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Biomedical subjects

I Klein

Publications and source records attributed to I Klein.

At least 127 records · Page 7Linked to original sources
PubMed1989

Fat emboli in bilateral total knee arthroplasty. Predictive factors for neurologic manifestations.

Fat embolism after bilateral total knee arthroplasty (TKA) occurred in 12% of the authors' patients having bilateral TKA with intramedullary instrumentation. Usually embolism was manifested as neurologic changes, most often changes of mental status. Death is a potential consequence, and this occurred in one patient. The present authors believe that fat embolism is not predictable preoperatively and propose that intraoperative guidelines can be used to reduce risk of this complication. Intraoperative monitoring by a Swan-Ganz catheter will permit measurement of the pulmonary arterial pressure, pulmonary vascular resistance, and pulmonary capillary wedge pressure. A sustained rise of any of these would be an indication to abort the second knee operation. If Swan-Ganz catheter is not available, a sustained fall of oxygen saturation to 90% or lower can be used as a criterion. The risk for fat embolism is increased with the use of intramedullary instrumentation, and the above guidelines are recommended for operations with this type of instrumentation. A fluted intramedullary rod and vent holes should be used.

Catheterization, Swan-Ganz↗
PubMed1988

Psychiatric and neuropsychological response to propranolol in Graves' disease.

We describe the endocrine, psychiatric, and neuropsychological assessments of 10 untreated, newly diagnosed Graves' disease subjects who were studied longitudinally at three stages: hyperthyroid (stage 1), after 2 weeks of propranolol treatment (stage 2), and after 6 months of antithyroid treatment (stage 3). Major depression, generalized anxiety disorder, and hypomania were diagnosed at stage 1. Elevations on psychiatric symptom rating scales and in motor activity monitoring at stage 1 were significantly decreased at stage 2 and again at stage 3. Psychiatric improvements paralleled improvements in endocrine symptoms. Neuropsychological improvements were noted on the more challenging memory and attention tasks at stage 3, whereas propranolol treatment was not associated with changes on attention tests. Results are discussed in relation to catecholamine-thyroid hormone interactions, in particular, the beta-adrenergic system.

Adult↗
PubMed1988

Pharmacokinetics of carboplatin after intraperitoneal administration.

The pharmacokinetics of carboplatin, ultrafilterable platinum, and total platinum after intraperitoneal (i.p.) administration were studied in peritoneal fluid, plasma, red blood cells (RBCs), and urine during a phase-I trial in patients with minimal, residual ovarian cancer. Samples were collected from 7 patients who had received carboplatin (200-500 mg/m2) in 21 dialysis fluid. The fluid was withdrawn after a 4-h dwell. Platinum concentrations were measured by flameless atomic absorption spectrometry, and intact carboplatin was determined by HPLC with electrochemical detection. Peak concentrations of carboplatin in plasma were obtained 2 h after the end of instillation. The mean ratio of peak concentrations of carboplatin in instilled fluid and plasma was 24 +/- 11. The peritoneal clearance of carboplatin was 8 +/- 3 ml/min, which was 12 times less than the plasma clearance (93 +/- 32 ml/min). Due to this clearance ratio, the AUCs for the peritoneal cavity were about 10 times higher than those for plasma. On average, 34% +/- 14% of the dose was still present in the instillation fluid that had been withdrawn after a dwell time of 4 h. In plasma, the mean value of AUC/Dnet (Dnet = Dose - amount recovered from the peritoneal cavity) after i.p. administration was comparable with that of AUC/D after i.v. administration. This means that unrecovered carboplatin (66%) was completely absorbed from the peritoneal cavity. It may be expected from this bioavailability that the maximum tolerated dose (MTD) of i.p.-administered carboplatin with a 4-h dwell is around 1.5 times higher than that after i.v. administration. Overall pharmacokinetic parameters of carboplatin and platinum in plasma were comparable after i.p. and i.v. administration.

Aged↗
PubMed1988

A psychiatric and neuropsychological study of patients with untreated Graves' disease.

We studied 13 untreated Graves' disease subjects in a clinical research unit using endocrine, psychiatric, and neuropsychological assessments. We used SADS interviews, RDC, standardized symptom rating scales, and motor activity monitoring to update earlier studies and quantified psychiatric symptoms to elucidate any correlations between endocrine and psychiatric status. Nine of 13 subjects had major depression, 8/13 had generalized anxiety disorder, and 3/13 were hypomanic. Anxiety levels were much higher than in other hospitalized medical patients. Using a broad battery of neuropsychological testing, we found mild deficits in attention, memory, and complex problem solving that were consistent with previous studies of hyperthyroid patients. The severity of psychiatric symptoms could easily result in an inappropriate referral to a psychiatrist prior to the diagnosis of hyperthyroidism. The relationship between psychiatric symptoms and possible CNS effects of excess levels of thyroid hormone is discussed.

Adult↗
PubMed1988

Pharmacokinetics of free and total platinum species after rapid and prolonged infusions of aqua (1,1-bis(aminomethyl)cyclohexane) sulfatoplatinum (II) (spiroplatin) during a phase I trial.

The pharmacokinetics of the second generation platinum complex aqua(1,1-bis-(aminomethyl)cyclohexane)sulphatoplatinum(II) (spiroplatin, TNO-6) were studied during a phase I evaluation. Thirty patients received 49 cycles of spiroplatin by short term (less than or equal to 10-min), 1-, 3- or 6-h infusion. Dosages given ranged from 5 to 40 mg/m2. Platinum determinations were performed by atomic absorption spectrometry. Up to 5 days after administration platinum concentrations in plasma decayed triexponentially. Pharmacokinetic parameters of total platinum in plasma after short-term and prolonged infusion were similar in terms of terminal half-life (3.7 +/- 1.1 and 3.6 +/- 0.5 days), AUC/dose (548 +/- 106 and 616 +/- 278 min.m2/l), volume of distribution (20 +/- 6 and 27 +/- 81) and total body clearance (2.9 +/- 1.0 and 3.4 +/- 1.8 ml/min), whereas peak plasma concentrations were two times lower after prolonged infusion. The cumulative urinary platinum excretion after short-term infusion was 20 +/- 6%, 30 +/- 6% and 47 +/- 7% of the administered dose after 6, 24 and 120 h, respectively. These values are comparable to those after administration of cisplatin. The half-life of ultrafilterable platinum was 4.4 +/- 0.7 min. The curves of free and total platinum diverged rapidly, reflecting the high reactivity of spiroplatin towards plasma proteins. This high reactivity, most likely caused by the abundant presence of aquated compounds in the injection fluid, may also account for severe and unpredictable nephrotoxicity induced by spiroplatin.

Adult↗
PubMed1988

Self-reactive delayed type hypersensitivity induced in mice by syngeneic lymphoblasts. II. Isolation of two distinct lymphoblast antigens, one of which reacts (or cross-reacts) with anti-H-2Dd monoclonal antibody.

X-irradiated (250 rad) or normal A mice injected with syngeneic concanavalin A-induced lymphoblasts (syn-Con A blasts) developed an inflammatory response in their footpads 24 to 72 h after injection of syngeneic lipopolysaccharide-induced lymphoblasts (syn-LPS blasts) into these tissues. This immunological activity was designated syngeneic delayed type hypersensitivity (syn-DTH), because T cells transferred the response to naive recipients. Analysis on Ultrogel or Sephadex G-50 columns revealed that a Con A-blast extract contains two syn-DTH-stimulating antigens: a small antigen (6000-7000) and a large antigen (apparent MW of 160,000-175,000). This conclusion held true even when protease inhibitors were included in the fractionation procedure. The approximate molecular weights of these antigens estimated by the gel filtrations were confirmed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). The large lymphoblast syn-DTH-stimulating antigen contains carbohydrate residues but not products of the H-2 genetic region. The small antigen does not contain sugar moieties, but it expresses affinity to anti-H-2Dd monoclonal antibody. The immune response to the small antigen but not to the large antigen is genetically restricted at both the induction and the elicitation phases of the DTH. A strain of mice immunized with the small antigen generated syn-DTH after challenge with lymphoblasts of B10.T (6R) mice, which share the H-2Dd subregion with A mice but not the H-2K or the H-2I subregions. Fast protein liquid chromatography of the small antigen yielded a purified material which appeared as a single band after Coomassie staining of its gel electrophoresis.

Animals↗
PubMed1988

Self-reactive delayed type hypersensitivity induced in mice by syngeneic lymphoblasts. III. Immunological characterization of the small and large antigens of the blast cells.

X-irradiated or normal A mice injected with syngeneic concanavalin A-induced lymphoblasts (syn-Con A blasts) developed inflammatory responses in their footpads 24 to 72 h after the injection of syngeneic lipopolysaccharide-induced lymphoblasts (syn-LPS blasts) into these tissues. This response was designated syngeneic delayed type hypersensitivity (syn-DTH). The Con A blast extracts contain small (apparent MW of 6000-7000) and large (apparent MW of 160,000-175,000) syn-DTH-stimulating antigens, which are found in the total volume (low molecular weight fraction) and the void volume (high molecular weight fraction), respectively, of AcA 44 gel filtrations of this extract. The small and large antigens exhibit different immunological properties. The small antigen of A mouse lymphoblasts induced syn-DTH in X-irradiated (250 rad) mice but not in normal mice, and this immunological activity was elicited with syngeneic but not allogeneic lymphoblasts. The syn-DTH induced with the small antigen was inhibited by Lyt-1+2+, I-Jk+ suppressor T cells or a factor extracted from these cells. In contrast to the small antigen, the large antigen of A mouse lymphoblasts induced syn-DTH in both normal and X-irradiated mice, and this immunological activity was elicited by both syngeneic and allogeneic LPS lymphoblasts. The small and large antigens do not immunologically cross-react, but their immunogenicity is not affected by ultraviolet irradiation, indicating that the immune response against both of them is relatively class II-independent. The possibility that the cellular autoanti-lymphoblast response observed in our studies is in fact a mechanism that down-regulates the lymphoblast activity and thus suppresses the immune response is discussed.

Animals↗
PubMed1988

Thyroxine-induced cardiac hypertrophy: time course of development and inhibition by propranolol.

To investigate the mechanism of thyroid hormone-induced cardiac hypertrophy, we have studied the in vivo changes in cardiac size and total myocardial content of both membrane and cytoskeletal enzymes in the rat after the administration of excess thyroid hormone. In response to 50 micrograms T4/day, there is a significant increase in heart rate and heart work associated with an increase in total heart size and protein content. Measurements of the specific activity of Na,K-ATPase and p-nitrophenol phosphatase demonstrate a small but significant increase in specific activity, while the specific activity of myosin ATPase is unchanged. To further probe the mechanism for T4-mediated hypertrophy we studied the in vivo effects of beta-adrenergic blockade on rat heart size. When animals were treated with both T4 and propranolol (10 mg/animal.day) cardiac hypertrophy was prevented. Propranolol alone at this dose did not affect heart rate, heart weight, or serum levels of T4 and T3. The present data suggest that 1) the hypertrophic response of the myocardium to excess thyroid hormone involves cytoplasmic as well as membrane proteins, 2) the increase in total myocardial protein, which can be blocked by propranolol, is indirectly mediated by increases in cardiac work rather than a direct effect of thyroid hormone.

Adenosine Triphosphatases↗
PubMed1988

Neonatal thyroid disease: differential expression in three successive offspring.

Neonatal thyroid disease, manifested as either hyperthyroidism or hypothyroidism, has been described in the offspring of women with autoimmune thyroid disorders. We report clinical and laboratory observations in a mother with autoimmune thyroiditis who gave birth to three children with different forms of thyroid dysfunction. The first child was clinically normal, the second child had transient neonatal hyperthyroidism, and the third child had neonatal hypothyroidism. After the birth of the second child, the mother was found to be biochemically hypothyroid. Long-acting thyroid stimulator and antithyroid microsomal antibodies were detected in her serum. She was treated with L-T4 (0.15 mg/day). After the birth of her third child, the mother was found to have thyroid-stimulating immunoglobulins and TSH-blocking inhibitory immunoglobulins in her serum. The latter also were detected in the third newborn. Six weeks later, TSH-blocking inhibitory immunoglobulins were not detected in the child, but they persisted in the mother. This report further expands the spectrum of neonatal thyroid disease and suggests that differing disease syndromes in the newborn can occur depending on whether stimulating or blocking antibodies predominate in the mother.

Adult↗
PubMed1988

Symptom rating scale for assessing hyperthyroidism.

A hyperthyroid symptom scale (HSS) was designed and administered to ten subjects with untreated Graves' disease. All subjects had clinical and chemical evidence of hyperthyroidism and reproducible HSS scores of 20 or more points. During sequential treatments with propranolol hydrochloride (phase 2) followed by propylthiouracil (phase 3) there was a significant decline in the HSS scores at each phase. Accompanying the decrease in HSS scores was a decrease in heart rate, but there was no change in thyroid function test results at phase 2 and a decrease in heart rate, thyroid function test results, and goiter size at phase 3. This new scale includes ten categories of symptoms, it is sensitive to changes in both the adrenergic and metabolic components of hyperthyroidism, and it is useful in the clinical assessment and management of patients with thyrotoxicosis.

Adult↗
PubMed1987

Comparative pharmacokinetics of cisplatin and three analogues in mice and humans.

Pharmacokinetics of cisplatin, spiroplatin, ethylenediaminemalonatoplatinum(II) (JM-40), and carboplatin was studied in BALB/c x DBA/2 F1 mice receiving 10% lethal doses of 15.5, 6.8, 100, and 165 mg/kg, respectively. Blood samples were collected for up to 5 days after a single i.v. bolus injection. Total platinum in plasma and non-protein-bound free platinum in plasma ultrafiltrate were determined by flameless atomic absorption spectrometry. Parent JM-40 and carboplatin were determined by high performance liquid chromatography. Calculated pharmacokinetic parameters (peak concentrations, half-lives, areas under the curve) were compared with the corresponding values in patients at the maximal tolerated dose. Peak plasma concentrations were 2.4- to 20-fold higher in mice than in humans. Initial and terminal half-lives in mice were up to 6 times shorter than in patients. However, the areas under the plasma concentration versus time curves (AUCs) were found to agree. The ratios of the AUCs of free platinum in patients (AUCp) and mice (AUCm) measured over the first part of the plasma concentration versus time curve were 1.2, 0.3, 1.1, and 0.9 for cisplatin, spiroplatin, JM-40, and carboplatin, respectively. These values changed to 1.3, 0.3, 2.5, and 1.0 when the time interval was extended to free platinum levels just above the detection limit. Ratios of the AUCs of total platinum in patients and mice measured over 5 days were 2.7, 2.6, 4.2, and 1.8, respectively. Using a ratio of 1 for free platinum originating from JM-40, the retrospectively calculated maximal tolerated dose from AUCp at low dosages was 1021 mg/m2 (n = 7; range, 836-1282), compared to 1200 mg/m2 as found in the phase I trial. This suggests that the AUCp/AUCm ratio of free platinum over the first part of the concentration versus time curve can possibly be used to predict the maximal tolerated dose of platinum analogues in humans, during the early stage of phase I studies.

Animals↗
PubMed1987

Chemical reactivity of cisplatin bound to human plasma proteins.

Human plasma was incubated with cisplatin over 24 h. Ultrafilterable platinum and platinum reactive with DDTC were determined at regular time intervals during incubation. At each time point more platinum reacted with sodium N,N1-diethyldithiocarbamate (DDTC) than was available as ultrafilterable platinum. At 24 h 70% of total platinum (10% ultrafiltrable platinum and 60% protein-bound platinum) reacted with DDTC. This means that cisplatin bound to plasma proteins can--at least in part--still react with strong nucleophiles.

Blood Proteins↗
PubMed1987

Regulation of cardiac myosin synthesis: studies of RNA content in cultured heart cells.

Contraction regulates the myosin content and the rate of myosin synthesis in cultured neonatal rat heart cells. To further explore the mechanism for this regulation we examined various parameters of RNA content and RNA synthesis in contacting versus noncontracting myocytes. While contraction stimulated myosin heavy chain (MHC) synthesis by 72% compared to that of KCl-arrested cells, simultaneous analyses of polysome profiles were no different under the two culture conditions. Incorporation of [3H]uridine monophosphate into cellular RNA revealed no change in the rate of total RNA or ribosomal subunits synthesis. In vitro translation of cellular RNA yielded similar incorporation of [35S]methionine into trichloroacetic acid precipitable protein. Specific transcription of the MHC gene was examined by dot-blot analysis and was unaltered by contraction. Northern blot analysis of the MHC sequences detected by a cDNA probe revealed an mRNA sequence corresponding to a molecular weight of approximately 30 S. These data suggest that RNA synthesis and RNA content are unaltered by contraction in cultured heart cells and therefore the changes in myosin synthesis may be mediated at a post-transcriptional control level.

Animals↗