Cognitive and psychiatric symptoms in genetically determined Parkinson's disease: a systematic review.

The aim was to review the existing reports on cognitive and behavioural symptoms in monogenic forms of Parkinson's disease (PD) and to identify recurring patterns of clinical manifestations in those with specific mutations. A systematic literature search was conducted to retrieve observational studies of monogenic PD. Data pertaining to cognitive and psychiatric manifestations were extracted using standardized templates. The PRISMA guidelines were followed. Of the 1889 citations retrieved, 95 studies on PD-related gene mutations were included: 35 in SNCA, 35 in LRRK2, four in VPS35, 10 in Parkin, three in DJ1 and eight in PINK1. Nineteen studies (20%) provided adequate data from comprehensive cognitive assessment and 31 studies (32.6%) outlined psychiatric manifestations through the use of neuropsychiatric scales. Cognitive impairment was reported in all monogenic PD forms with variable rates (58.8% PINK1, 53.9% SNCA, 50% DJ1, 29.2% VPS35, 15.7% LRRK2 and 7.4% Parkin). In this regard, executive functions and attention were the domains most affected. With respect to psychiatric symptoms, depression was the most frequent symptom, occurring in 37.5% of PINK1 cases and 41.7% of VPS35 and LRRK2 cases. Co-occurrence of cognitive decline with visual hallucinations was evidenced. Widespread accumulation of Lewy bodies, distinctive of SNCA, PINK1 and DJ1 mutations, results in higher rates of cognitive impairment. Similarly, a higher degree of visual hallucinations is observed in SNCA mutations, probably owing to the more widespread accumulation. The lower rates of α-synuclein pathology in LRRK2 and Parkin may underpin the more benign disease course in these patients.

Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU): Trial Satisfaction and Attitudes towards Future Clinical Trials.

BACKGROUND: Clinical trial satisfaction is increasingly important for future trial designs and is associated with treatment adherence and willingness to enroll in future research studies or to recommend trial participation. In this post-trial survey, we examined participant satisfaction and attitudes toward future clinical trials in the Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU). METHODS: We developed an anonymous, participant satisfaction survey tailored to participants enrolled in the DIAN-TU-001 double-blind clinical trial of solanezumab or gantenerumab and requested that all study sites share the survey with their trial participants. A total of 194 participants enrolled in the trial at 24 study sites. We utilized regression analysis to explore the link between participants' clinical trial experiences, their satisfaction, and their willingness to participate in upcoming trials. RESULTS: Survey responses were received over a sixteen-month window during 2020-2021 from 58 participants representing 15 study sites. Notably, 96.5% of the survey respondents expressed high levels of satisfaction with the trial, 91.4% would recommend trial participation, and 96.5% were willing to enroll again. Age, gender, and education did not influence satisfaction levels. Participants reported enhanced medical care (70.7%) and pride in contributing to the DIAN-TU trial (84.5%). Satisfaction with personnel and procedures was high (98.3%). Respondents had a mean age of 48.7 years, with most being from North America and Western Europe, matching the trial's demographic distribution. Participants' decisions to learn their genetic status increased during the trial, and most participants endorsed considering future trial participation regardless of the DIAN-TU-001 trial outcome. CONCLUSION: Results suggest that DIAN-TU-001 participants who responded to the survey exhibited high motivation to participate in research, overall satisfaction with the clinical trial, and willingness to participate in research in the future, despite a long trial duration of 4-7 years with detailed annual clinical, cognitive, PET, MRI, and lumbar puncture assessments. Implementation of features that alleviate barriers and challenges to trial participation is like to have a high impact on trial satisfaction and reduce participant burden.

The serotonin-1Dbeta receptor gene and severity of obsessive-compulsive disorder in women with bulimia nervosa.

BACKGROUND: There is significant evidence that eating disorders have an important biological overlap with obsessive-compulsive disorder (OCD), though the specific mediators of this relationship remain unclear. Recent evidence suggests that the G861C polymorphism of the 5HT-1Dbeta receptor gene and the G allele in particular may play a role in OCD. We thus hypothesized that, among a heterogenous group of probands with bulimia nervosa (BN), this same G allele might predict the presence and/or severity of OCD pathology. METHODS: 165 consecutive female probands with BN were genotyped for the G861C polymorphism of the 5HT-1Dbeta receptor gene. Rates of full syndrome OCD, partial syndrome OCD and no OCD were compared across the three genotypic groups defined by this polymorphism. RESULTS: 45 out of 165 BN probands (27.3%) had either full or partial syndrome OCD. In the full sample, there was a significant difference in the distribution of the three diagnostic groups by genotype (chi2=10.07, df=4, p=.039). The G861C polymorphism did not strongly predict which probands had any vs. no OCD pathology. However, among the 45 probands with OCD symptoms, the G861C polymorphism did strongly differentiate full syndrome vs. partial syndrome OCD (chi2=9.26, df=2, p=.01; odds ratio for full syndrome OCD with GG genotype=7.69, 95% CI=1.45-40.9). DISCUSSION: In women with BN, the G861C polymorphism of the 5HT-1Dbeta gene does not appear to be associated with the generation of OCD symptoms; however, it might directly or indirectly be associated with a modulatory effect on syndrome severity in probands otherwise predisposed to OCD. While preliminary and in need of replication in other samples, this is the first association study to suggest how a particular gene might influence OCD pathology in an eating disorder population.

Qualitative analysis of emergency department reports applied to a pilot project for the prevention of pediatric burns.

Accidents and burns are a major problem in Italy and in industrialized countries, due to the consequences they have on health, especially in children aged 0-4 years. In Italy, about 400 people die each year from burns, with over 70% of these occurring in the home. In the European Union, burns are one of the top five causes of death from accidents, accounting for 3% of all deaths from accidents and violence in those age groups. One percent of all deaths in children are due to burns. In this paper, we illustrate the results of qualitative analysis, conducted according to the methodology of content analysis, on narratives included in the anamnesis of clinical papers at the ED in 738 cases of burns in children (0-14 years) observed in a sample of Emergency Departments in the years 2005-2009. The results of content analysis show that the most frequent mechanism that leads to burns is contact with hot liquids and heating surfaces. Much of preventive action should be directed at controlling the child. The accidental event descriptions for the younger age group (0-4 years) reveal an unequivocal responsibility of the parents. The qualitative analysis of narratives was carried out to produce scientific evidence to identify the more frequent and severe burn accidents for specific target/age groups and to establish specific preventive measures. The study of qualitative analysis of burns observed at the ED was introductory to the pilot project PRIUS (Preventing burns among school-aged children). The objective of PRIUS is to increase awareness of the risks of burns in children and adults through a learning path tailored towards their prevention, and the promotion of appropriate standards of personal safe behaviour and first aid actions.

Les accidents et les brûlures représentent en Italie et dans les pays industrialisés, un problème majeur de santé publique, en particulier chez les enfants entre 0 et 4 ans. En Italie, environ 400 personnes meurent chaque année de brûlures, dont 70% sont survenues au domicile. Dans l'Union Européenne, les brûlures (3% des causes de mort violente ou accidentelle), entrent dans le groupe des cinq causes les plus fréquentes de décès dans cette tranche d'âge. Dans cet article, nous présentons les résultats de l'analyse qualitative, réalisée selon la méthodologie de l'analyse de contenu, des dossiers d'entrée aux urgences de 738 cas de brûlures chez les enfants (0-14 ans) survenues entre 2005 et 2009, dans un échantillon représentatif de la population italienne. L'analyse de contenu montre que les causes les plus fréquentes qui conduisent aux brûlures dans les groupes d'âge étudiés sont représentées par le contact avec des liquides chauds et les surfaces de chauffage. Donc, une grande partie des actions préventives doit être élaborée en direction de la surveillance de l'enfant. L'étude de l'événement accidentel, pour ce groupe d'âge (0-4 ans), révèle une responsabilité sans équivoque des parents. L'analyse qualitative des récits a aidé à produire les preuves scientifiques des circonstances de survenue des brûlures graves et étendues chez des enfants petits, afin préconiser des mesures spécifiques de prévention. Notre étude est une étude d'analyse qualitative réalisée avant de proposer le projet pilote Prius (Prévention des accidents et des brûlures chez les enfants d'âge scolaire). L'objectif de Prius est d'accroître la sensibilisation aux risques de brûlures chez les enfants et les adultes à travers un parcours d'apprentissage adapté à leur prévention et la promotion de protocoles appropriés de comportement et de premiers secours.

Pharmacogenetics of antipsychotic treatment: lessons learned from clozapine.

The reintroduction of clozapine, the prototype of atypical antipsychotics, in the late 1980s has led to significant advances in the pharmacological management of schizophrenia. Since then, there has been a rapid development of novel "atypical" antipsychotic agents that have been pharmacologically modeled, to a certain extent, after their predecessor clozapine. As with all antipsychotics, there is variability among individuals in their response to these "atypical" drugs. Pharmacogenetics can provide a foundation for understanding this interindividual variability in antipsychotic response. This review first provides a rationale for the pharmacogenetic investigation of this variable trait. Studies of pharmacokinetic and pharmacodynamic factors of antipsychotic therapy are considered in the development of this rationale. Next, the molecular genetic techniques used to study this interindividual variation in response are described. This is followed by a review and discussion of the published studies examining genetic factors involved in clozapine response. From this, several recommendations for future pharmacogenetic investigations of antipsychotic response are proposed. Although still in its early stages, psychiatric pharmacogenetics should provide a basis for individualized pharmacotherapy of schizophrenia, and may also lead to the development of newer, more efficacious antipsychotic agents.

Polymorphism of the serotonin 5-HT1B receptor gene (HTR1B) associated with minimum lifetime body mass index in women with bulimia nervosa.

BACKGROUND: Preclinical research has shown that the serotonin-1B receptor has important modulatory effects on feeding behavior and thus body weight. In the current study, we examined whether genetic variation of the serotonin-1B receptor was associated with minimum and maximum lifetime body mass indices (BMIs) in a sample of women with bulimia nervosa (BN). METHODS: Ninety-eight women with BN were genotyped based on the G861C polymorphism of the serotonin-1B receptor gene (HTR1B). Minimum and maximum lifetime BMIs were compared across the three genotypic groups using analysis of variance. RESULTS: There was a highly significant difference in minimum lifetime BMI across the three genotypic groups (p =.001). Both the G/C and C/C genotypes were associated with significantly lower minimum lifetime BMIs than was the G/G genotype. Maximum lifetime BMI was not significantly different across groups. These results were not attributable to different lifetime rates of anorexia nervosa across the three genotypic groups. CONCLUSIONS: These preliminary findings suggest a possible association between HTR1B genetic polymorphism and minimum lifetime BMI in women with BN. These findings may shed light on why, in response to dieting, some BN patients achieve lower BMIs, whereas others have a natural limitation to their weight loss. Pending replication in a larger sample, these findings point to a possible genetic factor of fundamental importance to the BN population.

Genetic association analysis of serotonin system genes in bipolar affective disorder.

OBJECTIVE: This study examined the putative role of serotonin genes in the etiology of bipolar affective disorder. METHOD: Genetic association analysis was performed for individuals with bipolar affective disorder and unaffected subjects closely matched in age, sex, and ethnic background (N=103 in each group). The allele and genotype frequencies of polymorphisms at the genes for serotonin receptors HTR1A, HTR1Dalpha, HTR1Dbeta, HTR2A, HTR2C, HTR7, tryptophan hydroxylase (TPH), and the serotonin transporter (hSERT) were compared in the two groups of subjects. RESULTS: Statistically significant positive associations were found for HTR2A and hSERT polymorphisms. However, results from an independent replication group of over 100 patients with bipolar affective disorder and their matched comparison subjects failed to confirm these associations. CONCLUSIONS: These results suggest that the serotonin genes studied are not associated with bipolar affective disorder, although transmission disequilibrium studies are required in order to confirm this conclusion.

Association of the MscI polymorphism of the dopamine D3 receptor gene with tardive dyskinesia in schizophrenia.

In 112 schizophrenic patients previously treated with typical neuroleptics, we investigated the putative role of the dopamine D3 receptor gene (DRD3) in tardive dyskinesia (TD). Patients were assessed for TD severity using the Abnormal Involuntary Movement Scale (AIMS) and were subsequently genotyped for the MscI polymorphism that identifies a serine to glycine substitution in DRD3. A modified analysis of covariance model, which incorporated several clinical risk factors for TD, was utilized to detect differences in TD severity among the various genotypic groups. The glycine allele of DRD3 was found to be associated with typical neuroleptic-induced TD (F[2,95] = 8.25, p < .0005). Higher mean AIMS scores were found in patients homozygous for the glycine variant of the DRD3 gene, as compared to both heterozygous and serine homozygous patients. Although replication is necessary, this finding supports a role for the dopamine D3 receptor in the pathogenesis of TD.

Serotonin subtype 2 receptor genes and clinical response to clozapine in schizophrenia patients.

Using a pharmacogenetic approach in 185 schizophrenics who have been prospectively assessed for clozapine response, we have examined the hypothesis that polymorphisms in the 5-HT2A (HTR2A), and 5-HT2C (HTR2C) genes are involved in its variable response. A-1438 A-->G polymorphism in the putative promoter and a silent T-->C 102 substitution in HTR2A were in almost complete linkage disequilibrium, and neither was associated with response (T-->C. 102 allele: chi 2 = 0.02; 1 df, p = .90; genotype: chi 2 = 0.02, 2 df, p = .99). A his452tyr HTR2A polymorphism was found to be associated with clozapine response (his452tyr allele: chi 2 = 6.43, 1 df, p = .01 [p = .04, Bonferroni corrected]; genotype: chi 2 = 6.54, 2 df, p = .04 [p = .16, Bonferroni corrected]). No HTR2A haplotype was associated with response. Interethnic differences were observed in the frequencies of the cys23ser HTR2C polymorphism. This polymorphism was not significantly associated with response in either of the ethnic groups (Caucasian and African American genotype: chi 2 = 3.46, 2 df, p = .18; chi 2 = .31, 2 df, p = .86, respectively). Although replication is required, the overall results suggest that the his452tyr HTR2A polymorphism may be involved in clozapine response.

Childhood inattention and dysphoria and adult obesity associated with the dopamine D4 receptor gene in overeating women with seasonal affective disorder.

There is significant evidence that altered dopamine activity plays a role in seasonal affective disorder (SAD). The current study examined three separate genetic hypotheses for SAD related to the 7-repeat allele (7R) of the dopamine-4 receptor gene (DRD4), a variant associated with decreased affinity for dopamine. We examined the possible contribution of 7R to the overall expression of SAD, attention deficit disorder (ADD) comorbidity, and body weight regulation. As part of an ongoing genetic study of increased eating behavior and mood in female subjects, 108 women with winter SAD and carbohydrate craving/weight gain were administered the Wender-Utah Rating Scale to measure childhood ADD symptomatology, and a questionnaire to assess maximal lifetime body mass index (BMI). To test for an association between 7R and the categorical diagnosis of SAD, the transmission disequilibrium test (TDT) was used in a subsample of probands providing familial DNA. Standard parametric tests were used to compare childhood ADD symptoms and maximal lifetime BMI across the two genotypic groups defined by the presence or absence of 7R. The TDT found no initial evidence for an association between 7R and the categorical diagnosis of SAD. However, 7R carriers reported significantly greater inattention and dysphoria in childhood (p=0.01 and 0.001, respectively) and a higher maximal lifetime BMI (p=0.007) than did probands without this allele. Furthermore, excluding probands with extreme obesity (maximal BMI >40), a strong correlation was found linking childhood inattentive symptoms and maximal lifetime BMI (r=0.35, p=0.001). In overeating women with SAD, the 7R allele of DRD4 may be associated with a unique developmental trajectory characterized by attentional deficits and dysphoria in childhood and mild to moderate obesity in adulthood. This developmental course may reflect different manifestations of the same underlying vulnerability related to central dopamine dysfunction. Given the possibility of population stratification when studying genotype/phenotype relationships, future use of genomic controls and replication of our findings in other overeating and/or ADD populations are needed to confirm these initial results.

Absence of linkage for schizophrenia on the short arm of chromosome 5 in multiplex Canadian families.

A VNTR for the human dopamine transporter gene (DAT-1) has been localized to chromosome 5p15.3. Silverman et al. [1996] found evidence for genetic linkage of the D5S111 locus, located just centromeric to DAT-1, to schizophrenia and related disorders in a large Hispanic family. We evaluated five markers on 5p, including D5S111 and the DAT-1 VNTR, in five multiplex schizophrenic families, assuming autosomal dominant transmission (subjects assessed n = 122, DNAs available n = 96, individuals with schizophrenia and schizoaffective disorder n = 36, broader spectrum disorders n = 14). LOD scores were negative across all families for all markers tested, and overall LOD scores were strongly negative (<-2.0, theta = 0) across all five families for each of the markers typed. Thus, there is no evidence to support the linkage of markers in this region of chromosome 5 to schizophrenia in this sample of families.

Genetic dissection of atypical antipsychotic-induced weight gain: novel preliminary data on the pharmacogenetic puzzle.

Atypical antipsychotics such as clozapine represent a significant improvement over typical antipsychotics in the treatment of schizophrenia, particularly regarding extrapyramidal symptoms. Despite their benefits, use is limited by the occurrence of adverse reactions such as sedation and weight gain. This article provides a comprehensive review and discussion of obesity-related pathways and integrates these with the known mechanisms of atypical antipsychotic action to identify candidate molecules that may be disrupted during antipsychotic treatment. Novel preliminary data are presented to genetically dissect these obesity pathways and elucidate the genetic contribution of these candidate molecules to clozapine-induced weight gain. There is considerable variability among individuals with respect to the ability of clozapine to induce weight gain. Genetic predisposition to clozapine-induced weight gain has been suggested. Therefore, genetic variation in these candidate molecules may predict patient susceptibility to clozapine-induced weight gain. This hypothesis was tested for 10 genetic polymorphisms across 9 candidate genes, including the serotonin 2C, 2A, and 1A receptor genes (HTR2C/2A/1A); the histamine H1 and H2 receptor genes (H1R/H2R); the cytochrome P450 1A2 gene (CYPIA2); the beta3 and alpha,alpha-adrenergic receptor genes (ADRB3/ADRAIA); and tumor necrosis factor alpha (TNF-alpha). Prospective weight gain data were obtained for 80 patients with schizophrenia who completed a structured clozapine trial. Trends were observed for ADRB3, ADRA1A, TNF-alpha, and HTR2C; however, replication in larger, independent samples is required. Although in its infancy, psychiatric pharmacogenetics will in the future aid clinical practice in the prediction of response and side effects, such as antipsychotic-induced weight gain, and minimize the current "trial and error" approach to prescribing.

Lack of association between the T-->C 267 serotonin 5-HT6 receptor gene (HTR6) polymorphism and prediction of response to clozapine in schizophrenia.

The affinity of clozapine for 5-HT2A, 5-HT2C, 5-HT6, 5-HT7, and 5-HT1A receptors has been suggested to contribute to various aspects of its complex clinical actions. This study examined the hypothesis that genetic variation in 5-HT1A, 5-HT6, and 5-HT7 receptor genes is involved in the variability observed in response to clozapine. We employed a pharmacogenetic approach in a group (n=185) of schizophrenia patients that have been clinically well characterized for clozapine response. Polymorphisms in the 5-HT6 (HTR6), 5-HT1A (HTR1A) and 5-HT7 (HTR7) receptor genes were genotyped. No evidence for either an allelic or genotypic association of the T-->C 267 HTR6 polymorphism with response to clozapine was found in our sample (allele: chi(2)=0.06, 1 df, P=0.80; genotype: chi(2)=1.21, 2 df, P=0.55). The pro16leu HTR1A polymorphism was not observed in our sample; all individuals genotyped were pro/pro 16 homozygotes. With respect to the pro279leu HTR7 polymorphism, one Caucasian male responder to clozapine was observed to be heterozygous (pro/leu 279 genotype). This individual was clinically similar to the other clozapine responders. Overall, our findings do not support a role for the T-->C 267 polymorphism of the 5-HT6 receptor gene in response to clozapine, although replication is required to confirm this finding.

Oxidative stress after moderate to extensive burning in humans.

Lipid peroxidation products, lipid antioxidants, and hematologic and blood chemistry changes were evaluated in plasma of patients after acute burning injury involving 10% (n=8), 20% (n=8), and 40% (n=5) of total body surface area (TBSA), 24 h after burning (baseline) up to 30 days after. Markedly increased plasma levels of malondialdehyde (MDA) were observed at baseline in all patients, according to the extent of the injury, then the values declined progressively. However, levels of MDA remained above normal up to 30 days even in less injured patients. On the other hand, the plasma level of conjugated diene lipid hydroperoxides was only slightly higher than control at the baseline, then dropped under the control value in all patients. Cholesterol showed a marked fall at baseline, followed by a rapidly progressive decrease, indicating a massive loss of circulating lipids by the acute thermal injury. Because of such an extensive and rapidly spreading oxidative degradation of lipids, decomposition of conjugated diene hydroperoxides, produced in early stages of the peroxidation process, occurs, so these compounds cannot be a suitable index to value lipid oxidation in burned patients. Aldehydic products of lipid peroxidation act as endotoxins, causing damage to various tissues and organs. Damage to liver and decrease of erythrocyte survival were assessed by increased plasma levels of asparate and alanine transaminases, within 7-15 days after injury, and by a decreased number of red blood cells, which remained under the normal value at 30 days. A marked decrease of lipid antioxidants, beta-carotene, vitamin A and vitamin E was observed at baseline. The level of beta-carotene remained low in all patients at the end of the 30-day observation. A complete recovery of vitamin A did not occur at 30 days post-burn, even in the patients with 10% of burned TBSA. Plasma levels of vitamin E decreased significantly in 1-7 days after burn in all patients, but these levels increased thereafter, with almost total recovery at 30 days. These data show evidence of a marked, long-lasting oxidant/antioxidant imbalance in burned patients, in accordance with the severity of the injury, which is also reflected as systemic oxidant stress.

Polymorphism of the serotonin-2A receptor gene (HTR2A) associated with childhood attention deficit hyperactivity disorder (ADHD) in adult women with seasonal affective disorder.

INTRODUCTION: Several lines of research point to a possible overlap between seasonal affective disorder (SAD) and attention deficit hyperactivity disorder (ADHD), particularly in females. There is also emerging evidence that variation of the 5-HT2A receptor gene (HTR2A) contributes to both SAD and ADHD. The current study investigated whether variation in HTR2A was associated with symptoms of childhood ADHD in adult women with SAD. METHOD: Sixty-six women with SAD were administered the Wender-Utah Rating Scale (WURS), which retrospectively assesses childhood ADHD, as part of an ongoing genetic study of SAD. WURS scores were compared across the three genotypic groups defined by the T102C polymorphism of HT2RA. RESULTS: Analysis of variance indicated a significant difference in mean 25-item WURS scores across the three genotypic groups (p = 0.035). Post-hoc tests revealed that the C/C genotypic group had a significantly higher mean score than both the T/T group and T/C group. Based on previously established WURS criteria, 38% of subjects with the C/C genotype, and none with the T/T genotype, had scores consistent with childhood ADHD. LIMITATIONS: The current sample size is small, and childhood ADHD diagnoses were based on retrospective recall. CONCLUSION: These preliminary results suggest a possible association between variation in HTR2A, childhood ADHD, and the later development of SAD in women.

Pharmacogenetic assessment of antipsychotic-induced movement disorders: contribution of the dopamine D3 receptor and cytochrome P450 1A2 genes.

Tardive dyskinesia (TD) is characterized by involuntary movements predominantly in the orofacial region and develops in approximately 20% of patients during long-term treatment with typical antipsychotics. The high prevalence of TD and its disabling and potentially irreversible clinical course is an important shortcoming for treatment with typical antipsychotics. The studies presented in this article evaluate the role of single nucleotide polymorphisms in dopamine D3 receptor (DRD3) and CYP1A2 genes for propensity to develop TD in patients with schizophrenia. In theory, a combined pharmacogenetic analysis of pharmacokinetic and pharmacodynamic targets for antipsychotics should improve our ability to identify subpopulations that differ in drug safety profile. This information may in turn contribute to the design of more efficient clinical trials and thus expedite the development and regulatory approval of newer antipsychotic compounds.

Increased burn patient survival with once-a-day high dose teicoplanin and netilmicin. An Italian multicenter study.

This is the final report of a large, controlled, multicenter Italian study on immuno- and chemotherapy in adult patients with burns affecting 20 to 95% of total body surface area (mean 35%). The antibiotic treatment of burn patients consisted of topical silver sulfadiazine, short-term antimicrobial chemoprophylaxis with pefloxacin (800 mg i.v. qd) for the first 4 days and polychemotherapy with teicoplanin (800 mg i.v. qd) together with netilmicin (300 mg i.m. qd) in one or more cycles of 5-12 days. At random, half of the patients received thymostimulin, 70 mg i.m. qd for the first month and every other day thereafter. The analysis at completion of 634 valid cases showed that when the results are stratified by means of the Roi risk index, 396 of the 530 patients who contracted wound infection (84%) after chemoprophylaxis were in the first three categories and a mean of 95% survived. Of the remaining 134 patients (Roi index 4-5) only 50% survived. There was no difference in survival of the immunotherapy group in comparison with the parallel group without thymostimulin. The short-term antimicrobial prophylaxis prevented wound infection in only 104 of 634 patients (16%) and they were at low risk (84% Roi index 1). Of the bacterial pathogens involved in septic complications Staphylococcus aureus and Pseudomonas aeruginosa were prevalent (86%): eradication was achieved in 43% of patients and clinical cure or improvement were seen with combination chemotherapy in 64% of all patients, mainly with only one treatment cycle. This value increased to 79% for the 395 protocol-complying patients and went down to 20% in the 135 non-compliers. The total survival of complier and non-complier patients was 447 of the 530 valid patients (84%). The overall mortality of the 634 evaluable patients was 13.1%, ranging from less than 2% to 68%. Burn mortality was directly proportional to the percentage of burned body surface area, to increasing age and other variables of the Roi index, a 50% mortality being associated with a 72.5% total body surface area burned. Normoergic burn patients had a mortality rate of 9.1% versus 35.7% in anergic patients.

Safe and successful endoarterial infusion of liposomal amphotericin B in treatment of mucormycosis.

Mucormycosis is a rare invasive mycotic infection treated by antifungini or amphotericin B. We describe the case of a patient with septic fever and a necrotic lesion, with phlegmon of medial left thigh. Surgery was performed to drain the abscess content and to remove the necrotic tissue; mucormycosis was diagnosized by histological and culture tests and treated by intravenous amphotericin B. Since the lesion worsened, liposomal amphotericin B was directly infused into the left common iliac artery, with progressive improvement, and treatment was continued until complete recovery. Therefore, the endoarterial infusion of liposomal amphotericin B was a safe and successful treatment of advanced lesions of mucormycosis. In such lesions, intravenous general antibiotic administration probably is not sufficient to reach the whole infected area.