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Biomedical subjects
Publications and source records attributed to A Sommer.
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The cDNA sequence coding for human basic fibroblast growth factor (bFGF) has been cloned downstream of a transcription promoter recognized by the bacteriophage T7 RNA polymerase. Initiation of translation at the fgf gene has been coupled to upstream translation of a fragment of the T7 phi 10 gene. Expression of the fgf gene in this system can lead to an accumulation of approximately 40 mg/liter/A600 unit of bFGF. This material can be purified close to homogeneity from a soluble protein extract on a heparin-Sepharose column. bFGF so obtained has been shown to have bioactivity indistinguishable from human placental fibroblast growth factor in mitogenicity, synthesis of plasminogen activator, and angiogenesis assays.
The value of biannual distribution of 200,000 IU of vitamin A in preventing xerophthalmia was assessed in a randomized, controlled community-based trial involving 25,000 preschool children in 450 villages of northern Sumatra. Results indicate that distribution was associated with a dramatic decline in xerophthalmia prevalence; that concurrent controls were critical for distinguishing spontaneous from program-related changes; and that the apparent level of benefit depended on the choice of clinical indicator(s). Night blindness ceases to be an accurate reflection of impact when prevalence rates are low, and comparison of Bitot's spot rates should be confined to new cases of disease.
The "reliability" of a subject's automated perimetric test result is generally assessed by three measures: fixation loss and false-positive and false-negative rates. These reliability criteria were examined for 76 glaucomatous and 248 normal subjects who underwent visual field testing (C-30-2 program; Humphrey Visual Field Analyzer, Allergan Humphrey, San Leandro, Calif). Of the examination results, 45% in glaucomatous subjects and 30% in normal controls were considered unreliable with the use of the manufacturer's reliability criteria. Most test results were unreliable because they failed to meet the criterion for fixation loss. The greater rejection rate among glaucomatous subjects was entirely due to their higher rate of false-negative responses. Factors such as age, pupil diameter, and visual acuity did not explain the difference between the false-negative rates of glaucomatous patients and normal subjects.
Basic fibroblast growth factor (bFGF) stimulates extracellular matrix metabolism, growth, and movement of mesodermally derived cells. We have previously shown that collagen content in polyvinyl alcohol sponges increased after bFGF treatment. We hypothesized that bFGF-treated incisional wounds would heal more rapidly. After intraperitoneal pentobarbital anesthesia, male, 200- to 250-g, Sprague-Dawley rats (n = 27) each underwent two sets of paired, transverse, dorsal incisions closed with steel sutures. On Day 3 postwounding, 0.4 ml of bFGF (recombinant, 400 ng. Synergen) or normal saline was injected into one of each paired incisions. Animals were killed with ether on postwounding Days 5, 6, and 7 and their dorsal pelts were excised. Fresh or formalin-fixed wound strips were subjected to tensile strength measurements using a tensiometer. Breaking energy was calculated. Wound collagen content (hydroxyproline) was measured in wound-edge samples following hydrolysis using high-performance liquid chromatography. There was an overall significant increase in fresh wound tensile strength (13.7 +/- 1.06 vs 19.1 +/- 1.99 g/mm, P less than 0.01) and wound breaking energy (476 +/- 47 vs 747 +/- 76 mm2, P less than 0.001) in bFGF-treated incisions. There was an increase in wound collagen content which was not statistically significant and there was no difference in fixed incisional tensile strength. Histologic examination showed better organization and maturation in bFGF wounds. Recombinant bFGF accelerates normal rat wound healing. This may be due to earlier accumulation of collagen and fibroblasts and/or to greater collagen crosslinking in bFGF-treated wounds.
Reliable measures of optic nerve status are important parameters for epidemiologic and clinical studies of glaucoma. Stereo fundus photography has been used to reduce interobserver variation, but little data have been reported quantifying the level of agreement in these situations. This article examines chance-corrected intraobserver and interobserver agreement for horizontal and vertical cup:disc ratios and width of the narrowest remaining neuroretinal rim on stereo, color, fundus photographs. Intraobserver agreement was substantial to almost perfect for both readers (kappas between 0.82 and 0.86 for horizontal and vertical cup:disc ratios and 0.71 for the neuroretinal rim). Interobserver agreement was also substantial (kappas of 0.71 for horizontal cup:disc ratio, 0.74 for vertical cup:disc ratio, and 0.58 for the neuroretinal rim). Both intraobserver and interobserver agreement were best for glaucoma patients followed by ocular hypertensives and controls. Dichotimizing cup:disc ratios into suspicious or not suspicious using a range of cutoff points (greater than or equal to 0.5, greater than or equal to 0.6, and greater than or equal to 0.7 disc diameters [DD]) had little effect on agreement levels. Estimation of the status of the optic nerve is complex, requiring judgment about the shape and structure of the cup. Agreement is optimized by using stereo photographs, using the same observer and, when evaluating progression, comparing photographs from different points in time at a single sitting.
The guide wire, an important requisite for the placement of endoscopic transpapillary biliary prostheses, should combine two, normally incompatible, properties: a high degree of flexibility for atraumatic passage through irregular or "bent" stenoses, and a high degree of stiffness, to prevent sidewise deviation during advancement of the prosthesis. These opposing, formerly incompatible, properties are combined in a new type of guide wire, known as the Varioguide. With the aid of a tension controller, the stiffness of the Varioguide can be varied steplessly. In 88.2% of 68 patients with stenosis of the bile duct we succeeded in placing a transpapillary endoprosthesis with the Varioguide. In 13 cases in which a previous attempt with the conventional guide wire was unsuccessful, placement of the endoprosthesis was successfully accomplished with the Varioguide; the reverse was true in only a single patient. In the case of very narrow, rigid high stenoses, in which placement of a transpapillary endoprosthesis is especially difficult, the Varioguide has proved highly suitable (stenoses of the bile duct bifurcation).
Cultured bovine capillary endothelial (BCE) cells were found to synthesize and secrete high molecular mass heparan sulfate proteoglycans and glycosaminoglycans, which bound basic fibroblast growth factor (bFGF). The secreted heparan sulfate molecules were purified by DEAE cellulose chromatography, followed by Sepharose 4B chromatography and affinity chromatography on immobilized bFGF. Most of the heparinase-sensitive sulfated molecules secreted into the medium by BCE cells bound to immobilized bFGF at low salt concentrations. However, elution from bFGF with increasing salt concentrations demonstrated varying affinities for bFGF among the secreted heparan sulfate molecules, with part of the heparan sulfate requiring NaCl concentrations between 1.0 and 1.5 M for elution. Cell extracts prepared from BCE cells also contained a bFGF-binding heparan sulfate proteoglycan, which could be released from the intact cells by a short proteinase treatment. The purified bFGF-binding heparan sulfate competed with 125I-bFGF for binding to low-affinity binding sites but not to high-affinity sites on the cells. Heparan sulfate did not interfere with bFGF stimulation of plasminogen activator activity in BCE cells in agreement with its lack of effect on binding of 125I-bFGF to high-affinity sites. Soluble bFGF was readily degraded by plasmin, whereas bFGF bound to heparan sulfate was protected from proteolytic degradation. Treatment of the heparan sulfate with heparinase before addition of plasmin abolished the protection and resulted in degradation of bFGF by the added proteinase. The results suggest that heparan sulfate released either directly by cells or through proteolytic degradation of their extracellular milieu may act as carrier for bFGF and facilitate the diffusion of locally produced growth factor by competing with its binding to surrounding matrix structures. Simultaneously, the secreted heparan sulfate glycosaminoglycans protect the growth factor from proteolytic degradation by extracellular proteinases, which are abundant at sites of neovascularization or cell invasion.
The vitamin A status of 16 children with normal eyes and liver disease was evaluated by plasma retinol concentration and by liver vitamin A concentration or iv relative-dose-response test. Conjunctival impression cytology was performed on each child. All children with normal vitamin A status had normal conjunctival impression cytology. All children with abnormal vitamin A status had abnormal conjunctival impression cytology despite their seemingly normal clinical ocular examination. These results suggest that impression cytology can identify individuals with physiologically significant, preclinical vitamin A deficiency.
Impression cytology was performed on 148 Indonesian preschool children of whom half had mild xerophthalmia and half were age-matched control subjects. Subjects were divided into subgroups that reflected the degree of confidence in their true vitamin A status as determined by serum vitamin A levels, clinical examination, and response to therapy. Impression cytology was considered normal if goblet cells were present and abnormal if they were absent. Thirteen of 14 (93%) children with vitamin A-responsive Bitot's spots and night blindness with base-line serum vitamin A less than 20 micrograms/dL (0.70 mumol/L) (group 1, definite deficiency) had abnormal cytology. In contrast, 17 of 18 (94%) children with normal ocular exam and serum vitamin A greater than 25 micrograms/dL (0.87 mumol/L) (group 7, least likely deficient) had normal cytology. Importantly, 12 of 26 (46%) clinically normal children with serum vitamin A levels less than 20 micrograms/dL (0.70 mumol/L) had abnormal impression cytology.
A randomized community trial was carried out in Aceh, Indonesia, 1982-1984, to assess the impact of semiannual vitamin A (VA) supplementation (60,000 micrograms RE) on preschool child growth: 229 villages were randomized to VA program and 221 to control status. One thousand thirty-two program and 980 control children aged 1-5 y were assessed and followed for 12 mo. VA program males gained an additional approximately 110 g weight at age 2-3 y (NS), 190 g at age 4 y (p less than 0.05), and 263 g at age 5 y over control males (p less than 0.01). Arm circumference and muscle area expanded 2 mm (p less than 0.05) and approximately 36 mm2 (p less than 0.05) more per year, respectively, from ages 3 to 5 y of age and more arm fat was retained at every age (p less than 0.05 at 1 and 3 y) in VA males. There were no group differences in ponderal growth for females or in linear growth for either sex. VA supplementation may improve growth where endemic deficiency exists.
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Visual field examinations are one of the commonest, presumably most sensitive practical indices of optic nerve dysfunction in glaucoma. Given the difficulties in training and retaining good technicians, and presumed vagaries of the Goldmann-type isopter examination technique, interest has turned to computer-controlled automated suprathreshold and threshold static perimetry. Despite the enthusiasm for these approaches, we lack rigorous tests of their value, criteria of abnormality and progressive deterioration, and even normal standards. These important issues are now being addressed. In the interim ophthalmologists must be cautious in their use and interpretation.
The vast majority of the world's 42 million blind are needlessly impaired. Epidemiologic studies are providing important insights into the cause of cataracts and provision of surgical services; ecologic approaches to the control of trachomatous corneal scarring; treatment and prevention of onchocerciasis; and early diagnosis and treatment of xerophthalmia among others. Continued research and application of existing knowledge can have a dramatic impact on the sight and lives of millions of people.
Olsalazine, 2 g/day, was compared with placebo in 126 patients with mild or moderate ulcerative colitis. Evaluation after 4 weeks revealed a significant improvement in endoscopic findings in the rectum and sigmoid colon and in the clinical parameters rectal mucus and blood discharge, whereas no significant difference was found between olsalazine and placebo groups in clinical parameters, such as stool frequency and consistency, urge to defecate, abdominal pain and biopsy findings. It is concluded that olsalazine, 2 g/day, is tolerated as well as placebo except that it caused diarrhoea in some patients.
Since its description in 1983 Campylobacter pylori (C.p.) has been discussed as possible pathogenic factor at least in duodenal ulcer disease. The therapeutic combination of H2-receptor-antagonists (= H2-RA) and ofloxacin (Tarivid) has shown to heal resistant duodenal ulcers in some preliminary cases, which did not respond to a three month standard dosage treatment with H2-RA. This paper describes the results of twelve patients whose duodenal ulcers were resistant to H2-RA. C.p. was detected in all patients before therapy. The combined treatment with ofloxacin and H2-RA healed the duodenal ulcers within 2 weeks in 6 patients, within 4 weeks in 2, and within 6 weeks in 4 patients as proven by fortnightly performed endoscopic controls. At the end of therapy C.p. was not detected in 11 of 12 patients. The MIC's of ofloxacin for C.p. ranged from 0.5-1 microgram/ml in six investigated patients. The results suggest a possible pathogenic role of C.p. in duodenal ulcer disease.
Impression cytology is a simple technique for detecting vitamin A deficiency. Methods of specimen collection, fixation, and staining are amenable to use in developing countries. Routine use of the technique requires good interobserver agreement. We compared the impression cytology results of 206 patient examinations analyzed by an experienced observer with those obtained by a newly trained observer. Percent agreement measured 96% (197/206) with a kappa of 0.90, indicating excellent agreement. Further improvement in interobserver agreement may be obtainable by simplification of the staining process to highlight the presence or absence of goblet cells, and by simplification of the staging criteria.
Reports about recent famine victims and refugees have described the occurrence of xerophthalmia and resultant blindness related to severe vitamin A deficiency. These populations are subject to high prevalences of childhood protein-energy malnutrition and infectious diseases, pre-existing marginal vitamin A status, and inadequate levels of vitamin A in relief rations. In order to prevent unnecessary morbidity and mortality when any of these risk factors arise, famine victims or refugees should receive vitamin A supplements as an early and essential component of the nutritional support provided by relief agencies. Such supplementation should not await the results of nutrition or blindness surveys but rather should be a standard component of the maternal and child health care provided to the affected population until sufficiency of dietary vitamin A has been clearly established.