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Biomedical subjects

R Stern

Publications and source records attributed to R Stern.

At least 19 recordsLinked to original sources
PubMed2006

Mutations in WNT7A cause a range of limb malformations, including Fuhrmann syndrome and Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome.

Fuhrmann syndrome and the Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome are considered to be distinct limb-malformation disorders characterized by various degrees of limb aplasia/hypoplasia and joint dysplasia in humans. In families with these syndromes, we found homozygous missense mutations in the dorsoventral-patterning gene WNT7A and confirmed their functional significance in retroviral-mediated transfection of chicken mesenchyme cell cultures and developing limbs. The results suggest that a partial loss of WNT7A function causes Fuhrmann syndrome (and a phenotype similar to mouse Wnt7a knockout), whereas the more-severe limb truncation phenotypes observed in Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome result from null mutations (and cause a phenotype similar to mouse Shh knockout). These findings illustrate the specific and conserved importance of WNT7A in multiple aspects of vertebrate limb development.

Amino Acid Sequence↗
PubMed2006

Cryogenic NMR spectroscopy of endohedral hydrogen-fullerene complexes.

We have observed 1H NMR spectra of hydrogen molecules trapped inside modified fullerene cages under cryogenic conditions. Experiments on static samples were performed at sample temperatures down to 4.3 K, while magic-angle-spinning (MAS) experiments were performed at temperatures down to 20 K at spinning frequencies of 15 kHz. Both types of NMR spectra show a large increase in the intramolecular 1H-1H dipolar coupling at temperatures below 50 K, revealing thermal selection of a small number of spatial rotational states. The static and MAS spectra were compared to estimate the degree of sample heating in high-speed cryogenic MAS-NMR experiments. The cryogenic MAS-NMR data show that the site resolution of magic-angle-spinning NMR may be combined with the high signal strength of cryogenic operation and that cryogenic phenomena may be studied with chemical site selectivity.

Journal Article↗
PubMed2006

Treatment of bone and joint infections caused by Gram-negative bacilli with a cefepime-fluoroquinolone combination.

A 3-year retrospective study evaluated the effectiveness and safety of cefepime plus a fluoroquinolone for treating bone and joint infections caused by Gram-negative bacilli (GNB) in 28 patients. Intra-operative cultures yielded primarily Pseudomonas spp. and Enterobacter cloacae. Full recovery (cure) was observed in 79% of patients. There were no serious adverse effects and no resistant organisms were isolated. The results of the study confirmed the safety and effectiveness of cefepime combined with a fluoroquinolone for the treatment of bone and joint infections caused by Gram-negative bacilli.

Adult↗
PubMed2005

Cutaneous bioassay of salicylic acid as a keratolytic.

Keratolytic efficacy of topical preparations containing salicylic acid was studied in humans utilizing adhesive tape stripping and quantifying SC removal by protein analysis. In combination with tape stripping, squamometry was used to evaluate the influence of salicylic acid on skin surface scaliness and desquamation. Furthermore, skin barrier perturbation and skin irritancy was recorded and related to the dermatopharmacological effect of the preparations. In contrast to squamometry, tape stripping combined with protein analysis was sensitive in detecting keratolytic effect of salicylic acid within hours of application. Importantly, whereas the pH of the preparations only minimally influenced efficacy, local dermatotoxicity was significantly increased at acidic pH. This indicates that the quest to increase the amount of free, non-dissociated SA is, in fact, counterproductive as the more acidic preparations resulted in skin irritation and barrier disruption.

Administration, Cutaneous↗
PubMed2004

Magnetic-field-induced condensation of triplons in Han Purple pigment BaCuSi2O6.

Besides being an ancient pigment, BaCuSi2O6 is a quasi-2D magnetic insulator with a gapped spin dimer ground state. The application of strong magnetic fields closes this gap, creating a gas of bosonic spin triplet excitations. The topology of the spin lattice makes BaCuSi2O6 an ideal candidate for studying the Bose-Einstein condensation of triplet excitations as a function of the external magnetic field, which acts as a chemical potential. In agreement with quantum Monte Carlo numerical simulations, we observe a distinct lambda anomaly in the specific heat together with a maximum in the magnetic susceptibility upon cooling down to liquid helium temperatures.

Journal Article↗
PubMed2004

Aberrant serum hyaluronan and hyaluronidase levels in scleroderma.

BACKGROUND: Scleroderma, or systemic sclerosis, is characterized by aberrations of extracellular matrix deposition. These changes parallel early stages of wound healing when increased deposition of hyaluronan (HA) and collagen occur. Both processes result ultimately in the formation of fibrotic scar tissue. Activities of HA synthase and hyaluronidase, the enzymes that synthesize and degrade HA, are critical in HA turnover. Both become elevated whenever increased matrix deposition occurs. HA deposition occurs early in wound healing, and increases are documented in the circulation of scleroderma patients. We postulated that elevated HA and hyaluronidase may both be indicators of early-stage disease in scleroderma, in parallel with early changes observed in wound healing. In an attempt to reduce HA accumulation and the associated fibrosis in scleroderma tissues, topical and intravenous hyaluronidase administrations have been used in the past as treatment modalities, with occasional success. This also suggested that hyaluronidase enzyme activity is involved in the disease process. It is now recognized that the hyaluronidases constitute an enzyme family. The somatic hyaluronidase Hyal-1 is the only activity present in human serum. OBJECTIVES: To determine levels of HA and Hyal-1 in the sera of scleroderma patients at various stages of their disease. METHODS: Levels of HA and Hyal-1 activity were determined in 25 scleroderma patients. Subjects were separated into two groups, those in the early stage with duration of disease of 2 years or less, and late-stage patients with disease duration of more than 2 years. RESULTS: In early-stage scleroderma, levels of HA were elevated significantly, as predicted, in comparison with late-stage patients and controls. Late-stage levels of HA were comparable with those found in control sera. By contrast, levels of Hyal-1 activity were normal in early-stage patients, similar to those in controls, but were decreased in late-stage patients, falling even below those of controls. CONCLUSIONS: We have confirmed that circulating levels of HA are elevated in scleroderma, but show for the first time that such elevations occur predominantly in early-stage disease. Patients with late-stage disease have decreased serum Hyal-1 activity, perhaps reflecting decreased levels of HA turnover. This study also represents the first time that hyaluronidase activity levels have been determined in scleroderma patients.

Adult↗
PubMed2004

High dose vancomycin for osteomyelitis: continuous vs. intermittent infusion.

OBJECTIVES: To compare the efficacy, ease of use and safety of intermittent vancomycin infusion (IVI) and continuous vancomycin infusion (CVI) in high-dose therapy of osteomyelitis. METHODS: Forty-four patients with an osteomyelitis requiring vancomycin for more than 4 weeks were prospectively included, 21 receiving IVI and 23, CVI. The target serum concentration of vancomycin was 20-25 mg/L. Pharmacokinetics, adverse effects, and clinical efficacy were recorded. RESULTS: The mean daily vancomycin dosing was the same in the two groups, but the serum vancomycin concentrations (trough or plateau) were lower in the IVI group than the CVI group (21.7 +/- 9.3 and 26.0 +/- 6.1 mg/L, respectively; P < 0.0001). The target concentrations were achieved quicker with CVI, and daily dosing was changed more frequently in the IVI group. After reaching the target, variability of vancomycin serum concentration (trough or plateau concentrations) was higher in the IVI group than in CVI group (standard deviation 7.9 mg/L vs. 5.6 mg/L, respectively; P = 0.001). CVI did not show clinical superiority, but adverse drug effects were more frequent in the IVI group as compared with the CVI group, 9 (42.9%) and 2 (8.7%), respectively (P = 0.03). Survival multiple regression using Cox's proportional hazard model showed that IVI (RR = 5.9, P = 0.03) and osteomyelitis of the foot (RR = 5.2, P = 0.01) were the only factors associated with adverse drug reactions leading to treatment termination. CONCLUSIONS: CVI is practical and effective, and may be a good alternative for patients requiring prolonged treatment with high vancomycin serum levels.

Anti-Bacterial Agents↗
PubMed2003

Serotonin syndrome after concomitant treatment with linezolid and citalopram.

Linezolid, a new synthetic antimicrobial, is an important weapon against methicillin-resistant Staphylococcus aureus (MRSA). Although there are reports of serotonin syndrome developing after concomitant use of linezolid and the selective serotonin reuptake inhibitor paroxitene, this report concerns a patient receiving citalopram who developed thrombocytopenia, serotonin syndrome, and lactic acidosis and died following long-term linezolid therapy.

Acetamides↗
PubMed2002

Evaluation of the age-adjusted incidence of hip fractures between urban and rural areas: the difference is not related to the prevalence of institutions for the elderly.

As many as 40% of hip fractures occur in institutions for the elderly. Several studies have demonstrated a higher age-adjusted incidence of hip fractures in urban areas compared with rural areas. To assess whether this difference could be due to a preferential location of institutions for the elderly in urban areas, we compared the incidence of hip fractures over a 5-year period in urban versus rural areas, as defined according to the population density (urban > 15 inhabitants/ha2). We then determined the age-adjusted incidence of hip fractures in institutional-dwelling elderly and home-dwelling elderly. Hip fracture incidence was 100.0/100,000 (150.5 in women and 43.8 in men) in urban areas, and 71.0/100,000 (107.2 in women and 32.8 in men) in rural areas (p<0.001). When only those patients living in their own homes were analyzed, the incidence was 66.7/100000 (94.6 in women and 35.7 in men) in urban regions and 36.8/100,000 (49.6 in women and 23.4 in men) in rural areas (p<0.001), a difference of even greater magnitude than when both home-dwelling and institutional-dwelling residents were considered together. In a logistic regression model including age class, gender, urban or rural areas and institutionalization for inhabitants 65 years of age and older, urban residents have a 31% significantly (p<0.001) higher incidence of hip fracture compared with rural residents; women have a 79% significantly (p<0.001) higher incidence of hip fracture compared with men; and institutional-dwelling elderly have a 351% significantly (p<0.001) higher incidence of hip fracture compared with home-dwelling elderly. These results confirm the existence of a higher age-adjusted incidence of hip fractures in urban compared with rural areas. Since this difference is increased when patients living at home were analyzed separately, it indicates that the difference between urban and rural areas is not due to a preferential urban location of institutions for the elderly.

Age Distribution↗
PubMed2001

Hyaluronidase can modulate expression of CD44.

CD44 is a family of transmembrane glycoproteins with multiple isoforms generated by alternative exon splicing of a single gene. CD44 and its variants are expressed on a wide variety of cells including cancer cells. The mechanisms by which splice variant exons are selected are unknown. The presence of hyaluronan in the environment of the cell appears to influence that selection process. The expression of particular splice variants of CD44 as well as the simultaneous presence of hyaluronan is important for motility, invasion, and the metastatic spread of some tumors. The influence of hyaluronidase digestion on the expression of CD44 in human cancer cell lines was examined. CD44 isoforms containing alternatively spliced exons were sensitive to hyaluronidase digestion in all lines examined, but differences between cell lines were observed. Expression of CD44s, the standard form, was resistant to digestion in two of three cell lines. A tentative model was formulated proposing that CD44 isoforms containing splice variants are unstable, requiring the continuous presence of ligand for expression. CD44s is relatively more stable, not requiring the continuous presence of hyaluronan. Additionally, a number of new CD44 variant isoforms, not previously observed, were identified.

Alternative Splicing↗
PubMed2001

Plasma hyaluronidase (Hyal-1) promotes tumor cell cycling.

Paradoxically, both hyaluronan (HA) and hyaluronidase are involved in malignant transformation and cancer progression. Their mechanisms of action, given the apparent disparities, are not understood. In many malignancies, levels of HA correlate with metastatic behavior while hyaluronidases suppress malignant progression. Hyal-1, product of one of six paralogous hyaluronidase-like sequences, is the predominant circulating hyaluronidase. HYAL1, the gene that codes for Hyal-1, is located on chromosome 3p21.3, a region containing a tumor suppressor gene. Loss of HYAL1 often correlates with tumor progression, particularly in tobacco-related cancers. In other malignancies, however, hyaluronidase functions as a tumor promoter. Testicular hyaluronidase (PH-20), used as an adjuvant in chemotherapy, is assumed to enhance drug permeability. By an unknown mechanism, hyaluronidases recruit tumor cells back into the cycling pool, making these malignancies more sensitive to chemotherapeutic drugs. Such contradictory observations might be resolved by assuming that HA and hyaluronidase are required at different times in the multiple steps that lead to malignant transformation. We have undertaken a systematic investigation of their roles in cancer progression. Here, we investigate the effect of Hyal-1 expression on cell cycle kinetics. A tumor cell line was constructed with an ecdysone-inducible promoter located upstream from the cDNA of HYAL1. Fluorescent-activated cell sorting was used to monitor cell cycle kinetics following Hyal-1 induction. Enhanced cell cycling was observed, with a 13.6% increase in S phase and 9.6% decrease in G(1)/G(0) phase cells.

Cell Cycle↗
PubMed2001

Dimethylnitrosamine-induced liver injury in rats: the early deposition of collagen.

Dimethylnitrosamine (DMN) is a potent hepatotoxin that can cause fibrosis of the liver. It's ability to provide a suitable rapid experimental murine model for early human cirrhosis was examined. The drug was administered to adult male albino rats in order to document sequential pathological and biochemical alterations. Injury was produced by intraperitoneal injections of DMN on three consecutive days of each week over a 3-week period. A rapid increase in collagen content was documented, with linear increases occurring from days 7 to 21. Livers were examined for histopathological changes on days 7, 14 and 21 following the beginning of exposure. Severe centrilobular congestion and haemorrhagic necrosis could be observed on day 7. Centrilobular necrosis and intense neutrophilic infiltration were observed on day 14. By day 21, collagen fiber deposition could be observed, together with severe centrilobular necrosis, with focal fatty changes, bile duct proliferation, bridging necrosis and fibrosis surrounding the central veins. A decrease in total protein and increase in DNA were also documented. DMN-induced liver injury in rats appears to be a potential animal model for early human cirrhosis and the rapid deposition of collagen, and may serve as a convenient procedure for screening antifibrotic agents.

Animals↗
PubMed2001

Distribution of hyaluronan in human endometrium across the menstrual cycle. Implications for implantation and menstruation.

Hyaluronan is a molecule with many known roles in cellular physiology and is often associated with tissue remodeling. The human endometrium undergoes dramatic remodeling during the course of the normal menstrual cycle but its regulation is not well understood. This study examined the levels of deposition of hyaluronan in human cycling endometrium by histochemical localization, using a highly specific hyaluronan-binding peptide. This was facilitated by avoiding conventional formalin fixation, which results in serious loss of the water-soluble hyaluronan. Peaks of hyaluronan deposition were observed in the stromal compartment during the mid-proliferative (days 5-10) and the mid-secretory phase (days 19-23) of the cycle. In physiological terms, the first phase corresponds to the time of rapid cellular proliferation of undifferentiated cells, whereas the second phase coincides with the time when the implantation of the conceptus would be initiated in a fertile cycle. By the time menstruation starts, very little hyaluronan remains in the stroma. In contrast with the stromal staining, hyaluronan deposition around blood vessels was constant throughout the cycle. The dramatic changes in hyaluronan deposition and their correlation with the cyclic growth and remodeling in the human endometrium suggest a major role for hyaluronan in the physiology of this tissue.

Endometrium↗
PubMed2001

The six hyaluronidase-like genes in the human and mouse genomes.

The human genome contains six hyaluronidase-like genes. Three genes (HYAL1, HYAL2 and HYAL3) are clustered on chromosome 3p21.3, and another two genes (HYAL4 and PH-20/SPAM1) and one expressed pseudogene (HYALP1) are similarly clustered on chromosome 7q31.3. The extensive homology between the different hyaluronidase genes suggests ancient gene duplication, followed by en masse block duplication, events that occurred before the emergence of modern mammals. Very recently we have found that the mouse genome also has six hyaluronidase-like genes that are also grouped into two clusters of three, in regions syntenic with the human genome. Surprisingly, the mouse ortholog of HYALP1 does not contain any mutations, and unlike its human counterpart may actually encode an active enzyme. Hyal-1 is the only hyaluronidase in mammalian plasma and urine, and is also found at high levels in major organs such as liver, kidney, spleen, and heart. A model is proposed suggesting that Hyal-2 and Hyal-1 are the major mammalian hyaluronidases in somatic tissues, and that they act in concert to degrade high molecular weight hyaluronan to the tetrasaccharide. Twenty-kDa hyaluronan fragments are generated at the cell surface in unique endocytic vesicles resulting from digestion by the glycosylphosphatidyl-inositol-anchored Hyal-2, transported intracellularly by an unknown process, and then further digested by Hyal-1. The two beta-exoglycosidases, beta-glucuronidase and beta-N-acetyl glucosaminidase, remove sugars from reducing termini of hyaluronan oligomers, and supplement the hyaluronidases in the catabolism of hyaluronan.

Amino Acid Sequence↗
PubMed2001

Efficacy of corticosteroids in acute experimental irritant contact dermatitis?

BACKGROUND/AIMS: Topical corticoids are used to treat irritant contact dermatitis (ICD) in humans. However, their clinical efficacy remains sub judice. This study was designed to assess the efficacy of low- and medium-potency corticosteroids on irritant dermatitis. METHODS: We induced an acute ICD via open application of sodium lauryl sulphate (SLS) on the hands of subjects. The dorsal side of hands was irritated with 10% SLS five times in one day. Once on day 1 and twice daily on days 2-5, 1% hydrocortisone, 0.1% betamethasone-17-valerate and vehicle cream (petrolatum) were applied subsequently. Visual grading, bioengineering techniques and squamometry were used to quantify skin response. RESULTS: Corticosteroids were found ineffective in treating the surfactant-induced irritant dermatitis when compared with the vehicle and with the untreated control. CONCLUSION: The counterintuitive result (in a relatively realistic and robust model) should be interpreted with caution until verified with other irritants of varying physicochemical properties.

Adult↗
PubMed2001

Exploring the factors that influence employees' perceptions of their organisation's culture.

The topic of organisational culture is of significant interest in the management literature since culture is so closely tied to organisational identity and work processes. Culture is usually measured as a set of shared symbols, values, and artifacts across an organisation. However, few studies have attempted to determine if cultures are indeed truly shared This study addresses this issue by examining cultural perceptions of employees to see whether their perceptions vary by demographic characteristics and/or across organisational units. The site of the study is one of the major companies in the long-term health-care industry. Using ten cultural dimensions, significant differences in perceptions were found by organisational unit, the age of the employee, the employee's gender, and their ethnicity. Interestingly, a much more tenuous relationship between work experiences and cultural beliefs was found. Implications for practice as well as areas for future research are provided.

Age Factors↗
PubMed2001

Effects of perfluorochemical distribution and elimination dynamics on cardiopulmonary function.

Based on a physicochemical property profile, we tested the hypothesis that different perfluorochemical (PFC) liquids may have distinct effects on intrapulmonary PFC distribution, lung function, and PFC elimination kinetics during partial liquid ventilation (PLV). Young rabbits were studied in five groups [healthy, PLV with perflubron (PFB) or with perfluorodecalin (DEC); saline lavage injury and conventional mechanical ventilation (CMV); saline lavage injury PLV with PFB or with DEC]. Arterial blood chemistry, respiratory compliance (Cr), quantitative computed tomography of PFC distribution, and PFC loss rate were assessed for 4 h. Initial distribution of PFB was more homogenous than that of DEC; over time, PFB redistributed to dependent regions whereas DEC distribution was relatively constant. PFC loss rate decreased over time in all groups, was higher with DEC than PFB, and was lower with injury. In healthy animals, arterial PO(2) (Pa(O(2))) and Cr decreased with either PFC; the decrease was greater and sustained with DEC. Lavaged animals treated with either PFC demonstrated increased Pa(O(2)), which was sustained with PFB but deteriorated with DEC. Lavaged animals treated with PFB demonstrated increased Cr, higher Pa(O(2)), and lower arterial PCO(2) than with CMV or PLV with DEC. The results indicate that 1) initial distribution and subsequent intrapulmonary redistribution of PFC are related to PFC properties; 2) PFC distribution influences PFC elimination, gas exchange, and Cr; and 3) PFC elimination, gas exchange, and Cr are influenced by PFC properties and lung condition.

Animals↗