Metastatic Renal Cell Carcinoma in a Renal Allograft: A Sustained Complete Remission After Stimulated Rejection.

We report the case of a 40-year-old woman who recovered from a diffuse metastatic renal cell carcinoma that developed from a kidney allograft. She was successfully treated by the induction of tumor rejection. Immunosuppression was discontinued, and transplant nephrectomy was deliberately delayed based on the expectation that the tumor mass would trigger the alloimmune response, which was stimulated with pegylated interferon-α-2a. Three years later, the patient remained in complete remission. Despite this severe context, the present case shows that the poor prognosis of allograft metastatic renal cell carcinoma could be dramatically reversed by taking advantage of the donor tumor origin to actively induce a specific alloimmune rejection of the tumor.

Fumagillin for treatment of intestinal microsporidiosis in renal transplant recipients.

We report 10 cases of intestinal microsporidiosis due to Enterocytozoon bieneusi in renal transplant (RT) recipients who were treated with fumagillin. All patients presented with afebrile subacute diarrhea (median of 2 weeks), associated with abdominal cramps (n = 5), and weight loss (n = 6), a mean of 68 months after RT. The diagnosis was made by the identification of microsporidial spores in stools with the use of appropriate staining and confirmed by a specific polymerase chain reaction assay for E. bieneusi in 7 patients. Median CD4 cell count was 292 cells/mm(3). All patients received a median of 14 days of oral fumagillin (20 mg tid), and four patients also discontinued or tapered their immunosuppressive regimen (mycophenolate mofetil in 3, and azathioprine in 2). Clinical symptoms resolved rapidly with the clearance of microsporidial spores from stools in all patients. A severe but reversible thrombocytopenia was observed in one patient during fumagillin therapy, and another patient presented with abdominal cramps. Trough levels of tacrolimus measured in seven patients dropped below 5 ng/mL in six of them after 7-14 days of fumagillin. Intestinal microsporidiosis can cause subacute diarrhea in RT recipients. Fumagillin is an effective treatment with an acceptable safety profile, but monitoring of tacrolimus levels is warranted.

Pharmacoeconomic assessment of specific immunotherapy versus current symptomatic treatment for allergic rhinitis and asthma in France.

OBJECTIVES: The therapeutic benefit of specific immunotherapy (SIT) in allergic rhinitis and asthma has been endorsed by expert consensus. This study compared the cost/efficacy (C/E) of SIT with current symptomatic treatments (CST) for allergic rhinitis and asthma. METHODS: A C/E analysis was performed using a decision tree model. The decision tree and medical and economic hypotheses were defined by a panel of experts. The perspective adopted was that of the French Social Security. The costs and efficacy of SIT and CST were compared for dust-mite and pollen allergies, in adults and children. Direct medical costs included diagnosis and follow-up, consultations, CST and SIT. End-point economic criteria were cost per stabilised patient and cost per asthma case avoided. A sensitivity analysis was performed for each model. RESULTS: In adults, the incremental costs per asthma case avoided with injectable SIT were 393 Euro and 1327 Euro for dust-mite and pollen allergy, respectively, over a 6-year period. For sublingual SIT, the costs per asthma case avoided were 3158 Euro and 1708 Euro, respectively. In children, over a 7-year period, the incremental costs per asthma case avoided with injectable SIT were 583 Euro and 597 Euro for dust-mite and pollen allergy, respectively. For sublingual SIT the incremental costs were 3938 Euro and 824 Euro. CONCLUSION: Compared to CST, SIT is a cost-effective treatment in pollen and dust-mite-induced allergic rhinitis and asthma. Sublingual SIT is an attractive option in pollen-induced rhinitis, particularly in children. SIT appears to be an economically relevant strategy compared to CST.

Germ-line effects of a mutator, mu2, in Drosophila melanogaster.

A mutator, mu2a, in Drosophila melanogaster potentiates terminal deficiencies. In the female germ line the gamma mutant frequency induced by irradiation of mature oocytes with 5 Gy increases approximately twofold in heterozygotes and 20-fold in homozygotes compared with wild type. The recovery of terminal deficiencies is not limited to breaks close to chromosome ends; high frequencies of deficiencies can be recovered with breakpoints located in centric heterochromatin or near the middle of a chromosome arm. Lesions induced by gamma-rays are repaired slowly in mu2a oocytes, but become "fixed" as terminal deficiencies upon fertilization. A few lesions induced in wild-type females also produce terminal deficiencies. Mutator males do not exhibit an increase in terminal deletions, regardless of the germ cell stage irradiated. In addition, there is no increase in the mutant frequency when mature sperm are irradiated and fertilize eggs produced by mu2a females. The data are consistent with the hypothesis that lesions induced in sperm chromosomes are repaired after fertilization, while lesions induced in oocyte chromosomes are shunted instead to a mechanism that stabilizes broken chromosome ends. We propose that mu2 affects chromosomal structure during oogenesis, thereby modulating DNA repair.

An evaluation of Tourette syndrome and medication use in Canada.

Self-report data were gathered from a national sample of over 200 Canadian Tourette Syndrome (TS) patients. Information regarding symptom severity both on and off medication was gathered along with an analysis of different medications in use, and patient ratings of effectiveness of those medications. Patients also rated their own mental health. Results indicated that approximately 60% of TS patients take some form of medication for relief from their symptoms. Of these, over 80% reported that symptoms are less severe when medicated. The most commonly prescribed medications in order of popularity are haloperidol, pimozide, clonidine and benztropine mesylate (Cogentin). Patient ratings of effectiveness of these medications places haloperidol first, pimozide second and clonidine third although all were found to be "somewhat" to "very" effective. Of those TS patients on medications, 50% rated their own mental health as good to excellent and 50% rated it as fair to poor.

Tourette syndrome and social functioning in a Canadian population.

Two hundred and ten patients with Tourette Syndrome (TS) and/or their parents completed a survey, answering questions about the frequency and disruptiveness of vocal and motor tics, behaviour problems and sleep disturbances. Respondents also rated the impact of TS symptoms on social relationships and level of personal and social functioning. Motor tics were reported to be more problematic than were vocal tics. Disruptive behavioural problems included obsessive-compulsive rituals, hyperactivity, anxiety, temper tantrums, mood swings, aggressiveness and coprolalia. Respondents also reported problems getting to sleep, bad dreams, somnambulism and enuresis. More than 40% of respondents reported problems in dating, and problems in making and keeping friends. Family members, friends and physicians were reported to be the most understanding and tolerant of TS symptoms; employers were rated as being the least understanding. More than 30% of respondents reported some problems in coping, but more than 50% of respondents also rated their mental health as good or excellent.

Tourette syndrome and educational problems in Canada.

A comprehensive survey of known Tourette Syndrome patients was conducted on a national basis in Canada. In addition to in-depth historical background information, symptomatology, geography and demographics, data were collected regarding educational issues. Approximately 70% of the sample were receiving some sort of education. The most commonly cited educational problems were with concentration, paying attention, and performance on time-limited tasks. In almost all cases the school had been informed of the Tourette Syndrome diagnosis, but in 78% of respondents the school personnel were rated as not at all knowledgeable regarding TS. Despite problems, 66% of TS patients reported being generally satisfied with the education being received. Patients made recommendations regarding how educational experiences could be made better. Of these suggestions, educating educators was the most frequent recommendation.

Tourette syndrome and medical treatment in Canada.

Self-report data were gathered from a national sample of over two hundred Canadian Tourette Syndrome (TS) patients. Included was previous use of stimulant medication and prior extended use of antihistamines for allergies or sinus condition. Patients were also asked information on Tourette Syndrome-precipitated hospitalization or boarding school placement, the type of physician treating them and on a five-point scale their level of satisfaction with their medical care. Results indicate that over 20% of TS patients have used stimulant medications and 30% have used antihistamine for extended periods. Many patients have spent time in psychiatric settings and most are under the care of psychiatrist or neurologist. Approximately 40% of TS patients reported being satisfied to very satisfied with the medical care they were receiving, and 20% having mixed feelings. Few patients receiving medical care were dissatisfied with their treatment.

Tourette syndrome: impact on Canadian family functioning.

An evaluation of the impact of Tourette Syndrome on the family. Self-report data were gathered from a Canadian sample of over two hundred Tourette Syndrome patients and/or their families regarding the effects of TS on family life. Patients rated the extent to which having TS interfered with the family's day-to-day activities. Also indicated was whether marital difficulties or difficulties with alcohol or drugs arose since the Tourette diagnosis was made. Data were also gathered on the number of TS patients or other family members who sought professional counselling and the extent to which counselling was found helpful.

Randomized phase III study comparing Best Supportive Care to Biafine as a prophylactic agent for radiation-induced skin toxicity for women undergoing breast irradiation: Radiation Therapy Oncology Group (RTOG) 97-13.

PURPOSE: To determine if Biafine compared to Best Supportive Care (BSC) is effective in minimizing or preventing radiation-induced dermatitis in women undergoing breast irradiation. METHODS AND MATERIALS: Patients were randomized between Biafine (n = 83) vs. BSC (n = 89). The institutions identified preference for BSC at the time of randomization. A no-treatment arm was allowed (16% received no treatment). Patients were instructed to apply randomized product three times a day, but not within 4 h of their daily RT session. Application began following their first radiation treatment and continued 2 weeks postradiation. Skin dermatitis was scored weekly utilizing the RTOG and ONS (Oncology Nursing Society) skin toxicity scales, a weekly patient satisfaction and quality-of-life questionnaire. RESULTS: Using the RTOG toxicity scale there was no overall difference for maximum dermatitis during RT between Biafine and BSC (p = 0.77). There was no difference in maximum toxicity by arm or breast size. There was an interaction between breast size and toxicity, with large-breasted women exhibiting more toxicity. Large-breasted women receiving Biafine were more likely to have no toxicity 6 weeks post RT. CONCLUSION: There was no overall difference between BSC and Biafine in the prevention, time to, or duration of radiation-induced dermatitis.

The teaching of crisis counseling skills to pediatric residents: a one-year study.

Pediatric residents should learn to manage family crises such as informing parents that their child has a potentially life-threatening illness. Unfortunately, few training programs prepare residents to counsel parents of a child with cancer. An experiential parent crisis counseling program has been developed at the Children's Hospital National Medical Center in Washington, DC; this program has demonstrated that pediatric residents, with limited instruction, can be taught to give bad news to parents using effective information-giving and interpersonal skills.

Bilateral retinoblastoma with ectopic intracranial retinoblastoma: trilateral retinoblastoma.

In 11 patients, bilateral retinoblastoma presented at a mean age of 6 months and pineoblastoma at 4 years. We suggest that the hereditary multicentric retinoblastoma arose in vestigeal photoreceptors in the pineal as well as in the hypothetical retinoblasts of the retina. In certain lower animals, the pineal functions as a photoreceptor organ, resembles the retina histologically, and is described as a "third eye." Hence, the patients we describe may be considered as having "trilateral retinoblastoma." Two possible variants of this entity were also noted: (1) three children without retinoblastoma with rosettes and photoreceptor differentiation characteristic of retinoblastoma, and (2) three additional cases involving children who presented with retinoblastoma-like tumors in the suprasellar or parasellar region 2 to 6 months before the discovery of intraocular retinoblastoma. These observations suggest that the retinoblastoma gene confers a previously unappreciated susceptibility to a narrow spectrum of neuroblastic tumors, which usually present in the retina but which can also occur ectopically.

Inductive effects of fenofibrate and metabolism of phenobarbital.

The inductive effects of fenofibrate (FF) and phenobarbital (PB) were investigated in male Wistar rats. FF treatment produced an inductive effect on liver weight, cytochrome P450 content, and aniline hydroxylase (AH) and bilirubin UDP-glucuronosyltransferase (UDP-GT) activities in liver microsome fraction. PB and FF inductive effects were additive on liver weight but were not additive on P450 microsomal concentrations. On the contrary, FF administration decreased the inductive effect of PB on bilirubin UDP-GT activity. When FF and PB treatment were coupled, plasma and liver PB concentrations were not affected, whereas OHPB concentrations, especially in liver homogenate, were greatly decreased. Thus it can be concluded that the production of OHPB from PB was probably not accelerated, but the elimination of OHPB, the main metabolite of PB, was considerably enhanced. These results are to be compared with recent reports of structure-dependent induction of bilirubin glucuronidation by arylcarboxylic acids chemically related to clofibrate.

Economic impact of providing workplace influenza vaccination. A model and case study application at a Brazilian pharma-chemical company.

OBJECTIVE: To develop and apply a model to assess the economic value of a workplace influenza programme from the perspective of the employer. DESIGN: The model calculated the avoided costs of influenza, including treatment costs, lost productivity, lost worker added value and the cost of replacing workers. Subtracted from this benefit were the costs associated with a vaccination programme, including administrative costs, the time to give the vaccine, and lost productivity due to adverse reactions. The framework of the model can be applied to any company to estimate the cost-benefit of an influenza immunisation programme. SETTING: The model developed was applied to 4030 workers in the core divisions of a Brazilian pharma-chemical company. RESULTS: The model determined a net benefit of $US121,441 [129,335 Brazilian reals ($Brz)], or $US35.45 ($Brz37.75) per vaccinated employee (1997 values). The cost-benefit ratio was 1:2.47. The calculations were subjected to a battery of 1-way and 2-way sensitivity analyses that determined that net benefit would be retained as long as the vaccine cost remained below $US45.40 ($Brz48.40) or the vaccine was at least 32.5% effective. Other alterations would retain a net benefit as well, including several combinations of incidence rate and vaccine effectiveness. CONCLUSIONS: The analysis suggests that providing an influenza vaccination programme can incur a substantial net benefit for an employer, although the size of the benefit will depend upon who normally absorbs the costs of treating influenza and compensating workers for lost work time due to illness, as well as the type of company in which the immunisation programme is applied.

Social and cognitive approaches to depression: towards a new synthesis.

A description of a social-cognitive theory of depression is presented which combines the concepts of mental models, personal goals and social roles. An analysis is made of how a number of proposals about the onset of depression can be summarized as the loss of a valued goal or social role in an individual who has few other sources of self-worth. In subsequent sections, limitations of the theory are outlined, and the relationship between the present theory and other theories of depression is briefly considered.

Cognitive approaches to depression: a theoretical critique.

Three cognitive approaches to depression are reviewed in terms of recent advances in cognitive psychology. The approaches considered are those based on associative networks, schemata, and explanatory styles. It is argued that each of these approaches has significant limitations that can be overcome if they are replaced by the theory of mental models (Johnson-Laird, 1983). A number of specific advantages for this theory are outlined and the basis is provided for a new cognitive approach to depression.

The development of a measure of social support: the Significant Others (SOS) Scale.

A description is presented of the development of a new scale to measure social support which is called the Significant Others (SOS) Scale. The scale measures different functional resources of social support that may be provided by a number of significant role relationships within an individual's social network. Preliminary results from a sample of mature students show that the scale has good six-month test-retest reliability, and significantly distinguishes between depressed and non-depressed respondents. Details of a short form of the scale currently being developed are also presented.

Nutritional factors of microsomal enzymatic induction: influence of lipidic components of the diet.

We compared the ability of two different diets containing 6 per cent of maize oil and 6 per cent of fish oil to modify: firstly the enzyme induction by phenobarbital and secondly the phenobarbital hydroxylation by the liver either in vivo or during in vitro perfusions. The presence of fish oil in the diet increased the cyt P 450 content and the bilirubin glucuronosyl transferase activity. The two induction effects promoted by the association of the phenobarbital treatment and the eating of the fish oil were not additive and it was found that the phenobarbital induction effect was decreased by the fish oil consumption. Phenobarbital and p-hydroxyphenobarbital kinetics were different in the two groups of animals. Phenobarbital was more slowly eluted in the fish oil fed than in the maize oil fed rats while p-hydroxyphenobarbital was more slowly eluted by the fish oil-fed rat livers.

[Information campaign in Aquitaine about protection against malaria for travelers going to tropical regions]. / Campagne d'information en Aquitaine pour la protection contre le paludisme des voyageurs se déplaçant en zone tropicale.

The incidence of imported malaria is increasing in France, in relation to the increasing frequency of travel to tropical areas and the extension of chemoresistant strains of Plasmodium falciparum throughout the world. Worsening morbidity and mortality due to this parasite in the last 5 years is having an impact in socioeconomic terms; this is all the more prejudicial in that a young healthy population is concerned. Traditional chemoprophylaxis is at present insufficient for adequately controlling this recrudescence. Both the public and general practitioners should be made more aware of the measures to be taken during, and especially after foreign travel, in order to reverse the present tendency concerning imported malaria, and to improve travellers' protection.

Tourette syndrome, epilepsy, and emotional disorder, a case of triple comorbidity.

We present a case report illustrating the complexity encountered in the diagnosis and treatment of patients with multiple diagnoses. The clinical presentation in Tourette syndrome, and the behavioural manifestations in some cases of complex partial seizures can both be misunderstood and misdiagnosed. The paper, within the framework of a case, emphasises the need for a multidisciplinary approach in the assessment and management of such cases.