[Progression of hepatitis C in a woman with primary immunologic deficiency].
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Adult↗
Biomedical subjects
N Kaufman
Publications and source records attributed to N Kaufman.
Nocturnal serum melatonin profile in major depression in children and adolescents.
BACKGROUND: In major depression, biological rhythm disturbances in sleep, appetite, and mood suggest dysregulation in neuroendocrine functions, possibly in the pineal gland. In this study, pineal gland function was examined by measuring nocturnal serum melatonin levels during both wakefulness and sleep in depressed children and adolescents. METHODS: Twenty-two youths aged 8 to 17 years primarily with major depression were compared with 19 controls. Blood samples were drawn every half hour from 6 PM to 7 AM. Nocturnal serum melatonin levels were measured by radioimmunoassay. RESULTS: The overall nocturnal serum melatonin profile from 6 PM to 7 AM was significantly higher (mean +/- SD, 0.18 +/- 0.14 nmol/L) in the depressed group than in the controls [mean +/- SD, 0.15 +/- 0.10 nmol/L, F(1,26) = 4.37, P < .05]. In dim light, when the subjects were awake, no difference existed between the 2 groups. After lights-out, from 10 PM to 7 AM, the melatonin profile rose in both groups; however, the depressed group had a significantly higher increase (mean +/- SD, 0.24 +/- 0.14 nmol/L) than the controls [mean +/- SD, 0.18 +/- 0.07 nmol/L, F(1,26) = 4.93, mean square error = 0.11, P = .04]. Post hoc analysis showed a significantly higher melatonin profile in depressed subjects without psychosis (n = 15) than in depressed subjects with psychosis (n = 7) or in the controls. CONCLUSIONS: Measuring the overall nocturnal serum melatonin profile during darkness may help to differentiate children and adolescents with major depression without psychosis from those with psychosis and from controls.
Adolescent↗
Short communication: Total craniofacial photon shell technique for radiotherapy of extensive angiosarcomas of the head.
Effective radiotherapy for extensive angiosarcomas of the face and scalp is technically difficult due to the complex shape of the volume at risk, which can consist of the superficial tissues of the entire head. This work reports the details of a rotational X-ray technique used to deliver a large part of the tumour dose. The technique consists of four consecutive 90 degree arcs with changing centre blocks to protect critical midline structures. Multilevel CT based treatment planning is carried out to determine the centre block dimensions and beam weights. As a result the radiation dose is delivered with acceptable uniformity over the entire shell of superficial tissues of the head. The overall treatment combines the rotational fields with large lateral field irradiation and/or local boosts with photons or electrons. Two of three patients treated with this technique had local control of the disease until their deaths at 13 and 18 months. A third patient responded well, with only a small region of stable disease at 9 months.
Aged↗
Prevalence of cognitive dysfunction and hypothyroidism in an elderly community population.
Cognitive function was assessed in 801 elderly subjects (aged 65-92 years) using the Mini Mental State Examination (MMSE). The mean (+/- SD) MMSE score in the age group 65-70 years was 27.8 +/- 5.6, and the score declined to 22.3 +/- 7.8 at the age 85-90 (P = 0.001). Abnormal MMSE scores (less than 24) were found in 5.2% of the subjects aged 65-70 and gradually increased with age to 35.5% in the age group of 85-90. Serum thyroid-stimulating hormone (TSH) levels were determined in 751 subjects. Elevated TSH (> 4.5 mIU/l) were detected in 112 people (14%). The prevalence of hypothyroidism was higher in females (18.2%) than in males (9.7%). MMSE scores in 39 patients (14 males and 25 females) with untreated hypothyroidism were compared to the scores of 570 euthyroid elderly controls (235 males and 335 females). The mean +/- SD MMSE scores were 27.0 +/- 2.1 in hypothyroid males vs. 26.0 +/- 4.7 in male controls and 25.0 +/- 7.7 in hypothyroid females vs. 25.0 +/- 6.6 in female controls. The scores in the hypothyroid patients were not significantly different from the controls. Our data suggest that: a) the average cognitive performance declines with age; b) the percentage of subjects with abnormal MMSE scores increases with age, and is higher in females than in males; c) the prevalence of hypothyroidism in the elderly population is 14% and is higher in females (18%) than in males (10%); and d) mild untreated hypothyroidism is not associated with cognitive impairment.
Aged↗
[Extensive postpartum, bilateral ovarian vein thrombosis].
A 29-year-old woman with extensive pelvic thrombophelebitis complicating postpartum, ovarian vein thrombosis is described. The phlebitic process involved both ovaries, extending upwards to the inferior vena cava above the level of the renal veins and downwards to the ileo-femoral system, obstructing the venous drainage of the lower limbs. Extensive postpartum thrombophlebitis is now rarely encountered, since its early clinical diagnosis using CT and US techniques allows early treatment, obviates this complication. Postpartum bedside alertness, aided by modern imaging techniques, may prevent serious, life-threatening complications.
Adult↗
Caveat emptor. Scoping out the primary care practice game.
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Decision Making, Organizational↗
Heuristically derived tumor burden score as a prognostic factor for stage IIIB carcinoma of the cervix.
PURPOSE: A retrospective analysis of radiotherapeutic management of locally advanced carcinoma of the uterine cervix was performed to evaluate the effect of various treatment parameters and disease extent upon treat outcome. METHODS AND MATERIALS: Between 1976 and 1989, 89 patients with Stage IIIB disease were treated with external beam radiotherapy and brachytherapy. Treatment outcomes were evaluated by dose to Point A, the proportion of Point A dose delivered by brachytherapy, clinical response at 3 months, and a newly developed tumor burden scoring system that quantifies the anatomical extent of disease. Kaplan-Meier estimates of tumor control and survival parameters were determined. RESULTS: Loco-regional control (LRC), disease-free survival (DFS), and overall survival (OVS) at 5 years were 52.9%, 45.5%, and 50.3%, respectively. Clinical response at 3 months was highly predictive of local and distant tumor control. There was no correlation between proportion of brachytherapy dose and treatment outcome. The tumor burden scoring system demonstrates that FIGO Stage IIIB disease can be clinically divided into two prognostic groups of low and high tumor burden. Five year LRC was 62.9% and 40.2% for the low and high tumor burden groups, respectively (p = 0.024). Within the high tumor burden group the LRC was 53.0% and 22.5% when the point A dose given was > 78 Gy and < or = 78 Gy, respectively (p = 0.047). This correlated with improved DFS and OVS. CONCLUSION: The tumor burden scoring system subdivides FIGO Stage IIIB cervical carcinoma into two prognostic groups, predicting for overall survival and demonstrating a dose response in the high tumor burden group. This system may serve to improve future comparison of treatment outcome and to guide selection of patients who may benefit from a more aggressive treatment approach.
Adult↗
Eight guidelines for developing a strategy for the '90s.
Regardless of the outcome of federal reform initiatives, health care is undergoing structural change of unprecedented magnitude. Structural change occurs when there is a fundamental, sustainable change in the values and purchasing behavior of buyers. During such times, market leaders are extremely vulnerable to competitive threats due to internal bureaucratic barriers. Witness the U.S. computer and automobile industries. As Robert Lutz, president of Chrysler, points out, "Being large doesn't mean being safe. The large won't eat the small. The swift will eat the slow." During this dynamic period in health care, it is critical that strategy be on target. Periods of structural change are filled with numerous threats as well as opportunities. The following are eight guidelines for developing health care strategy during the structural changes of the '90s.
Economic Competition↗
Top 10 reasons why many PHOs are failing and hospitals would have been better off doing nothing.
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Decision Making, Organizational↗
Activation of the kallikrein-kinin system after endotoxin administration to normal human volunteers.
The objective of this study was to determine the role of the kallikrein-kinin system in healthy humans after intravenous administration of either Escherichia coli endotoxin or saline. We studied a total of 18 healthy nonsmoking volunteers, 23 to 38 years old, in an open-label study at the Critical Care Medicine Department, Clinical Center, National Institutes of Health (Bethesda, MD) in which some of the patients served as their own controls. After baseline data collection, the subjects received intravenously either E coli endotoxin (n = 15, 4 ng/kg of body weight) or saline (n = 8, controls). Signs, symptoms, systemic blood pressure, factor XII, plasma prekallikrein (PK), factor XI (FXI), antithrombin III (AT-III), high molecular weight kininogen (HK), and alpha 2-macroglobulin-kallikrein complexes were measured at baseline and 1, 2, 3, 5, and 24 hours after injection of either saline or endotoxin. After infusion of endotoxin, we found the functional plasma levels of FXI decreased at 2 hours (P < .05) and at 5 hours (P < .05). Functional PK was significantly depressed by 2 hours (P < .05), at 5 hours (P < .05), and at 24 hours (P < .01), whereas the PK antigen was only low at 5 hours (P < .05). These changes were accompanied by a significant increase in circulating alpha 2-macroglobulin-kallikrein complexes at 3 hours (P < .05) and 5 hours (P < .01). No significant changes occurred in the plasma levels of factor XII or HK. We concluded that clinical response to intravenous endotoxin in healthy human volunteers is associated with activation of the kallikrein-kinin systems. Further investigation is needed with specific inhibitors of the kallikrein-kinin system to define its primary or secondary role in the endotoxin-mediated reactions.
Adult↗
The contact system contributes to hypotension but not disseminated intravascular coagulation in lethal bacteremia. In vivo use of a monoclonal anti-factor XII antibody to block contact activation in baboons.
The hypotension and disseminated intravascular coagulation (DIC) in bacteremia is thought to be mediated by the combined actions of cytokines, prostaglandins, and complement. The contact system, via the release of bradykinin and the activation of Factor XI, has been postulated to be contributing to the observed hypotension and DIC. Using a mAb to Factor XII (C6B7), we blocked the activation of the contact system in an established experimental baboon model in which Escherichia coli was infused to produce lethal bacteremia with hypotension. The untreated group (n = 5) displayed contact activation, manifested by a significant decrease in high molecular weight kininogen (HK) and a significant increase in alpha 2 macroglobulin-kallikrein complexes (alpha 2M-Kal). The C6B7-treated group (n = 5) showed an inactivation of Factor XII and the changes in HK and alpha 2M-Kal complexes were prevented. Both groups developed DIC manifested by a decrease in platelet, fibrinogen, and Factor V levels. The untreated group developed irreversible hypotension. The treated group experienced an initial hypotension that was reversed and extended the life of the animals. This study suggests that irreversible hypotension correlates with prolonged activation of the contact system, and specific antibody therapy can modulate both the pathophysiological and biochemical changes.
Animals↗
Activation of the contact system in lethal hypotensive bacteremia in a baboon model.
The hypotension in septicemia is believed to be mediated by the combined action of many mediators including cytokines, prostaglandins, and complement components. To evaluate the contribution of the contact/kinin-forming system to hypotension, the authors used an established experimental baboon model of bacteremia in which two concentrations of Escherichia Coli (E. coli) were used to produce lethal and nonlethal hypotension. The lethal group (n = 5) developed irreversible hypotension that significantly correlated with the decline in levels of high molecular weight kininogen (HK) and an increase in alpha 2 macroglobulin-kallikrein complexes (alpha 2M-kal). The nonlethal group (n = 9) experienced reversible hypotension, a less striking decline in HK, and only slight elevation in alpha 2M-kal. No significant changes were found in levels of factor XII, prekallikrein, and factor XI in either group. A significant change in the contact system, which reflects the fatal outcome, is the rise in alpha 2M-kal. This study suggests that irreversible hypotension correlates with prolonged activation of the contact system.
Animals↗
Effect of heparin on the activation of factor XII and the contact system in plasma.
We examined in purified systems and in human plasma whether heparin serves as a contact system activating compound. Purified human factor XII zymogen was not activated by heparin through an autoactivation mechanism, but was activated in the presence of purified prekallikrein. Zn2+ (12 microM) did not support autoactivation by heparin. The activation of factor XII and the contact system by heparin in plasma anticoagulated with citrate or with hirudin (not chelating ions) was examined by the cleavage of 125I-labeled factor XII and high molecular weight kininogen (HK). Heparin at 1.6 and 16 USP U/ml was not able to produce activation, in contrast to dextran sulfate (20 micrograms/ml) which supported activation of both factor XII and HK. This study indicates that heparinized plasma does not support activation of the contact system mediated through activation of factor XII. It is not expected that heparin anticoagulant therapy will contribute to activation of the contact system.
Complement C1 Inactivator Proteins↗
Alpha 2-macroglobulin-kallikrein complexes detect contact system activation in hereditary angioedema and human sepsis.
Activation of the contact system has been documented in severe sepsis and hereditary angioedema, but a sensitive, specific, and quantitative assay for assessing the degree of involvement of this proteolytic enzyme cascade is not yet available. We have developed a quantitative sandwich enzyme-linked immunosorbent assay (ELISA) for the alpha 2-macroglobulin-kallikrein (alpha 2M-Kal) complex using an F(ab')2 derivative of a monospecific polyclonal antibody against alpha 2 M as the capture antibody and a unique murine monoclonal antibody, 13G11, against the heavy chain of kallikrein as the detector antibody. The assay does not detect complexes in normal plasma but reacts with complexes generated by activating normal plasma with dextran sulfate at 4 degrees C in a range of 5 to 375 nmol/L. A close correlation of the ELISA with an amidolytic assay for alpha 2M-Kal was documented. Patients with sepsis syndrome but negative bacterial blood cultures did not show elevated plasma complexes, whereas a majority of those with positive blood cultures did show modest elevation and a single patient with septic shock showed a very high level of alpha 2M-Kal complex. Similarly, a patient with classic hereditary angioedema (HAE) showed increased concentration of complexes on three separate occasions during attacks but normal levels between attacks. Two other HAE patients did not show elevated levels at quiescent periods. The ELISA for alpha 2M-Kal appears to be sensitive, specific, and quantitative, and it can be used to reflect the degree of contact system activation in human sepsis and in HAE attacks.
Angioedema↗
Proctor and Gamble's model for repositioning.
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Hospital Administration↗
Brachytherapy in the treatment of solitary colorectal metastases to the liver.
It is well-established that 30-40% of patients with solitary liver metastases from primary colorectal tumors can be cured by resection. Conventional radiation therapy has had only a palliative role in treating liver metastases because the dose that the liver will tolerate is far below a tumoricidal dose. In contrast, brachytherapy allows one to deliver a tumoricidal dose to the tumor while limiting the dose to surrounding normal tissue to the tolerance dose. As a pilot study, 125I seeds were implanted into unresectable hepatic metastases, or positive margins of resection, at the time of surgery. This report concerns six patients whose liver lesions were the only known site of disease and in whom precipitous drops in carcinembryonic antigen (CEA) levels followed the implants. Recurrence was observed in only one of the 11 implanted site, with a median follow-up of 12 months.
Adenocarcinoma↗
Bone marrow transplantation using unrelated donors for patients with advanced leukemia or bone marrow failure.
Thirty-four patients received bone marrow transplants from unrelated donors. Donors and recipients were phenotypically matched for 6 of 6 HLA-A, B, and DR antigens in 27 cases and at 5 of 6 antigens in 7 cases. Twenty-three patients had leukemia, six had myelodysplasia, and five had aplastic anemia. Twenty-four patients had durable engraftment. Five died of sepsis prior to engraftment. Five patients failed to engraft; 2 of these patients had autologous bone marrow recovery. Seventeen patients developed grade greater than or equal to II acute graft-versus-host disease for an actuarial probability of 67 +/- 20%. The severity of acute graft-versus-host disease and its mortality appeared increased for recipients matched for 5 of 6 HLA-A, B, and DR antigens. Of the 34 patients, 13 (38%) are alive; actuarial survival beyond 6 months is 44 +/- 17%. None of the 25 leukemia and myelodysplasia patients achieving engraftment have relapsed. For leukemia and myelodysplasia recipients of 6 of 6 HLA-matched grafts, actuarial survival at 6 months was 55 +/- 21% compared with 14 +/- 26% for recipients matched for 5 of 6 HLA loci (P = 0.19). Infection and acute graft-versus-host disease were the primary causes of death in the engrafted patients. Survival for aplastic anemia patients was 20%. Late deaths due to pneumonia and bronchiolitis obliterans occurred after one year in 2 patients. Closely matched unrelated donor bone marrow transplants are associated with a higher incidence of graft failure and graft-versus-host disease than typically reported for transplants from HLA-identical siblings, but these preliminary data suggest a lower rate of relapse.
Acute Disease↗