Glucocorticoid withdrawal schemes in chronic medical disorders. A systematic review.

This systematic review highlights the uncertainty about the safety and efficacy of glucocorticoid withdrawal in many chronic diseases, elucidating the need for further research in this area. The problem of glucocorticoid withdrawal seems to be good example for wide variation in physicians' approaches to weaning patients off glucocorticoids. This practice variation appears justified, given the well known extraordinary array of individual reactions to systemic glucocorticoid therapy [44], the obligation to individualize treatment, and scientific uncertainty. Moreover, only sparse information concerning health-related quality of life, well-being and symptoms, and socioeconomic sequelae after glucocorticoid withdrawal is available from published randomized trials. In conclusion, clinicians and patients need many more--and in a number of conditions, initial--high quality studies to assess the safety and efficacy of systemic glucocorticoid withdrawal schedules in chronic diseases.     

Anal Ultra Slow Waves (A Smooth Muscle Phenomenon Associated with Dyschezia)

Anal ultra slow waves (USWs) have been describedin a variety of anorectal disorders, all of which may beassociated with constipation. We investigated whetherthey represent a marker for dyschezia and whether their occurrence can be modified.Manometric and endosonographic studies were performed in25 patients with dyschezia, in 25 age- and sex-matchedcontrols, and in an equal number of patients with hemorrhoids. Patients exhibiting ultra slowwaves were repeatedly studied with and without localadministration of isosorbide dinitrate. In addition, wedetermined whether stimulatory maneuvers modify the occurrence of USWs. Anal USWs were persistentlyfound in 56% of patients with dyschezia, in 8% ofpatients with hemorrhoids, and in none of the healthycontrols. They were stimulated by anal squeeze and completely abolished by local administration ofisosorbide dinitrate. Ultra slow waves always occurredin conjunction with an increase in anal resting pressureand were tightly associated with a fluctuation in slow wave amplitude. Anal sphinctermorphology was similar in patients with dyschezia and incontrols. We conclude that anal USWs occur mostfrequently in patients with dyschezia and indicatesmooth muscle dysfunction. Treatment directed atabolishing this motor phenomenon may represent a novelapproach to the management of patients withdyschezia.     

Mechanisms and time course for the disappearance of thallium-201 defects at rest in dogs: Relation of time to peak activity to myocardial blood flow

The kinetics of thallium (Tl)-201 in ischemic myocardium was studied with a balloon constrictor to create a fixed reduction in distal left anterior descending coronary arterial pressure in 19 dogs. After 30 to 60 minutes of partial occlusion, Tl-201 was administered intravenously. Tracer activity was monitored continuously for 4 hours in both the normal and reduced flow zones using implanted miniature cadmium telluride radiation detectors. Microsphere-determined regional myocardial blood flow, heart rate, mean arterial pressure, mean left atrial pressure, mean distal left anterior descending coronary arterial pressure and sonomicrometer-determined myocardial wall thickness did not change significantly during each study. Thallium-201 time-activity curves for the normal zones (flow 1.00 ml/min per g or more) demonstrated an initial rapid increase to 80 to 90 percent of peak, an early peak (mean 20 minutes) and then a monoexponential decrease in activity (decay constant λ = 0.0013 min^?1). Thallium-201 time-activity curves for mildly and moderately ischemic zones (flow = 0.40 to 0.99 ml/min per g) demonstrated a progressive delay in the time to peak activity with progressive reductions in flow (r = 0.84). Thallium-201 time-activity curves for severely ischemic zones (flow less than 0.40 ml/min per g) demonstrated a rapid initial increase, and then no further increase in activity, probably because of cell death with a resultant decreased ability to accumulate Tl-201.When the Tl-201 activity ratio (reduced/normal flow zone) was calculated as a function of time for each dog, there was a progressive increase in this ratio over time for all dogs, although the rate of increase was slower for dogs with increasing degrees of flow reduction. This increasing ratio over time would correspond to disappearance of an initial Tl-201 resting scintiscan defect over time. The mechanism for the increasing ratio in dogs with mild or moderate flow reduction was both clearance of Tl-201 from normal zones and accumulation of Tl-201 by ischemic zones. However, the mechanism for the increasing ratio in dogs with severe flow reductions was a faster rate of Tl-201 loss from the normal compared with the reduced flow zone.     

Role of estradiol as a biological amplifier of gonadotropin action in the ovary: in vitro studies using swine granulosa cells and homologous lipoproteins

Swine granulosa cells cultured under serum-free conditions in vitro exhibit significant responsivity to the stimulatory actions of estradiol (E2) and FSH or LH. Under these conditions, granulosa cells harvested from either immature or mature Graafian follicles synthesized significantly increased quantities of progesterone in response to homologous low density lipoprotein (LDL) and, to a lesser degree, homologous high density lipoprotein (HDL) particles. The effects of LDL and HDL were dose dependent and saturable. The stimulatory influence of E2, FSH, or LH alone was significantly enhanced in the presence of pig LDL or HDL. Moreover, the synergism between E2 and FSH or between E2 and LH was significantly augmented by porcine LDL and, to a lesser degree, porcine HDL. To assess the physiological relevance of these observations, the lipoprotein contents of swine blood and follicular fluid were determined by heparin-manganese precipitation and after differential ultracentrifugation. The majority (greater than 70%) of cholesterol in pig blood resided in the LDL fraction, but follicular fluid was essentially devoid of LDL. On the other hand, follicular fluid contained large quantities of a presumptive HDL species with a density between 1.063-1.210. The HDL particle in follicular fluid was further characterized by agarose gel and sodium dodecyl sulfate-polyacrylamide gel electrophoreses, which demonstrated an alpha-migrating species whose major apoprotein exhibited an apparent mol wt of 28,000 and comigrated with human apoprotein A-1. Analytical ultracentrifugation of the pig follicular fluid HDL revealed a sedimentation coefficient (S20,w) of 4.93, similar to that of serum HDL (S20,w = 5.0). The physiological relevance of the HDL particle purified from follicular fluid was further demonstrated by its ability to significantly increase progesterone production by granulosa cells cultured under serum-free conditions in vitro. In summary, we have demonstrated striking responsivity of cultured pig granulosa cells to exogenously supplied LDL and, to a lesser degree, HDL, with further stimulation when cells are treated with estrogen and/or LH and FSH. Although LDL is the predominant lipoprotein in swine blood, it is essentially undetectable in the antral fluid of the intact Graafian follicle. Thus, the unambiguous in vitro responsiveness of granulosa cells to LDL that we observe suggests that the marked increase in availability of blood-borne LDL to granulosa-luteal cells that presumptively occurs at ovulation would contribute significantly to augmented rates of progesterone biosynthesis by luteal tissues in the pig.(ABSTRACT TRUNCATED AT 400 WORDS)     

An ambulatory ventricular function monitor: validation and preliminary clinical results

A device for the continuous measurement of left ventricular (LV) function was tested in a series of 34 subjects. The instrument consisted of 2 arrays of radiation sensitive cadmium telluride detectors held in place over the region of the left ventricle and lung by a vest-like garment (hence the name VEST). The VEST electronic instrumentation included analog-to-digital converters, a battery pack, microprocessor and gating device, which were worn in a back pack. Data generated by the VEST, including the digitized average electrocardiogram, RR interval, counts/13 ms in each radiation detector, and time since commencement of data recording, were recorded on a cassette tape recorder every 2 minutes for subsequent analysis. At the conclusion of conventional multigated blood pool imaging, the VEST was positioned and worn by the subjects while supine, standing in place and walking. The correlation of ejection fraction calculated independently from the VEST and scintillation camera data was greater than 0.95. The inter-record reproducibility of the ejection fraction measured by the VEST in sedentary subjects was less than 3%.     

False hyperphosphoremia in multiple myeloma. Interference of monoclonal immunoglobulin G with the determination of blood phosphorus level]

A case of pseudohyperphosphataemia detected in a male patient with multiple IgG myeloma is reported. Phosphataemia, measured by a technique without previous deproteinization, reached 5.66 mM before any treatment and varied with treatment-induced changes in monoclonal immunoglobulin levels. Conversely, normal phosphataemia levels were found in blood samples taken before and after treatment when serum was deproteinized. This pseudohyperphosphataemia resulted from an increase in optic density due to interference between monoclonal immunoglobulin and the molybdic reagent used to determine phosphataemia. A retrospective investigation yielded three similar cases: two in patients with myeloma and one in a patient with non-myelomatous monoclonal dysglobulinaemia. A brief prospective study showed that this phenomenon was relatively frequent, as it was found in 2 out of 9 patients with monoclonal immunoglobulin (IgG in all 9 cases). These data indicate that the finding of marked hyperphosphataemia in subjects with monoclonal dysglobulinaemia should always prompt a control assay performed on deproteinized blood.     

Antigenic analysis of hematopoiesis. IV. The My-11 hematopoietic cell surface antigen is expressed by myelomonocytic and lymphoid, but not erythroid, progenitor cells

The anti-My-11 murine monoclonal antibody reported on in this work identifies a KG-1a cell surface glycoprotein with apparent molecular mass of 210,000 daltons. Peripheral blood B-lymphocytes, and a novel subset of T-lymphocytes (not coinciding with helper or cytotoxic subsets) express My-11 antigen; granulocytes, red cells, and platelets are antigen negative. In normal bone marrow, lymphoid progenitors (TdT positive) and most granulocyte-monocyte progenitors express My-11, but erythroid and multilineage progenitors are My-11 negative. Approximately half of acute leukemia blast cell specimens are My-11 positive. The My-11 antigen distinguishes between lymphohematopoietic cells on the basis of lineage, and assists in the purification of hematopoietic progenitor cells and the subclassification of leukemias and normal lymphocytes.