Minimally invasive lateral plating for diaphyseal fractures with extension into the proximal humerus and its implications for the deltoid muscle and its distal insertion: functional analysis and MR-imaging.

BACKGROUND: In minimally invasive lateral plate osteosynthesis of the humerus (MILPOH) the plate is introduced through a deltoid split proximally and advanced through the central portion of the deltoid insertion and between bone and brachial muscle to the distal aspect of the humerus. The fracture is then indirectly reduced and bridged by the plate. Whereas it has been shown that the strong anterior and posterior parts of the distal deltoid insertion remain intact with this maneuver, its impact on deltoid muscle strength and muscular morphology remains unclear. It was the aim of this study to evaluate deltoid muscle function and MR-morphology of the deltoid muscle and its distal insertion after MILPOH. METHODS: Six patients (median age 63 years, range 52-69 years, f/m 5/1) who had undergone MILPOH for diaphyseal humeral fractures extending into the proximal metaphysis and head (AO 12B/C(i)) between 08/2017 and 08/2020 were included. Functional testing was performed for the injured and uninjured extremity including strength measurements for 30/60/90° shoulder abduction and flexion at least one year postoperatively. Constant-Murley-Score (CMS) including an age-and gender-adjusted version, were obtained and compared to the uninjured side. Oxford Shoulder Score (OSS) and the Disability of the Arm, Shoulder and Hand (DASH) questionnaire were acquired for the affected extremity. Quality of life was measured using the EQ visual analogue scale (EQ-5D-5 L VAS). MR imaging was performed for both shoulders accordingly at the time of follow-up to assess the integrity of the distal insertion, muscle mass and fatty degeneration of the deltoid muscle. Muscle mass was determined by measuring the area of the deltoid muscle on the axial MR image at the height of the center of the humeral head. RESULTS: Median follow-up was 29 months (range 12-48 months). Median difference of abduction strength after MILPOH was + 13% for 30°, 0% for 60° and - 22% for 90°. For flexion, the difference to the uninjured side was measured 5% for 30°, -7% for 60° and - 12% for 90°. Median CMS was 75 (66-82) for the operated extremity compared to 82 (77-90) for the uninjured side. Age- and gender-adapted CMS was calculated 88 (79-99) vs. 96 (89-107). Median OSS was 47 (40-48). DASH was 26 (15-36). EQ-5D-5 L VAS ranged from 81 to 95 with a median of 90. The median difference of the deltoid muscle area on MRI was 2% (-21% to + 53%) compared to the uninjured side. No fatty degeneration of the deltoid muscle was observed. The weaker central part of the distal deltoid insertion was exclusively perforated by the plate, leaving the strong anterior and posterior parts of the insertion intact in all patients. CONCLUSIONS: MILPOH was associated with good functional and subjective outcome. Minor impairment of abduction strength was observed with increasing abduction angles. The reason for this impairment is unclear since MILPOH did not affect the structural quality of the deltoid muscle and the integrity of the strong anterior and posterior parts of its insertion remained intact. TRIAL REGISTRATION: 26/05/2023: ISRCTN51786146.

A phase II study of interferon-alpha for the treatment of refractory Churg-Strauss syndrome.

OBJECTIVE: Uncontrolled vasculitis is the major cause of early death in Churg-Strauss syndrome and standard therapy is not always effective. This study was carried out to examine the safety and efficacy of interferon-alpha for induction of remission in patients with refractory Churg-Strauss syndrome. METHODS: In a prospective open-label trial, seven patients with Churg-Strauss syndrome refractory to cyclophosphamide or methotrexate received interferon-alpha (3 million. I.U. 3 times weekly s.c.) for induction of remission. Primary end point was the successful induction of remission. Prednisolone was tapered according to the study protocol. RESULTS: All seven patients entered remission after 3 months of treatment. Five patients reached complete remission while in two patients, residual asthmatic complaints persisted. The mean Birmingham Vasculitis Activity Score (BVAS) decreased from 6.4 (+/-2.8) to 0 (+/-0) (p=0.017). Clinical improvement in response to interferon-alpha allowed to taper concomitant prednisolone according to the protocol from a mean dose of 20.4 mg/d (+/-13.3) to 6.9 mg/d (+/-1.9) (p=0.068). During a follow up of 6 months all patients remained in remission. In one patient, leukencephalopathy without clinical symptoms was seen on MRI after 61 months of treatment, as previously reported. In this cohort, no other cases of leukencephalopathy were observed during long-term follow-up. Constitutional symptoms related to the injection of interferon-alpha responded well to paracetamol. A transient leukopenia was found in two patients. CONCLUSION: Interferon-alpha appears to be an effective and well-tolerated treatment for induction of remission in patients with refractory Churg-Strauss syndrome.

The leucotriene receptor antagonist montelukast and the risk of Churg-Strauss syndrome: a case-crossover study.

BACKGROUND: There has been some concern that leucotriene receptor antagonists might precipitate the onset of Churg-Strauss syndrome (CSS). A study was undertaken to investigate the relationship between the leucotriene receptor antagonist montelukast and the onset of CSS. METHODS: Medication histories of 78 patients with CSS from France and Germany were retraced by questioning the patients, treating physicians and dispensing pharmacists, and from medical records. Using a case-crossover research design, exposures to montelukast and other asthma medications during the 3-month "index" period immediately preceding the onset of CSS were compared with those of four previous 3-month "control" periods. Odds ratios (ORs) were computed by conditional logistic regression. RESULTS: The ORs for CSS onset were 4.5 (95% CI 1.5 to 13.9) for montelukast, 3.0 (95% CI 0.8 to 10.5) for inhaled long-acting beta(2) agonists, 1.7 (95% CI 0.5 to 5.4) for inhaled corticosteroids and 4.0 (95% CI 1.3 to 12.5) for oral corticosteroids. Montelukast exposure during control periods increased temporally over three consecutive calendar periods of CSS onset from 1999 to 2003 (p(trend) <0.0001). CONCLUSION: Montelukast use was associated with a 4.5-fold higher risk of CSS onset within 3 months. However, the positive estimates obtained for other long-term asthma control medications suggest that this link might be confounded by a general escalation of asthma therapy before CSS onset. The association between montelukast and CSS observed in this study is probably also explained by the increasing use of this medication over time.

Elevated relapse rate under oral methotrexate versus leflunomide for maintenance of remission in Wegener's granulomatosis.

OBJECTIVES: Results from open-label trials suggest that methotrexate (MTX) and leflunomide (LEF) are effective for maintenance of remission in Wegener's granulomatosis (WG), but data from randomized controlled clinical trails are not yet available. METHODS: In this multicentre, prospective randomized controlled clinical trial, patients with generalized WG were treated either with oral LEF 30 mg/day or oral MTX (starting with 7.5 mg/week reaching 20 mg/week after 8 weeks) for 2 yrs following induction of remission with cyclophosphamide. The primary endpoint was the incidence of relapses. Secondary outcome parameters were DEI, BVAS, SF-36, cANCA-titre, ESR and CRP. RESULTS: Fifty-four patients were included in the study, 26 in the LEF-limb, 28 in the MTX-limb. In the LEF-group, six patients relapsed after a median time of 7 months, thereof one major relapse with a new pulmonary manifestation. In the MTX-group, 13 relapses occurred in 6 months, of which seven were major: rapidly progressive glomerulonephritis (n = 4), pulmonary haemorrhage (n = 2) and one cerebral granuloma. The significantly higher incidence of major relapses in the MTX-limb (P = 0.037) led to premature termination of the study. In the LEF-limb, four patients were withdrawn due to hypertension (n = 2), peripheral neuropathy (n = 1) and leucopenia (n = 1). CONCLUSION: LEF at a dosage of 30 mg/day appears to be effective in the prevention of major relapses in WG, however, this is associated with an increased frequency of adverse events. Further studies testing other dosing regimens of lower doses of LEF are needed to confirm these promising results in larger patients cohorts.

Maintenance of remission with leflunomide in Wegener's granulomatosis.

OBJECTIVE: To investigate the safety and efficacy of leflunomide plus low-dose prednisolone for the maintenance of remission in Wegener's granulomatosis (WG). METHODS: This was a Phase II, single-centre, open-label clinical investigation of patients with generalized WG treated with leflunomide after the induction of complete (n = 4) or partial (n = 16) remission by cyclophosphamide/prednisolone combination therapy. Leflunomide treatment was initiated at 20 mg/day and increased to 30 mg/day after 12 weeks and, in patients with partial remission, to 40 mg/day after 24 weeks. Concomitant low-dose prednisolone (< or =10 mg/day) was allowed during the study. In addition to the frequency of relapse, treatment efficacy was assessed by the standard measures of disease activity/extent. RESULTS: A total of 20 patients were enrolled in the trial. During a treatment period of up to 2.5 yr (median 1.75 yr, range 1-2.5 yr), one patient had a major relapse and required retreatment with cyclophosphamide/prednisolone. Eight patients had minor relapses that were successfully treated by dose increases to 40 mg/day leflunomide. Disease activity remained unchanged for the duration of the study. The most frequently reported adverse events were mild respiratory infection (40%), arthralgia (35%) and hypertension (35%); dry skin, nail disorder and diarrhoea were each reported by 30% of patients. Despite the aggressive pretreatment with cyclophosphamide, adverse events with leflunomide treatment at the higher dose (30-40 mg/day) were comparable with those seen with the standard dose (20 mg/day) for rheumatoid arthritis patients. CONCLUSION: Leflunomide appears to be safe and well tolerated for the maintenance of complete or partial remission of WG. The results of this pilot study encourage further controlled trials comparing leflunomide with alternative remission maintenance therapies.

Churg Strauss syndrome--successful induction of remission with methotrexate and unexpected high cardiac and pulmonary relapse ratio during maintenance treatment.

OBJECTIVE: To examine the safety and efficacy of methotrexate (MTX) plus low-dose prednisolone for induction of remission in non life- or organ-threatening courses and for remission maintenance in Churg-Strauss syndrome (CSS). METHODS: In an open-label study 11 patients were treated with MTXfor induction of remission at initial diagnosis and relapse. Twenty-five patients received MTX for maintenance of remission. Primary endpoints were the achievement of remission and the incidence of relapses, respectively. Doses of concomitant prednisolone (PRD) and side effects were secondary endpoints. RESULTS: Induction of remission was achieved in 8/11 patients with MTX/PRD. Median time to remission was 5 months (range 2-9). Remission was maintained in 12 of 23 with available long-term follow-up (median 48 months). Eleven patients experienced 8 major and 3 minor relapses with a median time from remission to first relapse of 9 months. With MTX, the median cumulative PRD dose during the induction phase was 6.2 g. In the maintenance phase PRD could be reduced by 53% in responders. Apart from one case of MTX-induced pneumonitis, adverse events were confined to mild/moderate episodes of infection and leucopenia. No opportunistic infections occurred, neither did steroid-specific adverse events. CONCLUSIONS: MTX is safe and effective for the induction of remission in non-life-threatening CSS. It allows a considerable reduction of PRD and thus avoidance of PRD-related adverse events. However, the ability of MTX to prevent relapses in CSS appears limited. The identification of an optimal maintenance regimen and prognostic factors for treatment response requires trials with larger patient numbers.

[Efficacy and safety of mouthwash diclofenac in oral or periodontal surgery]. / Efficacia e tollerabilità di diclofenac collutorio nella chirurgia orale o parodontale.

BACKGROUND: In a multicentre clinical study was evaluated the efficacy and safety of a mouthwash containing diclofenac 0.074% in patients undergone to oral or periodontal surgery. METHODS: Multicentre clinical open study. The patients rinsed for 1 min twice a day with diclofenac mouthwash for 7 days. After the baseline measurements of all parameters, spontaneous pain and burning were evaluated daily, while redness and oedema after 3 and 7 days of treatment. Seventy-nine patients (48 F, 31 M), mean aged 42.5 years+/-13.1 SD, with pain intensity at the end of anaesthesia effect equivalent to 54.8 mm+/-15.1 SD of a visual analogue scale were evaluated for efficacy. RESULTS: Spontaneous pain was significantly reduced by diclofenac mouthwash, versus baseline, in the first day of treatment. After a week of treatment, intensity was reduced more than 88% (p<0.01). Burning, redness and oedema too evidenced a similar behaviour, with absence of the sign respectively superior to 87%, 72% and 91 % (p<0.01). The physician's and patient's final judgement overlapped, recording a resolution/improvement in 94.1% of cases, particularly improvement in 77.2% for the physician and in 70.9% for the patients. Palatability was judged pleasant/acceptable in all cases. CONCLUSIONS: Diclofenac mouthwash is endowed by very good efficacy and safety in the treatment of inflammatory condition of the buccal cavity following oral or periodontal surgery.

Elevated interleukin-4 and interleukin-13 production by T cell lines from patients with Churg-Strauss syndrome.

OBJECTIVE: To investigate cytokine production patterns of T cell lines (TCL) from patients with Churg-Strauss syndrome (CSS). METHODS: Short-term polyclonal TCL were generated from peripheral blood of patients with CSS or Wegener's granulomatosis (WG) and healthy controls (HC). TCL were established in the presence of interleukin-2 (IL-2) and phytohemagglutinin and were phenotypically characterized by flow cytometry. Th1/ Th2 cytokine production by stimulated TCL (72 hours) was analyzed by enzyme-linked immunosorbent assay. RESULTS: TCL that represented the progeny of in vivo-activated T cells from CSS patients displayed a heterogeneous immunophenotype, with a predominance of CD4+ T cells when compared with WG TCL, which were predominantly CD8+. All CSS TCL shared the ability to produce large amounts of interferon-gamma (IFNgamma), IL-4, and IL-13 compared with HC (P = 0.014 for all 3). Production of IL-4 and IL-13 was higher in CSS TCL than in WG TCL (P = 0.014 for both). IL-5 production was up-regulated in WG TCL compared with CSS TCL (P = 0.014). Compared with HC, WG TCL showed increased production of IFNgamma (P = 0.021), IL-5 (P = 0.043), and IL-13 (P = 0.021). CONCLUSION: Our results indicate that, while there is evidence for both a type 1 and a type 2 response in CSS, type 2 cytokine production pattern appears to predominate in this disease when compared with WG and HC.

Development of adolescent problem behavior.

The developmental model of adolescent antisocial behavior advanced by Patterson and colleagues (e.g., Patterson, Reid, & Dishion, 1992) appears to generalize the development of a diverse set of problem behaviors. Structural equation modeling methods were applied to 18-month longitudinal data from 523 adolescents. The problem behavior construct included substance use, antisocial behavior, academic failure, and risky sexual behavior. Families with high levels of conflict were less likely to have high levels of parent-child involvement. Such family conditions resulted in less adequate parental monitoring of adolescent behavior, making associations with deviant peers more likely. Poor parental monitoring and associations with deviant peers were strong predictors of engagement in problem behavior. These constructs accounted for 46% of the variance in problem behavior. Although association with deviant peers was the most proximal social influence on problem behavior, parental monitoring and family factors (conflict and involvement) were key parenting practices that influenced this developmental process.

Skin resurfacing utilizing a low-fluence Nd:YAG laser.

OBJECTIVE: The purpose of this clinical study was to determine the effectiveness of low fluence topical carbon suspension assisted Q-switched Nd:YAG laser treatment of fine rhytids. MATERIALS AND METHODS: Some 242 solar-damaged anatomical sites on 61 human subjects were treated with three laser treatments at two study centers. The treatment involved applying a carbon suspension to the skin surface and irradiating the exogenous chromophore with a Q-switched Nd:YAG laser. Cosmetic skin-resurfacing was accomplished using a wavelength of 1064 nm, a fluence of 2.5 J/cm2, a pulse duration of 6-20 ns, a pulse repetition rate of 1-10 Hz and a fixed beam size of 7 mm. The treatment sites were evaluated at baseline, 4, 8, 14, 20 and 32 weeks for skin texture, skin elasticity and rhytid reduction. All sites were treated at baseline, 4 and 8 weeks. Skin replicas taken prior to treatment and at the conclusion of the study were analyzed for wrinkle and cosmetic improvement using the Magiscan digital image process system. Adverse events were recorded throughout the study. RESULTS: At 8 months the investigators reported improvement in both skin texture and skin elasticity, as well as rhytid reduction compared to baseline. In self-assessments, subjects also reported noticeable skin texture and cosmetic improvement, but assessed wrinkle reduction less favorably than seen by the investigators. The majority of adverse events were limited to mild, brief erythema. CONCLUSIONS: Topical carbon suspension assisted Q-switched Nd:YAG laser treatment offers a safe cosmetic method of resurfacing solar-damaged skin. The effect, as reported by investigators and subjects in this study, and confirmed by skin replica analyses, included improvement in skin texture, elasticity and rhytid appearance.

Single-unit responses of serotonergic dorsal raphe neurons to specific motor challenges in freely moving cats.

Serotonin has been hypothesized to play an important role in the central control of motor function. Consistent with this hypothesis, virtually all serotonergic neurons within the medullary nuclei raphe obscurus and raphe pallidus in cats are activated in response to specific motor challenges. To determine whether the response profile of serotonergic neurons in the midbrain is similar to that observed in the medulla, the single-unit activity of serotonergic dorsal raphe nucleus cells was studied during three specific motor activities: treadmill-induced locomotion, hypercarbia-induced ventilatory response and spontaneous feeding. In contrast to the results obtained for medullary raphe cells, none of the serotonergic dorsal raphe cells studied (n=26) demonstrated increased firing during treadmill-induced locomotion. A subset of serotonergic dorsal raphe cells (8/36) responded to the hypercarbic ventilatory challenge with increased firing rates that were directly related to the fraction of inspired carbon dioxide, and a non-overlapping subset of cells (6/31) was activated during feeding. All feeding-on cells demonstrated a rapid activation and de-activation coincident with feeding onset and offset, respectively. Although the proportions of serotonergic cells activated by hypercarbia or feeding in the dorsal raphe nucleus were similar to those found in the medullary raphe, there were several major distinctions in the response characteristics for the two cell groups. In contrast to the medullary serotonergic neurons, only a minority of dorsal raphe nucleus serotonergic neurons responded to a motor challenge. Overall, the above results suggest very different roles for the midbrain and medullary serotonergic neurons in response to motor activities.

Response of serotonergic caudal raphe neurons in relation to specific motor activities in freely moving cats.

Serotonergic neuronal responses during three specific motor activities were studied in nuclei raphe obscurus (NRO) and raphe pallidus (NRP) of freely moving cats by means of extracellular single-unit recordings. Responses to treadmill-induced locomotion were primarily excitatory, with 21 of 24 neurons displaying increased firing rates, directly related to treadmill speed. Individual regression analyses determined three response patterns: maximal activation at low speed (0.25 m/sec), augmentation of neuronal activity only at high treadmill speed (0.77 m/sec), and a linear increase. A smaller fraction of NRO and NRP serotonergic neurons (6 of 27) also responded to hypercarbic ventilatory challenge with increased firing rates. The magnitude of neuronal response was dependent upon the fraction of inspired CO2 and was related to ventilatory motor output, specifically, inspiratory amplitude. A subgroup of neurons responsive to hypercarbia in wakefulness demonstrated significant reductions in neuronal response to hypercarbia in slow-wave sleep. Finally, unit activity for 12 of 29 cells increased in response to spontaneous feeding, displaying two distinct patterns of neuronal response in relation to onset and termination of feeding: rapid activation and deactivation versus a gradual increase and decrease. More than half of the cells studied under all three conditions were responsive to more than one motor task. These results indicate that serotonergic caudal raphe neurons are responsive to specific motor system challenges, with many neurons responsive to multiple motor tasks, and that the responsiveness of serotonergic neurons to at least one motor task, hypercarbic ventilatory challenge, is state dependent.

Continuous intravenous dosing with ciprostene using a portable pump in ambulatory patients.

Parenteral compounds present special drug delivery challenges. This open-label study evaluated a portable infusion pump as a means to deliver intravenous ciprostene, a stable prostacyclin analog. Ten patients with peripheral vascular disease and claudication received ciprostene (titrated to 120 ng/kg/min) infused over 8 hours 1 day per week for 4 consecutive weeks. Patients successfully maintained the pump strapped to the waist. The mean +/- standard deviation delivery error, with volumes of 6 to 10 mL over 8 hours, was -0.895 +/- 3.177%. Accordingly, the pump performed well with a potent drug under these clinical conditions. Headache, flushing, and infusion site irritation during infusion were the most frequent side effects. Blood pressure remained unchanged during infusion; however, heart rate increased significantly (P < .05, maximum increase was 13.9 +/- 2.1 beats per minute [mean +/- standard error of the mean]. Mean (+/- standard error of the mean) relative claudication times on treadmill remained unchanged; however, absolute claudication times increased (P < .05) from 6.6 +/- 1.8 to 10.0 +/- 2.2 minutes. Ciprostene inhibited adenosine diphosphate-induced platelet aggregation by 56.0 +/- 12.7% (mean +/- standard error of the mean). Mean template bleeding times and plasma concentrations of platelet-specific proteins (beta-thromboglobulin, platelet factor 4) did not change.

Social and behavioral factors associated with high-risk sexual behavior among adolescents.

Relationships among risky sexual behaviors, other problem behaviors, and the family and peer context were examined for two samples of adolescents. Many adolescents reported behaviors (e.g., promiscuity or nonuse of condoms) which risked HIV or other sexually transmitted disease infection. Such risky behaviors were significantly intercorrelated. Consistent condom use was rare among those whose behavior otherwise entailed the greatest risk of infection. In both samples, an index of high-risk sexual behavior was significantly related to antisocial behavior, cigarette smoking, and illicit drug or alcohol use. Social context variables, including family structure, parenting practices, and friends' engagement in problem behaviors, were associated with high-risk sexual behavior. Finally, for sexually active adolescents, problem behaviors and social context variables were predictive of nonuse of condoms. Results were consistent across the two studies and regression weights held up well under cross-validation.

The effects of cefmetazole and latamoxef on platelet function in healthy human volunteers.

This study has compared the effects of normal saline (placebo), cefmetazole, and latamoxef (moxalactam) on platelet function in healthy human volunteers. Twenty-nine volunteers were randomized to receive placebo (n = 10), cefmetazole 2 g (n = 9) or latamoxef 2 g (n = 10) intravenously every 6 h for six days. Under double-blind conditions template bleeding time and ex-vivo adenosine diphosphate (ADP) induced platelet aggregation were measured before drug dosing, after the first, ninth, and last drug doses and one and three days after the last drug dose. Latamoxef caused progressive impairment of platelet function with statistically significant increases in the mean bleeding time to 7.4 +/- 3.7 min (P = 0.02) and the amount of ADP (0.2 mM) required to induce 50% platelet aggregation to 77.3 +/- 91.1 microliters (P = 0.03) on day 6 of treatment compared with values before drug administration (4.2 +/- 0.7 min; 3.7 +/- 22 microliters, respectively). These changes were reversible following discontinuation of drug dosing. Cefmetazole and placebo had no significant effects on either measure of platelet function at any time during the study.

Clinical experience with cefmetazole sodium in the United States: an overview.

The clinical development programme for cefmetazole sodium included over 4000 patients treated by 78 investigators. Cefmetazole therapy was compared with that of cefoxitin sodium (cefoxitin) for the treatment of urinary tract, skin and soft tissue, lower respiratory, abdominal, and gynaecological infections (with cefoxitin-sensitive pathogens) and for the prevention of postoperative wound infection in patients undergoing surgical procedures. Both cefmetazole and cefoxitin were administered intravenously in all studies. Cefmetazole was as effective as cefoxitin in the treatment of the infections studied. In the surgical wound infection prophylaxis studies, multiple-dose cefmetazole therapy was more effective than multiple-dose cefoxitin therapy in patients undergoing lower gastrointestinal surgery; this difference approached statistical significance. Both multiple-dose and single-dose cefmetazole therapy were as effective as multiple-dose cefoxitin treatment in the other types of surgery studied. Clinical laboratory findings and adverse medical events reported among cefmetazole patients were similar to those observed in patients treated with cefoxitin.