Oncologists' identification of mental health distress in cancer patients: Strategies and barriers.

The purpose of this research was to examine oncologists' perspectives on indicators of mental health distress in patients: what strategies they use to identify these indicators, and what barriers they face in this task. Twenty-three oncologists were interviewed, and the grounded theory method of data collection and analysis was used. Oncologists perceived distress to be a normative part of having cancer and looked for affective, physical, verbal and behavioural indicators using a number of strategies. Barriers to identification of mental health distress included difficulty in differentiating between mental health distress and symptoms of the disease, and lack of training. A systematic, time-efficient assessment of symptoms of emotional distress is critical for identification of psychiatric disorders among patients and differentiating normative emotional responses from psychopathology. Clinical bias and misdiagnosis can be a consequence of an ad hoc, intuitive approach to assessment, which can have consequences for patients and their families. Once elevated risk is identified for mental health distress, the patient can be referred to specialised care that can offer evidence-based treatments.

Ambulatory physical activity during the initial training phase in a Naval Commando Unit.

BACKGROUND: There is a positive correlation between the volume of physical activity performed and the incidence of lower extremity overuse injuries. Difficulty in evaluating the amount of activity in which highly specialised military units are engaged has prevented the implementation of a strict training programme designed to minimise overuse injuries. PURPOSE: To quantify the ambulatory physical activity performed by trainees during the initial training phase in a Naval Commando Unit, with a view to developing more exact physical performance guidelines for the unit and the Israel Defense Forces, in general. METHODS: Twenty-four accelerometers were worn by two teams each day. Trainees were instructed to wear the device on their non-dominant wrist 24 h a day, during all types of activities. Twice a week, the devices were collected, checked for damage and recharged, and the data were transferred to a computer. RESULTS: Six trainees failed to complete the 9-week training period. Of the total 1512 accelerometer-days, 1075 readings (71%) were included in the study data. Trainees ambulated on average a distance of 15.5±8.61 km/day and 95.5 km/week. Accelerometer readings (estimated distances) were averaged each week for the two teams. The total distance measured over the 9-week study period was 911.15 km in team A and 808.38 km in team B. The total distance measured in both teams was, thus, almost double the planned 440 km (p=0.001). CONCLUSIONS: Trainees greatly exceeded the planned safe distance. High variability was observed between trainees from the same team.

Molecular analysis of the induction of immunoglobulin E synthesis in human B cells by interleukin 4 and engagement of CD40 antigen.

The molecular events leading to immunoglobulin E (IgE) synthesis in human sIgE- B cells stimulated with interleukin 4 (IL-4) and anti-CD40 monoclonal antibody (mAb) 626.1 were analyzed. Anti-CD40 mAb increased the levels of IL-4-induced germline C epsilon transcripts and induced the production of mature C epsilon mRNA. These effects were dependent on the presence of IL-4. Nested primer PCR revealed deletional switch recombination occurring only in B cell stimulated with both IL-4 and anti-CD40 mAb. DNA sequence analysis of switch fragments showed direct S mu/S epsilon joining, without the deletions or duplications within S mu often found in B cells stimulated with IL-4 and Epstein-Barr virus. Analysis of the switch junction map sites showed "hot spots" for recombination within S mu, but not within S epsilon. These findings indicate that IL-4 provides a signal to B cells to induce germline C epsilon transcription and concurrent CD40 engagement induces S mu/S epsilon deletional switch recombination, production of mature C epsilon mRNA, and IgE synthesis.

The tumor suppressor neurofibromin confers sensitivity to apoptosis by Ras-dependent and Ras-independent pathways.

Neurofibromatosis type 1 (NF1) is characterized by a high incidence of benign and malignant tumors attributed to loss of function of Nf1, which encodes neurofibromin, a tumor suppressor with Ras-GAP activity. Neurofibromin deficiency typically causes chronic activation of Ras, considered the major contributor to manifestation of NF1. Resistance to radio- and chemotherapy are typical of NF1-associated tumors, but the underlying mechanism is unknown. Here, we investigated interrelationships between neurofibromin expression, Ras activity, and sensitivity to apoptosis. Neurofibromin-deficient mouse embryonic fibroblasts (MEFs) and human NF1 tumor cells were more resistant than neurofibromin-expressing cells to apoptosis. Moreover, Nf1(-/-), Nf1(+/-), and Nf1(+/+) MEFs exhibited gene-dosage-related resistance to apoptosis. Resistance of the Nf1-deficient cells was mediated by two survival pathways: a Ras-dependent pathway, and a Ras-independent pathway promoted by the lack of an NF1-GRD-independent proapoptotic action of neurofibromin. Therefore, besides its Ras-dependent growth inhibition, neurofibromin can exert tumor suppression via a proapoptotic effect.

Eight years experience with enzyme replacement therapy in two children and one adult with Pompe disease.

Pompe disease (type 2 glycogenosis, acid maltase deficiency) is a disorder affecting skeletal and cardiac muscle, caused by deficiency of acid alpha-glucosidase. In 2006 enzyme therapy with recombinant human alpha-glucosidase received marketing approval based on studies in infants. Results in older children and adults are awaited. Earlier we reported on the 3-year follow-up data of enzyme therapy in two adolescents and one adult. In the present study these patients were followed for another 5 years. Two severely affected patients, wheelchair and ventilator dependent, who had shown stabilization of pulmonary and muscle function in the first 3 years, maintained this stabilization over the 5-year extension period. In addition patients became more independent in daily life activities and quality of life improved. The third moderately affected patient had shown a remarkable improvement in muscle strength and regained the ability to walk over the first period. He showed further improvement of strength and reached normal values for age during the extension phase. The results indicate that both long-term follow-up and timing of treatment are important topics for future studies.

Primary Care Provider Management of Congenital Hypothyroidism Identified Through Newborn Screening.

OBJECTIVE: To assess Primary Congenital Hypothyroidism (CH) management patterns and feasibility of providing long-term care for patients with CH identified through newborn screening by Primary Care Providers (PCPs) in California and Hawaii. STUDY DESIGN: A survey was mailed to all physicians (N=823) listed as the referral doctor for confirmed patients with CH identified through newborn screening programs in both states between 01/01/2009-12/31/2013. Information was collected on CH management patterns, barriers to providing care, and knowledge on CH treatment. Descriptive statistics and bivariate logistic regression results were reported. RESULTS: 206 PCPs completed the survey. Among these, 78% currently have patients with CH and 91% indicated willingness to provide long-term care to new patients with CH. Among PCPs currently caring for patients with CH, 17% managed CH by themselves with limited assistance from endocrinologists; 63% were involved in managing CH but endocrinologists played a larger role than PCPs; 19% were not involved in CH care. Only 49% of PCPs correctly answered questions regarding recommended follow-up frequencies and 23% knew the correct age for a trial off levothyroxine for suspected transient CH. Top two perceived barriers to providing long-term care included "need guidance or support from endocrinologists" (61%) and "not familiar with CH treatment guidelines" (28%). CONCLUSION: The majority of PCPs surveyed are willing to provide long-term care to patients with CH, but need support from endocrinologists and increased knowledge about current treatment guidelines.

Percutaneous transluminal angioplasty of proximal subclavian artery stenosis after left internal mammary to left anterior descending artery bypass surgery.

A patient is described who underwent percutaneous transluminal angioplasty, through a brachial approach, of a high grade stenosis at the proximal portion of the left subclavian artery 1.5 years after coronary artery bypass grafting including left internal mammary to left anterior descending artery anastomosis. Symptoms of class IV angina, vertebrobasilar insufficiency and occupational arm claudication that developed after bypass surgery were promptly relieved after balloon dilation. Percutaneous transluminal angioplasty of the subclavian artery can be performed safely and provides an alternative to carotid-subclavian or axillary-axillary bypass surgery for treatment of internal mammary artery graft malfunction.

Hybrid protein thymidine kinase gene fusions: plasmid vectors for the study of transcription and translation initiation signals.

The thymidine kinase (TK) gene (tk) from Herpes simplex virus type 1 has been used to form gene fusions encoding enzymatically active hybrid proteins. The promoter, translation initiation region, and the first three codons of the tk gene were removed and replaced with a series of DNA restriction sites. DNA fragments containing gene initiation regions were cloned into these sites and shown to synthesize enzymatically active proteins in Escherichia coli. These gene fusions were shown to complement an E. coli strain which is deficient in TK function. Gene initiation regions were used from the lac operon, the tnpR gene of Tn3, and the insA gene of ISl. TK synthesis was regulated by the control signals of the promoter fused to tk, and was dependent upon the phase alignment of the codons at the fusion joint. The size of the resulting protein was shown to be increased over the size of the original TK protein by the length of the coding region fused to TK. This demonstrated that the tk gene has non-essential N-terminal amino acids that can be replaced by other amino acid sequences with the retention of TK enzymatic activity. Such tk gene fusions are useful in situations where fusions with other genes cannot be conveniently selected or assayed.

New versatile plasmid vectors for expression of hybrid proteins coded by a cloned gene fused to lacZ gene sequences encoding an enzymatically active carboxy-terminal portion of beta-galactosidase.

A new class of plasmid cloning vectors has been constructed with cleavage sites in a variety of translational reading phases of the promotorless lacZ gene. Fused hybrid proteins can be produced by these vectors by cloning DNA fragments containing the promoter, translation initiation site, and the amino terminal portion of a gene, all with proper orientation, into the correct translational reading frame of the lacZ gene. Enzymatically active hybrid-beta-galactosidase proteins are formed, which have amino-terminal amino acids encoded by the cloned gene segment. Another class of these vectors retains an active lac promoter and lacZ translation-initiation region, which can direct hybrid protein synthesis from DNA fragments that do not have gene initiation regions. These vectors allow transcription from the lacZ initiation region to proceed across, or to stop and restart within, an inserted fragment into the essential part of the beta-galactosidase gene. Also described is a small lacZ gene fragment (cartridge), without a plasmid replicon and without any other lac genes, which can be inserted directly into other genes to form hybrid protein fusions. Polyrestriction site sequences were easily moved into some of these vectors by incorporating drug-resistance genes that serve as markers for the selection and detection of these sequences; those markers can be easily removed afterwards.

Butyrylcholinesterase and acetylcholinesterase prophylaxis against soman poisoning in mice.

Human butyrylcholinesterase (BChE, EC 3.1.1.8) or acetylcholinesterase (AChE, EC 3.1.1.7) from fetal bovine serum (FBS), administered i.v. in mice, sequestered at approximately 1:1 stoichiometry the highly toxic anti-ChE organophosphate, 1,2,2-trimethylpropyl methyl-fluorophosphonate (soman). A quantitative linear correlation was demonstrated between blood-ChE levels and the protection conferred by exogeneously administered ChE. Results presented here demonstrate that either human BChE or FBS-AChE is an effective prophylactic measure sufficient to protect mice from multiple LD50S of soman without the administration of post-treatment supportive drugs.

Constitutional mosaicism for a chromosome 9 inversion resulting in recombinant aneusomy in an offspring.

We report on a case of constitutional mosaicism for a large pericentric inversion of chromosome 9 in a man whose daughter had recombinant aneusomy resulting in partial 9q duplication and partial 9p deletion. At age 6 months, the girl was evaluated because of congenital anomalies [corrected] and developmental delay. Chromosomal analysis on this infant showed a derivative chromosome 9 which was later determined to be a recombinant chromosome with trisomy of 9q34.1-->qter and monosomy of pter-->9p24. Chromosomal analysis in her father showed the presence of two cell lines; 75% of lymphocytes had a 46,XY pattern, and 25% had a 46,XY,inv(9)(p24q34.1) karyotype. The infant's physical findings represent a composite of the reported cases of both trisomy 9q34.1-->qter and monosomy pter-->9p24. The infant's father was phenotypically and cognitively normal. This case broadens the spectrum of reported cases of mosaicism for an autosomal structural rearrangement generating unbalanced gametes, and further supports the tenet that constitutional mosaicism has clinical relevance for genetic counseling.

Submicroscopic deletions at 22q11.2: variability of the clinical picture and delineation of a commonly deleted region.

DiGeorge anomaly (DGA) and velo-cardiofacial syndrome (VCFS) are frequently associated with monosomy of chromosome region 22q11. Most patients have a submicroscopic deletion, recently estimated to be at least 1-2 Mb. It is not clear whether individuals who present with only some of the features of these conditions have the deletion, and if so, whether the size of the deletion varies from those with more classic phenotypes. We have used fluorescence in situ hybridization (FISH) to assess the deletion status of 85 individuals referred to us for molecular analysis, with a wide range of DGA-like or VCFS-like clinical features. The test probe used was the cosmid sc11.1, which detects two loci about 2 Mb apart in 22q11.2. Twenty-four patients carried the deletion. Of the deleted patients, most had classic DGA or VCFS phenotypes, but 6 deleted patients had mild phenotypes, including 2 with minor facial anomalies and velopharyngeal incompetence as the only presenting signs. Despite the great phenotypic variability among the deleted patients, none had a deletion smaller than the 2-Mb region defined by sc11.1. Smaller deletions were not detected in patients with particularly suggestive phenotypes who were not deleted for sc11.1, even when tested with two other probes from the DGA/VCFS region.

De novo proximal interstitial deletions of 14q: cytogenetic and molecular investigations.

We report on 2 unrelated patients who had chromosome analysis performed because of psychomotor delay, failure to thrive, and minor anomalies. Each patient had a novel proximal 14q deletion (q11.2 to q21.1 in patient 737 and q12 to q22 in patient 777). Polymorphic (C-A)n microsatellite markers distributed along the length of chromosome 14q were examined in both patients and their parents in order to determine which marker loci were deleted. The deletion in patient 737 was found to be paternal in origin, based on the analysis of 2 marker loci (D14S54 and D14S70), thus assigning these loci to the deleted interval q11.2 q21.1. Furthermore, 3 loci were not deleted (TCRD, D14S50, and D14S80), suggesting that they are within or proximal to 14q11.2. In the other family (patient 777), none of the markers were fully informative, but the deleted chromosome was determined to be paternally derived based on cytogenetic heteromorphisms. Despite having overlapping proximal 14q deletions, these 2 patients shared few phenotypic similarities except for failure to thrive, micrognathia, and hypoplasia of the corpus callosum. Therefore, a distinct proximal 14q deletion syndrome is not yet apparent. However, the molecular analyses facilitated the localization of several 14q DNA markers to the deletion regions in these 2 patients, while excluding other markers from each deletion.

Normal expression of the Fanconi anemia proteins FAA and FAC and sensitivity to mitomycin C in two patients with Seckel syndrome.

Seckel syndrome is a rare autosomal recessive disorder. The classical presentation includes pre- and postnatal growth deficiency, mental retardation, and characteristic facial appearance. There have been several reports of associated hematological abnormalities and chromosomal breakage, findings suggestive of Fanconi anemia (FA). We tested for these findings in two Arabic patients with this syndrome. We compared the growth profile of lymphoblastoid cells from our patients and their parents with the FA group A cell line HSC72 in the presence and absence of mitomycin C (MMC). By Western analysis, we also determined the expression of FAA and FAC, two FA disease gene products that together account for approximately 80% of FA. Unlike HSC72 cells, cells from the patients were resistant to MMC, and both FAA and FAC proteins were expressed at similar levels in all cell lines. There is an increasing recognition of clinical variability and perhaps genetic heterogeneity in Seckel syndrome. Our results demonstrate that cross-link sensitivity comparable to FA is not a uniform finding in patients with Seckel syndrome.

Inherited duplication Xq27-qter at Xp22.3 in severely affected males: molecular cytogenetic evaluation and clinical description in three unrelated families.

We describe the clinical phenotype in four males from three families with duplication (X)(qter-->q27::p22.3-->qter). This is an unusual duplication of the distal long arm segment, Xq27-qter, onto the distal short arm of the X chromosome at Xp22.3, as shown by fluorescent in situ hybridization analysis with multiple X-specific probes. The patients are young male offspring of three unrelated, phenotypically normal carrier women. The affected males have similar clinical manifestations including severe growth retardation and developmental delay, severe axial hypotonia, and minor anomalies. Such clinical similarity in three unrelated families demonstrates that this chromosome abnormality results in a new and distinct clinical phenotype. Replication studies, performed on two of the mothers, provided evidence that inactivation of the abnormal X chromosome permitted the structural abnormality to persist in these families for a generation or more in females without phenotypic expression.

Anomalous behavior of superconducting-normal mesoscopic structures near T(c)

We observe a maximum in the conductance of Al/n-GaAs junctions at temperatures 20 mK lower than the superconducting transition temperature (T(c)). This is the first observation of a peak in the conductance near the superconducting transition in superconducting-normal (S/N) junctions. To accommodate this effect we calculate the full temperature dependence of the conductance of these structures, invoking quasiclassical Green's functions in the diffusive limit. In addition to the well-known low-temperature peak at temperatures on the order of the Thouless energy, we find a maximum near T(c). This peak has the same origin as the subgap conductance observed in S/N junctions at low temperatures.

Interband scattering and the "Metallic Phase" of two-dimensional holes in GaAs /AlGaAs

The "metallic" characteristics of high density holes in GaAs/AlGaAs heterostructures are attributed to inelastic scattering between the two split heavy hole bands. Landau fan diagrams and weak field magnetoresistance are employed to measure the interband scattering rate. The inelastic rate is found to depend on temperature with an activation energy similar to that characterizing the longitudinal resistance. It is argued that acoustic plasmon mediated Coulomb scattering might be responsible for the Arrhenius dependence on temperature. The absence of standard Coulomb scattering characterized by a power-law dependence upon temperature is pointed out.

Dose-dependent effect of nitric oxide synthase inhibition following transient forebrain ischemia in gerbils.

The extensive research concerning the interaction between nitric oxide (NO) and ischemic brain tissue has yielded contradictory results. The present study was designed to explore the effect of gradual inhibition of NO production on brain ischemia. Gerbils were administered (i.p.) either saline (control-ischemia), or 5, 10, 25 or 50 mg/kg of NG-nitro-L-arginine (NARG), a specific inhibitor of NO synthase (NOS), and 4 h later were subjected to 5 min of forebrain ischemia. A group receiving 50 mg/kg NARG with sham operation served as a second control (control-NARG) group. Body weights and spontaneous activity were monitored daily until day 6, when the gerbils were sacrificed and their brains processed for histologic-morphometric evaluation. All ischemia groups displayed significant decreases in body weights starting on day 1, as compared to control-NARG (non-ischemic) gerbils. At 24 h post-ischemia spontaneous activity was increased in all ischemia groups in a dose-dependent manner, reaching a peak at 25 mg/kg. Typical ischemia-induced neuronal cell degeneration was observed at the hippocampal CA1 layer in control-ischemia and in each of the dose-groups of 10 mg/kg NARG and above. The 5 mg/kg group displayed damage which was not different from control-NARG, and was milder (P < 0.01) than control-ischemia gerbils and each of the other dose-groups. It is suggested that during ischemia, NO activates a series of processes which are beneficial to brain tissue, whereas an excess amount of NO causes neurotoxic effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Selective hippocampal lesion following omega-conotoxin administration in rats.

Histopathological evaluation of rat brains 3 days following unilateral i.c.v. injections of omega-conotoxin GVIA (omega-ctx), 0.032 and 0.1 nmol/kg, was performed. An isolated unilateral lesion confined to the injected hemisphere was found in the hippocampal CA3 neurons. Morphometric analysis of these cells revealed a significant reduction in cell area in both dose groups compared to i.c.v. injected vehicle, and to the contralateral hemisphere. These data indicate a specific degenerative process and suggest that CA3 cells possess omega-ctx-sensitive Ca2+ channels which are essential to their viability.

The accumulated experience of the Israeli Advanced Trauma Life Support program.

BACKGROUND: Between January 1990 and May 1995 one faculty in Israel taught Advanced Trauma Life Support (ATLS) courses to 3,700 physicians. Two types of courses were given to three subpopulations. We studied the influence of demographic variables on students' achievements in the course and compared students' achievements as a function of their course type. STUDY DESIGN: This study was conducted as a concurrent longitudinal study. RESULTS: Achievements of 3,700 students were analyzed. The precourse grade, type of course, and their interaction were found to have a significant effect on the postcourse grades. Physicians practicing surgical subspecialties, in general, did better, as did students educated in English-speaking countries. Students who took part in the Combat Trauma Life Support (CTLS) course, which included the entire ATLS course and additional lectures and exercises, also ended with better scores. CONCLUSIONS: Physician's country of origin and clinical subspecialty have a significant effect on the cognitive achievement in the ATLS course provided in Israel. An expanded ATLS course (CTLS), to include additional military trauma topics as well as additional skill station training, can improve the results of the postcourse grades.