Over-the-counter-drugs for the treatment of mood and anxiety disorders--the views of German pharmacists.

INTRODUCTION: Depression, anxiety, agitation and sleep disorders are highly prevalent in the general population, but few persons receive psychiatric care. METHODS: Our aim was to study the views of 690 German pharmacists on "over-the counter" (OTC) drugs for these indications. RESULTS: They reported dispensing OTC medication to an average of 12 customers per day, and this corresponded to almost one quarter of the medications provided for these indications. Herbal drugs and complex homeopathic formulations were used most frequently. Patients preferring OTC substances were described as being younger, with shorter durations of illness and less severe symptoms, and more skeptical regarding psychopharmacology. While genuine pharmacological effects were considered as most relevant, pharmacists were highly aware of placebo and interpersonal factors. Symptoms, comorbidity and advice on drug intake were prominent topics during pharmacy consultations. CONCLUSION: German pharmacists report dispensing large amounts of OTC drugs for anxiety, agitation, sleep disturbances or depression. It is unclear whether this constitutes a rational and cost effective method to deal with mild courses of high prevalence diseases or must be seen critically.

The prospective Hemophilia Inhibitor PUP Study reveals distinct antibody signatures prior to FVIII inhibitor development.

Preventing factor VIII (FVIII) inhibitors following replacement therapies with FVIII products in patients with hemophilia A remains an unmet medical need. Better understanding of the early events of evolving FVIII inhibitors is essential for risk identification and the design of novel strategies to prevent inhibitor development. The Hemophilia Inhibitor Previously Untreated Patients (PUPs) Study (HIPS; www.clinicaltrials.gov #NCT01652027) is the first prospective cohort study to evaluate comprehensive changes in the immune system during the first 50 exposure days (EDs) to FVIII in patients with severe hemophilia A. HIPS participants were enrolled prior to their first exposure to FVIII or blood products ("true PUPs") and were evaluated for different immunological and clinical parameters at specified time points during their first 50 EDs to a single source of recombinant FVIII. Longitudinal antibody data resulting from this study indicate that there are 4 subgroups of patients expressing distinct signatures of FVIII-binding antibodies. Subgroup 1 did not develop any detectable FVIII-binding immunoglobulin G (IgG) antibodies. Subgroup 2 developed nonneutralizing, FVIII-binding IgG1 antibodies, but other FVIII-binding IgG subclasses were not observed. Subgroup 3 developed transient FVIII inhibitors associated with FVIII-binding IgG1 antibodies, similar to subgroup 2. Subgroup 4 developed persistent FVIII inhibitors associated with an initial development of high-affinity, FVIII-binding IgG1 antibodies, followed by IgG3 and IgG4 antibodies. Appearance of FVIII-binding IgG3 was always associated with persistent FVIII inhibitors and the subsequent development of FVIII-binding IgG4. Some of the antibody signatures identified in HIPS could serve as candidates for early biomarkers of FVIII inhibitor development.

Long-term measurement of endogenous diurnal oscillations of the electrical potential in an individual Acetabularia cell.

In Acetabularia mediterranea the transcellular electrical potential along the cell is subjected to diurnal oscillations which persist under constant conditions. The frequency may significantly differ between individual cells even in simultaneous measurements. The free running period of a distinct cell may be subjected to slow changes during long-term measurements. Such measurements have been performed over about 100 days.

Regulation of UDPG pyrophosphorylase in Acetabularia mediterranea.

The kinetic properties of UDPG pyrophosphorylase (glucosyl-1-phosphate uridyl transferase, EC 2.7.7.9) suggest that it may play a key role in the regulation of metabolism in Acetabularia mediterranea. The enzyme-catalyzed reaction is readily reversible in vitro, and has been assayed in both directions. The enzyme shows substrate inhibition by UDPG and UTP at substrate concentrations in excess of 2 mM. The kinetic behavior of the enzyme is consistent with the hypothesis that it catalyzes an ordered bisubstrate biproduct reaction in which G-1-P is the leading substrate, and UTP is the leading product. A plot of initial velocity vs. PPi concentration is sigmoid, indicating a cooperative homotropic effect. PGAL inhibits the reaction in the direction: UTP + G-1-P leads to UDPG + PPi It has no effect on the reverse reaction. The responses of the enzyme may serve to regulate the allocation of G-1-P between anabolic and catabolic pathways.

Deoxycytidine monophosphate deaminase in Acetabularia: properties and regulation in the early generative phase.

The occurrence of a dCMP deaminase in Acetabularia mediterranea has been demonstrated. The enzyme which is found in a particulate fraction is substantially stimulated by the addition of dCTP. The activity of the enzyme is increased at the beginning of the generative phase in nucleate as well as in anucleate cells. This regulation is due to de novo synthesis of the enzyme. By means of inhibitor studies, it has been shown that the enzyme is translated on 70S ribosomes of and coced for in cell organelles.

Cytosolic protein kinase activity associated with the maturation of the malaria parasite Plasmodium berghei.

Seven cytosolic phosphoproteins with relative molecular masses of 110, 58, 52, 46, 38, 36 and 34kDa and isoelectric points between 4.2 and 5.0 are identified from the rodent malaria parasite Plasmodium berghei. Similar patterns of phosphorylated proteins are obtained from parasite cytosol after incubation of intact infected erythrocytes with [32P]orthophosphate, or from parasite cytosol incubated with [gamma-32P]ATP. The characteristics of the phosphorylation reaction are similar to the previously described Plasmodium protein kinase [Wiser, M.F., Eaton, J.W. and Sheppard, J.R. (1983) J. Cell. Biochem. 21, 305-314], suggesting that the same protein kinase is involved. More protein phosphorylation activity is associated with the mature parasites than the immature forms, suggesting that these phosphoproteins may play some role in the parasite's erythrocytic stage cycle.

Somatosensory-evoked potentials during carotid artery surgery: experience in 400 operations.

A prospective study was undertaken to determine the efficacy of monitoring somatosensory-evoked potentials (SEP) during carotid artery surgery in predicting a new ischemic neurologic deficit. Three hundred seventy-six patients underwent 400 reconstructions of the internal carotid artery. The mortality rate of the entire series was 0.8%. In 383 procedures, SEP amplitudes were always present during cross-clamping of the internal carotid artery. In spite of that, three neurologic deficits occurred, but all were associated with technical failures and not related to clamping ischemia. Complete loss of SEP amplitudes was noted in 17 procedures. Five of seven patients without an indwelling shunt showed a neurologic deficit after surgery, whereas shunt insertion in 10 resulted in three neurologic deficits. It is concluded that at present SEP recording is an accurate monitoring method in detecting clamping-related cerebral ischemia during carotid artery surgery.

The effect of N-terminal substitutions on the biological activity of MSH fragments.

In order to study the role of N-terminal substitutions of peptide sequences related to the active site of alpha-melanotropin, [Glp5]alpha-MSH(5-10), [Glp5,D-Phe7]alpha-MSH(5-10), [Sar5,D-Phe7]alpha-MSH(5-10), [Nle4,D-Phe7]alpha-MSH(4-10), [N-carbamoyl]alpha-MSH(5-10), and formyl and acetyl derivatives of alpha-MSH(5-10), [Gly5]alpha-MSH(5-10) and [Gly5,D-Phe7]alpha-MSH(5-10), were synthesized in solution. The N-terminal acylations enhance by 2 to 10 times the melanin-dispersing activity of the unsubstituted sequences. Alkylation of the N-terminus does not change the biological activity of the parent peptide, suggesting the necessity of a carbonyl group for increasing the hormonal effect.

Chromatographic characterization of HSV-1 gD 268-284 and IL-6 179-185 synthetic oligopeptides by reversed-phase high-performance liquid chromatography, automated Edman degradation and mass spectrometric analysis.

Two groups of synthetic oligopeptides (namino acid = 7 and 17) were prepared by solid-phase peptide synthesis using the Boc-polystyrene strategy. After deprotection, cleavage and gel permeation, the crude products were analysed by conventional RP-HPLC methods. Separation and isolation of major components were performed on a semi-preparative RP-HPLC column. In order to clarify the primary structure of these products, amino acid analysis, Edman degradation sequence determination and analytical RP-HPLC characterization were applied. The isolated fractions were further assessed by direct molar mass investigation utilizing the fast atom bombardment and 252Cf plasma desorption mass spectrometry. The results with an interleukin-6 oligopeptide corresponding to the 179LRALRQM185 sequence indicate that the single peak product obtained by RP-HPLC separation contains only one component, as verified by amino acid analysis and mass spectrometry. In contrast, the analysis of 268LAPEDPEDSALLEDPVG284-NH2 from HSV-1 gD protein suggests that this large peptide amide showing a single peak after repeated purification by RP-HPLC contains microheterogeneities as revealed by mass spectrometry and sequencing, but not by amino acid analysis.

In vitro cytotoxic effect of difluoromethylomithine increased nonspecifically by peptide coupling.

Difluoromethylomithine (DFMO)-peptide conjugates were synthesized as prodrugs to improve the cytotoxic efficacy of DFMO. All conjugates inhibited cell growth in different cell lines more effectively than DFMO itself. The best cytotoxic effect was achieved in all cell lines by DFMO-Glu-His-Phe-Arg-Trp-Gly-OMe, where the carrier peptide is a melanotropin hormone fragment. Although this conjugate is capable of displacing labeled melanotropin from its receptor, its cytotoxic effect on the receptor-positive human melanoma cell line has not been proven to be receptor-mediated. The differences in the cytotoxicities of the congeners seem to be influenced, at least in part, by the nature of the carrier molecule.

Monitoring during carotid surgery: somatosensory evoked potentials vs. carotid stump pressure.

In the following prospective study of 125 carotid endarterectomies, we compared monitoring of somatosensory evoked potentials (SEPs) with carotid stump pressure (CSP) measurement in order to determine the efficacy of both methods in reliably predicting cerebral ischemia caused by cross-clamping of the carotid artery. A complete flattening of the cortical SEP was the sole criterion for selective shunting. Two patients suffered from transitory neurological deficits in the postoperative period. Both experienced complete disappearance of postcentral SEP components after carotid cross-clamping. In a further 10 cases, an intraoperative loss of SEP amplitudes occurred, but could be reversed by the insertion of a shunt or by induced hypertension. All of these patients showed a normal neurological examination postoperatively as did all of the patients with identifiable SEPs after cross-clamping. In all of the 12 patients with complete flattening of the cortical waveform, we found CSP levels less than 50 mm Hg. A further 61 patients had a CSP less than 50 mm Hg, but neither an intraoperative loss of SEP amplitudes nor postoperative neurological deficits were detected in any of these patients. We conclude that, in contrast to CSP, SEPs not only help to identify patients with insufficient collateral blood flow who benefit from specific cerebral protection, but also to avoid improper and hazardous application of these measures in patients with sufficient cerebral perfusion.

[Adaptability of fine-needle biopsy for preoperative and postoperative studies in femoro-crural vascular reconstruction]. / Eignung der Feinnadelpunktion (FNP) zur prä- und postoperativen Darstellung bei femoro-kruralen Gefäss-Rekonstruktionen.

During two years we performed 199 pre- and postoperative angiograms on 99 patients with femoro-crural reconstruction. 133 of these were by FNP. In 4.2% of postoperative FNPs (fully anticoagulated patients), there was significant bleeding from the puncture or the operative scar. It was not necessary to reoperate on any bypasses and there were no late complications. As regards the demonstration of the calf vessels. FNP proved itself superior as a pre- and postoperative method. Because of the rapidity of the method, the small amount of contrast required and the minimal trauma, FNP is the method of choice for pre- and post-operative studies of the calf vessels for femoro-crural reconstructions.

Methotrexate-resistant Somatic Cells of Glycine max (L.) Merr.: Selection and Characterization.

A total of 70 methotrexate-resistant cell lines were isolated from UV-irradiated fast growing suspensions of Glycine max(L.) Merr. The resistant cells grew in 4 X 10(-4) M MTX without significant reduction in growth rate, whereas 100 % of wild type cells died in 2.2 x 10 (-7) M within 24 h. The frequency of resistant cell clones was 2 x 10(-8) per cell generation. Two different selection strategies, a single-step and a multiple-step protocol yielded phenotypically identical resistant lines. All resistant lines have retained their resistance over more than 500 cell generations in the absence of selection. Resistant cells plated on MTX could be selected from an excess of wild type cells. Ten percent of the resistant lines internalized MTX at a reduced rate. DHFR activity in wild type and resistant cells was equally sensitive to inhibition by MTX. Resistant cells did not display an increased activity of DHFR. Likewise MTX binding to cell extracts was the same for all cell lines. In the wild type MTX-blockage of cell division could be partially released by 2 x 10(-4) M thymidine. In the presence of MTX thymidine had no influence on the growth of resistant cells.

Results of long-term venacavography study after placement of a Greenfield vena caval filter.

Digital subtraction venacavography (DSV) as a follow-up examination was performed in 46 patients after placement of a standard stainless steel Greenfield vena caval filter (SGF). DSV is an exact method of visualizing the lumen of the inferior vena cava as well as intraluminal or captured thrombi. Eccentric filters with an angulation of more than 15 degrees were found in 8 patients causing a higher risk of pulmonary embolism from smaller emboli and propagating thrombi. Penetration of the caval wall by filter struts was however frequent (41%), without any damage to adjacent structures as demonstrated by CT scans. The long-term caval patency rate was 90%, with 4 cases of caval thrombosis. Two patients with an occluded inferior vena cava showed no venostasis. Although changes of the filter position usually remain asymptomatic, regular follow-up examinations seem necessary to recognize any impairment of the filter's clot trapping efficiency. Filters should only be used in patients with a risk of recurrent pulmonary embolism despite anticoagulation and patients with contraindications to anticoagulation therapy.

Late results with Dardik-biograft in peripheral arterial surgery.

A total of 117 vascular reconstructions below the inguinal ligament were performed using Dardik's human umbilical vein. The indication for surgery was limb salvage in 91.5%. In 61.5% a previous reconstruction had failed. The distal anastomosis was done with the popliteal artery above the knee in 9 cases, below the knee in 41, and with a tibial or the peroneal artery in 60 cases. The umbilical vein was combined with a prosthesis or the autologous saphenous vein in 20 cases. The cumulative patency rates of all reconstructions were 59.6% after 3, and 46.7% after 6 years. Crural reconstructions had a cumulative patency rate of 52% 3 years after surgery. The main factors influencing patency were the preoperative grade of ischemia, the site of the distal anastomosis and the angiographic run-off. It is concluded that the human umbilical vein is the graft material of choice in long length revascularization whenever the saphenous vein is not available.

Surgical treatment of renal artery occlusive disease: long term results.

68 patients were operated on for renal artery occlusive disease. After a mean follow-up of 61 months renovascular hypertension was cured or markedly improved in 79.2%. The results depended mostly on the duration of preexisting hypertension and on the histology of the renal artery lesion. Forty-four months after surgery, 37 reconstructions were examined by angiography. Mostly digital subtraction technique was used. Total occlusion rate was 24%. Patency rates of autogenous vein bypass grafts were similar to prosthetic grafts. It is concluded that prosthetic grafts like PTFE are a reasonable alternative in aortorenal bypass procedures.

Digital transvenous angiography in follow-up examinations after carotid reconstruction: early results.

A total of 187 check-up examinations by DVSA were carried out after various types of carotid reconstructions. The results were inconclusive in only 2.7% of the cases. A good or very good postoperative result could be demonstrated in 77.5%. A slight stenosis was present in 16%, a significant stenosis in 2.7% and a complete occlusion of the internal carotid artery in 1.1%. Patch plasty alone showed the best results followed by endarterectomy and endarterectomy with patch plasty. Segmental carotid resections and dilatations led to the poorest results. Most of those cases, where a stenosis recurred, it was already present immediately after the operation and only rarely caused by progression of the basic disease or intimal proliferation. The complication rate of DVSA was low. It is concluded that DVSA is a low risk and reliable method which can routinely be used in the postoperative evaluation of patients with carotid reconstructions.

Investigations on the biochemical characteristics of chronically underperfused muscle.

During operation, biopsies from the gastrocnemius muscle and, in some cases, from the sartorius muscle were taken from 32 patients with peripheral arterial occlusive disease and from 5 subjects with normal peripheral circulation. In patients with inadequate circulation only during exercise, when compared with the control group, increased activities of enzymes involved in oxidative metabolism (malate dehydrogenase, nicotinamide adenine dinucleotide phosphate-dependent isocitrate dehydrogenase, cytochrome C oxidase, creatine kinase), in amino acid metabolism (asparate aminotransferase, alanine aminotransferase), and in anaerobic glycoysis (lactate dehydrogenase) were found. In patients with circulatory disturbances that manifested themselves already at rest, enzyme activities were, with the exception of LDH, lower than those of patients with exclusively exercise-related insufficiency. By means of intraindividual comparisons with the corresponding enzyme activities in the sartorius muscle, the author was able to show that the changes found were not simply the result of differences in training conditions. The diminished concentrations of energy-rich phosphate are an expression of the anaerobic metabolic state in patients with inadequate circulation at rest. It is concluded that chronic ischemia of muscle leads to changes in the energy metabolism of the cell. In the presence of more nearly adequate circulation at rest, the portion of oxidative potential of the total energy metabolism increases. In contrast, if there is an inadequate circulation at rest, the mainly anaerobic glycolysis becomes quantitatively predominant.

Extraanatomic bypass in the treatment of prosthetic vascular graft infection manifesting in the groin.

BACKGROUND: Infection of an alloplastic vascular graft is a serious complication and often involves the groin. We propose a therapeutic concept using extraanatomic bypass to avoid the septic groin in case of an infected alloplastic vascular reconstruction. PATIENTS AND METHODS: The course of 25 patients (18 men, 7 women, mean age 61 years) with a grade III inguinal infection following placement of an aortic or femoro-distal synthetic graft made of Dacron or PTFE was analysed. The treatment consisted of excision of the infected graft material and extraanatomic reconstruction with ringed PTFE grafts in all patients. Mean follow-up after the extraanatomic procedure was 21 months (1-91 months). RESULTS: Direct surgical exploration definitely secured graft infection in almost three-quarters of the cases. The most common organism isolated was Staphylococcus aureus (13/22 = 59%). At the time of infection 60% of the patients had critical limb ischemia necessitating vascular reconstruction simultaneously with total or partial excision of the infected graft. Complications of the extraanatomic bypass occurred in 7 cases (overall morbidity 28%). Postoperatively, one patient required major amputation. Hospital mortality was 8%. Primary patency and secondary patency rates of extraanatomic grafts amounted to 78.0% (+/- 10.0 SD) and 84.1% (+/- 8.7 SD) respectively after two years. Limb salvage rated 78.4% (+/- 11.6 SD) after 2 years, the 2-year-survival rate was 73.8% (+/- 9.3 SD). CONCLUSIONS: According to the favourable long-term limb salvage and survival rates, we support simultaneous vascular reconstruction by extraanatomic bypass and explanation of the infected graft material in case of grade III inguinal infection of alloplastic vascular reconstructions.

Knitted double-velour Dacron prostheses in aortobifemoral position--long-term performance of different coating materials.

BACKGROUND: The purpose of this prospectively randomized study was to evaluate intraoperative as well as long-term performance of different coating materials for knitted Dacron aortobifemoral prostheses. PATIENTS AND METHODS: Between 1989 and 1992 a total of 150 consecutive patients who underwent aortobifemoral bypass were randomized for three different coating materials: gelatine (Unigraft; n = 49), collagen (Hemashield; n = 50) and human albumin (USCI; n = 51). Intra- and perioperative data such as duration of operation, clamping time, blood loss, and early complications were obtained as well as yearly follow-up examinations up to five years. Frequency of late complications, graft patency, and patient survival were observed. RESULTS: No statistically significant difference of intraoperative data could be obtained. In every group 6% of patients presented with anastomotic aneurysm in the groin. Primary patency rates were Unigraft 92%, Hemashield 91%, USCI 92% (no significant difference, n.s.), secondary patency rates after 5 years were Unigraft 98%, Hemashield 95%, USCI 94% (n.s.). CONCLUSIONS: Overall superiority of one particular type of prosthesis could not be stated. In order to prevent sudden graft failure associated with progressive arteriosclerotic disease or from late anastomotic aneurysm regular follow-up examinations should follow aorto-bifemoral bypass.