Renin-angiotensin system transgenic mouse model recapitulates pathophysiology similar to human preeclampsia with renal injury that may be mediated through VEGF.

Using a transgenic cross, we evaluated features of preeclampsia, renal injury and the sFlt1/VEGF changes. Transgenic hAGT and hREN, or wild-type (WT) C57Bl/6 mice were cross-bred: female hAGT × male hREN for preeclampsia (PRE) model and female WT × male WT for pregnant controls (WTP). Samples were collected for plasma VEGF, sFlt1, and urine albumin. Blood pressures (BP) were monitored by telemetry. Vascular reactivity was investigated by wire myography. Kidneys and placenta were immunostained for sFlt1 and VEGF. Eleven PRE and 9 WTP mice were compared. PRE more frequently demonstrated albuminuria, glomerular endotheliosis (80% vs. 11%; P = 0.02), and placental necrosis (60% vs. 0%; P < 0.01). PRE group demonstrated declining BPs with advancing gestation. Plasma sFlt1 increased across pregnancy in PRE; VEGF did not vary. IHC demonstrated the presence of sFlt1 in glomeruli, lymphatics, and collecting tubules of PRE kidneys, suggesting excretion. VEGF immunostaining was increased specifically in the glomeruli of PRE kidneys. Placenta in PRE showed marked immunostaining for sFlt1. We conclude that this transgenic model of preeclampsia recapitulates human preeclamptic state with high fidelity, and that, vascular adaptation to pregnancy is suggested by declining BPs and reduced vascular response to PE and increased response to acetylcholine. Placental damage with resultant increased release of sFlt1, proteinuria, deficient spiral artery remodeling, and glomerular endotheliosis were observed in this model of PRE. Increased VEGF binding to glomerular endothelial cells in this model of PRE is similar to human PRE and leads us to hypothesize that renal injury in preeclampsia may be mediated through local VEGF.

Enhanced Intraoperative Communication of Tumor Margins Using 3D Scanning and Mapping: The Computer-Aided Design Margin.

We have implemented a novel intraoperative communication system for head and neck surgical pathology using 3D scanning technology and computer-aided design (CAD) software. Here, we highlight our CAD margin protocol, in which we 3D scan head and neck oncologic surgical specimens and map frozen section results. This enhances the communication of margin status between surgeons and pathologists and delivers visual anatomic guidance for re-resection when needed. Laryngoscope, 133:1914-1918, 2023.

Choice of antenatal testing significantly effects a patient's work obligations.

OBJECTIVE: We sought to compare two approaches to antenatal testing for their impact on the workforce. STUDY DESIGN: This is a prospective observational study of women who presented for antenatal testing. All women were given a survey upon presentation. As per hospital protocol, nonstress testing (NST) was performed semiweekly and biophysical profile (BPP) was performed weekly. The choice of testing was determined by the attending physician. chi2- and Student's t-tests were performed where appropriate. A P-value of <0.05 was considered significant. RESULT: A total of 195 women were surveyed. Among them, 94 women had an NST and 101 had a BPP. Overall, 59.2% were multiparous, 33.1% had to arrange for child care and 97.2% felt reassured by the testing. There were no differences in demographic characteristics, education, type of insurance or employment status between the groups. Women who had NSTs were more likely to lose time from work than those who had BPPs (218.4 versus 68.9 min; P<0.001). Of the women who had semiweekly NSTs, 80.6% would have preferred weekly testing. If the 94 women who received semiweekly testing had weekly testing, a total of 534.4 h would have been available for the workforce. CONCLUSION: Twice-weekly NST results in a significant increase in time lost from the workforce compared with weekly BPP.

Neonatal hearing assessment in very low birth weight infants exposed to antenatal steroids.

OBJECTIVE: We sought to evaluate neonatal hearing assessment by the otoacoustic emission (OAE) test in very low birth weight (VLBW) infants exposed to antenatal steroids. STUDY DESIGN: This is a retrospective cohort study of infants <1500 g delivered between July 1998 and July 2004 who completed hearing screens on discharge. All screens were performed by the OAE. Only infants who failed or passed the exam were included in the analysis. Infants with a partial or an inadequate exam were excluded. Neonates exposed to antenatal steroids were then compared to unexposed infants for the results of their OAE. RESULT: A total of 68,000 deliveries were performed during the study period. There were 703 VLBW infants who had hearing exams, of which 548 (78%) passed the screen, 95 (14%) failed and 59 (8%) were indeterminate. Gestational age, birth weight, score for neonatal acute physiology and severe intraventricular hemorrhage were associated with a failed screen (P<0.01). Antenatal steroid exposure was not associated with a failed screen (odds ratio: 0.83 (95% confidence interval 0.5-1.4), P=0.43). CONCLUSION: In our population, antenatal steroids were not associated with a positive or negative effect on hearing assessment of VLBW infants.

Bone trauma and related benign disease: assessment by bone scanning.

The radionuclide investigation of skeletal trauma in the past was confined generally to scintimetry and an occasional bone scan. The development of improved radiopharmaceuticals, including 99mTc-labeled compounds with their enhanced sensitivity, and the refinement of imaging devices offering superior resolution and speed have allowed a more detailed assessment of conditions resulting from trauma. Practical approaches to the diagnosis of subtle bone injury resulting in stress fracture, the differentiation between delayed healing and nonunion, and early recognition of avascular necrosis and osteomyelitis are now available. The changing pattern of radionuclide uptake in bone following damage by radiation and other abnormalities as a consequence of trauma also can be easily studied.

Assessment of myocardial hypertrophy by echocardiography in adult patients receiving tacrolimus or cyclosporine therapy for prevention of acute GVHD.

The incidence of myocardial hypertrophy was determined in a comparative study of tacrolimus-based immunosuppression with cyclosporine-based immunosuppression for prevention of acute graft-versus-host disease (GVHD) after unrelated donor bone marrow transplantation. Patients were evaluated for clinical and echocardiographic abnormalities at baseline (prior to pretreatment conditioning and the first dose of study drug) and at 5-8 weeks after transplant when stable levels of oral tacrolimus or cyclosporine had been achieved. Left ventricular geometry and performance were assessed by echocardiography which included 2-D measurements and one Doppler measurement. Derived echocardiographic measurements and left ventricular mass index (LVMI) were also determined. A cut-off of <111 g/m(2) was used for the upper limit of normal for LVMI. Forty-four patients were included in this study (21 tacrolimus and 23 cyclosporine), of which 31 were evaluable for a comparison with both baseline and post-transplant values. There was no significant difference in the changes from baseline for mean left ventricular mass (LVM) or LVM index (LVMI) between treatment groups. Also, within the tacrolimus group there were no significant changes for these variables from baseline to post-transplant evaluations. Within the cyclosporine group there were significant increases from baseline for mean LVM (P = 0.011) and LVMI (P = 0.007). The incidence of myocardial hypertrophy (change of LVMI from <111 g/m(2) baseline to >111 g/m(2) post transplant) was 20% in the tacrolimus group and 56% in the cyclosporine group (P = 0.109). Changes in the LVMI from baseline to post baseline were greater with cyclosporine than with tacrolimus therapy, and there was no evidence that tacrolimus causes myocardial hypertrophy or significant clinical changes in adult bone marrow transplant patients. The increase in LVMI after transplant in the cyclosporine group was greater than in the tacrolimus group but was not associated with any significant clinical events.

Radionuclide ejection fractions in the evaluation of patients being considered for bone marrow transplantation: risk for cardiac toxicity.

One hundred thirty-six patients underwent radionuclide ventriculography as part of an evaluation prior to bone marrow transplantation. One hundred twenty-six who were considered suitable transplant candidates began conditioning chemotherapy or chemoradiotherapy and were retrospectively evaluated for development of cardiac toxicity. The cumulative pretransplant anthracycline dose in patients who began the conditioning regimen was not a significant predictor for decreased pretransplant ejection fraction (EF) or severe cardiac toxicity following transplantation. Fourteen patients (10%) had EFs less than 50%. Of these, 10 began the preparative regimen and two (20%) experienced grade III or IV cardiac toxicity (95% confidence interval (CI) 2.5-56%) versus five of 116 patients (4%; CI 1.4-9.8%) with EFs greater than or equal to 50% (p = 0.096). The incidence of grade III or IV cardiac toxicity among patients with any history of cardiac dysfunction or with an abnormal physical examination prior to transplant was 9% (two of 22) versus 5% among the remaining patients (five of 104) (p = 0.605). Though transplant-related cardiac toxicity may be more common in patients with mildly reduced EFs, the small number of patients with reduced EFs referred for transplant does not warrant the routine pretransplant screening of all patients with radionuclide ventriculography.

Effect of methandrostenolone on postmenopausal bone wasting as assessed by changes in total bone mineral mass.

To assess the efficacy of methandrostenolone in the treatment of osteoporosis a 26-mo double-blind study was performed with 13 treated and 13 control (placebo) postmenopausal osteoporotic females. Drug effect was assessed primarily by determinations of total body calcium (TBC) by neutron activation analysis, essentially a measurement of total bone mineral mass. Results in the 16 patients completing the study (10 treated and 6 placebo), as well as in all 26 patients participating in the study, showed significant (p less than 0.01) differences in the change in TBC between treated and control groups. In patients dropping out, TBC changes through the time of dropout were similar to those in patients completing the study. In those patients completing the study, TBC increased 2% in the treated group and decreased 3% in the placebo group. An approximate sixfold difference in extraskeletal calcium balance would be required to explain the magnitude of the observed intergroup TBC difference. The drug effect appeared to persist throughout the 26-mo observation period. Thus these data strongly suggest that long-term use of methandrostenolone in postmenopausal osteoporosis prevented bone loss; the possibility that it increased bone mass above initial values is less certain.

A review of attitudes to splintage in Dupuytren's contracture.

A questionnaire on the use of splintage before and after operations for Dupuytren's contracture has been completed by 45 hand surgeons and ten hand therapists. None considered that preoperative splintage was beneficial, but nearly all used some form of splintage after operation. The types of splint and programmes for using them varied widely, and these are discussed.

Terrorism. Part III--Response procedures for terrorist/tactical violence incidents.

A safe and effective response to a terrorist/tactical violence incident involves the following critical factors: Identify and train all potential convergent responders. 2-in/2-out--your partner is your life; have a plan to rescue the rescuers. Orient all responders to LACES. Search your command, staging and treatment areas for a secondary device. Restrict media coverage. Control the scene and relocate/evacuate if necessary. Alert medical receiving facilities early in the event chain to enable them to prepare for a patient onslaught.

Earthquake.

On January 25, 1 week after the most devastating earthquake in Los Angeles history, the Southern California Hospital Council released the following status report: 928 patients evacuated from damaged hospitals. 805 beds available (136 critical, 669 noncritical). 7,757 patients treated/released from EDs. 1,496 patients treated/admitted to hospitals. 61 dead. 9,309 casualties. Where do we go from here? We are still waiting for the "big one." We'll do our best to be ready when Mother Nature shakes, rattles and rolls. The efforts of Los Angeles City Fire Chief Donald O. Manning cannot be overstated. He maintained department command of this major disaster and is directly responsible for implementing the fire department's Disaster Preparedness Division in 1987. Through the chief's leadership and ability to forecast consequences, the city of Los Angeles was better prepared than ever to cope with this horrendous earthquake. We also pay tribute to the men and women who are out there each day, where "the rubber meets the road."

Uptake of 125I-labelled C3a by cultured human endothelial cells.

The interactions of C3a anaphylatoxin with vascular endothelium were studied in vitro using human endothelial cells in culture and 125I-labelled human C3a. Cultured endothelial cells took up 125I-C3a in a time- and concentration-dependent manner and inactivated it. Uptake was not associated with binding to specific receptors since the amount of radioactivity accumulated by the cells was not influenced by treatment with excess unlabelled peptide, metabolic inhibitors or by low temperature. Further, we observed that uptake was not saturated during 90 min of incubation or within the concentration range of C3a tested (10(-9)--10(-6) M). C3a was taken up more rapidly than other labelled, less basic compounds, including Tyr5-bradykinin, lysozyme and albumin. Examination of the cells by autoradiographic electron microscopy revealed labelled material within the cell cysoplasm but not within specific intracellular structures, such as vesicles or vacuoles. C3a was partially inactivated after incubation with endothelial cells for 15 min, but some spasmogenic activity was retained even after 90 min incubation. Since the peptide is readily inactivated by the cells, the radioactivity in the cytoplasm may be inactive C3a and possibly C3a fragments. The combination of uptake and inactivation of C3a by endothelial cells may be an effective means of removing the peptide from circulation.

Comparison of 85Sr, 87mSr, 18F, and 99mTc-labeled phosphates for bone scanning.

The observation by Subramanian and his co-workers that a 99mTc-labeled polyphosphate had excellent affinity for bone has led to widespread use of 99mTc-labeled phosphates as bone scanning agents. Initially, only polyphosphate was employed, but because of somewhat inconstant results and difficulty in preparation of this product, other phosphate compounds were sought. We soon discovered that an inorganic compound, pyrophosphate, appeared to have certain advantages over polyphosphate. Other workers formulated diphosphonates (organic phosphates) which also demonstrated advantages over polyphosphates. Comparison studies in rabbits utilizing 85Sr, 87mSr, 18F, and several phosphates (inorganic and organic) proved the 99mTc-labeled phosphates to be clearly superior in delineating normal skeletal anatomy. Studies in humans confirmed that excellent visualization of bone was obtained with 99mTc-labeled phosphates using either a gamma camera or a rectilinear scanner. What was not known, however, was just how reliable this class of agents would prove to be in detecting bone disease when compared to bone-seeking radiopharmaceuticals such as 85Sr, 87mSr, and 18F. Further comparative analyses have clearly demonstrated that both inorganic and organic 99mTc phosphate complexes are extremely sensitive in revealing more bone disease than the older bone scanning agents.

Ultrasonic evaluation of radiation therapy ports.

Radiation therapy is useful in the palliative treatment of large, unresectable abdominal and pelvic malignancies. The purpose of this study is to evaluate the effectiveness of B mode ultrasound scanning as an adjunct in radiation treatment planning of these patients. Fifty-one patients with large abdominal or pelvic masses had radiation therapy ports established using findings from surgery, radiographs, and physical examination. All the patients then had B mode ultrasound examinations. The position of the therapy ports was marked on the echogram. Thirty-one of the 51 patients studied (61%) had evidence of extension of tumor beyond the therapy ports. This was often due to "iceberging", i.e. when the deep portion of the tumor was considerably larger than the palpable margins of the superficial portion. B mode ultrasound scanning is a valuable adjunct in planning palliative radiation therapy of patients with large, unresectable, abdominal and pelvic malignancies.

Anticapsin, a new biologically active metabolite: screening and assay procedures.

In addition to its implication in the virulence of Streptococcus pyogenes, the hyaluronic acid capsule produced by this bacterium renders it resistant to infection by bacteriophage. A method employing S. pyogenes and a bacteriophage incorporated into an agar plate was devised as a screen to detect compounds that inhibit the formation of the hyaluronic acid capsule. Filter-paper discs saturated with experimental compounds were applied to the surface of test plates containing host plus phage and control plates of host only. After incubation, inhibition of capsule synthesis was indicated by the presence of clear zones where phage infection and lysis had occurred. Zones of growth inhibition on control plates represented classical antibacterial activity. During the testing of over 6,000 fermentation samples, anticapsin, a unique metabolite, was discovered. Modification of incubation temperature, thickness of agar layers, and host-phage input ratios resulted in a quantitative assay method having a dose-response range of 4 to 160 mug of anticapsin.

Autosomal dominant polycystic kidney disease: early diagnosis and data for genetic counselling.

Because of the onset of symptoms in patients with autosomal dominant polycystic kidney disease is generally delayed until adulthood, genetic counseling is imprecise. In an attempt to identify patients early, 261 offspring of subjects with the gene for polycystic disease were tested. Agreement between the results of excretory urography with nephrotomography and radionuclide imaging was excellent. In the 15-19 year age group, polycystic kidney disease was diagnosed in only 30% of 33 subjects at risk, whereas the expected figure was 50%. The disease was diagnosed in 57% of 228 subjects at risk who were aged over 19. When the probands were excluded, this figure was 43% and did not differ significantly from the expected 50%. These data suggest that persons at risk aged over 19 years who have normal urograms and radionuclide images have less than a 5% chance of having inherited the gene for polycystic kidney disease.