The feasibility of local anesthesia for the surgical treatment of umbilical hernia: a systematic review of the literature.

BACKGROUND: Yearly approximately 4500 umbilical hernias are repaired in The Netherlands, mostly under general anesthesia. The use of local anesthesia has shown several advantages in groin hernia surgery. Local anesthesia might be useful in the treatment of umbilical hernia as well. However, convincing evidence is lacking. We have conducted a systematic review on safety, feasibility, and advantages of local anesthesia for umbilical hernia repair. METHODS: A systematic review was conducted according to the PRISMA guidelines. Outcome parameters were duration of surgery, surgical site infection, perioperative and postoperative complications, postoperative pain, hernia recurrence, time before discharge, and patient satisfaction. RESULTS: The systematic review resulted in nine included articles. Various anesthetic agents were used, varying from short acting to longer acting agents. There was no consensus regarding the injection technique and no conversions to general anesthesia were described. The most common postoperative complication was surgical site infection, with an overall percentage of 3.4%. There were no postoperative deaths and no allergic reactions described for local anesthesia. The hernia recurrence rate varied from 2 to 7.4%. Almost 90% of umbilical hernia patients treated with local anesthesia were discharged within 24 h, compared with 47% of patients treated with general anesthesia. The overall patient satisfaction rate varied from 89 to 97%. CONCLUSION: Local anesthesia for umbilical hernia seems safe and feasible. However, the advantages of local anesthesia are not sufficiently demonstrated, due to the heterogeneity of included studies. We, therefore, propose a randomized controlled trial comparing general versus local anesthesia for umbilical hernia repair.

Role of Erbium:YAG laser in the treatment of aged skin.

Laser resurfacing procedures in actinic skin damage and the treatment of disorders associated with skin ageing are becoming more popular. For both purposes Erbium:YAG laser-technology enables us to perform a highly precise skin ablative work, which can be most helpful in the removal of circumscribed skin lesions of ageing skin as well as in larger skin resurfacing procedures. In most circumstances, superficial skin ablation is not technically demanding, is not associated with major discomfort, and can be controlled with precision. Tissue sparing ablation is of special value in the treatment of disorders in atrophic skin of elderly patients or in more delicate areas, where it can avoid prolonged healing and unwarranted side-effects.

Calcipotriol solution for the treatment of scalp psoriasis: evaluation of efficacy, safety and acceptance in 3,396 patients.

BACKGROUND: Psoriasis of the scalp is a very common disease, cosmetically disturbing and therapeutically difficult to manage. OBJECTIVE: The aim of our study was to investigate the efficacy, safety and cosmetic acceptance of calcipotriol solution in a large number of patients with mild to moderate scalp psoriasis and to compare this treatment with previous therapies used. METHODS: In this multicentre prospective observational cohort study 3,396 patients were treated with calcipotriol solution (50 microg/ml) twice daily over an 8-week period either alone or in combination with other treatments. The psoriasis scalp severity index (PSSI) and investigator/patient global assessment were used for the evaluation of clinical response. RESULTS: All psoriasis severity parameters measured were reduced with a significant decrease in PSSI scores from 18.4 to 5.6 after 8 weeks of therapy (p < 0.001). About 80% of the patients showed very good or good clinical improvement. Combination of calcipotriol solution with other treatment modalities e.g. corticosteroids or salicylic acid, showed an increased treatment response. In only 2.4% of the patients side effects occurred (e.g. irritation). CONCLUSION: Calcipotriol solution is an effective, safe, well-tolerated and cosmetically acceptable treatment modality. By patients and physicians, this treatment was found to be a valuable supplement to previously available and established treatments for scalp psoriasis.

Kinetics and dose-response of photosensitivity in cream psoralen plus ultraviolet A photochemotherapy: comparative in vivo studies after topical application of three standard preparations.

BACKGROUND: Topical photochemotherapy with bath psoralen plus ultraviolet (UV) A irradiation (PUVA) has been developed to reduce possible side-effects of oral PUVA therapy. Although the efficacy of bath PUVA therapy appears to be similar to oral PUVA therapy, provision of bathing facilities has obvious economic, logistic and sanitary implications. Cream PUVA therapy has recently been developed as a variation of topical PUVA. OBJECTIVES: To understand the photobiological effects and to increase the safety and effectiveness of this novel topical PUVA therapy, we assessed the kinetics and dose-response of phototoxicity of 8-methoxypsoralen (8-MOP) cream in order to develop a treatment schedule for this treatment option. METHODS: Ninety-eight patients (63 men and 35 women) undergoing cream PUVA therapy were studied. The phototoxic properties of topically applied 8-MOP in three different water-in-oil creams as vehicles were assessed. In a dose-response study, four concentrations of 8-MOP cream (0.0006-0.005%) were used for determination of the minimal phototoxic dose (MPD). The kinetics of photosensitization were tested by determination of MPDs after different application times of 8-MOP cream (10, 20, 30 and 60 min). The persistence of phototoxicity was assessed by UVA exposure at defined time intervals after application of 8-MOP cream (0, 30, 60 and 120 min). RESULTS: The concentration required to produce sufficient but not undue photosensitization of the skin was 0.001% 8-MOP. The duration of application leading to the lowest MPD was 30 min. Greatest photosensitization was achieved when UVA irradiation was performed between 0 and 30 min after 8-MOP removal. These findings showed no significant difference between the three vehicles used. CONCLUSIONS: Based on our data we recommend application of 0.001% 8-MOP in a water-in-oil cream for 30 min. Irradiation with UVA should be performed within 30 min after removal of 8-MOP cream, as there is a rapid decrease in photosensitivity thereafter.

Cream psoralen plus ultraviolet A therapy for granuloma annulare.

BACKGROUND: Treatment modalities for granuloma annulare (GA) often remain unsatisfactory or can be accompanied by potentially hazardous side-effects. Psoralen plus ultraviolet (UV) A (PUVA) bath photochemotherapy has been reported to be highly effective in the treatment of GA. Another form of topical PUVA therapy, using 8-methoxypsoralen-containing cream or gel preparations, has been proven to be as effective as bath PUVA therapy in the treatment of palmoplantar dermatoses. OBJECTIVES: To assess the efficacy of cream PUVA photochemotherapy in patients with GA. METHODS: Five patients with GA were treated. The diagnosis was confirmed by pretreatment skin biopsies. Cream PUVA therapy was performed four times a week: the mean number of treatments was 26 (range 17-40) and mean cumulative UVA dose was 55.9 J cm-2 (range 18.2-109.2). RESULTS: Cream PUVA photochemotherapy induced significant clinical improvement (one patient) or clearance (four patients) of GA in all patients. Clearance was documented clinically and histopathologically. CONCLUSIONS: Cream PUVA phototherapy can be highly effective in patients affected by localized forms of GA.

[Treatment of plaque-type psoriasis with cream-PUVA therapy]. / Creme-PUVA-Photochemotherapie bei chronisch stationärer Psoriasis vulgaris.

PUVA-bath therapy has developed into first line topical PUVA therapy in the treatment of psoriasis. Because of logistical and economic problems, bath PUVA may be difficult to administer. Recently, cream-PUVA therapy has been described as an alternative mode of topical therapy. We treated two patients with moderate plaque-type psoriasis with this new topical approach. 0,0006% 8-methoxypsoralen cream was applied for 1 hour, directly followed by increasing doses of UVA. The number of treatments needed for clearance were 34 and 40. The cumulative UVA dosages were 71.6 and 84 J/cm(2) respectively. Our data document that cream-PUVA therapy is an effective and safe variation of topical PUVA therapy, which may develop into first line photochemotherapy for patients with moderate plaque-type psoriasis.

PUVA-cream photochemotherapy for the treatment of localized scleroderma.

BACKGROUND: The efforts to treat localized scleroderma, including therapies with potentially hazardous side effects, are often unsatisfactory. Recently, PUVA-bath photochemotherapy has been proven highly effective in the treatment of localized scleroderma. Another form of topical PUVA therapy, 8-methoxypsoralen (8-MOP) containing cream or gel preparations, has been proven to be as effective as PUVA-bath therapy for palmoplantar dermatoses. OBJECTIVE: We sought to assess the efficacy of PUVA-cream photochemotherapy in patients with localized scleroderma. METHODS: Four patients with localized scleroderma were included in the study. Diagnosis was confirmed by 20 MHz ultrasound assessment as well as pretreatment skin biopsy specimens from lesional skin. PUVA-cream therapy was performed 4 times a week; all patients received 30 treatments. RESULTS: PUVA-cream photochemotherapy induced significant clinical improvement or clearance of localized scleroderma in all patients. Clearance was documented by clinical features as well as by 20 MHz ultrasound and histopathologic analysis. CONCLUSION: PUVA-cream phototherapy can be highly effective in patients with localized scleroderma even if previous therapy was unsuccessful.

Perinuclear localization of the protein-tyrosine phosphatase SHP-1 and inhibition of epidermal growth factor-stimulated STAT1/3 activation in A431 cells.

The SH2 domain protein-tyrosine phosphatase SHP-1 has been shown earlier to bind to the epidermal growth factor receptor and to have the capacity for receptor dephosphorylation. New bi- and tricistronic expression vectors (pNRTIS-21 and pNRTIS-33, respectively) based on the tetracycline system were constructed and employed to generate stable cell lines with inducible expression of SHP-1. Inducible overexpression of SHP-1 in A431 cells led to attenuation of epidermal growth factor (EGF) receptor autophosphorylation and of EGF-induced DNA binding of 'signal transducers and activators of transcription' (STAT) 1 and 3. SHP-1 was localized in the cytoplasm with an enrichment in the perinuclear compartment. Association of SHP-1 with perinuclear structures may form the basis for a partial cofractionation with nuclei observed in different types of transfected cells and also with endogenous SHP-1 in U-937 cells. Treatment of SHP-1-overexpressing A431 cells or of HaCaT human keratinocytes expressing SHP-1 endogenously with the Ca2+-ionophore A23187 resulted in partial nuclear accumulation of SHP-1. Thus, SHP-1 may interact with substrates or regulatory proteins in perinuclear or nuclear structures.

[The UV record. Document for quality control, therapy planning and risk assessment in dermatologic photo- and photochemotherapy]. / Der UV-Pass. Instrument der Qualitätskontrolle, Therapieplanung und Risikoabschätzung bei dermatologischer Photo- und Photochemotherapie.

Ultraviolet (UV-) radiation therapy as a mono- or combination therapy (UV-A, UV-A1, UV-B, SUP, UV-B311) or as photochemotherapy with photosensitization (systemic PUVA-, bath PUVA-, topical PUVA-therapy) are successfully used for the treatment of several dermatological disorders. Long-term side effects of natural UV (sun light) include photoaging and induction of skin tumors. At present, the relevance of in-vitro findings of potential tumor induction in animals through therapeutic levels of UV radiation is a matter of debate. To assess these risks, information on treated location, kind of UV radiation and cumulative UV doses are required. Practically this information is barely accessible. This makes decisions on possible therapies difficult. To solve this problem we propose to use an "UV pass". At the end of each UV radiation cycle, the body location, the type of radiation and the cumulative dose are documented and this pass is given to the patient. This will improve the information transfer if the doctor is changed, as well as facilitating decisions about certain therapies and calculation of long-term risks of UV radiation. Finally it will improve the quality of UV photo- and photochemotherapy.

Dipetalogastin, a potent thrombin inhibitor from the blood-sucking insect. Dipetalogaster maximus cDNA cloning, expression and characterization.

A cDNA coding for the thrombin inhibitor dipetalogastin has been isolated from a stomach library of Dipetalogaster maximus, a blood-sucking insect. The open reading frame of the cloned inhibitor cDNA codes for a protein of 344 amino-acid residues. Sequence analysis reveals the existence of three repeated homologous main regions, indicating that the inhibitor consists of three domains. Each domain shows a double-headed structure with an internal sequence homology like rhodniin, the thrombin inhibitor from the blood-sucking insect Rhodnius prolixus. Peptide sequence comparisons of the deduced amino-acid sequence exhibit a high homology of the domains I and II to the natural inhibitor dipetalogastin from the stomach content of D. maximus and to rhodniin, respectively. Significant sequence similarities to Kazal-type inhibitors, like the conserved sequence CGXDXXTYXNXC and several cysteine residues, indicate that the thrombin inhibitor from D. maximus is a further blood-sucking insect which belongs to the Kazal-type family (besides rhodniin). A biologically active recombinant protein corresponding to domain II of the dipetalogastin cDNA was expressed in Escherichia coli. The isolated recombinant dipetalogastin with a molecular mass of 12.91 kDa has proved to be a specific thrombin inhibitor similar to its natural counterpart as well as rhodniin and hirudin. The Ki value of the recombinant dipetalogastin was determined to be 49.3 +/- 22.28 fM.

Phototherapy for atopic eczema with narrow-band UVB.

Management of atopic dermatitis has been less than satisfactory. Conventional therapy has not been particularly successful, and prolonged use of topical corticosteroids and systemic immunosuppressant drugs (eg, corticosteroids, cyclosporine, azathioprine) can result in severe cutaneous and systemic effects. We decided to evaluate the effect of UVB at 311 nm to treat 5 patients with moderate to severe atopic dermatitis. In each patient a mean cumulative dose of 9.2 J/cm2 was applied over a mean of 19 irradiations. Narrow-band UVB notably reduced atopic dermatitis after 3 weeks in all patients.

Phototoxic effects of Hypericum extract in cultures of human keratinocytes compared with those of psoralen.

Extracts of Hypericum perforatum (St. John's wort) are used in the treatment of depression. They contain the plant pigment hypericin and hypericin derivates. These compounds have light-dependent activities. In order to estimate the potential risk of phototoxic skin damage during antidepressive therapy, we investigated the phototoxic activity of hypericin extract using cultures of human keratinocytes and compared it with the effect of the well-known phototoxic agent psoralen. The absorbance spectrum of our Hypericum extract revealed maxima in the whole UV range and in parts of the visible range. We cultivated human keratinocytes in the presence of different Hypericum concentrations and irradiated the cells with 150 mJ/cm2 UVB, 1 J/cm2 UVA or 3 h with a white light of photon flux density 2.6 mumol m-2 s-1. The determination of the bromodeoxyuridine incorporation rate showed a concentration- and light-dependent decrease in DNA synthesis with high hypericin concentrations (> or = 50 micrograms/mL) combined with UVA or visible light radiation. In the case of UVB irradiation a clear phototoxic cell reaction was not detected. We found phototoxic effects even with 10 ng/mL psoralen using UVA with the same study design as in the case of the Hypericum extract. These results confirm the phototoxic activity of Hypericum extract on human keratinocytes. However, the blood levels that are to be expected during antidepressive therapy are presumably too low to induce phototoxic skin reactions.

Pharmacological characterization of CCKB receptors in human brain: no evidence for receptor heterogeneity.

In this paper, cholecystokinin (CCK) B-type binding sites were characterized with receptor binding studies in different human brain regions (various parts of cerebral cortex, basal ganglia, hippocampus, thalamus, cerebellar cortex) collected from 22 human postmortem brains. With the exception of the thalamus, where no specific CCK binding sites were found, a pharmacological characterization demonstrated a single class of high affinity CCK sites in all brain areas investigated. Receptor densities ranged from 0.5 fmol/mg protein (hippocampus) to 8.4 fmol/mg protein (nucleus caudatus). These CCK binding sites displayed a typical CCKA binding profile as shown in competition studies by using different CCK-related compounds and non peptide CCK antagonists discriminating between CCKA and CCKB sites. The rank order of agonist or antagonist potency in inhibiting specific sulphated [propionyl-3H]cholecystokinin octapeptide binding was similar and highly correlated for the brain regions investigated as demonstrated by a computer-assisted analysis. Therefore it is concluded that CCKB binding sites in human cerebral cortex, basal ganglia, cerebellar cortex share identical ligand binding characteristics.

In vitro and in vivo effects of photodynamic therapy in cutaneous T cell lymphoma.

Photodynamic therapy consists of the combination of photosensitizers absorbing light in the visible spectral region and irradiation with light of corresponding wavelengths. We analysed its effects in comparison to PUVA treatment on cell lines MyLA and HuT78, established from patients with cutaneous T cell lymphomas. Proliferation was reduced to 50% by exposure to 7.5 J/cm2 UV-A (= ED50). This effect was increased more than 10-fold in the presence of 10 micrograms/ml 8-methoxypsoralen. The ED50 for photodynamic therapy using 630 nm light emitted by a dye laser and 10 micrograms/ml Photosan-3 was found to be about 1 J/cm2. In vivo fluorescence recordings during topical photodynamic therapy of mycosis fungoides lesions showed photo-bleaching and thus documented the triggering of photochemical reactions. Our observations document the capability of photodynamic therapy to inhibit proliferation of transformed T cells similar to PUVA, pointing out its potential in the treatment of cutaneous T cell lymphomas.