[Oral glucocorticoids : Therapeutic use and treatment monitoring in inflammatory rheumatic diseases]. / Orale Glukokortikoide : Anwendung und Therapiemonitoring bei entzündlich-rheumatischen Erkrankungen.

Glucocorticoids (GC) have been proven drug substances in rheumatology for more than 70 years. They act very rapidly in high doses through membrane stabilizing effects. Genomic therapeutic effects of GC even in very low doses are mainly due to inhibition of the functions of the transcription factor nuclear factor kappa B (NFkB), which promotes the synthesis of proinflammatory mediators, adhesion molecules and other regulatory proteins. Indications for the use of GC in high doses in rheumatology are always given when a life-threatening, dangerous or treatment-resistant situation is involved. Lower doses of GC, usually administered orally, are particularly used in rheumatoid arthritis, vasculitis and collagenosis. In clinical practice the general principle is to use the smallest possible effective dose of GC for the shortest possible time in order to achieve the therapeutic effect of GC without running the risk of unacceptably severe side effects.

[Oral glucocorticoids : Therapeutic use and treatment monitoring in inflammatory rheumatic diseases]. / Orale Glukokortikoide : Anwendung und Therapiemonitoring bei entzündlich-rheumatischen Erkrankungen.

Glucocorticoids (GC) have been proven drug substances in rheumatology for more than 70 years. They act very rapidly in high doses through membrane stabilizing effects. Genomic therapeutic effects of GC even in very low doses are mainly due to inhibition of the functions of the transcription factor nuclear factor kappa B (NFkB), which promotes the synthesis of proinflammatory mediators, adhesion molecules and other regulatory proteins. Indications for the use of GC in high doses in rheumatology are always given when a life-threatening, dangerous or treatment-resistant situation is involved. Lower doses of GC, usually administered orally, are particularly used in rheumatoid arthritis, vasculitis and collagenosis. In clinical practice the general principle is to use the smallest possible effective dose of GC for the shortest possible time in order to achieve the therapeutic effect of GC without running the risk of unacceptably severe side effects.

[Controlling glucocorticoid treatment in critically ill patients with rheumatism exemplified by systemic lupus erythematosus]. / Zur Steuerung einer Glukokortikoidtherapie beim kritisch kranken Rheumapatienten am Beispiel des systemischen Lupus erythematodes.

BACKGROUND: Infections are one of the most common clinical problems in patients with rheumatic diseases who need to be treated with glucocorticoids in an intensive care unit. To date, there are no recommendations for the standardized control of glucocorticoid treatment in such situations. OBJECTIVE: Based on a literature search this paper provides an overview of evidence-based and eminence-based recommendations for the control of glucocorticoid treatment under intensive care conditions using the example of systemic lupus erythematosus. METHODS: A systematic literature search was carried out using a MeSH term search in the PubMed database. RESULTS: Infections are one of the most common causes for the treatment of patients with rheumatic diseases in intensive care units. In the case of systemic lupus erythematosus it is particularly challenging to distinguish the infection from increased disease activity or to treat the parallel occurrence. Patients in an intensive care unit are exposed to an increased level of physical stress due to the severity of the disease, which is why special attention should be paid to symptoms of adrenocortical insufficiency. Evidence-based recommendations for prophylaxis of an adrenal crisis only exist in relation to perioperative procedures and not for the situation of severe infections. CONCLUSION: The use of glucocorticoids in systemic lupus erythematosus is often chronic and there is an increased risk of infections. In the case of infections (or simultaneous disease flare) adequate anti-infective treatment should be administered, the treatment with glucocorticoids should be adjusted accordingly and symptoms of adrenocortical insufficiency should simultaneously be looked for.

[Higher prevalence of depressive and anxiety symptoms in early arthritis patients in comparison to the normal population]. / Höhere Prävalenz von depressiven und ängstlichen Symptomen bei Früharthritispatienten im Vergleich zur Normalbevölkerung.

BACKGROUND: Many studies and registry data confirm that depression, often associated with anxiety disorders is very often found in patients with rheumatoid arthritis (RA). To what extent these psychiatric disorders are already relevant at a very early stage of the disease, has currently not been adequately investigated. METHODS: In this study 176 patients with early joint symptoms (<1 year) were surveyed in an early arthritis consultation (EAC). The hospital anxiety and depression scale (HADS) was completed by the patients to examine the prevalence of depressive and anxiety symptoms. The results were compared to normative data of the general German population and between the diagnosis groups. RESULTS: With 47.7% the prevalence of global distress for EA patients was almost twice as high compared to the corresponding group from the general population. This was also confirmed for depressive and anxiety symptoms. The EA patients without confirmed evidence of musculoskeletal inflammatory rheumatic disease (RD) showed nearly the same point prevalence as patients with confirmed RD. In multiple logistic regression the health assessment questionnaire (HAQ) was positively associated with global distress (odds ratio, OR 3.63) while the visual analogue scale (VAS) for global disease activity was positively associated with symptoms of depression (OR 1.03). Female EA patients (OR 5.45) appear to have a higher probability for experiencing corresponding symptoms, whereas patients over 60 years old appear to have less anxiety than younger patients (OR 0.11). CONCLUSION: The high prevalence of symptoms of depression and anxiety in EA patients compared to the general population is a challenge for rheumatologists, orthopedists and general practitioners, particularly with respect to the differentiation of possible psychosomatic components in noninflammatory joint complaints. The results suggest that screening for psychiatric problems in patients with rheumatism should be evaluated as soon as possible as these can have a great impact on the perception of pain and physical functional status from the very beginning.

The absent role of prophylactic antibiotics in low-risk patients undergoing laparoscopic cholecystectomy.

A retrospective chart review was done to determine the infection rate and the use of prophylactic antibiotics in consecutive laparoscopic cholecystectomies done in a single community. Incisional infections were discovered in 11 of 566 cases, 10 of whom had received prophylactic antibiotics. The infected patients were significantly older, had longer procedures, and had more comorbidity than the uninfected patients. They were also more likely to have a palpable mass preoperatively and past biliary surgery. A second, prospective study was done to evaluate the efficacy of the use of antibiotic prophylaxis in low-risk patients. Fifty-three patients were randomized into two double-blinded groups. No incisional infections occurred in either group within 30 days postoperatively. This suggests prophylactic antibiotics are not needed to prevent infections for low-risk patients undergoing laparoscopic cholecystectomy.

Dynamic alterations of serotonergic metabolism and receptors during social isolation of low- and high-active mice.

Alterations induced by social isolation (1 day to 18 weeks) in low- and high-active mice (LAM and HAM) were studied in respect to serotonin metabolism, [3H]-8-OH-DPAT binding of presynaptic (midbrain), postsynaptic (hippocampus) 5-HT1A receptors and [3H]-ketanserin binding of cortical 5-HT2A receptors. Individual housing of mice was associated with reduction of serotonin metabolism, depending on isolation time and brain structure. Whereas a transient decrease in the striatum and cortex was detected between 1 week and 6 weeks, reduction of cerebellar and hippocampal serotonin metabolism was found later (12-18 weeks). Serotonergic systems of HAM were found to be more reactive to environmental disturbances, and their serotonin metabolism was more affected by social isolation. Isolation-induced upregulation of cortical 5-HT2A receptors was measured only in HAM. Densities of postsynaptic 5-HT1A receptors in the hippocampus did differ either in grouped or isolated mice. However, there were significant differences in hippocampal 5-HT1A receptor affinity, especially between 1 day and 3 weeks. Transient downregulation of presynaptic 5-HT1A receptors in the midbrain was found in isolated mice between 3 and 6 weeks. These results are discussed in terms of interactions between serotonergic alterations and isolation-induced aggression.

A mechanism of action for morphine-induced immunosuppression: corticosterone mediates morphine-induced suppression of natural killer cell activity.

Morphine is a drug of abuse with an ability to down-regulate immune responsiveness that could have potentially serious consequences in both heroin addicts and in the clinical environment. The exact mechanism of action by which morphine induces immunosuppression has yet to be clearly determined. A direct mechanism of action is suggested to operate through lymphocyte opiate receptors, but the nature of such receptors is still in question. The alternative, an indirect mechanism of action is proposed to be mediated by two possible pathways, hypothalamic-pituitary-adrenal axis activation with increased production of adrenal corticosteroids, or activation of the sympathetic nervous system and concomitant catecholamine release. Natural killer (NK) cell activity was used to determine potential indirect mechanisms of action for morphine. NK activity in the B6C3F1 mouse was suppressed between 12 and 48 hr after implantation of 75 mg timed-release morphine pellets. Morphine suppressed NK activity in a dose-responsive manner. The opiate antagonists naloxone and naltrexone completely blocked morphine-induced suppression of NK activity, whereas naloxone methiodide, a congener that crosses the blood-brain barrier much more slowly than naloxone, produced very little blockade. Implantation of the 75-mg morphine pellets produced a significant elevation in serum corticosterone levels. In vitro exposure to corticosterone is known to suppress NK activity directly, whereas in vitro morphine was unable to alter directly NK activity. The glucocorticoid receptor antagonist Roussel-Uclaf 38486 blocked morphine-induced suppression of NK activity in a dose-responsive fashion. Naltrexone (10-mg pellet) antagonized the morphine-induced elevation in serum corticosterone.(ABSTRACT TRUNCATED AT 250 WORDS)

Pheochromocytoma and pregnancy: the epitome of high risk.

BACKGROUND: Past review has shown that one half of the fetuses and nearly that many mothers died of pheochromocytoma if the tumor was not detected in the mother before delivery. The rarity of the occurrence adds to the potential danger because experience with diagnosis and management is unusual. However, the diagnosis is straightforward when considered because pregnancy does not alter diagnostic levels of catecholamines. Management must be individualized and can be done safely. METHODS: The cases of five patients with pheochromocytomas during pregnancy are presented here. Diagnosis was made by urinary catecholamine measurement. Localization methods included caval catheterization and ultrasonography. Blood pressure control was done with alpha- and beta-adrenergic blockers. Treatment strategy was planned by a team of internists, obstetricians, surgeons, and anesthesiologists. RESULTS: All five mothers and three fetuses survived. The two fetal deaths were planned terminations. Two mothers and one fetus had multiple endocrine neoplasia type 2B syndrome. One mother had two recurrences, one of which was involved with the pregnancy. CONCLUSIONS: Pregnancy does not alter urinary catecholamine levels to confuse the diagnosis of pheochromocytoma. Localization by ultrasonography and magnetic resonance imaging is safe to the fetus. alpha- And beta-adrenergic blockers are well tolerated. Every effort should be made to save a normal fetus when the tumor is first discovered during the third trimester. Timing of excision is a decision best done by team planning.

Morphine-induced alterations in thymocyte subpopulations of B6C3F1 mice.

Morphine has been reported to possess immunosuppressive actions in both in vitro as well as in vivo assays of immune function. Our work in female B6C3F1 mice, surgically implanted with a 75-mg time release morphine pellet, has confirmed previous reports of a rapid loss in the cellularity of the spleen and thymus. To evaluate the effect of morphine on the subpopulations of cells in the thymus, two color fluorescence flow cytometry studies were performed. Fluorescently conjugated monoclonal antibodies specific for the murine cell surface CD4 and CD8 markers were used to identify the four major subpopulations of thymocytes. These studies indicated that morphine pellet-implanted mice suffered a loss in each of the four thymocyte subpopulations in comparison to placebo-implanted mice. However, the loss (> 90%) in the important CD4+/CD8+ subpopulation of immature thymocytes greatly exceeded that which was observed for any other subpopulation. Kinetic studies of morphine's effect on the thymocyte subpopulations revealed that the maximal depletion of the CD4+/CD8+ cells occurs approximately 4 days after pellet implantation. Thymocyte cell populations recovered by 14 days, with an increase above placebo for the double positive cells. Naltrexone administration blocked thymic alterations, suggesting that these immunologic consequences of morphine may be mediated through an opiate receptor. Measurements in thymocytes from morphine pellet-implanted mice showed an increased level of DNA fragmentation, whereas in vitro exposure to morphine (1-100 microM) produced no such increases. This suggests morphine may be working indirectly to induce apoptosis of immature thymocytes.

Villous tumors of the duodenum and ampulla of Vater.

Polypoid epithelial tumors of the duodenum and ampulla of Vater are rarely diagnosed preoperatively without wide application of fiberoptic endoscopy. The symptoms are nonspecific. Only a high index of suspicion will lead to early diagnosis. Life-threatening complications and increased incidence of malignant transformations are associated with delayed diagnosis. This paper reviews 11 patients (nine previously unreported) with villous tumor of the ampulla of Vater and two with this neoplasm in the duodenum. It also reviews the important principles of management illustrated by the behavior of the tumors of these 11 patients compared to those of previous reports. For favorable results, all lesions must be excised in toto and evidence of invasive malignancy must lead to aggressive treatment whenever feasible.

Management of cecal diverticulitis.

A case of solitary cecal diverticulum is presented. Acute inflammation of a solitary diverticulum in the cecum appears rare. Preoperative diagnosis is difficult, and the disease is frequently confused with appendicitis or carcinoma. Right colectomy is a safe effective therapy in patients with this condition.

Changes in concentration of amino acids and other metabolites during hypothermic perfusion of the canine kidney.

Changes in the concentration of amino acids and other metabolites were determined in the perfusate during 24 hr of ex vivo hypothermic perfusion of dog kidneys. There was an increase in concentration of most of the amino acids. Two patterns were identified. One showed an increase in concentrations up to 12 hr, and then a leveling off as exemplified by alanine, serine, and glutamate. The other pattern was one of persistent elevation as exemplified by phenylalanine, threonine, and methionine. Glucose, lactate, pyruvate, sodium, potassium, pH, and pO2 were also measured in the perfusate. The results suggest that a degradation of kidney protein may occur during the first 24 hr of perfusion. The levels of other metabolites measured support the fact that glycolysis is responsible for a considerable portion of the total energy production in the kidney under hypothermia.

Gastroduodenal and pancreaticoduodenal artery aneurysms: a complication of pancreatitis causing spontaneous gastrointestinal hemorrhage.

Aneurysmal degeneration of gastroduodenal and pancreaticoduodenal arteries due to acute and chronic forms of pancreatitis is uncommon. Gastrointestinal hemorrhage secondary to these vascular lesions has been recognized in only 23 patients. Eight of these patients, including five with gastroduodenal and three with pancreaticoduodenal artery aneurysms, have been encountered at the University of Michigan Medical Center. Selective mesenteric arteriography provided the greatest diagnostic specificity. Computerized axial tomography was of discriminate diagnostic value in two patients. Seven of eight patients underwent surgical therapy: transcystic arterial ligation and external pancreatic pseudocyst drainage (four), arterial ligation with abscess drainage (two), and pancreaticoduodenectomy (one). Three patients died after operation from intraabdominal sepsis as well as delayed arterial hemorrhage. Earlier operative intervention, dictated by the patient's clinical status and relevant anatomic findings, may improve survival rates in this complex disease state.

Pheochromocytoma. A persistently problematic and still potentially lethal disease.

Fifty patients with pheochromocytomas have had their conditions diagnosed and have been treated by these authors during a 13-year peneod. Three patients died in the postoperative period, for an overall mortality of 6%. Thirty-two patients underwent primary excision without fatality. Eighteen patients had more complicated illnesses associated with recurrences, notable other disease, acute catecholamine crisis, and/or pregnancy. All three postoperative deaths occurred in this group. Diagnosis was made by urinary catecholamine analysis of epinephrine, norepinephrine, metanephrine, and normetanephrine. Localization was done by plain films, ultrasonograms, computerized tomograms, radioactive isotope scans, intravenous pyelograms, caval samples, venograms, and arteriograms. Management of these complicated cases requires prompt and accurate diagnosis, availability of sophisticated methods of tumor localization, and thoughtful awareness of the potential outcome by an experienced team of surgeons and anesthesiologists.

Adrenal medullary disease in multiple endocrine neoplasia type II.

The diagnosis of multiple endocrine neoplasia type II (MEN-II) was made in 18 patients from 1966 through 1978 at the University of Michigan Medical Center. Eight patients had adrenal medullary disease. Seven had bilateral adrenal pheocyromocytomas (two with concomitant medullary hyperplasia) and one had a unilateral pheochromocytoma with contralateral medullary hyperplasia. No malignant or extraadrenal pheochromocytomas were found. Pheochromocytomas in patients with MEN-II are multiple and involve both adrenal glands. Adrenal venography is advocated as the primary diagnostic tool for localization of adrenal medullary disease in MEN-II patients.