Autoregulation by eicosanoids of human Kupffer cell secretory products. A study of interleukin-1, interleukin-6, tumor necrosis factor-alpha, transforming growth factor-beta, and nitric oxide.

OBJECTIVE: Methods employed previously to analyze the secretory behavior of rodent Kupffer cells (KC) were used to examine the human KC's secretory response to lipopolysaccharide (LPS). SUMMARY BACKGROUND DATA: As the resident hepatic macrophage, the KC resides at the interface between the portal and systemic circulations. Consequently, this cell may play an integral role in the immune response to antigens and bacteria in the sinusoid. Study of cytokine production by the KC has relied predominantly on the rat as the source of these cells. Whether human KCs respond similarly to rat KCs after LPS stimulation has been a matter of speculation. METHODS: Kupffer cells obtained from seven human livers were tested under conditions identical to those used to study rat KCs. Kupffer cells rested for 12 hours after isolation were stimulated with LPS (2.5 micrograms/mL). Arginine concentration in the culture medium varied from 0.01 to 1.2 mM. To examine the role of eicosanoids, parallel culture wells received indomethacin (10 microM). Culture supernatants were assayed for interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta), prostaglandin E2 (PGE2), and nitric oxide. RESULTS: Similar to the rat KC, LPS-stimulated human KCs released IL-1, IL-6, TNF-alpha, TGF-beta, and PGE2. However, unlike rat KCs, nitric oxide could not be detected, regardless of whether the human KCs were exposed to LPS, interferon-gamma (INF-gamma), or LPS + IFN-gamma. Similar to rat KCs, indomethacin prevented PGE2 release while significantly upregulating TNF-alpha, IL-1, and IL-6, but not TGF-beta, consistent with an autoregulatory control of eicosanoids over proinflammatory cytokines. As has been shown in the rat, physiologic levels of L-arginine (0.01 mM) significantly enhanced LPS-induced PGE2 secretion relative to the response in medium containing standard L-arginine concentration (1.2 mM); however, unlike the rat KC, the human's cytokine response to LPS was not downregulated by this enhanced PGE2 release. CONCLUSIONS: Although many functional features are shared by rat and human KCs, significant differences do exist. Such discrepancies reinforce the need to proceed with caution when generalizing from the results obtained in other species to human physiology.     

Chirurgie bei immunsupprimierten Patienten unter Notfall- und Elektivbedingungen

Zusammenfassung. Die Auswirkungen einer Immunsuppression auf perioperative pathophysiologische Vorg?nge stellen besondere Anforderungen sowohl in bezug auf die Indikationsstellung zu einem operativen Eingriff als auch an das perioperative Management. Eine immunsuppressive Therapie kann ein ver?ndertes oder v?llig fehlendes Abwehrverhalten bei entzündlichen Prozessen bewirken, so da? die hierfür typischen klinischen Anzeichen nur schwach oder gar nicht ausgepr?gt werden. Dies kann zu einer gef?hrlichen Latenz in der Diagnostik akut lebensbedrohlicher Erkrankungen bei immunsupprimierten Patienten führen. Darüber hinaus tragen die ver?nderte Reaktivit?t des Patienten auf Stre?, eine verz?gerte und verminderte Wundheilung sowie insbesondere die erh?hte Infektanf?lligkeit zu einem gesteigerten Operationsrisiko bei. Perioperativ sind daher eine konsequente klinische überwachung des Patienten und ein lückenloses Monitoring der Immunsuppression unverzichtbar. Für den klinischen Umgang mit immunsupprimierten Patienten ergeben sich hieraus 2 unterschiedliche Pr?missen hinsichtlich der Indikationsstellung bei Elektiv- und Notfalleingriffen. W?hrend unter Elektivbedingungen eine sorgf?ltige Operationsplanung unter besonderer Berücksichtigung der m?glichen Risiken für Patient und Transplantat unabdingbar ist, so lassen die oftmals gro?en diagnostischen Unsicherheiten bei entzündlichen Vorg?ngen sowie die erheblichen Risiken eines verz?gerten Therapiebeginns eine eher etwas gro?zügigere Indikationsstellung zur operativen Intervention in Zweifelsf?llen berechtigt erscheinen. Operativ technisch ist generell auf ein gewebeschonendes und atraumatisches Vorgehen zu achten, weiterhin sollte eine besondere Sorgfalt bei Anastomosenn?hten und Wundverschlu? bestehen. Darüber hinaus sind von Seiten des Chirurgen die Einflu?m?glichkeiten auf den postoperativen Verlauf begrenzt.      

Upper Airway Obstruction With Hypoxaemia And Sleep Disruption In Down Syndrome

Six of 12 children with Down syndrome (DS) tested by means of long-term tape-recordings of oxygen saturation, breathing movements and expired CO2 were found to have previously undetected and severe upper airway obstruction during sleep. In five cases the obstruction occurred in the pharynx and in the sixth it was due to bilateral choanal stenosis. When compared with age-matched controls, overnight tape-recordings showed episodes of abnormal arterial hypoxaemia and an abnormally elevated end-tidal CO2. Episodes of obstruction were most marked during sleep associated with a non-regular breathing pattern. Abnormal episodes of hypoxaemia were associated with continued breathing movements. Sometimes there was no airflow (complete obstruction); at other times airflow continued normally or was reduced in amplitude (partial obstruction). During episodes of partial or complete airway obstruction the inspiratory waveform showed a characteristic shape. These results show sleep-related upper airway obstruction to be an often undetected complication of DS and all necessary measures should be taken to overcome the obstruction when it reaches the stage of producing abnormal hypoxaemia. Choanal dilatation and tracheostomy were successful in treating two of the children. Tonsillectomy and adenoidectomy were successful for one child, but only of marginal benefit for two others.     

CLINICAL ANALYSIS OF FOUR CHINESE HEMOPHILIACS WITH HUMAN IMMUNODEFICIENCY VIRUS INFECTION

Human immunodeficiency virus (HIV) is now considered as the causative agent of acquired immunodeficiency syndrome (AIDS). A high risk of AIDS has been reported among patients with hemophilia who received lyophilized commercial factor VIII and IX concentrates of American origin. At a prevalent survey from September to December 1985, HIV antibodies were found in all four patients with hemophilia treated with the batch number W87307, 955 I.U. of American commercial factor VIII concentrate supplied by Armour Pharmaceutical Company, USA. One of the sero-positive patients developed AIDS-related complex (ARC) and died of cerebral hemorrhage. The other three sero-positive patients had abnormalities in cell-mediated immunity. Of them two developed left lumbosacral radiculopathy and hemorrhagic herpes zoster and one remained well so far.     

Regional blood flow during continuous low-dose endotoxin infusion

Escherichia coli endotoxin (ET) was administered to adult rats by continuous IV infusion from a subcutaneously implanted osmotic pump (Alzet). Cardiac output and regional blood flow were determined by the radiolabeled microsphere method after 6 and 30 hr of ET or saline infusion. Cardiac output (CO) of ET rats was not different from time-matched controls, whereas arterial pressure was 13% lower after 30 hr of infusion. After both 6 and 30 hr of ET, pancreatic blood flow and percentage of cardiac output were lower than in controls. Estimated portal venous flow was decreased at each time point, and an increased hepatic arterial flow (significant after 30 hr) resulted in an unchanged total hepatic blood flow. Blood flow to most other tissues, including epididymal fat, muscle, kidneys, adrenals, and gastrointestinal tract, was similar between treatments. Maintenance of blood flow to metabolically important tissues indicates that the previously reported alterations in in vitro cellular metabolism are not due to tissue hypoperfusion. Earlier observations of in vitro myocardial dysfunction, coexistent with the significant impairment in pancreatic flow, raise the possibility that release of a myocardial depressant factor occurs not only in profound shock but also under less severe conditions of sepsis and endotoxemia.     

Sexually transmitted diseases in abused children and adolescents

The prevalence of abnormal physical signs (e.g., bleeding, scars, or bruises) and genital infections, notably Chlamydia Trachomatis, Neisseria Gonorrhea, and Herpes Simplex Genitalis was studied in 219 female children with validated sexual abuse. They were compared to 113 nonabused female children. The average abused child was 8.3 years old, with 69% having been abused on multiple occasions. Most offenders were family members (65%) or a close family friend (22%). Stranger-perpetrated sexual assault, in the sample, was low (9.1%). Few children had severe vaginal tears, though 56% showed signs of subtle anatomical injury to their genitalia. No similar anatomical abnormalities were present in nonabused children. Among the sexually abused children and adolescents, 35% were colonized with a pathogen or a potential pathogen, compared to a prevalence rate of 18.5% in non-abused children. The proportion of abused children colonized with Ureaplasma Urealyticum and Mycoplasma Hominis was not significantly different from that found in nonabused children. At present, Neisseria gonorrhea and Chlamydia Trachomatis remain the only conclusive markers for sexual abuse. It is recommended that routine cultures of the pharyngeal, rectal, and vaginal areas be taken in all cases of suspected child sexual abuse, regardless of clinical findings.     

Hypoosmolare Hyponatri?mie als Leitsymptom bei Hypothyreose

Zusammenfassung Anamnese und Diagnostik: Ein 75-jähriger Patient wies neben unspezifischen anamnestischen Symptomen (Appetitverlust, Merkfähigkeitsstörung und Muskelschwäche) klinisch diskrete Beinödeme, abgeschwächte Muskeleigenreflexe und eine deutliche Gedächtnisstörung auf. Aufgrund einer euvolämischen, laborchemisch hypoosmolaren Hypoatriämie und eines Urinnatriums im Normbereich wurde als Arbeitsdiagnose von einem Syndrom der inadäquaten ADH-Sekretion (SIADH) ausgegangen. Während sich weder in der Anamnese noch in den folgenden Untersuchungen eine dem SIADH zugrunde liegende Pathologie eruieren ließ, ergab sich in den weiteren Laboruntersuchungen der Befund einer ausgeprägten Hypothyreose. Die Hyponatriämie bei Hypothyreose spiegelt eine Komponente der renalen Funktionsstörung bei Schilddrüsenhormonmangel wider. Therapie und Verlauf: Nach Flüssigkeitsrestriktion und Hormonsubstitution erreichte der Patient schnell normale Natriumwerte und zeigte eine deutliche Besserung seiner kognitiven Fähigkeiten. Schlussfolgerung: Als Schlussfolgerung aus dieser Kasuistik wird Zurückhaltung bei der Diagnose eines SIADH empfohlen, bevor nicht eine sorgfältige Untersuchung des Nebennieren- und Schilddrüsenhormonstatus erfolgt ist. Abstract Case History and Diagnosis: A 75-year-old male patient presented with a history of anorexia, muscle weakness, and increasing memory loss. He had mild pedal edema and decreased deep tendon reflexes. As the laboratory tests showed hypoosmolar hyponatremia and urinary sodium within the normal range, a syndrome of inappropriate ADH secretion (SIADH) was presumed. While neither the medical history nor any of the diagnostic procedures revealed any underlying pathology explaining the SIADH, laboratory tests showed significant hypothyroidism. Hypothyroid states are associated with significant changes in renal function, one of which is hypoosmolar hyponatremia. Treatment and Course: Treatment included fluid restriction and hormone substitution and resulted in a quick correction of the hyponatremia and a clear improvement of the patient's cognitive function. Conclusion: It is concluded that the diagnosis of SIADH should only be made after thorough investigation of the adrenal and thyroid hormone status.     

The rehabilitation potential of geriatric patients from the cardiologic viewpoint

The potential of rehabilitation for geriatric patients depends on physiological considerations about the aging organism, as well as diseases, accompanied by the natural aging process. A common feature of the aging process of human organs is a general loss of adaptability that contributes to hypocirculation. The potential for rehabilitation may be considerably limited by diseases which burden the circulatory system (atherosclerosis, coronary heart disease, hypertension, and hypotension). Cardiac arrhythmias occurring during rehabilitation procedures call for special care. Mode and intensity of the rehabilitation program will be determined by cardiac and circulatory reactions following active rehabilitation procedures. Isometric exercise stress in conjunction with pressure breathing leads to an excessive rise of blood pressure in systemic and pulmonary circulation. Therefore dynamic muscle actions should be preferred as the most reasonable active training, but there is the possibility of heart-circulation problems arising, depending on the intensity of training.     

Psychosocial aspects of disease duration and control in young adults with type I diabetes

Self-report questionnaires completed by young adults with Type I diabetes were examined to determine if individuals differing in recent metabolic control (Poor, Moderate or Very Good) or disease duration (Long, Short) also vary in either occurrence or type of life events during the past year or occurrence of recent emotional distress. Subjects in Poor control reported more positive and neutral life events during the past year, suggesting even those life changes individuals view benignly may be associated with metabolic control difficulties. Individuals in Poor control also reported more recent symptoms of depression, anxiety and hostility than did individuals in Moderate or Very Good control--symptomatology which may further impair their ability to adhere to a complex self-care regimen. Individuals with Long disease duration reported more positive and negative recent life experiences than did subjects with Short disease duration, but did not evidence concomitant disruptions in metabolic control. The role experience with a chronic disease may play in this finding was unclear, however. Although more research is required to clarify the exact relation of psychosocial variables and diabetic control, these findings suggest that clinically relevant subgroup parameters, subjects' perceptions of life change, and demographic variables may be important factors to assess.