Approaches to end-of-life decision-making in the NICU: insights from Dostoevsky's The Grand Inquisitor.

For many parents stopping life-sustaining medical treatment on their dying infant is psychologically impossible. Dostoevsky's insights into human behavior, particularly the fact that individuals do not want the anxiety and guilt associated with responsibility for making difficult decisions, might change the way physicians approach parents for permission to withdraw life-prolonging medical interventions on dying infants.     

Confounders contributing to the reported associations of coffee or caffeine with disease

The role of caffeine or coffee in causing or promoting the incidence of serious disease is equivocal. Two design factors may account for the discrepancies in reported findings on the effects of coffee drinking: (a) imprecision of measurement and (b) confounding variables. A study of 2,714 white U.S. adults disclosed that, of 32 risk factors analyzed by linear and logistic regression, only sex and cigarette smoking were found to be important potential confounders of caffeine and coffee intake. Partial R2 values of the other 30 risk factors were relatively small and were inconsistent for each sex. It is unlikely that any of these factors could explain any of the reported associations between caffeine or coffee consumption and certain diseases. However, certain weak associations with caffeine or coffee intake should be included in the study design when they are known to be risk factors of a disease under investigation. These factors for men are dietary fat intake, vitamin C intake, and body mass index; and for women are vitamin use, alcohol intake, stress, and perceived health status.     

A negative correlation between the induction of long-term potentiation and activation of immediate early genes.

In the present study we examined the relationship between the induction of long-term potentiation (LTP) in the dentate gyrus of anesthetized rats and activation of immediate early genes (IEGs; c-fos and zif/268) using several different high-frequency stimulation paradigms. Stimulation parameters that effectively induced LTP were not associated with IEG activation. Conversely, stimulation parameters that failed to induce LTP consistently resulted in IEG activation. These results suggest that there is a negative correlation between IEG activation and LTP, and that activation of IEGs is neither necessary nor sufficient for the induction of LTP.     

Nuclear magnetic resonance proton imaging of bone pathology

Thirty-two patients with diversified pathology were examined with a supraconductive NMR imager using spin echo with different TR and TE to obtain T1 and T2 weighted images. They included 20 tumors (12 primary, eight metastasis), six osteomyelitis, three fractures, two osteonecrosis, and one diffuse metabolic (Gaucher) disease. In all cases except for the stress fractures, the bone pathology was clearly visualized in spite of the normal lack of signal from the compact cortical bone. Nuclear magnetic resonance (NMR) imaging proved to be at least as sensitive as radionuclide scintigraphy but much more accurate than all other imaging procedures including computed tomography (CT) and angiography to assess the extension of the lesions, especially in tumors extended to soft tissue. This is due both to easy acquisition of sagittal and coronal sections and to different patterns of pathologic modifications of T1 and T2 which are beginning to be defined. It is hoped that more experience in clinical use of these patterns will help to discriminate between tumor extension and soft-tissue edema. We conclude that while radionuclide scintigraphy will probably remain the most sensitive and easy to perform screening test for bone pathology, NMR imaging, among noninvasive diagnostic procedures, appears to be at least as specific as CT. In addition, where the extension of the lesions is concerned, NMR imaging is much more informative than CT. In pathology of the spine, the easy visualization of the spinal cord should decrease the need for myelography.     

Within-gene interaction between c.135 G/A genotypes and RET proto-oncogene germline mutations in HSCR families.

Hirschsprung disease (HSCR) is considered a model for a complex inheritance disorder. Several genes, including the major HSCR-susceptibility RET proto-oncogene, play an aetiological role in the development of HSCR. Genetic linkage analysis in familial HSCR with both long- and short-segment phenotypes has demonstrated a tight linkage to the RET locus, while the phenotype within a HSCR family is characterised by an incomplete penetrance or a variable extension of the aganglionosis. Therefore, additional genetic alterations of RET are postulated in the aetiology or modification of the HSCR phenotype. In this study, the coding region of all 21 exons of the RET proto-oncogene, including the flanking intronic sequences, were investigated by direct DNA sequencing in a HSCR population. We genotyped the c.135 G/A polymorphism and resolved haplotypes comprising the mutation locus and the c.135 G/A polymorphism. Twenty different mutations were detected in 18 of 76 HSCR patients. In ten families the mutations were inherited from the parents, while only four patients had a positive family history for the disease. Moreover, in all ten families an incomplete penetrance of the HSCR phenotype was observed. We have investigated the effect of the non-mutated wild-type allele as well as the c.135 G/A polymorphism on the phenotype within the HSCR families. Our findings support the notion that both RET alleles are involved in the pathogenesis of a subgroup of HSCR patients in a dose-dependent fashion. Additionally, we have shown a modifying effect of the c.135 G/A polymorphism on the HSCR phenotype within HSCR families.     

Improved Performance of Hip DXA Using a Novel Region of Interest in the Upper Part of the Femoral Neck: In Vitro Study Using Bone Strength as a Standard of Reference

We tested the hypothesis that bone mineral density (BMD) and bone mineral content (BMC) in proximal human femur specimens in the upper neck region of interest (ROI) and femoral neck axis length (FNAL) provide a significantly better prediction of femoral bone strength than standard ROIs in vitro. BMD and BMC were measured in 110 proximal femur specimens using a standard dual-energy X-ray absorptiometry (DXA) scanner. The analysis included a new ROI in the upper neck as well as the standard ROIs. FNAL was obtained from the scan images. The specimens' failure-load was measured in a mechanical loading device, simulating a fall on the greater trochanter. For the standard ROIs, correlations between failure-load and BMD ranged from R2 = 0.64 (shaft ROI) to R2 = 0.70, p < 0.001 (femoral neck). Prediction of strength by BMD did not significantly differ from those of BMC (R2 ranging from 0.65 to 0.75, p < 0.001). In the upper neck ROI, for both BMD and BMC correlations with failure-load were higher (R2 = 0.76 and 0.81, respectively; p < 0.001). A lower, yet still significant, correlation was found between FNAL and bone strength (R2 = 0.23, p < 0.001). Normalization of failure-load with respect to FNAL did not significantly increase the correlations with densitometric measures. This study provides in vitro evidence indicating that among the ROIs of the proximal femur the newly defined upper neck ROI provides the best prediction of bone strength. Only a weak association was observed between failure load and FNAL.     

A rapid and accurate spectrofluorometric method for quantification and screening of urinary porphyrins

We describe a fluorescence method for screening and quantifying urinary porphyrins. New and effective approaches are used to oxidize prophyrinogens, correct the baseline, and ensure that uroporphyrin (uro) and coproporphyrin (copro) are equally detected, mole for mole. No preliminary purification is required. A 45-microL aliquot of urine is oxidized with 3 mmol/L iodine in 3 mol/L HCl to convert porphyrinogens to porphyrins, and then decolorized with 5 mL of 0.45 mmol/L sodium thiosulfate. An excitation scan is done from 350 nm to 440 nm, monitoring emission at 650 nm. Total porphyrin content is determined at the isosbestic point for uro and copro, and the mole fractions of uro and copro are estimated from the wavelength of the signal maximum. There is no interference from protein, glucose, bilirubin, or hemoglobin in high concentration. The limit of detection is less than 30 nmol/L and linearity is maintained up to 3200 nmol/L. Recoveries and precision are excellent. This is a rapid, sensitive screen for porphyrinuria as well as an accurate and precise quantitative method. We compared the method with existing methods and discuss some shortcomings common to many of them.     

Metastatic bone disease from occult carcinoma: a profile

Summary To assess the general profile of metastatic bone disease from occult primary carcinoma, the records of 172 patients with skeletal metastases seen between 1965 and 1985 were reviewed. In 51 patients (30%), the origin of the primary could not be identified when bone metastases were first diagnosed. This group were predominantly male with a high incidence of spinal metastases, cord compression and pathological fractures, and a significantly shorter (P<0.1) survival compared with bony metastases when the primary was known. The site of the primary was established in 33 patients (65%), mostly at autopsy. Lung carcinoma was by far the most common primary tumour in 52% of the cases, while it accounted for only 7% of those with a diagnosed primary. We believe that the onset of bony metastases from an occult source must initially raise the possibility of lung carcinoma. If the primary remains undetected, it appears justifiable to assume it to be in the lung, since the probability of a missed lung tumour being responsible for the metastases is high.

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Résumé Les auteurs ont revu les observations de 172 malades porteurs de métastases osseuses, vus entre 1965 et 1985, afin d'apprécier l'aspect général des métastases provenant d'un cancer primitif méconnu. Chez 51 malades (30%) l'origine du cancer primitif n'avait pu être découverte lors du diagnostic de métastase osseuse. Ce groupe était à prédominance masculine, comportant un nombre élevé d'atteintes vertébrales, de compressions médullaires et de fractures pathologiques, et un taux de survie significativement plus court (P<0,1) comparativement à celui des métastases d'un cancer primitif connu. La localisation du cancer primitif a été découverte dans 33 cas (65%), la plupart du temps à l'autopsie. Le cancer du poumon était le plus fréquemment en cause (52%), alors qu'il n'était responsable que de 7% des cas quand le cancer primitif était connu. Il semble que l'apparition de métastases osseuses d'origine inconnue doive faire évoquer d'emblée la possibilité d'un cancer du poumon. Si le cancer primitif ne peut être découvert il est vraisemblable qu'il siège au niveau du poumon, la probabilité d'un cancer du poumon méconnu, responsable des métastases, étant élevée.

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Presented in part at the International Symposium on Bone Metastases, Rome, Italy, June 1986     

Physiologic responses to loud tones in Israeli patients with posttraumatic stress disorder.

Orbicularis oculi (eye blink) electromyogram, skin conductance, and heart rate responses to 15 consecutive 95-dB, 500-millisecond, 1000-Hz tones with 0-millisecond rise and fall times were measured in 14 patients with posttraumatic stress disorder, 14 patients with other anxiety disorders, 15 mentally healthy subjects with past traumatic experiences, and 19 mentally healthy subjects with no trauma history. The patients with posttraumatic stress disorder showed significantly larger skin conductance and heart rate responses and a trend toward larger electromyogram responses to the tones than every other group. These effects were not explained by subjective anxiety, resting physiologic arousal, physiologic arousal preceding the tone trials, or initial physiologic responsivity. The group with posttraumatic stress disorder was the only one that failed to show habituation of skin conductance responses.