Substitution Urethroplasty with Closure Versus Nonclosure of the Buccal Mucosa Graft Harvest Site: A Randomized Controlled Trial with a Detailed Analysis of Oral Pain and Morbidity

Background

Optimal surgical management of the buccal mucosa harvest site in patients with urethral stricture disease during buccal mucosa graft urethroplasty (BMGU) remains controversial.

Immunophenotypic characterization of peripheral B cells. During short-term immunotherapy with tree pollen allergoid and the immunoadjuvant monophosphoryl lipid A.

The effects of immunotherapy (IT) on the activation and functions of B cells are not well described yet. We therefore measured the expression of several surface markers on peripheral B cells during short-term IT. Twelve patients with seasonal allergic rhinoconjunctivitis, sensitized to hazel, alder, and birch pollen proven by positive history, skin test, sIgE, and nasal provocation test, were included in the study. Eight patients received short-term IT with TA tree pollen and the immunoadjuvant monophosphoryl Lipid A; 4 patients received a placebo suspension containing 2% tyrosine. After separation of PBMCs, the expression of surface molecules on peripheral B cells were analyzed by flow cytometry before the start of IT, before the 3rd injection, at the end of IT, and after the pollen season. The expression of CD23, CD54, and HLA-DR-II on CD19+ B cells decreased during IT and then increased again after the pollen season. In the placebo group, the expression of CD23, CD54, and HLA-DR-II remained unchanged during the first three measurements. After the season, the expression of CD23, CD54 and HLA-DR-II increased in both groups. CD86 expression was decreased during treatment in both groups. Although CD86 expression increased in both groups after the season, the increase was more pronounced in the placebo group. No changes in the expression of CD32, CD40, and HLA-ABC-I were registered during the study. The results show that expression of CD23, CD54, and HLA-DR-II on peripheral B cells decreases during IT, which indicates reduced B-cell activation. Whether these effects are a result of direct allergen action on the B cells or whether they are mediated by T cells and their clinical relevance remains to be elucidated.     

A novel missense mutation in a neonate with nonketotic hyperglycinemia

Nonketotic hyperglycinemia (OMIM #605899), also known as glycine encephalopathy, is an autosomal recessive disorder of glycine metabolism caused by a defect in the glycine cleavage system. A term neonate developed progressive lethargy, muscular hypotonia, and respiratory insufficiency on day 2 after birth, but no overt clinical seizures. Amplitude-integrated electroencephalography indicated a continuous burst-suppression pattern. The diagnosis of nonketotic hyperglycinemia was made biochemically and was confirmed by genetic studies, which revealed two missense mutations (one not previously described) within the glycine decarboxylase gene, GLDC. Nonketotic hyperglycinemia should be incorporated into the differential diagnosis of neonatal hypotonia, to avoid an erroneous diagnosis of sepsis or hypoxic ischemic injury. Amplitude-integrated electroencephalography may be helpful in the initial assessment of severely sick and hypotonic neonates without overt clinical seizures, and may direct further diagnostic evaluation.     

Symptomatic lymphoceles after kidney transplantation – multivariate analysis of risk factors and outcome after laparoscopic fenestration

Ulrich F, Niedzwiecki S, Fikatas P, Nebrig M, Schmidt SC, Kohler S, Weiss S, Schumacher G, Pascher A, Reinke P, Tullius SG, Pratschke J. Symptomatic lymphoceles after kidney transplantation – multivariate analysis of risk factors and outcome after laparoscopic fenestration.
Clin Transplant 2009 DOI: 10.1111/j.1399‐0012.2009.01073.x
© 2009 John Wiley & Sons A/S. Abstract: Lymphocele formation is a common complication after kidney transplantation, and laparoscopic surgery has become a widely accepted treatment option. The aim of this retrospective study was to analyze the risk factors of lymphocele development and to assess the treatment outcome after laparoscopic fenestration. We analyzed 426 renal allograft recipients operated between 2002 and 2006 receiving triple immunosuppression with calcineurin inhibitors. The incidence of lymphocele was 9.9%, while 24 (5.6%) patients with symptomatic lymphoceles required laparoscopic surgery. Serum creatinine at diagnosis was significantly higher in patients with lymphoceles treated surgically (3.2 ± 0.7 vs. 1.7 ± 0.6 mg/dL; p < 0.001). After successful laparoscopic intervention, creatinine concentrations recovered until discharge and were comparable to other patients (1.6 ± 0.5 vs. 1.5 ± 0.5 mg/dL; p = NS). While we observed a significant association of lymphocele formation with diabetes, tacrolimus therapy, and acute rejection in univariate testing, only diabetes remained a significant factor after multivariate analysis. Laparoscopic fenestration proved to be a safe and efficient method without any associated mortality and a low recurrence rate of 8.3% (n = 2). We conclude that diabetes is an independent risk factor for lymphocele development, and laparoscopic fenestration should be the treatment of choice for larger and symptomatic lymphoceles, as it is safe and offers a low recurrence rate.     

Snapping elbow caused by hypertrophic synovial plica in the radiohumeral joint: a report of three cases and review of literature

The snapping elbow caused by hypertrophic synovial radiohumeral plica is a rare form of lateral elbow impingement. In this article we report on hypertrophic radiohumeral synovial folds in three male patients, aged 54, 65 and 27 years. All three patients suffered isolated lateral elbow pain, painful snapping and unsuccessful conservative treatment over at least 5 months (range 5–9 months, mean 7.7 months) prior to surgical treatment. None of the patients had lateral epicondylitis, instability, osteochondrosis dissecans, loose bodies, arthritis or neurological disorders. Upon clinical examination the range of motion in the respective painful elbows was found to be normal in all three cases, but a painful snapping occurred between 80° and 100° of flexion with the forearm in pronation. While there were no pathologic findings in standard radiographs, magnetic resonance imaging (MRI) revealed hypertrophic synovial plicae in the radiohumeral joints associated with effusion in each of the diseased elbows. Arthroscopic examinations confirmed the presence of a hypertrophic synovial plica in all three radiocapitellar joints, and revealed a transient interposition and compression of the folds in the articulation from extension until 90°–100° elbow flexion, with replacement beyond 90° elbow flexion with a visible jump. Surgical management in all three cases comprised arthroscopic diagnosis confirmation and removal of the synovial plicae, leading to excellent outcomes at 6–12 months follow-up.     

Meta-analysis of Functional Outcomes and Complications Following Transurethral Procedures for Lower Urinary Tract Symptoms Resulting from Benign Prostatic Enlargement

Context

There is a continuous decline in the number of transurethral resections of the prostate (TURP) and an increase use of minimally invasive surgical therapy (MIST) for lower urinary tract symptoms resulting from benign prostatic enlargement. Current results from randomised controlled trials (RCT) and methodologically sound prospective studies suggest that some of the proposed procedures have the potential to replace TURP.

Objective

To determine the contemporary status of TURP and of the currently most commonly applied transurethral MISTs: (1) bipolar TURP, (2) bipolar transurethral vaporisation of the prostate (bipolar TUVP), (3) holmium laser enucleation of the prostate (HoLEP), and (4) potassium-titanyl-phosphate (KTP) laser vaporisation of the prostate.

Evidence acquisition

This meta-analysis was based on a systematic Medline search assessing the period 1997–2009. All RCTs comparing TURP and the most commonly discussed ablative treatments were included. The end points of our analyses were functional outcomes and treatment-related adverse events.

Evidence synthesis

Twenty-seven publications involving 23 different RCTs with a total of 2245 patients provided the highest level of evidence available (level 1b) and were fully assessed. Meta-analysis was conducted with SAS v.9.1.3 (SAS Institute, Cary, NC, USA). Forest plots were produced using the R software. Pooled odds ratios and 95% confidence intervals were calculated between various operative techniques versus TURP. Functional results between the specific transurethral procedures versus TURP were summarised as differences in means.

Conclusions

This meta-analysis demonstrates statistically comparable efficacy and overall morbidity for MISTs versus contemporary TURP. Type, category (minor vs major), and the number of complications (safety profile) vary specifically for each of the different transurethral techniques. We feel that the individual patient's clinical profile should be carefully assessed to identify the most appropriate transurethral technique.     

In vivo assessment of antiemetic drugs and mechanism of lycorine-induced nausea and emesis

Lycorine is the main alkaloid of many Amaryllidaceae and known to cause poisoning with still unknown mechanisms. Longer lasting toxicological core symptoms of nausea and emesis may become a burden for human and animal patients and may result in substantial loss of water and electrolytes. To optimise the only empirical symptomatic antiemetic drug treatment at present, it is important to elucidate the causative involved targets of lycorine-induced emesis. Therefore, in the current study, we have tested the actions of a various antiemetic drugs with selective receptor affinities on lycorine-induced nausea and emesis in vivo in dogs. Beagle dogs were pre-treated in a saline vehicle-controlled crossover and random design with diphenhydramine, maropitant, metoclopramide, ondansetron or scopolamine prior lycorine administration (2 mg/kg subcutaneously). In vivo effects were assessed by a scoring system for nausea and emesis as well as by the number and lag time of emetic events for at least 3 h. Moreover, plasma pharmacokinetic analysis was carried out for ondansetron before and after lycorine injection. The data show that histaminergic (H₁), muscarinic and dopaminergic (D₂) receptors are presumably not involved in lycorine-induced emetic effects. While ondansetron significantly reduced the number of emetic events, lycorine-induced emesis was completely blocked by maropitant. Only ondansetron also significantly decreased the level of nausea and was able to prolong the lag time until onset of emesis suggesting a preferential participation of 5-HT₃ receptors in lycorine-induced nausea. Thus, it is the first in vivo report evidencing that predominantly neurokinin-1 (NK₁) and to a lesser extent 5-hydroxytryptamine 3 (5-HT₃) receptors are involved in lycorine-induced emesis facilitating a target-oriented therapy.     

Triptolide in the treatment of psoriasis and other immune-mediated inflammatory diseases

Apart from cancer chronic (auto)immune-mediated diseases are a major threat for patients and a challenge for physicians. These conditions include classic autoimmune diseases like systemic lupus erythematosus, systemic sclerosis and dermatomyositis and also immune-mediated inflammatory diseases such as rheumatoid arthritis and psoriasis. Traditional therapies for these conditions include unspecific immunosuppressants including steroids and cyclophosphamide, more specific compounds such as ciclosporin or other drugs which are thought to act as immunomodulators (fumarates and intravenous immunoglobulins). With increasing knowledge about the underlying pathomechanisms of the diseases, targeted biologic therapies mainly consisting of anti-cytokine or anti-cytokine receptor agents have been developed. The latter have led to a substantial improvement of the induction of long term remission but drug costs are high and are not affordable in all countries. In China an extract of the herb Tripterygium wilfordii Hook F. (TwHF) is frequently used to treat autoimmune and/or inflammatory diseases due to its favourable cost-benefit ratio. Triptolide has turned out to be the active substance of TwHF extracts and has been shown to exert potent anti-inflammatory and immunosuppressive effects in vitro and in vivo. There is increasing evidence for an immunomodulatory and partly immunosuppressive mechanism of action of triptolide. Thus, compounds such as triptolide or triptolide derivatives may have the potential to be developed as a new class of drugs for these diseases. In this review we summarize the published knowledge regarding clinical use, pharmacokinetics and the possible mode of action of triptolide in the treatment of inflammatory diseases with a particular focus on psoriasis.     

Single dose pharmacokinetics of the transdermal rotigotine patch in patients with impaired renal function

AIM

To evaluate the influence of different stages of chronic renal insufficiency on the pharmacokinetics and safety/tolerability of the transdermally applied dopamine agonist rotigotine in an open label group comparison including 32 subjects (healthy, mild, moderate or severe impairment of renal function and patients with end-stage renal insufficiency requiring haemodialysis).

METHODS

All subjects received a single transdermal 10 cm² patch (24 h patch-on period) containing 4.5 mg rotigotine (nominal drug release 2 mg 24 h⁻¹). Main evaluations included relative bioavailability and renal elimination of rotigotine and its metabolites.

RESULTS

Point estimates for the ratios between the groups with moderate to severe renal impairment and healthy subjects for the pharmacokinetic parameters AUC(0,t_last) and C_max for the active substance unconjugated rotigotine were near 1:0.88 for AUC and 0.93 for C_max for moderate renal impairment, 1.14 and 1.18 for severe renal impairment and 1.05 and 1.25 for end-stage renal insufficiency requiring haemodialysis. There was no correlation of these parameters with creatinine clearance. The amount of unconjugated rotigotine excreted into urine and renal clearance decreased with increasing severity of renal insufficiency but had no observable effect on total clearance as the amounts excreted were below 1% of the administered dose. Occurrence of adverse events did not increase with the degree of renal insufficiency.

CONCLUSIONS

The pharmacokinetic profiles of unconjugated rotigotine were similar in healthy subjects and subjects with impaired renal function indicating that no dose adjustments are required for transdermal rotigotine in patients with different stages of chronic renal insufficiency including patients on haemodialysis.