The adrenocorticotrophic hormone (4-9) analog ORG 2766 benefits autistic children: report on a second controlled clinical trial.

In a second controlled crossover trial, 20 autistic children received 40 mg/day of the neuropeptide ORG 2766, a synthetic analog of ACTH (4-9), for 8 weeks. Parents' checklist ratings (ABC) as well as clinicians' ratings (CGI) pointed to significant improvements after the course of treatment; improvements were clearest on the ABC social withdrawal subscale. The analysis of individual target symptoms and the parents' treatment preferences substantiated the beneficial effects of ORG 2766. In an ethologically analyzed playroom session, ORG 2766 treatment was associated with an improvement in the children's play behavior and a significant increase in the social interaction between child and experimenter. Gaze coordination between child and experimenter also was improved.     

Non-opiate effects of neuropeptides derived from beta-endorphin

Brain enzymes convert the opioid peptide beta-endorphin (beta E-(1-31)) to alpha- and gamma-endorphin and to several non-opioid fragments by further cleavage of the tyrosine residue or acetylation. Several of these peptides selectively affect brain functions. alpha-Endorphin (beta E-(1-16)) and relate non-opioid fragments (beta E-(2-16), beta E-(2-9) a.o.) like amphetamine, delay extinction of pole-jumping avoidance behavior and facilitate passive avoidance behavior. In addition these peptides enhance the stereotyped sniffing response induced by the injection of apomorphine into the nucleus caudatus. The fragment beta E-(10-16) inhibits, like serotonin and antidepressants, the behavioral effects of melatonin injected into the nucleus accumbens. gamma-Endorphin (beta E-(1-17)) has inherent opioid and neuroleptic-like properties, e.g. demonstrated by a naloxone reversible inhibition of hypermotility induced by apomorphine following injection into the nucleus accumbens. Also the non-opioid gamma-type endorphins (e.g. DT gamma E (beta E-(2-17) and DE gamma E (beta E-(6-17)) mimic certain effects of neuroleptics. These peptides facilitate extinction of pole-jumping avoidance behavior, attenuate passive avoidance behavior and antagonize the hypomotility and stereotyped sniffing induced by apomorphine injected into the nucleus accumbens and pyriform cortex respectively. These and other behavioral studies, including grasping responses, brain stimulation reward, food and other positively rewarded behavior, indicate that the action of alpha-type endorphins is in some aspects comparable to that of psychostimulants, while the effects of gamma-type endorphins are comparable to those of classical as well as atypical neuroleptics. Indeed, gamma-type endorphins have antipsychotic effects in a category of schizophrenic patients.     

Stromal macrophage-histiocytes in Hodgkin's disease. Their relation to fever

Morphologic variations of Concanavalin A-binding histiocytes were studied in biopsy specimens of 140 untreated patients with Hodgkin's disease (72 asymptomatic, and 68 with constitutional symptoms). Fever was the most common symptom, present in 57 of the 68 patients. Three morphologic types of stromal histiocytes were recognized: medium-sized cells similar to those seen in reactive follicles, characterized by distinct cytoplasm and cell borders, and uniform nuclei (Type A); damaged-appearing Type A cells marked by rarefied or ragged cytoplasm, disrupted or indistinct cell borders, and varying sized nuclei (Type B); and large spindling or stellate cells (Type C). Type A cells were predominant in 52 patients; Type B cells in 51; Type C cells in seven; and Type A cells were mixed with Type B in 30. Fever was present in one of 52 patients (1.9%) with Type A predominance; 43 of 51 (84.3%) with Type B cell predominance; none of seven (0%) with Type C predominance; and 13 of 30 (43.3%) with mixed Type A and B cells. Logistic regression analysis of the data showed that the association of fever with Type B cell predominance was highly significant, and was not attributable to the known association of fever with other variables. Morphologic evidence suggests that fever in Hodgkin's disease may be a clinical manifestation of damaged macrophage-histiocytes rather than an acute-phase response of inflammatory or immune reaction.     

Human immunodeficiency virus-associated Hodgkin's disease. Clinicopathologic studies of 24 cases and preponderance of mixed cellularity type characterized by the occurrence of fibrohistiocytoid stromal cells

Hodgkin's disease (HD) was diagnosed in 24 patients who were either seropositive for human immunodeficiency virus (HIV) (21) or members of a high-risk group (three), but had not developed acquired immune deficiency syndrome (AIDS). Clinical presentation of the disease was characterized by constitutional symptoms in all, especially fever (23/24) and disseminated disease (22/24) at diagnosis. Mediastinal adenopathy was rare. Bone marrow involvement was particularly frequent (12/24), and a positive bone marrow biopsy preceded lymph node biopsy in 5 of the 12. Histopathologic features of these tumors included an increased number of nonlymphoid stromal cells, i.e., histiocytic and/or fibroblastoid. In some tumors these fibrohistiocytoid stromal cells were arranged in bundles, but distinct nodule with birefringent collagen band formation was not observed. Twenty-two patients were treated, most with combination chemotherapy; one was untreated; one, unknown. Sixteen, including the one untreated, died with disease at 3 to 25 months; one died of an unrelated cause; four were alive at 3 to 24 months; three were lost to follow-up. Frequent bone marrow involvement at presentation suggests the usefulness of the bone marrow biopsy for diagnosis in subjects at risk, especially when they present with spiking fever of unknown origin. Contrary to most previous series, virtually all of our cases were of mixed cellularity type, characterized by increased fibrohistiocytoid stromal cells in place of depleting lymphocytes. The classic nodular sclerosing feature with birefringent collagen band formation was not observed. In conclusion, HIV-associated HD was characterized by advanced stage with fever at presentation, preponderance of mixed cellularity histologic type with increased fibrohistiocytoid stromal cells, and poor outcome. Hodgkin's disease in AIDS patients presents an intriguing biological model to study the role of stromal histiocytes in immunodeficient patients.     

Alpha-methyldopa induces a naltrexone-insensitive antinociception and hypomotility in rats.

1. This study served to investigate whether endogenous opioid peptides play a role in the putative antinociceptive and the sedative actions of alpha-methyldopa. 2. In conscious normotensive rats, alpha-methyldopa induced hypotension, starting around 1 h and reaching a maximum 3-4 h after administration. Pretreatment with naltrexone resulted in an inhibition of alpha-methyldopa-induced hypotension. 3. alpha-Methyldopa dose-dependently increased hot plate latency which became evident after a 4 h lag period and reaching a maximum effect at 6 h. The antinociceptive effect of alpha-methyldopa was not affected by naltrexone. 4. In a small open field, alpha-methyldopa dose-dependently suppressed locomotion and sniffing behaviour. These effects of alpha-methyldopa were apparent 1 h after administration and were naltrexone-insensitive. 5. No changes in the level of beta-endorphin-like immunoreactivity in plasma and cerebrospinal fluid were observed after administration of alpha-methyldopa. 6. The results indicate that endogenous opioid peptides are involved in the hypotensive action of alpha-methyldopa but not in alpha-methyldopa-induced hypomotility and antinociception.     

Anti-interleukin-1 reactive cells in Hodgkin's disease

Constitutional symptoms (or B-symptoms) of Hodgkin's disease may be mediated by interleukin 1 (IL-1), a product of macrophage-histiocytes. To further study this relation, the authors examined the cells that reacted with anti-human IL-1 antibody in biopsy specimens from 140 untreated patients with Hodgkin's disease (72 asymptomatic patients and 68 with B-symptoms). Fever was the most common symptom, present in 57 of the 68 patients. Anti-IL-1 reactive cells were observed in 62 cases. A positive staining reaction was observed in three types of cells: Reed-Sternberg and related (R-S) cells (33 cases); small to medium cells of undetermined origin (18); and granulocytes (11). The staining was negative in 78 cases, including 42 with B-symptoms. The majority of tumors (27/33) with positively stained R-S cells were from asymptomatic patients. Most tumors (14/18) with positively stained small to medium sized cells were from patients with B-symptoms. Large numbers of granulocytes were positively stained in five asymptomatic patients and six with B-symptoms. The immunohistochemical demonstration of IL-1-bearing cells in tumors does not correlate with the manifestation of constitutional symptoms in Hodgkin's disease.     

Effectiveness of a Multidisciplinary Education Protocol in Children with Asthma (0-4 Years) in Primary Health Care

This paper describes the results of an asthma self-management protocol delivered to parents of children aged 0-4 years. The protocol was delivered by general practitioners (GPs), community nurses, asthma nurses, and doctors in child health centers. It consisted of 16 educational modules developed after an initial needs assessment of parents and a task analysis of primary care practitioners. The program was evaluated by means of an experimental design. Parents participating in the program had significantly more knowledge, a more favorable attitude toward asthma, and a higher self-efficacy score with respect to performing asthma self-management behaviors. Also, they reported performing self-management behaviors more frequently than parents in the control group. One-year follow-up results, which were collected for parents in the treatment group only, showed that the described changes were sustained. Further, the treatment group was found to have decreased its emergency and nonemergency use of the physician's office and to have a reduction in (reported) asthma severity. Process evaluation indicated that most modules were provided by the GPs to nearly all parents. After parents had read the modules at home, almost all the information was discussed in the next contact. GPs seldom referred patients to the community nurses, although this was suggested in the protocol.     

Long-term results of the Cox-Maze III procedure for persistent atrial fibrillation associated with rheumatic mitral valve disease: 10-year experience.

OBJECTIVE: We evaluated the long-term results of the Cox-Maze III procedure (CM-III) for persistent atrial fibrillation (AF) associated with rheumatic mitral valve (MV) disease. METHODS: We analyzed 127 patients who underwent the CM-III combined with a rheumatic MV procedure between 1994 and 2004. In-hospital mortalities were excluded from the study. RESULTS: There were 10 late deaths and the mean follow-up duration was 7.1+/-2.8 years (range, 13 months to 11.5 years). Normal sinus rhythm was restored in 88.2% (112/127) after the CM-III. Right atrial contractility was demonstrable in 100% (112/112) and left atrial contractility in 68.8% (77/112) of the patients restored to sinus rhythm. Fifteen patients never regained sinus rhythm after the CM-III (AF treatment failure). Permanent pacemakers were implanted in 4.7% (6/127) of the patients during the follow-up. Late recurrence of AF developed in 34 of 112 patients at 44+/-27 months postoperatively, and sinus rhythm was restored in 29 of 34 patients by administration of an antiarrhythmic medication. Independent risk factors for late AF recurrence were longer duration of AF (>60 months) (odds ratio (OR)=2.758, p=0.025), increased left atrial size (OR=1.113, p=0.004). Freedom from AF recurrence was 93% at 1-year, 82% at 3 years, 71% at 5 years, and 63% at 7 years. Risk factors for AF treatment failure were longer duration of AF (>60 months) (p<0.001) and increased patient age (p=0.030). A higher prevalence of significant late tricuspid regurgitation was observed in patients with AF treatment failure and those with late AF recurrence. CONCLUSIONS: The CM-III for persistent AF associated with rheumatic MV disease demonstrated a progressively decreased cure rate during the follow-up period. Early surgical therapy, aggressive left atrial reduction, and correction of tricuspid regurgitation at the time of surgery may increase the long-term success rate.     

Cleaved variant of plasmacytoma with myelomonocytic differentiation--immunohistochemical and ultrastructural studies.

Although plasma cells are terminally differentiated B cells, neoplastic plasma cells frequently express not only pre-B cell antigen, but also megakaryocytic, myelomonocytic, or erythroid markers. Since morphologic diagnosis of plasmacytoma is based on the recognition of neoplastic cells closely resembling normal plasma cells, unusual morphologic variants of neoplastic cells associated with these aberrant immunohistochemical features frequently cause diagnostic difficulty. The authors report a case of plasmacytoma with cleaved nuclei and myelomonocytic features occurring in the clavicle. The tumor was composed of immature plasma cells showing irregular, cleaved, and multilobated nuclei and abundant cytoplasm with prominent eosinophilic granules. A few tumor cells showing recognizable plasmacytic differentiation were admixed within the tumor. Immunohistochemically, the tumor cells expressed CD45RB, CD68, lysozyme, myeloperoxidase and kappa light chain with focal positivity for lambda chain. Ultrastructurally, the tumor cells contained numerous membrane bound electron dense lysosomal granules, some of them resembling Auer rods, as well as rough endoplasmic reticula arranged in lamellated stacks. Small biopsied nasal mucosal tissue in same patient revealed well differentiated plasmacytoma composed of tumor cells showing round, eccentric nuclei devoid of marked nuclear cleavage and cytoplasmic granularity. Immunohistochemically, these cells were kappa(+), lambda(-), myeloperoxidase(-), lysozyme(-) and CD68(-).     

Bilateral versus unilateral sudden sensorineural hearing loss.

OBJECTIVES: To analyze the clinical characteristics and treatment results between bilateral (bi-) and unilateral (uni-) sudden sensorineural hearing loss (SSNHL). STUDY DESIGN AND SETTING: A retrospective study. METHODS: Three hundred twenty-four patients with SSNHL were classified into two groups; simultaneous bi-SSNHL (n = 16) and uni-SSNHL (n = 308). We compared clinical characteristics, medical history, hearing level, and treatment results between the 2 groups. RESULTS: The incidence of bi-SSNHL was 4.9 percent of overall patients with SSNHL. Bi-SSNHL occurs more commonly in patients of older age, with preexisting diabetes mellitus, and lipid panel abnormalities compared with uni-SSNHL. Ten patients (62.5%) in the bi-SSNHL group showed hearing recovery in 1 or both ears compared with 56.5 percent of patients with uni-SSNHL. Only 12 (37.5%) of all 32 ears recovered in bi-SSNHL, which was significantly lower than in uni-SSNHL. CONCLUSION: Bi-SSNHL has a very low incidence and lower recovery rate than uni-SSNHL. Recognition of similarities and differences between bilateral and unilateral SSNHL can help in counseling and managing the patients.