Prostaglandin inhibition prevents the fall in pulmonary vascular resistance as a result of rhythmic distension of the lungs in fetal lambs

Prostaglandins (PG) are vasoactive factors involved in the regulation of pulmonary vascular resistance at birth. However, their physiologic importance is unclear. We hypothesized that PG are important regulators of pulmonary vascular resistance during static and rhythmic distension of the lungs. To test this hypothesis, we studied seven near-term fetal lambs treated with meclofenamate (a PG synthetase inhibitor) and six controls. The fetal lambs were instrumented on a long-term basis with vascular catheters to measure pulmonary arterial pressures, left atrial pressures, and pulmonary blood flow (radionuclide-labeled microsphere method). The fetal airway was intubated, and the ductus arteriosus wall was infiltrated with formalin to assure full patency during the study period. Pulmonary vascular resistance was calculated during baseline and during sequential in utero static distension of the fetal lungs, rhythmic distension, and ventilation with oxygenation. We found that during rhythmic distension, inhibition of PG synthesis abolished the 4-fold decrease in pulmonary vascular resistance seen in the control group. In contrast, during static distension, pulmonary vascular resistance did not change in either group, and during ventilation with oxygenation, pulmonary vascular resistance decreased 12-fold in both groups. We conclude that PG are important regulators of pulmonary vascular resistance during rhythmic distension but are not essential for the regulation of pulmonary vascular resistance during static distension or during ventilation with oxygenation.     

Nocturnal growth hormone secretion in schizophrenic patients and healthy subjects.

Plasma growth hormone concentrations were measured at hourly intervals between 10 p.m. and 8 a.m. the next morning in 15 drug-free chronic schizophrenic male inpatients and 14 healthy males. Growth hormone secretion was significantly lower in the patients as compared with the controls. Growth hormone release peaked around 1 a.m. in the controls, but a growth hormone peak was absent in the patient group. Increased dopamine activity, increased serotonin activity, or both could explain the absence of a nocturnal growth hormone surge in the schizophrenic patients.     

Infrared analysis of the mineral and matrix in bones of osteonectin-null mice and their wildtype controls.

Osteonectin function in bone was investigated by infrared analysis of bones from osteonectin-null (KO) and wildtype mice (four each at 11, 17, and 36 weeks). An increase in mineral content and crystallinity in newly formed KO bone and collagen maturity at all sites was found using FTIR microspectroscopy and imaging; consistent with osteonectin's postulated role in regulating bone formation and remodeling. Mineral and matrix properties of tibias of osteonectin-null mice and their age- and background-matched wildtype controls were compared using Fourier-transform infrared microspectroscopy (FTIRM) and infrared imaging (FTIRI) at 10- and 7-mm spatial resolution, respectively. The bones came from animals that were 11, 17, and 36 weeks of age. Individual FTIRM spectra were acquired from 20 x 20 microm areas, whereas 4096 simultaneous FTIRI spectra were acquired from 400 x 400 microm areas. The FTIRM data for mineral-to-matrix, mineral crystallinity, and collagen maturity were highly correlated with the FTIRI data in similar regions. In general, the osteonectin-null mice bones had higher mineral contents and greater crystallinity (crystal size and perfection) than the age-matched wildtype controls. Specifically, the mineral content of the newly forming periosteal bone was increased in the osteonectin-null mice; the crystallinity of the cortical bone was decreased in all but the oldest animals, relative to the wildtype. The most significant finding, however, was increased collagen maturity in both the cortical and trabecular bone of the osteonectin-null mice. These spectroscopic data are consistent with a mechanism of decreased bone formation and remodeling.     

Unique variant of partial anomalous pulmonary venous connection with intact atrial septum

Summary Partial anomalous pulmonary venous connections (PAPVCs) are rare in association with an intact atrial septum. However, the diagnosis should be considered in patients with otherwise unexplained findings of left-to-right shunt and right heart enlargement. An unusual variant is presented, which we considered unsuitable for operative repair, based on findings at catheterization. Developmental, hemodynamic, and surgical considerations are discussed.     

Evaluation of non-invasive blood pressure measurement by the Finapres method at rest and during dynamic exercise in subjects with cardiovascular insufficiency

The accuracy and precision of the Finapres in recording rest and exercise blood pressure compared with the intra-arterial (aortic and brachial) and random-zero sphygmomanometer methods was assessed in 84 ischaemic patients in three different studies. Firstly, comparison at rest with the aortic intraarterial pressure in 50 ischaemic patients demonstrated that the Finapres systolic (136.5 ± 21.1 vs. 129.3 ± 19.0 mmHg;p < 0.001) and mean (92.4 ± 13.4 vs. 90.7 ± 11.4 mmHg;p < 0.001) arterial pressures were higher and diastolic pressures lower (70.4 ± 11.5 vs. 71.5 ± 9.8 mmHg;p < 0.001). The reproducibility of the Finapres and invasive method was similar for systolic (4.6% vs. 4.0%), diastolic (2.8% vs. 2.7%) and mean (3.3% vs. 3.0%) blood pressures. Second, in seven subjects studied twice at rest and during 4 min supine bicycle exercise, the exercise increase in blood pressure was greater on the Finapres compared with the brachial intra-arterial pressure (systolic +10.2 ± 6.3 vs. +3.6 ± 9.8 mmHg; diastolic +9.6 ± 11.1 vs. +0.2 ± 2.1 mmHg;p = 0.02 for each); however, at steady-state the peak/trough differences in pressure between the methods were similar. Thirdly, compared under rest conditions, to random zero sphygmomanometer (RZO), the Finapres systolic pressure was higher (6.8 ± 3.5 mmHg) and diastolic pressure lower (–6.0 ± 1.9 mmHg). During upright bicycle exercise, the difference between the Finapres and RZO in systolic blood pressure increased at each level of exercise (+14.3 ± 4.2, +17.9 ± 4.0 and +22.2 ± 4.1 mmHg respectively at each exercise stage:p < 0.01). For RZO, diastolic blood pressure fell as exercise workload increased whereas Finapres diastolic blood pressure increased on exercise (3.1 ± 2.6, 7.0 ± 2.1 and 8.1 ± 2.0 mmHg respectively:p < 0.01). Thus there were systematic differences between the values recorded by the Finapres and proximal blood pressure methods and limited agreement in the rest to exercise increments related to light exercise. Calibration of the Finapres values in terms of the other methods is limited by the variable relationship to these related changes in arterial distensibility.     

Red blood cell methotrexate and folate levels in children with acute lymphoblastic leukemia undergoing therapy: a Pediatric Oncology Group pilot study

Summary We enrolled children with acute lymphoblastic leukemia (ALL) in a Pediatric Oncology Group (POG) pilot study to monitor erythrocyte (RBC) methotrexate (MTX) and folate (F) levels before and during treatment. The mean value for RBCF at diagnosis was 0.86±0.46 nmol/ml RBC in the 214 patients who achieved remission and 1.21±0.74 nmol/ml RBC in the 10 patients who did not (P=0.020). Folate levels tended to increase during remission induction, but they dropped following an intensive consolidation with methotrexate to levels that were sustained throughout chemotherapy treatment. Methotrexate levels reached mean values of approximately 0.15 nmol/ml RBC at the end of an intensive methotrexate consolidation, then fell to levels that were sustained throughout maintenance therapy. There was a weak correlation between improved event-free survival and higher RBCMTX levels after consolidation, but no correlation was found between improved survival and the level of RBCMTX or RBCF during maintenance therapy. A larger study with more complete data is needed to determine whether RBCMTX or RBCF might be useful in predicting event-free survival in patients with ALL.This work was supported in part by grants from the National Cancer Institute and the National Institute of Health (CA-30969, CA-28476, CA29139, CA-159-89, and CA-33587)     

In vitro effects of methotrexate on peripheral blood monocytes: modulation by folinic acid and S-adenosylmethionine.

The mechanism of action of low dose methotrexate in rheumatoid arthritis has not been established. It has been shown to have an anti-inflammatory effect and to inhibit neutrophil chemotaxis, but the effect on monocytes has not been widely studied. Normal donor peripheral blood monocytes were incubated with methotrexate in vitro and their superoxide production, chemotaxis, and phagocytosis subsequently assessed. Additionally, the influence of different culture media, and of folinic acid, and the methyl donor S-adenosylmethionine, and spermidine on the methotrexate mediated effects were evaluated. It was found that methotrexate in low concentrations inhibited in vitro monocyte chemotaxis and superoxide production but only after prolonged incubation. This inhibition was augmented by incubation in medium containing a low methionine concentration and was abolished by folinic acid and S-adenosylmethionine, suggesting that methotrexate may interfere with specific methylation reactions.     

Flow-independent angiography for peripheral vascular disease: Initial in-vivo results

Flow-independent angiography (FIA), an approach that isolates arterial blood using MR relaxation characteristics rather than flow effects, was evaluated for application in peripheral vascular disease (PVD). First, pilot studies were conducted in which FIA coronal projection images were obtained from controls and symptomatic patients with PVD to assess clinical utility. All control images corresponded to the expected leg arterial anatomy with little interference from deep veins (one of five) and muscle (zero of five). Superficial venous signal was less well suppressed in comparison to deep veins (four of five). Images of symptomatic patients were less consistent with difficulty suppressing muscle and deep venous signal in some cases and edema when present. We then compared T2 values for muscle (T2_m, tibialis anterior), arterial blood (femoral and popliteal arteries), and venous blood (femoral, popliteal, and saphenous veins) in controls (n = 8) and symptomatic patients with intermittent claudication (n = 5) or ischemic rest pain (n = 7). Changes in T2 measurements of various tissues accounted for poorer contrast in symptomatic patients. Patients with ischemic rest pain had significantly higher T2_m compared with controls (T2_m = 39.3 ± 2.1 (1 standard error of the mean [SEM]) versus 30.9 ± .4, P < .01). For all measurements, other than saphenous vein, variances were greater in symptomatic patients. To realize the inherent advantages of FIA for this clinical application, additional work on suppression of signals from muscle, veins, and edema is required. One promising approach involves shifting from projection images to three-dimensional acquisitions for improved tissue suppression.     

Neonatal compartment syndrome.

Two cases of forearm compartment syndrome in neonates are presented. The compartment syndrome may be initiated before actual delivery and may appear in an advanced stage. In both children good clinical results were achieved when standard guidelines for managing compartment syndrome and established Volkmann's contracture were applied. Although uncommon, compartment syndrome should be considered in the differential diagnosis of the neonate who is unable to move an extremity.