Global publication productivity in dermatology: a bibliometric description of the past and estimation of the future.

BACKGROUND: In the past two centuries, generations of dermatologists around the world have created an enormous number of publications. To our knowledge, no bibliometric analysis of these publications has been performed so far, nor have registered trials been analysed to anticipate future publication trends. OBJECTIVES: To determine the global distribution of national publication productivity, most published topics, institutions and funding sources contributing most to publications and to anticipate future trends based on registered clinical trials. METHODS: Following pre-assessment on PubMed, Embase, Web of Science and Scopus, the number of publications for 'dermatology' was determined for each of 195 countries, normalized per 1 Mio inhabitants and bibliometrically analysed. Dermatology-related trials registered at clinicaltrials.gov were specified by the top-10 diagnoses for the top-10 countries. RESULTS: The search yielded 1 071 518 publications between 1832 and 2019 with the top-5 diagnoses being melanoma, basal cell carcinoma, psoriasis, pruritus/itch and atopic dermatitis. The top-3 countries with highest absolute numbers of publications were the USA (30.6%), Germany (8.1%) and the UK (8.1%), whereas Switzerland, Denmark and Sweden had the highest publication rates when normalized by inhabitants. The most productive affiliation was the Harvard Medical School, the leading funding source the National Institutes of Health. Currently, maximum number of trials are registered in the USA (8111), France (1543) and Canada (1368). The highest percentage of all dermatology-related trials in a specific country were as follows: Melanoma in the Netherlands (24.8%), psoriasis in Germany (21.7%) and atopic dermatitis in Japan (15.9%). CONCLUSION: The top-10 countries including the USA, Canada, a few European and Asian countries contributed more than 3/4 of all publications. The USA hold the dominant leader position both in past publication productivity and currently registered trials. While most Western countries continue to focus their research on the top-10 topics, China and India appear to prioritize their scope towards other topics.

The effect of body composition and serum inflammatory markers on the functional muscle-bone unit in premenopausal women.

BACKGROUND/OBJECTIVES: A number of recent studies dealing with the relationship between the effects of high body mass (BM) and fat mass (FM) on bone mass and strength exhibit a range of contrasting variations in their findings. These diverse findings have led to an ongoing controversy as to whether high BM and FM positively or negatively affect bone mass and strength. Excessive FM and the associated low-grade inflammation might overturn the higher mechanical stimulus arising from a higher BM. Therefore, we aimed at quantifying the functional muscle-bone unit in premenopausal women with markedly diverging body composition. SUBJECTS/METHODS: Sixty-four young women with BMs ranging from 50 to 113 kg and body fat percentages between 20.7% and 51.8% underwent jumping mechanography and peripheral quantitative computed tomography measurements. Maximum voluntary ground reaction force during multiple one-legged hopping (Fm1LH), as well as bone characteristics at 4, 14 and 38% of tibia length, were determined. Body composition was assessed by dual-energy X-ray absorptiometry, and serum inflammatory markers were analyzed from blood samples. RESULTS: Fm1LH predicted volumetric bone mineral content at the 14% site by 48.7%. Women with high body fat percentage had significantly higher Fm1LH, significantly lower relative bone mass, relative bone strength and relative bone area, as well as higher serum inflammatory markers in comparison to women with lower body fat percentage. CONCLUSIONS: In conclusion, high body fat percentage was associated with lower relative bone mass and strength despite normal habitual muscle force in premenopausal women, indicating that high body fat percentage compromised the functional muscle-bone unit in these individuals.

Reliability of parameters during stair ascent measured with Leonardo Mechanograph(®) Stair A in healthy subjects.

OBJECTIVES: Stair climbing (SC) as daily activity is assessed with different SC-tests, but none directly measures ground reaction force over several steps. The Leonardo Mechanograph Stair A has five steps and four force sensors. This study aimed at investigating the reliability of the Stair A test for force, power and time to SC. METHODS: 55 healthy participants (age: 48±14 years) were five times tested during SC with self-chosen and fast speed. 30 participants were examined for test-retest-reliability, calculated with the intraclass correlation coefficient (ICC). The variability was examined with the coefficient of variation (CV). To determine potential associations between SC and jumping performance or daily activity, squat and countermovement jumps were additionally performed and the International physical activity questionnaire (IPAQ) was completed. RESULTS: The inter-visit ICCs of self-chosen and fast SC were good to excellent 0.63-0.77. The intra-visit ICCs were excellent after three trials (0.78-0.88). The CVs for SC with self-chosen speed were lower (2.1-6.6%) than those for fast SC (4.9-10.8%). There were no significant correlations between SC and jump parameters and only moderate correlations with the IPAQ. CONCLUSION: The Stair A is a reliable tool for the assessment of SC.

[An Unusual Cause of Increased Light Sensitivity]. / Eine ungewöhnliche Ursache für erhöhte Blendempfindlichkeit.

Photophobia is in many cases linked to pathologies of the anterior segment of the eye, e.g. cataract or iritis. We report an unusual case of increased light sensitivity due to a compressing lesion of the chiasm. Pituitary adenomas are among the most frequent intracranial tumours and can affect the chiasm - the site where all the visual afferences meet. A lesion of the chiasm is therefore particularly dangerous. Fortunately, in two-thirds of all cases, pituitary adenomas lead to hormonal dysfunction, so that magnetic resonance imaging of the brain is conducted. However, in the remainder of the cases, the ophthalmologist may be the first physician to see the patient because of visual problems. Usually patients report reduced vision or show typical visual field defects, such as bitemporal hemianopsia. However, the only pathological symptom may be increased light sensitivity. In rare cases of photophobia which cannot be explained by pathologies of the anterior segment, a compressing lesion of the chiasm should be considered.

Regulation of bile acid synthesis in man. Presence of a diurnal rhythm.

Regulation of bile acid synthesis in man is incompletely understood, in part because of difficulty in making measurements over short time periods when the enterohepatic circulation is intact. We investigated the possibility of a diurnal rhythm of bile acid synthesis in three human subjects given [26-14C]cholesterol. When this isotope of cholesterol, which is randomly labeled in the 26 and 27 positions, is converted to bile acid, the 14C is released as propionic acid randomly labeled in the 1 and 3 positions. The labeled propionic acid is then oxidized to 14CO2, output of which is a function of bile acid synthesis. However, delays in transit of the 14C through propionic acid and CO2-HCO-3 pools would shift the phase and dampen the amplitude of 14CO2 output relative to an existing diurnal rhythm of bile acid synthesis. Therefore, using constant infusion methods, we determined the turnover constants for conversion to 14CO2 of [1-14C]propionic acid and [3-14C]propionic acid to be 0.36-0.59 h-1 and 0.14-0.16 h-1, respectively. Using these constants and modeling the diurnal rhythm as a cosine function, we determined that amplitude of 14CO2 output from [26-14C]cholesterol was reduced 35% and acrophase was delayed 2.4-3.0 h relative to the diurnal rhythm of bile acid synthesis. None of the diurnal rhythm in 14CO2 output from [26-14C]cholesterol resulted from diurnal variation in propionic acid or CO2-HCO-3 metabolism since constant infusion of [1-14C]propionic acid and [3-14C]propionic acid for 30 h revealed no diurnal variation in output of 14CO2. These studies demonstrate for the first time that humans with an intact enterohepatic circulation have a diurnal rhythm of bile acid synthesis with an amplitude of +/- 35-55% around mean synthesis, and an acrophase at about 9 a.m.

Medium perfusion enhances osteogenesis by murine osteosarcoma cells in three-dimensional collagen sponges.

In this study, we examined in vitro histogenesis by murine K8 osteosarcoma cells maintained in three-dimensional (3D) collagen sponges. We tested the hypothesis that perfusion of medium enhances cell viability and their biosynthetic activity as assessed by expression of the osteoblastic phenotype and mineral deposition. At intervals, samples were harvested and analyzed histologically, biochemically, and by Northern hybridization for type I collagen, osteopontin (OPN), osteocalcin (OC), and core binding factor alpha 1 (Cbfa1). Histologic evaluation showed greater viability, more alkaline phosphatase (ALP)-positive cells, and more mineralized tissue in the perfused sponges after 21 days. Immunohistological assessment of proliferating cell nuclear antigen revealed 5-fold more proliferating cells in the perfused sponges compared with the controls (p = 0.0201). There was 3-fold more ALP activity in the perfused sponges than the controls at 6 days and 14 days (p = 0.0053). The perfused sponges contained twice the DNA and eight times more calcium than the nonperfused controls after 21 days (p < 0.0001 for both). Northern hybridization analysis revealed more mRNA for collagen type I (2-fold) and 50% more for OC at 14 days and 21 days, whereas OPN and Cbfa1 mRNA expression remained unaffected by the medium perfusion. These results show that medium perfusion had beneficial effects on the proliferation and biosynthetic activity of this osteosarcoma cell line. This system mimics the 3D geometry of bone tissue and has the potential for revealing mechanisms of regulation of osteogenesis.

Longitudinal study of the hindquarter vasculature during development in spontaneously hypertensive and Dahl salt-sensitive rats.

The purpose of this study was to examine vascular structural alterations longitudinally in spontaneous and Dahl genetic hypertension. Hypertensive and control animals were studied at 5,9-11, and 17-19 weeks of age to permit analysis of prehypertensive, early and established hypertensive stages. Minimal and maximal resistance of the hindquarter vasculature was used as a functional assessment of structural alterations. At 5 weeks of age, the minimal vascular resistance of the spontaneously hypertensive rats (SHR) was elevated over Wistar-Kyoto (WKY) (p less than 0.02) but there was no difference between Dahl salt-sensitive (S) and resistant (R) rats. In both sets of animals, the minimal vascular resistance of the hypertensive group was significantly elevated over controls with age: p less than 0.001 in SHR; p less than 0.001 in Dahl S. The maximal vasoconstrictor response was significantly greater with age in SHR than in WKY, (p less than 0.001), but was not different in Dahl S compared to R. Thus, structural alterations, determined by assessing minimal vascular resistance, are present in both spontaneous and Dahl salt-sensitive hypertension, but the origin of the two differ. An increase in smooth muscle mass, assessed by maximal constriction, contributes importantly to the structural alterations in spontaneous hypertension; in Dahl S, other factors appear to contribute to structural alterations. Further, structural alterations precede frank hypertension in SHR but not in Dahl S hypertension.

Effect of chronic hypertension on the blood-brain barrier.

Disruption of the blood-brain barrier (BBB) during acute hypertension may contribute to hypertensive encephalopathy. In this study we tested the hypothesis that, in chronic hypertension, vascular changes might influence the susceptibility of the BBB to disruption. Spontaneously hypertensive rats (SHR) and normotensive rats (WKY), 3-4 months of age, were anesthetized and acute hypertension was produced by infusing phenylephrine intravenously (i.v.). Permeability of the BBB was studied with radioactive iodine serum albumin (RISA) injected i.v. The ratio of brain-to-blood RISA was used as an index of permeability of the BBB expressed as protein transfer. In both SHR and WKY at resting arterial pressure, the protein transfer was less than 0.10%. In WKY exposed to acute hypertension (mean arterial pressure increased by 87 +/- 7 mm Hg), the protein transfer was 2.77 +/- 0.60%. In SHR with acute hypertension superimposed on chronic hypertension (arterial pressure increased by 80 +/- 7 mm Hg), the protein transfer was 1.16 +/- 0.45% (p less than 0.05, SHR vs WKY). These data suggest that cerebral vessels are less susceptible to disruption of the BBB by acute hypertension in SHR than in WKY. We speculate that the finding of reduced susceptibility to BBB disruption in chronic hypertension may explain, in part, the apparent susceptibility of previously normotensive patients to acute hypertensive encephalopathy.

Enlarged cerebral ventricular system in infant achondroplastic dwarf.

The cause of the enlarged head found in achondroplastic dwarfs has been disputed. We studied an infant achondroplastic dwarf who had an enlarged (90%) head at age 2 months without enlarged cerebral ventricles. At age 10 months, her head size further enlarged (95%) and the cerebral ventricles were dilated. Megalencephaly may be the major factor contributing to the enlarged head in newborn achondroplastic dwarfs. Later, enlarged cerebral ventricles also contribute.

Neurologic complications of phenylpropanolamine use.

Eleven patients had neurologic symptoms after taking "look-alike" pills thought to contain amphetamines but actually containing phenylpropanolamine. Phenylpropanolamine, a nonregulated drug, is structurally and functionally similar to amphetamines. Acute onset of headache, psychiatric symptoms, or seizures in young patients may be due to phenylpropanolamine use.

Reversal of emissary vein blood flow in achondroplastic dwarfs.

We used a noninvasive technique--the directional Doppler examination--to determine the direction of flow in an emissary vein of achondroplastic dwarfs. Normally, the direction of flow in this emissary vein is into the orbit. The direction of flow in all 10 achondroplastic dwarfs whom we studied was away from the orbit. This indicates that ophthalmic vein blood flow is reversed in achondroplastic dwarfs, perhaps because there is a pressure gradient between the intracranial and extracranial venous systems.

Achondroplasia and hydrocephalus. A computerized tomographic, roentgenographic, and psychometric study.

Nine achondroplastic dwafts were studied with computerized tomography, skull and cervical spine films, and psychometric testing. All had large ventricles that ranged from the top limits of normal to severe hydrocephalus. Three had enlarged cortical sulci. Skull and cervical spine films were typical for achondroplasia, but in addition significant asymmetry of the petrous ridge was noted. Psychometric testing disclosed generally average intelligence quotients which fell below the expected performance level in each case. These findings may be explained on the basis of the abnormal endochondral bone formation found in achondroplasia.

Meniscus cells seeded in type I and type II collagen-GAG matrices in vitro.

The objective of this study was to determine the proliferative and biosynthetic activity of calf meniscus cells seeded in type I and type II collagen-glycosaminoglycan (GAG) copolymers with the overall goal to develop a cell-seeded implant for future investigations to improve the regeneration of the knee meniscus. The cell-seeded matrices were digested in protease and analyzed for GAG by a modification of the dimethyl-methylene blue method and assayed for DNA content. Other specimens were evaluated histologically after 1, 7, 14 and 21 days. Contraction of the same types of matrices, seeded with adult canine meniscus cells, was measured at the same time points. After three weeks, cells were observed throughout the type II matrix, whereas the type I matrix was densely populated at the margins. The cell morphology and the cell density after three weeks in both matrices was consistent with the normal meniscus. DNA assay for the type I matrix showed a 40% decrease over the first week and a final amount of DNA that was not significantly different from the initial value, whereas the type II matrix doubled its DNA content over the same time period. The cells continued their biosynthesis of GAG and type I collagen. GAG content of the type II matrix increased by 50% more than the type I matrix after three weeks. Over the same time period, the type I matrix displayed a significant shrinkage to approximately 50% of its initial value whereas in contrast, the type II matrix and the unseeded controls showed no significant shrinkage. The number of cells and the higher GAG synthesis in the type II matrix, and its resistance to cell-mediated contracture, commend it for future investigation of the regeneration of meniscus in vivo.

Eradication of a dysfunctional HLA-haploidentical T cell system by a second HLA-identical BMT.

A 12-year-old boy treated for SCID at 1 month of age by HLA-haploidentical BMT developed a lymphoproliferative disease of unknown etiology at the age of 9 years characterized by sustained, marked elevation of circulating CD8+ donor T cells and by diffuse infiltration of the liver by CD8+ T cells. Because of progressive liver disease, the patient underwent a second BMT from a younger HLA-matched sister. This treatment induced an effective graft-versus-graft reaction and led to complete replacement of the HLA-nonidentical, dysfunctional T cell system, resolution of the hepatopathy and full reconstitution of T and B cell functions.

Expression of alpha-smooth muscle actin in canine intervertebral disc cells in situ and in collagen-glycosaminoglycan matrices in vitro.

The objective of this study was to investigate the presence of a contractile actin isoform, alpha-smooth muscle actin, in annulus fibrosus cells in situ and in two and three-dimensional cultures. Annulus fibrosus cells were isolated from healthy adult dogs, serial passaged, and then injected into porous collagen-glycosaminoglycan copolymers consisting of either type-I or type-II collagen. Alpha-smooth muscle actin was detected in the cells in tissue samples and in culture by immunohistochemistry. The number of cells and glycosaminoglycan content of the matrices were determined after 1, 7, and 14 days, and the diameters of the specimens were measured every 2 days. Although few annulus fibrosus cells in vivo displayed the presence of the alpha-smooth muscle actin isoform, most cells in two-dimensional culture demonstrated this phenotype. The contractile behavior of these cells was shown by the cell-mediated contraction of type-I collagen-glycosaminoglycan scaffolds after 8 days in culture. Glycosaminoglycan production was not significantly different in the seeded type-I matrices than in the unseeded matrices, whereas the seeded type-II matrices had a significant increase in glycosaminoglycan production between days 1 and 14 compared with the unseeded controls. This is the first report of both the expression of the contractile alpha-smooth muscle actin isoform in intervertebral disc cells and the ability of the cells to contract a collagen matrix. This finding could aid in better understanding the nature of cells in the annulus.

Insulin treatment prevents vascular dysfunction in early juvenile alloxan-induced diabetes mellitus.

Microvascular pathology and sympathetic autonomic dysfunction have been described early in alloxan-induced diabetic juvenile rats. To determine the longitudinal development of these changes and whether insulin treatment can alter them, vascular and sympathetic function were studied in alloxan-induced (42.5 mg/kg) juvenile diabetic rats and saline-treated controls. The rats were examined 1 and 14 days after induction of diabetes. An insulin-treated group was studied with the 14-day group. Hindquarter perfusion with an artificial solution at constant flow/100 g hindquarter wt was used. After 14 days of diabetes mellitus, the diabetic group showed a significantly depressed response to central ischemia (P less than 0.001), maximal vasoconstriction (P less than 0.02), and maximal dilation (P less than 0.001) compared with both the control and insulin-treated group. The threshold response to norepinephrine did not differ. After 1 day of glucose elevation no differences were present between the control and diabetic animals during any of the testing procedures. These results suggest that severe vascular dysfunction develops early in juvenile-onset alloxan diabetes and that it can be prevented with insulin treatment.

Adult sympathetic and vascular dysfunction in experimental juvenile-onset diabetes mellitus.

This study was designed to determine if vascular dysfunction and enhanced norepinephrine sensitivity occurring in early experimental juvenile diabetes (S. M. Mueller, T. M. Mueller, and P. J. Ertel, 1982, Amer. J. Physiol. 243, H139-H144) persist, improve, or worsen in adulthood. Alloxan was administered to rats at 4 weeks of age and they were studied 14 weeks later. After Seconal anesthesia, the hindquarters of diabetic and control rats were perfused at a constant flow rate per 100 g through the abdominal aorta with oxygenated Tyrode solution containing dextran. Efflux was from the ligated and severed inferior vena cava. In order to test the effect of a strong sympathetic stimulus producing reflex peripheral vasoconstriction, the cephalad portions of the rats were rapidly hemorrhaged. The time to the maximal increase was significantly longer in the diabetics (122 +/- 6 sec, P less than 0.05) than in the controls (102 +/- 5 sec) and the increase in perfusion pressure was markedly less in the diabetics (D) (48 +/- 9 mm Hg, P less than 0.01) than in the age-matched controls (C) (88 +/- 10 mm Hg). The threshold to norepinephrine in the perfusate was determined. The threshold was significantly lower in D than in age-matched C [0.112 +/- 0.026 (P less than 0.05) vs 0.265 +/- 0.057 micrograms/ml, respectively]. The maximum vasoconstrictor capacity of the vasculature was tested with supramaximal doses of vasopressin and was significantly lower in D than in C [190 +/- 10 (P less than 0.001) vs 284 +/- 15 mm Hg, respectively]. These data suggest that both vasculopathy and enhanced norepinephrine sensitivity persist in chronic uncontrolled experimental diabetes mellitus. However, when the severity of the abnormalities was compared to early experimental diabetes mellitus, mild improvement had occurred--an apparent adaptation to the diabetic state as the animal grew.