Donning devices (foot slips and frames) enable elderly people with severe chronic venous insufficiency to put on compression stockings.

OBJECTIVE/BACKGROUND: Compression therapy is highly effective in the treatment of post-thrombotic syndrome and venous leg ulcer. On average, 50-60% of the patients cooperate with compression therapy. Therefore, it is necessary to improve the user-friendliness. This prospective study investigated whether the use of donning devices can contribute to improving user-friendliness. METHODS: Forty patients aged >65 years with severe chronic venous insufficiency (CVI; C4-C6) successively donned compression stockings in a randomized order: one 40 mmHg (CS40) or two superimposed 20 mmHg (CS20+20), each with open toe (CS-o-t) and closed toe (CS-c-t), using donning devices (three foot slips for CS-o-t; two foot slips and three frames for CS-c-t). The study endpoint was that the stocking was completely donned and correctly positioned on the patient's leg. The success rate and its association with age, sex, first time versus second time user, body mass index, abdominal circumference, ability to reach the forefoot with the hand, and hand grip strength were analyzed. Additionally, subjective evaluation by the patients was performed. RESULTS: Without donning devices, success with CS40-c-t was 60% (24/40 patients) and with CS20+20-c-t 70% (28/40 patients) (p = .220). Using donning devices increased success rates significantly. With CS40-o-t the success rate was 88% (35/40 patients; p = .001) and with CS40-c-t it was 90% (36/40 patients; p = .002). With CS20+20-o-t and CS20+20-c-t, the success rate was 88% (35/40 patients; p = .016). The proportion of patients who successfully used either CS40 or CS20+20 increased from 73% to 93%. Relevant for the patients' success was the ability to reach the forefoot with the hand, and hand grip strength. Subjectively, donning with a device was rated significantly better than without. CONCLUSION: Donning devices significantly improve the ability of elderly patients with CVI to don compression stockings successfully. However, there are differences in user-friendliness among the devices..

Preliminary time-of-flight neutron diffraction studies of Escherichia coli ABC transport receptor phosphate-binding protein at the Protein Crystallography Station.

Inorganic phosphate is an essential molecule for all known life. Organisms have developed many mechanisms to ensure an adequate supply, even in low-phosphate conditions. In prokaryotes phosphate transport is instigated by the phosphate-binding protein (PBP), the initial receptor for the ATP-binding cassette (ABC) phosphate transporter. In the crystal structure of the PBP-phosphate complex, the phosphate is completely desolvated and sequestered in a deep cleft and is bound by 13 hydrogen bonds: 12 to protein NH and OH donor groups and one to a carboxylate acceptor group. The carboxylate plays a key recognition role by accepting a phosphate hydrogen. PBP phosphate affinity is relatively consistent across a broad pH range, indicating the capacity to bind monobasic (H2PO4-) and dibasic (HPO4(2-)) phosphate; however, the mechanism by which it might accommodate the second hydrogen of monobasic phosphate is unclear. To answer this question, neutron diffraction studies were initiated. Large single crystals with a volume of 8 mm3 were grown and subjected to hydrogen/deuterium exchange. A 2.5 Šresolution data set was collected on the Protein Crystallography Station at the Los Alamos Neutron Science Center. Initial refinement of the neutron data shows significant nuclear density, and refinement is ongoing. This is the first report of a neutron study from this superfamily.

Evidence that venous hypertension causes stasis dermatitis.

A clinical model to examine the hypothesis that venous hypertension of the lower leg per se can cause lower leg stasis dermatitis is described. To prove this concept, we retrospectively studied a consecutive series of 38 patients with lower leg dermatitis who underwent phlebological examination at our consultation over a period of four years. Among those patients who had an insufficiency of the superficial veins only, without insufficiency of the deep veins, 22 had undergone patch testing to common allergens in phlebology. We found 10 patients with a stasis dermatitis of the lower leg and an incompetent great saphenous vein, six of whom had no detectable contact sensitization at all and another four exclusively to phlebologically irrelevant substances, e.g. nickel, cobalt, chromate or epoxid resin. All these 10 patients showed long saphenous vein incompetence from the groin to the medial aspect of the leg. All were operated by classical flush ligation and saphenectomy. Lower leg dermatitis healed in all 10 patients within 8-12 weeks and no recurrence was observed (1 year follow-up). These results support clinical experience that venous hypertension alone indeed can cause lower leg dermatitis.

Cutaneous vasomotion in patients with chronic venous insufficiency and the influence of compression therapy.

We investigated in patients with chronic venous insufficiency (CVI) and after compression therapy the fluxmotion within characteristic frequency bands, which were described earlier by Bracic and Stefanovska (Bull. Math. Biol. 60 (1998), 919-935).Therefore, the frequency spectra of laser Doppler flux data of the 36 patient's legs were compared with 41 legs of healthy subjects. In addition, 14 patients with CVI wore a compression stocking (interface pressure: 25-32 mmHg) or compression bandages and were measured after 4 weeks therapy. Data were analyzed by means of a Wavelet packet transformation (a combination of the Daubechies filter of order 4 and the Haar filter).We found significant differences between the patients and the healthy subjects in the frequency intervals of myogenic 0.06-0.16 Hz, respiratory 0.16-0.6 Hz and heart activity 0.6-1.6 Hz (p<0.05, Mann-Whitney U test). Furthermore, the main energy peak height in these frequency intervals increased with the severity of venous disease and was highest in patients with venous leg ulceration. Compression therapy had a significant influence in myogenic vessel activity, which has been proved by a positive frequency shift of 20% (p=0.007, one-sided by the exact Wilcoxon test).In venous disease fluxmotion was increased. Compression therapy over a period of 4 weeks improved myogenic vessel activity.

[Compression therapy in chronic venous insufficiency. New test procedures and therapeutic options]. / Kompressionstherapie bei chronischer venöser Insuffizienz. Neue Prüfverfahren und therapeutische Optionen.

Chronic venous insufficiency (CVI) has a significant socioeconomic impact. The existent venous hypertension and the subsequent capillary hypertension result in trophic skin damage culminating in an ulcer. Venous ulcers affect 1-3% of the adult population. Compression therapy provides the basis for noninvasive treatment of CVI. It can be applied alone or in combination with invasive strategies. A variety of materials are available for phlebological compression therapy in the form of compression bandages and compression hosiery. Knowledge of the different qualities of the compression materials and their mode of action is important in choosing the correct means of compression with regard to clinical findings and the patient's needs. As far as possible, the compression method applied should be monitored for any loss of effectivity during regular follow-up examinations of the patients. The following article deals with this topic. A new option for compression therapy of crural ulcers is presented and the possibility for checking the effectiveness of the compression stockings during outpatient

Amniotic membrane surgery.

Human amniotic membrane (AM) is composed of three layers: a single epithelial layer, a thick basement membrane, and an avascular stroma. Amniotic membrane has anti-adhesive properties and is felt to promote epithelialization and decrease inflammation, neovascularization, and fibrosis. Amniotic membrane transplantation (AMT) is currently being used for a continuously widening spectrum of ophthalmic indications. Amniotic membrane transplantation has been shown to be effective in the reconstruction of the corneal surface in the setting of persistent epithelial defects, sterile corneal ulcerations, and partial limbal stem cell (LSC) deficiency states, including those secondary to chemical or thermal burns. Amniotic membrane transplantation also has been used in conjunction with limbal stem cell transplantation (LSCT) both in a concurrent fashion as well as in preparation for LSCT. Amniotic membrane transplantation also has been used in place of conjunctival autografting after pterygium excision and to reconstruct the conjunctival surface after removal of conjunctival lesions. Most recently, ex vivo cultivation and expansion of limbal epithelial cells has been performed utilizing AM as a matrix. However, the superiority of AMT over other treatment modalities in many of these settings needs to be substantiated by controlled clinical trials.

Frequency of somatic and germ-line mosaicism in retinoblastoma: implications for genetic counseling.

Although mosaicism can have important implications for genetic counseling of families with hereditary disorders, information regarding the incidence of mosaicism is available for only a few genetic diseases. Here we describe an evaluation of 156 families with retinoblastoma; the initial oncogenic mutation in the retinoblastoma gene had been identified in these families. In 15 ( approximately 10%) families, we were able to document mosaicism for the initial mutation in the retinoblastoma gene, either in the proband or in one of the proband's parents. The true incidence of mosaicism in this group of 156 families is probably higher than our findings indicate; in some additional families beyond the 15 we identified, mosaicism was likely but could not be proven, because somatic or germ-line DNA from key family members was unavailable. Germ-line DNA from two mosaic fathers was analyzed: in one of these, the mutation was detected in both sperm and leukocyte DNA; in the other, the mutation was detected only in sperm DNA. Our data suggest that mosaicism is more common than is generally appreciated, especially in disorders such as retinoblastoma, in which a high proportion of cases represent new mutations. The possibility of mosaicism should always be considered during the genetic counseling of newly identified families with retinoblastoma. As demonstrated here, genetic tests of germ-line DNA can provide valuable information that is not available through analysis of somatic (leukocyte) DNA.

Evaluation of the human arrestin gene in patients with retinitis pigmentosa and stationary night blindness.

PURPOSE: To establish the DNA sequence of the coding regions of the human arrestin locus and to determine whether defects in this sequence are present among patients with retinitis pigmentosa (RP) or types of stationary night blindness in addition to Oguchi disease. METHODS: The human genomic locus encoding arrestin was cloned in bacteriophage and P1 vectors. The sequence of the intron DNA flanking each exon was determined from these clones. Single-strand conformation polymorphism analysis and direct genomic sequencing techniques were used to screen 272 unrelated patients, comprising 177 patients with autosomal dominant RP, 85 with recessive RP, and 10 with stationary night blindness. RESULTS: The arrestin gene is divided into 16 exons ranging in size from 10 bp to 194 bp, with the open reading frame spanning exons 2 through 16. The authors identified several discrepancies between the genomic sequence the authors obtained and the previously published cDNA and genomic sequences. In the set of patients with dominant RP, the authors found one of three heterozygous missense changes (Arg84Cys, Thr125Met, and Val378Ile) in each of four unrelated patients; none of these changes cosegregated with disease in the respective families. In the set of patients with recessive RP, the authors found one of two heterozygous missense changes in each of two unrelated patients with recessive RP (Pro364Leu and Arg384Cys). One of the patients was the offspring of a consanguineous marriage; because the Arg384Cys change in him was heterozygous, it is unlikely to have been the cause of his RP. Cosegregation studies could not be performed on the patient with the Pro364Leu change. The authors confirmed the existence of two previously described polymorphisms (Ile76Val and a multiallelic polymorphism at codon 403), and the authors identified several silent polymorphisms and rare sequence variants. No sequence changes, other than polymorphic changes also found in some patients with RP, were identified in the patients with stationary night blindness. CONCLUSIONS: We found no evidence that mutations in arrestin are a cause of RP or stationary night blindness other than Oguchi disease. According to the genomic sequence obtained, a region in exon 8 that has been postulated to represent the site of interaction between arrestin and rhodopsin is 100% conserved between humans and all other mammals studied to date.

Consultation with physical and occupational therapists to promote the motor development of young children.

Increased survival of infants with complex medical needs combined with fiscal constraints have resulted in more young children receiving home care nursing. Home care nurses can enhance their role by understanding how physical and occupational therapists provide consultation to the family and nursing staff.

Defects in the rhodopsin kinase gene in the Oguchi form of stationary night blindness.

Oguchi disease is a recessively inherited form of stationary night blindness due to malfunction of the rod photoreceptor mechanism. Patients with this disease show a distinctive golden-brown colour of the fundus that occurs as the retina adapts to light, called the Mizuo phenomenon. Recently a defect in arrestin, a member of the rod phototransduction pathway, was found to cause this disease in some Japanese patients. As rhodopsin kinase works with arrestin in shutting off rhodopsin after it has been activated by a photon of light, it is reasonable to propose that some cases of Oguchi disease might be caused by defects in rhodopsin kinase. This report describes an analysis of the arrestin and rhodopsin kinase genes in three unrelated cases of Oguchi disease. No defects in arrestin were detected, but all three cases had mutations in the rhodopsin kinase gene. Two cases were found to be homozygous for a deletion encompassing exon 5, predicted to lead to a nonfunctional protein. The third case was a compound heterozygote with two allelic mutations, a missense mutation (Val380Asp) affecting a residue in the catalytic domain, and a frameshift mutation (Ser536(4-bp del)) resulting in truncation of the carboxy terminus. Our results indicate that null mutations in the rhodopsin kinase gene are a cause of Oguchi disease and extend the known genetic heterogeneity in congenital stationary night blindness.

Nongenomic effects of aldosterone on phosphocreatine levels in human calf muscle during recovery from exercise.

Nongenomic in vitro effects of aldosterone on the sodium-proton antiport and intracellular second messengers have been described in human mononuclear leukocytes, vascular smooth muscle cells, and endothelial cells. To test the potential physiological relevance of these effects, an in vivo 31P magnetic resonance spectroscopy study on the human calf at rest and during exercise was performed in 10 healthy volunteers receiving either 1 mg aldosterone or placebo iv in a double blind, randomized, cross-over trial. Spectra were analyzed for phosphocreatine, ATP, phosphomonoesters, inorganic intracellular phosphate, and intracellular pH. Resting values remained unchanged by aldosterone. After isometric contraction of the calf (50% body weight for 3 min), phosphocreatine recovered to significantly higher levels after application of aldosterone compared with placebo. Other parameters were not significantly changed by aldosterone. Effects appeared immediately after isometric contraction and, thus, occurred within 8 min of aldosterone administration. They are, therefore, likely to represent the first contemporary evidence of nongenomic in vivo effects of aldosterone in man. These findings also point to an involvement of aldosteron in the acute stress adaptation of cellular oxidative metabolism in human muscle physiology.

Further studies on immunoglobulin G- and albumin-binding properties of streptococci of serological group L.

In this study, all 88 streptococci of serological group L isolated from cows, pigs, poultry and humans bound 125I-immunoglobulin G, and, in addition, 22 cultures interacted with 125I-albumin. IgG- and albumin-binding sites were solubilized from the streptococcal surface by heat extraction at an acid pH and also by mutanolysin treatment of the bacteria. Western blot analysis of these binding proteins revealed that almost identical protein bands were responsible for 125I-IgG and -albumin binding. Certain protein fractions of the cultures interacted exclusively with 125I-IgG, indicating that there are two groups of IgG receptors among streptococci of this serogroup.

Rapid aldosterone signaling in vascular smooth muscle cells: involvement of phospholipase C, diacylglycerol and protein kinase C alpha.

Rapid in vitro effects of aldosterone (ALDO) on intracellular sodium, potassium and calcium, cell volume and the sodium-proton-antiport have been described in human mononuclear leukocytes and rat vascular smooth muscle cells (VSMC). These nongenomic effects are signaled through membrane receptors with a high affinity for aldosterone, but not for hydrocortisone. Effects of ALDO on the production of diacylglycerol (DAG) and protein kinase C alpha (PKC) were measured in VSCM by enzymatic assay and immunoblotting. DAG production was stimulated twofold by ALDO (> or = 1 nM) within 30 sec while hydrocortisone was inactive at concentrations of up to 1 microM. The inhibitors of phospholipase C, neomycin and U-73122 completely blocked this effect. PKC translocation from cytosol to membranes by ALDO occurred within 5 min, the extent of this effect was comparable to that of angiotensin II. These data demonstrate rapid intracellular signaling for ALDO in VSMC through phospholipase C, DAG and PKC in addition to calcium and inositol-1,4,5-trisphosphate as determined earlier.

Characteristic properties of streptococci of serological group L.

This study was designed to characterize further 88 streptococci of serological group L, isolated from bovines, pigs, poultry and humans. Most group L streptococci from bovines grew as granular sediment with long chains in fluid media and with compact colonies in soft agar. Most group L streptococci from pigs grew with a uniform turbidity in fluid media, short chains, and with diffuse colonies in soft agar. The biochemical characteristics, determined with the Strepzym identification system, revealed no significant differences between the group L streptococci of various origins. A positive opacity factor reaction could mainly be observed with group L streptococci from bovines and humans, but was less pronounced with group L streptococci from pigs and poultry. In addition, 27 group L streptococci reacted with type antigen X or R and 9 cultures with M1 or M6 specific antiserum. The determination of antibiotic resistance patterns revealed that all group L streptococci were resistant to tetracycline and minocycline, part of the cultures were resistant to chloramphenicol, erythromycin and gentamicin, and all cultures were susceptible to penicillin, bacitracin, cefoxitin and nitrofurantoin. All these data allowed an individual characterization of group L streptococci, possibly useful for epidemiological studies.

T lymphocyte T cell-B cell-activating molecule/CD40-L molecules induce normal B cells or chronic lymphocytic leukemia B cells to express CD80 (B7/BB-1) and enhance their costimulatory activity.

Activation-induced cell surface molecules are involved in mediating bidirectional T-B lymphocyte signaling that is important in the induction of T or B lymphocyte effector functions. In this regard, T-BAM/CD40-L is an activation-induced CD4+ T cell surface molecule known to be important in inducing B cell effector functions. This report demonstrates that T-BAM/CD40-L molecules on a Jurkat T cell leukemia subclone (D1.1) or nonlymphoid 293 kidney cell transfectants induce B cells or B-CLL cells to express CD80 (B7/BB-1) in a manner that is specifically inhibited by anti-T-BAM/CD40-L mAb 5C8. Because activation-induced B cell surface molecules, such as CD80, deliver costimulatory signals to T cells that augment T cell proliferation, the functional costimulatory capacity of T-BAM/CD40-L-primed B cells and B-CLL cells was studied. T-BAM/CD40-L-primed B cells or B-CLL cells augment the proliferative responses of allogenic T cells. Furthermore, T-BAM/CD40-L priming is specifically inhibited by mAb 5C8. Together, these studies demonstrate that T-BAM/CD40-L induces CD80 expression on resting B cells or B-CLL cells. Moreover, T-BAM/CD40-L signaling enhances B cell costimulatory capacity. These studies suggest that T-BAM/CD40-L molecules not only induce B cell differentiative processes that result in Ab secretion, but also enable B cells to prime Ag-specific T cells for subsequent clonal expansion.

Non-classical receptors for aldosterone in plasma membranes from pig kidneys.

Rapid, nongenomic in vitro effects of aldosterone on intracellular electrolytes, cell volume and the sodium-proton antiporter have been found in human mononuclear leukocytes (HML), as have related membrane receptors. In the present study, binding of 125I-labeled aldosterone to plasma membrane preparations from pig kidneys was studied, since nongenomic in vitro effects of aldosterone have also been described in cultured kidney cells. In this preparation, binding of aldosterone shares important features with both functional and binding data in HML. These include a very low apparent Ki of approximately 0.1 nM for aldosterone, a high turnover rate and binding selectivity for aldosterone and fludrocortisone. Desoxycorticosterone acetate and corticosterone show intermediate affinity, with apparent Ki values of approximately 1 and 100 nM, with hydrocortisone even less active. Thus binding of aldosterone to kidney plasma membranes is compatible with the major features of its nongenomic renal effects.

CD40 molecules induce down-modulation and endocytosis of T cell surface T cell-B cell activating molecule/CD40-L. Potential role in regulating helper effector function.

The T-BAM/CD40-L molecule on CD4+ T cells interacts with B cell CD40 molecules to deliver contact-dependent signals that drive B cell activation and Ig secretion. Cell surface T-BAM/CD40-L expression is transient and may be closely regulated in order to limit the activation and clonal selection of noncognate B cells. We demonstrate that B cells, but not non-B cells, rapidly and specifically down-modulate surface T-BAM/CD40-L expression in a contact-dependent and temperature-sensitive manner that renders T cells unable to activate resting bystander B cells. Because the ability to down-modulate T-BAM/CD40-L correlated with CD40 expression, the role of CD40 molecules in down-modulating its ligand was directly assessed. Anti-CD40 mAb, but not control mAb, block B cell-induced T-BAM/CD40-L down-modulation. Furthermore, CD40+ nonlymphoid transfectants specifically down-modulate surface T-BAM/CD40-L expression. B cells induce T-BAM/CD40-L internalization into cytoplasmic compartments in a process that is inhibited by cytochalasin B. Pretreatment of activated T cells with lysosomotropic agents does not affect CD40-induced down-modulation of surface T-BAM/CD40-L but results in a marked accumulation of T-BAM/CD40-L in cytoplasmic vesicles. Together, these studies strongly suggest that CD40 induced T-BAM/CD40-L down-modulation occurs, in part, by receptor-mediated endocytosis followed by lysosomal degradation and may represent a mechanism to regulate CD4+ T cell helper effector functions.

[Autologous 131J-tagged human fibrinogen for early detection of venous thrombosis (preparation, biological and in vivo properties) (author's transl)]. / Autologes 131J-Humanfibrinogen zur Thrombosefrühdiagnostik. (Herstellung, biochemische Eigenschaften und Verhalten in vivo).

A method for preparation of autologous 131J-tagged human fibrinogen is demonstrated. In vitro the preparation is characterized by content of fibrinogen, protein, plasminogen, clottability and molecular weight. Total plasma radioactivity, specific radioactivity, non-protein-bound radioactivity, biologic half-life and the local activity at the thrombus define the properties in vivo. With the above criteria autologous 131-J-tagged human fibrinogen was shown to be useful for early diagnosis of venous thrombosis.