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Biomedical subjects

S Klein

Publications and source records attributed to S Klein.

At least 181 records · Page 10Linked to original sources
PubMed1996

Radioimmunoassay of leptin in human plasma.

Recent studies suggest that leptin, the ob gene product absent in ob/ob mice, is a negative regulator of adiposity. We developed an RIA to measure human leptin in plasma or serum. The minimum detectable concentration by the assay is 0.5 microg/L leptin and the limit of linearity is 100 microg/L. Recovery of leptin added to serum was 99-104% over by the linear range of the assay. The RIA agreed reasonably well with rough quantification by Western blot (RIA = 0.90 blot + 3.7 microg/L, Sy/x = 10.9 microg/L). CVs within- and between-run ranged from 3.4% to 8.3% and from 3.6% to 6.2%, respectively. Variation in plasma leptin concentrations in specimens collected on consecutive mornings was large (CVs of 10.9% and 22.5%). After an overnight fast, leptin concentrations were similar to those 1-2 h after 1-2 meals. Plasma leptin concentrations in specimens from 83 lean and obese adults correlated directly with body mass index (BMI; kg/m2): r = 0.72, P <0.001. Correlations were significantly improved by separating results by gender (men r = 0.84, women r = 0.87; p <0.001). The increase in leptin concentrations with increasing BMI was greater in women than in men (slope 2.53 vs 0.97 microg/L per unit BMI, respectively). Leptin concentrations determined in lean subjects (BMI between 18 and 25) were higher in women (7.36 +/- 3.73 microg/L) than in men (3.84 +/- 1.79 microg/L) (P <0.001). Plasma leptin varied little with age and no significant difference was observed between whites and blacks. We conclude that: (a) plasma leptin concentrations are accurately and precisely measured by this new RIA; (b) leptin concentrations vary little due to short-term fasting, age, or race; but (c) plasma leptin concentrations are gender specific.

Adolescent↗
PubMed1996

Modified venovenous bypass technique for resection of renal and adrenal carcinomas with involvement of the inferior vena cava.

Peripheric tumours with extension into the inferior vena cava pose difficult management problems. Venovenous bypass using a centrifugal pump to decompress the inferior vena cava may be useful adjunct during vascular isolation of the tumour. We have modified the technique by adding portal decompression to avoid visceral accumulation of toxic metabolites. We have used this technique in two patients who had intracaval extension of tumours, one renal and one adrenal carcinoma.

Adenocarcinoma↗
PubMed1996

[Surgery in elderly patients].

The percentage of elderly people among surgical patients has been continuously rising. The purpose of this study was to show the course of operation and hospitalization of seniors in a department for general surgery. 191 patients aged 75 or older underwent surgery during the six months of observation. Information about preoperative social and environmental conditions, operative and postoperative treatments, complications, secondary symptoms and rehabilitation and homecare after discharge was retrospectively compiled. Women comprised 76.4% (146 cases) of the patients; men 23.6% (45 cases). Mandatory surgery was necessary in 37.7% of all operations, while 62.3% were required to be handled on an emergency basis. The average age was 83.2 years (+/- 5.26). 33 (17.3%) of the patients on whom had been operated did not survive. 84.8% (28) of these cases had undergone emergency surgery, 15.2% (5) had been operated on routinely. For 66% (126) of the patients the course of hospitalization was without any complications. Discharge into the accustomed environment was possible for 74.7% (118) of the successful cases. Old patients show a good physical and psychological acceptance of surgery and hospitalization, if they are well prepared and secondary symptoms are appropriately therapied. The decision for routine operation in sufficient time can help avoid an emergency operation with poor prognosis.

Activities of Daily Living↗
PubMed1996

Managed care: what to expect as Medicare-HMO enrollment grows. 1.

Managed care is restructuring the American health care system and is beginning to make inroads into the Medicare-eligible population. Advantages of managed care for older patients include an emphasis on prevention, more flexibility in care delivery, and fewer restrictions and wider coverage (eg, prescriptions) than Medicare fee-for-service, and opportunities to develop measures for quality of care. Disadvantages include limitations on access and choice and a potential for professional conflict of interest. Early managed care enrollment favors the healthy "young-old;" questions remain about whether HMOs can provide quality care to the frail elderly with complicated and expensive health care needs.

Aged↗
PubMed1996

Imaging inflammatory diseases with neutrophil-specific technetium-99m-labeled monoclonal antibody anti-SSEA-1.

UNLABELLED: Imaging inflammatory diseases with a 99mTc-labeled neutrophil-specific agent that can be injected directly intravenously continues to be a challenge. METHODS: The antibody, anti-SSEA-1, chosen from studies of 10 neutrophil-specific MAbs, recognizes CD-15 antigens (5.1 x 10(5)/human PMN) with a high association constant (kd = 10(-11) M). One hundred micrograms of MAb labeled with 10-20 mCi 99mTc either by a direct or DTPA conjugation method were injected intravenously into 12 patients (9 men, 3 women, aged 19-48 yr) with clinical evidence of ongoing inflammatory processes. Vital signs of all patients were recorded before and up to 3 hr following administration of the MAb. HAMA was determined in two patients. Anterior and posterior spot views and whole-body images were obtained. All patients except one underwent biopsy, US or CT examinations and/or surgical procedures. Blood samples collected from five patients were analyzed. In nine patients, quantitative organ distribution was determined and radiation dosimetry was calculated. RESULTS: Labeling yields were 94.8% +/- 1.4% and 95.8% +/- 3.5%, respectively. All patients had unequivocally positive images within 3 hr of the MAb injection. Eleven of these were confirmed by other modalities. One patient recovered on antibiotics and was sent home without surgery or other procedures. The lack of radioactivity in the thyroid or gastrointestinal tract indicated that the in vivo stability of the agent was excellent. At 3 hr postinjection, bladder activity in six patients was 1.3% +/- 0.4% of the administered dose. At this time, splenic uptake (7.7% +/- 1.0% ad. dose) and red marrow uptake (14 +/- 1.8%) were lower than those of 111In-WBC. At 49.0% +/- 3.2% administrated dose, liver uptake was at the upper limit with 111In-WBC uptake. Renal uptake was only 2.4% +/- 0.03% administered dose. At 2 hr postinjection, 14% to 51% of the radioactivity was associated with PMN. Radioactivity with lymphocytes was 0.7% to 10.9%, 1.2% to 4.3% with platelets and 1.1% to 2.4% with RBC. No HAMA were detectable in either patient, and no adverse reaction was detectable in any patient. CONCLUSION: Results are highly encouaging and have prompted us to prepare a kit for instant preparation and to initiate clinical trials.

Abscess↗
PubMed1996

Managed care: new challenges, new roles for the primary care physician. 2.

Managed care is revolutionizing health care, according to panelists in this roundtable discussion. Primary care physicians need to see patient care not as episodic but as a total, preventive package. In managed care, physicians hire nonphysician extenders for patient screening and function as a manager and consultant to an interdisciplinary team that extends beyond the four walls of the office practice. Patients need to know that primary care physicians can handle most of their problems; the specialist should be referred cases that are complicated and require procedures or second opinions. Outcome studies in managed care are lacking in important areas of geriatric medicine, such as treatment of psychiatric illnesses and Alzheimer's disease.

Fee-for-Service Plans↗
PubMed1996

[Immunoregulation of murine mammary tumor growth].

The function of the immune system during tumor growth is very controversial. Although there were great hopes that a proper stimulation of immunity would erradicate tumor cell proliferation this objective has still not been attained. We review and analyze some of the immunologic studies performed in our laboratory using spontaneous murine mammary adenocarcinomas. In early stages of tumor growth our studies showed a specific immune response in vivo and in vitro by delayed type hypersensitivity tests, and syngeneic lymphocyte induced angiogenesis assay. These activated lymphocyte responses were not involved in mechanisms effective for tumor rejection. The lymphocyte activation vanished with tumor growth. Soluble factors shed from splenocytes of tumor bearing hosts and factors secreted by tumor cells enhanced tumor and metastatic growth. Other cell populations, such as mastocytes and neutrophils were also altered during tumor growth. We conclude that soluble factors released by tumor cells induce the production of suppressor cells or factors that stimulate tumor and metastatic growth.

Animals↗
PubMed1995

Pneumocystis carinii pneumonia in Zimbabwe.

Pneumocystis carinii pneumonia (PCP) is said to be rare in Africa, with reported rates of 0-22% in human-immunodeficiency-virus (HIV) infected individuals with respiratory symptoms. Over one year in a central hospital in southern Africa, 64 HIV-infected patients with acute diffuse pneumonia unresponsive to penicillin and sputum smear-negative for acid-fast bacilli underwent fibreoptic bronchoscopy. Bronchoalveolar lavage fluid was assessed for bacteria, fungi, Pneumocystis carinii, and mycobacteria. 21 patients (33%) had PCP and 24 (39%) had tuberculosis; 6 of these had both infections. 5 patients had Kaposi's sarcoma (KS) associated with PCP, tuberculosis, or another infection, in 1 patient KS was the only finding, and in 21 no pathogen was identified. A logistic regression model was used to assess clinical, radiographic, and arterial blood gas predictors of PCP and tuberculosis. Fine reticulonodular shadowing on the chest radiograph (nodular component < 1 mm) was the strongest independent predictor of PCP (odds ratio 8.5 [95% CI 6.1-10.9]). A respiratory rate of more than 40/min was the best clinical predictor of PCP (odds ratio 11.2 [95% CI 8.8-13.6]). Median CD4+ T cell count for all cases of PCP was 134/microL (range 5-355) and for tuberculosis without PCP 206/microL (range 61-787). In resource-limited countries, a regionally appropriate management algorithm is required.

AIDS-Related Opportunistic Infections↗
PubMed1995

Persistent genital human papillomavirus infection as a risk factor for persistent cervical dysplasia.

BACKGROUND: Cervical dysplasia, also referred to as squamous intraepithelial lesion (SIL) in cytology or cervical intraepithelial neoplasia in histopathology, is thought to have the potential to advance in progressive stages to cervical cancer. However, not all cases of SIL progress, and most of the mild lesions spontaneously regress. Factors that govern regression, persistence, and progression of SIL are poorly understood. PURPOSE: Our analysis sought to identify factors that determined persistence or regression of SIL. METHODS: Seventy subjects with histopathologically confirmed cervical dysplasia were followed at 3-month intervals for 15 months. At each visit, the cervix was evaluated by Pap smear and colposcopy, and exfoliated cervicovaginal cells were analyzed for human papillomavirus (HPV) DNA. For each subject, data from every two consecutive visits were grouped as a pair. Persistent SIL was considered present if a lesion was detected at a visit (t) as well as at the next visit (t + 1) and absent if a lesion was detected at visit t but not at visit t + 1. A statistical model for time-dependent data correlated persistent SIL with various risk factors. RESULTS: Age, ethnicity, education, sexual behavior, smoking, and the use of oral contraceptives did not correlate with persistent SIL. The risk of persistent SIL was associated with continual HPV infection in visits t and t + 1 (HPV positive by Southern blot analysis: odds ratio [OR] = 3.91, and 95% confidence interval [CI] = 1.58-9.65; HPV positive by polymerase chain reaction [PCR]: OR = 2.42, and 95% CI = 1.03-5.67) and a persistent high viral load (OR = 4.07, and 95% CI = 1.35-12.30). When typed by PCR, individuals with type-specific persistent infection in visits t and t + 1, and particularly those with a continual high viral load (OR = 4.97; 95% CI = 1.45-17.02), had the highest risk for persistent SIL compared with those with a low level of type-specific persistent infection or non-type-specific persistent infection. The presence of persistent HPV infection in visits t-1 (the preceding time interval) was also predictive of persistent SIL in visits t and t + 1, although the strength of association was weaker, suggesting that persistent HPV and SIL occur synchronously. CONCLUSION: HPV infection and its associated cervical lesions tend to occur concurrently, and type-specific persistent HPV infection, particularly with a high viral load, produces chronic cervical dysplasia. IMPLICATIONS: The natural history of genital HPV infection directly influences the prognosis of cervical dysplasia as measured by persistence of the lesion. Testing for HPV infection may be valuable in the clinical management of women with cervical dysplasia.

Adult↗
PubMed1995

Assessment of immunoglobulins after hip replacement.

Operative stress, blood loss and transfusion affect general and local immunity after operation. This study concerns the humoral immunity mediators IgG, IgM and IgA. In 16 patients who had total hip replacements blood loss was made up by transfusion of the patient's own blood and with homologous blood; the immunoglobulins showed a significant reduction compared to the preoperative values. The same was true in a second group of 16 patients who had hip replacement and total homologous transfusion. A third group of 17 patients who had femoral and pelvic osteotomies were given autologous blood, donated before operation, and no changes were found in the immunoglobulins compared with the preoperative values. These results indicate the immunosuppressive effect of homologous transfusion. The balance of immunoglobulins remains relatively stable when blood loss is replaced with the patient's own blood.

Adult↗
PubMed1995

Acute appendicitis in pregnancy and the occurrence of major intraventricular hemorrhage and periventricular leukomalacia.

BACKGROUND: Infection and endotoxemia have been associated with neurologic injury in the newborn. In addition, recent reports have noted an increased incidence of fetal neurologic injury in the presence of intrauterine infection. CASES: Three pregnancies complicated by acute appendicitis and refractory preterm labor resulting in the delivery of neonates who developed early major intraventricular hemorrhage and/or periventricular leukomalacia are described. CONCLUSION: We hypothesize that extrauterine infections like acute appendicitis may play a role in the occurrence of neonatal neurologic injury.

Acute Disease↗
PubMed1995

Reinforcing effects of triazolam in sedative abusers: correlation of drug liking and self-administration measures.

Six male subjects with histories of sedative abuse were allowed to orally self-administer a maximum of 18 color-coded triazolam and placebo capsules during daily 3-h sessions. The schedule of reinforcement was a signaled fixed-interval 10-min schedule in which triazolam and placebo were concurrently available as mutually exclusive choices. Triazolam was shown to be a reinforcer in four of the six subjects. The two subjects who did not self-administer triazolam in preference to placebo also had lesser histories of drug dependence. Self-administration of triazolam (0.125 or 0.25 mg per capsule) was generally stable over 7-10 days. Manipulations of triazolam dose (0.0312-0.25 mg) per capsule in two subjects showed that the number of capsules self-administered was inversely related to capsule dose. Subject ratings of drug liking obtained from experimenter-administered doses of triazolam were correlated with self-administration behavior occurring 1-7 days later. Of the subject ratings, next day ratings obtained on the day after dosing resulted in significant correlations whereas same day ratings obtained while subjects were under the influence of triazolam did not. These results have important implications for abuse liability prediction and suggest that next day ratings have greater predictive validity than measures collected while subjects are under the influence of benzodiazepines.

Adult↗
PubMed1995

Differential modulation of cell phenotype by different molecular weight forms of basic fibroblast growth factor: possible intracellular signaling by the high molecular weight forms.

To study possible functional differences of the 18-kD and high molecular weight forms of basic fibroblast growth factor (bFGF), we have examined the effect of endogenous production of different bFGF forms on the phenotype of NIH 3T3 cells. Cells transfected with cDNAs coding for either 18-kD bFGF (18-kD bFGF) or all four molecular forms (18, 22, 22.5, 24 kD; wild type [WT] bFGF) exhibit increased migration and decreased FGF receptor number compared to parental cells. However, migration and FGF receptor number of cells transfected with a cDNA coding only for high molecular weight bFGF (22, 22.5, and 24 kD; HMW bFGF) were similar to that of parental cells transfected with vector alone. Cells expressing HMW, 18 kD, or WT bFGF grew to high saturation densities in 10% serum. However, only cells expressing HMW or WT bFGF grew in low serum. Cell surface or metabolic labeling of the different cell types followed by immunoprecipitation with anti-bFGF antibody showed primarily cell surface-associated 18-kD bFGF. In addition, when cells expressing exclusively HMW bFGF were transfected with a cDNA coding for 18-kD bFGF, migration was increased, bFGF receptors were down-regulated, and 18-kD bFGF was found on the cell surface. Cells expressing 18-kD bFGF transfected with a cDNA encoding FGF receptor-2 lacking the COOH-terminal domain (dominant negative bFGF receptor) exhibited a flat morphology and decreases in migration and saturation density. Cells expressing HMW bFGF transfected with the dominant negative bFGF receptor continued to grow to a high saturation density, proliferated in low serum, and exhibited no morphological changes. These results indicate that increased cell migration and FGF receptor down-regulation are mediated by the extracellular interaction of 18-kD bFGF with its cell surface receptor. Growth in low serum may be stimulated by the intracellular action of HMW bFGF through mechanisms independent of the presence of a cell surface receptor. Thus, the different molecular forms of bFGF may act through distinct but convergent pathways.

3T3 Cells↗
PubMed1995

Clinical experience with CD3 x CD19 bispecific antibodies in patients with B cell malignancies.

In extensive preclinical testing, a CD3 x CD19 bispecific antibody (BsAb) induced killing of malignant B cells by resting T cells even in an autologous situation. In a 14 day clonogenic assay using a CD19+ pre-B cell line (REH), BsAb required repeated administration together with IL-2 to achieve a 5 log kill by resting peripheral blood T cells. Intravenously administered BsAb in an intrapatient dose escalation study of 3 patients with B cell non-Hodgkin's lymphoma showed limited toxicity (WHO grade II fever and chills) due to tumor necrosis factor-alpha (TNF-alpha) release by T cells. Pharmacokinetics with 2.5 mg BsAb showed peak levels of 200-300 micrograms/ml and a t1/2 of 10.5 h. The next patient, with chronic lymphocytic leukemia (CLL), received 0.6 mg BsAb/m2 as an i.v. infusion preceded by 1 MU IL-2/m2 s.c. Improved T cell activation was noted, as indicated by an increase in IFN-gamma, IL-6, IL-8, and IL-10, in addition to high TNF-alpha increases. TNF-alpha increases were highest on the first day. Toxicity remained restricted to grade II fever and chills, observed every day after the infusion of BsAb. No clear clinical effects were seen in this chemotherapy-resistant CLL patient with a high tumor burden. If subsequent patients also show limited toxicity, treatment of patients with a lower tumor load seems to be warranted to evaluate the efficacy of CD3 x CD19 BsAb therapy.

Animals↗
PubMed1995

Effect of energy compared with carbohydrate restriction on the lipolytic response to epinephrine.

Fasting enhances the lipolytic sensitivity of adipose tissue to beta-adrenergic stimulation. The importance of carbohydrate compared with total energy restriction in regulating the lipolytic response to epinephrine was evaluated. Five normal volunteers participated in two study protocols in a randomized cross-over design separated by a 3-wk period. In one study (total energy restriction) the subjects fasted for 84 h, whereas in the other (carbohydrate restriction) a lipid emulsion was infused for 12-15 h each day to meet resting energy requirements during an 84-h oral fast. Glycerol flux, an index of whole-body lipolysis, was measured by infusing [2H5]glycerol. Each subject was studied in the basal state and during a 1-h infusion of epinephrine (0.015 microgram kg(-1 min(-1) after 84 h of total energy restriction and after 84 h of carbohydrate restriction (12 h after the final lipid infusion). The lipolytic response to epinephrine, defined as the total area between the glycerol flux curve and baseline during 1 h of epinephrine infusion, was similar after total energy restriction (241 +/- 141 mumol/kg) and carbohydrate restriction (294 +/- 58 mumol/kg). We conclude that carbohydrate restriction, not total energy restriction, is responsible for the increase in lipolytic sensitivity observed during fasting.

Adipose Tissue↗
PubMed1995

Endocrinologic and metabolic effects of interleukin-6 in humans.

Interleukin-6 (IL-6) is one of the major circulating cytokines in catabolic states. To investigate its endocrinologic and metabolic actions in vivo, we studied eight patients with metastatic renal cell cancer two times, once during infusion of saline (control) and once during a 4-h infusion of 150 micrograms recombinant human IL-6 (rhIL-6). Rates of appearance (Ra) of glucose and free fatty acids (FFA) in plasma were measured by using the isotope dilution method. Energy expenditure and substrate oxidation were determined by indirect calorimetry. rhIL-6 induced increases in plasma norepinephrine (+261 +/- 97%, P < 0.001), cortisol (+210 +/- 48%, P < 0.001), and glucagon (+70 +/- 18%, P < 0.001), in resting energy expenditure (+25 +/- 2%, P < 0.001 vs. control), and in plasma FFA concentration (+60 +/- 30%, P < 0.001), FFA Ra (+105 +/- 18%, P < 0.001), and fat oxidation (+38 +/- 16%, P < 0.001). Glucose Ra increased by 20 +/- 5% (P < 0.01) during rhIL-6 infusion with a concomitant increase in the metabolic clearance rate of glucose. In conclusion, our data demonstrate that rhIL-6 induces many of the endocrinologic and metabolic changes found in catabolic states and thus may mediate some of the metabolic effects previously ascribed to other cytokines.

Blood↗
PubMed1995

Quantification of incorporation of [15N]ammonia into plasma amino acids and urea.

The incorporation of 15N into individual plasma amino acids and urea was quantified in five human subjects who received 15NH4Cl either orally or intravenously for 6 h. After oral tracer administration, the highest enrichment was achieved by arginine, followed by urea and glutamine; distribution of 15N within glutamine was 55% amide and 45% amino N. Glutamine achieved the highest enrichment after the intravenous administration of tracer, with a distribution of 92% amide and 8% amino N. The relative distribution pattern of 15N incorporation was quantified from the rate at which 15N initially appeared in each plasma component. Amino acids (especially arginine, glutamine, and glutamate) accounted for greater than one-half (54%) of the orally administered tracer that was initially recovered in plasma components, compared with 46% initial appearance for urea; for the intravenous tracer, amino acids accounted for 78% of initial appearance of tracer compared with 22% for urea. Our results highlight the involvement of the splanchnic bed in the utilization of orally administered ammonia (preferential incorporation of oral tracer into arginine, urea, glutamate, and the amino N of glutamine) in contrast to the preferential incorporation of systemically administered ammonia into the amide N of glutamine and alanine.

Administration, Oral↗