Fructose-1,6-diphosphate suppresses T-lymphocyte proliferation, promotes apoptosis and inhibits interleukins-1, 6, beta-actin mRNAs, and transcription factors expression.

The overall objective of this study was to determine the role fructose 1,6-diphosphate (FDP), a naturally occurring glycolytic intermediate, plays in activated T-lymphocytes. The hypothesis is twofold. First, we propose that FDP inhibits T cell proliferation to a greater extent than fructose-1-phosphate (F1P), fructose-6-phosphate (F6P) and mannose-6-phosphate (M6P); second, we argue that FDP suppresses immune activation by inhibiting inflammatory cytokine expression, inhibiting expression of key transcription factors, and by inducing apoptosis in immune cells. Rat spleen cells were incubated with concanavalin A (ConA) and increasing concentrations of FDP. Proliferation was determined by tritiated thymidine uptake. FDP inhibited splenocyte proliferation in a dose-related manner while F1P, F6P, M6P demonstrated inhibition only at high concentrations (5000 microg/ml). RNA was harvested from FDP and ConA-treated cells and IL-1 and IL-6 gene expression was analyzed by RT-PCR. IL-1 and IL-6 mRNA expression was completely inhibited at 500-5000 microg/ml FDP. Apoptosis in FDP-treated lymphocytes was determined by DNA fragmentation and flow cytometry. Propidium iodide (PI) staining demonstrated a 39% rate of apoptosis in splenocytes treated with ConA and 5000 microg/ml FDP. Extensive DNA fragmentation was present at 250-5000 microg/ml FDP, and maximal inhibition occurred at 5 microg/ml. F1P, F6P and M6P showed maximal inhibition only at 5000 microg/ml. Nuclear extracts from FDP-treated splenocytes were analyzed by electrophoretic mobility shift assay. ConA activation of NF-kappaB and AP-1 was dramatically inhibited by FDP. Interestingly, beta-actin showed extensive inhibition with FDP and ConA, thus suggesting new possibilities of its being used as a therapeutic modality in arterial injury where the beta-actin, an important cytoskeleton element, plays a very important role. These data indicate that FDP may be a useful immunosuppressive agent. In conclusion, FDP is not only an immunosuppressant but also an anti-inflammatory agent.

Venous flow restriction: the role of vein wall motion in venous admixture.

OBJECTIVE: There are wide differences in flow between vascular beds at rest, even more during stress. The hydrodynamic energy (Energy grade line or EGL) of venous outflows must also vary considerably between vascular beds. We explored the mechanism of venous admixture of differing energy flows using a mechanical model. MATERIALS AND METHODS: The model simulated two venous flows coalescing at a venous junction and then flowing through collapsible venous pumps. Flow rates and pressures were monitored when the venous pumps were full (steady state) and when they were compressed and allowed to refill inducing wall motion (pump flow). RESULTS: With increasing EGL differences between two coalescing venous flows, reduction or cessation (venous flow restriction) of the weaker flow occurred during steady state; higher base EGL of both flows ameliorated venous flow restriction and lower base EGL the opposite. Outflow obstruction favoured venous flow restriction. Pump action in the vicinity of the venous junction abolished venous flow restriction and maximized both venous flows. CONCLUSION: The model suggests a pivotal role for vein wall motion in venous admixture and regional perfusion. Observations in the model are explained on the basis of network flow principles and collapsible tube mechanics.

Effect of poverty and other socioeconomic variables on renal allograft survival.

BACKGROUND: Socioeconomic variables including low income and noncompliance impact negatively upon long-term renal allograft survival, especially in African Americans. We sought to determine whether other socioeconomic variables contributed to noncompliance and allograft survival. METHODS: A detailed history of socioeconomic variables was made at the time of renal transplant evaluation in 450 consecutive candidates, 128 of whom (89 African American, 39 Caucasian) have thus far undergone transplantation. Variables evaluated included household income, zip code income, insurance coverage, years of education, literacy, marital status, pretransplantation compliance, and history of substance abuse as well as the usual pre- and posttransplantation demographics. RESULTS: Immunologic graft loss occurred primarily in young African Americans with income below the federal poverty level, whereas nonimmunologic graft loss was distributed across racial, income, and other socioeconomic variables. Immunologic graft loss was also associated with a greater number of HLA mismatches, lower levels of education, and noncompliance with transplant medications and follow-up visits. Recipients with gross illiteracy, however, had excellent graft survival. Pretransplantation substance abuse, but not pretransplantation compliance, was predictive of posttransplantation noncompliance. By multivariate analysis, posttransplantation compliance emerged as the single most important factor predictive of graft survival. CONCLUSIONS: Immunologic graft loss in our population is related to noncompliance with transplant medications, which occurred primarily in recipients with a pretransplantation history of substance abuse and is not related to an inability to pay for medications at the time of graft loss. A change in criteria for acceptance of transplant candidates with a prior history of substance abuse might significantly improve graft survival in this patient population.

Studies in calf venous pump function utilizing a two-valve experimental model.

OBJECTIVES: to explore the hydrodynamic mechanisms involved in the regulation of ambulatory venous pressure. DESIGN: an experimental model of calf venous pump was constructed with collapsible tubes and valves. MATERIAL: the model consisted of a conduit and a pump with an intervening competent valve. Another valve that could allow reflux into the pump was mounted above the pump. METHODS: conduit pressure and recovery times were monitored under conditions of different degrees of ejection fraction and reflux into the pump. Model variables included using poorly compliant tubes for the pump, the conduit and for both the pump and conduit. RESULTS: the latex tube exhibited a non-linear volume-pressure relationship and a bi-modal regimen of compliance. This bestowed pressure-buffering properties. Ambulatory venous hypertension resulted when reflux beyond buffering capacity occurred. Substituting less compliant PTFE for latex at the pump had a relatively minor effect on post-ejection pressure and recovery times. Using PTFE at the conduit had a profound but divergent effect on both of these parameters. Conduit capacitance reduction had a similar effect. CONCLUSION: conduit elastance plays a significant role in the regulation of ambulatory venous pressure in this experimental model. The hydrodynamic principles illustrated by the model may enhance our understanding of the human calf venous pump.

Axillary vein transfer in trabeculated postthrombotic veins.

PURPOSE: This study assessed whether axillary vein transfer can be successfully performed in trabeculated veins and whether patients with this severe form of postthrombotic syndrome can be helped by an aggressive approach. METHODS: A total of 102 axillary vein transfer procedures were carried out in 83 limbs with trabeculated veins. More than one venous segment was repaired in 38 limbs with a second axillary valve in 19, and a different technique was used in the remainder. The superficial and deep femoral veins were the most common target sites. "Bench repair" of leaky axillary valves was performed before the transfer in 32 cases. Venous stasis dermatitis or ulceration was present in 90% of the limbs. The operability rate and chance of successful valve reconstruction was high, even in the presence of severe venographic appearance. RESULTS: The actuarial transplant patency rate was 83% at 10 years. The actuarial freedom from recurrent ulceration rate was more than 60% at 10 years, similar to the results obtained in a matched group of axillary vein transfers to nontrabeculated veins. Severe preoperative ambulatory venous hypertension (venous filling time [VFT] of less than 5 seconds), which was present in 67% of patients, did not adversely affect outcome, but short VFTs that persisted after surgery did. VFT and VFI90 (venous filling index, air plethysmography) improved after valve transfer. Swelling disappeared or was significantly reduced in 55% of patients (11 of 20 patients) who had moderate or severe preoperative swelling. In 82% of patients (31 of 37 patients) who had mild or no preoperative swelling, the swelling remained stable after surgery, and in 18% of patients (6 of 37 patients), it became worse. Pain was significantly diminished in 70% of patients; 23% of patients with severe pain had complete resolution. CONCLUSION: Axillary vein transfer, in combination with other antirefluxive procedures when indicated, is safe, effective, and durable in patients with trabeculated veins and severe forms of postthrombotic syndrome. It may be considered as an option when conservative therapy or other types of surgery fail.

The case for trial of labor in the patient with a prior low-segment vertical cesarean incision.

OBJECTIVE: Our purpose was to review recent obstetric literature detailing the subsequent delivery experience of patients with a prior low-segment vertical cesarean incision and to derive recommendations for practice on the basis of this information. STUDY DESIGN: Ten studies that included information about pregnancy outcome in patients with prior low-segment vertical cesarean operations were retrieved and reviewed from the American obstetric literature since 1981 and from a review of all abstracts presented annually since 1981 to the Society of Perinatal Obstetricians. RESULTS: Altogether, information about subsequent pregnancy outcome for 382 patients with prior low-segment vertical cesarean delivery was available for analysis. Among the 372 patients with complete patient population information, vaginal delivery was safely accomplished in 306 (82%). Four uterine ruptures (1.05%) have been reported, only one of which occurred after a single prior unextended low-segment vertical cesarean incision. Two ruptures occurred elsewhere on the lateral or posterior aspect of the uterus in subsequent pregnancies, and the fourth rupture occurred at the juncture of prior low vertical and transverse incisions. No perinatal mortality or permanent perinatal morbidity was encountered with these pregnancies. CONCLUSIONS: In the otherwise uncomplicated pregnancy the patient with one previous nonextended low-segment vertical cesarean incision should be considered to have a prior low-segment scar and as such be a candidate for trial of labor in her current singleton pregnancy. The same care, counseling, and caution should be exercised for this patient as for one with a prior low-segment transverse incision.

Survival of carcinoma of the prostate patients less than 55 years old compared to older patient groups.

Both incidence and death rate from cancer of prostate are rising. Prostate cancer is the most common malignancy in man and second most common cause of death in men. Lung cancer is the leading cause of death in men. Carcinoma of prostate is generally a disease of older men. Carcinoma of prostate can also occur in the middle-aged men. This study was performed to find whether the middle-aged men survived longer than older men when both groups of patients were compared according to equivalent stage of the disease. In this series, survival is slightly better in younger age groups when patients of all stages are pooled together. Due to small number of patients in younger age groups, survival difference cannot be calculated for each stage of the disease.

Remote umbilical arterial blood pH analysis: accuracy, utility, and limitations.

It is not always possible or feasible to perform routine umbilical artery blood sampling at birth. This study was undertaken to assess the accuracy of selective remote umbilical arterial blood analysis to retrospectively predict the original birth pH of any newborn. Umbilical arterial blood samples were obtained in two preheparinized syringes immediately following 1007 deliveries. One sample was analyzed within 60 minutes of delivery. The other was placed on ice and later analyzed at variable time intervals up to 180 hours postpartum. The results of each remote analysis were adjusted using a previously published regression equation to accurately identify which newborns had pH values < 7.00, < or = 7.10, or < 7.20 at birth. Among the 1007 newborns, there were 14 (1.3%), 44 (4.3%), and 187 (18.5%) who had pH values < 7.00, < or = 7.10, and < 7.20, respectively, at birth. Remote umbilical arterial samples analyzed within 72 hours of delivery correctly identified newborns with an original pH < 7.00, < or = 7.10, or < 7.20 with: (1) a sensitivity of 100, 82, and 84%, respectively; (2) positive predictive values of 100, 93, and 66%, respectively; and (3) a test efficiency of 100, 99, and 89%, respectively. Up to 72 hours after delivery, remote umbilical arterial blood pH analysis can be reliably used to accurately identify the newborn that was acidotic at birth.

Effect of birth order on incidence of periventricular-intraventricular hemorrhage in very low birth weight twins.

The purpose of the study was to determine whether the incidence of periventricular-intraventricular hemorrhage (PV-IVH) is significantly different between the firstborn and secondborn of very low birth weight twins. The firstborn and secondborn of 102 sets of twins were compared by incidence of PV-IVH, mode of delivery, birth weight, 5-minute Apgar score, pH, duration of oxygen therapy, duration of ventilator support, and occurrence of patent ductus arteriosus, air leak, bronchopulmonary dysplasia, or hyaline membrane disease. PV-IVH was graded by the Papile classification. Statistical data were analyzed by either the paired t test or McNemar's test. Major PV-IVH (grades III and IV) occurred in 11 firstborn and 14 secondborn infants. Minor PV-IVH (grades I and II) occurred in 11 firstborn and 8 secondborn twins. Neither these findings nor those from other measured variables showed a statistically significant difference.

Cooperative stroke management project by a peer-review organization.

To improve the care of patients in Mississippi through increased adherence to nationally accepted ischemic stroke management guidelines, patterns for ischemic stroke services were determined from hospital chart review. Hospital-specific education and data feedback were performed to encourage international systems improvements. The Mississippi Foundation for Medical Care, Inc, reviewed records of Medicare beneficiaries discharged with the principal diagnosis of acute ischemic stroke from four hospitals over a 1-year period. Records were analyzed for compliance with stroke management guidelines. Hospital-specific and aggregate data were presented to the staffs of each hospital and the hospitals were encouraged to develop internal quality improvement projects. The Foundation reviewed 427 records of acute stroke patients, of whom 375 (87.8%) had ischemic stroke. Among the 427 stroke patients, there were 76 (17.8%) in-hospital deaths. Notable variances from the ischemic stroke management guidelines included those for emergent hypertension management, deep vein thrombosis prophylaxis, evaluation for cause of ischemic stroke, and use of antithrombotic therapy on discharge of ischemic stroke patients. Thus, the management of acute stroke patients in these four regional hospitals in Mississippi often differed from nationally accepted guidelines. We hope to improve the care of stroke patients by using the expertise of academic stroke physicians and hospital-specific analyses that are personally meaningful but not personally threatening to treating physicians.

Hypertension, cardiac hypertrophy, and neurohumoral activity in a new animal model of obesity.

Although obesity is a major risk factor for morbidity and mortality, the mechanisms mediating cardiovascular abnormalities in response to weight gain are unclear. One reason for the paucity of information in this area is the lack of appropriate animal models for the study of human obesity. Therefore, the goal of the present study was to develop a small animal model of dietary-induced obesity that mimics many of the characteristics of human obesity. We studied female New Zealand White rabbits fed either a normal (n = 17) or high-fat diet (n = 15) and examined the cardiovascular consequences of obesity, including changes in blood pressure, humoral activation, and end-organ effects such as cardiac hypertrophy. After 12 wk, rabbits on the high-fat diet were 46% heavier than their lean counterparts (5.49 +/- 0.09 vs. 3.77 +/- 0.06 kg, respectively; P = 0.0001). Obese rabbits had higher resting heart rates than lean rabbits (220 +/- 7 vs. 177 +/- 6 beats/min; P = 0.0001) and developed hypertension (96 +/- 2 vs. 85 +/- 1 mmHg; P = 0.0001), hyperinsulinemia (32.5 +/- 3.4 vs. 15.5 +/- 1.0 microU/ml; P = 0.0001), hyperglycemia (162.4 +/- 2.9 vs. 141.9 +/- 2.7 mg/dl; P = 0.0001), and elevated triglycerides (102.3 +/- 9.1 vs. 48.5 +/- 4.0 mg/dl; P = 0.0001). Obese rabbits also developed cardiac hypertrophy, as evidenced by left ventricular (LV) dry weights that were 52% greater in obese than in lean rabbits (P = 0.0003). In addition, LV total protein was increased in proportion to the increase in LV weight. The results of this study suggest that rabbits fed a high-fat diet for a period of 12 wk develop many of the characteristics of human obesity. The obese rabbit should provide a small and relatively inexpensive animal model to investigate mechanisms of obesity-related cardiovascular abnormalities.

Order of rotation in third-year clerkships. Influence on academic performance.

OBJECTIVE: To determine if student performance during the third-year clerkship is influenced by the order of departmental rotation. STUDY DESIGN: In this retrospective, descriptive study, the National Board of Medical Examiners (NBME) scores, departmental examination grade (DE) and final block grade (FG) were stratified into six segments based on the order of block time in obstetrics-gynecology, pediatrics, psychiatry, internal medicine, surgery and family medicine. Consistency was validated by comparing these performance criteria from 1988 to 1992. RESULTS: When all six clerkships were assessed by year, there was no uniform trend of improved performance over time. In the obstetrics-gynecology block, however, NBME scores and FGs were highest for students assigned to the fifth and sixth rotation as compared to the first two groups (P < .02). No such trend was noted with the departmental written examination. In surgery, DE and FG were always lower in the first rotation (P = .0001). Psychiatry DE scores were significantly higher on the second or third blocks as compared to the fifth and sixth rotation positions (P < .001). Students had a higher FG in pediatrics when the sixth position was compared to the second block (P = .02), but the DE grades and NBME scores were not altered by rotational schema. In family medicine and internal medicine, no effect of rotation was noted. CONCLUSION: Third-year clerks tended to have higher NBME scores and FGs in obstetrics-gynecology if they selected this rotation later in the academic year. Surgery DEs and FGs were lowest if selected first in the academic year. There was no similar trend in other nonsurgical specialties. These data suggest that prior clinical rotations positively influence student performance in obstetrics-gynecology.

Use of plant-derived therapies in a rural, biracial population in Mississippi.

Exploring the use of plant-derived medicines has recently received much attention in both scientific and popular journals. A study conducted in central Mississippi on medicinal plants investigated the frequency of use, types of plants used, and symptoms treated. A randomly selected probability sample of 223 households found that over 70 percent of the adults used at least one plant-derived medicine during the past year. The most frequently used plants included lemon, aloe, castor, turpentine, tobacco, and garlic. Frequency of use varied by race with a higher proportion of African-Americans than Caucasians reporting use of a plant-derived medicine. Due to the possible presence of toxic compounds or potential drug interactions, it is recommended that health care professionals investigate the use of plant-derived therapies as part of the patient's medical history.

Infection control knowledge, practice, and attitudes of Mississippi dental hygienists.

PURPOSE: The purpose of this study was to assess Mississippi dental hygienists' knowledge and use of infection control techniques, attitudes pertaining to universal precautions and the risk of clinician/patient cross-infection, and attitudes toward treatment of patients with infectious diseases. METHODS: A 41-item questionnaire was mailed to all 508 licensed dental hygienists in Mississippi. Inactive, retired, and out-of-state hygienists (n = 59) were deleted from this study. The data were tested for significant associations using Chi-square. RESULTS: After adjusting for the 59 unusable returns, the response rate for analysis was 58% (n = 297). Dental hygienists reported using infection control techniques including sterilization or disposal of common items such as prophylaxis angles, suction tips, and air/water syringe tips. Although 98% of the respondents believed that barrier techniques were effective, some believed patients infected with HIV/AIDS (43%), hepatitis B (31%), or tuberculosis (40%) are best treated in public clinics rather than in private settings and that these clients pose a threat to dental hygiene practitioners. Further, a majority of the respondents believed that all oral healthcare workers and patients should be tested for HIV/AIDS. CONCLUSIONS: The incongruity between perceived knowledge, reported practice, and attitudes suggests the need for continuing education courses designed to allow dental hygienists to explore the affective domain regarding the care of patients with infectious diseases. In addition, courses on working with patients with HIV/AIDS should be offered in smaller cities for greater accessibility.

How dentists perceive the effects of orthodontic extraction on facial appearance.

In recent years, orthodontic treatment, particularly that involving premolar extractions, has been alleged to cause flat facial profiles. Those who make such assertions also claim to be able to instantly identify from a distance faces of patients who have received orthodontic treatment. These are strong claims that could profoundly affect the public's perception of dentistry and its specialties. This study examined whether dentists could distinguish between profiles of treated and untreated patients as well as between patients who had undergone extraction and those who had not.

Comparison of unscheduled hospital admission following ambulatory operative laparoscopy at a teaching hospital and a community hospital.

The objective was to identify and compare causes of unscheduled admission following ambulatory major operative gynecologic laparoscopy in a university hospital and a community hospital setting. Each patient admitted on an unscheduled basis was compared with 2 patients who did not require admission. Twenty-seven variables were evaluated by univariate analysis. Significant factors (p < 0.5) were analyzed by multivariate stepwise logistic regression. Patients admitted at the university hospital were compared with patients at a community hospital. In a 7-year period, 43 patients at the University of Mississippi Medical Center and, in a 6-year period, 30 patients at Gilmore Memorial Hospital required unscheduled admission following ambulatory major operative gynecologic laparoscopy. Site-specific analysis was performed, and these groups also were combined for analysis. The only factor associated with admission by multivariate analysis was estimated operative blood loss. Postoperative emesis was the most common reason for unscheduled admission at both hospitals and occurred in 27 patients. An additional 17 patients were admitted because of the severity of postoperative pain. Operative blood loss seems to be associated with extensive operations. Furthermore, increased blood loss typically leads to a very conservative approach to the postoperative patient, whereas minimal blood loss allows patients to be managed in a routine fashion. Patients at the university hospital seem to be generally comparable to patients at a community hospital. Postoperative nausea and pain resulted in over one half of admissions. Successful therapy for nausea and pain may reduce unscheduled admissions.

Relationship of cranial midline shift to outcome of very-low-birth-weight infants with periventricular hemorrhagic infarction.

The purpose of this study was to determine the relationship of a cranial midline shift accompanying periventricular hemorrhagic infarction to subsequent handicap in very-low-birth-weight infants. A study group of 44 infants with intraventricular hemorrhage and an associated periventricular hemorrhagic infarction was retrospectively selected from 1,080 very-low-birth-weight infants evaluated by cranial sonography. A cranial midline shift is defined sonographically as displacement of the septum pellucidum (or cavum septi pellucidi) more than 3 mm from the spatial midline. The midline is measured as half the distance between the right and left inner tables on an anterior coronal view. Other sonographic data recorded were the size of the lateral ventricle, the intracranial hemisphere, and the periventricular hemorrhagic infarction. Also noted was the appearance of the area of infarction at the time of initial detection of a midline shift. After discharge, the infants were periodically evaluated for major handicap in vision, hearing, cognition, and motor activity. A midline shift was identified in 29 (66%) of 44 infants with periventricular hemorrhagic infarction. Seven (24%) of the 29 infants with midline shift and 3 (20%) of the 15 infants without a midline shift died. In all of the 22 surviving infants with a midline shift and in 3 (25%) of 12 survivors without a midline shift, a handicap developed (p < 0.01). As a predictor of handicap, midline shift showed a sensitivity of 88% and a specificity of 100%. Predictability was not improved by combining midline shift with the size of the parenchymal infarct.(ABSTRACT TRUNCATED AT 250 WORDS)

Postpartum corticosteroids: accelerated recovery from the syndrome of hemolysis, elevated liver enzymes, and low platelets (HELLP).

OBJECTIVE: Because most morbidity and mortality associated with atypical preeclampsia and the syndrome of hemolysis, elevated liver enzymes, and low platelets is a postpartum phenomenon, we undertook this investigation to evaluate the use of high-dose corticosteroids to minimize maternal morbidity and accelerate postpartum recovery in patients with this form of severe preeclampsia. STUDY DESIGN: Into this prospective, randomized study 40 parturients with the syndrome were recruited. The syndrome was defined by a clinical presentation consistent with a diagnosis of severe preeclampsia or eclampsia in addition to laboratory evidence of hemolysis, hepatic dysfunction, and thrombocytopenia. Immediately post partum 20 parturients assigned to the treatment group received four doses of intravenous dexamethasone at 12-hour intervals (10 mg, 10 mg, 5 mg, 5 mg) over 36 hours. Patients assigned to the control group received no corticosteroids. All study subjects were intensively monitored by mean arterial pressure and urinary output every 2 hours, hematocrit and platelet count every 6 hours and lactic dehydrogenase, aspartate aminotransferase, and alanine aminotransferase every 12 hours for the first 48 hours post partum. RESULTS: The steroid-treated group with the syndrome of hemolysis, elevated liver enzymes, and low platelets had significant changes over time in mean arterial pressure, urinary output, platelet count, lactic dehydrogenase and aspartate aminotransferase versus the control group with the syndrome. Relative to the control group, the mean arterial pressure became significantly decreased at 22 hours in the steroid-treated group (p < 0.03), urinary output increased significantly by 16 hours (p < 0.02), the platelet count increased significantly by 24 hours (p < 0.05), and both lactic dehydrogenase and aspartate aminotransferase decreased significantly by 36 hours (p < 0.04 and p < 0.05, respectively). CONCLUSIONS: In association with high-dose corticosteroid administration, parturients with the syndrome of hemolysis, elevated liver enzymes, and low platelets recovered from the disease process more rapidly than did control subjects, as measured by urinary output, mean arterial pressure, platelet count, lactic dehydrogenase, and aspartate aminotransferase. In this disease process, which has significant associated morbidity and mortality, especially in patients with advanced cases, high-dose corticosteroid therapy appears to significantly hasten recovery and lessen the severity of the disease post partum. We postulate that use of this therapeutic approach in properly selected patients could result in lessened overall maternal morbidity and mortality, shorter patient stays in recovery and intensive-care areas, and shorter overall hospitalization with reduced medical care costs.