Ovarian Steroid Levels inSalamandra salamandra infraimmaculataduring the Reproductive Cycle

Gonadal steroid levels were determined in the ovary ofSalamandra salamandra infraimmaculataduring the reproductive cycle in populations from a xeric region in northern Israel. Varying proportions of previtellogenic and vitellogenic oocytes were present throughout the year, and mature oocytes were present in winter and spring. The numbers of mature oocytes were greater between December and April, after parturition. The levels of 17β-estradiol and testosterone rose during oocyte vitellogenesis and maturation. Levels of progesterone and 17α-hydroxy progesterone appeared to be related to the level of vitellogenesis. Gravid females contained greater quantities of all four steroids than did nongravid females.     

Synthesis of 14C‐labeled piperidines and application to synthesis of [14C]SCH 351125, a CCR5 receptor antagonist

1‐Benzyl‐4‐hydroxy[2‐¹⁴C]piperidine, a useful intermediate in labeled compound synthesis, was prepared from [¹⁴C]formaldehyde in high yield. The distribution pattern of ¹⁴C in the product is consistent with a mechanism involving reversible iminium ion formation and rapid equilibration of the iminium ion through a cationic aza‐Cope rearrangement. These steps precede the rate‐determining intramolecular cyclization step. SCH 351125 is a potent, selective CCR5 receptor antagonist with potential as a treatment for HIV infection. [¹⁴C]SCH 351125, required for metabolism studies, was prepared from 1‐benzyl‐4‐hydroxy[2‐¹⁴C]piperidine in six steps. [¹⁴C]SCH 351125 is a mixture of four atropisomers. Preparation of [¹⁴C]SCH 351125 besylate salt of the desired atropisomer pair is also described. Copyright © 2007 John Wiley & Sons, Ltd.     

Changing patterns of intellectual strengths and weaknesses in males with fragile X syndrome

Examined the changing profiles of intelligence in males with fragile X syndrome as these individuals increased in chronological age. Using a psychometric instrument designed to measure styles of information processing, 21 males aged 4 to 27 years were examined cross-sectionally in sequential processing, simultaneous processing, and achievement. The age of the subject was associated with age-equivalent levels of both simultaneous processing and achievement, but fragile X males did not show higher levels of sequential processing with increasing chronological age. Compared to younger fragile X males, the older subjects were more delayed in sequential processing skills relative to their abilities in other areas. A smaller longitudinal study confirmed the presence of a plateau in sequential processing among those subjects tested two times after the age of 10 years. Implications are discussed for diagnosis, intervention, and the matching of subject groups in mental retardation research.This research was supported in part by the John Merck Fund, the Joseph P. Kennedy, Jr. Foundation, NIH grants RR00125 and HD03008, and NIMH grants MH18268 and MH30929. We thank Wendy Marans and Joel Bregman for their comments on an earlier draft of this paper.     

Aberrant expression of tight junction-related proteins ZO-1, claudin-1 and occludin in synovial sarcoma: an immunohistochemical study with ultrastructural correlation.

Synovial sarcoma demonstrates epithelial differentiation, either by light microscopy (biphasic synovial sarcoma) or by immunohistochemical/ultrastructural methods only (monophasic) and poorly differentiated synovial sarcoma. Although the glands of synovial sarcoma are known to have tight junction-like structures, far less is known about junction formation in the spindled component of synovial sarcomas. Additionally, it is unknown whether the tight junctions of synovial sarcoma are normally constituted. The tight junction is a multiprotein complex consisting of numerous proteins that include ZO-1, claudin-1 and occludin. A total of 35 cases of synovial sarcoma (13 biphasic, 14 monophasic and eight poorly differentiated) were immunostained for ZO-1, claudin-1 and occludin using commercially available antibodies, heat-induced epitope retrieval and standard avidin-biotin technique. When available, corresponding electron micrographs were reviewed. For five cases, the presence of either an SYT-SSX1 (three cases) or SYT-SSX2 (two cases) gene fusion was known. Positive cases showed particulate membrane staining. The glands of biphasic synovial sarcomas expressed ZO-1 (13/13), claudin-1 (12/13) and occludin (11/13) in a manner identical to normal glandular epithelia, at the apical portion of the lateral membrane. The spindle cells of biphasic synovial sarcomas showed abnormal circumferential membranous expression of ZO-1 (12/13), claudin-1 (6/13) and occludin (3/13). Monophasic synovial sarcomas expressed ZO-1 in a circumferential pattern (13/14) but less often claudin-1 (4/14) or occludin (3/14). Poorly differentiated synovial sarcomas expressed ZO-1 (8/8) and claudin-1 (6/8) but only rarely occludin (2/8). By electron microscopy, recognizable tight junctions were seen only in glands. No correlation was seen between histologic subtype or fusion type and expression of tight junction proteins. We conclude that the glands of biphasic synovial sarcomas show well-organized, true epithelial tight junctions. In contrast, the spindled cells of all synovial sarcomas show significant abnormalities in the expression and localization of tight junction proteins, suggesting partial and/or aberrant epithelial differentiation.     

Chronic Fatigue: A Survey, Outcome Study and Proposals

Background:  Sample sizes in studies of childhood chronic fatigue remain small and there is a need to integrate research findings and establish common criteria.
Method:  This is a detailed report of 20 children with medically unexplained fatigue, referred to as Chronic Fatigue Syndrome (CFS). It includes an uncontrolled outcome study of treatment based on a pragmatic cognitive-behavioural model adapted for children at Great Ormond Street Hospital for Children.
Results:  The data revealed psychological distress at 30 times the prevalence found in the normal child population, with specific high-ranking symptoms, including headache, social withdrawal and decreased appetite. Onset tended to occur at 11 years of age with some earlier problems at school age, suggesting it might be possible to identify those most at risk. Follow-up demonstrated improvement in 87% of the sample (parental report), a significant increase in school attendance and a significant decrease in symptom severity. Factors associated with good outcome were short duration of fatigue (less than a year) and behaviours that tended to combat the cycle of avoidance, such as carefully planned home-tuition.
Conclusions:  Recording a comprehensive range of symptoms and factors facilitates comparisons within and between child studies. It is proposed that symptom severity is a particularly relevant measure for Chronic Fatigue Syndrome which is characterised by persisting symptoms.     

Coordinated diagnostic approach for adult obstructive lung disease in primary care.

AIMS: To present an age-stratified approach to the diagnosis of obstructive lung disease based on asthma and COPD guidelines and epidemiology. METHODS: Asthma guidelines emphasize the role of the history and physical examination, with pulmonary function used primarily to confirm the diagnosis. COPD guidelines begin with symptoms and risk exposure, presenting spirometry as the primary diagnostic maneuver. Data from the National Health Interview Survey and the Third National Health and Nutrition Examination Survey illustrate relationships in prevalence of asthma and COPD in nationally representative samples. RESULTS: Asthma prevalence in adults declines with age from 5-10% at age 20-40 to 4-8% above age 60. COPD is uncommon in adults under age 40 but increases with age, surpassing asthma in older adults. CONCLUSIONS: These trends suggest that asthma screening is most useful in adults up to age 40, after which COPD screening and differential diagnosis are of comparable or greater utility.     

Soft-tissue infection: necrotizing fasciitis.

Necrotizing fasciitis (NF) is a potentially fatal infection of the skin and soft tissue. The early presentation may first appear as cellulitis. The skin stays intact in the early stages of NF; this leads to a deceptive benign appearance. The skin typically appears red, hot and exquisitely tender. Blisters may or may not be present. Severe local pain, which is out of proportion to the size and type of wound, is a hallmark sign seen in NF. Recognition of the signs and symptoms, as well as timely diagnosis and treatment of this condition is imperative. This is necessary in order to assist in preventing widespread tissue destruction, and enhance favorable patient outcomes. The purpose of this paper is to increase the knowledge and understanding of NF and to discuss the nurses' role in minimizing unfavorable outcomes.