Lower extremity reconstruction after necrotising fasciitis and necrotic skin lesions using a porcine-derived skin substitute.

Seven consecutive clinical cases of necrotising fasciitis or necrotic skin lesions (42-78 years old; average 65.0 years of age, three females and four males) due to group A Streptococcus, group B Streptococcus, methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa in the lower extremities, who demonstrated rapid systemic symptoms, were investigated for the usefulness of a bilayer artificial dermis, derived from porcine tendons, over 4 +/- 2.4 years (1-7 years). All surgical debridement was confirmed as sufficiently deep and wide for clinically infected lesions and artificial dermis was applied to all wounds. The average interval to secondary split-thickness skin grafting was about 17.5 days (17.5 +/- 2.44 days, 21 days max., 14 days min.) and the average thickness was 0.009 +/- 0.0022 in. (range: 0.006 - 0.012 in.). No clinical problems were noted during the application of the artificial dermis and the subsequent skin grafting. Since, the donated skin graft was thin, the morbidity was minimised. The use of artificial dermis after extensive surgical debridement in necrotising fasciitis was easy and effective. Local or systemic infection was negligible.     

The future of 5-HT1A receptor agonists. (arylpiperazine derivatives)

Mitsukuni Murasaki and Sadanori Miura: The Future of 5-HT_1A Receptor Agonists. (Aryl-Piperazine Derivatives) Prog. Neuro- Psychopharmacol-& Biol Psychiat, 1992, 16(6): 833–845.

1. 1. At present the dominant position among anti-anxiety medications has changed from meprobamate to the benzodiazepine derivatives.

2. 2. In order to avoid benzodiazepine's (BZ) undesirable side effects such as impairment of psycho-motor function, memory impairment, low dose dependence and withdrawal symptoms, a third generation anxiolytic agent, buspirone, the focus of the aryl-piperazine group of anti-anxiety agents, has been introduced recently.

3. 3. Aryl-piperazine derivatives work as 5-HT_1A receptor partial agonists and are known as serotonin normalizers.

4. 4. Therefore, they are expected to have not only an anxiolytic function but also an anti-depressant effect as well.

5. 5. A characteristic of the aryl-piperazine derivatives is that they have no sedative and muscle relaxant effects, and they do not have BZ's undesirable side-effects, especially in regard to withdrawal symptoms. However they have a rather weak anxiolytic action and a slow onset of action.

6. 6. Aryl-piperazine derivatives will not take the place of BZ, but the use of BZ and buspirone as bridge medications, making the most of the strong points of both, can be proposed as a way to compensate for their respective disadvantages.

Pharmacokinetic study of iminodibenzyl antipsychotic drugs,clocapramine and Y-516 in dog and man

The pharmacokinetic properties of the iminodibenzyl antipsychotic drugs clocapramine (CCP, 3-chloro-5-[3-(4-carbamoyl-4-piperidino piperidino) propyl]-10, 11-dihydro-5H-dibenzo[b, f]azepine) and Y-516 (3-chloro-5-[3-(2-oxo-1, 2, 3, 5, 6, 7, 8, 8a-octahydroimidazo [1,2-a] pyridine-3-spiro-4-piperidino) propyl]-10, 11-dihydro-5H-dibenzo[b, f]azepine) were investigated in dog and man. Dogs were administered CCP and Y-516 intravenously, intraperitoneally, and orally, and the concentrations of the parent drugs and their metabolites in the plasma and urine were determined. Half-life (t1/2) was approximately the same by all three administration routes, being approximately 5 h for CCP and 3 h for Y-516. Bioavailability following oral administration was 0.16±0.01 (mean ± SD, n=3) for CCP and 0.29±0.07 for Y-516. The fractions of dose absorbed following oral administration were 0.43±0.07 and 0.79±0.24, and the fractions of dose metabolized in the liver due to the first-pass effect were 0.63±0.05 and 0.63±0.04 for CCP and Y-516, respectively. Y-516 was detected in the plasma after intraperitoneal and oral administration of CCP. The ratio of the AUC of Y-516 to that of CCP was 0.06 following intraperitoneal administration and 0.40 following oral administration. This indicated that while the metabolism of CCP into Y-516 may occur partly in the liver due to the first-pass effect, it occurs mostly within the gastrointestinal tract itself or its mucosa. When CCP and Y-516 were given orally to man, the plasma concentrations of both parent drugs increased in a dose-dependent manner. The t1/2 of CCP at a dose of 50 mg was 46±6 h (n=3) while that of Y-516 at a dose of 25 mg was 15±2 h (n=5), so that elimination from the circulation was slower than in the dog in both cases. As in the dog, Y-516 was detected in the plasma following administration of CCP, but its concentration was approximately one fifth that of CCP and lower than that found in the dog. From the ratios of Y-516 produced upon oral administration of CCP in dog and man, we concluded that Y-516 is involved to a considerable degree in the pharmacological action of CCP in the dog and, though to a lesser degree, in man as well.     

A multicenter phase II study of carboplatin and paclitaxel with a biweekly schedule in patients with advanced non-small-cell lung cancer: Kyushu thoracic oncology group trial

Purpose: This multicenter phase II study was conducted to investigate the efficacy and safety of carboplatin in combination with paclitaxel administered according to a biweekly schedule as a first-line chemotherapy for advanced non-small-cell lung cancer (NSCLC). Patients and methods: Eligibility criteria included histologically or cytologically confirmed NSCLC (stage IIIb or IV), no prior treatment, and measurable or evaluable disease. Paclitaxel (140 mg/m²) was administered intravenously on day 1, in combination with carboplatin at an area under the concentration time curve (AUC) of 3, every 2 weeks. Results: Seventy-four patients (45 men) with a median age of 62 years (range 40–74) and a median ECOG performance status of 1 (range 0–2) were enrolled. The response rate was 35.1% [95% confidence interval (CI): 24.4–47.1%], with 26 partial responses. The median survival was 357 days, and the median time to progression was 218 days. Toxicity was generally mild; National Cancer Institute-Common Toxicity Criteria (NCI-CTC) grades 3 and 4 neutropenia was observeded in 50.0% of the patients, and grades 3 and 4 nausea/vomiting in 4.1%. Conclusions: Biweekly carboplatin combined with paclitaxel demonstrated anti-tumor activity in advanced NSCLC, with response and survival rates similar to those of carboplatin combined with paclitaxel administered every 3 weeks but with a more favorable toxicity profile, and the present data indicate that the regimen is suitable for use on an outpatient basis.     

Does short-term cessation of smoking before lung resections reduce the risk of complications?

BackgroundSmoking cessation is a highly important preparation before thoracic surgery. We examined the effects of short-term smoking cessation intervention before pulmonary resection on postoperative pulmonary complications (PPCs).MethodsA retrospective analysis of prospectively collected data was performed for 753 patients who underwent curative surgical resection for thoracic malignancy at 3 institutions. Patients with a smoking history were instructed to quit smoking. After confirming smoking cessation by at least four weeks before surgery, surgical resection was performed. Subjects were classified into three groups based on their smoking status: abstainers (anyone who had stopped smoking for at least 4 weeks but less than 2 months), former smokers (anyone who had abstained from smoking for more than two months prior to surgery), and never smokers (those who had never smoked). We examined the relationship between the preoperative smoking status and PPCs.ResultsSurgery was performed for 660 primary lung cancers and 93 metastatic lung tumors. The smoking statuses were classified as follows: abstainers (n=105, 14%), former smokers (n=361; 48%) and never smokers (n=287, 38%). The incidence of PPCs among abstainers, former smokers and never smokers was 15%, 8% and 6%, respectively (P=0.01). The mean duration of post-operative chest tube drainage among abstainers, former smokers and never smokers was 3.2, 2.2 and 2.2 days, respectively (P=0.04). The mean post-operative hospital stay among abstainers, former smokers and never smokers was 12.1, 10.6 and 10.2 days, respectively (P=0.07). There was no 30-day mortality in the cohort.ConclusionsShort-term smoking cessation intervention did not enough reduce the PPCs as much as in former or never smokers.     

No evidence of association between 8q24 and susceptibility to nonsyndromic cleft lip with or without palate in Japanese population

Objective : Recent genome-wide association studies identified susceptibility loci for nonsyndromic cleft lip with or without cleft palate (NSCL±P) on 8q24.21, 10q25.3, 13q31.1, 15q13.3, 17q22, and 18q22 in populations of European origin. The purpose of this study was to determine, using DNA samples, whether 8q24.21 was a susceptibility locus for the development of NSCL±P in Japanese patients. Methods : We used DNA from 167 Japanese NSCL±P patients (45 cleft lip without cleft palate and 122 cleft lip with cleft palate patients) and 190 Japanese unaffected control individuals. We performed an association study using 13 single nucleotide polymorphisms (SNPs) selected on the 8q24.21 locus. Genotyping of each SNP was carried out by direct sequencing of genomic DNA. Additionally, a haplotype block was constructed using the selected SNPs. Results : The 13 selected SNPs were successfully genotyped in 357 individuals. The p values obtained were not low enough to indicate a significant association between the haplotypes and the development of NSCL±P in this population. Conclusions : Our results suggest that the 8q24.21 locus is not associated with susceptibility to NSCL±P in Japanese patients and provide further evidence that ethnicity is a strong factor in determining susceptibility loci, albeit using a limited number of samples. Further studies are needed to identify regions involved in the development of NSCL±P in the Japanese population.     

Quality of Pediatric Second-degree Burn Wound Scars Following the Application of Basic Fibroblast Growth Factor: Results of a Randomized, Controlled Pilot Study

Pediatric burn wounds present unique challenges. Second-degree burns may increase in size and depth, raising con- cerns about healing and long-term scarring. Results of a clinical study in adults with second-degree burn wounds sug- gest that application of basic fibroblast growth factor (bFGF) may reduce time to second-intention healing and result in a more cosmetically acceptable scar. To evaluate the effect of this treatment on pediatric patients with deep second- degree burn wounds, 20 pediatric patients ranging in age from 8 months to 3 years (average 1 year, 3 months [± 6 months]) with a total of 30 burn wounds from various causes were allocated either the growth factor (treatment, n = 15) or an impregnated gauze treatment (control, n = 15). Wounds still exudative (not healed) after 21 days were covered with a split-thickness skin graft. All wounds were clinically assessed until healed and after 1 year. A moisture meter was used to assess scars of wounds healing by secondary intention. A color meter was used to evaluate grafted wounds. Five wounds in each group required grafting. Skin/scar color match was significantly closer to 100% in the treatment than in the control group (P <0.01). Wounds not requiring grafting were no longer exudative after 13.8 (± 2.4) and 17.5 (± 3.1) days in the treatment (n = 10) and control group (n = 10), respectively (P <0.01). After 1 year, scar pigmentation, pliability, height, and vascularity were also significantly different (P <0.01) between the groups. Hypertrophic scars developed in 0 of 10 wounds in the treatment and in three of 10 wounds in the control group, and effective contact coefficient, tran- sepidermal water loss, water content, and scar thickness were significantly greater in control group (P <0.01). Both the short- and long-term results of this treatment in pediatric burn patients are encouraging and warrant further research.