Late toxicities in concurrent chemoradiotherapy using high-dose-rate intracavitary brachytherapy plus weekly cisplatin for locally advanced cervical cancer: a historical cohort comparison against two previous different treatment schemes.

PURPOSE: To determine the long-term toxicity of concurrent chemoradiotherapy (CCRT), using high-dose rate intracavitary brachytherapy (HDRICB) compared to radiation (RT) alone in patients with advanced cervical cancer using a control-cohort study. METHODS: A total of 332 cases of Stage IIB-III disease were included in this comparative study. Seventy-three patients were treated with a 3-insertion schedule and labeled group A, whereas the other 146 patients with a 4-insertion schedule became group B. One hundred and thirteen patients treated by a 4-insertion protocol with concurrent weekly cisplatin were labeled group C. RESULTS: The cumulative rate of grade 2 or above rectal complication was 13.7% for group A, 9.6% for the group B and 15.9% for group C (p = 0.76), whereas the grade 3 to 4 non-rectal radiation-induced intestinal injury was 6.8% for group A, 6.2% for group B and 9.7% for group C (p = 0.20). Grade 2 to 4 late bladder toxicity was higher in group C, with the cumulative rate being 5.5% for group A, 4.8% for group B and 15.0% for group C (p = 0.004). The independent factor for a rectal complication was the occurrence of a bladder complication (p = 0.01, hazard ratio 3.06). The independent factors for bladder complications were the use of CCRT (p = 0.01, hazard ratio 2.08), and the occurrence of rectal complications (p = 0.02, hazard ratio 2.77). CONCLUSIONS: When treating advanced cervical cancer, HDRICB consisting of four 6 Gy insertions and weekly cisplatin shows a trend of increasing late bladder complications. The interval between drug administration and HDRICB should be kept long enough to avoid any synergistic effect of both regimens.

Comparison of a new modified laparoscopic presacral neurectomy and conventional laparoscopic presacral neurectomy in the treatment of midline dysmenorrhea.

OBJECTIVE: To describe a newly modified laparoscopic presacral neurectomy procedure and to evaluate the long-term benefits of the surgery as a treatment for midline dysmenorrhea. METHOD: Eighty-eight reproductive female patients with midline dysmenorrhea were enrolled in the non-randomized prospective study. There were fifty-five patients in the modified laparoscopic presacral neurectomy (MLPSN) group and thirty-three patients in the conventional laparoscopic presacral neurectomy (LPSN) group. All patients received post-surgery follow-up of more than eight years for evaluation with respect to pain relief, recurrence, and complications. RESULTS: Upon receipt of surgery, the MLPSN and the LPSN groups both demonstrated a significant decrease (P<0.001) in the mean pain score when compared to the pre-surgery mean pain scores. However, the probability of recurrence during the eight years of follow-up was 81.8% (27 patients) in the LPSN group, compared to 43.6% (24 patients) in the MLPSN group, resulting in a significantly lower long-term recurrence rate in the MLPSN group, compared to the LPSN group (P<0.05). No patients in the MLPSN group had long-term complications and one patient had constipation after surgery in the LPSN group. CONCLUSION: The modified laparoscopic presacral neurectomy procedure provides an alternative for those patients who suffer intractable midline dysmenorrhea. This surgery is relatively simple and safe and could result in a satisfactory long-term outcome in the intervention of midline dysmenorrhea.

Protein Information Resource: a community resource for expert annotation of protein data.

The Protein Information Resource, in collaboration with the Munich Information Center for Protein Sequences (MIPS) and the Japan International Protein Information Database (JIPID), produces the most comprehensive and expertly annotated protein sequence database in the public domain, the PIR-International Protein Sequence Database. To provide timely and high quality annotation and promote database interoperability, the PIR-International employs rule-based and classification-driven procedures based on controlled vocabulary and standard nomenclature and includes status tags to distinguish experimentally determined from predicted protein features. The database contains about 200,000 non-redundant protein sequences, which are classified into families and superfamilies and their domains and motifs identified. Entries are extensively cross-referenced to other sequence, classification, genome, structure and activity databases. The PIR web site features search engines that use sequence similarity and database annotation to facilitate the analysis and functional identification of proteins. The PIR-Inter-national databases and search tools are accessible on the PIR web site at http://pir.georgetown.edu/ and at the MIPS web site at http://www.mips.biochem.mpg.de. The PIR-International Protein Sequence Database and other files are also available by FTP.

Effects of leflunomide and cyclosporine on myocutaneous allograft survival in the rat.

The immunosuppressive effects of leflunomide and cyclosporine were evaluated in a rat neurovascularized myocutaneous allograft model. Inbred Brown-Norway and Lewis rats were served as donors and recipients, respectively. All recipients were observed for 60 days or until allograft rejection occurred. All isograft controls (Lewis to Lewis, n=6) survived uneventfully. All control allografts (n=6) were rejected within 6 days. Allograft recipients (n=6) administered leflunomide (10 mg/kg/24 hr) rejected their allografts in 28.50+/-6.12 days, and allograft recipients (n=6), administered cyclosporine (5 mg/kg/24 hr) rejected their allografts in 24.33+/-10.48 days. When allograft recipients were administered a combination of leflunomide and cyclosporine (10 mg/kg/24 hr and 5 mg/kg/24 hr, respectively), all allografts survived to 60 days with only partial rejection of the skin of one graft. The neuromuscular function of the allografts of the rats receiving combination therapy was comparable to that of the isografts. The combination of leflunomide and cyclosporine controlled myocutaneous allorejection despite a strong immunological challenge.

Combination leflunomide and cyclosporine prevents rejection of functional whole limb allografts in the rat.

Whole rear limbs were transplanted from Brown Norway or Lewis rat donors to Lewis rat recipients (n=6 per group). One group of allograft recipients was treated with leflunomide (10 mg/kg/24 hr/orally) and cyclosporine (5 mg/kg24 hr/orally) starting 2 days before to surgery. Treatment continued for 60 days or until graft rejection. Untreated allografts were rejected over 6-8 days. After isograft transplantation, weight bearing began by day 17-25 after surgery. Sensory function was restored by 50 days after surgery. All allografts in the drug-treated group survived the 60-day period; survival in this group was significantly longer (P=0.0001) than the untreated controls. Weight bearing began by day 30, but was incomplete in two rats at 60 days. Peroneal nerve function was present in half the rats at 60 days after surgery. Leflunomide combined with cyclosporine prevented whole limb allograft rejection across a major histocompatibility barrier.

Homologues of catalytic domains of Cellulomonas glucanases found in fungal and Bacillus glycosidases.

We demonstrate homology between the catalytic domains of exoglucanase (1,4-beta-D-glucan cellobiohydrolase, EC 3.2.1.91) from Cellulomonas fimi and those of endoxylanases (1,4-beta-D-xylan xylanohydrolases, EC 3.2.1.8) from Bacillus sp. strain C-125 and the fungus Cryptococcus albidus; and between the catalytic domains of endoglucanase (1,4-(1,3:1,4)-beta-D-glucan 4-glucanohydrolase, EC 3.2.1.4) from Cellulomonas fimi and exoglucanase II from Trichoderma reesei. These five enzymes apparently evolved by reshuffling of two catalytic domains and several substrate-binding domains.

Reactions of proteins with dehydroalanines.

Reactions of proteins with dehydroalanine or derivatives of dehydroalanine were studied as models for protein crosslinking. Treatment of casein, bovine serum albumin, lysozyme, wool or polylysine with acetamido- and phenylacetamido acrylic acid methyl esters at pH 9-10 converted varying amounts of lysine to lysinoalanine residues. Howver, complete transformation was not achieved. Incomplete reaction is atributed to partial hydrolysis of the esters to the less reactive acrylic acids under the reaction conditions. Similar studies were made of the reactivities of protein SH groups generated by reduction of disulfide bonds by tributylphosphine. The SH groups could be completely alkylated at pH 7.6 in aqueous propanol, as shown by nearly quantitative recovery of lanthionine. Such a procedure might therefore be used to estimate cystine contents of proteins.

A functional model for whole limb transplantation in the rat.

To develop a functional model for the study of whole limb transplantation, inbred Lewis rats were used as both donors and recipients. In this model, the recipient biceps femoris muscle was elevated from its distal attachment to preserve part of the adductor function of the limb after surgery. The tibial, peroneal, and sural branches of the sciatic nerve were anastomosed separately to provide faster and more precise functional recovery. For control sensory evaluation, the saphenous branches of the femoral nerve were not reattached. A flat intramedullary pin stabilized with methyl methacrylate was used to rigidly immobilize the femur. The transplanted limbs started bearing weight at 17 to 22 days. Walking on the plantar surface of the hock and adduction of the toes gradually decreased, and the rats developed a normal walking pattern. Sciatic and tibial function indexes, based on walking track analysis, correlated well with clinical observations. In this study, a new model for limb transplantation was developed that provided good and reliable sensory and ambulatory recovery.

Intramural pregnancy with negative maternal serum beta-hCG. A case report.

BACKGROUND: Intramural pregnancy is the rarest form of ectopic pregnancy. The diagnosis depends upon the sonographic finding of intramural gestational sac-like growth and persistent high beta-human chorionic gonadotropin (beta-hCG) levels after dilatation and curettage. No authors mentioned negative beta-hCG result in such situation. Rarely has the literature contained preoperative sonograms and photographs of postoperative gestational tissue. CASE: A 31-year-old woman presented with vaginal spotting for five months. Six months earlier she underwent dilatation and curettage for blighted ovum at 8 weeks' gestation. Since then, incidental vaginal spotting was noted. Sonography demonstrated an intramural cyst with fetal pole-like growth. Serum beta-hCG, diagnostic dilatation and curettage, and hysteroscopic examination were negative. Laparotomy for excision of the cyst confirmed an intramural pregnancy. CONCLUSION: Because of the long period after fetal wastage, negative serum beta-hCG was noted in this case. Negative serum beta-hCG was unreliable in the exclusion of intramural pregnancy. With the sonographic appearance of intramural gestational sac-like growth, in spite of a negative serum beta-hCG the clinician should be alert to the possibility of intramural pregnancy.

Successful prenatal digoxin therapy for Ebstein's anomaly with hydrops fetalis. A case report.

BACKGROUND: Ebstein anomaly is a rare tricuspid valve anomaly. Some fetuses with Ebstein's anomaly have concurrent severe cardiac function impairment, which results in hydrops fetalis. Most of these fetuses are inevitably terminally ill. No reports have demonstrated the potential prenatal therapy for fetuses under such conditions. CASE: Ebstein's anomaly and hydrops fetalis were detected at 28 weeks' gestation. Tricuspid regurgitation with congestive heart failure was observed. From 28 to 34 weeks' gestation, intrauterine therapy with digoxin, 0.75 mg/d, was administered. The fetal hydrops status improved gradually, while the tricuspid valve regurgitation persisted. At 36 weeks' gestation the fetus was delivered normally. During the neonatal phase, digoxin was continued and gradually tapered off. The tricuspid valve regurgitation and cardiomegaly gradually improved. CONCLUSION: The favorable outcome in this case supports the positive effect of prenatal digoxin therapy for Ebstein's anomaly with hydrops fetalis. In such conditions, upon the appearance of hydrops and congestive cardiac failure, immediate digoxin therapy may be useful. This successful trial encouraged us to manage such fetuses more aggressively.

Laparoscopic radical hysterectomy with low paraaortic, subaortic and pelvic lymphadenectomy. Results of short-term follow-up.

OBJECTIVE: To describe a detailed operative procedure for type III laparoscopic radical hysterectomy with bilateral low paraaortic, subaortic and pelvic lymphadenectomy. STUDY DESIGN: Between January 1992 and December 1995, eight patients with cervical carcinoma IA2 or IB1 underwent laparoscopic radical hysterectomy at China Medical College Hospital, Taichung, Taiwan, R.O.C. The procedure of laparoscopic radical hysterectomy was separated into eight segmental steps. RESULTS: No major complications, including ureteral injury and lymphocyst formation, were noted in any case. Mean hospitalization was 6.5 days. The follow-up period ranged from 16 to 62 months. Only one case recurred, in the lung. CONCLUSION: Laparoscopic radical hysterectomy is a safe procedure. A complete pelvic and paraaortic lymphadenectomy and type III radical hysterectomy can be performed laparoscopically. This approach allows shorter hospitalization and carries less morbidity than the open type. Short-term follow-up (1.3-5.1 years) indicated a favorable prognosis.

Efficacy of pelvic floor rehabilitation for treatment of genuine stress incontinence.

To assess the clinical efficacy of a pelvic floor rehabilitation (PFR) program for treatment of genuine stress incontinence (GSI), we studied 72 patients with slight to moderate (2-10 g of urine loss per hour) or severe (11-50 g of urine loss per hour) GSI who underwent PFR. Objective and subjective assessments were performed before and 3, 6, 12, 18, and 24 months after the start of treatment. The overall success rate (complete cure or marked improvement in symptoms) was 61% (44/72) at the 2-year follow-up. The number of leakages per 24 hours and urine loss in the 1-hour pad test were significantly reduced, and vaginal muscle strength was significantly increased in successfully-treated patients. Significant changes were also observed in symptoms of micturition frequency and nocturia and in volume at first desire to void during cystometry in the treatment success group. Patient compliance with the exercise program was a significant predictor of success. The success rate during the 2-year follow-up period, estimated according to patient compliance, also differed significantly among groups, with good, moderate, and poor compliance. Patients experienced no serious adverse effects. These results show that the PFR program used in this study is an effective alternative to surgical intervention for the treatment of GSI in selected patients.

Modified perineal urethrostomy using preputial mucosa in cats.

A modified perineal urethrostomy was performed in 14 males cats with partial or complete urethral obstruction. Follow-up information was available for 2 to 18 months. By use of this method, the preputial tissues were preserved, and the penile urethra was anastomosed to the preputial mucosa to enlarge and lengthen the urethra. Urine flow was reestablished in all cats without evidence of urethral stenosis or other major complications. Appearance of the perineal region and prepuce was not substantially altered.

A multiple case study comparison of normal private preparatory school and substance abusing/mood disordered adolescents and their families.

This multiple case study of ten families of normal private preparatory school adolescents and five families of substance abusing/mood disordered adolescents was an effort to identify factors that may suggest a relationship between the abuse of substances in adolescents who also have mood disorders and the following family factors: parental marital discord, degree of family satisfaction, and family problem-solving styles. The fifteen families completed four assessment instruments and participated in a videotaped problem-solving exercise. The results of this study showed that all members of the substance abusing/mood disordered adolescents' families rated themselves as dysfunctional in all major areas of family life. In contrast, the normal private preparatory school families reported satisfaction with most areas of family functioning. Communication styles also differed considerably between the two small groups of families. These results appear to support the importance of family evaluation and treatment when addressing the issue of adolescent substance abusers with mood disorders.

The innervation of canine hip joint capsule: an anatomic study.

To clarify the contributions of the nerves supplying the canine hip joint capsule for clinical application, cadaver study of six healthy mongrel dogs was performed. The pelvises and hindlimbs of cadavers were dissected and fixed in formaldehyde. Innervation of the joint capsule was investigated with the aid of an operative microscope. As a result, the canine hip joint capsule receives multiple innervations from articular branches of four nerves. They are articular nerve fibres of femoral, obturator, cranial gluteal and sciatic nerves from the cranioventral, caudoventral, craniolateral and dorsolateral directions of the joint, respectively. No branch originating from the caudal gluteal nerve was observed innervating the hip joint capsule. Our data provides useful information for research on the canine hip joint, including pain analysis with hip disorders and surgical nerve blockade to relieve pain.

Mutation analysis of the tumor suppressor gene PPP2R1B in human cervical cancer.

Protein phosphatase 2A (PP2A) holoenzyme plays a critical role in cell cycle control and growth factor signaling. The PPP2R1B gene encodes the beta isoforms of the subunit A of the PP2A. We aimed to evaluate the role of the PPP2R1B gene in the pathogenesis of cervical cancer. Twenty-four women with primary cervical cancer were included. All resected specimens were divided into two groups: (1) cervical cancers (n = 24), (2) nearby noncancerous tissues (n = 24). We performed nested reverse transcriptase-polymerase chain reaction analysis and complementary DNA sequencing on the genomic DNA samples of all specimens. The aberrant transcripts and gene mutation as well as the genotype and allele frequencies of codon 66 CTA/CTG of PPP2R1B genes in both groups were compared. The percentages of aberrant transcripts between both groups were nonsignificantly different (20.8% vs 33.3%). There was no mutation in all specimens. The genotype and allele frequencies between both groups were non-different. Proportions of CTA homozygote/heterozygote/CTG homozygote were (1) 66.7/8.3/25% and (2) 58.3/12.5/29.2%. Proportions of CTA/CTG alleles in both groups were (1) 70.8/29.2% and (2) 64.6/35.4%. We conclude that PPP2R1B genes may not play a role in the carcinogenesis of cervical cancer. Mutations of PPP2R1B gene are not frequent in cervical cancer.