt that this decision should be taken by the child's parents. The majority of the physicians inform the parents of the uncertain long-term prognosis and the possible need for future heart transplantation. The majority of the physicians also stated that it is difficult to give unbiased information. A surprisingly high number of the physicians consider the media and other parents to have as great an influence on the parents' choice of treatment as the paediatricians themselves have. Few Norwegian physicians considered the expenses related to the treatment to be the most difficult ethical dilemma. The majority of the physicians felt that the children should be treated in Norway or in another Nordic country.     

Assessment of the interphotoreceptor matrix proteoglycan-1 (IMPG1) gene localised to 6q13-q15 in autosomal dominant Stargardt-like disease (ADSTGD), progressive bifocal chorioretinal atrophy (PBCRA), and North Carolina macular dystrophy (MCDR1)

We have recently characterised the genomic organisation of a novel interphotoreceptor matrix proteoglycan, IMPG1, and have mapped the gene locus to chromosome 6q13-q15 by fluorescence in situ hybridisation. As the interphotoreceptor matrix (IPM) is thought to play a critical role in retinal adhesion and the maintenance of photoreceptor cells, it is conceivable that a defect in one of the IPM components may cause degenerative lesions in retinal structures and thus may be associated with human retinopathies. By genetic linkage analysis, several retinal dystrophies including one form of autosomal dominant Stargardt-like macular dystrophy (STGD3), progressive bifocal chorioretinal atrophy (PBCRA), and North Carolina macular dystrophy (MCDR1) have previously been localised to a region on proximal 6q that overlaps the IMPG1 locus. We have therefore assessed the entire coding region of IMPG1 by exon amplification and subsequent single stranded conformational analysis in patients from 6q linked multigeneration families diagnosed with PBCRA and MCDR1, as well as a single patient from an autosomal dominant STGD pedigree unlinked to either of the two known STGD2 and STGD3 loci on chromosomes 13q and 6q, respectively. No disease associated mutations were identified. In addition, using an intragenic polymorphism, IMPG1 was excluded by genetic recombination from both the PBCRA and the MCDR1 loci. However, as the autosomal dominant Stargardt-like macular dystrophies are genetically heterogeneous, other forms of this disorder, in particular STGD3 previously linked to 6q, may be caused by mutations in IMPG1.