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.

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.

Lack of evidence for the association of tumor necrosis factor-alpha gene promoter polymorphism with calcium oxalate stone and bladder cancer patients.

Urinary stone disease and bladder cancer are two of the most commonly seen urologic diseases in Taiwan. Tumor necrosis factor-alpha (TNF-alpha) is one of the cytokines secreted by macrophages and is related to a sequence of events in response to inflammation and cancer formation. We investigated the polymorphism of the TNF-alpha gene promoter -308 as a genetic marker in searching for the association between these two commonly seen urologic diseases. One hundred and fourteen patients with transitional cell carcinoma of the urinary bladder and 103 patients with calcium oxalate stone were compared with 150 healthy controls. The polymorphism was detected by polymerase chain reaction-based restriction analysis (Nco I endonuclease). The results revealed no significant differences between normal individuals and the patients with the two commonly seen urologic diseases (P > 0.05). We concluded that the polymorphism of the TNF-alpha promoter -308 is not a valid genetic marker for these two urologic diseases.

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.

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.

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.

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.

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.

Repair of a mandibular defect with a free vascularized coccygeal vertebra transfer in a dog.

Bilateral mandibular defects in a male mongrel dog were repaired. On the left side, a free vascularized coccygeal bone graft that included the median caudal artery and caudal vein was used to correct the defect. On the right side, the defect was bridged with a bone plate and screws. For further immobilization, the muzzle was temporarily taped for 3 weeks and a pharyngostomy tube was used for nutritional support. The dog was able to eat dry commercial food satisfactorily within 2 months of surgery despite mild malocclusion. Radiographs taken 2 months and 18 months postoperatively showed bony union with graft hypertrophy in the left mandible, whereas the right mandibular defect showed protracted nonunion. The results indicate that vascularized coccygeal vertebra transfer provides an alternative for the management of canine mandibular defects.

Vascularized autogenous canine coccygeal bone transfer.

Based on cadaver studies in dogs, the 8th, 9th, or 10th canine coccygeal vertebra with overlying skin was designed for free vascularized bone transfer. In six dogs the coccygeal osteocutaneous flap was transferred to fill a defect of the tibia, anastomosing the median caudal artery and one of the two caudal veins to the tibial vessels. The overlying skin provided a reliable monitoring system for the transferred tissue. The behavior of the vascularized coccygeal vertebrae was then evaluated with radiographic and histologic examination and compared with control vertebrae transferred without reconnection of the blood vessels. The results revealed that the canine coccygeal bone graft is a reliable vascularized osteocutaneous flap, which can be applied either in clinical veterinary surgery or in orthopedic microsurgical research.

New perspectives on bacterial ferredoxin evolution.

Recent evidence indicates that a gene transposition event occurred during the evolution of the bacterial ferredoxins subsequent to the ancestral intrasequence gene duplication. In light of this new information, the relationships among the bacterial ferredoxins were reexamined and an evolutionary tree consistent with this new understanding was derived. The bacterial ferredoxins can be divided into several groups based on their sequence properties; these include the clostridial-type ferredoxins, the Azotobacter-type ferredoxins, and a group containing the ferredoxins from the anaerobic, green, and purple sulfur bacteria. Based on sequence comparison, it was concluded that the amino-terminal domain of the Azotobacter-type ferredoxins, which contains the novel 3Fe:3S cluster binding site, is homologous with the carboxyl-terminal domain of the ferredoxins from the anaerobic photosynthetic bacteria. A number of ferredoxin sequences do not fit into any of the groups described above. Based on sequence properties, these sequences can be separated into three groups: a group containing Methanosarcina barkeri ferredoxin and Desulfovibrio desulfuricans ferredoxin II, a group containing Desulfovibrio gigas ferredoxin and Clostridium thermoaceticum ferredoxin, and a group containing Desulfovibrio africanus ferredoxin I and Bacillus stearothermophilus ferredoxin. The last two groups differ from all of the other bacterial ferredoxins in that they bind only one Fe:S cluster per polypeptide, whereas the others bind two. Sequence examination indicates that the second binding site has been either partially or completely lost from these ferredoxins. Methanosarcina barkeri ferredoxin and Desulfovibrio desulfuricans ferredoxin II are of interest because, of all the ferredoxins whose sequences are presently known, they show the strongest evidence of internal gene duplication.(ABSTRACT TRUNCATED AT 400 WORDS)

Identification of the probable coding region for exon 2 of cytochrome oxidase polypeptide I from Aspergillus nidulans mitochondrion.

Hypothetical protein URFe of Aspergillus nidulans mitochondrion is homologous with the amino end of cytochrome oxidase (EC 1.9.3.1) polypeptide I. Unidentified reading frame URFe does not contain a suitable initiation codon and codes for a protein with a length of only 91 residues, corresponding to about 20% of cytochrome oxidase polypeptide I. It is proposed that this region codes for the second exon of the cox 1 gene of Aspergillus mitochondrion. Possible candidates for the 2- to 3-residue amino-terminal exon 1 are discussed.

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.