Eight-week Intervals Research Articles

Endoscopic Mucosal Resection: Early Experience in British Columbia

Endoscopic mucosal resection (EMR) has been proposed as a primary method of managing patients with dysplasia- or mucosal-based cancers of the esophagus. To evaluate the use of EMR for the treatment of Barrett's esophagus with dysplasia or early adenocarcinoma, assessing efficacy, complication rates and long-term outcomes. All patients who underwent EMR at St Paul's Hospital (Vancouver, British Columbia) were reviewed. Eligible patients were assessed with aggressive biopsy protocols. Detected cancers were staged with both endoscopic ultrasound imaging and computed tomography. Appropriate patients were offered EMR using a commercially available mucosectomy device. EMR was repeated at six- to eight-week intervals until complete. Patients with less than one year of follow-up or who were undergoing other ablative methods were excluded. Twenty-two patients (all men) with a mean (+/- SD) age of 67+/-10.6 years were identified. The mean duration of gastroesophageal reflux disease was 17 years (range four to 40 years) and all were receiving proton pump inhibitor therapy. The mean length of Barrett's esophagus was 5.5+/-3.5 cm. One patient had no dysplasia (isolated nodule), three had low-grade dysplasia, 15 had high-grade dysplasia (HGD) and three had adenocarcinoma. A mean of 1.7+/-0.83 endoscopic sessions were performed, with a mean of 6+/-5.4 sections removed. Following EMR, three patients developed strictures; two of these patients had pre-existing strictures and the third required two dilations, which resolved his symptoms. There were no other complications. Three patients underwent esophagectomy. Two had adenocarcinoma or HGD in a pre-existing stricture. The third patient had an adenocarcinoma not amenable to EMR. One patient with a long segment of Barrett's esophagus underwent radiofrequency ablation. At a median follow-up of two years (range one to three years), the remaining 18 patients (82%) had no evidence of HGD or cancer. Most patients with esophageal dysplasia can be managed with EMR. Individuals with pre-existing strictures require other endoscopic andor surgical methods to manage their dysplasia or adenocarcinoma.

Efficacy and safety of OK‐432 immunotherapy of lymphatic malformations

To determine the efficacy and safety of the immunostimulant OK-432 (Picibanil) as a treatment option in the management of children with cervicofacial lymphatic malformations. A prospective, randomized, multi-institutional phase II clinical trial at 27 U.S. academic medical centers. 182 patients with lymphatic malformations (LM) were enrolled between January 1998 and November 2004. Of the 151 patients with complete case report forms, 117 patients were randomized into immediate or delayed treatment groups; 34 patients were nonrandomized and assigned to the open-label group. Treatment consisted of a four-dose intralesional injection series of OK-432 at eight-week intervals. Patients randomized into the delayed treatment group served as observational controls for spontaneous regression. Response to therapy was measured radiographically by quantitating change in lesion size and graded as complete (90%-100%), substantial (60%-89%), intermediate (20%-59%), or none (<20%). Of 117 patients randomized with intent-to-treat, 68% demonstrated a complete or substantial response to OK-432 immunotherapy. Response data for macrocystic LM were higher, with a complete or substantial response in 94% of patients; 63% of patients with mixed macrocystic-microcystic LM responded to treatment; no patients with microcystic LM responded to treatment. Spontaneous resolution occurred in less than 2% of patients. Median follow-up of 2.9 years demonstrated a 9% recurrence rate. Major adverse effects related to therapy occurred in 11 patients. As compared to historical surgical data on LM, OK-432 immunotherapy is more effective (P < .001) and has a lower morbidity (P < .001). OK-432 immunotherapy is an effective, safe, and simple treatment option for the management of macrocystic cervicofacial LM. ClinicalTrials.gov Identifier: NCT00010452.

Cytomegalievirus-Infektion und Koronarsklerose nach Herztransplantation

Serological tests for cytomegalovirus (CMV) after cardiac transplantation were performed at six to eight-week intervals on 26 patients (3 females and 23 males; mean age 46 [15-62] years) with angiographic or ultimately autopsy evidence of coronary atherosclerosis (group 1) and 24 patients (5 females and 19 males; mean age 45 [25-56] years) without coronary disease in the transplanted heart. A positive result meant an at least fourfold increase in CMV IgG titre, demonstration of CMV IgM or direct viral isolation from blood or other body fluid. In 20 patients of group 1 (77%) a CMV infection had occurred after the transplantation, but in only six patients (25%) in the group 2 (P less than 0.0001). These results are interpreted as demonstrating a relationship between CMV infection and rapidly progressive coronary atherosclerosis after cardiac transplantation.

Male Hormonal Contraception: Effects of Injections of Testosterone Undecanoate and Depot Medroxyprogesterone Acetate at Eight-Week Intervals in Chinese Men

Surveys indicate that one form of acceptable male hormonal contraception would consist of injections given at 2- to 3-month intervals. This report describes a study of depot medroxyprogesterone acetate (DMPA) and testosterone undecanoate (TU) injected at 8-wk intervals for suppression of spermatogenesis in healthy Chinese men. After screening, 30 healthy volunteers were enrolled and randomly assigned to one of three dose groups (n = 10/group): 1000 mg TU (group A); 1000 mg TU plus 150 mg DMPA (group B); 1000 mg TU plus 300 mg DMPA (group C). All doses were given as im injections at 8-wk intervals. The study consisted of an 8-wk control (baseline) period, a 24-wk treatment period, and a 24-wk recovery period. Consistent azoospermia or severe oligozoospermia was achieved and maintained in all volunteers during the treatment period, except for two men in the TU-alone group who experienced a rebound in sperm concentrations. An 8-wk regimen of TU plus DMPA at both tested combination doses effectively suppressed spermatogenesis to azoospermia in Chinese men. All volunteers tolerated the injections; no serious adverse effects were reported. The lower-dose combination is recommended for further testing in an expanded clinical trial or contraceptive efficacy study.

Treatment of Crohn's disease with infliximab.

The role of infliximab in managing Crohn's disease (CD) is described. CD is characterized by chronic transmural inflammation at various sites of the gastrointestinal tract, particularly the ileum and colon. The major symptoms are diarrhea, abdominal pain, enterocutaneous and perianal fistulas, and weight loss. Management goals include alleviating symptoms, inducing remission, promoting healing of the intestinal mucosa and fistulas, and modifying the disease process. Drugs traditionally used to manage CD are aminosalicylates, antimicrobials, immunomodulatory agents, and corticosteroids. Infliximab is a chimeric (human-mouse) monoclonal antibody targeted at human tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine important in the pathogenesis of CD. Infliximab antagonizes the biological activity of TNF-alpha by binding to it on macrophage and T-cell surfaces. Clinical trials have shown infliximab to be effective in producing and maintaining a clinical response in patients with refractory, moderate to severe CD. Treatment helps promote healing of intestinal mucosa and closure of fistulas. Infliximab may act more rapidly than most traditional agents and produces less severe adverse effects. The most frequent adverse effects are headache, nausea, and upper-respiratory-tract infections. The recommended dosage is 5 mg/kg i.v. infused over a two-hour period. Infliximab may be given at eight-week intervals for maintenance or management of flare-ups. Infliximab appears useful in the treatment of CD and may improve patients' quality of life.

Low Prevalence of VRE Gastrointestinal Colonization of Hospitalized Patients in Manitoba Tertiary Care and Community Hospitals

To determine the prevalence of vancomycin-resistant enterococci (VRE) bowel colonization in hospitalized patients in Manitoba who had stool specimens collected for Clostridium difficile toxin and/or culture testing. Two tertiary care and five community hospitals in Winnipeg and three rural Manitoba community hospitals participated in this study. From January 1 to December 31, 1997 stool specimens, one per patient, submitted to hospital microbiology laboratories for C difficile toxin and/or culture testing were screened for VRE on colistin-nalidixic acid-vancomycin (6 microg/mL) (CNAV) agar plates. The study was divided into six, eight-week intervals. Stool specimens received in the first two weeks of each eight week interval were screened for VRE. A total of 1408 stool specimens were submitted over the 48-week study period. Sixty-seven (4.8%) patients with VRE colonization of their lower gastrointestinal tract were identified. Three of the 67 (4.5%) VRE isolates were Enterococcus faecium, with the remaining 64 (95.5%) were Enterococcus gallinarum. The three vancomycin-resistant E faecium -VREF- (from two different Winnipeg hospitals) demonstrated the vanA genotype, and were resistant to vancomycin, teicoplanin and ampicillin. All three VREF isolates also demonstrated high level resistance to both gentamicin and streptomycin but were susceptible to quinuprisitin/dalfopristin and LY333328. VRE colonization in hospitalized patients in Manitoba is infrequent and most commonly due to E gallinarum. The prevalence of VREF colonization in the patients studied was 0.2% (three of 1408).

Intravenous immunoglobulin (IVIg) for the treatment of birdshot retinochoroidopathy

Intravenous polyclonal immunoglobulin (IVIg) treatment has been successfully used in a number of autoimmune conditions. Birdshot retinochoroidopathy (BRC) is a bilateral autoimmune posterior uveitis which, in its progressive form, frequently requires immunosuppressive therapy. We report a clinical study aimed at determining the tolerance and efficiency of IVIg treatment in patients with active BRC. The study was conducted in an open manner. Eighteen patients were included. The initial visual acuity (VA) was =20/30 in 26 eyes, 20/25 in five eyes, and 20/20 in five eyes. IVIg was given as sole treatment at 1.6 g/kg every four weeks for six months, followed by injections of 1.2-1.6 g/kg at six to eight-week intervals. The mean follow-up was 39 months, ranging between 12 and 53 months. The results showed that the final VA of the 26 eyes with an initial VA of =20/30 was increased by two lines or more in 14 eyes (53.8%) and decreased in two (7.7%). Of the five eyes with an initial VA of 20/25, four had improved to 20/20 and one remained stable. Of the five eyes with an initial VA of 20/20, four remained stable and one deteriorated to 20/25. When present, macular edema was improved in half of the eyes on fluorescein angiography. Benign side effects were observed in 12 patients: moderate transient arterial hypertension (7), headache (6), eczematous lesions (6), and hyperthermia (4). The results suggest that IVIg may represent a safe alternative therapy for patients with BRC.

Prevention of Relapse in Reflux Esophagitis: A Placebo Controlled Study of Ranitidine 150 mg BID and 300 mg BID

To compare the efficacy and safety of long term use of ranitidine 150 mg bid, 300 mg bid and placebo in prevention of endoscopic and symptomatic relapse of reflux esophagitis in an international, double-blind, placebo controlled, parallel group study. A total of 279 patients at least 18 years old from hospital out-patient departments with healed esophagitis (grade 0) with no or mild symptoms entered the study. Patients were randomly allocated to receive ranitidine 150 mg, 300 mg placebo twice daily for 48 weeks. Patients returned for symptom assessments at eight-week intervals and for re-endoscopy every 16 weeks. Both ranitidine regimens were significantly more effective than placebo in preventing endoscopic and symptomatic relapse of reflux esphagitis (p = 0.003 for ranitidine 150 mg bid; P < 0.001 for ranitidine 300 mg bid). No statistically significant differences were observed in relapse rates between the two ranitidine regiments. The percentage of patients with endoscopic relapse (grade 2) after 48 weeks were 60%, 37% and 27% for placebo, ranitidine 150 mg bid and ranitidine 300 mg bid, respectively (P = 0.002 for ranitidine 150 mg bid versus placebo; P < 0.001 for ranitidine 300 mg bid versus placebo). Ranitidine was well tolerated. Ranitidine 150 mg bid and 300 mg bid are safe and effective treatments in the prevention of reflux esophagitis relapse.

Transendoscopic biopsy of the horse's airway mucosa

Summary Transtracheal wash and bronchoalveolar lavage are diagnostic techniques that have been adopted from human medicine for monitoring inflammatory changes in the airway of the horse. Transendoscopic biopsy has also proven to be a valuable tool for obtaining samples of the airway mucosa in human patients. A transendoscopic technique was developed in this study for obtaining a respiratory mucosal biopsy from standing, sedated horses. Six normal adult horses were sampled at eight-week intervals for a total of three sample periods. Horses were monitored for adverse effects of the technique and none were noted. Sample sites were completely healed after eight weeks with no gross or histologic abnormalities. Biopsy samples were 3 to 4 millimeters in diameter, and 17 of 18 samples provided interpretable histological sections. Methods for handling, staining and evaluating tissue were also developed. The results of this study demonstrated that airway mucosal biopsy is a safe, repeatable technique that can be performed in the sedated, standing horse.

Quantitative Estimation of Hair Growth I. Androgenetic Alopecia in Women: Effect of Minoxidil

Quantitative growth of hair over a 40-week period is reported for eight women with androgenetic alopecia. Using a random, double-blind protocol, the women were given either a 2% minoxidil solution or a placebo of vehicle only. Hair in a permanently marked site on the fronto-parietal scalp was pulled through a 1-cm-square clear plastic template, and the outline of the template was drawn on the scalp. The hair was carefully hand clipped and collected at five eight-week intervals (one untreated and four treated), using great care to collect only hairs within the marked area. Subsequent measurements included the total weight of hair grown in the marked area, the total number of hairs, and, on a randomized 50-hair subsample, the weight, lengths, and optical diameters. Calculated quantities included average weight per hair, average length, and average optical width. The average total hair weight of minoxidil-treated subjects increased over the 32-week test period by 42.5%, compared to 1.9% for the placebo-treated subjects (average p = 0.018). Changes for the average number count were 29.9% and -2.6%, respectively (average p = 0.022). These increases, observed using an unusually small number of subjects, clearly distinguished the treated subjects from the untreated. During the same test period, the averaged quantities of weight, diameter, and length from the 50-hair subsample showed insignificant change (p usually greater than 0.5). In addition to showing a larger percentage increase than did the total number, the total weight is not only easier to obtain, but less prone to error during sampling and measurement. Therefore, we recommend that total weight from a defined area be considered as the primary quantitative estimator for hair growth.

Observations on equine strongyle control in southern temperate USA.

A program of rotational anthelmintic treatments at eight-week intervals had failed to provide satisfactory equine strongyle control at a stable in southern USA. Anthelmintic resistance had rendered benzimidazoles ineffective, and intervals between treatments with other drugs were too great to prevent environmental contamination with ova. Ivermectin treatments at eight week intervals or pyrantel pamoate treatments at four week intervals successfully reduced egg counts for the majority of the summer grazing period. In southern temperate USA, translation of strongyle ova to larvae was most efficient during autumn and winter. Minimal larval translation occurred during summer when meteorological conditions limited pasture infectivity as effectively as anthelmintic treatments.

Muscle capillary basement-membrane thickness and long-term glycemia in type I diabetes mellitus.

We explored the relation between the thickness of the quadriceps-muscle capillary basement membrane and the glycemia level in 102 young patients with Type I diabetes (median age, 17 years; range, 12 to 29). Membrane thickness was measured in serial biopsy specimens obtained after two consecutive 2 1/2-year observation periods, and glycemia was assessed in terms of glycosylated hemoglobin and fasting blood glucose levels determined at eight-week intervals. An association between membrane thickness and glycemia level was apparent in both cross-sectional and longitudinal analysis. Cross-sectional analysis of data on 39 postpubertal patients (growth less than 1.0 cm during the five years) showed a positive association of membrane thickness to glycosylated hemoglobin (r = 0.53, P = 0.0002) and blood glucose values (r = 0.37, P = 0.01) averaged over the antecedent 2 1/2-year period. By contrast, in 32 pubertal patients (growth greater than 7.5 cm) there was a significant negative association of membrane thickness to both glycosylated hemoglobin (r = -0.40, P = 0.01) and blood glucose (r = -0.42, P = 0.009). In longitudinal analysis, there was no correlation between changes in membrane thickness and average glycemia levels during the two follow-up periods in 32 pubertal patients (for glycosylated hemoglobin, r = 0.11; P = 0.25), but in the postpubertal group (n = 20) there was a significant positive covariation (r = 0.57, P = 0.0004). The data indicate that in postpubertal diabetic patients, the thickness of the muscle capillary basement membrane is positively related to the level of glycemia, but this relation does not obtain in the pubertal state.

Postabortal contraception with norethisterone enanthate injections

Intramuscular injection of 200 mg norethisterone enanthate (NET-EN) was given to five women on the day of first trimester abortion. The injection was repeated twice at eight-week intervals, and thereafter at twelve-week intervals for one year. Plasma samples were collected for FSH, LH/hCG, estradiol, progesterone and norethisterone (NET) determinations. NET-EN did not affect the elimination of hCG, estradiol or progesterone. Plasma NET concentrations reached a peak (5.5–11 ng/ml) in about ten days after the injection and declined constantly thereafter, to levels of 0.18–0.64 ng/ml at 8 weeks after the injection. NET-EN postponed the increase in FSH secretion until 17–20 days after the injection, i.e. until plasma NET concentrations fell below 3 ng/ml. In three out of five women some follicular activity was present 5 weeks after NET-EN injection as evidenced by increased plasma estradiol concentrations. No ovulation occurred within 8 weeks after NET-EN injection, as judged by low progesterone values. There was a definite accumulation of NET during the first six months, when NET-EN injections were given at eight-week intervals. Mean plasma NET concentrations increased from 0.34 ng/ml at eight weeks to 0.78 ng/ml at 24 weeks. When the injection interval was increased to twelve weeks, the plasma NET concentrations prior to the next injection started to decrease. This was accompanied by increased follicular activity, culminating with one ovulation observed. It is concluded that in this population of women, an injection interval of less than twelve weeks is needed for ovulation inhibition.

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Intramuscular injection of 200 mg norethisterone enanthate (NET-EN) was given to five women on the day of first trimester abortion. The injection was repeated twice at eight-week intervals, and thereafter at twelve-week intervals for one year. Plasma samples were collected for FSH, LH/hCG, estradiol, progesterone and norethisterone (NET) determinations. NET-EN did not affect the elimination of hCG, estradiol or progesterone. Plasma NET concentrations reached a peak (5.5–11 ng/ml) in about ten days after the injection and declined constantly thereafter, to levels of 0.18–0.64 ng/ml at 8 weeks after the injection. NET-EN postponed the increase in FSH secretion until 17–20 days after the injection, i.e. until plasma NET concentrations fell below 3 ng/ml. In three out of five women some follicular activity was present 5 weeks after NET-EN injection as evidenced by increased plasma estradiol concentrations. No ovulation occurred within 8 weeks after NET-EN injection, as judged by low progesterone values. There was a definite accumulation of NET during the first six months, when NET-EN injections were given at eight-week intervals. Mean plasma NET concentrations increased from 0.34 ng/ml at eight weeks to 0.78 ng/ml at 24 weeks. When the injection interval was increased to twelve weeks, the plasma NET concentrations prior to the next injection started to decrease. This was accompanied by increased follicular activity, culminating with one ovulation observed. It is concluded that in this population of women, an injection interval of less than twelve weeks is needed for ovulation inhibition.

Nephrotoxicity of nitrosoureas.

Irreversible and progressive renal parenchymal damage and functional impairment occurred in the majority of patients receiving at least six courses (200 mg/m2 of BCNU and/or methyl CCNU at eight-week intervals) of nitrosoureas for therapy of malignant brain tumors. Seventeen of 18 patients who received at least six courses and all nine patients who received more than ten courses developed impaired renal function as judged by elevation of blood urea nitrogen and/or serum creatinine or decrease in filtration rate as determined by inulin clearance. Four patients have developed uremia. Renal tissue obtained from seven patients demonstrated tubular atrophy, interstitial fibrosis and glomerular sclerosis. This remarkably high incidence of renal damage occurred without a phase of acute renal failure and in the absence of significant urinary abnormalities, while producing an insidiously progressive interstitial renal lesion.

Immunization of Indochinese Refugees

To the Editor.— In follow-up of the description of Deinard et al (243:2156, 1980) of a patient with otogenous tetanus, we would like to comment on one of their conclusions and to inform readers about an immunization program for Indochinese refugees who are coming to the United States. The recommended schedule for unimmunized children between the ages of 2 months to 7 years consists of three doses of diphtheria and tetanus toxoids and pertussis vaccine (DTP) given at four- to eight-week intervals followed by a fourth dose 12 months later and a booster dose at the time of school entry. 1 These recommendations provide for optimal protective antibody titer responses. In the patient described by Deinard et al, the clinical onset of tetanus occurred within five days of immunization, and only one dose of DTP had been documented with certainty. Consequently, it is not surprising that the child had not

A clinical and metabolic study of norethisterone oenanthate in Thai women

Norethisterone oenanthate was given as an injectable contraceptive to 126 Thai women. Only healthy informed volunteers aged 18–35 years were admitted to the study. One ml of oily solution containing 200 mg of steroid was administered into the gluteal muscles. The first injection was given during days 1–5 of a normal menstrual period. The second, third and fourth injections were given at eight-week intervals and were followed by subsequent injections at 12-week intervals. All injections were given within seven days of the scheduled date. Volunteers were instructed to record any vaginal bleeding in diary cards. At each visit, weight, blood pressure and menstrual bleeding were recorded. Complaints and adverse effects were also noted. Prior to admission for study, an oral glucose tolerance test (OGTT), serum transaminase, cholesterol and triglycerides were simultaneously studied in 21 women and then repeated at three, six and twelve months. The 12-month continuation rate was 63 100 women-years with 5 accidental pregnancies. Two pregnancies occurred during the second injection intervals and the other three pregnancies occurred during the third, fourth and fifth injection intervals. The 12-month study revealed 11 100 and 25 100 women-years of amenorrhea and heavy bleeding, respectively. There was a statistically significant increase in the serum glucose tolerance test (P < 0.05) at the 30-minute time intervals after 12 months of use, but the areas under the curves were within normal limits. The total cholesterol and triglycerides showed a significant transient decrease (P < 0.01) at the third month of study and returned to normal after 6 months.

Adjuvant long-term chemotherapy in complex treatment of operable breast cancer.

Prophylaxis of distant metastases in primary breast cancer should be regarded both as a prevention of secondary tumor foci which might develop from the tumor cells circulating in die blood and lymph, and as a treatment of latent metastases in distant organs which were not found prior to operation. Chemotherapy is best achieved in patients with multiple regional metastases. The postoperative application of these complex therapeutic procedures produces nearly double the number of survivors in patients without distant metastases (40% compared to 21.5% in the controls). Chemotherapy in conjunction with surgery-plus-irradiation of patients with single and multiple metastases serves to increase the 5-year survival by 27-30%. Chemotherapy should be started during mastectomy and be continued in three to four consecutive courses at six- to eight-week intervals, since its effectiveness depends on its impact to the whole population of tumor cells at states G and S. The maximum tolerable total dose causing cytotoxic responses I and II may be used as an indication of the full effect of the chemotherapeutic agents. In patients with multiple regional metastases, the combination of chemotherapy and oophorectomy is most advantageous with a chromatin-positive primary tumor.

Prediction of anxiety and depression patterns among coronary patients using a Markov process analysis.

A Markov process analysis was applied in a study of anxiety and depression patterns among 31 male patients with coronary heart disease and 46 healthy male controls. Anxiety and depression were measured at six- to eight-week intervals over a period of 15 months by the subjects' completion of shortened versions of the Bendig Anxiety and Welsh Depression subscales of the MMPI. The sequence of anxiety and depression states for each subject at each examination was used as input to the Markov analysis system. Patients had significantly higher anxiety scores over time than the controls. Patients under age 50 showed a fivefold greater incidence of anxiety and a higher degree of retention of high anxiety over time than controls in the same age group. The anxiety level of controls was low irrespective of age. While depression was a more persistent state among patients than controls, it was not found to be age-related among either patients or controls. The implication of these findings in planning strategies of therapeutic intervention to circumvent the cumulative effects of anxiety and depression is discussed.

AUTOLOGOUS TRANSFUSIONS IN URÆMIC PATIENTS

In 10 patients in whom uræmia was diagnosed before maintenance hæmodialysis or kidney transplantation became necessary, the interval was used for regular collection of blood, which was frozen and stored in liquid nitrogen. Despite anæmia (hæmoglobin 7·0-12·2 g. per 100 ml.) and uræmia (serum-creatinine 5-16 mg. per 100 ml.) the patients did not react unfavourably to regular blood donations at eight-week intervals. 52 units were collected. So far, 33 units have been autologously transfused into 7 patients, mainly at the time of maintenance hæmodialysis and kidney transplantation. In 4 patients the autologous blood was sufficient; in 3 additional homologous blood had to be given. Severely ill patients can be used as blood-donors. It seems to be worth the cost and effort to institute a regimen of prophylactic blood donation for hæmodialysis and transplantation candidates.