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.

[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.

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.

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.

Age-related decline in the osteogenic potential of human bone marrow cells cultured in three-dimensional collagen sponges.

Studies with human and animal culture systems indicate that a sub-population of bone marrow stromal cells has the potential to differentiate into osteoblasts. There are conflicting reports on the effects of age on human marrow-derived osteogenic cells. In this study, we used a three dimensional (3D) culture system and quantitative RT-PCR methods to test the hypothesis that the osteogenic potential of human bone marrow stromal cells decreases with age. Marrow was obtained from 39 men aged 37 to 86 years, during the course of total hip arthroplasty. Low-density mononuclear cells were seeded onto 3D collagen sponges and cultured for 3 weeks. Histological sections of sponges were stained for alkaline phosphatase activity and were scored as positive or negative. In the group < or = 50 years, 7 of 11 samples (63%) were positive, whereas only 5 of 19 (26%) of the samples in the group > or = 60 years were positive (p = 0.0504). As revealed by RT-PCR, there was no expression of alkaline phosphatase or collagen type I mRNA before culture, however there were strong signals after 3 weeks, an indication of osteoblast differentiation in vitro. We performed a quantitative, competitive RT-PCR assay with 8 samples (age range 38-80) and showed that the group < or = 50 years had 3-fold more mRNA for alkaline phosphatase than the group > or = 60 years (p = 0.021). There was a significant decrease with age (r = - 0.78, p = 0.028). These molecular and histoenzymatic data indicate that the osteogenic potential of human bone marrow cells decreases with age.

Age-related decline in osteoprotegerin expression by human bone marrow cells cultured in three-dimensional collagen sponges.

With advancing age, an increase in bone resorption relative to bone formation results in bone loss. Bone marrow stromal cells and their products support osteoclastogenesis from hematopoietic progenitors. Another of their products, osteoprotegerin (OPG), blocks the osteoclast-stimulatory effects of OPG ligand. We tested the hypothesis that with advancing age there is a decrease in OPG expression by human bone marrow cells. Bone marrow cells were obtained from 18 subjects (age range 38-84 years). Expression of mRNA transcripts of OPG was assessed by quantitative competitive RT-PCR. Median number of OPG transcripts in the younger group was 0. 3 zetptomoles (range 0.01 to 1.30) and was higher than in the older group's median of 0.06 (range 0 to 0.5; p < 0.05). The decline in the expression of OPG with age may increase the capacity of stromal/osteoblast cells to support osteoclastogenesis.

alpha-smooth muscle actin and contractile behavior of bovine meniscus cells seeded in type I and type II collagen-GAG matrices.

Many types of injuries to the meniscus of the knee joint result in defects that do not heal, leading to pain and dysfunction. Several ongoing investigations are developing porous absorbable matrices to be used alone or seeded with cultured cells to facilitate regeneration of this tissue. The objective of this study was to evaluate in vitro the contractile behavior of meniscal cells seeded in type I and type II collagen matrices. In many connective tissues, fibroblasts that have assumed a contractile phenotype (myofibroblasts) have been found to play an important role in healing and in pathological conditions. This phenotype, if expressed by meniscal cells, could affect their behavior in cell-seeded matrices developed for tissue engineering. In this study, the presence of a contractile actin isoform, alpha-smooth muscle (alpha-SM) actin, was assessed by immunohistochemistry in normal calf meniscal tissue and in meniscal cells in 2- and 3-dimensional culture. Calf meniscus cells were seeded in type I and type II collagen-glycosaminoglycan (GAG) matrices. The diameter of the matrices was measured every 2-3 days. Immunohistochemical staining of the 2-dimensional cultures for alpha-SM actin was performed after 1, 3, and 7 days and the staining of the seeded matrices was at 1, 7, 14, and 21 days. Transmission electron microscopy (TEM) was performed on selected samples. After 3 weeks the seeded type I matrices displayed a significant shrinkage of almost 50% whereas the type II matrix and both types of unseeded controls showed almost no contraction over the same time period. Positive staining for the alpha-SM actin phenotype was seen in 10% of the cells of the normal tissue but was present in all cells seeded in monolayer and in both types of matrices. TEM of representative cell-seeded matrices showed microfilaments approximately 7 nm thick, consistent with the myofibroblast phenotype. This is the first report of alpha-SM actin containing cells in the knee meniscus. The finding that, under certain conditions, meniscal cells can express the myofibroblast phenotype warrants study of their role in meniscal healing and the tissue response to implants to facilitate tissue regeneration.

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.

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.

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.

Quantitative importance of the 25-hydroxylation pathway for bile acid biosynthesis in the rat.

During biosynthesis of bile acid, carbons 25-26-27 are removed from the cholesterol side chain. Side-chain oxidation begins either with hydroxylation at the 26-position, in which case the three-carbon fragment is released as propionic acid, or with hydroxylation at the 25-position, in which case the three-carbon fragment is released as acetone. In the present study, we have quantitated the relative importance of these two pathways in vivo by measuring production of [14C] acetone from [14C]-26-cholesterol. Four days after intraperitoneal injection of 20 to 40 muCi [14C]-26-cholesterol and 1 day after beginning a constant intravenous infusion of unlabeled acetone at 25 mumoles per kg per min, 6 male and 2 female Sprague-Dawley rats underwent breath collections. Expired acetone was trapped and purified as the 2,4-dinitrophenylhydrazine derivative. 14CO2 was trapped quantitatively using phenethylamine. Specific activity of breath acetone was multiplied times the acetone infusion rate to calculate production of [14C]acetone. [14C] Acetone production averaged 1.7% of total release of 14C from [14C]-26-cholesterol, estimated by 14CO2 output. The method was validated by showing that [14C] acetone production from [14C]isopropanol averaged 111% of the [14C]isopropanol infusion rate. We conclude that, in the normal rat, the 25-hydroxylation pathway accounts for less than 2% of bile acid synthesis.

Evidence for a captopril-sensitive angiotensin converting enzyme in the hindquarter vasculature of SHR and WKY.

Vascular angiotensin converting enzyme could contribute to the elevated vascular resistance found in hypertension. The purpose of this study was to determine if angiotensin converting enzyme activity was present in the hindquarter vasculature of one model of hypertension, the spontaneously hypertensive rat (SHR) and its normotensive control, the Wistar-Kyoto rat (WKY). We evaluated the effect of a maximal blocking dose of captopril (0.5 mg) on the angiotensin I pressor response during the infusion of the hindquarter with an artificial perfusate. Angiotensin I (1000 ng/ml) produced a significant increase in peripheral vascular resistance (PVR) in both SHR and WKY, but the increase was greater in SHR. Captopril inhibited the elevation in PVR in both. A lower concentration of angiotensin I (250 ng/ml) produced a significant and similar pressor response in SHR (less than the pressor response to 1000 ng/ml) and WKY (same as the pressor response to 1000 ng/ml). Again, captopril prevented the elevation in PVR to A1 in both SHR and WKY. Because these studies were performed using an artificial perfusate, angiotensin converting enzyme must be present in the SHR and WKY hindquarter vasculature including resistance vessels.

Sympathetic nerve activity: a link to stroke?

Spontaneously hypertensive rats (SHR) have been shown to have an increased capacity for superior cervical sympathetic nerve activity which may protect against stroke (Mueller et al: Stroke 13: 115, 1982). Sympathetic nerve activity has never been examined in the stroke-prone substrain of SHR (SP). In this study we measured superior cervical sympathetic nerve activity during rest and during a maximal sympathetic response in SHR, SP, and their normotensive controls, Wistar-Kyoto (WKY). The resting superior cervical sympathetic nerve activity of SP was significantly less than SHR (p less than 0.02) but not different from WKY. During central ischemia, used to induce maximal sympathetic response, the increase in SP sympathetic nerve activity was significantly less than SHR (p less than 0.001) but was not different from WKY. This diminished capacity for elevated superior cervical sympathetic nerve activity in stroke-prone SHR may relate to their increased predisposition to stroke because sympathetic hyperactivity cannot protect cerebral vessels during acute hypertension.

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.