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Biomedical subjects

S Klein

Publications and source records attributed to S Klein.

At least 253 records · Page 14Linked to original sources

Hodgkin and Reed-Sternberg cells express interleukin 6 and interleukin 6 receptors.

Interleukin 6 (IL-6) is a pleiotropic lymphokine which can stimulate a variety of cells including B and T lymphocytes. It has been suggested that IL-6 plays a crucial role in several diseases such as human plasmacytoma, cardiac myxoma or Castleman's Disease by autocrine or paracrine stimulation. To analyse whether IL-6 is involved in the biology of Hodgkin's Disease (HD), we investigated the expression of IL-6 and IL-6 receptor (IL-6R) in cell lines and primary specimens from patients with HD. IL-6 specific transcripts were detected in three out of six HD derived cell lines by Northern blot analysis and in the culture supernatants of four HD derived cell lines by ELISA. Its biological activity was confirmed by proliferation of an IL-6 dependent cell line. By in-situ hybridization experiments IL-6 specific transcripts were detected in Hodgkin (H) and Reed-Sternberg (RS) cells in primary tissues in two out of three patients. mRNAs specific for the IL-6 receptor were detected in five HD derived cell lines. Staining of HD derived cell lines revealed expression of the receptor molecules in five cell lines; Western blot experiments confirmed the 80kDa receptor protein in the cells. Immunohistology in primary specimens revealed expression of the receptor molecules on H and RS cells in 8 out of 16 cases with HD. Expression was mostly detected in the mixed cellularity subtype of HD. Elevated levels of IL-6 were detected in the sera of more than 50% of patients with HD. Taken together our data suggest that IL-6 might be involved in the biology of HD.

Adolescent↗

[Cyclosporin A in therapy of chronic uveitis].

48 patients with chronic severe uveitis of pressumed noninfectious origin resistent to corticosteroids have been treated with Cyclosporin A. All patients had an initial loading dose of 5 mg/kg/day followed by a dose reduction according to ocular inflammatory activity and tolerability and according the guidelines by BenEzra, Nussenblatt and Timonen. Most of the patients received additional corticosteroids in a low dose. 35 out of these 48 patients (13 suffering from intermediate uveitis, 11 from retinal vasculitis, 5 panuveitis, 4 "pressumed histoplasmosis" and 2 sympathetic ophthalmia) were treated for 1 year and observed after withdrawing of Sandimmun for at least 6 months. The majority of these patients have manifested a positive therapeutic response to Cyclosporine, in particular patients suffering from vasculitis, panuveitis and sympathetic ophthalmia. All 35 patients were treated before for a long time with steroids without success, 19 out of these 35 in addition with cytotoxic agents. The immunosuppressive effect of Cyclosporine was not permanent, frequently the inflammation relapsed on reduction of dosage or withdrawing of the drug. Guidelines for combined regimen (Cyclosporine and corticosteroids and vitrectomy) were given. Although a large variety of side effects were reported the compliance was good.

Administration, Oral↗

[Measuring retinal vascular diameter using the scanning laser ophthalmoscope and computer. Initial results].

The diameter of the large retinal vessels is an important factor in retinal microcirculation. A system configuration was developed that uses SLO images to measure the diameter of retinal branch vessels off-line. The place for measurement is defined in the image by the investigator, and the diameter is measured automatically. The mean standard deviation of the diameter of arterial vessels was 2.37% and for veins 3.43% by repeat measurement in sequential pictures by optimal scanner settings. The reproduction of vessel diameters was unsatisfactorily for repeat examinations. The course of these results may be changes in the fundus image connected with changes in the position of the scanner-bulbus (e.g., new examination, poor fixation). The scanner-bulbus position is not yet precisely defined and not reproducible enough.

Adult↗

Effectors of hypercarbia during experimental pneumoperitoneum.

Hypercarbia occurs during laparoscopy with carbon dioxide (CO2) insufflation. This may be due to increased ventilatory dead space after expansion of the peritoneal cavity with impairment of diaphragmatic excursion, or to increased absorption of CO2 from the peritoneum. To separate these effects, the authors examined the consequences of different insufflating gases and of diminished tissue perfusion on hypercarbia and dead space during pneumoperitoneum. Helium was chosen as an alternate insufflating gas because it is both inert and minimally absorbed. Eight swine (18 to 20 kg) were anesthetized, paralyzed, and mechanically ventilated at constant minute volume. Pneumoperitoneum with helium was maintained at 15 mm Hg for 45 minutes. After desufflation and stabilization for 1 hour, pneumoperitoneum was repeated with CO2. The sequence was again repeated after hemorrhagic shock to constant mean arterial pressure of 50 mm Hg. Data was analyzed by analysis of variance; significance levels are P < 0.01 unless otherwise listed. Arterial PCO2 increased significantly with CO2 insufflation within 15 minutes in normotensive animals and within 30 minutes during hypotension. Arterial pH decrease with CO2 pneumoperitoneum was significant in both groups at 30 minutes. Mixed venous PCO2 also increased with CO2 pneumoperitoneum within 30 minutes. Hypotension did not alter these changes. No significant changes were seen with helium pneumoperitoneum. Neither helium nor CO2 pneumoperitoneum significantly altered dead space. The authors make the following conclusions: 1) Absorption of CO2 from the abdomen during CO2 pneumoperitoneum produces respiratory acidosis, which is not seen with helium insufflation; 2) Pneumoperitoneum does not significantly increase dead space with either gas; 3) Transperitoneal absorption of CO2 is only partly related to perfusion because significant hypercarbia occurs during hemorrhagic shock.

Absorption↗

Increased ambulatory utilization in IPA plans among children receiving hyposensitization therapy.

There is concern that children with chronic conditions are less likely to be enrolled in managed care systems and that they may not receive optimal care. We studied the relationship between enrollment in an Independent Practice Association (IPA) plan and utilization of ambulatory services among children in a suburban pediatric practice with one mild chronic condition--those receiving hyposensitization therapy for allergic diseases. Ambulatory utilization by IPA patients (N = 102) was determined by medical chart review for one year before and one year after each patient switched from Blue Cross to IPA coverage. Blue Cross hyposensitization patients (N = 57) matched for age served as controls. Patients receiving hyposensitization were more likely to have enrolled in an IPA than those not receiving hyposensitization (70% vs 45%, p < .001). Before enrollment pre-IPA patients had 41% fewer well-child care (WCC) visits than Blue Cross patients (p < .01); both underutilized WCC visits according to established guidelines. Controlling for age and baseline utilization, we found a significant increase in WCC and acute care visits after IPA enrollment (p < .05), but no change in hyposensitization visits or referrals. In this setting, there was no evidence for reduced access to ambulatory services but rather evidence for improved utilization of primary care.

Adolescent↗

[Does timolol modify retinal hemodynamics in patients with normal pressure glaucoma?].

In 31 patients with normal-pressure glaucoma, retinal blood flow, diameter of the retinal vessels and velocity were measured with 2-point fluorometry and automatic measurement of the diameters before and after administration of 0.5% timolol over 2 weeks. After timolol therapy the tension was significantly decreased (before therapy: 18.26 +/- 2.50; after therapy: 15.61 +/- 2.56 mm Hg, P < or = 0.01). The arterial and venous diameters and blood flow were nearly unchanged, but a slight increase in the arterial and venous velocity was noted. We conclude that timolol does not significantly influence the retinal hemodynamics in patients with normal-pressure glaucoma.

Adult↗

Isolated cerebellar metastasis from ovarian carcinoma. Case report and review of the literature.

Isolated cerebellar metastasis from ovarian cancer is a very rare entity with only one other reported case in the literature. We report an additional case. This patient had a single 3 x 3 cm cerebellar lesion that was removed revealing metastatic papillary carcinoma consistent with a known ovarian primary. We also present a review of the literature concerning central nervous system (CNS) metastases from ovarian cancer and the various methods of treatment currently being used. Current literature suggests that patients with isolated resectable lesions should be managed surgically.

Cerebellar Neoplasms↗

[Diagnosis of glaucoma using fundus spectrometry in areas outside the papilla].

As a result of the statistical evaluation of spectra on the basis of discriminant analysis, it can be stated that spectrometric measurements on fundus areas are suited for glaucoma diagnosis also outside the papilla. For early recognition of glaucoma, measurements of the papillomacular bundle are more sensitive than measurements in the parapapillary region. Late stages of glaucoma and normal findings are most reliably separated by measurements in the parapapillary region. With increasing severity of the glaucoma, the spectrum of the macular pigment can be demonstrated in the papillomacular bundle. A spectrometrically recognizable lack of erythrocytes documents an impaired retinal microcirculation.

Adolescent↗

Prospective analysis of cardiopulmonary responses to laparoscopic cholecystectomy.

This prospective study evaluates the extent and temporal course of the cardiorespiratory effects of CO2 during laparoscopic cholecystectomy in otherwise healthy patients. Sixteen patients (M:F = 3:13, average age = 40.2 +/- 14.1 years) were monitored with capnography, transesophageal cardiac output, continuous blood pressure, heart rate, and pulse oximetry. Arterial blood gases were obtained immediately before insufflation of the abdomen with CO2 and before desufflation. Average operative time was 137 +/- 13 minutes. Patients were paralyzed and mechanically ventilated. Minute ventilation was increased if EtCO2 exceeded 45 mmHg or rose by more than 12 mmHg from baseline. End tidal (EtCO2) and arterial CO2 (PaCO2) increased from 31.4 +/- 0.7 mmHg to 42.1 +/- 1.6 mmHg and 33.3 +/- 0.7 mmHg to 43.7 +/- 1.2 mmHg, respectively, during the course of the procedure. Arterial pH decreased from 7.43 +/- 0.01 to 7.34 +/- 0.01, while bicarbonate concentration remained unchanged. Thirteen of the 16 patients required increased minute ventilation due to hypercarbia detected by capnography. Blood pressure increased from 78 +/- 2 mmHg (mean) at the start to 98 +/- 2 mmHg. This increase was coincidental with the maximal PaCO2. Good agreement was observed between paired EtCO2 and PaCO2 measurements. Laparoscopic cholecystectomy with carbon dioxide insufflation causes significant respiratory acidosis and associated cardiovascular changes in otherwise healthy patients. Careful monitoring and cautious application of this technique in patients with pre-existing cardiopulmonary disorders will be required to prevent acute decompensation.

Acidosis, Respiratory↗

Lipolytic response to metabolic stress in critically ill patients.

OBJECTIVE: To measure whole-body lipolysis and fatty acid re-esterification in critically ill patients. DESIGN: The rates of appearance of glycerol and palmitic acid in blood plasma were measured by infusing stable isotope tracers [2H5]glycerol and [1-13C]palmitic acid, respectively. Energy expenditure was measured by indirect calorimetry. SETTING: Medical ICU of The University of Texas Medical Branch Hospital, a university-based referral center. PATIENTS: Five uninjured critically ill patients. Four patients were hospitalized because of respiratory insufficiency and one because of myocardial infarction. Three patients died during their hospitalization. INTERVENTIONS: Metabolic studies were performed in each patient after an overnight (12-hr) fast. MEASUREMENTS AND MAIN RESULTS: Mean +/- SE glycerol and fatty acid rates of appearance were 4.5 +/- 1.0 and 11.5 +/- 0.8 mumol/kg.min, respectively. The ratio of fatty acid to glycerol rate of appearance was 2.9 +/- 0.5. Resting energy expenditure was 132 +/- 6% of predicted. CONCLUSIONS: An accelerated rate of lipolysis is part of the metabolic response to severe stress, regardless of its etiology. Because the rate of fatty acid release far exceeded energy requirements, fatty acids that were not oxidized as fuel were re-esterified to triglyceride, presumably in the liver.

Acute Disease↗

Effect of short-term fasting on the lipolytic response to theophylline.

We investigated the hypothesis that the increase in lipolysis that occurs in short-term (86-h) fasting is due to a decreased inhibitory influence of adenosine. In normal volunteers who fasted for 14 and 86 h, the response to adenosine receptor blockade was assessed by the infusion of theophylline at a rate sufficient to produce plasma concentrations (30 microM) that blocked adenosine receptors but that were well below the threshold for inhibition of phosphodiesterase. Lipolysis was assessed by determining the rate of appearance of glycerol using D-5-glycerol infusion. Fatty acid flux was also determined by means of [1-13C]palmitate infusion, and total fatty acid oxidation was determined by indirect calorimetry. There was a mild stimulatory effect of theophylline on lipolysis at 14 h. After the subjects fasted for 86 h, theophylline infusion caused a much greater increase in both lipolysis and fatty acid oxidation. These results suggest that the inhibitory effect of adenosine on lipolysis is increased during short-term fasting.

Adult↗

Comparative effects of two acycleonucleoside derivatives on ultrastructure and replication of guinea pig cytomegalovirus in cultured cells.

Two antiviral agents, compound 164, also known as 2'-nor-cGMP, 9-[(2-hydroxy-1-3-2-dioxophosphorinan-5-yl)-oxymethyl]-guani ne P-oxide, and compound 102, 4-amino-5-bromo-7-(2-hydroxyethoxymethyl)-pyrrolo-(2-3-d)-pyrimidine, together with their parental drugs, 2-deoxyguanosine (DHPG) and acyclovir (ACV), were evaluated for their antiviral activities against guinea pig cytomegalovirus (GPCMV) infection in cultured guinea pig embryo (GPE) cells. The two compounds were demonstrated to be more potent against GPCMV replication when compared to their parental drugs DHPG and ACV. Compound 164 was the most potent of the four compounds tested, with ED50 values being approximately 20-, 80-, and 180-fold more potent than those of DHPG, compound 102, and ACV, respectively. Compounds 164 and 102 were slightly more cytotoxic to uninfected GPE cells, but their selectivity (therapeutic) indexes were higher than those of their parental drugs. Of the four antiviral agents tested, compound 164 had the highest selectivity index which was 8-, 30-, and 50-fold higher than that of DHPG, compound 102, and ACV, respectively. Ultrastructural studies suggest that compounds 164 and 102 have different mechanisms of inhibiting GPCMV replication in cultured GPE cells.

Acyclovir↗

[Automated measurement of retinal vascular diameter].

We describe a new unit of the Jena retinal camera for automatic measurement of retinal vessel diameter. The brightness profile perpendicular to the vessel is registered by CCD line sensor and the signal is transmitted to the computer. An adaptive computer program recognizes the edges of vessels and estimates the vessel diameters automatically. Applying several measurements per vessel, the intraindividual standard deviation may be smaller than 3%. By using the same objective measuring edge criterion, the measuring results are comparable between different observers and methods. Error sources are discussed. Measured vessel reactions to oxygen breathing and reduced perfusion pressure are presented to demonstrate the efficiency of this new method.

Adult↗

[Multisubstance analysis. Detection of changes in the optical density in individual layers of the optic fundus].

A promising method for noninvasive objective diagnosis and monitoring of the course of a therapy is spectrometric investigation of the human ocular fundus. Application of this method in clinical practice depends on the development of suitable procedures for deconvolution of the measured spectra. The availability of microcomputers permits the performance of complicated calculations directly at the measuring device. Based on the two-photon flux theory, the influence of absorption and scattering in anatomically determined layers of the fundus will be considered. For this reason, an iterative principle for radiation transport into the fundus is introduced, allowing derivation of a physical model for calculation of the spectral course of the reflected light. In the multisubstance analysis a measured spectrum is approximated by the model function. During this analysis the optical densities of photosensitive and nonphotosensitive pigments and the reflection at intermediate layers can be calculated. As an example of multisubstance analysis, the deconvolution of foveal reflection spectra of normals and type I diabetics is demonstrated. This method makes it possible to show that early diabetic alternations occur in the choroid.

Adolescent↗