Total knee arthroplasty: do newer CR implants yield better results? A single center prospective study.

The aim of this study was to compare whether the newest TKA prosthesis (Persona) gives improved clinical outcomes due its more anatomical design in comparison to older prostheses (balanSys). This study included a total of 89 patients planned for TKA from June 2018 to September 2019. Outcomes such as Knee Injury and Osteoarthritis Outcome Score (KOOS), range of motion (ROM), numeric pain rating scale (NRS), analgesics and alignment were recorded next to patient characteristics and complications. Our results showed a significant improvement in NRS, ROM and functional scores postoperatively compared to preoperatively for both the Persona and the balanSys implants. Although the flexion ROM for the Persona group was higher at 6 and 12 months postoperative compared to the balanSys, this was mainly a regaining of the preoperative ROM. Throughout all timepoints, there were no statistically significant differences observed in NSAID and opioid usage between the balanSys and Persona groups. Both implants are safe and efficient to use in the treatment of knee osteoarthritis. Although Persona had an improved postoperative flexion, this did not have an impact on any of the patient-reported outcomes.

Fast rehab after midshaft clavicula fractures in elite cyclists and motocross riders.

Clavicle fractures are one of the most common injuries in cyclists and motocross riders. Although a fast return to sport is imperative for athletes, there is only limited literature on short-term functional outcomes after open reduction internal fixation of a clavicle fracture in a homogenous group of athletes. The aim of this study is to evaluate early (first 6 weeks) functional outcomes, return to sports and complications of elite or high-level recreational (± 8000 km per year) cyclists and motocross riders after surgical treatment of a midshaft clavicle fracture. The main study parameters were Quick Disabilities of the Arm, Shoulder and Hand (QuickDash); QuickDash sports module, pain in rest and movement (Numeric Pain Rating Score) and time to return to sports (training indoor/outdoor and competition). All parameters were taken pre-operatively and at 2/4/6/12/24 weeks post-operative. A total of 34 cyclists (6 LTFU) and 9 motocross riders (2 LTFU) were included at baseline. A significant decrease in Quick dash scores between preoperative (33 ± 1.2) and 2 weeks PO (21.5 ± 1.2) and between 2 and 4 weeks PO (16.1 ± 1.3) was found for cyclists. The QuickDash scores of the motocross riders statistically improvement from preoperative (31.6 ± 3.3) to 6 weeks PO (14.1 ± 3.3). NRS score in rest for cyclists decreased significantly from 3.6 ± 0.2 to 1.0 ± 0.2 after two weeks. After 4 weeks, 93% of cyclists and 57% of motocross riders were training outside. After 6 weeks, 56% of cyclists and 57% of motocross riders had returned to competition. Our results show that early surgical treatment of midshaft clavicle fractures in elite cyclists and motocross riders is a safe method with few complications and good functional outcomes.

Proximal row carpectomy versus four-corner arthrodesis in the treatment of SLAC and SNAC wrist: meta-analysis and literature review.

A systematic literature review was performed on 84 articles from 2000 to 2020 on proximal row carpectomy (PRC) or four-corner arthrodesis (FCA) in patients with posttraumatic wrist osteoarthritis. Qualitative assessment was conducted on 14 articles. Pain, range of motion (ROM), grip strength and complications were analyzed using weighted average means. Meta-analysis with a random effects model was performed for the flexion-extension arc and grip strength. A total of 1,066 PRCs and 2,771 FCAs were analyzed, with a mean follow-up of 9 and 7 years respectively. Mean flexion after PRC and FCA respectively was 36.2 ° and 31.1 °, mean extension 41.4 ° and 32.4 °, and mean grip strength 26.4 kg and 27.5 kg. PRC had a larger flexion-extension arc than FCA, with a standard mean difference (SMD) of 0.41 (range, 0.02-0.81). No significant difference was found for grip strength. Osteoarthritis occurred in 42.2% of PRC cases, independently of capitate shape. Conversion to wrist arthrodesis was performed in 10.1% of failed PRCs. Revision was chosen in 4.7% of FCAs and conversion to wrist arthrodesis in 4.6%. We conclude that the functional results of both techniques are similar, but prefer PRC to FCA because of the lower complications rate.

Serum autoantibody reactivity in bullous pemphigoid is associated with neuropsychiatric disorders and the use of antidiabetics and antipsychotics: a large, prospective cohort study.

BACKGROUND: Bullous pemphigoid (BP), the by far most frequent autoimmune blistering skin disease (AIBD), is immunopathologically characterized by autoantibodies against the two hemidesmosomal proteins BP180 (collagen type XVII) and BP230 (BPAG1 or dystonin). Several comorbidities and potentially disease-inducing medication have been described in BP, yet a systematic analysis of these clinically relevant findings and autoantibody reactivities has not been performed. OBJECTIVE: To determine associations of autoantibody reactivities with comorbidities and concomitant medication. METHODS: In this prospective multicenter study, 499 patients diagnosed with BP in 16 European referral centers were included. The relation between anti-BP180 NC16A and anti-BP230 IgG ELISA values at the time of diagnosis as well as comorbidities and concomitant medication collected by a standardized form were analysed. RESULTS: An association between higher serum anti-BP180 reactivity and neuropsychiatric but not atopic and metabolic disorders was observed as well as with the use of insulin or antipsychotics but not with dipeptidyl peptidase-4 (DPP4) inhibitors, inhibitors of platelet aggregation and L-thyroxine. The use of DPP4 inhibitors was associated with less anti-BP180 and anti-BP230 reactivity compared with BP patients without these drugs. This finding was even more pronounced when compared with diabetic BP patients without DPP4 inhibitors. Associations between anti-BP180 and anti-BP230 reactivities were also found in patients using insulin and antipsychotics, respectively, compared with patients without this medication, but not for the use of inhibitors of platelet aggregation, and L-thyroxine. CONCLUSION: Taken together, these data imply a relation between autoantibody reactivities at the time of diagnosis and both neuropsychiatric comorbidities as well as distinct concomitant medication suggesting a link between the pathological immune mechanisms and clinical conditions that precede the clinically overt AIBD.

Updated S2 K guidelines for the management of bullous pemphigoid initiated by the European Academy of Dermatology and Venereology (EADV).

BACKGROUND: Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disease of the skin and mucous membranes. This disease typically affects the elderly and presents with itch and localized or, most frequently, generalized bullous lesions. A subset of patients only develops excoriations, prurigo-like lesions, and eczematous and/or urticarial erythematous lesions. The disease, which is significantly associated with neurological disorders, has high morbidity and severely impacts the quality of life. OBJECTIVES AND METHODOLOGY: The Autoimmune blistering diseases Task Force of the European Academy of Dermatology and Venereology sought to update the guidelines for the management of BP based on new clinical information, and new evidence on diagnostic tools and interventions. The recommendations are either evidence-based or rely on expert opinion. The degree of consent among all task force members was included. RESULTS: Treatment depends on the severity of BP and patients' comorbidities. High-potency topical corticosteroids are recommended as the mainstay of treatment whenever possible. Oral prednisone at a dose of 0.5 mg/kg/day is a recommended alternative. In case of contraindications or resistance to corticosteroids, immunosuppressive therapies, such as methotrexate, azathioprine, mycophenolate mofetil or mycophenolate acid, may be recommended. The use of doxycycline and dapsone is controversial. They may be recommended, in particular, in patients with contraindications to oral corticosteroids. B-cell-depleting therapy and intravenous immunoglobulins may be considered in treatment-resistant cases. Omalizumab and dupilumab have recently shown promising results. The final version of the guideline was consented to by several patient organizations. CONCLUSIONS: The guidelines for the management of BP were updated. They summarize evidence- and expert-based recommendations useful in clinical practice.

Simultaneous bilateral opening-wedge high tibial osteotomy with structural allograft impaction results in excellent early recovery and pain reduction similar unilateral osteotomy.

BACKGROUND: Patients suffering from bilateral combined medial osteoarthritis and varus alignment of the knee are eligible for bilateral high tibial osteotomy (HTO) in two-staged surgery. The impact of bilateral HTO surgery on rehabilitation and early outcomes have not yet been reported in the literature, even though these features are decisive in establishing whether a patient is preferably treated in one or two stages. METHODS: A total of 29 patients were followed after simultaneous bilateral HTO surgery. Numeric Rating Scale (NRS), Knee injury and Osteoarthritis Outcome Score - Physical Function Short Form (KOOS-PS) and Lysholm scores were recorded at 3, 6 and 12 months. Results were compared with outcomes of unilateral HTO surgery to asses the additional impact of simultaneous bilateral HTO surgery on the early rehabilitation and recovery of simultaneous bilateral HTO surgery. RESULTS: Three months after surgery, NRS pain scores decreased from 60.5 to 40.9 and subsequently to 30.4 and 24.3 after 6 and 12 months, respectively. KOOS-PS scores improved from 50.0 to 44.3 after 3 months, to 33.9 and 29.8 after 6 and 12 months, respectively. Lysholm scores did not improve after 3 months (45.2-44.2), but significantly improved after 6 and 12 months (66.1 and 75.7, respectively). Compared with unilateral HTO surgery, similar improvements were seen after 6 and 12 months. CONCLUSION: Simultaneous bilateral HTO surgery generates similar clinical outcomes compared with unilateral HTO surgery and moreover it does not excessively prolong time to achieve these outcomes. It is safe and presumably a more effective approach to treat patients suffering bilateral medial osteoarthritis and varus alignment of the knee compared with two-staged surgery.

Long-term follow-up of the three-ligament tenodesis for scapholunate ligament lesions: 9-year results.

We report on a retrospective cohort of 50 cases of three-ligament tenodesis for scapholunate instability. Fifteen cases (30% of our cohort) needed salvage surgery (11 proximal row carpectomies, 2 partial and 2 total wrist fusions) at an average of 33 months and are considered "failures". Of the 35 remaining cases ("success"), 16 (32% of our cohort) were reviewed at average 111 months and had good functional outcomes (QuickDASH 18/100, PRWE 11/100, pain 1/10, satisfaction 9/10). Return to work was 81% and grip strength was 80% of the opposite side. Radiological review found no significant correction in the short-term: scapholunate angle (SLA) from 72° to 69° (p = 0.544), scapholunate distance (SLD) from 3.4 mm to 3.4 mm (p = 0.833) and radiolunate angle (RLA) from 17° to 13° (p = 0.253). A significant deterioration in SLA from 72° to 80° (p = 0.014), not correlated to function, was seen at final follow-up. Radiographic progression to wrist degeneration was seen in 63% of successful cases. In failed cases, we noticed inferior radiographic parameters in the short-term: SLD of 4.6 mm in failed versus 3.4 mm in successful cases (p = 0.038) and RLA of 22° in failed versus 13° in successful cases (p = 0.046). Complication rate was 10% (2 scaphoid necroses, 1 septic arthritis and 2 complex regional pain syndromes). Despite radiological deterioration of SLA and development of degeneration in most cases, three-ligament tenodesis can give satisfactory wrist function in some patients, but we observed a significant number of failures and a high complication rate. LEVEL OF EVIDENCE: IV.

Incidence of pemphigoid diseases in Northern Germany in 2016 - first data from the Schleswig-Holstein Registry of Autoimmune Bullous Diseases.

BACKGROUND: Autoimmune bullous diseases (AIBD) are rare disorders characterized by autoantibody formation against components of adhesion molecules; in pemphigoid diseases (PD), these are proteins of hemidesmosomes and basement membrane, important for cell-matrix adhesion in skin and/or mucous membranes. Incidences of these diseases vary considerably between different populations. OBJECTIVES: To establish a registry prospectively recruiting all AIBD patients in a geographically well-defined region in Northern Germany (Schleswig-Holstein). METHODS: Only patients with verified disease (by clinical presentation, histology, direct and/or indirect immunofluorescence and /or ELISA) living in Schleswig-Holstein were included. Incidences of PD were estimated based on the total number of inhabitants in Schleswig-Holstein, stratified by birth year and sex. RESULTS: Of 67 patients with PD [35 male, 32 female, mean age 75 (standard deviation 14.3 years)], 83% were patients with bullous pemphigoid [n = 56, 28 male, 28 female, mean age 78 (SD 9.9)]. The resulting crude incidences were 23.4 patients/million/year for all pemphigoid patients, 19.6 patients/million/year for bullous pemphigoid (age-standardized 16.9 patients/million/year) with a strong increase in bullous pemphigoid patients in the age group of 85-90 years with 262 patients/million/year. Incidences for bullous pemphigoid were higher in urban compared to rural areas. Other PD (mucous membrane pemphigoid, linear IgA disease, anti-p200 pemphigoid) were less frequent with crude incidences of 2.1, 1.0 and 0.7 patients/million/year, respectively. CONCLUSIONS: This study prospectively analyses the incidence of PD in a carefully defined geographical area. The highest incidence among PD patients was found for bullous pemphigoid. The incidence of bullous pemphigoid is considerably increased compared to previous reports and reveals regional differences. Further studies are needed in order to clarify these findings.

Portal placement for endoscopic surgery in the deep gluteal area: a cadaveric study.

Partial or complete avulsion of the insertion of the proximal hamstrings at the level of the ischial tuberosity is most often treated by open exploration and reinsertion. However, endoscopic reinsertion could be considered to minimize the soft tissue damage. In this study, we aimed to determine the most optimal location of four endoscopic portals that allow for a safe exploration of the proximal hamstring insertion site. The reference points for the portals run vertically through the center of the sciatic tuberosity and through a horizontal line which lies on the inferior edge of the tuberosity. The distance and relationship between the sciatic, the inferior gluteal and posterior femoral cutaneous nerves and the four proposed endoscopic portals was documented. Our results showed that it was best to start with the inferior portal followed by the medial and lateral portal. The inferior portal allowed for a clear visualization of the sciatic nerve and was along with the medial portal at a distance of >5 cm from any of the surrounding nerves. Care must be taken with the lateral portal, as the distance to the surrounding nerves varied between specimens. A fourth portal could be used as a viewing portal when necessary. Our study showed that the sequence and position of the proposed endoscopic portals provide a safe approach to the proximal part of the hamstrings and the ischial tuberosity. These findings can be helpful for endoscopic procedures to the ischium and the sciatic nerve in the gluteal region.

[Therapy of pemphigus]. / Aktuelle Therapie des Pemphigus.

BACKGROUND: Pemphigus diseases are a heterogeneous group of potentially life-threatening autoimmune bullous disorders. Therefore, rapidly acting and effective therapeutic approaches are essential. OBJECTIVES: In this review, current therapeutic options in line with available guidelines are presented and new therapeutic approaches are discussed. METHODS: A literature search was performed using PubMed. RESULTS: Treatment of pemphigus is based on systemic glucocorticosteroids, frequently combined with potentially corticosteroid-sparing immunosuppressants such as azathioprine and mycophenolate mofetil/mycophenolic acid. Recently, the impressive efficacy of the anti-CD20 antibody rituximab has been shown in a prospective randomized trial. In severe or treatment-refractory cases, immunoadsorption or high-dose intravenous immunoglobulins (IVIG) are recommended. Adjuvant immunoadsorption also seems to be useful within the first 8-12 weeks of therapy in patients with very high autoantibody levels. A variety of new therapeutic approaches is currently evaluated in phase IIa studies. CONCLUSION: Therapy of pemphigus has been greatly improved by the employment of rituximab. The use of glucocorticosteroids, associated with a high number of adverse events and elevated mortality, could be reduced by the additional use of rituximab. After approval of rituximab for the treatment of pemphigus by the US Food and Drug Administration in 2018, licensing in Europe is expected in 2019.

A sensitive and specific assay for the serological diagnosis of antilaminin 332 mucous membrane pemphigoid.

BACKGROUND: Antilaminin 332 mucous membrane pemphigoid (MMP) is an autoimmune subepidermal blistering disease with predominant mucosal involvement and autoantibodies against laminin 332. Malignancies have been associated with this disease; however, no standardized detection system for antilaminin 332 serum antibodies is widely available. OBJECTIVES: Development of a sensitive and specific assay for the detection of antilaminin 332 antibodies. METHODS: An indirect immunofluorescence (IF) assay using recombinant laminin 332 was developed and probed with a large number of antilaminin 332 MMP patient sera (n = 93), as well as sera from patients with antilaminin 332-negative MMP (n = 153), bullous pemphigoid (n = 20), pemphigus vulgaris (n = 20) and noninflammatory dermatoses (n = 22), and healthy blood donors (n = 100). RESULTS: In the novel IF assay, sensitivities with the laminin 332 heterotrimer and the individual α3, ß3 and γ2 chains were 77%, 43%, 41% and 13%, respectively, with specificities of 100% for each substrate. The sensitivity for the heterotrimer increased when an anti-IgG4 enriched antitotal IgG conjugate was applied. Antilaminin 332 reactivity paralleled disease activity and was associated with malignancies in 25% of patients with antilaminin 332 MMP. CONCLUSIONS: The novel IF-based assay will facilitate the serological diagnosis of antilaminin 332 MMP and may help to identify patients at risk of a malignancy.

A musculoskeletal model of the hand and wrist: model definition and evaluation.

To improve our understanding on the neuromechanics of finger movements, a comprehensive musculoskeletal model is needed. The aim of this study was to build a musculoskeletal model of the hand and wrist, based on one consistent data set of the relevant anatomical parameters. We built and tested a model including the hand and wrist segments, as well as the muscles of the forearm and hand in OpenSim. In total, the model comprises 19 segments (with the carpal bones modeled as one segment) with 23 degrees of freedom and 43 muscles. All required anatomical input data, including bone masses and inertias, joint axis positions and orientations as well as muscle morphological parameters (i.e. PCSA, mass, optimal fiber length and tendon length) were obtained from one cadaver of which the data set was recently published. Model validity was investigated by first comparing computed muscle moment arms at the index finger metacarpophalangeal (MCP) joint and wrist joint to published reference values. Secondly, the muscle forces during pinching were computed using static optimization and compared to previously measured intraoperative reference values. Computed and measured moment arms of muscles at both index MCP and wrist showed high correlation coefficients (r = 0.88 averaged across all muscles) and modest root mean square deviation (RMSD = 23% averaged across all muscles). Computed extrinsic flexor forces of the index finger during index pinch task were within one standard deviation of previously measured in-vivo tendon forces. These results provide an indication of model validity for use in estimating muscle forces during static tasks.

Prospective study in bullous pemphigoid: association of high serum anti-BP180 IgG levels with increased mortality and reduced Karnofsky score.

BACKGROUND: Bullous pemphigoid (BP) is a subepidermal blistering disease characterized by autoantibodies against the two hemidesmosomal proteins, BP180 (type XVII collagen) and BP230. The multicentre prospective BLISTER (Bullous Pemphigoid Steroids and Tetracyclines) trial randomized 253 patients with BP to compare the benefits and harms between initial treatment with doxycycline or prednisolone. OBJECTIVES: To analyse distinct autoantibody profiles for the prediction of the disease course in a well-characterized cohort of BP sera. METHODS: One hundred and forty-three patients of the BLISTER trial consented to participate in this serological study. Sera taken at baseline were analysed by (i) indirect immunofluorescence, (ii) anti-BP180 NC16A (16th noncollagenous domain) and anti-BP230 enzyme-linked immunosorbent assay and (iii) immunoblotting with various substrates. Results were then linked with clinical parameters including age, Karnofsky score, number of blisters, related adverse events and mortality. RESULTS: Disease activity correlated with immunoglobulin (Ig)G anti-BP180 levels but not with levels of anti-BP230 IgG and anti-BP180 IgE. High levels of both anti-BP180 IgG and anti-BP230 IgG were associated with a low Karnofsky score. The presence of anti-BP230 IgG was more frequent in older patients. Those with higher total IgE serum levels suffered from fewer adverse events. Higher IgG anti-BP180 levels were associated with an increased 1-year mortality rate. CONCLUSIONS: Analysis of the autoantibody profile is not only of diagnostic relevance but may also be helpful in predicting the course of the disease.

Serum autoantibodies against the dermal-epidermal junction in patients with chronic pruritic disorders, elderly individuals and blood donors prospectively recruited.

BACKGROUND: Bullous pemphigoid (BP) is a subepidermal blistering autoimmune disease characterized by autoantibodies against two structural proteins of the epidermal basal membrane zone (BMZ), BP180 (type XVII collagen) and BP230. Patients are usually old and suffer from severe pruritus. Advanced age and severe pruritus have been hypothesized as potential risk factors for the development of autoantibodies in BP. OBJECTIVES: To prospectively determine anti-BMZ antibodies in sera from patients with advanced age and/or pruritus compared with regular blood donors. METHODS: Sera from (i) patients with chronic pruritic skin disorders (PSD, n = 78; mean age 62 years), (ii) patients with noninflammatory skin disease aged ≥ 70 years (n = 93; mean age 78 years), and (iii) blood donors (n = 50; mean age 41 years) were included. A large panel of validated test systems used for routine diagnosis were employed comprising indirect immunofluorescence (IF) microscopy on monkey oesophagus and human salt-split skin, BP180 NC16A- and BP230-specific enzyme-linked immunosorbent assay (ELISA) systems, and immunoblotting with various substrates, including LAD-1 (the soluble ectodomain of BP180), BP180, BP230, laminin 332, p200 antigen, laminin γ1 and type VII collagen. RESULTS: No statistically significant difference was seen between the three study groups. The same result was obtained when data for IF microscopy, ELISA and immunoblotting were analysed separately. CONCLUSIONS: Neither advanced age nor chronic pruritus have been verified as risk factors for autoantibodies against the epidermal BMZ.

[Primary antiphospholipid syndrome: newly developed leg ulcer and history of stroke]. / Diagnose eines primären Antiphospholipidsyndroms bei Ulcus cruris unter Marcumar-Therapie.

Antiphospholipid syndrome features not only deep vessel thrombosis but also may have cutaneous manifestations such as Raynaud phenomenon, acral necrosis, livedo reticularis, subcutaneous nodules, and leg ulcers. A 72-year-old man presented with a rapidly progressing leg ulcer. He was already on anticoagulation with warfarin due to atrial fibrillation and disclosed a history of stroke with temporary paresis of the left leg. Histopathology of a biopsy of the edge of the ulcer revealed occlusive arteriosclerosis of medium-sized arteries. Serology showed autoantibodies against cardiolipin, ß2- glycoprotein I, and phosphatidylserine which led to the diagnosis of antiphospholipid syndrome. Therapy with low molecular weight heparin, dexamethasone, and azathioprine in combination with stage-adjusted wound care led to complete healing of the ulcer within 5 months.

Heterogeneity in liquid shaken cultures of Aspergillus niger inoculated with melanised conidia or conidia of pigmentation mutants.

Black pigmented conidia of Aspergillus niger give rise to micro-colonies when incubated in liquid shaken medium. These micro-colonies are heterogeneous with respect to gene expression and size. We here studied the biophysical properties of the conidia of a control strain and of strains in which the fwnA, olvA or brnA gene is inactivated. These strains form fawn-, olive-, and brown-coloured conidia, respectively. The ΔolvA strain produced larger conidia (3.8 µm) when compared to the other strains (3.2-3.3 µm). Moreover, the conidia of the ΔolvA strain were highly hydrophilic, whereas those of the other strains were hydrophobic. The zeta potential of the ΔolvA conidia in medium was also more negative when compared to the control strain. This was accompanied by the near absence of a rodlet layer of hydrophobins. Using the Complex Object Parametric Analyzer and Sorter it was shown that the ratio of individual hyphae and micro-colonies in liquid shaken cultures of the deletion strains was lower when compared to the control strain. The average size of the micro-colonies of the control strain was also smaller (628 µm) than that of the deletion strains (790-858 µm). The size distribution of the micro-colonies of the ΔfwnA strain was normally distributed, while that of the other strains could be explained by assuming a population of small and a population of large micro-colonies. In the last set of experiments it was shown that relative expression levels of gpdA, and AmyR and XlnR regulated genes correlate in individual hyphae at the periphery of micro-colonies. This indicates the existence of transcriptionally and translationally highly active and lowly active hyphae as was previously shown in macro-colonies. However, the existence of distinct populations of hyphae with high and low transcriptional and translational activity seems to be less robust when compared to macro-colonies grown on solid medium.

Anxiety sensitivity in children of panic disorder patients.

Anxiety sensitivity (AS), which refers to the tendency to interpret anxiety-related bodily sensations as having potentially harmful somatic, psychological or social consequences, has been proposed as a vulnerability factor for the development of panic disorder (PD). The current study examined the anxiety sensitivity levels in children of parents with panic disorder. Children of panic disorder patients (n = 68) and children of healthy parents (n = 68) filled out the Childhood Anxiety Sensitivity Index, while parents completed the Anxiety Sensitivity Index. Children of parents with panic disorder did not display higher levels of anxiety sensitivity than children of healthy parents. Furthermore, no association between anxiety sensitivity levels of parents with panic disorder and their children was found. Anxiety sensitivity is not clearly manifest in children of parents with panic disorder and might be a developing vulnerability factor that may increase towards late adolescence or early adulthood.

Anxiety sensitivity in first-degree relatives of patients with panic disorder.

Anxiety sensitivity (AS) has been proposed as a risk factor for the development of panic disorder. Strong familial-genetic influences in panic disorder (PD) have been reported. AS may be familial too. The current study therefore examined whether first-degree relatives of PD patients are more anxiety-sensitive than normals. Twenty-three first-degree relatives of PD patients, 38 PD patients and 30 normals were given the Anxiety Sensitive Index and the Body Sensations Questionnaire. It was found that the first-degree relatives were, indeed, more anxiety-sensitive than the normals, but less so than the PD patients, suggesting that AS runs in families.

Conditions influencing the in vitro antifungal activity of lactoferrin combined with antimycotics against clinical isolates of Candida. Impact on the development of buccal preparations of lactoferrin.

Lactoferrin, an iron-binding glycoprotein, is a potential agent for the treatment of oropharyngeal Candidiasis. The aim of the present study was to test the capability of lactoferrin, combined or not combined with conventional antifungal agents, to inhibit the growth of different Candida species under various experimental conditions to be of guidance in the development of a suitable pharmaceutical formulation containing lactoferrin. The anti-Candida activities of lactoferrin were considerably higher using RPMI instead of SLM as assay medium. They were moreover increased by raising the medium pH from 5.6 to 7.5. With the 'standard' antifungal agent fluconazole similar results were found as for lactoferrin, but the medium type and pH did not affect MIC values of amphotericin B. The addition of saliva to medium did not reduce the antifungal activities of the individual compounds. Synergistic inhibitory effects on Candida growth were found for combinations of lactoferrin and fluconazole or amphotericin B, irrespective of the medium type and pH, or the addition of saliva. This indicates that for treatment of oral Candidiasis a formulation containing lactoferrin seems appropriate; results may be optimized if the formulation is provided with buffer capacity to attain pH 7.5 in the mucosal fluid. The synergistic effects between lactoferrin and 'standard' antifungals indicate that combinations should be considered in such a formulation.