Maternity rights and the law.

This article outlines the main points relating to Maternity Rights and the law. It emphasises the wisdom of being knowledgeable of these aspects, and ensuring they are understood by relevant members of staff.

Proton NMR sequence-specific assignments and secondary structure of a receptor binding domain of mouse gamma-interferon.

Previous studies using synthetic peptides and monoclonal antibodies have implicated the N-terminal 39-residue segment as a receptor binding region of mouse gamma-interferon (MuIFN gamma). In this work, we report the solution structure of this fragment (dissolved in water with 40% trifluoroethanol) as determined by proton NMR spectroscopy. The proton sequence-specific assignments were determined from TOCSY and NOESY spectra using established procedures. The secondary structure is characterized by two well-defined alpha-helical regions composed of residues 5-16 and 22-37. These two helices are joined by a loop. No NOESY contacts between the two helical regions were detected. Molecular models consistent with the NMR data were generated for MuIFN gamma (1-39) using distance geometry and restrained molecular dynamics/energy minimization calculations. Comparison with similar N-terminal domains in the published NMR and crystallographic studies on the dimeric human and rabbit IFN gamma suggests some similarities in the structures except that the helical regions in the fragment are longer, and considerable variation may exist in the relative orientation of the two helices in the solution phase. The presence of stronger alpha N sequential NOE's suggests that this peptide is flexible. The absence of NOESY contacts involving the N-terminal tripeptide suggests that this region undergoes rapid segmental motion. The data presented here on MuIFN gamma (1-39), combined with the studies on human and rabbit IFN gamma, suggest that the N-terminal receptor binding domain of the protein can undergo structural changes, the understanding of which may provide insight into the basis for receptor interaction by this lymphokine.

31P NMR spectroscopy and HbO2 cryospectrophotometry in prediction of tumor radioresistance caused by hypoxia.

The aim of this study was to search for possible relationships between the fraction of radiobiologically hypoxic cells in tumors and their 31P NMR spectral parameters and intracapillary HbO2 saturations. Four different tumor lines, two murine sarcomas (KHT, RIF-1) and two human ovarian carcinoma xenografts (MLS, OWI), were used. When tumor volume increased from about 200 mm3 to about 2000 mm3, hypoxic fraction increased from 12 to 23% for the KHT line, from 0.9 to 1.7% for the RIF-1 line, and from 9 to 28% for the MLS line. The OWI line showed similar hypoxic fractions at 200 (17%) and 2000 mm3 (15%). Tumor bioenergetic status decreased, that is, the inorganic phosphate (Pi) resonance increased and the phosphocreatine (PCr) and nucleoside triphosphate beta (NTP beta) resonances decreased, with increasing tumor volume for the KHT, RIF-1, and MLS lines, whereas the OWI line did not show any changes in the 31P NMR spectral parameters during tumor growth. Similarly, tumor HbO2 saturation status, that is, the fraction of vessels with HbO2 saturation above 30%, decreased with increasing tumor volume for the KHT, RIF-1, and MLS lines, but remained unchanged during tumor growth for the OWI line. Although the data indicated a relationship between hypoxic fraction and tumor bioenergetic status as well as tumor HbO2 saturation status within a specific line during tumor growth, there was no correlation between hypoxic fraction and tumor bioenergetic status or tumor HbO2 saturation status across the four tumor lines. This may have occurred because cell survival time under hypoxic stress as well as fraction of non-clonogenic, but metabolically active hypoxic cells differed among the tumor lines. This indicates that 31P NMR spectroscopy and HbO2 cryospectrophotometry data have to be supplemented with other data to be useful in prediction of tumor radioresistance caused by hypoxia.

31P NMR spectroscopy in vivo of two murine tumor lines with widely different fractions of radiobiologically hypoxic cells.

Energy and lipid metabolism as well as tumor pH in two murine tumor lines, the KHT and RIF-1 sarcomas, were studied using 31P NMR spectroscopy. Possible relationships between spectral parameters on the one hand and volume fraction of necrosis and fraction of radiobiologically hypoxic cells on the other were investigated. For both tumor lines the PCr and NTP beta resonances decreased and the Pi resonance increased significantly with increasing tumor volume in the volume range 100-4000 mm3. This decrease in bioenergetic status was accompanied by a decrease in tumor pH from about 7.2 to about 6.8. The NTP beta resonance and the tumor pH tended to be somewhat higher and the Pi resonance somewhat lower for the KHT than for the RIF-1 tumors. Linear relationships were found between tumor pH and Pi or (PCr + NTP beta)/Pi for both tumor lines (P much less than 0.05). The PME resonance increased slightly and the PDE resonance decreased slightly during tumor growth and were not significantly different for the KHT and the RIF-1 tumors. The volume fraction of necrosis was about 5 per cent in both lines at a tumor volume of 100 mm3 and increased to about 30 per cent (KHT) and 50 per cent (RIF-1) at a tumor volume of 4000 mm3. The fraction of radiobiologically hypoxic cells was found to increase from 12 to 23 per cent for the KHT line and from 0.9 to 1.7 per cent for the RIF-1 line when tumor volume was increased from about 200 to about 2000 mm3. The volume-dependence of the 31P NMR spectral parameters indicated increased nutritional deprivation and development of hypoxia and necrosis during tumor growth, and was thus qualitatively in good agreement with the changes observed in necrotic and hypoxic fraction. However, quantitative relationships between any spectral parameter and necrotic or hypoxic fraction across tumor lines were not found, implying that other physiological parameters and/or cellular characteristics may contribute significantly to a 31P NMR tumor spectrum. Consequently, 31P NMR spectra of untreated tumors have to be supplemented with other tumor data, e.g. rate of oxygen consumption, cell survival time under hypoxic stress and/or fraction of metabolically active, non-clonogenic hypoxic cells, to be useful in quantitative determination of tumor hypoxia and hence prediction of tumor radioresistance caused by hypoxia.

31P nuclear magnetic resonance spectroscopy studies of tumor energy metabolism and its relationship to intracapillary oxyhemoglobin saturation status and tumor hypoxia.

Relationships between tumor bioenergetic status on the one hand and intracapillary oxyhemoglobin (HbO2) saturation status and fraction of radiobiologically hypoxic cells on the other were studied using two murine sarcoma lines (KHT, RIF-1) and two human ovarian carcinoma xenograft lines (MLS, OWI). Tumor energy metabolism was studied in vivo by 31P nuclear magnetic resonance (NMR) spectroscopy and the resonance area ratio (PCr + NTP beta)/Pi was used as parameter for bioenergetic status. Intracapillary HbO2 saturation status reflects the oxygen supply conditions in tumors and was measured in vitro using a cryospectrophotometric method. The KHT, RIF-1, and MLS lines showed decreasing bioenergetic status, i.e., decreasing PCr and NTP beta resonances and an increasing Pi resonance, with increasing tumor volume, whereas the OWI line showed no changes in these resonances during tumor growth. The volume-dependence of the HbO2 saturation status differed similarly among the tumor lines; HbO2 saturation status decreased with increasing tumor volume for the KHT, RIF-1, and MLS lines and was independent of tumor volume for the OWI line. Moreover, linear correlations were found between bioenergetic status and HbO2 saturation status for individual tumors of the KHT, RIF-1, and MLS lines. These observations together indicated a direct relationship between 31P-NMR spectral parameters and tumor oxygen supply conditions. However, this relationship was not identical for the different tumor lines, suggesting that it was influenced by intrinsic properties of the tumor cells such as rate of respiration and ability to survive under hypoxia. Similarly, there was no correlation between bioenergetic status and fraction of radiobiologically hypoxic cells across the four tumor lines. This indicates that 31P-NMR spectroscopy data have to be supplemented with other data, e.g., rate of oxygen consumption, cell survival time under hypoxic stress, and/or fraction of metabolically active, nonclonogenic hypoxic cells, to be useful in quantitative determination of tumor hypoxia and hence prediction of tumor radioresistance caused by hypoxia.

31P NMR spectroscopy measurements of human ovarian carcinoma xenografts: relationship to tumour volume, growth rate, necrotic fraction and differentiation status.

31P NMR spectroscopy was used to study lipid and energy metabolism as well as tumour pH in three human ovarian carcinoma xenograft lines with widely differing growth rate, necrotic fraction and differentiation status. Two of the lines showed decreasing PCr (phosphocreatine) and NTP beta (nucleoside triphosphates beta) resonances and an increasing Pi (inorganic phosphate) resonance with increasing tumour volume range 100-4000 mm (3). This decrease in bioenergetic status was accompanied by a decrease in tumour pH from 7.15 to about 6.95. The volume-dependence of these spectral parameters probably reflected increased nutritional deprivation and development of hypoxia and necrosis during tumour growth. The phosphomonoesters (PME) and phosphodiesters (PDE) resonances did not change significantly with tumour volume. The third xenograft line did not show changes in the intensity of any of the resonances during tumour growth, in agreement with the observation that necrotic fraction and tumour pH (about 7.0) remained constant over the entire volume range. The spectral parameters differed significantly among the xenograft lines at given tumour volumes, but no correlations with volume-doubling time, necrotic fraction or differentiation status were found. The xenograft lines showed less extensive volume-dependence of the spectral parameters than did the KHT and RIF-1 murine tumour lines under identical experimental conditions.

A clinical trial of the Braden Scale for Predicting Pressure Sore Risk.

The purpose of this article was to describe the protocol by which predictive instruments can be tested for validity and to evaluate the usefulness of an instrument for predicting pressure sore risk in an AICU. The Braden Scale for Predicting Pressure Sore Risk was described. Methods for measuring predictive validity and for calculating sensitivity, specificity, and per cent predictive value of positive and negative tests were discussed. Sixty consecutively admitted AICU patients who were pressure sore free were rated for pressure sore risk within 24 to 72 hours after admission. The skin condition of each patient was systematically assessed every 2 days. Twenty-four subjects developed pressure sores during the study period. The critical cut-off point at which the patient could be judged to be at risk for pressure sore formation was a Braden Scale score equal to or less than 16. The sensitivity and specificity of the scale at this score were 83 to 64 per cent, respectively. The per cent predictive value of a positive and negative test were 61 and 85 per cent, respectively. The Braden Scale compared favorably with the Norton Scale in respect to sensitivity. The specificity, or the tendency of a scale to overpredict, was greater for the Norton than for the Braden Scale. The Norton Scale overpredicted by 64 per cent, whereas the Braden Scale overpredicted by 36 per cent. This difference may be important clinically if all patients who were judged to be at risk received additional nursing care or protective devices. A greater number of patients may receive unnecessary and expensive treatments using the Norton Scale.

Moderate sucrose ingestion and blood pressure in the rat.

Four related hypotheses were tested: 1) substitution of sucrose for starch at moderate levels will significantly elevate blood pressure; 2) most urinary sucrose is endogenous; 3) a change in endogenous sucrose production will alter sodium excretion and blood pressure, and 4) dietary sucrose inhibits endogenous sucrose production. The systolic blood pressures of 25 male rats, 100 days of age, and 25 female rats, 1 year of age, were measured weekly for 8 months. In four experiments, they consumed diets in which 38% of energy came from fat, 15% from protein, 7% from lactose and the remaining 40% from five different sucrose/starch ratios. In experiment 4, a 10% maltose/30% starch diet was fed to one-half the rats fed sucrose in experiment 3. All rats were fed similar amounts of each diet so that there were no significant body weight differences between groups at the end of the 8 months. At periodic intervals all rats were injected with 1 micro c of [U-14C]glucose and placed in metabolism cages where a 24 hour urine sample was obtained. Urine was analyzed for sodium, sucrose and sucrose-14C content. Endogenous sucrose production was estimated from the percent of [U-14C]glucose recovered as urine sucrose-14C in 24 hours. All four hypotheses were confirmed.

Staphylococcus aureus bacteriuria.

One hundred twenty-seven episodes of Staphylococcus aureus bacteriuria were reviewed retrospectively in two hospitals to establish the rate of occurrence, clinical importance, and associated predisposing factors. Staphylococcus aureus was an infrequent urinary isolate, and accounted for only about 1% of all positive urine cultures. Although almost all cases in a Veterans Hospital occurred in elderly men, episodes in a community hospital were observed in women and children as well. Patients usually had pyuria (71%) but only 39% had urinary symptoms of fever. Among predisposing factors, serious underlying diseases were uncommon, but urinary tract manipulations or abnormalities were present in nearly two thirds of patients. Fifty-five percent of cases were nosocomial, and 73% of these were associated with urinary catheterization or other invasive urinary tract procedures. Most patients (61%) were not treated for their bacteriuria, and there was a secondary bacteremia rate of 5.5% in the Veterans Hospital. Although infrequently encountered, the presence of S aureus in urine should be treated with at least as much concern as more frequently encountered bacteria.