Localization of calcium in murine epidermis following disruption and repair of the permeability barrier. Perturbation of the cutaneous permeability barrier results in rapid secretion of epidermal lamellar bodies, and synthesis and secretion of new lamellar bodies leading to barrier repair. Since external Ca2+ significantly impedes the repair response, we applied ion capture cytochemistry to localize Ca2+ in murine epidermis following barrier disruption. In controls, the numbers of Ca2+ precipitates in the basal layer were small, increasing suprabasally and reaching the highest density in the stratum granulosum. Barrier disruption with acetone produced an immediate, marked decrease in Ca2+ in the stratum granulosum, accompanied by secretion of lamellar bodies. Loss of this pattern of Ca2+ distribution was associated with the appearance of large Ca2+ aggregates within the intercellular spaces of the stratum corneum. The Ca(2+)-containing precipitates progressively reappeared in parallel with barrier recovery over 24 h. Disruption of the barrier with tape stripping also resulted in loss of Ca2+ from the nucleated layers of the epidermis, but small foci persisted where the stratum corneum was not removed; in these sites the Ca2+ distribution did not change and accelerated secretion of lamellar bodies was not observed. Following acetone-induced barrier disruption and immersion in isoosmolar sucrose, the epidermal Ca2+ gradient did not return, and both lamellar body secretion and barrier recovery occurred. However, with immersion in isoosmolar sucrose plus Ca2+, the epidermal Ca2+ reservoir was replenished, and both secretion of lamellar bodies and barrier recovery were impeded. These results demonstrate that barrier disruption results in loss of the epidermal Ca2+ reservoir, which may be the signal that initiates lamellar body secretion leading to barrier repair.


Appearance and endocytic activity of epithelial cells from human efferent ducts in primary monolayer culture. The culture of epithelial cells lining human efferent ducts, obtained from prostatic carcinoma patients, is described. Ciliated cells were observed to beat for at least one month on plastic. On previous filters low cuboidal cells characterized the monolayers. Cells comprising monolayers over the filter were 5 to 9 microns in height whereas taller cells were found over the original fragments (14 microns). Some non-ciliated cells contained dark and light vacuoles, others were found to lack them. Both non-ciliated and ciliated cells maintained tight junctional complexes restricting the paracellular movement of horseradish peroxidase. Both types of cultured cells exhibited fluid-phase and adsorptive endocytosis from both apical and basal surfaces. It is reported for the first time that the monolayers form high resistance barriers (150 omega.cm2) that prevent the apical medium from draining to the basal compartment over 24 h.


Structure and protein composition of sites of papillary muscle attachment to chordae tendineae in avian hearts. Most cardiac myocytes transmit force across fasciae adherentes, specialized sites of cell-cell adhesion. However, some cardiac myocytes in papillary muscle terminate on collagenous connective tissue in the chordae tendineae. These papillary myotendinous junctions (MTJs) are specialized for force transmission from myocytes to extracellular matrix. In the present study, we compared structural molecules at papillary MTJs to those at fasciae adherentes and skeletal MTJs. By using indirect immunofluorescence, we found that papillary MTJs more closely resemble skeletal MTJs in their molecular composition in that they are enriched in talin, vinculin, integrin, and fibronectin. Zeugmatin and alpha-actinin, both components of fasciae adherentes, are absent from papillary MTJs. Although papillary MTJs and skeletal MTJs display strong similarities in structural protein composition, ultrastructural organization of the two junctions is different. Papillary MTJs display little folding of the junctional membrane and, according to morphological criteria, more closely resemble sites of thin filament-membrane association in smooth muscle than skeletal MTJs. Thus, papillary MTJs display a combination of structural characteristics described previously in skeletal and smooth muscles but exhibit few structural features observed previously in cardiac fasciae adherentes.


Immunohistochemical localisation of natriuretic peptides in the brains and hearts of the spiny dogfish Squalus acanthias and the Atlantic hagfish Myxine glutinosa. The avidin-biotin peroxidase technique was used to determine the distribution of natriuretic peptides in the hearts and brains of the dogfish Squalus acanthias and the Atlantic hagfish Myxine glutinosa. Three antisera were used: one raised against porcine brain natriuretic peptide which cross-reacts with atrial natriuretic and C-type natriuretic peptides (termed natriuretic peptide-like immunoreactivity); the second raised against porcine brain natriuretic peptide which cross-reacts with C-type natriuretic peptide, but not with atrial natriuretic peptide (termed porcine brain natriuretic peptide-like immunoreactivity); and the third raised against rat atrial natriuretic peptide (termed rat atrial natriuretic peptide-like immunoreactivity). Only natriuretic peptide-like immunoreactivity was observed in the heart of S. acanthias which was most likely due to the antiserum cross-reacting with C-type natriuretic peptide. No immunoreactivity was found in the M. glutinosa heart. In the brain of S. acanthias, natriuretic peptide-like immunoreactive fibres were located in many areas of the telencephalon, diencephalon, mesencephalon, rhombencephalon, and spinal cord. Extensive immunoreactivity was observed in the hypothalamo-hypophyseal tract and the neurointermediate lobe of the hypophysis. Natriuretic peptide-like immunoreactive perikarya were found in ventromedial regions of the telencephalon and in the nucleus preopticus. Most perikarya had short, thick processes which extended toward the ventricle. Another group of perikarya was observed in the rhombencephalon. Porcine brain natriuretic peptide-like immunoreactive fibres were observed in the telencephalon, diencephalon, mesencephalon, and rhombencephalon, but perikarya were only present in the preoptic area. In the M. glutinosa brain, natriuretic peptide-like immunoreactive fibres were present in all regions. Immunoreactive perikarya were observed in the pallium, primordium hippocampi, pars ventralis thalami, pars dorsalis thalami, nucleus diffusus hypothalami, nucleus profundus, nucleus tuberculi posterioris, and nucleus ventralis tegmenti. Porcine brain natriuretic peptide-like immunoreactive perikarya and fibres had a similar, but less abundant distribution than natriuretic peptide-like immunoreactive structures. Although the chemical structures of natriuretic peptides in the brains of dogfish and hagfish are unknown, these observations show that a component of the natriuretic peptide complement is similar to porcine brain natriuretic peptide or porcine C-type natriuretic peptide. The presence of natriuretic peptides in the brain suggest they could be important neuromodulators and/or neurotransmitters. Furthermore, there appears to be divergence in the structural forms of natriuretic peptides in the hearts and brains of dogfish and hagfish.


Surface cap modifications in cold-treated Drosophila melanogaster embryos. When early Drosophila embryos were allowed to develop at 0 degree C, several abnormalities in the surface cap organization were observed. Scanning electron microscopy showed that exposure to cold mainly lead to the deformation of the cortical caps and to their partial fusion with adjacent caps. The process of cellularization was presumably affected and large uncellularized areas were observed. Rhodamine-phalloidin staining showed that cap deformation was closely related to the altered microfilament distribution, which was presumably responsible for the failure of large syncytial areas to cellularize. During the process of cellularization, F-actin localization did not depend on the microtubules forming the baskets around the elongating nuclei, but was related to the subpopulation of microtubules radiating from the centrosomes toward the plasma membrane. Only these microtubules seemed to be affected by cold treatment.


Uveoscleral permeability to intracamerally infused ferritin in eyes of rabbits and monkeys. The permeability of the uveoscleral outflow pathway from the anterior ocular chamber was examined in rabbit and monkey eyes using anionic ferritin as a tracer. Ferritin, infused intracamerally, had ready access to the choroidal interstitium, and the degree of penetration was generally correlated with the time and pressure relationships during infusion. In both species, there were accumulations of tracer in intercellular spaces at the lamina fusca, but tracer was also present in the sclera. Thus, in contrast to the situation in the eyes of hamsters, the uveoscleral outflow pathway in the eyes of rabbits and monkeys includes the choroidal connective tissue and allows passage of relatively large molecular weight substances.


Immuno-electron-microscopic localization of basic fibroblast growth factor in the dystrophic mdx mouse masseter muscle. The localization of basic fibroblast growth factor (bFGF)-like immunoreactivity in the masseter muscle of dystrophic mdx mice on postnatal day 28 was investigated by immunoblot analysis and electron microscopy. Crude homogenate of the masseter muscle, when subjected to immunoblotting with a bFGF antiserum, exhibited a main band with the same molecular weight (18 kDa) as bovine bFGF. By electron microscopy, bFGF immunoreactivity was detected in small regenerating myocytes; the smaller cells were the premature myocytes, the most intense staining was the immunoreactivity within the cytoplasm. Putative precursors of the muscle cells with a few myofilaments, which were most intensely labeled with anti-bFGF, contacted each other and possibly developed into multinucleated myocytes through cell fusion. Mature myocytes with densely packed myofilaments and peripherally located nuclei did not exhibit bFGF immunoreactivity; they formed myoneural junctions with motor nerve endings immunoreactive for bFGF. Early differentiating myocytes with intense bFGF-like immunoreactivity did not make contact with immunoreactive nerve terminals. Degenerating large myocytes with a limited number of distorted and/or disrupted myofilaments exhibited electron-dense deposits in the cristae of mitochondria; these deposits were not abolished by immunoadsorption control experiments. Thus, the cell-size-dependent decrease in bFGF immunoreactivity in regenerating but not in degenerating myocytes provides a morphological basis for an autoregulatory role of bFGF in muscle regeneration. This study suggests that neuronal bFGF is not involved in initial muscle regeneration in the dystrophic mdx mouse.


Expression of mRNA of parathyroid hormone-related peptide in fetal bones of the rat. Previous studies have indicated that 19-day-old fetal long bones of the rat contain an adenylyl cyclase-stimulating activity antigenically related to parathyroid hormone-related peptide. To ascertain its origin, Northern blotting and in situ hybridization histochemistry were performed. Results demonstrate that mRNA of parathyroid hormone-related peptide is present in RNA extracted from fetal long bones of the rat and that cells responsible for its production are localized in the periosteum. These cells are not mature osteoblasts because they do not synthesize mRNA of osteocalcin. Thus the present study shows that parathyroid hormone-related peptide could be produced locally, at least in part, in the skeleton of fetal rats.


Immunocytochemical identification of some regulatory peptides (gastrin, gastrin-releasing peptide, neurotensin and vasoactive intestinal polypeptide) in the Harderian gland of the green frog, Rana esculenta. The presence and distribution of gastrin-, gastrin-releasing peptide-, neurotensin- and vasoactive intestinal polypeptide-like immunoreactivity in the Harderian gland of Rana esculenta were studied at different times of the annual cycle. Gastrin-releasing peptide, neurotensin and vasoactive intestinal polypeptide-like substances were found either in the glandular cells, or in the nerve fibers surrounding the glandular acini. Gastrin-like immunoreactivity was confined to the glandular cells. The immunoreactivity varied during the annual cycle, with the greatest concentration being noted during the recovery phase of glandular secretory activity.


Progress in the control of schistosomiasis in Zimbabwe since 1984. Schistosomiasis remains the second most important parasitic disease in Zimbabwe. In terms of its combined morbidity and prevalence, schistosomiasis is thought to be the most important helminth infection of man. Since 1984, a number of control programmes have commenced around the country and a national control programme aimed at reducing morbidity is being implemented. The strategy adopted in Zimbabwe is a community based approach integrated in the primary health care system.


Norplant in Zimbabwe: preliminary report. During an ongoing study of a pre-introduction trial of Norplant in Zimbabwe, 197 women had the subdermal implant of six capsules containing levonorgestrel inserted between June and December 1991, at Parirenyatwa, Harare Hospital and Spilhaus. Acceptability and efficacy were high and no significant side effects had been observed. Three implants were removed due to local infection. Our initial experience indicates that the Norplant continuation rate is much higher than for any other reversible method of contraception and it is highly acceptable as a long term contraceptive.


The effects of cluster sampling in an African urban setting. Cluster sampling was popularised by the sampling procedure promoted by the WHO/UNICEF for the evaluation of the expanded programme of immunisation (EPI). Without a clear understanding of the limitations of the sampling strategy used, this sampling strategy has been extended to other types of surveys. This article shows how to approach the assessment of cluster sampling techniques scientifically by calculating design effects (DEFFs) and rates of homogeneity (roh) and illustrates this scientific assessment with three case studies from Alexandra in South Africa. We report on the DEFFs and rohs for variables studied in these surveys. The DEFF for all the variables relating to housing tended to exceed two and was as high as 6.99 for the variable new development. The variables relating to health service utilisation and health practices, namely immunisation status, nutrition status, presence of Road to Health Cards (RTDCs), breast-feeding and knowledge of diarrhoea and oral rehydration all had a DEFF close to one. The variables relating to contraception use, literacy and schooling had DEFFs close to one and a half. For a few variables the DEFFs were below one and the rates of homogeneity less than zero. The highest values of roh were for environment factors (all above 0.1433). Rohs for factors related to utilization of PHC services were mostly between 0.0200 and 0.0499. No single class of factors seemed to be related to very low values of roh. These results are then discussed.


The use of drug level measurements in adult patients receiving theophylline, anti-epileptic drugs and amikacin. This prospective study was conducted to determine how frequently measurement of drug levels was used in the management of adult patients receiving theophylline, phenytoin, phenobarbitone, carbamazepine or aminoglycosides in a large hospital. Fifty consecutive outpatients with asthma and 40 with epilepsy were interviewed and their records reviewed to determine which drugs had been prescribed and whether a level of the appropriate drug had been measured in the previous six months. Also, the records of 40 in-patients who were currently receiving amikacin were studied to determine whether serum levels had been measured at any stage during therapy with this drug. Serum theophylline levels were measured in only four (eight pc) patients who were taking this drug and were below the target range in two patients. Serum levels had been measured in 21 (52.5 pc) of 40 patients who were receiving 45 anti-epileptic drugs and were within the target in only nine. Serum amikacin levels were measured in 15 (37.5 pc) patients; blood had been taken for both peak and trough levels in 10 patients and found to exceed the target range in two patients. This study revealed that measurement of serum concentrations of theophylline, anti-epileptic drugs and amikacin was underutilised in the management of adult patients receiving these drugs at this hospital.


Early natural history of untreated Perthes' disease. Thirty patients with Legg-Calve'-Perthes' Disease (LCPD) presenting in Gwynedd, North Wales over a ten year period were reviewed with the aim of determining retrospectively the short-term clinical and anatomical outcome of the untreated condition. They were all allowed unrestricted activity irrespective of their radiological appearances. The mode of presentation, activity levels, analgesic requirements and physical signs during the active phase and at the final review were assessed. The clinical end-result assessment was based on a modification of the Harris hip assessment system. The radiological end-result was based on the Stulberg-End-Result Classification. The clinical results were satisfactory, with only 3.3 pc poor results; 23.3 pc fair and 73.3 pc good. The radiological results were 10 pc poor; 30 fair and 60 pc good. It is concluded that the short-term outcome of untreated LCPD is satisfactory in the majority of patients.


Incidence of hypo-parathyroidism following thyroidectomy in a prospective study of 108 consecutive African patients. In a prospective study of 108 consecutive African patients in the University of Benin Teaching Hospital undergoing thyroidectomy over the period 1986-1990, one patient had overt hypoparathyroidism while six others presented with the latent form, giving an overall incidence of 6.5 pc. Hypoparathyroidism was associated with large adherent goitres involving extensive dissection. Routine post-operative serum calcium is advocated so as not to miss latent hypoparathyroidism. Identification of the parathyroids with preservation of the blood supply should be carefully observed so as to minimise the incidence of hypoparathyroidism.


Ultrasonography as an adjunct to hydrotubation in the management of female infertility. Thirty one female patients who were being investigated for infertility had hydrotubation with ultrasound monitoring (sonosalpingography) in addition to the standard tubal patency tests of hysterosalpingography (HSG) and dye test at laparoscopy. Compared to the standard tests, sonosalpingography (SSG) had a sensitivity of 90 to 100 pc and a specificity of 95 pc in detecting bilateral tubal occlusion. In the detection of side-specific patency of the tubes, SSG had a sensitivity of 94 pc and 89 pc when compared with HSG and laparoscopy respectively. The corresponding specificity values were 83 pc and 85 pc. Hydrotubation enhanced the ability of ultrasonography to detect such uterine abnormalities as uterine synechae, intrauterine septa and submucous fibroids. It was concluded that sonosalpingography is a sensitive and relatively safe screening method for assessing tubal patency in infertile women. It also provides valuable information about the uterine wall and uterine cavity.


Seizures associated with chloroquine therapy. Three cases of tonic-clonic seizures following therapeutic doses of chloroquine for malaria are presented. A casual relationship between seizures and chloroquine therapy is suggested. There have been no previous reports of this adverse effect of chloroquine therapy in patients normally resident in a holoendemic area for malaria.


[Phacoemulsification. The method of choice in cataract surgery]. Complications and problems in the first 300 patients operated on by phacoemulsification technique are described. In the first 100 cases the procedure began with the creation of the corneoscleral incision and the anterior capsule was opened in a "can opener" fashion. In the second group of 200 patients we preferred the scleral incision, and the anterior capsule was opened mainly by capsulorhexis. The phacoemulsification was predominantly performed in the capsular bag or in the iris plane. The wound was closed with interrupted sutures. The most common and the most serious complication as well in the first 100 cases was posterior capsule rupture (11%). Then the percentage of this most common complication was diminished significantly with increasing experience of the surgeon (2.5% in 200 cases). The same problems which the authors had in their first operations appeared again, though in a smaller amount as soon as they started to work with phacoemulsification as a method of choice of cataract surgery.


[Results of 52 operations for traumatic cataracts]. The authors are presenting the results of the traumatic cataract surgery in 52 patients (45 male, 7 female). The cataract was caused in 7 cases by blunt trauma, in 43 cases by penetrating trauma (in 16 cases with intraocular foreign body). The mean age of patients was 29 years, ranging from 4 to 73 years. In 2 cases was indicated the intracapsular extraction for the subluxation of the lens, in 2 eyes the discision was done and in 2 eyes the primary evacuation. In all other cases the extracapsular extraction was performed (19 with IOL implantation). Before the operation the visual acuity was 0.1 and worse in 90.4%, 0.16-0.33 in 7.7% and 0.5 and better in 1.9% of the patients. The visual acuity at the time of the last follow-up visit (3 months to 3.5 years after the operation-average 15.6 months) was 0.1 and worse in 16.7% of cases, 0.16-0.33 in 19% and 0.5 and better in 64.3%. The visual acuity 0.5 and better was in 85.7% of patients with IOL implantation. The most serious complication was the hypotony of the eye (in 3 cases) followed by the atrophy of the eye (1 eye was enucleated). Although we could expect more complications of the surgery of traumatic cataract it is possible to gain good visual acuity results. The IOL implantation is indicated in cases where it is not excluded by the condition of the eye.


[Cataract operations and implantation of intraocular lenses in children and adolescents]. The authors are presenting the results of 60 cataract operations performed in 54 patients younger then 18 years. Traumatic cataract was operated in 33 patient (29 boys, 4 girls), congenital cataract in 19 eyes and complicated cataract in 8 eyes. The visual acuity 0.5 and better was gained in 40% of the eyes in which it was possible to find out the visual acuity. This visual acuity was achieved in 50% of 19 patients with IOL implantation (the youngest was 4 years old). The visual acuity was 0.5 and better in 75% of 12 patients regularly wearing contact lens. The worse results were in patients with congenital cataract-just one eye from 10, in which the visual acuity was possible to evaluate, had the visual acuity 0.5. In one case it was necessary to replace the luxated posterior chamber IOL. The IOL implantation in children, especially in those with traumatic cataract, is becoming more frequent.


[Diabetic retinopathy in children and adolescents under 18 years of age]. We found ophthalmoscopically microaneurysms in 22 patients from 189 diabetics (11.6%). The youngest patients with microaneurysms were two 11-years-old girls with 3 and 5 years lasting disease. The chance of retinopathy was growing with the duration of the diabetes. By fluorescein angiography we discovered retinopathy in 52 patients out of 126 diabetics (41.3%). The retinopathy was more often found among girls. Just in one case we found the early stage of preproliferative retinopathy. The retinopathy was more often found in diabetics with higher levels of glyconated hemoglobin. The extent of foveolar avascular zone is decreasing with the longer course of the diabetes. We recorded lower occurrence of diabetic retinopathy in patients treated at the Ist Department of Pediatrics in Bratislava. In the group evaluated in the years 1986-89 the occurrence of the diabetic retinopathy diagnosed ophthalmoscopically was lower than in the group of 1981-84.


[The clinical picture of Fuch's heterochromic cyclitis]. The authors are presenting their experience with the diagnosis and treatment of Fuchs' heterochromic cyclitis. They followed-up 13 patients with this disease for 0.5-3 years. Most often the patients were sent to the clinic with the diagnosis of recurrent anterior uveitis not responding to the treatment with corticosteroids and mydriatics. Patients underwent numerous investigations including neurological, internal and rheumatological examinations. Antibodies against EBV, HSV and CMV were detected. The examination of humoral immunity and HLA was done. The authors describe the ophthalmological findings, the course of the disease and the treatment. They did not find any correlation in the laboratory investigations and the course of the disease, the diagnosis is based on the clinical picture. They point out the advantage of the small incision in the extracapsular extraction of cataract in these patients.


[Charlin's syndrome--nasociliary nerve neuralgia]. The history, etiopathogenetical factors, clinical symptomatology, differential diagnosis and therapy of neuralgia nervi nasociliaris--Charlin's syndrome are described. The authors give an account of an 18-years-old male patient.


[Levobunolol HCl--a beta-blocker produced by the firm Allergan]. Vistagan is a new beta-blocker produced by Allergan that is used for treatment of glaucoma. The results of a clinical trial with 18 patients with open-angle glaucoma, previously treated with Timoptol, are presented. Vistagan was as effective as Timoptol in reducing the intraocular pressure and was better tolerated by patients.


[Use of hypnosis in certain forms of childhood strabismus]. The authors describe the case of a mentally very labile boy suffering from strabism. When he was excited, the deviation of the affected eye increased, diplopia, nausea and headache developed. Hypnosis was applied and the condition improved after 12 sessions. His behaviour changed and progress in school improved. The authors draw attention to new therapeutic possibilities of some forms of strabism in mentally labile children by application of hypnosis.


[Contrast sensitivity and vision].

[Contrast sensitivity and vision]. From results of the contrast sensitivity test (n = 65, r = 0.834) it is possible to estimate visual acuity with considerable provedes, however, in addition also information on vision at low contrast conditions and on vision of large objects. It may therefore be expected that in future the two-dimensional visuogram will replace in clinical practice the commonly used test used for assessment of visual acuity.


[The argon laser in the prevention of retinal detachment]. In a group of 57 eyes in 51 patients the authors analyze seven years' experience with the use of an argon laser in the prophylaxis of detachment of the retina. The advantages of the argon laser were most marked in traumatic ruptures of the retina and in peripheral vitreoretinal degenerations. In eyes with not closed ruptures after episcleral filling argon laser coagulation proved successful in 77%.


[An intraorbital foreign body with fulminant phlegmon]. The authors describe the case of an intraorbital foreign body of plant origin. An extensive phlegmon in the orbit caused by the foreign body led in the end to enucleation. The authors discuss diagnostic possibilities for detection and localization of foreign bodies in the orbit, focused in particular on CT.


[Prognostically important features of uveal melanoma in histopathologic examinations]. The prognostic value of various morphological features of the uveal melanoma (i.e. histological type, maximal distance and shape of the tumour, the extension of the tumour, it's site in various parts of the uvea and the mitotic activity and pleomorphism within the tumour) is described. The description and evaluation is based mainly on the histopathologic examination of enucleated globe. The possibilities of the clinical examination or using of specialized methods are mentioned.


[Overview of the clinical use of the specular reflex in intraocular lenses]. On both surfaces of the intraocular lens, due to its physical properties, an intense and homogenous reflex develops suitable for retrograde illumination of the cornea, anterior chamber, the remainder of the lenticular capsule, for examination of amorphous, cellular and fibrinous membranes on the surface of the intraocular lens and visualization of defects of the intraocular lens. Based on experience from specular routine microscopic examinations the author considers that visualization of defects of the Descemet's membrane is most useful as well as of precipitates on the endothelium in opaque structures of the cornea, evaluation of the immunological reaction on the surface of the intraocular lens as a picture of the dynamics of the reaction and biocompatibility of the material of the intraocular lens, detection of defects which occur during manufacture and manipulation in the operation theatre in vivo and defects during YAG-laser therapy with possible subsequent adjustment of the intensity and focusing.


[Significance of immunologic reactions on the surface of intraocular lenses]. The authors summarize their experience assembled during specular examinations of immunological processes on the surface of the intraocular lens. They describe the incidence of significant components of the immunological reaction--of "large cells", "fibroblast-like cells", round elements, fibrous and acellular membranes on the surface of the intraocular lens. The "large cells" are considered the most important components of the reaction from the clinical aspects. Their incidence depends most frequently on a change in the position of the intraocular lens and non-adherence to therapy in the early postoperative stage. The authors present findings assembled in patients with late changes of the position and formation of synechiae and subluxation, most probably traumatic, and occur in patients who did not respect local corticoid treatment in the early postoperative period. A similar character of the specular finding indicates uniformity of the non-specific reaction which is potentiated by interference with the haemotoocular barrier for various reasons.


[Personal experience in the treatment of proliferative diabetic retinopathy using an argon laser]. The authors evaluate a group of 44 eyes treated by panretinal photocoagulation by means of an argon laser on account of proliferative diabetic retinopathy. Complete regression of neovascularizations was achieved in 64%, partial regression in 23%, treatment failed in 13%. The resulting visual acuity of 6/12 or better was achieved in 57%, at least stabilization of visual acuity was achieved in 80%, the mean follow-up period being 2.3 years. The results of treatment with an argon laser was analyzed also separately for proliferative diabetic retinopathies of different grades. The authors confirm that advanced stages of proliferative diabetic retinopathy respond more poorly to panphotocoagulation and explain this by an assumed certain grade of autonomy in very advanced proliferative diabetic retinopathy. Therapeutic failure was observed only in a group of eyes with very advanced proliferative retinopathy. The authors also confirm the observation, that if a positive response to laser therapy develops within 3-6 weeks, this is a favourable prognostic sign. In neovascularizations of the retina they observed a more favourable response to panphotocoagulation than in neovascularizations on the disc of the optic nerve.


Risk factors contributing to acute diarrhoeal disease in children below five years. Data regarding factors contributing to acute diarrhoea in children under five years in urban populations in Sri Lanka is meagre. Studies of diarrhoeal disease have been limited mainly to descriptive epidemiological investigations. A case control study on 200 families in the Galle Municipality was undertaken to identify some of the social, behavioural and environmental factors contributing to childhood diarrhoea. Twelve variables were studied by logistic regression, and the following variables were identified as conferring a significant risk of causing diarrhoeal disease in children below five years in an urban setting in Sri Lanka; (1) unavailability of pipe-borne water in the house (2) lack of water-seal latrine in the household (3) low level of mother's education and her lack of awareness regarding infectious nature and mode of spread of diarrhoea (4) not disposing of children's faeces in a latrine (5) improper disposal of garbage.


Effects of transcutaneous needle stimulation on the immune response in rabbits. Studies in the field of neuroimmunomodulation have shown that endorphins such as methionine-encephalin may have an immunomodulatory role. This study was undertaken to test whether transcutaneous needle stimulation, which is known to release such peptides from the central neurones, has an effect on immune response in rabbits. Twelve healthy rabbits, in three similar subgroups, were exposed to pathogenic Escherichia coli and their immune response was studied under different experimental conditions. Our results show that needle stimulation causes a reversal of stress induced suppression of antibody production. Further studies are necessary to evaluate any therapeutic uses these observations may have in humans.


The General Hospital Colombo Rehabilitation Project. The General Hospital Colombo (GHC) Rehabilitation Project was to be implemented in 6 phases in about 25 years. The proposed funding was a grant of 100% from Finland for technical assistance and training, and 85% for investments. The development objective was to reinforce the status of the hospital as the apex of the medical care system. In Phase I (1985-1990) an 8 storeyed accident and orthopaedic services building with modern facilities has been commissioned. A water tower and a 'septic' operating theatre have been built. Infection control and maintenance organizations have been started. Phase I cost Rs.960 million. In the Bridging Phase, the existing six storeyed building is being renovated. Phase II has been drastically curtailed. It will concentrate on infrastructure development such as water supply, kitchen, stores and transport, and the construction of four new medical wards. The project will end in 1993.


Mycobacterium ulcerans infection; is the "Bairnsdale ulcer" also a Ceylonese disease? Mycobacterium ulcerans infection produces progressive skin ulceration in man and other mammalia. The disease was first described in 1984 in patients from the Bairnsdale district in Australia, but was known in Africa well before this time. It has since been reported from many, mostly tropical countries in Africa, central and south America, and south-east Asia. The infection characteristically occurs in closely defined areas which are related to river or lacustrian systems draining tropical or warm temperate rain forest. Like the flora to which it relates, the mycobacterium shows a Gondwanian distribution which is evidence of its great antiquity. There is evidence that cases of the infection have occurred on the Indian subcontinent. Infection if it does occur would support the theory that the mycobacterial infection is related to tropical or warm temperate rain forest plant species with a Gondwanian distribution.


Survey of blood donors in Sri Lanka, 1985. Of 26,932 blood donors at the Central Blood Bank and at three mobile units that covered most parts of the Island during 1985, 81.4% were men and 18.6% women. The age range acceptable for blood donations is 18 to 55 years. The largest number of donors in both sexes were in the 21 to 30 year age group, with the next common group being 31 to 40 years for men and 18 to 20 years for women.


A near fatal case of corrosive burns from decomposed chloral hydrate administration. A case of corrosive burns to the face and upper airway from administration of chloral hydrate is presented. Events leading to the accident and dispensing of the drug are discussed.


Efficient preparation of steroidal 5,7-dienes of high purity. Protected forms of dehydroepiandrosterone, delta 5 cholenic acid, (25R)-26-hydroxycholesterol and diosgenin were converted to the corresponding delta 5,7 dienes by successive treatment with 1,3-dibromo-5,5-dimethylhydantoin (dibromantin), tetrabutylammonium bromide and tetrabutylammonium fluoride. The crude products, which contained the delta 5,7 species contaminated by minor amounts of the delta 5 and delta 4,6 steroids, were purified by silica gel-AgNO3 chromatography to give the following steroids in approximately 99% purity and at least 50% yield: 3 beta-acetoxyandrosta-5,7-dien-17-one, methyl 3 beta-acetoxychola-5,7-dien-24-oate, (25R)-3 beta,26-diacetoxycholesta-5,7-diene and (25R)-3 beta-acetoxyspirosta-5,7-diene. Analogous treatment of acetate derivatives of pregnenolone and stigmasterol gave 3 beta-acetoxypregna-5,7-dien-20-one and 3 beta-acetoxystigmasta-5,7,22-triene in approximately 50% yield but of lower purity. Full 1H and 13C NMR assignments are given for seven delta 5,7 steroid acetates and the corresponding delta 5 starting materials. Coupling constants for rings A, B and C of delta 5,7 steroids are presented and stereochemical assignments have been made for the following 1H NMR signals: the C-11 protons of delta 5,7 steroids, the C-16 protons of sterols and bile acids, the C-22 and C-23 protons of bile acid esters and the C-28 protons of stigmasterol derivatives.


Monolayer properties of archaeol and caldarchaeol polar lipids of a methanogenic archaebacterium, Methanospirillum hungatei, at the air/water interface. Monolayer studies at the air/water interface were carried out on the major tetraether (caldarchaeol-) derived phosphoglycolipid, Glcp-alpha(1-2)-Galf-beta(1-1)-caldarchaeol-phosphoglycerol (PGC-I), the major diether (archaeol-) derived glycolipid, Glcp-alpha(1-2)-Galf-beta(1-1)-archaeol (DGA-I), the major archaeol-derived phospholipids, phosphatidyl-N,N dimethylaminopentanetetrol (PPDAA) and phosphatidyl-N,N,N-trimethylaminopentanetetrol (PPTAA) and the minor caldarchaeol-derived glycolipid, Glcp-alpha(1-2)-Galf-beta(1-1)-caldarchaeol (DGC-I) isolated from the methanogenic archaebacterium, Methanospirillum hungatei. The compression isotherms obtained showed that the two tetraether lipids had molecular surface areas about twice those of the diether lipids at all surface pressures, suggesting that both polar headgroups of the tetraether lipids are anchored into the aqueous subphase, even at the collapse pressure pi c. A U-shaped hydrocarbon chain conformation thus appears to be preferred for the tetraether lipids at the air/water interface, rather than an extended chain arrangement. The compression isotherms of the two tetraether lipids PGC-I and DGC-I were very similar at pH 0, both molecules being uncharged, but at pH 5.6 or 8, PGC-I films were much more expanded than the neutral DGC-I, due to ionization of the phosphate group in PGC-I and the resulting charge-charge repulsion. Monolayers of the zwitterionic diether phospholipids PPDAA and PPTAA were much less compressible than the glycosylated lipids, PGC-I, DGC-I and DGA-I, because the latter lipids contain the more compressible diglycosyl headgroup, oriented in horizontal conformation at low surface pressures, compared to the lower compressibility of the zwitterionic headgroup in the vertical conformation, particularly at pH 0 and 5.6.(ABSTRACT TRUNCATED AT 250 WORDS)


High pressure FTIR study of interaction of melittin with dimyristoylphosphatidyl glycerol bilayers. Infrared spectra of hydrated dimyristoylphosphatidyl glycerol (DMPG) and of aqueous dispersions of melittin and DMPG at peptide:lipid molar ratios of 1:10 and 1:4 were recorded as a function of pressure from atmospheric to 22 kbar. Spectral features corresponding to vibrations of the amide linkages in melittin and to various functional groups in DMPG (carbonyl, methlylene, phosphate) were monitored in order to investigate the structure and dynamics of melittin:DMPG dispersions. Melittin was found to cause conformational and orientational disordering of the acyl chains in DMPG bilayers. The magnitude of these disorders was higher for higher concentration of melittin in DMPG. The higher concentration of melittin was also found to disrupt the DMPG bilayers through interactions with the lipid head groups. Such disruption may be related to some of the biological properties of melittin.


Dextran sulfate-dependent fusion of liposomes containing cationic stearylamine. The incorporation of the positively charged stearylamine into phosphatidylcholine liposomes was studied by measuring electrophoretic mobilities. Up to a molar ratio SA/PC = 0.5 an increase of the positive zeta potential can be observed. Addition of the negatively charged macromolecule dextran sulfate leads to a change of the sign of the surface potential of the PC/SA liposomes indicating binding of the macromolecule to the surface. This process is accompanied by an increase in turbidity, which is dependent on the molecular weight of the dextran sulfate and the SA concentration (measured by turbidimetry). Using the NBD/Rh and Pyr-PC fluorescence assays the fusion of SA containing liposomes was investigated. A strong influence of the SA content and molecular weight of dextran sulfate on the fusion extent was observed. The fusion extent is proportional to the SA content in the PC membrane and the molecular weight of dextran sulfate. PC/SA/PE liposomes exhibit a higher fusion extent after addition of dextran sulfate compared to PC/SA liposomes indicating that PE additionally destabilizes the bilayer. Freeze-fracture electron microscopy reveals that the reaction products are large complexes composed of multilamellar stacks of tightly packed, straight membranes and aggregated vesicles. The tight packing of the membranes in the stacks (and the narrow contact of the aggregated vesicles) indicates a strong adherence of opposite membrane surfaces induced by dextran sulfate.


Inhibitions of the autoxidation of linoleic acid by flavonoids in micelles. The activities of five flavonoids as chain-breaking antioxidants have been studied for the autoxidation of linoleic acid in cetyl trimethylammonium bromide (CTAB) micelles at 37 degrees C. Flavonols such as quercetin, rutin and morin exhibited antioxidant activities, while two flavanones, naringin and hesperidin, did not suppress the oxidation appreciably. The ratio of rate constants for inhibition and propagation kinh/kp and stoichiometric factor n were determined.


Molecular weight determination of methyl esters of mycolic acids using thermospray mass spectrometry. Methyl esters of normal fatty acids, corynomycolate and corynomycolenate were used as model compounds for thermospray mass spectrometric procedures for molecular weight determination of the related nocardial mycolic acids. By using ammonium acetate at the positive ion generator, in both cases, a family of ions was produced. The following members were found and corresponded to the adducts: (1) M + H; M + NH4 and M + H + NH4 for methyl esters of normal fatty acids, whereas M + H, M + 2H and M + H + NH4 were the adducts most frequently observed with methyl corynomycolates. The methyl esters of C40-C48 mycolic acids from Rhodococcus rhodochrous exhibited prominent peaks corresponding to adducts M + H + NH4 whereas those corresponding to M + 2H showed slightly lower intensities. The structure M + H had no significant representatives with this subclass of mycolic acids. A similar pattern was observed with methyl esters of C50-C54 mycolic acids from Nocardia asteroides GUH-2. Ion peaks C50-C54 representing adducts M + 2H and M + H + NH4 prevailed in the mass spectrum. In this case, the intensities of peaks corresponding to M + 2H were slightly higher than those of the M + H + NH4. Essentially three main species of nocardomycolic acids were detected: (1) monounsaturated C50:1, C52:1 and C54:1; (2) diunsaturated C50:2, C52:2 and C54:2 and (3) triunsaturated C52:3 and C54:3 mycolic acids. The most abundant mycolic acid was C52:2 followed in decreasing abundance by C52:1, C54:2, C50:2, C52:3 and C54:3 mycolic acids.


Effect of alcohol chain length on tubule formation in 1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphocholine. Aqueous dispersions of 1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphocholine, on cooling below the chain melting temperature, form hollow cylindrical structures known as 'tubules'. We have studied the formation of tubules in methanol/water, ethanol/water and n-propanol/water. For each alcohol, there is a defined window of alcohol/water ratios in which the lipid precipitates with the tubule morphology. As the chain length of alcohol is increased, the window shifts towards lower alcohol fraction. Light scattering studies show that at very low lipid concentrations the tubules self-assemble directly from the isotropic phase where as for lipid concentrations greater than 4 mg/ml an intermediate L alpha phase is observed. These results indicate that the mechanism of tubule formation may be dependent on lipid concentration.


Effect of ionic strength on the transfer of 1-pyrenemethyl-3 beta-hydroxy-22,23-bisnor-5-cholenate between bilayer vesicles containing phosphatidylserine. The influence of ionic strength or the concentration of K+ ([K+]) of the aqueous phase on the spontaneous transfer of cholesterol between negatively charged bilayer vesicles composed of dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylserine (DPPS) (1:1, mole:mole) was studied using a pyrene-labelled cholesterol analogue, 1-pyrenemethyl-3 beta-hydroxy-22,23-bisnor-5-cholenate (PMC), as the probe. The decrease in PMC excimer fluorescence was best fitted to a bi-exponential function. Increasing [K+] from 0.1 M to 0.3 M had little effect on the shorter half-time (1.4 +/- 0.2 min) but increased the longer half-time from 16.3 +/- 1.9 min to 26.7 +/- 2.1 min. Fluorescence quenching and titration of an interface-located fluorophore, 1-anilinonaphthalene-8-sulfonic acid (ANS) revealed an increase in interfacial hydrophobicity upon increasing in ionic strength. The physical state of the acyl chains was not affected by ionic strength as indicated by a constant PMC excimer:monomer fluorescence intensity ratio. However, an increase in enthalpy change of the lipid phase transition from 15.7 kJ/mol ([K+] = 0.1 M) to 21.3 kJ/mol ([K+] = 0.3 M), together with a slight increase in the transition temperature, implies that interactions between adjacent molecules in the charged lipid bilayer vesicles became stronger at higher ionic strength. Our results suggest that the van der Waals attraction between PMC and phospholipid molecules could be affected by conformation changes in the charged head group region brought about by changes of ionic strength in the aqueous phase, with consequent effects on the desorption of cholesterol from the bilayer surface.


Inhibitors of sterol synthesis. Chemical syntheses and spectral properties of 26-oxygenated derivatives of 3 beta-hydroxy-5 alpha-cholest-8(14)-en-15-one and their effects on 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in CHO-K1 cells. 26-Oxygenated derivatives of delta 8(14)-15-ketosterols have been synthesized from (25R)-3 beta,26-diacetoxy-5 alpha-cholest-8(14)-en-15-one (IX) as part of a program to prepare potential metabolites and analogs of 3 beta-hydroxy-5 alpha-cholest-8(14)-en-15-one (I), a potent regulator of cholesterol metabolism. Partial hydrolysis of IX gave a mixture, from which the 3 beta,26-diol II and the 26-acetate (XI) and 3 beta-acetate (X) monoesters were isolated. Mitsunobu reaction of XI followed by hydrolysis gave (25R)-3 alpha,26-dihydroxy-5 alpha-cholest-8(14)-en-15-one (VI). Oxidation of XI with pyridinium chlorochromate followed by hydrolysis of the acetate gave (25R)-26-hydroxy-5 alpha-cholest-8(14)-ene-3,15-dione (VII). Oxidation of X with Jones reagent followed by hydrolysis of the acetate gave (25R)-3 beta-hydroxy-15-keto-5 alpha-cholest-8(14)-en-26-oic acid (IVa). Jones oxidation of II gave (25R)-3,15-diketo-5 alpha-cholest-8(14)-en-26-oic acid (VII). 1H and 13C nuclear magnetic resonance assignments and analyses of mass spectral fragmentation data are presented for each of the new compounds and their derivatives. The 3,15-diketone VII was found to be highly active in lowering the levels of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in CHO-K1 cells, with a potency comparable to that of I. In contrast, 3 alpha,26-diol VI was less potent than I or VII. The two carboxylic acid analogs IVa and VIII were considerably less potent than VI in lowering the levels of HMG-CoA reductase activity.


Structure and functions of a dimeric form of surfactant protein SP-C: a Fourier transform infrared and surfactometry study. Surfactant proteins SP-B (M(r) = 8700, reduced) and SP-C (M(r) = 3000-6000, major form, non-reduced) interact with surfactant phospholipids to enhance their surface active properties. In the present study, we describe the structural and functional characteristics of a novel dimeric form of bovine SP-C (M(r) = 9000, non-reduced), which is identified as [SP-C]2. Dimeric SP-C exhibits surface tension-lowering properties differing from those of monomeric SP-C and enhances the surface properties of bovine SP-B/phospholipid mixtures. Chemical analysis indicated that [SP-C]2 was not acylated at the cysteinyl residues. Fourier transform-infrared spectroscopy (FT-IR) was utilized to determine the secondary structures of [SP-C]2 in DPPC films. Relative percentages of alpha-helical, beta-sheet, beta-turn and random coil structures were calculated by peak fit analysis of the amide I band of the FT-IR spectra indicating that, in contrast to the helical structure of monomeric SP-C, [SP-C]2 exhibits almost exclusively beta-sheet structure. In addition, only 10% of the amide (backbone) hydrogens exchanged with deuterium of D2O, indicating that the remaining 90% of amide hydrogens were not accessible to D2O due to strong hydrogen bonding or their location in a hydrophobic environment. Dimerization of SP-C effects a major change in secondary structure, a factor which may play a role in the interaction of SP-C with phospholipids in pulmonary surfactant.


Can non-pharmacological interventions reduce doses of drugs needed for the treatment of hypertension? World Hypertension League. This article describes the impact of non-pharmacological interventions--salt restriction, weight control, alcohol consumption, exercise, and potassium supplementation--on the effects of drug treatment of hypertension, and their potential to reduce the patient's drug requirements. Although consensus on all aspects of such interventions has not yet been reached, the evidence that these approaches may reduce the need for drugs is considered satisfactory.


Use of monoclonal antibodies for rapid diagnosis of respiratory viruses: memorandum from a WHO meeting. A monoclonal antibody diagnostic kit (using immunofluorescence) to detect directly viral antigens of respiratory syncytial virus, influenza virus A, influenza virus B, parainfluenza viruses (types 1, 2, and 3), and adenovirus has been developed by WHO. During 1990 and 1991 a total of 16 laboratories in different parts of the world were invited to test the kit in clinical use. This Memorandum summarizes the results obtained as well as the discussions and recommendations made by participants at a WHO Consultation on Global Surveillance of Respiratory Viruses, held in Geneva on 25-27 March 1992.


The magnitude of the global problem of diarrhoeal disease: a ten-year update. In order to update global estimates of diarrhoeal morbidity and mortality in developing countries, we carried out a review of articles published from 1980 to the present and calculated median estimates for the incidence of diarrhoea and diarrhoeal mortality among under-5-year-olds. The incidence of diarrhoea obtained (2.6 episodes per child per year) was virtually the same as that estimated by Snyder & Merson in 1982, while the global mortality estimate was lower (3.3 million deaths per year; range, 1.5-5.1 million). The mortality estimate is based on a small number of active surveillance and prospective studies, and thus associated with a large degree of uncertainty, reflecting the weakness of the global database. However, many surveys reporting reductions in mortality in several locations are consistent with a decreased estimate for mortality. More accurate execution of WHO survey methods, including population-based sampling in representative locations, and repeat surveys every 5 years, are needed to monitor the progress of diarrhoeal disease control programmes and trends in diarrhoeal morbidity and mortality over time.


The causal model approach to nutritional problems: an effective tool for research and action at the local level. Reported are the results of a case study from Kirotshe rural health district, Northern Kivu, Zaire, where a workshop on the causal model approach to nutrition was organized in 1987. The model has since been used in the field for research design, training of health professionals, nutrition intervention, and community development. The rationale behind this approach is reviewed, the experience accumulated from Kirotshe district is described, and the ways in which the causal model contributes to comprehensive health and nutrition care are discussed. The broad range of possible policy implications of this approach underlines its usefulness for future action.


[Nutritional status of 0-to-59-month-old children in urban and rural areas of Cameroon]. The nutritional status of preschool-age children (0-59 months) in the Littoral Province of Cameroon was studied in a representative sample of the population of this age group in rural and urban areas, with a total of 2011 children. The nutritional indicators weight-for-height, weight-for-age, and height-for-age were compared with reference data from the United States National Center for Health Statistics. A high prevalence of stunting (15.2% in urban and 21.8% in rural areas, P < 0.0008) was found among the children. The prevalence of wasting was 4.0% in urban and 6.5% in rural areas (P < 0.03). In all age groups, rural children were shorter than urban children with no significant difference between the sexes. The increase in the prevalence of acute malnutrition (8.4%) since the last nutritional survey in 1978 (0.7%), which is probably due to a deterioration in the economic situation in recent years, indicates that urgent measures should be taken to improve the nutritional situation of these children, especially in the villages. The findings of the study could serve as baseline data for the evaluation of the effectiveness of future nutrition programmes.


Tolerance of young infants to a single, large dose of vitamin A: a randomized community trial in Nepal. A randomized, double-masked trial was carried out in rural Nepal to investigate the incidence and severity of acute side-effects among neonates ( < 1 month of age) and infants aged 1-6 months who received a large, oral dose of vitamin A (15,000 retinol equivalents (RE) (50,000 IU) and 30,000 RE (100,000 IU), respectively) or placebo (75 RE (250 IU) and 150 RE (500 IU), respectively) in oil. Infants (vitamin A group, n = 1461; controls, n = 1379) were assessed for vomiting, loose stools, fever, and irritability during the 24 hours before and after dosing. Fontanelles were palpated 24 hours after dosing. Neonates exhibited no excess risk of adverse side-effects after receiving 15,000 RE. Compared with controls the older infants who ingested 30,000 RE had a 1.6% excess rate of vomiting (95% confidence interval (CI): 0.2-3.0%) and a 0.5% excess rate (95% CI: -0.1 to 1.1%) in the occurrence of bulging fontanelles. There were no other significant differences in the older infants. The controlled, periodic distribution of a single 15,000 RE dose of vitamin A therefore confers no apparent acute risk to young infants; a 30,000 RE dose is associated with a minimum risk of transient, acute side-effects.


Measles in a west African nomadic community. A serological survey was conducted among Tuareg nomads to determine their level of immunity to measles. More than half (57.9%) of the children under 10 years of age did not have detectable antibodies to measles, suggesting that transmission of the disease is low in this mobile population. Mothers' reports of their children's history of measles were accurate (positive predictive value 93.9% for under-5-year-olds). Nomads are a reservoir of susceptible individuals who require immunization strategies adapted to their particular life-styles. These can be implemented at relatively low cost.


Diagnosis of measles by clinical case definition in dengue-endemic areas: implications for measles surveillance and control. In many countries, measles surveillance relies heavily on the use of a standard clinical case definition; however, the clinical signs and symptoms of measles are similar to those of dengue. For example, during 1985, in Puerto Rico, 22 (23%) of 94 cases of illnesses with rashes that met the measles clinical case definition were serologically confirmed as measles, but 32 (34%) others were serologically confirmed as dengue. Retrospective analysis at the San Juan Laboratories of the Centers for Disease Control showed also that at least 28% of all laboratory-confirmed cases of dengue in Puerto Rico in 1985 met the measles clinical case definition. If the true measles vaccine efficacy (VE) is assumed to be 90%, the occurrence of laboratory-confirmed dengue cases that meet the measles clinical case definition results in a reduction of the apparent measles VE to only 64% (a 29% relative reduction from the true VE). The results of the study demonstrate the importance of a laboratory-based surveillance system in measles control or elimination efforts in dengue-endemic areas.


An alternative approach to confirming anti-HIV reactivity: a multi-country collaborative study. The confirmation of positive screening assay reactions for antibodies to human immunodeficiency virus type 1 (anti-HIV-1) by Western blot is expensive and often gives indeterminate results. We therefore carried out a collaborative study to investigate the confirmation of screening assay reactions using a second screening assay. For this purpose, seven laboratories prospectively tested sequential specimens, using at least one additional screening assay, until about 50 confirmed anti-HIV-1-positive specimens had been identified in each test centre. The reactions of 16 assays were analysed in pairs (assay A and assay B), using assay B on specimens reactive in assay A: A+/B+ reactions were considered positive and A-, negative anti-HIV results. These outcomes were compared with those obtained using confirmatory Western blot. In all, 7950 specimens were tested, and 359 were reported as positive by the laboratories. Within the test centres, eight screening assay pairings gave rise to no false-positive or false-negative results, and these combinations were at least as accurate as a single screening assay followed by Western blot. From 6.3% to 8.3% of the Western blot results were indeterminate. The number of specimens examined was too small to justify recommending for general use named pairs of screening assays; the choice of these would, in any case, depend on local conditions. However, individual laboratory managers may wish to investigate the large potential savings to be made by confirming HIV infection using a second screening assay on initially reactive specimens. If the more sensitive screening assay is used first, the sensitivity of this approach may be improved by further investigation of specimens that react as A+B-.


Cost-benefit analysis of a nationwide inoculation programme against viral hepatitis B in an area of intermediate endemicity. The large decrease in the cost of vaccines against hepatitis virus B prompts a re-examination of nationwide vaccination campaign strategies. The present study estimates the costs and benefits that would result from a viral hepatitis B prevention programme (with no prior screening) targeted at all under-16-year-olds in Israel in 1990 and only neonates in the period 1991-2034. Israel is situated in an area of intermediate endemicity, where the majority of HBsAg carriers are anti-HBe positive. Such a policy would reduce the number of cases of viral hepatitis B in the vaccinated cohort from 654,000 to 270,000 over the period 1990-2059, yielding a benefit-to-cost ratio of 1.88: 1 for the health services only. Inclusion also of the indirect benefits of reduced work absences and mortality would increase the benefit-to-cost ratio to 2.77:1. Even when the benefits arising from the reduction in hepatocellular carcinoma and liver transplants were excluded, the benefit-to-cost ratio for the health services alone would still be 1.41:1. The adoption of such a nationwide inoculation policy appears therefore to be not only medically but also economically justifiable.


Long-term efficacy of single-dose mass treatment with diethylcarbamazine citrate against diurnally subperiodic Wuchereria bancrofti: eight years' experience in Samoa. A single-dose of diethylcarbamazine citrate (DEC, 6 mg per kg body weight) was administered in three mass treatment campaigns to > 80% of the estimated total Samoan population (160,000) in 1982, 1983, and 1986. The effect of the drug was evaluated before and after each campaign by conducting four blood surveys covering 9600 to 13,700 people from 26-34 villages on each occasion. The drug reduced the prevalence of Wuchereria bancrofti microfilariae from 5.6% to 2.5% (a 55% reduction), while the transmission potential (the estimated mosquito infection rate if everyone is equally exposed to mosquito bites) dropped from 2.18 to 0.67 (a 70% reduction). The total number of microfilariae in the Samoan population is estimated to have been reduced by 80%. A spaced, single-dose treatment with DEC at a 1-2-year interval therefore seems to be an effective control measure against diurnally subperiodic W. bancrofti.


Comparison of combinations of parenteral artemisinin derivatives plus oral mefloquine with intravenous quinine plus oral tetracycline for treating cerebral malaria. A total of 141 cases of strictly defined cerebral malaria were studied in a controlled trial of three regimens: (1) intramuscular artemether plus oral mefloquine, (2) intravenous artesunate plus oral mefloquine, and (3) intravenous quinine (with or without an initial loading dose) plus oral tetracycline. The overall mortalities in each group were 14%, 8.3% and 34.3% respectively. The average parasite clearance time was 27.30 +/- 19.62 hours in regimen 1, 41.84 +/- 17.55 hours in regimen 2, and 47.30 +/- 21.95 hours in regimen 3. No recrudescence was observed in regimens 1 and 2, but 12.1% recrudesced in the third.


Prevalence of oral submucous fibrosis in the high natural radiation belt of Kerala, south India. Oral submucous fibrosis (OSMF) is a crippling disorder which is confined almost exclusively to the Indian subcontinent. Despite its association with a significantly increased risk of cancer, the etiology is still not clear. An epidemiological assessment showed 0.4% prevalence for OSMF in Kerala, South India, which is among the highest recorded. Recently the National Tumour Registry in Trivandrum reported the highest recorded site-specific incidence rate for oral cancer (ICD 140-145) in this area. The coastal belt of the Trivandrum and Quilon districts of Kerala has a very high natural radioactivity (over 1500 mR (387 microC) per year); about 500 mR (129 microC) per year is considered to be the maximum permissible dose for populations in general. An epidemiological survey in this area and in a comparable population (without exposure to high background radiation) as a control showed that the percentage prevalence of OSMF in the study area was 0.27 and in the control area 0.32. It appears highly improbable that the OSMF in the study area was induced by high background radiation.


Measurement and utilization of healthy life expectancy: conceptual issues. The periodic calculation of healthy life expectancies permits the evaluation of the impact of new health policies at a given moment, as well as the assessment of trends under changing health conditions. In spite of their apparent simplicity, the results obtained will have to be interpreted by experts. Useful reference values can be provided by international comparisons. However, several choices remain to be made, such as (i) the types of morbidity and disability data to be associated with mortality data; (ii) the multiple indicators available; (iii) the type of observations to be recorded, i.e., "abilities" or "performances"; (iv) whether or not the recovery of lost functions should be considered; (v) the mode of computation, i.e., life expectancy before the first morbid event or global healthy life expectancy; and (vi) the determination of thresholds based on either relative or absolute criteria.


A new quantitative assay for glycosaminoglycans. A direct dye-binding technique has been developed to measure total glycosaminoglycans in urine. Fifty or 100 microliters of urine was mixed with a solution of Azure A (10 mg/l) and Azure B (10 mg/l) and the resulting decrease in absorbance at 610 nm was measured. The standard curve with chondroitin sulfate C was linear from 1 to 20 micrograms/assay. The normal value for total urinary glycosaminoglycans in adults was 1.8 +/- 0.6 g/mol creatinine. Other normal values were age-dependent. The assay is inexpensive, simple, precise, sensitive and suitable for screening for the mucopolysaccharidoses in pediatric patients.


Adaptation of transferrin protein and glycan synthesis. We report the patterns of variability in transferrin structure in pregnancy, iron deficiency anemia, women using oral contraceptives, nonanaemic rheumatoid arthritis, iron deficient rheumatoid arthritis and anemia of the chronic diseases. Changes in microheterogeneity were assessed by crossed immuno isoelectric focusing of serum transferrin. Intra-individual variation in the control group was minimal. Equally, inter-individual variation in controls and groups with established stable disease was very limited. In pregnancy an increase in transferrin concentration was accompanied by redirection of glycan synthesis to the highly sialylated and highly branched glycans, an effect also shown in women using oral contraceptives. Iron deficiency anemia was accompanied by increased protein core synthesis without the large shifts in the microheterogeneity pattern as seen in pregnancy at similar transferrin concentration. In contrast to this, rheumatoid arthritis was accompanied by decreased protein synthesis while the microheterogeneity pattern shifted significantly towards the highly branched glycans. Interpreted in the respective pathophysiological contexts results show that: (1) N-linked glycosylation of transferrin is a strictly controlled process, both in the physiological states and in disease. (2) Microheterogeneity is determined independently from transferrin protein synthetic rate. (3) Provisionally observed changes in the glycosylation can modulate the biological activity of the glycoprotein and as a result redirect internal iron fluxes. This proposition can be applied to altered iron metabolism in both pregnancy, oral contraceptives and rheumatoid arthritis. Changes are not operative in iron deficiency because qualitatively iron metabolism is not altered in this state.


Measurement of glycated albumin by the nitroblue tetrazolium colorimetric method. A method has been developed for the measurement of glycated albumin (albumin-fructosamine) by the nitroblue tetrazolium (NBT) colorimetric method. In this method, polyethylene glycol was added to the serum and then the mixture was centrifuged to separate globulin proteins from albumin proteins. This made it possible to measure the glycated albumin in the supernatant by the NBT colorimetric method, without the interference of globulin proteins. This measurement method correlated with the measurement of glycated albumin using boronate affinity chromatography with an r value of 0.942 (P < 0.001). Our method using polyethylene glycol permits easy measurement of albumin fructosamine and is therefore useful as an index of diabetic control and for diabetic screening.


Effects of methylprednisolone and uremia on renal and intestinal calbindin-D in the rat. The effects of glucocorticoids on renal and intestinal calcium binding protein (calbindin-D28K and calbindin-D9K) were examined in normal and uremic rats. Chronic uremic rats and normal controls were treated with either methylprednisolone (MP) 1.3 mg/kg/d or isotonic saline given as a continuous intraperitoneal infusion for 1 week before sacrifice. Renal calbindin-D28K was measured by rocket immunoelectrophoresis and intestinal calbindin-D9K was measured by an enzyme-linked immunoadsorbent assay. Methylprednisolone treatment of chronic uremic rats increased plasma phosphate levels (P < 0.05), but plasma calcium and 1,25-dihydroxyvitamin D3 were unchanged in all groups. MP treatment did not affect the renal calbindin-D28K in either normal or uremic rats. In normal rats, MP treatment reduced intestinal calbindin-D9K by 28% when compared to placebo (P < 0.05). In contrast, chronic uremia increased renal calbindin-D28K by 51% and 38% (P < 0.001) in placebo and MP treated uremic rats, respectively, while intestinal calbindin-D9K was unchanged. Thus, MP treatment and chronic uremia induced different changes in renal and intestinal calbindin-D of the rat suggesting that different mechanisms are involved in the regulation of these vitamin D dependent proteins.


Parathyroid hormone-related protein: a possible endocrine function in lactation. Parathyroid hormone-related protein (PTHrP), initially discovered as the factor responsible for the syndrome of humoral hypercalcaemia of malignancy, has also been found to be expressed in placenta, in pregnant uterus, in the fetus at many locations, and in the lactating mammary gland. This study sought to establish whether PTHrP reaches the maternal circulation when it is expressed in mammary tissue during lactation or in the maternal reproductive tract during gestation. Blood samples were collected from 53 subjects: 18 pregnant women in all stages of gestation, 19 lactating mothers and 16 non-lactating post-partum controls. PTHrP was measured using a specific and validated radioimmunoassay. Parathyroid hormone was measured by two-site immunoradiometric assay. Total calcium was measured by atomic absorption spectrophotometry. Circulating levels of PTHrP were readily detectable in 12 of 19 nursing mothers (range 2.7-7.8 pmol/l) but in none of the mothers who were bottle feeding. PTHrP was also detected in one of 18 pregnant subjects. Parathyroid hormone concentrations were lower in lactating mothers (2.3 +/- 1.0 pmol/l), than in non-lactating mothers (3.5 +/- 1.2 pmol/l) (P < 0.01). PTHrP reaches the maternal circulation during lactation in amounts which could produce a systemic effect.


Circulating lipids and minor abnormalities of thyroid function. We determined the effect of subclinical hyperthyroidism (defined as low circulating TSH with normal serum free T4) and subclinical hypothyroidism (raised serum TSH with normal free T4) on fasting levels of blood lipids. Prospective study of lipid concentrations in patients identified as having abnormal TSH. Patients were identified in a population screening study of those over 60 years, with persistently low TSH with normal free T4 (n = 27) or high TSH but normal free T4 (n = 57). Patients were matched to controls with normal serum TSH by age, sex and body mass index. Serum TSH, free T4, free T3, total cholesterol, low density lipoprotein (LDL) cholesterol and high density lipoprotein (HDL) cholesterol. Serum free T4 measurements were significantly higher in those with subclinical hyperthyroidism than in their controls (P < 0.001) and lower in those with subclinical hypothyroidism than in matched controls (P < 0.001). Measurement of fasting lipids in patients and controls revealed a marked (12.2%) reduction in serum total cholesterol in subclinical hyperthyroidism (P < 0.01); no significant difference in fasting lipids between patients with subclinical hypothyroidism and controls was observed. Differences in free T4 between those with low or high TSH and controls with normal TSH suggest that abnormalities of TSH directly reflect thyroid hormone excess and deficiency. A reduction in cholesterol in those with subclinical hyperthyroidism suggests a direct influence of thyroid hormone excess on lipid metabolism in these patients.


Thyroid function and thyroid autoimmunity independently modulate serum concentration of soluble interleukin 2 (IL-2) receptor (sIL-2R) in thyroid diseases. The serum concentration of soluble interleukin-2 receptor (sIL-2R) is a marker of T-lymphocyte activation. Increased circulating sIL-2R has been reported in untreated Graves' disease. This finding has been interpreted as the consequence of the autoimmune activation, but recent data suggest that sIL-2R is directly correlated to thyroid state. The aim of this study was to elucidate the respective roles of autoimmunity and thyroid function in modulating serum sIL-2R. sIL-2R was evaluated in 20 normal euthyroid subjects and in a large series of patients with autoimmune and non-autoimmune thyroid disorders in different functional state. sIL-2R was assayed by a solid-phase monoclonal antibody assisted ELISA method. Serum sIL-2R in normals was 461 +/- 186 U/ml (mean +/- SD). Increased sIL-2R was found in 61 hyperthyroid patients with Graves' disease (1610 +/- 962 U/ml, P < 0.0001) and in 23 with toxic adenoma (1121 +/- 598 U/ml, P < 0.0001). Restoration of euthyroidism lowered to normal sIL-2R in both groups. Serum sIL-2R was higher in euthyroid Graves' disease patients with active than in those with non-active ophthalmopathy. Decreased serum sIL-2R (228 +/- 93 U/ml, P < 0.0001) was found in 30 patients hypothyroid after total thyroidectomy. Highly variable circulating sIL-2R (range 100-1456 U/ml, mean +/- SD: 379 +/- 301 U/ml) was found in 49 patients with hypothyroid Hashimoto's thyroiditis (P = NS vs normals; P < 0.02 vs post-thyroidectomy hypothyroid patients). Treatment with L-thyroxine increased sIL-2R in all thyroidectomized and in the majority of Hashimoto's thyroiditis patients. In individual Hashimoto's thyroiditis patients (mostly with increased serum sIL-2R), L-thyroxine caused a decrease of circulating sIL-2R, sIL-2R was normal in 29 patients with euthyroid Hashimoto's thyroiditis. Both in Graves' disease and in Hashimoto's thyroiditis, no correlation was found between sIL-2R and anti-thyroglobulin, anti-thyroid peroxidase and anti-thyrotrophin-receptor autoantibodies. Highly significant positive correlation between serum thyroid hormones and sIL-2R was found in all study groups. In thyroid disorders thyroid hormones are the main regulator of serum sIL-2R concentration. The contribution of autoimmune activation may be detected only in some patients with autoimmune hypothyroidism, while in Graves' disease the role of the immune system is masked by the hyperthyroid state.


Failure to find an association of blood group P1 with thyroid-associated ophthalmopathy. Genetic factors have been proposed to account for the development of ophthalmopathy in a proportion of patients with Graves' disease. The aim of this study was to confirm the previously reported association between blood group P1 and thyroid-associated ophthalmopathy. A prospective study of sequential Caucasian patients. We studied 169 patients with Graves' disease, 84 of whom had grade 3, 4 or 6 ophthalmopathy and 85 had no eye signs. Blood group P1 was measured by a standard serological technique. The frequency of the P1 blood group was 74.1% in the patients without eye signs and 77.4% in those with ophthalmopathy (chi 2 = 0.25, P > 0.1). By Woolf's method there was no significant difference in the test for heterogeneity of estimates between the present and the previously reported series of Graves' patients. Combining the results (n = 279), the pooled relative risk for ophthalmopathy with blood group P1 did not differ significantly from 1.0 (chi 2 = 2.33, P > 0.1). The presence of blood group P1 in patients with Graves' disease does not appear to be associated with an increased risk of developing thyroid-associated ophthalmopathy.


Body composition and bone mass in post-menopausal women. We aimed to assess total body composition and to study the interrelationships between fat and lean tissue mass with total and regional bone mass in healthy British post-menopausal women. Total body composition and regional bone mass were measured in 97 healthy post-menopausal women recruited from the general community. The mean age was 57.9 years, range 49-65. Total body composition (fat, lean tissue and bone mineral) and regional bone density in the lumbar spine and femur were measured by dual energy X-ray absorptiometry on a Lunar DPX. Significant negative correlations with age were found for total body bone mineral density (r = -0.200, P = 0.049), and lumbar spine bone mineral density (r = -0.28, P = 0.006); the calculated rate of bone loss from these two sites was 0.33 and 0.7% per annum respectively. Fat tissue mass showed a positive correlation with age (r = 0.22, P = 0.03). High correlations were observed between total body and regional bone mineral density (r = 0.755-0.829, P < 0.001). After adjustment for age and lean mass, statistically significant correlations were seen between fat tissue mass and all bone mass measurements (P < 0.01-0.001), the strongest correlations being found for total body bone mineral content and density (r = 0.477 and 0.488 respectively). Lean tissue mass showed a strong correlation with total body bone mineral content (r = 0.580, P < 0.001), after adjustment for age and fat mass; it was less strongly correlated with other bone mass measurements than fat mass, showing only weak correlations with total body, trochanteric and lumbar spine bone mineral density (r = 0.228-0.246, P < 0.05). Age-adjusted body weight showed stronger correlations with total and regional bone mass than did either body mass index or height. Both fat and lean tissue mass are related to total and regional bone mass in post-menopausal women, the relationship being strongest for fat mass. Body weight shows stronger correlations with bone mass than either height or body mass index. In view of the direction and magnitude of changes in fat, lean tissue and bone mineral after the menopause, adiposity and muscularity are more likely to be determinants of peak bone mass than of the rate of post-menopausal bone loss.


Correlation between ovarian steroids and lipid fractions in relation to age in premenopausal women. We evaluated the effect of sex steroids on the lipid fractions (cholesterol, triglycerides, LDL-C, HLD-C and subfractions HDL2-C and HDL3-C) and on the apolipoproteins (A-1 and B) in relation to age in women. Twenty-eight normally cycling women belonging to three age groups (20-29, n = 11; 30-39, n = 10; 40-49, n = 7) had blood samples taken daily during one cycle. Serum lipid fractions, apolipoproteins (Apo) and ovarian steroids were measured daily during the menstrual cycle. Diet and exercise were also evaluated. Each age group had comparable profiles for daily serum concentrations of oestradiol, progesterone and testosterone. There were no significant variations of the lipid fractions or of the ApoA-I and ApoB during the menstrual cycle in each group. Using regression analysis, modifications of cholesterol, triglycerides, LDL-C and ApoB were partially but significantly correlated with age. These changes occurred in spite of similar serum concentrations of oestradiol, progesterone and testosterone in the three groups. Lipid fractions were also affected by the increase of body mass index with age, especially HDL-C and HDL2C. However, there were no differences in lipid and energy intake or in energy expenditure during physical leisure activities. These results indicate that physiological fluctuations of ovarian steroids have no effects on lipids and Apo in normally cycling women of increasing age. In this study, the age related changes in the lipid fractions were partially correlated with body mass index but not with energy intake or exercise.


The significance of a single serum LH measurement in women with cycle disturbances: discrepancies between immunoreactive and bioactive hormone estimates. We evaluated the significance of single serum LH estimates (as assessed by radiometric assay (IRMA) and Leydig cell in-vitro bioassay (BIO)) for the diagnosis of polycystic ovary syndrome (PCOS) in women with infertility and cycle abnormalities. Hormonal and clinical comparisons between subgroups were made based on classification according to (a) rigid clinical and endocrine (excluding LH) characteristics of PCOS, (b) elevated IRMA-LH concentrations, (c) BIO-LH levels. In addition, androgen modulation of LH biopotency was studied in these patients. Ninety-nine women presenting at our infertility Unit with oligo/amenorrhoea. Of the total study group, 35 women were diagnosed positive as PCOS and 42 showed elevated IRMA-LH levels. Only 51% (n = 18) of PCOS patients showed elevated IRMA-LH levels, and in PCOS significantly higher levels of BIO-LH, androstenedione, oestrone, and BIO/IRMA-LH ratios were found as compared to non-PCOS patients. In the group with elevated IRMA-LH only 43% (n = 18) of subjects were diagnosed as PCOS, and no difference in BIO/IRMA-LH ratios was found. With increasing BIO-LH levels the probability of PCOS rises sharply (P < 0.001), whereas this probability is of only marginal significance (P < 0.06) for IRMA-LH. In the total study group a correlation is observed between serum testosterone (T) levels and IRMA-LH (r = 0.47), and BIO-LH (r = 0.51) concentrations. This correlation is absent comparing serum T and BIO/IRMA-LH ratios (r = 0.15). Results presented in this study indicate that (1) women with infertility and oligo/amenorrhoea classified based on signs of PCOS or IRMA-LH levels, exhibit different clinical and endocrine characteristics, (2) only 51% of PCOS women exhibit elevated IRMA-LH concentrations, and only 43% of women with elevated IRMA-LH were diagnosed as PCOS, (3) IRMA-LH levels are a poor predictor of PCOS, whereas the predictive value of BIO-LH is better, (4) elevated BIO/IRMA-LH ratios in PCOS are dependent on alterations in BIO-LH, rather than IRMA-LH concentrations, and (5) no correlation was observed between serum T levels and BIO/IRMA-LH ratios.


Comparison of measures of body composition in a trial of low dose growth hormone replacement therapy. We assessed the effects of the administration of low dose growth hormone in growth hormone deficient adults on body composition and physical performance. We compared the validity of different measures of body composition in GH treated adults. An uncontrolled longitudinal study of eight patients with GH deficiency who were treated with 4 units of biosynthetic growth hormone (Norditropin), three times a week. Subjects were studied for 8 weeks. Eight patients with acquired growth hormone deficiency as defined by < 5 mU/l GH following standard provocative investigations in whom other hormone replacement was optimized. IGF-I was measured on day 1 and after 4 and 8 weeks of treatment with recombinant human growth hormone. Body composition was estimated by dual energy X-ray absorptiometry, bioelectrical impedance, skinfold anthropometry, total body potassium measurement and by computerized tomography of a representative cross-sectional area of thigh on day 1 and following 8 weeks of treatment. Exercise capacity was measured on an electromechanical bicycle and palmar grip strength was measured using a Jamar dynamometer on day 1 and after 8 weeks. IGF-I increased significantly. Exercise capacity and maximum heart rate achieved on the electromechanical bicycle increased significantly. Grip strength did not change. There was a significant increase in fat-free mass and a decline in fat mass as shown by dual energy X-ray absorptiometry and bioelectrical impedance. However, this was not confirmed by other methods. No side-effects were noted. This study shows that a low dose of biosynthetic growth hormone can elevate IGF-I levels and have a pronounced physical impact in the growth hormone deficient adult without the side-effects seen at higher dosage schedules. Over a 2 month period the increase in fat-free mass may be due to an increase in total body water; however, the decline in fat mass is a genuine effect.


Painful thyroid gland: an atypical presentation of Graves' disease. An adolescent with Graves' disease presented with acute painful swelling of the thyroid gland and overlying erythema simulating acute suppurative or subacute thyroiditis. She had an elevated radioactive iodine uptake, thyroid stimulating antibodies, thyrotrophin binding inhibiting immunoglobulins, and a normal sedimentation rate and leucocyte count. The course of the thyrotoxicosis and painful thyroid was protracted, and the pain and tenderness of the thyroid recurred on two subsequent relapses.


A new polymorphism in exon 11 of the LDL receptor gene in healthy people and in familial hypercholesterolemia subjects. We have screened exon 11 of the low density lipoprotein receptor (LDLR) gene from familial hypercholesterolemia (FH) heterozygotes for point mutations by using analysis of single strand conformation polymorphisms (SSCP). A variant pattern was observed in three out of 39 subjects. By DNA sequencing, this variant pattern was found to be due to a C-->T transition at nucleotide 1617 that affects the third base of codon 518. A PCR method was developed to screen FH heterozygotes and normal subjects for this mutation. The gene frequencies in FH heterozygotes and normal subjects were 4% and 4.5%, respectively. Thus, the mutation cannot be in linkage disequilibrium with a mutation that causes FH. Rather, the mutation may be a useful genetic marker at the LDLR locus. Haplotype analysis at the LDLR locus in two FH families where the proband possessed the mutation revealed that the mutation was on two different haplotypes. This finding is consistent with the mutation occurring at a mutational hot spot.


Deletion of 15q12 in Angelman syndrome: report of 3 new cases. Deletion of 15q12 has been reported in patients with Angelman syndrome (AS). We report chromosome studies showing del(15q12) in three new cases, diagnosed as having AS. We were also able to determine, through heteromorphism studies, that the origin of the deleted chromosome in all three probands is maternal. This is a consistent finding in previously reported cases of AS.


Fertility in myotonic dystrophy in Saguenay-Lac-St-Jean: a historical perspective. Myotonic dystrophy (MD) is an autosomal dominant disorder that has a high prevalence in Saguenay-Lac-St-Jean. A case-control study, based on a population register, of 373 MD patients who married in this region between 1855 and 1971 was conducted to determine whether their fertility was affected by the disorder. Six demographic parameters, that is the number of children, the age at marriage, the ages at the time of birth of the first and the last child, the interval between the marriage and the birth of the first child, and the interval between consecutive births, were analyzed. The mean number of children born to MD and control individuals was not different (P > 0.05). However, MD males had more children than MD females although they have started delaying their marriage since 1921. Fertility fell significantly in both the MD and control groups during the period of observation. This change reflects the decline in fertility of French Canadians in general during this period, but mainly after 1940.


The Dyggve-Melchior-Clausen syndrome in Indian siblings. The clinical and radiographic features of a brother and sister with the Dyggve-Melchior-Clausen syndrome are presented. These features differentiate this syndrome from other bone dysplasias causing short trunk dwarfism. In addition to the vertebral, pelvic and proximal limb defects typical of this syndrome, both these patients have more severe distal limb involvement than has been described previously. Their parents are first cousins and have four other unaffected children, which supports an autosomal recessive mode of inheritance for this syndrome. The ancestors of this kindred emigrated to South Africa from India in the 19th century.


De novo interstitial deletion 16(q12.1q13) of paternal origin in a 10-year-old boy. A 10-year-old boy with a de novo del(16)(q12.1q13) and many features of the deletion 16q phenotype is described. The deletion occurred in a paternal chromosome as demonstrated by DNA studies with polymorphic (AC)n microsatellite repeat markers. Comparison with published cases suggests that deletion of either of two regions (q13 and q22.1) on the long arm of chromosome 16 is associated with an apparently identical phenotype. No parental imprinting of this region was demonstrated.


Deletion delta F508 and clinical expression of cystic fibrosis-related liver disease. A study of liver function in 108 adult cystic fibrosis patients showed that 20 had established liver disease, and that these had significantly better pulmonary function than the subgroup without liver disease. The relative risk of liver disease for homozygotes vs heterozygotes was 2:1 in our series. Four of the liver patients had a sibling with CF, but three of the sibships were discordant for liver disease. Environmental or genetic factors other than the deletion Delta F508 may influence the development of cystic fibrosis-related liver disease.


Is the prevalence of atopic dermatitis increasing? Several studies have suggested that the prevalence of atopic dermatitis has increased over the last three decades, and similar trends have been reported with asthma and hay fever. However, in common with other 'allergic' disease, the definition and measurement of atopic dermatitis in populations has been fraught with problems and has led to difficulties in separating any real changes in disease prevalence from secular changes in diagnosis. In this article, the evidence surrounding the claims of an increased prevalence of atopic dermatitis is examined, and possible reasons for such a change are suggested.


Once-weekly oral doses of fluconazole 150 mg in the treatment of tinea corporis/cruris and cutaneous candidiasis. Ninety-five adult out-patients with tinea corporis and/or tinea cruris participated in a multicentre open non-comparative study investigating the safety and efficacy of 1-4 once-weekly doses of oral fluconazole 150 mg. Trichophyton rubrum was isolated most frequently (67 of 86 mycologically evaluable patients). A mean of 2.6 doses of fluconazole was administered; patients infected with Candida albicans or Epidermophyton floccosum required an average of 2 doses compared to 3-4 doses in patients infected with other organisms. Clinical cure was obtained in 85 of 92 (92%) patients at the last post-treatment evaluation, with the remaining seven patients being substantially improved. At long-term follow-up, 28-30 days after the last dose, 80 of 91 (88%) patients were assessed as clinically cured, three (3%) patients were improved and eight (9%) patients failed. Among the long-term clinical failures, there was one diagnosis of tinea corporis (3% failure rate) and seven diagnoses of tinea cruris (12% failure rate). Mycological evidence of infection occurred in only 1 of 86 patients assessed at the last post-treatment follow-up. Mycological relapse occurred in nine (11%) patients at long-term follow-up; one patient was infected with Trichophyton mentagrophytes and eight patients were infected with T. rubrum. Relapse occurred in 2 of 29 (7%) patients with tinea corporis and eight of 57 (14%) patients with tinea cruris (one patient who relapsed had both tinea corporis and cruris). There was no correlation between the number of doses received and the mycological response or relapse rates at long-term follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)


Once-weekly oral doses of fluconazole 150 mg in the treatment of tinea pedis. Seventy adult out-patients with tinea pedis participated in a multicentre open non-comparative study of the safety and efficacy of once-weekly doses of oral fluconazole 150 mg. A mean of 3 doses of fluconazole was administered; patients infected with Candida required an average of 2 doses compared to 3-4 doses in patients infected with other organisms. Clinical cure was obtained in 45 of 61 (74%) evaluable patients at the last post-treatment evaluation, with 15 patients being substantially improved and one patient failing clinically. At long-term follow-up, 28-30 days after the last dose was administered, 46 of 60 (77%) patients were clinically cured, 13 (22%) patients were improved and one patient failed. Trichophyton rubrum was isolated most frequently (47 of 60 mycologically evaluable patients). Mycological evidence of infection was eradicated from 52 of 60 (87%) patients post-treatment. At the long-term follow-up, infection was eradicated from 46 of 59 (78%) patients, persisted in five (8%) patients and relapsed in eight (14%) patients, six of whom were infected with T. rubrum and two of whom were infected with both T. rubrum and Candida. The number of doses received did not correlate with either the mycological response or relapse rates at long-term follow-up. The subgroup of 16 patients with infection of the sole of the foot, which is often considered to be more difficult to eradicate, responded similarly. Only 5 of 70 (7%) fluconazole-treated patients reported adverse effects, which were mild to moderate in severity, transient and did not result in discontinuation of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)


An epidemiological profile of in-patient workload in dermatology. Trends in admission rates, patterns of readmission, lengths of stay and clinical caseload for in-patient dermatology from 1976 to 1985 are described using data from the Oxford record-linkage study. Age-specific admission rates were considerably higher in people aged 50 years and over than in younger people. Admission rates declined over time in most age-sex groups below the age of 70 years, but increased over time for the over 70s. In dermatology, unlike most other specialties, the length of patients' stay did not decrease substantially over the 10 years. In-patient workload consisted predominantly of leg ulcers, psoriasis, and eczema. This did not change appreciably over time. New out-patients at dermatology clinics rose by 41% from 1976 to 1985, and all out-patient visits rose by 20% during the 10-year period. Because the profile of in-patient workload changed relatively little over time, we speculate that the impact of innovations in dermatological practice has been much greater in the ambulatory setting than in the management of those patients requiring prolonged in-patient care. Future routine measures of workload in dermatology should include demographic and clinical data on out-patients.


The anchoring strengths of various chest hair root types. The force required to epilate single chest hairs was measured electronically during a slow (0.09 m/s) machine-driven extraction. Telogen hairs showed a mean anchoring strength of 70 g (s.d. = 16). Anagen hairs, with variable amounts of surrounding root sheaths, had a mean of 71 g (s.d. = 10) whereas bare anagen hairs had a mean of 66 g (s.d. = 13). The catagen phase had a mean of 62 g (s.d. = 8). It is highly likely that the anchoring mechanisms of anagen and telogen roots are as different physiologically as these roots are different anatomically yet both are sufficiently strong to resist the ordinary tractions and pullings to which hair is subject.


Cholesterol embolism to the skin.

Cholesterol embolism to the skin. The clinical features of a patient with cholesterol embolism are presented. Histopathological examination showed the typical clefts of cholesterol in the skin and renal vessels. We believe this entity is under-reported in the dermatological literature.


Role of sulphydryl-containing agents in the management of venous (varicose) ulceration. A new approach. This randomized double-blind controlled study examined whether sulphydryl-containing agents influence the healing of venous ulceration occurring for the first time on the medial side of the leg. Graduated compression bandaging, which exerted a mean ankle pressure of 40.6 +/- 0.4 mmHg, and a mean below-knee pressure of 17.1 +/- 0.2 mmHg, healed 70% of ulcers within 12 weeks (n = 46). The addition of the sulphydryl-containing agents DL-cysteine (n = 46) or DL-methionine-methyl sulphonium chloride (n = 45) to the compression bandaging (daily application of the powder for 7 days, followed by once weekly applications until the end of the study 3 months later) significantly (P < 0.01) stimulated healing of venous ulceration relative to control values when studied 4, 8 and 12 weeks after commencing treatment. After 3 months of treatment, both sulphydryl-containing compounds healed 93% of the ulcers. The results show that sulphydryls stimulate healing of venous ulceration.


Diagnosis of lichen planus pemphigoides in the absence of bullae on normal-appearing skin. A case of lichen planus pemphigoides is described in which bullae and erosions affected the areas of lichen planus only. The diagnosis was confirmed by the finding of linear C3 and IgG deposition in the basement membrane zone (BMZ) of perilesional skin. Indirect immunofluorescence revealed circulating IgG anti-BMZ antibodies and a lamina lucida split was demonstrated by electron microscopy. This case challenges the clinical dogma that the occurrence of bullae on normal-appearing skin is essential for the diagnosis of lichen planus pemphigoides.


Pyoderma gangrenosum--response to topical nitrogen mustard. We report a 69-year-old caucasian male patient with long-standing pyoderma gangrenosum; the lesions preceded the appearance of an IgA monoclonal gammopathy by 2 years. A number of systemic treatments, including high dose steroids and immunosuppressive agents, were poorly tolerated and resulted in serious side-effects. The skin and haematological conditions, however, were kept under control for 2 years with regular plasmapheresis. Pyoderma gangrenosum recurred as vascular access became exhausted but new lesions healed completely with topical application of 20% nitrogen mustard.