Final Results of a Phase I Trial of WST-11 (TOOKAD Soluble) Vascular-targeted Photodynamic Therapy for Upper Tract Urothelial Carcinoma.

PURPOSE: Vascular-targeted photodynamic therapy with the intravascular photosensitizing agent padeliporfin (WST-11/TOOKAD-Soluble) has demonstrated therapeutic efficacy as an ablative treatment for localized cancer with potential adaptation for endoscopic management of upper tract urothelial carcinoma. This Phase I trial (NCT03617003) evaluated the safety of vascular-targeted photodynamic therapy with WST-11 in upper tract urothelial carcinoma. MATERIALS AND METHODS: Nineteen patients underwent up to 2 endoscopic vascular-targeted photodynamic therapy treatments, with follow-up for up to 6 months. Patients who had residual or recurrent upper tract urothelial carcinoma (any grade/size) failing prior endoscopic treatment or unable or unwilling to undergo surgical resection were eligible for inclusion. The primary endpoint was to identify the maximally tolerated dose of laser light fluence. A dose escalation model was employed, with increasing light fluence (100-200 mW/cm) using a modified continual reassessment method. The secondary endpoint was treatment efficacy, defined by absence of visible tumor and negative urine cytology 30 days posttreatment. RESULTS: Fourteen (74%) patients received the maximally tolerated dose of 200 mW/cm, 2 (11%) of whom experienced a dose-limiting toxicity. The initial 30-day treatment response rate was 94% (50% complete, 44% partial). Eight patients underwent a second treatment, with a final observed 68% complete response rate. Leading toxicities were flank pain (79%) and hematuria (84%), which were transient. No ureteral strictures associated with treatment were identified during follow-up. CONCLUSIONS: Vascular-targeted photodynamic therapy with WST-11 has an acceptable safety profile with strong potential as an effective, kidney-sparing endoscopic management option for upper tract urothelial carcinoma. The recently initiated multicenter Phase 3 ENLIGHTED trial (NCT04620239) is expected to provide further evidence on this therapy.

Platelet-rich plasma as a therapy for androgenic alopecia: a systematic review and meta-analysis.

OBJECTIVE: The past decade has seen platelet-rich plasma (PRP) become a popular therapy around the world as a treatment for androgenetic alopecia (AGA). These systematic review and meta-analyses assess the effectiveness and adverse effects of PRP to determine the role of PRP as a treatment for AGA among the other non-surgical treatment modalities. METHODS: This study follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and is registered under the PROSPERO ID CRD42019136329. Seven databases were searched from inception through May 2019. Meta-analyses of randomized controlled trials (RCTs) were performed to evaluate the effect of PRP treatments on hair density and hair thickness. RESULTS: Thirty studies, including 687 patients, met our inclusion criteria. Twenty-nine studies reported beneficial results, and 24 studies reached statistical significance on a measured outcome. Ten RCTs were included. Our meta-analyses show that PRP treatment increases hair density and hair thickness. CONCLUSIONS: PRP is an autologous treatment that lacks serious adverse effects and effectively improves hair density and hair thickness in men and women with AGA. Future research should include low risk-of-bias RCTs to optimize treatment protocols, investigate variability among studies, and to obtain more data on hair thickness changes.

Rejuvenating the periorbital area using platelet-rich plasma: a systematic review and meta-analysis.

Intradermal injection of autologous platelet-rich plasma (PRP) is a non-surgical cosmetic therapy to rejuvenate the periorbital area pathologies of wrinkles, periorbital hyperpigmentation (POH), and photoaging. The past decade has seen the adoption of this novel therapy around the world. This is the first systematic review and meta-analysis evaluating PRP treatment of periorbital pathologies. This is a PRISMA compliant review that includes a comprehensive search of the databases Cochrane Library, Ovid Medline, Ovid Embase, and clinicaltrials.gov. The search was performed in June 2019 to obtain all peer-reviewed articles published in English that describe the application of PRP to periorbital pathologies. A meta-analysis of patient satisfaction was performed for randomized controlled trials. Nineteen studies treating 455 patients (95% female, age range 28-60) were included. Studies were categorized based on reported outcomes: wrinkles (11 studies), POH (7 studies), and photoaging (6 studies). Patients were treated a mean of 3 times (range 1-8) in mean intervals of 23 days (range 14-56 days). Follow-up averaged 3 months (range 1-6 months). Meta-analysis of 3 randomized controlled clinical trials (RCTs) shows that patients treated with PRP have increased satisfaction above controls of saline, platelet-poor plasma, mesotherapy, and as an adjunct to laser therapy (overall effect p = 0.001, heterogeneity I2 = 64%). PRP treatment of periorbital area pathologies results in histologic improvements of photoaging, subjective satisfaction score increases, and blind evaluator assessments of rejuvenated skin appearance. Future studies are needed to address limitations of the current literature and should include long-term follow-up, delineation of the POH etiology that is treated, RCTs with low risk of bias, and be absent conflicts of interest or industry sponsors.Trial registration: Prospero Systematic Review Registration ID: CRD42019135968.

Efficacy and toxicosis of VELCAP-C treatment of lymphoma in cats.

BACKGROUND: Lymphoma is the most common malignancy affecting cats. A protocol employing vincristine, l-asparaginase, cyclophosphamide, doxorubicin, and prednisone (VELCAP-S) is effective and well tolerated in dogs with lymphoma. A 24-week variation of this protocol (VELCAP-C) was developed for treatment of cats. HYPOTHESIS: That VELCAP-C will result in survival times for cats with lymphoma that are similar to those obtained when cats are treated with a protocol that includes fewer chemotherapy agents. ANIMALS: Sixty-one cats with lymphoma. METHODS: Retrospective study. Outcomes evaluated were response to VELCAP-C therapy, toxicosis, and survival time. The effect of signalment, staging, CBC, and serum chemistry profile and dosage on these outcomes was examined. RESULTS: Six cats (10%) completed the protocol with a median survival of 1189 days. Forty-three percent (23 of 61) of the cats achieved complete response (CR) with a median survival time of 62 days. Cats that required a dose reduction of any drug during induction were more likely to achieve CR. Weight loss and hepatomegaly at diagnosis were negatively associated with response to treatment. Increased lactate dehydrogenase (LDH) serum activity at the time of initial treatment correlated with decreased survival times. CONCLUSIONS AND CLINICAL IMPORTANCE: This multi agent protocol did not provide improved survival over historical data using protocols with fewer agents. Serum LDH activity levels might provide useful prognostic information for cats with lymphoma.

In vivo axial dynamization of canine tibial fractures using the Securos external skeletal fixation system.

Bilateral transverse mid-shaft tibial osteotomies, with a 4-mm gap, were performed in purpose-bred research dogs and stabilized using a Securos Type 2 external skeletal fixotor (ESF). Full (100%) axial dynamization of one randomly selected ESF in each dog was performed at 31 days postoperatively. Caudo-cranial radiographs were obtained at weekly intervals, which were qualitatively and quantitatively evaluated (densitometry and ImageJ analysis). The dogs were euthanatized 13 weeks postoperatively, at which time dual energy x-ray absorptiometry (DEXA), peripheral quantitative computed tomography (pQCT), mechanical testing in torsion, and qualitative histological analysis were performed. A two-tailed paired Student's t-test was performed for statistical analysis of all parameters of interest, with significance set at p < 0.05. Three of five dynamized bones bridged quicker, and four of five dynamized bones appeared to have greater callus formation, however, statistically significant differences could not be definitively determined. Statistically significant differences were not found with densitometry (any time frame), DEXA, pQCT, torsional stiffness or maximum torque. Despite the lack of statistically relevant data, trends were observed with larger callus size and density in the dynamized tibiae. The dynamized tibiae appeared to fracture more consistently outside of the area of the healing callus as compared to the control tibiae. Histological evaluation showed greater remodelling in four of five control limbs when compared to the dynamized limb. Dynamization at 31 days post-operatively may delay bone remodelling, despite a trend towards a larger callus size. The results of this study failed to show a definitive role for early full axial dynamization.

Risk factors and prognostic variables for survival of foals with radiographic evidence of pulmonary disease.

The medical records of 163 neonatal foals that had thoracic radiographs taken within 48 hours of admission to a referral hospital were reviewed. The objectives of this study were (1) to identify risk factors for the development of thoracic radiographic changes and (2) to identify prognostic indicators for survival in foals with radiographic evidence of pulmonary disease. Failure of transfer of passive immunity (IgG concentration < or = 400 mg/dL) was the only risk factor for radiographic evidence of respiratory disease identified by multivariate analysis. Hypoxemic patients (PaO2 < or = 60 mm Hg) were 4.9 times more likely to reveal radiographic abnormalities in a subset of foals for which arterial blood gas results were available. Foals with a serum creatinine concentration > 1.7 mg/dL upon presentation, dyspnea, and a history of dystocia were significantly more likely to die based on the multivariate statistical outcome analysis. An anion gap > or = 20 mEq/dL was strongly associated with nonsurvival in a subset of foals with arterial blood gas results. These hematologic and biochemical variables can be readily obtained during the initial evaluation of sick foals. The presence of a high anion gap appeared to have the greatest clinical impact and may be a useful prognostic indicator in foals with radiographic evidence of respiratory disease. In contrast, the majority of physical examination variables, including evaluation of tachypnea, abnormal respiratory sounds, fever, weakness, and milk reflux from the nares, which are usually obtained during the general respiratory evaluation of foals, were unrelated to outcome.

Clinical and prognostic significance of radiographic pattern, distribution, and severity of thoracic radiographic changes in neonatal foals.

A total of 207 thoracic radiographs obtained from 128 foals were evaluated to assess the impact of pulmonary radiographic pattern, distribution, and severity of pulmonary changes on short-term survival of neonatal foals. The association between selected clinical variables and the radiographic manifestation of neonatal respiratory disease was also investigated. The evaluation of interstitial and alveolar-interstitial radiographic patterns within the caudodorsal, caudoventral, and cranioventral lung regions proved to be highly reliable between viewers in the study. A diagnosis of systemic inflammatory response syndrome was related to increased pulmonary infiltrates within the caudodorsal lung region. Dyspneic foals had more extensive pulmonary infiltrates within the cranioventral lung, advanced respiratory disease, and lower survival rates. A fibrinogen concentration >400 mg/dL was associated with increased cranioventral radiographic abnormalities. In addition, tachypnea most consistently related to diffuse (caudodorsal, caudoventral, and cranioventral) pulmonary changes. Neutropenia, milk reflux from the nares, upper airway pathology, abnormal respiratory sounds, failure of transfer of passive immunity (IgG concentration <400 mg/dL), immaturity, or fever, however, were not related to radiographic pattern, distribution, or severity of radiographic changes. Sixty-five percent of foals with radiographic pulmonary disease were discharged alive from our referral hospital. Concurrent caudodorsal and caudoventral radiographic disease was most frequently observed in this foal population. Increased caudodorsal radiographic scores retained statistical significance as a prognostic indicator for nonsurvival in a multiple stepwise logistic regression analysis.

Leptin, body composition and bone mineral density in premenopausal women.

Body weight is known to be associated with bone mass, however, it is unclear whether body composition, as reflected by the percent of total weight that is fat tissue (%fat), is associated with bone mass independently of weight. Fat tissue is metabolically active, and hormonal factors may mediate an association of %fat with bone mass. Leptin, a hormone produced in fat tissue, has recently been shown to be inversely related to bone mass in mice, but whether it is related to human bone mass is uncertain. We sought to investigate the associations of %fat and of serum leptin concentration with bone mineral density (BMD) in a cohort of 153 premenopausal women. BMD measurements of the total hip, lumbar spine and total body as well as body composition were measured by dual energy X-ray absorptiometry (DXA). Serum leptin levels were established using a commercial competitive binding assay. Individually, body weight, %fat and leptin were each positively associated with BMD at all three sites. However, when we examined BMD either as a function of both body weight and %fat together, or as a function of both body weight and leptin together, we found that for a given body weight, BMD appeared to be inversely associated with %fat and similarly appeared to be inversely associated with leptin. When BMD was examined as a function of %fat and leptin together, we found that for a given %fat, leptin appeared to be inversely associated with BMD. In summary, the results of this study suggest that for a given body weight, a higher proportion of fat and a higher serum leptin concentration have negative associations with bone mass in premenopausal women.

Binge eating disorder in extreme obesity.

OBJECTIVE: To determine whether extremely obese binge eating disorder (BED) subjects (BED defined by the Eating Disorder Examination) differ from their extremely obese non-BED counterparts in terms of their eating disturbances, psychiatric morbidity and health status. DESIGN: Prospective clinical comparison of BED and non-BED subjects undergoing gastric bypass surgery (GBP). SUBJECTS: Thirty seven extremely obese (defined as BMI > or = 40 kg/m(2)) subjects (31 women, six men), aged 22-58 y. MEASUREMENTS: Eating Disorder Examination 12th Edition (EDE), Three Factor Eating Questionnaire (TFEQ), Structured Clinical Interview for the Diagnostic and Statistical Manual-IV (SCID-IV), Short-Form Health Status Survey (SF-36), and 24 h Feeding Paradigm. RESULTS: Twenty-five percent of subjects were classified as BED (11% met full and 14% partial BED criteria) and 75% of subjects were classified as non-BED. BED (full and partial) subjects had higher eating disturbance in terms of eating concern and shape concern (as found by the EDE), higher disinhibition (as found by the TFEQ), and they consumed more liquid meal during the 24 h feeding paradigm. No difference was found in psychiatric morbidity between BED and non-BED in terms of DSM-IV Axis I diagnosis. The health status scores of both BED and non-BED subjects were significantly lower than US norms on all subscales of the SF-36, particularly the BED group. CONCLUSION: Our findings support the validity of the category of BED within a population of extremely obese individuals before undergoing GBP. BED subjects differed from their non-BED counterparts in that they had a greater disturbance in eating attitudes and behavior, a poorer physical and mental health status, and a suggestion of impaired hunger/satiety control. However, in this population of extremely obese subjects, the stability of BED warrants further study.

Household tobacco smoke exposure is negatively associated with premenopausal bone mass.

Subjects exposed to environmental tobacco smoke have been found to be at increased risk for several health problems. Whether exposure to passive tobacco smoke is associated with reduced bone mineral density (BMD) is unknown. In order to examine this, we measured BMD in 154 healthy premenopausal women (age range 40-45 years). BMD of the total hip, femoral neck, lumbar spine and total body was measured by dual-energy X-ray absorptiometry (DXA). Data were collected on exposure to household tobacco smoke from age 10 years to the present as well as on other lifestyle factors related to bone mass. We found that 67.5% of the subjects had a history of household tobacco smoke exposure. Subjects exposed to household tobacco smoke had a mean adjusted BMD that was significantly lower at the total hip ( p = 0.021) and femoral neck ( p = 0.018) compared with subjects who were not exposed. In addition, duration of household tobacco smoke exposure was negatively associated with BMD at the total hip ( p = 0.010), femoral neck ( p = 0.004), lumbar spine ( p = 0.037) and total body ( p = 0.031). Subjects exposed to household tobacco smoke for 15 years or more had mean adjusted BMD that was 4% lower at the total body, and more than 8% lower at the total hip, femoral neck and lumbar spine, compared with subjects who were not exposed. In conclusion, household tobacco smoke exposure during adolescence and young adulthood was found to be negatively associated with BMD at the total hip and femoral neck, and duration of exposure was negatively associated with BMD at the total hip, femoral neck, lumbar spine and total body in premenopausal women.

Recall of early menstrual history and menarcheal body size: after 30 years, how well do women remember?

The validity of recall of early menstrual characteristics is of interest because of their putative role in the etiology of breast cancer and other diseases. A retrospective follow-up of the Newton Girls Study (1965-1975) provided an opportunity to assess the accuracy and precision of recall of several early menstrual characteristics. In 1998-1999, 57 percent of the original 793 Newton Girls Study participants completed a mailed questionnaire to assess the accuracy of recall for age and body size at menarche, usual cycle length during the first 2 years, and age at regularity. Recalled and original age at menarche were highly correlated (r = 0.79, p < 0.001). The body mass index percentile at menarche was well correlated with recalled body size at menarche (r = 0.61, p < 0.001), but with some evidence of systematic bias. Overall, a woman's recall of menarcheal age and body size was better than recall of cycle length and occurrence of regularity. The failure to identify certain menstrual characteristics as exposures for subsequent disease may reflect limitations in the accuracy and precision of the recalled measures.

Erratum to: Traffic injury data, policy, and public health: Lessons from Boston Chinatown.

In the March 2002 issue, the following credit line was omitted from Fig. 1(a) on p. 90 (Brugge D, Lai Z, Hill, C, Rand W. Traffic Injury Data, Policy, and Public Health: Lessons from Boston Chinatown. J Urban Health. 2002;79(1):87-103): "This figure is reprinted with permission from Brugge D, A Leong, Z Lai. Can a community inject public health values into transportation questions? Public Health Rep. 1999:114:44."

Peripheral vascular endothelial function testing as a noninvasive indicator of coronary artery disease.

OBJECTIVES: We studied whether assessment of endothelium-dependent vasomotion (EDV) with brachial artery ultrasound (BAUS) imaging predicts the presence or absence of coronary artery disease (CAD) as defined by exercise myocardial perfusion imaging (ExMPI). BACKGROUND: Abnormalities in EDV can be detected in arteries before the development of overt atherosclerosis, and its presence may predict poor long-term prognosis. Brachial artery ultrasound during reactive hyperemia is a noninvasive method of assessing peripheral EDV. METHODS: Clinically-indicated ExMPI along with BAUS were performed in 94 subjects (43 women, 51 men). Coronary artery disease was defined by myocardial ischemia or infarction on single photon emission computed tomography images. Flow-mediated dilation (FMD) after upper arm occlusion was defined as the percent change in arterial diameter during reactive hyperemia relative to the baseline. RESULTS: Subjects with CAD by ExMPI (n = 23) had a lower FMD (6.3 +/- 0.7%) than those without CAD by ExMPI (n = 71) (10.5 +/- 0.6%; p = 0.0004). Flow-mediated dilation was highly predictive for CAD with an odds ratio of 1.32 for each percent decrease in FMD (p = 0.001). Based on a receiver-operator analysis, an FMD of 10% was used as a cut-point for further analysis. Twenty-one of 23 subjects who were positive for ExMPI had an FMD < 10% (sensitivity 91%), whereas only two of 40 subjects with an FMD > or =10% were ExMPI-positive (negative predictive value: 95%). There was a correlation between the number of cardiac risk factors and FMD. Individuals with an FMD < 10% exercised for a shorter duration than those with an FMD > or =10% (456 +/- 24 vs. 544 +/- 31 s, respectively; p = 0.02). CONCLUSIONS: Assessment of EDV with BAUS has a high sensitivity and an excellent negative predictive value for CAD and, thus, has the potential for use as a screening tool to exclude CAD in low-risk subjects. Further standardization of BAUS is required, however, before specific cut-points for excluding CAD can be established.

Reduced kidney function and anemia as risk factors for mortality in patients with left ventricular dysfunction.

OBJECTIVES: We sought to evaluate the relationship between the level of kidney function, level of hematocrit and their interaction on all-cause mortality in patients with left ventricular (LV) dysfunction. BACKGROUND: Anemia and reduced kidney function occur frequently in patients with heart failure. The level of hematocrit and its relationship with renal function have not been evaluated as risk factors for mortality in patients with LV dysfunction. METHODS: We retrospectively examined the Studies Of LV Dysfunction (SOLVD) database. Glomerular filtration rate (GFR) was predicted using a recently validated formula. Kaplan-Meier survival analyses were used to compare survival times between groups stratified by level of kidney function (predicted GFR) and hematocrit. Cox proportional-hazards regression was used to explore the relationship of survival time to level of kidney function, hematocrit and their interaction. RESULTS: Lower GFR and hematocrit were associated with a higher prevalence of traditional cardiovascular risk factors. In univariate analysis, reduced kidney function and lower hematocrit, in men and in women, were risk factors for all-cause mortality (p < 0.001 for both). After adjustment for other factors significant in univariate analysis, a 10 ml/min/1.73 m(2) lower GFR and a 1% lower hematocrit were associated with a 1.064 (95% CI: 1.033, 1.096) and 1.027 (95% CI: 1.015, 1.038) higher risk for mortality, respectively. At lower GFR and lower hematocrit, the risk was higher (p = 0.022 for the interaction) than that predicted by both factors independently. CONCLUSIONS: Decreased kidney function and anemia are risk factors for all-cause mortality in patients with LV dysfunction, especially when both are present. These relationships need to be confirmed in additional studies.

Short-term comparative outcomes associated with the use of GP IIb/IIIa antagonists in patients undergoing coronary intervention.

BACKGROUND: Platelet glycoprotein (GP) IIb/IIIa antagonists reduce the occurrence of death, myocardial infarction (MI) and urgent revascularization among patients undergoing percutaneous coronary intervention (PCI). Despite a similar mechanism of platelet inhibition, the three currently approved agents vary widely in cost. PURPOSE: The purpose of this prospectively designed, retrospective analysis was to determine clinical outcomes for patients receiving abciximab, tirofiban or eptifibatide as adjunctive therapy during PCI at a single center. We hypothesized that there would be no difference in outcomes during hospitalization following PCI in patients receiving tirofiban or eptifibatide compared with those patients who received abciximab. Outcomes examined included in-hospital mortality, hemorrhagic procedural complications, need for recatheterization, peak creatine kinase following intervention and length of hospital stay (LOS). RESULTS: Two hundred and sixty seven consecutive patients in whom GP IIb/IIIa antagonist therapy was initiated in the catheterization laboratory for PCI were analyzed. Abciximab-treated patients were more likely to be undergoing primary (p<0.001) and rescue (p=0.022) PCI and to have received fibrinolytic therapy (p=0.013) when compared to patients receiving tirofiban or eptifibatide. There were no significant differences between abciximab- and non abciximab-treated patients in either the primary PCI or non primary PCI groups in any of the studied endpoints. In patients undergoing primary PCI, abciximab-treated patients when compared with non abciximab-treated patients exhibited a trend toward an increase in hospital LOS (7.8+/-7.0 d vs 6.2+/-3.9, p=0.19) and in the frequency of hemorrhagic complications (22.1% vs 5.3%, p=0.11). In patients not receiving fibrinolytic therapy, abciximab-treated patients experienced a trend toward increased hemorrhagic complications following PCI when compared to non abciximab-treated patients (10.2% vs 6.0%, p=0.28). Complications distant from the vascular access site comprised 62.5% of hemorrhagic complications in the abciximab-treated group, but only 20% of the complications in the non-abciximab treated population (p<0.001). These data suggest no differences in acute outcomes between groups of patients receiving abciximab or other approved GP IIb/IIIa antagonists highlighting a potential significant cost saving. These data will require interpretation following the publication of comparative trials.

Weight and body mass index at menarche are associated with premenopausal bone mass.

Adolescence is a critical time for skeletal growth and mineralization. Exposure to protective or detrimental factors during this period may influence peak bone mass attainment and subsequent development of osteoporosis. In order to evaluate the association of body size during adolescence with subsequent adult bone mass, we conducted a follow-up study of a community-based cohort of girls who participated in a growth and sexual maturation study 30 years ago. Data from the original study included age at menarche, height at menarche and weight at menarche. Follow-up evaluation of 119 subjects, now premenopausal women ages 40-45 years, included bone mineral density (BMD) measurements of the total body, lumbar spine, femoral neck, total hip, and ultradistal radius by dual-energy X-ray absorptiometry. After adjustment for current adult weight and other factors related to bone mass, weight at menarche was found to be positively associated with subsequent adult BMD. Similarly, body mass index (BMI) at menarche was positively associated with adult BMD. In contrast, age at menarche was not found to predict adult BMD. When the subjects were divided into quartiles based on their BMI at menarche, subjects in the lowest quartile of BMI at menarche had adult mean BMD that was 8-15% lower at the measured sites compared with subjects in the highest quartile of BMI at menarche. In conclusion, low body weight and low BMI at menarche appear to be significant predictors of reduced bone mass in healthy premenopausal women ages 40-45 years.

Cognitive therapy, nutritional therapy and their combination in the treatment of bulimia nervosa.

BACKGROUND: This study compared the effectiveness of cognitive therapy (CT), nutritional therapy (NT), the combination of cognitive and nutritional therapy (CNT), against a control condition of support group (SG) in the treatment of bulimia nervosa. METHODS: One hundred female out-patients who fulfilled DSM-III-R criteria for bulimia nervosa were randomized to the four treatment groups. NT and CT were designed to cover different areas with minimal overlap, and CNT provided all of the features of both of these treatments. The control condition was conducted in a group self-help format. Each of the treatments lasted 14 weeks. RESULTS: All three active treatments as well as SG produced significant decreases in binge/vomit episodes. Intent-to-treat analysis found CNT and CT to be significantly more effective than SG in retaining subjects in treatment and completion of study, as well as in producing greater improvements in dysfunctional attitudes and self-control. CNT was superior to SG in achieving abstinence from bulimic behaviour. NT was superior to SG only in increase of self-control. Logistic regression found that the cognitive component, whether given alone or in conjunction with NT, and higher pre-treatment self-control scores were significant predictors for both completion of study and abstinence. CONCLUSION: CT (either alone, or in combination with nutritional therapy) remains the treatment of choice for bulimia nervosa. A treatment escalation approach should be tested for the treatment of bulimia with the more intensive and less widely available CT (with or without nutritional counselling) offered after patients have failed the less intensive and more widely available support group treatment.

Evaluation of a discontinuous treatment protocol (VELCAP-S) for canine lymphoma.

Eighty-two dogs with lymphoma received a single 15-week course of chemotherapy, after which treatment was ceased until relapse. Fifty-six dogs (68%) achieved complete remission for a median 1st remission duration of 20 weeks. Forty-eight dogs relapsed, of which 30 repeated the induction cycle. In 22 of these dogs, 1st remission had been short, and they received maintenance chemotherapy; the other 8 dogs received 2 or 3 cycles of induction chemotherapy. Second remission rate for these 30 dogs was 87% (26 dogs). Overall disease control for the 38 dogs that remained on protocol was 44 weeks, which was not markedly shorter than for dogs treated with a previously reported protocol in which maintenance chemotherapy was instituted in all dogs after an identical 1st induction (VELCAP-L). Dogs that were febrile and dogs that were dyspneic were less likely to achieve a complete remission to induction chemotherapy. Of dogs that achieved a complete remission, those that were thrombocytopenic at entry had a shorter 1st remission, and dogs that were anorexic at entry had shorter overall disease control. There was a correlation between 1st remission duration and length of any subsequent remission obtained. The incidence of toxicity was high, particularly after the combination of doxorubicin and vincristine. Dose reductions because of toxicity did not markedly reduce remission duration. We conclude that discontinuous chemotherapy may reduce patient visits in a small number of patients because of long-term disease control. Delaying maintenance chemotherapy until after 2nd remission is achieved does not markedly affect overall disease control.

Neuropeptide Y has a central inhibitory action on the hypothalamic-pituitary-thyroid axis.

Recent evidence suggests that neuropeptide Y (NPY), originating in neurons in the hypothalamic arcuate nucleus, is an important mediator of the effects of leptin on the central nervous system. As these NPY neurons innervate hypophysiotropic neurons in the hypothalamic paraventricular nucleus (PVN) that produce the tripeptide, TRH, we raised the possibility that NPY may be responsible for resetting of the hypothalamic-pituitary-thyroid (HPT) axis during fasting. To test this hypothesis, the effects of intracerebroventricularly administered NPY on circulating thyroid hormone levels and proTRH messenger RNA in the PVN were studied by RIA and in situ hybridization histochemistry, respectively. NPY administration suppressed circulating levels of thyroid hormone (T(3) and T(4)) and resulted in an inappropriately normal or low TSH. These alterations were associated with a significant suppression of proTRH messenger RNA in the PVN, indicating that NPY infusion had resulted in a state of central hypothyroidism. Similar observations were made in NPY-infused animals pair fed to the vehicle-treated controls. These data are reminiscent of the effect of fasting on the thyroid axis and indicate that NPY may play a major role in the inhibition of HPT axis during fasting.