Topical treatment for human papillomavirus-associated genital warts in humans with the novel tellurium immunomodulator AS101: assessment of its safety and efficacy.

BACKGROUND: Various methods are currently used for the treatment of anogenital warts. However, a complete cure is unlikely, and the rate of recurrence is high. OBJECTIVES: The purpose of this open-label, multicentre trial was to evaluate the safety and clinical efficacy of a new treatment using the immunomodulator ammonium trichloro (dioxoethylene-O,O') tellurate (AS101; Biomas Ltd, Kefar Saba, Israel) 15% w/w cream to clear vulval/perianal condylomata acuminata. METHODS: Study participants comprised 48 women and 26 men, age range 18-62 years. Of the 48 woman, 44 were diagnosed with vulval condylomata and four with perianal condylomata. All 26 men were diagnosed with perianal condylomata. All the patients in the study received AS101 15% w/w cream twice a day. Maximal treatment duration was 16 weeks. To evaluate the safety and clinical efficacy, patients were examined and lesional areas photographed on a biweekly basis. RESULTS: By the end of the treatment, 56 of 74 (76%) patients were considered completely cleared. Complete cure was achieved in 35 of 44 (80%) patients with vulval condylomata and in 21 of 30 (70%) patients with perianal condylomata. No scarring of treated areas was observed. Complete cure was achieved within a time range of 10-109 days. The most frequent side-effects observed were mild-to-moderate itching, soreness, burning and erythema. In post-treatment follow up of up to 6 months, disease recurrence was observed in two patients (4%), at 105 and 144 days following completion of treatment. CONCLUSIONS: AS101 15% w/w cream is an effective and safe, self-administered therapy used for the treatment of external vulval and perianal warts. The cream is applied topically twice daily for up to 16 weeks. A very low recurrence rate was reported.

Overground and walkway ambulation with unilateral hip osteoarthritis: comparison of step length asymmetries and reproducibility of treadmill mounted force plate readings.

The purpose of this study was to analyze and compare the degree of step length asymmetry of patients with hip osteoarthritis during free walking and treadmill ambulation and to determine the reproducibility of treadmill based vertical ground reaction force parameters. Twelve subjects with monoarticular hip osteoarthritis undergoing total hip replacement surgery were assessed preoperatively. The assessed parameters were step length, maximal forces at heel strike and push off minimum force, force inclining and declining rate and relative stance time. The results indicated significant step length differences when comparing overground and treadmill ambulation. The extent of step length asymmetry did not have a consistent expression in different gait conditions. The study demonstrated sufficient intraday reliability for mean GRF measurements. While comparing data from treadmill and walkway locomotion of patients with osteoarthritis it should be taken into account that the amount of step length asymmetry is not identical. Patients with gait disabilities seem to have a somewhat lower level of repeatability and it appears that an increased number of practice or acclimatization trials are necessary.

Atrophic remodeling of the artery-cuffed artery.

Increased arterial wall tension stimulates growth and remodeling of arteries, but little is known about the effects of decreased wall tension, despite its developmental and pathological significance. Consequently, we cuffed 1 carotid artery in rabbits with a portion of the contralateral artery to off-load circumferential wall tension. The model produced rapid and extensive atrophy of the cuffed artery that yielded decreases in the DNA content of the cuffed artery (a measure of cell number) from 8.0+/-0.5 microgram/cm of in situ vessel length to 5.6+/-0.5 microgram/cm at 21 days postoperatively. The elastin content of the cuffed artery was also significantly reduced, from 399+/-17 to 283+/-17 microgram/cm, and collagen content was reduced from 468.0+/-59.0 to 154+/-24 microgram/cm (P<0.05) at 21 days postoperatively. Detection of DNA oligonucleosomes by gel electrophoresis implicated apoptotic cell death in remodeling due to cuffing. Upregulation of matrix metalloproteinases (MMPs), including MMP-2, MMP-9, and unidentified gelatinases, indicated that these enzymes may also be involved in remodeling. No further changes in wall structure were seen between 3 weeks and 6 months, and the excised artery that was used as a cuff exhibited normal medial morphology for at least 6 months postoperatively. We infer from these experiments that off-loading of arterial wall tension induces rapid and extensive atrophy of the arterial media.

Initial TPS serum level as an indicator of relapse and survival in colorectal cancer.

BACKGROUND: Tissue polypeptide specific antigen (TPS) measures a soluble fragment of cytokeratine 18 and may be regarded as a proliferative marker. MATERIALS AND METHODS: TPS was measured in 173 consecutive patients with colorectal cancer. Median follow up time was 36 months. Of 137 evaluable patients 39 developed metastases (P.D.) and 98 remained with no evidence of disease (N.E.D.). RESULTS: Initial TPS levels were elevated in 75% of P.D. patients compared to 32% of N.E.D. patients (p < 0.001), CEA levels were elevated in 26% of P.D. patients had elevated initial TPS compared to 35.5% of N.E.D. patients (p < 0.001), CEA was elevated in 33.3% of the P.D. patients compared to 1.3% of N.E.D. patients (p < 0.001). Survival and disease free survival were significantly shorter for patients with initial high TPS level. TPS was more sensitive than CEA in predicting relapse. CONCLUSIONS: These preliminary data suggest that TPS may be a prognostic factor for relapse and may help to allocate Dukes'B2 patients for adjuvant chemotherapy.

Rubber band ligation of hemorrhoids. Convenient and economic treatment.

We have reviewed and summarized 12 years of experience in treating hemorrhoids, a condition that affects 4.4% of the Western population, of whom a third are symptomatic and need treatment. During this time, in a proctological outpatient clinic of an urban hospital, 2,934 patients with second- and third-degree hemorrhoids were treated by rubber band ligation (RBL), usually one ligation per session. Of these patients, 79% were completely cured, 18% needed one or more additional sessions of treatment, and 2.1% failed to be cured by RBL and were referred for conventional hemorrhoidectomy. We found that by using this safe and convenient treatment we can save hundreds of hospitalization days and thousands of sick-leave days per year.

Selected operative management of fistula-in-ano in Crohn's disease.

PURPOSE: The operative management of patients with fistula-in-ano in the presence of Crohn's disease has been controversial. Our aim was to review the results of operative treatment in this clinical setting. METHODS: Twenty-eight such patients treated between 1976 and 1990 were reviewed. The duration of local symptoms, location of the Crohn's disease, medications, and previous operations were noted. An effort was made to classify the fistula-in-ano according to Parks' classification, but many fistulas were complicated and did not neatly fit into one of the described categories (intersphincteric 9, transsphincteric 10, complex 9). Patients underwent fistulotomy (three with a seton). RESULTS: Complete healing was achieved in 71.4 percent of cases with an average healing time of 3.5 months (range, 3 weeks-26 months). With an average follow-up of 71 months (range, 12 months-14 years), postoperative function was good in 20 (71.5 percent) patients. Of the remaining eight patients, five ultimately underwent total proctocolectomy because of the severity of their colorectal disease, one patient developed alteration of continence, and two patients developed stenosis. There were two recurrences, (one at nine months and one at six years). CONCLUSION: Operative treatment should be offered to selected patients with fistula-in-ano in the presence of Crohn's disease.

The Bard Rotary Atherectomy System (BRAS): initial experience in patients with peripheral vascular disease.

Sixteen patients with a mean age of 65.4 +/- 9.8 years and suffering from peripheral vascular disease underwent peripheral atherectomy using a new mechanical device--the BARD Rotary Atherectomy System (BRAS). The BRAS is an "over the wire" system that consists of a spiral guidewire and a handheld motor drive unit, which rotates at 1,500 rpm. Prior to the procedure angiography demonstrated the presence of 18 obstructions (1 tibial, 2 popliteal, 15 superficial femoral arteries) with a mean stenosis of 95.7 +/- 8%. Successful atherectomy was achieved in 16 of 18 lesions and resulted in an 89% immediate success rate and a significant (P less than 0.01) reduction of stenosis to 37.8 +/- 12.5%. There were no significant complications. The excised and removed material embedded over the spiral guidewire demonstrated the presence of fibrotic tissue, fatty lesions, and calcium deposits. Medial or adventitial layers were not present in the removed atherosclerotic material. Mean ABI was significantly (P less than 0.01) increased from 0.38 +/- 0.17 to 0.55 +/- 0.21 following atherectomy. Angiographic follow-up obtained in ten patients 8.8 +/- 5.2 months following the procedure demonstrated restenosis in six of those ten patients. The ABI at this time remained unchanged. These results demonstrated that the new BRAS mechanical atherectomy system is feasible and safe for recanalization of severely stenosed arteries in patients with peripheral vascular disease.

[Myiasis in female travelers to the tropics]. / Myiasis bei Tropenurlauberinnen.

Myiasis is a rare disease in Europe and the USA; it is defined by the development of parasitic, mostly tropical maggots in the human body. They are best identified by the pattern of their terminal spiracles and the shape of their stigmal plates. In spite of the size of the larvae of Cordylobia anthropophaga, there is only low-grade inflammation; the clinical course is benign.

The differential expression of statin in the nuclei of human colonic crypts adjacent to a cancer: an immunohistochemical study.

Statin, a non-proliferation-specific nuclear antigen, was used here to assess the colonic crypt kinetics of the mucosa bordering a human colon cancer. Mucosal strips adjacent to a colon cancer obtained from operative specimens were immediately cut into five one cm segments and stored in liquid nitrogen. An immunohistological technique using the statin antibody as a nuclear marker was used to determine the labelling indices of the non-cycling compartment at the varying distances. Optical density measurements of the nuclear reaction product served to objectively identify the statin-positive nucleus. The results indicate that there is a statistically significant reduction (P < 0.0001) in the statin-positive labelling index in the entire crypt length for a distance of three cms. The division of the entire crypt into four levels (A, B, C and D) demonstrates that this effect is principally due to the upward extension of the statin-negative cell mass into levels B and C with a corresponding decrease in the labelling index of the statin-positive nuclei in these levels. The in vivo expression of nuclear statin demonstrates its usefulness in accurately determining the size of the non-proliferative compartment in the human colonic crypt adjacent to a colon cancer.

Modulation of nuclear statin expression in rat thyroid follicle cell following administration of thyroid stimulating hormone.

This study was designed to examine the state of proliferation in the rat thyrocyte following the administration of thyroid stimulating hormone (TSH). An immunohistochemical technique involving the use of a monoclonal antibody to statin, a nonproliferation-specific nuclear antigen, was developed to measure the subpopulation of cells that have ceased to divide. Following the random assignment of young male Sprague-Dawley rats into various groups, the rats in the control group received a single intraperitoneal (i-p) injection of normal saline, whereas the experimental groups received single i-p injections of TSH at doses of 0.25, 0.50, and 1.0 IU, respectively. All rats were subsequently sacrificed in groups of three at 1, 2, 4, and 24 hours. The statin antibody label was readily identified within the follicle cell nucleus. Results revealed a statistically significant transient decrease in the mean percent statin-positive nuclei in the TSH-treated groups. The time- and dose-dependent effect of TSH was maximal at 2 hours and no longer discernible at 24 hours. A second experiment involving the chronic administration of TSH (i-p 0.25 IU twice daily) resulted in a cumulative response with a statistically significant progressive decrease in the mean percent of statin-positive nuclei at 5 and 10 days, returning to near normal values 5 days following the cessation of treatment. Determination of the nuclear optical density of the statin reaction product by image analysis techniques revealed that a single injection of TSH resulted in a rapid disappearance of the statin nuclear protein. This result suggests that the disappearance of statin in the nucleus appears to reflect the event of cells leaving the nondividing quiescent state to resume the cell cycle traverse following the administration of TSH. The disappearance of statin appears as an early nuclear event that parallels the earliest known cytoplasmic pinocytotic response to TSH in the rat thyroid follicle cell.

Development of a paraprofessional home visiting program for low-income mothers and infants.

This article reports the development of a paraprofessional home visiting program based upon empirically documented client needs, maintenance of the qualities of mutuality and cooperation found in the indigenous paraprofessionals, and methods of ongoing program revision. Three studies are described that suggested four areas of program emphasis: (1) continuity of services from pregnancy through infancy, (2) needs assessment procedures sensitive to a broad range of health and social problems, (3) an ongoing personal relationship with an indigenous paraprofessional, and (4) reduction of barriers to prenatal care inherent in the health care system itself. We provide examples of program application and revision through training of paraprofessionals, case management procedures, and interventions within the perinatal health care system.

Amino acid 55 plays a central role in tetramerization and function of Escherichia coli single-stranded DNA binding protein.

The histidine at position 55 of the amino acid sequence of the Escherichia coli single-stranded DNA binding protein was replaced by tyrosine, glutamic acid, lysine, phenylalanine, and isoleucine. The properties of the mutant proteins were determined using analytical ultracentrifugation, NMR spectroscopy, gel filtration, and fluorimetric detection of their single-stranded DNA binding ability. While the phenylalanine and isoleucine substitutions did not change the properties of the protein measurably, tyrosine and lysine mutants dissociate into subunits and loose some of their binding affinity for poly(dT). For the lysine mutant we show by electron microscopy that the protein, although fully dissociated and possibly denatured in the free state, binds to poly(dT) as a tetramer indistinguishable from the wild-type protein. The process of tetramerization as observed via single-stranded DNA binding ability is composed of a variety of steps ranging in time from some milliseconds to several hours; it probably involves several forms of dissociated and non-native protein.

New approach to surgical treatment of ulcerative colitis and polyposis coli without pelvic pouch. Experimental study in dogs.

A new method for the surgical treatment of ulcerative colitis and polyposis coli is described. Instead of preparing a pelvic pouch, the natural rectal pouch stripped of the diseased mucosa was used experimentally in dogs. The undisturbed muscular cuff of the rectum (12 cm from the anal verge) was covered by healthy vascularized mucosa of small bowel in such a manner that the dog could use its rectum as usual before surgery. The results are encouraging. The rectal reservoir is spared, with its sensitivity, continence and motor activity covered by healthy mucosa. The dogs thrived.

Modulation of the affinity of the single-stranded DNA-binding protein of Escherichia coli (E. coli SSB) to poly(dT) by site-directed mutagenesis.

A vector for site-directed mutagenesis and overproduction of the Escherichia coli single-stranded-DNA-binding protein (E. coli SSB) was constructed. An E. coli strain carrying this vector produces up to 400 mg pure protein from 25 g wet cells. The vector was used to mutate specifically the Phe60 residue of E. coli SSB. Phe60 had been proposed to be located near the single-stranded-DNA-binding site. Substitution of the Phe60 residue by Val, Ser, Leu, His, Tyr and Trp gave proteins with no or only minor conformational changes, as detected by NMR spectroscopy. The affinity of the mutant E. coli SSB proteins for single-stranded DNA decreased in the order Trp greater than Phe (wild-type) greater than Tyr greater than Leu greater than His greater than Val greater than Ser, leading to the conclusion that position 60 is a site of hydrophobic interaction of the protein with DNA.

Esophageal transection with automatic stapler device for bleeding esophageal varices. Case report and review of the literature.

The EEA stapler offers a relative easy technique for the control of severe bleeding from esophageal varices. Two cases are reported in which this technique in combination with proximal gastric devascularization and splenectomy was found to be superior to the performance of portosystemic shunt in emergency cases. The results of portocaval shunts created during severe bleeding from esophageal varices are not satisfactory because of the high mortality rate varying between 36% and 47% (1, 2) and the development of postoperative encephalopathy. For these reasons the tendency today, in cases of severe bleeding from esophageal varices where conservative treatment was unsuccessful, is that the surgeon should attack the bleeding area itself (3). Support for this opinion may be found in the publications of Sugiura and Futagawa (4, 5) and of Koyama et al. (6) about their long-term good results obtained after esophageal transection for bleeding esophageal varices.

Bleeding esophageal varices in pregnancy. A report of two cases.

Hemorrhage from esophageal varices during pregnancy in women with cirrhosis is a rare occurrence with a high mortality rate. Two such women, previously treated surgically for bleeding varices, one with additional sclerotherapy, had massive hemorrhages at 35 weeks necessitating cesarean section for fetal distress. Both neonates were healthy. One woman died one week postpartum. Pregnancy does not appear detrimental to the maternal prognosis despite the theoretical probability of raised portal pressure. About 70% of those with demonstrable varices will bleed during pregnancy; the overall mortality rate is 20%. Endoscopy and sclerotherapy before and in early pregnancy may help reduce the mortality rate. An awareness of the possibility of unpredictable bleeding and of the available treatments in a pregnant woman with esophageal varices is essential.