Behaviour problems, maternal internalising symptoms and family relations in families of adolescents and adults with fragile X syndrome.

BACKGROUND: Studies have linked the behaviour problems of children with fragile X syndrome (FXS) to maternal well-being, but less is known about how behaviour problems relate to important family factors such as marital satisfaction and family cohesion. METHODS: Married mothers of 115 adolescents and adults with FXS completed questionnaires and interviews, and maternal CGG repeat length was obtained by medical/laboratory records or by blood analysis. RESULTS: Indirect effects were present between behaviour problems and family variables in that behaviour problems were positively related to maternal internalising symptoms which were, in turn, negatively associated with both family cohesion and marital satisfaction. Direct associations between behaviour problems and family relationship variables were not significant. CONCLUSIONS: Findings suggest the importance of intervening with behaviour problems in individuals with FXS and identify maternal mental health as a potentially powerful conduit for the effects of child behaviour on relationships within these families. Implications for targeted interventions are discussed.

Thinking about feelings: emotion focus in the parenting of children with early developmental risk.

BACKGROUND: Children with developmental delays exhibit more difficulty with certain emotional processes than their typically developing peers, which seems to partially account for the increased risk for the development of social problems in this population. Despite considerable study with typically developing populations, research on parental emotion socialisation in families of children with delays is scarce. This study examined the degree to which parents of children with early delays prioritized emotion relative to other important areas of child development and the degree to which they focused on emotion during relevant interactions with their children. METHOD: Families of 8-year-old children with (n = 42) and without (n = 89) early developmental delays completed questionnaires and interviews, and participated in a parent-child emotion discourse task. RESULTS: As predicted, parents of children with developmental delays reported lower prioritization of emotion and focused less on emotion during discourse than did parents of typically developing children. A model was supported in which a pathway existed from developmental status through prioritization to emotion focus. Emotion focus, in turn, predicted children's social skills as reported on by multiple informants. CONCLUSIONS: Parents of children with early developmental delays may focus upon emotion less in their parenting than parents of typically developing children, and related behaviours show associations with children's social skill outcomes. Findings are discussed as an initial step in thinking about the role of emotion socialisation in the families of children with delays.

Expression of integrins, degradative enzymes and their inhibitors in uveal melanoma: differences between in vitro and in vivo expression.

Posterior uveal melanoma is the most common intraocular malignancy in adults. Metastasis occurs in approximately 40% of all cases and spread is primarily to the liver. Once secondary hepatic disease has developed the prognosis is poor. Metastasis involves a series of adhesion and de-adhesion events, coupled with regulated tissue degradation to facilitate tumour cell invasion and spread to both local and distant sites. These processes are assisted by the expression of integrins and degradative enzymes by both tumour and host cells. Using a series of 10 uveal melanomas, we investigated the expression of a panel of integrins, degradative enzymes and their inhibitors that have been shown to be associated with metastasis. In addition, we undertook to establish if there might be differential expression in response to growth under artificial conditions. All the tumours expressed matrix metalloproteinases (MMP)-2 and-9, tissue inhibitor of metalloproteases (TIMP)-2, urokinase plasminogen activator (u-PA), plasminogen activator inhibitor (PAI)-1 and PAI-2. Differences in the expression of the integrins alpha1beta1, alpha2beta1 and alpha6beta1 were observed; in particular, these differences appeared to relate to expression as a consequence of growth in culture. In summary, uveal melanoma cells express both degradative enzymes and their respective inhibitors, which are important in metastasis. It would appear that differential expression of integrins is present, probably as a response to in vitro stimulation.

Measuring outcomes: a nursing report card.

Balancing quality health care with the pressures of managed care and restructuring requires monitoring and measuring outcomes. The "nursing report card" organizes data in an informative manner, allowing nursing's contributions to patient outcomes to be assessed and reported to all customers in an ongoing fashion.

Identification of the glucuronides of the hydroxylated metabolites of the antimalarial arteether in rat plasma and urine by thermospray high-performance liquid chromatography/mass spectrometry.

A method was developed to quantitate the glucuronide conjugates (phase II metabolites, log P = 0.6-1.8) of the phase I hydroxylated metabolites (log P = 2.6-2.7) of beta-arteether (2) (log P = approximately 4.0) in rat plasma and urine. The biological fluids were extracted with a C-18 solid-phase cartridge, then subjected to analysis by thermospray high-performance liquid chromatography/mass spectroscopy with a C-18 reversed-phase analytical column in the selected ion monitoring mode. The detection limits for these glucuronide conjugates in plasma and urine ranged from 25 to 60 ng/mL, and the detection limits were appropriate for the biological activity of these glucuronide conjugates in plasma. Following intravenous administration of arteether (11.6 mg/kg), the formation of these glucuronide conjugates in rat urine was undetected (below detection limit) over 24 h. However, in rat plasma, formation of 9alpha-hydroxyarteether glucuronide (13; 255 ng/mL, IC50 = 6560 ng/mL, log P = 0.93) was noted at 15 min post-injection. Although several of the glucuronide metabolites of arteether retained sufficient in vitro antimalarial activity to be potentially useful antimalarial agents if administered as prodrugs, the levels of the glucuronides formed from arteether were too low to contribute to the antimalarial activity observed for the parent compound.

Microbial and mammalian metabolism studies on the semisynthetic antimalarial, deoxoartemisinin.

PURPOSE: Deoxoartemisinin is a semisynthetic antimalarial with potential for treatment of multiple drug resistant malaria. Metabolism studies were conducted to aid in future drug development. METHODS: Microbial model systems were employed which have been shown to be good predictors of mammalian drug metabolites. Metabolism studies using rats were also performed. RESULTS: Three microbial metabolites of deoxoartemisinin were identified (2, 3, and 4). Metabolite 3 was also found in rat plasma. HPLC/MS analyses were performed on the rat plasma using 2, 3, and 4 as standards. All metabolites were thoroughly characterized by 1H and 13C-NMR. An additional rat plasma metabolite was revealed and it was shown not to be 9 alpha-hydroxyartemisinin. CONCLUSIONS: Deoxoartemisinin was metabolized to three microbial metabolites. Metabolism by rats showed the presence of two metabolites in the plasma, one of which was the same as the microbial metabolite.

Synthesis, characterization, and antimalarial activity of the glucuronides of the hydroxylated metabolites of arteether.

The hydroxylated metabolites (log P 2.6-2.7) of beta-arteether (1) in rat liver microsomes that retain their endoperoxide moiety showed comparable in vitro antimalarial activity to that of the parent drug arteether (log P = 3.89). The search for analogs of artemisinin (7) more suitable for intravenous use led to the synthesis of the glucuronide conjugates of the phase I hydroxylated metabolites of arteether which were found to have good water solubility, yet retained moderate lipophilicity (log P = 0.6-1.8). While a strong correlation was observed between the log P value of the glucuronides, the phase I metabolites, and the parent compound, it was found that 9 beta-hydroxyarteetherglucuronide (26) was the most active and the most polar (log P = 0.61) of the glucuronides. While the in vitro antimalarial activity of 26 (IC50 = 89.3 ng/mL) was found to be much less than that for the parent compound, the activity of 26 was within a range that would have potential therapeutic use.

Arthrodesis of the ankle with lateral plating.

A modification of internal fixation compression arthrodesis for ankle fusion is described using two 6.5-mm cancellous bone screws and a lateral T plate. Using this technique, 20 consecutive arthrodeses by one surgeon were reviewed. Solid union was attained in 19 of 20 patients (95%). Average follow-up was 18 months (range 6-59 months). Time to obtain solid arthrodeses averaged 18 weeks. In 11 patients who returned for follow-up, clinical grading using the Mazur scale score averaged 70 of 90 points. Diagnoses included posttraumatic degenerative arthritis, failed ankle arthrodesis and rheumatoid arthritis (2 each), failed ankle arthroplasty, and post-tuberculous arthritis (1 each). Complications included one malunion and one asymptomatic screw malposition. All patients attaining union were pleased with the procedure.

Microbial and mammalian metabolism studies of the semisynthetic antimalarial, anhydrodihydroartemisinin.

Microbial metabolism studies of the semisynthetic antimalarial anhydrodihydroartemisinin (1), have shown that it is metabolized by a number of microorganisms. Large scale fermentation with Streptomyces lavendulae L-105 and Rhizopogon species (ATCC 36060) have resulted in the isolation of four microbial metabolites. These metabolites have been identified as a 14-carbon rearranged product (2), 9 beta-hydroxyanhydrodihydroartemisinin (3), 11-epi-deoxydihydroartemisinin (4), and 3 alpha-hydroxydeoxyanhydrodihydroartemisinin (5). Microbial metabolites were completely characterized by spectral methods, including 1H-NMR and 13C-NMR spectroscopy. The structure and stereochemistry of metabolite 2 were unequivocally established by X-ray crystallographic analysis. Thermospray mass spectroscopy/high-performance liquid chromatographic analyses of plasma from rats used in mammalian metabolism studies of 1 have shown microbial metabolite 3 to be the major mammalian metabolite. In vitro antimalarial testing has shown metabolite 3 to possess antimalarial activity.

Cyst of the ligamentum flavum.

STUDY DESIGN: A patient with sciatica resulting from a hemorrhagic cyst of the ligamentum flavum is reported. Surgical removal of the cyst relieved the patient of her sciatic symptoms. SUMMARY OF BACKGROUND DATA: Cyst of ligamentum flavum is an uncommon cause of radiculopathy. There are 13 cases in the literature. CONCLUSIONS: The differential diagnosis of benign interspinal extradural mass lesions includes spinal synovial cysts, ligamentum flavum cysts, perineural cysts, dermoid cysts, and parasitic cysts.

Vascular injury in anterior lumbar surgery.

Anterior approaches to the lumbar spine are rapidly gaining popularity for decompressive and reconstructive procedures. A recognized hazard to this approach to the spine is possible injury to the great vessels. This retrospective study is a review of 102 consecutive anterior lumbar spinal procedures. All approaches were performed by one of two fellowship-trained vascular surgeons. Both have extensive experience with this approach. All injuries to the inferior vena cava, common iliac vein, or other great vessels that required suture repair were recorded. The authors were surprised to note an overall rate for this vascular complication of 15.6%. These injuries included 11 tears of the common iliac vein, four tears of the inferior vena cava, and one avulsion of the iliolumbar vein. Two different approaches were used during this study. Twenty-six cases were performed through a flank incision, with the dissection proceeding through the external and internal oblique muscles as well as the transversus abdominis. The average number of levels exposed was 2.3. Two vascular complications resulted, for an incidence of 7.7%. Seventy-six procedures were carried out through a small (5-10 cm) incision overlying the rectus abdominis muscle. The retroperitoneal space was entered through the posterior rectus sheath without division of any muscle tissue. This resulted in 14 vascular complications, for an incidence of 18.4%. Although the authors are unaware of any major long-term morbidity from this complication in their patient group, they believe feel that the true incidence of this potentially quite serious complication may be underestimated.(ABSTRACT TRUNCATED AT 250 WORDS)

Decomposition of arteether in simulated stomach acid yielding compounds retaining antimalarial activity.

In simulated stomach acid (aqueous 0.01 M HCl, 37 degrees C) beta-arteether decomposed (half-life, 441 +/- 17 min) to dihydroartemisinin, which subsequently rearranged to a new compound (1) having an endoperoxide group and an aldehyde group. The in vitro antimalarial activity of dihydroartemisinin is similar to that of beta-arteether, whereas compound 1 had approximately 1/10th the activity of beta-arteether. Compound 1 was prepared in sufficient quantities to afford samples for biological evaluation and a complete chemical characterization with 1H- and 13C-NMR and mass spectrometry. While beta-arteether would be somewhat unstable in the stomach, if the drug were administered on an empty stomach (emptying time, approximately 30 min) as a suspension or tablet, sufficient quantities of intact arteether may reach the small intestines, where it would be stable and readily absorbed. Its decomposition products, dihydroartemisinin and 1, may also contribute to the antimalarial activity of the administered drug following oral administration.

Intramedullary fixation for congenital pseudarthrosis of the tibia.

Eighteen consecutively seen patients who had a congenital pseudarthrosis of the tibia were treated operatively. The mean age when the patients were first seen was four years. Seventeen previous procedures had failed: six patients had had one previous procedure; three, two previous procedures; and one, five previous procedures. At an average follow-up interval of ten years (range, three to nineteen years), healing with re-formation of the medullary canal was seen in thirteen of the eighteen tibiae, including one tibia that had united after a Boyd amputation. Five patients did not have healing of the tibia: four of them had a below-the-knee amputation, and one declined additional treatment. The average residual angulation was 12 degrees in the sagittal plane and 5 degrees in the coronal plane. Union occurred in ten of the thirteen patients who had been managed with intramedullary fixation. Of these thirteen, eight had been managed with intramedullary fixation, bone-grafting, and implantation of an electrical stimulator, and seven of them had union. Five of the thirteen patients had been managed with intramedullary fixation and bone-grafting, and three of them had union. Union occurred in one of two patients who had been managed with vascularized free fibular transfer, one who had been managed with delayed bone-grafting, and one who had been managed with a Boyd amputation. Four of the five patients who did not have union were subsequently managed with a below-the-knee amputation, and one patient refused additional treatment.

Synthesis and the biological evaluation of the structural units of drummondin C.

Drummondin C (1) is an antibiotic isolated from a bioassay-directed fractionation of Hypericum drummondii (Grev. & Hook.)T.&G. It showed significant activity against the Gram-positive bacteria Staphylococcus aureus and Bacillus subtilis and the acid-fast bacterium Mycobacterium smegmatis. Two structural units of drummondin C, the 8-acetyl-5,7-dihydroxy-2,2-dimethylchromene (6) and 5-acetyl-3-methyl-filicinic acid (9), were synthesized to determine the relative importance of the two substructure portions to the antibiotic activity of the compound. The low antimicrobial activity of 6 and 9 demonstrates the necessity of both units for the antibiotic activity of drummondin C.

Identification of the in vivo metabolites of the antimalarial arteether by thermospray high-performance liquid chromatography/mass spectrometry.

The thermospray mass spectra of arteether and 16 of its potential metabolites all showed strong [M + NH4]+ ions and with only a few exceptions these compounds also showed spectral peaks corresponding to [M + NH4 - HOR]+ and [M + H - HOR]+, where OR represents the alkoxy or hydroxy group at the 12-position. A method for quantifying the metabolites was developed in which the plasma was spiked with an internal standard (the propyl ether analog of arteether), extracted using a C-18 solid-phase cartridge, then subjected to thermospray high-performance liquid chromatographic/mass spectrometric analysis using selected ion monitoring and a C-18 reversed-phase analytical column. Following the intravenous administration of arteether (11.6 mg kg-1), the plasma was found to contain 12 metabolites of arteether in the 10-1000 ng ml-1 range 15 min post-injection, and within 60 min two of these metabolites attained higher concentrations than that of the parent compound, while several other of the metabolites attained concentrations similar to the parent compound. The pseudo-first-order half-life of arteether was found to be 10.0 +/- 0.6 min, while the apparent half-lives of most of the metabolites were in the 15-30 min range. Nine of these metabolites were identified by comparison to authentic reference standards and the structures of three remaining metabolites were tentatively assigned from their spectral and chromatographic properties. The metabolic pathways leading to these 12 metabolites was a rather complex, multiple-step process, but most of the metabolites arose from an enzymatic oxidation at one of three sites; 3 alpha, 9 alpha, or the CH2 of the side-chain. Conversion of the endoperoxide group to an cyclic ether was not a major pathway. The in vitro antimalarial activity of reference standards of several of the metabolites was determined and all of those tested were found to be active in the low nanogram per milliliter range.

One-dimensional and two-dimensional 1H- and 13C-nuclear magnetic resonance (NMR) analysis of vitamin E raw materials or analytical reference standards.

Two-dimensional spectral analysis (COSY, HETCOR) was utilized to make the complete 13C- and 1H-NMR assignments for alpha-, beta-, gamma-, and delta-tocopherol as well as for the acetate and succinate esters of alpha-tocopherol. 13C-NMR was found to be especially useful in distinguishing between the various tocopherols and distinguishing between the d-isomer and the d,l-racemic mixture. HETCOR spectra were also found to be useful for the qualitative identification of mixtures of the tocopherols and sesame oil. Using a procedure designed to minimize errors arising from spin relaxation and nuclear Overhauser effects, 13C-NMR peak integrals were used to quantitate alpha-tocopherol and delta-tocopherol in the presence of sesame oil using benzoic acid as the standard for calibration of the quantitation. The NMR results were compared to a capillary column gas chromatographic analysis of the individual alpha-tocopherol and delta-tocopherol reference materials.

Structure elucidation and thermospray high-performance liquid chromatography/mass spectroscopy (HPLC/MS) of the microbial and mammalian metabolites of the antimalarial arteether.

Microbial metabolism studies of the antimalarial drug arteether (1) have shown that arteether is metabolized to six new metabolites in addition to those previously reported (3). Large-scale fermentations with Cunninghamella elegans (ATCC 9245) and Streptomyces lavendulae (L-105) have resulted in the characterization of these metabolites primarily by two-dimensional nuclear magnetic resonance (2D-NMR) methods as 9 beta-hydroxyarteether (2), a ring rearrangement metabolite (3), 3 alpha-hydroxy-11-epi-deoxydihydroartemisinin (4), 9 alpha-hydroxyarteether (5), 2 alpha-hydroxyarteether (6), and 14-hydroxyarteether (7). Thermospray mass spectroscopy/high-performance liquid chromatographic analyses have shown that four of these metabolites (2, 5, 6, 7) are also present in rat liver microsome preparations.