Patient perception and approval of faecal microbiota transplantation (FMT) as an alternative treatment option for obesity.

INTRODUCTION: Fecal microbiota transplantation (FMT) represents a treatment option for some diseases, e.g. recurring Clostridium difficile-associated colitis. However, there is also evidence that FMT can be effective in treating obesity. This pilot study established the approval and willingness of obese patients to undergo FMT. METHODS: We conducted a survey of adults with obesity using a questionnaire containing 21 both multiple choice and open questions was dispatched to a cohort of 101 persons with obesity. It included questions aiming at the process of FMT itself, donors as well as possible concerns. Additionally aspects of social background and disease activity were dealt with. RESULTS: The response rate amounted to 30.1% (n = 31). In our population, mean BMI was 40.5 kg/m2 while the vast majority already tried out treatment modalities to lose weight before. 25.8% of persons with obesity were aware of FMT. 62.1% were willing to undergo FMT if the donor was healthy and anonymous while only 6.9% clearly refused this option. Sixty preferred an anonymous donor or a person proposed by their doctor while colonoscopy was the preferred application by 76.7%. The absence of risks of the procedure (47.8%) formed the principal motivation while reduction of medication was considered as least important reason (in 26.1). Insufficient testing of the faeces concerning infections raised the most concerns (in 61.6%). CONCLUSION: For the majority of the persons with obesity surveyed FMT represents a treatment option. Approximately two thirds of the questionees would consider FMT as an alternative treatment option, even in spite of a satisfactory disease response to current standard therapies. Unsurprisingly there are concerns in regard to the transmission of possible infectious agents as well as to the hygieneic implementation of FMT itself.

Dermatophagoides farinae-specific immunotherapy in atopic dogs with hypersensitivity to multiple allergens: a randomised, double blind, placebo-controlled study.

A randomised, placebo-controlled, double blind study was conducted on 25 dogs that had atopic dermatitis, together with skin test reactivity and elevated serum IgE to Dermatophagoides farinae (Df) and at least one additional allergen. Dogs were treated with either a Df-restricted immunotherapy solution (n=14) or a placebo (n=11) and evaluated 6 weeks and 3, 5, 7 and 9 months after the initiation of treatment using a clinical scoring system (SASSAD) and pruritus analogue scale scores. The Df-restricted solution and the placebo had an equal effect on both pruritus and the skin manifestations (P>0.05). The results of this study indicate that in dogs with atopic dermatitis based on hypersensitivity to environmental allergens in addition to D. farinae, Df-restricted immunotherapy is insufficient to control the disease. Consequently, a solution for allergen-specific immunotherapy should remain customised.

Immune function in healthy inner-city children.

The importance of investigating immunity in healthy children has been underscored in the last few years by studies of the immune pathology of childhood illnesses, including human immunodeficiency virus. This study reports both ennumerative and functional immune measures in healthy inner city children. A total of 152 of 207 children studied were completely heathy at the time of venipuncture and were included in this study. Laboratory immune batteries were completed (or begun) the same day as venipuncture. Relationships between age, gender, ethnicity, and immunity were then analyzed. We found that gender predicted both the absolute number and the percentage of T cells and helper cells and the percentage of natural killer cells. Total leukocyte counts and percentages of lymphocytes and granulocytes were related to ethnicity, as was the response to mitogen stimulation (concanavalin A and pokeweed mitogen) and phagocytic ability. In conclusion, age, gender, and ethnicity factors were found to contribute to differences in various immune measures in children and require further investigation.

Immune changes in alcohol-dependent patients without medical disorders.

INTRODUCTION: We examined a battery of in vitro immune measures in inner city alcohol-dependent (as determined by the Structured Clinical Interview for DSM-III-R (SCID) persons who were without liver or other medical disorders and free of other substance abuse. These subjects were seeking treatment at an ambulatory alcohol treatment center. METHODS: Alcohol-dependent subjects (n = 44) were compared with healthy, nonabusing community subjects (n = 34). Subjects, both male and female, had a mean age of 41 years and were primarily African American. Many were homeless. An extended battery of enumerative and functional immune measures was obtained, as well as information about alcohol consumption. RESULTS: CONTROLLING for age and gender, ANCOVA revealed no differences (p > 0.1) between alcohol-dependent and control subjects in leukocyte and lymphocyte subsets or in circulating CD56+ (natural killer) cells. There were also no significant differences in responses to the mitogens phytohemagglutinin, concanavalin A, or pokeweed mitogen ( > 0.1) or in natural killer cell activity (p > 0.1). There was, however, altered granulocyte function in the alcohol-dependent sample, with decreased phagocytic activity in the alcohol-dependent males (p < 0.04) and gender and age dependent differences in the number of circulating granulocytes (p < 0.01). Granulocyte killing of Staphylococcus aureus, however, did not differ between the groups. CONCLUSIONS: The findings suggest that although males with chronic alcohol dependence have compromised phagocytic function, chronic alcohol-dependent subjects who are free of medical disorders do not have substantial abnormalities in many immune system functions.

Depression and immunity: clinical factors and therapeutic course.

While many reports describe associations between depressive disorders and altered immunity, findings have not been fully consistent. Diagnostic subtype, demographic factors such as age and gender, medical characteristics, and the immune measures selected for assessment may have contributed to the heterogeneous findings. In a study of 21 medically healthy young adults with major depression, we found, consistent with previous reports, evidence of increased lymphocyte activation to mitogen challenge and decreased natural killer (NK) cell numbers and function during acute depression. Fifteen subjects were followed longitudinally. T, CD4+, CD29+, and CD45RA+ lymphocytes and T-cell mitogen responses decreased significantly (P<0.05) during 6 weeks of pharmacotherapy and concurrent clinical improvement. There was no change in NK activity or CD56+ cells. The longitudinal effects appeared unrelated to tricyclic antidepressant levels. Changes in the immune system with short-term clinical improvement in depressed patients are not uniform providing further evidence that several mechanisms are involved in the altered immunity associated with clinical depression.

Adjustment disorder: a multisite study of its utilization and interventions in the consultation-liaison psychiatry setting.

The consultation-liaison (C-L) psychiatry services of seven university teaching hospitals in the United States, Canada, and Australia (the MICRO-CARES Consortium) used a common clinical database to examine 1039 consecutive referrals. A diagnosis of adjustment disorder (AD) was made in 125 patients (12.0%); as the sole diagnosis, in 81 (7.8%); and comorbidly with other Axis I and II diagnoses in 44 (4.2%). It had been considered as a rule-out diagnosis in a further 110 (10.6%). AD with depressed mood, anxious mood, or mixed emotions were the commonest subcategories used. AD was diagnosed comorbidly most frequently with personality disorder and organic mental disorder. Sixty-seven patients (6.4%) were assigned a V code diagnosis only. Patients with AD were referred significantly more often for problems of anxiety, coping, and depression; had less past psychiatric illness; and were rated as functioning better--all consistent with the construct of AD as a maladaptation to a psychosocial stressor. Interventions were similar to those for other Axis I and II diagnoses, in particular, the prescription of antidepressants. Patients with AD required a similar amount of clinical time and resident supervision. It is concluded that AD is an important and time-consuming diagnostic category in C-L psychiatry practice.

Immune function in healthy adolescents.

In the present study, we examine immunological functioning in normal healthy African-American and Latino/Latina adolescents recruited from an inner-city high school and an inner-city clinic. A battery of tests was performed with enumerative and functional measures which encompassed both innate and adaptive immunity. We found immune differences related to age, gender, and race on both the enumerative and the functional immune measures. This data expands the available body of information concerning normal immunity in healthy adolescents.

Organic mental disorders in the consultation-liaison psychiatry setting. A multi-site study.

Interventions recommended by consultation-liaison psychiatrists for inpatients they diagnosed as having DSM-III-R organic mental disorder (OMD) were studied to see to what extent specific variables distinguished the OMD patients and differentiated the subgroups of patients with OMD. Prospective data and Mini-Mental State Exam (MMSE) scores on 625 consecutive referrals at 3 general hospitals in Australia and the United States were collected by using the MICRO-CARES database system. The OMD group differed from the other patients because they were significantly more likely to have been referred for "organic brain syndrome" or "agitation," had less mood disorder and lower MMSE scores, and received more recommendations for antipsychotics and for ward-environment manipulation and fewer recommendations for psychological management. The many differences among the OMD subgroups were also consistent with their DSM constructs. A pilot exploration of the validity of the DSM-IV constructs of cognitive disorder and its subgroups performed on the redistributed data suggested that these constructs have similar usefulness.

Phagocytosis and killing of Staphylococcus aureus: effects of stress and depression in children.

While a large body of literature depicting relationships between depression or stress and immunity exists, few such studies have dealt with children, and none investigated myeloid cell-derived immunity. We investigated both phagocytosis and bactericidal activity against Staphylococcus aureus in children with major depressive disorder (MDD). We found that both MDD and stress influence the bactericidal but not the phagocytic activity of polymorphonuclear leukocytes. The data support the existence of psychobiologic effects in children and suggest possible mechanisms by which depression and stress may affect health.

Formation and persistence of N7- and O6-methyl-guanine in DNA of chick embryo brain cells in ovo following administration of N-nitroso-N-methylurea.

Previously, O6-methyl-guanine-DNA alkyltransferase (AT) of the chicken embryo has been investigated in vitro. In the present studies, the effect of in vivo (in ovo) treatment with methylnitrosourea (MNU) was examined at a developmental stage of 15 days and doses of 1.25-20 mg/egg, yielding about 1-16 mmol MNU/kg embryo weight. At intervals of 1-24 h, DNA of the brain was prepared. N7-methylguanine and O6-methylguanine were quantified by combining a rapid method of DNA isolation, high-pressure-liquid-chromatography (HPLC) and electrochemical detection of the guanine-alkyl adducts. In parallel, the AT activity of brain homogenates was determined. Within the range of the detection limits (N7-methylguanine: 16 nM, O6-methylguanine: 2.5 nM), no repair of the guanine adducts, being about 500 nmol O6-methyl- and 1800 nmol N7-methyl-adducts per mmol guanine 1 h following administration of 10 mg MNU/egg, was evident. The rather low acute toxicity of MNU in the chicken embryo at the 15th day of development DL50/24 h being > 4 mg MNU/embryo, argues, therefore, for an additional repair mechanism, e.g. cell replacement repair.

O6-alkylguanine-DNA alkyltransferase, DNase I, nucleic acid synthesis and nucleoids in vitro under the influence of pentosan polysulfate.

The in vitro influence of pentosan polysulfate (CAS 116001-96-8, PPS) on DNase I activity as well as on O6-alkylguanine-DNA alkyltransferase (AT), nucleic acid synthesis, nucleoid sedimentation and viscosity of alkaline lysates of chicken embryo brain cells was studied. PPS inhibited the activities of AT and DNase I in a dose-dependent manner, with ED50 values being about 13 and 380 micrograms/ml. Scheduled DNA synthesis was depleted by PPS. The ED50 values ranged between 45 and 55 micrograms PPS/ml. A slight increase in RNA synthesis could be observed at polyanion concentrations of 28-112 micrograms/ml. Nucleoid sedimentation and viscosity of alkaline cell lysates reflected a decrease in chromatin compactness at lower (7-25 micrograms/ml) and an increase in chromatin compactness at higher (> or approximately = 112 micrograms/ml) PPS concentrations. From the present results it is concluded that PPS, at clinically relevant concentrations, is able to interact in vitro with enzyme systems being critical to important nuclear functions. The remarkably high sensitivity of the nuclear enzyme AT deserves further investigations with regard to a possible synergism of polyanions and chemotherapeutically used alkylating agents.

Immunity in young adults with major depressive disorder.

OBJECTIVE: The authors previously found evidence for an age-related association between major depression and altered immunity. The present study was designed to assess a range of immune measures in young adults with major depression. METHOD: A homogeneous group of 21 unmedicated, ambulatory young adults with unipolar major depressive episode, as determined with the Structured Clinical Interview for DSM-III-R, were assessed in comparison with 21 matched nondepressed subjects. An extended battery of quantitative and functional immune measures was obtained on the same day from depressed and nondepressed subjects. RESULTS: Young adult subjects with major depression had more circulating leukocytes and granulocytes, fewer CD56+ (natural killer [NK]) cells, and, when the number of circulating NK cells was controlled, less NK cell activity. Mitogen responses, consistent with the authors' previous report, showed little difference between the young adults with and without major depression except for a possibly greater response at the highest dose of phytohemagglutinin. CONCLUSIONS: Major depression in young adults is associated with alterations in aspects of the immune system primarily involving NK cells. Some but not all these immune changes differ from those found in older depressed adults.

Human immunodeficiency virus-type 1 infection in an inner-city alcohol treatment program.

The human immunodeficiency virus (HIV) infection rate was examined in a selected cohort of healthy clients of an inner-city alcohol treatment center from 1990 through 1993. These subjects were also participating in a research protocol (n = 258) designed to assess immunity and HIV risk behaviors in inner city alcohol-dependent persons. Healthy alcohol-abusing heterosexual clients (165) had HIV testing conducted in an inner-city ambulatory alcohol treatment center between September 1990 and December 1993. Respondents were 93.9% African-American and 3.6% Hispanic; 72.1% were male. Anonymous HIV-1 antibody testing was conducted retrospectively for an additional 80 subjects who participated in the research protocol during the same interval, but for whom HIV-1 antibody testing was not conducted clinically at the time. HIV infection rate among the clinic-tested subjects (n = 165) was 4.4% for individuals who were exclusively alcohol-dependent, 1.4% for non-injecting drug use (IDU) mixed substance abusers, and 46.8% for clients with a history of IDU. Rates did not differ among cohorts tested in different years. Among non-injecting drug users tested in the clinic, all infected respondents (n = 3) were women (p = 0.03). Among those tested anonymously (n = 80), however, infection rate for exclusively alcohol-dependent persons was 16.7%, non-IDU mixed abusers 11.1%, and injecting drug users 48.3%, with seropositive males as well as females in each group. HIV infection rates for the pooled samples (n = 245) were 8.7% for exclusively alcohol-dependent persons, 5.1% for mixed abusers, and 54.5% for injecting drug users. Among non-injecting drug users, exclusively alcohol-dependent women had a significantly higher (p < 0.01) infection rate (20.0%) than the remaining females and males. Infection rates among exclusively alcohol-dependent males, male and female polysubstance non-IDU abusers, and injecting drug users were comparable with that seen in an earlier screening in the same clinic in 1989, with apparently little diffusion of infection from the IDU population to other substance abusers. An exception seemed to be exclusively alcohol-dependent females, who show substantially elevated rates. Age, housing, and other social differences may help segregated substance-abusing populations in the relatively small Newark metropolitan area, although not protecting exclusively alcohol-dependent females.

Adaptive response of the chicken embryo to low doses of x-irradiation.

Chicken embryos were x-irradiated in ovo with 5-30 cGy (=priming dose) at the 13th-15th day of development. After 3-48 h, brain- and liver-cell suspensions were x-irradiated in vitro with (challenge) doses of 4-32 Gy. Significantly less radiation damage was observed when the radiation response was measured by scheduled DNA synthesis, nucleoid sedimentation and viscosity of alkaline cell lysates 12-36 h after the priming exposure. In vivo, pre-irradiation with 10 cGy enhanced regeneration as evidenced by the DNA content of chicken embryo brain and liver 24 h following a challenge dose of 4 Gy. From nucleoid sedimentation analyses in brain and liver cells immediately after irradiation with 16 Gy and after a 30-min repair period in the presence of aphidicolin, dideoxythymidine and 3-aminobenzamide or in the absence of these DNA repair inhibitors, it is concluded that a reduction of the initial radiation damage is the dominant mechanism of the "radio-adaptive" response of the chicken embryo. Sedimentation of nucleoids from ethidium bromide (EB) (0.75-400 micrograms/ml)-treated cells suggests a higher tendency of "radio-adapted" cells to undergo positive DNA supercoiling in the presence of high EB concentrations.

Radiation biochemistry of the chicken embryo: DNA synthesis and DNA degradation following X-irradiation.

Chicken embryos were X-irradiated with a dose of 8 Gy. At a developmental stage of 15 days, desoxyribonucleic acid (DNA) synthesis, nucleoid sedimentation, viscosity of the alkaline cell lysates and DNA fragmentation were examined in brain and/or liver cells. Further studies aimed at the appearance of acid-soluble nucleic acid metabolites in the allantoic fluid. Complementary investigations comprised the in vitro activities of a DNase I and a DNase II of liver and brain cells as well as of the allantoic fluid of X-irradiated embryos. It could be shown for the first time that, following acute X-irradiation of the chicken embryo, the inhibition of DNA synthesis is accompanied by at least two enzymatic DNA degradation phases. The early phase comprises a period of 6 (-12) h, whereas the second phase lasts, with organ-specific peculiarities, > or = 24 h. During the early period, some apoptotic phenomena are seen, whereas at the later stages of radiation response signs of necrolysis become evident. The excretion of DNA metabolites, probably oligonucleotides, in the allantoic fluid is enhanced following X-irradiation > 2 Gy and may be used as an additional parameter of the overall radiation damage. Therefore, the chicken embryo may be regarded as a radiobiological and possibly toxicological alternative to laboratory animals with respect to the nucleic acid metabolism.

Alteration of immune system function in tetraplegics. A pilot study.

Over the past 20 yr, evidence has accumulated that implicates the autonomic nervous system as a central modulator of immune function. We hypothesized that injury to the cervical spinal cord would affect immune function by dysregulation of the sympathetic outflow tract. To test this hypothesis, peripheral blood lymphocytes were obtained from five individuals with complete cervical spinal cord injury (SCI) and from five age- and sex-matched neurologically intact controls. Immunologic parameters studied included cell counts by flow cytometry, lymphocyte proliferation response to three mitogens and a natural killer cell cytotoxicity assay. In addition the Ilfeld Psychiatric Symptom Index was completed by all subjects and controls. Repeated measures analysis of variance revealed an impaired lymphocyte proliferation response in the SCI group. Our results suggest that individuals who have sustained complete cervical SCI have alteration in immune function as compared with neurologically intact controls. This may contribute to infections after spinal cord injury. The mechanism may involve dysregulation of the sympathetic arm of the autonomic nervous system.

Electrical stimulation of the dorsal midbrain periaqueductal gray suppresses peripheral blood natural killer cell activity.

This study examined the effects of dorsal midbrain periaqueductal gray (PAG) stimulation on both splenic and peripheral blood natural killer (NK) cell function as well as the proliferative response of lymphocytes to phytohemagglutinin mitogen. Male Sprague-Dawley rats were implanted with bipolar electrodes in the dorsal PAG. Following recovery, bipolar electrical stimulation eliciting a flight response was delivered at the rate of one/min for 30 min to freely moving rats. While dorsal PAG stimulation did not alter mitogen response or splenic NK activity, stimulation of this region of the PAG produced a marked decrease in peripheral blood NK response. In order to begin to explore a possible mechanism regulating suppression of peripheral blood NK activity, naltrexone (10 mg/kg) was administered prior to dorsal PAG stimulation. The results of this experiment replicated the findings that demonstrated suppression of peripheral blood NK following dorsal PAG stimulation. Naltrexone did not effect PAG induced suppression of peripheral blood NK. These findings point to the importance of the dorsal aspect of the PAG in the regulation of peripheral blood NK activity and further suggest that this phenomenon may not be opioid mediated.