Search PubMed⌕ Search

Biomedical subjects

L Klein

Publications and source records attributed to L Klein.

At least 163 records · Page 9Linked to original sources

The murmur of papillary muscle dysfunction in acute myocardial infarction: clinical features and prognostic implications.

The systolic murmur of papillary muscle dysfunction is a well-recognized feature of acute myocardial infarction (AMI), but no large prospective studies have determined its incidence, associated variables, and prognostic implications. Of 1653 patients who entered our data base with MI, 283 (17%) were classified as having a systolic murmur suggesting mitral regurgitation. At hospital discharge, there was a 5% incidence. There was a higher incidence of systolic murmur in non-Q wave AMI than in inferior or anterior Q wave MI (24% vs 13% and 15%, p less than 0.001). Advanced age, previous MI, and heart failure were all associated with systolic murmur (p less than 0.01). Persistent pain in the coronary care unit occurred more often in those with systolic murmur (45% vs 26%, p less than 0.0001). Systolic murmur was associated with an S3 and bibasilar rales (p less than 0.001) in the hospital; however, it was inversely related to peak creatine kinase and unrelated to heart failure or ejection fraction at discharge. Univariate predictors of mortality associated with systolic murmur included complex premature ventricular contractions at discharge and a non-Q wave location. Patients with systolic murmur had higher hospital and 1-year mortalities than those without systolic murmurs (p less than 0.01). When systolic murmur was present during hospitalization, the average time to reinfarction was 2.5 times earlier than when no systolic murmur was present (84 vs 214 days, p less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Collagen degradation and synthesis in experimental corneal grafts.

Thirty-two weanling New Zealand white rabbits were labelled repeatedly with [2,3-3-H]-proline for 4 weeks. Four weeks after the end of labelling, 32 rabbits underwent bilateral 6 mm trephinations for donor purposes. One control cornea of each pair was frozen at -70 degrees C. The contralateral corneas were used for autografts, allografts, and xenografts. Grafts were observed from 7-200 days, then retrephined out for determination of loss in total radioactivity in hydroxyproline (specific for collagen), increase in newly synthesized collagen, and net change in collagen mass, by comparing with the matched, ungrafted control corneas. For all three transplant groups there was a small, but significant, decrease early in total radioactivity (loss of original collagen) and a significant increase in new collagen. These data also indicated that the loss of original collagen was replaced by an equivalent or greater increase in new collagen in all transplant groups. Significant relationships between graft clarity and collagen turnover were noted in both the auto- and allograft groups. The degradation of old collagen was significantly greater in the cloudy vs. the clear grafts; however, there was no significant difference in the increase in new collagen between these groups. A progressive loss of original collagen over time was noted in the cloudy autografts, but not the allografts. A trend toward a progressive increase in new collagen was noted over time in both the cloudy auto- and allografts. No relation for these variables to time, however, was noted in the clear grafts.

Animals↗

Cytotoxic T lymphocytes discriminate between isomeric forms of the same hapten.

We have analysed the ability of fluorescein-specific cytolytic T lymphocytes (CTLs) to lyse a variety of hapten-derived target cells. Our data demonstrate that: (i) fluorescein-specific CTLs distinguish between target cells conjugated with isomeric forms of the hapten in a way that is not attributable to differences in the target cell density of the two hapten isomers; (ii) the relative orientation of the haptenic moiety with respect to the target cell membrane is more important than the chemical nature of the hapten/protein linkage. We interpret these data as supporting a model of the T-cell receptor in which the elements that recognize the extrinsic and the restricting Class 1 major histocompatibility complex (MHC) antigens are sterically constrained and unable to rotate independently of one another.

Animals↗

Anesthesia for neonatal foals.

A brief discussion of those aspects of neonatal physiology that pertain to anesthetic risk and selection of anesthetic techniques is followed by discussion of suggested techniques for anesthetic management in healthy foals. Preoperative preparation and management of foals with selected serious surgical conditions are also considered.

Anesthesia, General↗

The effect of renal function on enalapril kinetics.

Enalapril maleate (MK-421), a nonmercapto-containing angiotensin converting enzyme (ACE) inhibitor, is converted in vivo to enalaprilat (MK-422), the active diacid. We evaluated serum profiles and urinary excretion of oral enalapril maleate in patients with renal disease (group I, creatinine clearance less than 3 ml/min, patients undergoing dialysis, n = 10; group II, creatinine clearance 10 to 79 ml/min, n = 9) compared with healthy subjects (group III, creatinine clearance greater than 80 ml/min, n = 10). Group I received a 10 mg dose during a day while not receiving dialysis and a 10 mg dose 1 hour before dialysis 2 weeks later. Groups II and III received a single 10 mg dose. Blood samples and urine were collected for 48 hours. Impaired renal function resulted in elevated serum and plasma concentrations of enalapril maleate and decreased excretion rates and urinary recovery of enalapril maleate and enalaprilat. The data suggest an apparent increase in the extent of metabolism of enalapril maleate to enalaprilat or an increase in nonrenal elimination of unchanged enalapril maleate in renal disease compared with normal health. Enalaprilat was dialyzable.

Administration, Oral↗

Effect of 1,25(OH)2D3 on the relative contributions of skeletal 45Ca and intestinal 40Ca to blood calcium in normal and thyroparathyroidectomized dogs.

The effects of gradually increasing doses of 1,25(OH)2D3 on plasma calcium and 45Ca radioactivity were studied in young dogs that had been extensively prelabelled with 45Ca. The effects of orally and intravenously administered 1,25(OH)2D3 were evaluated in normal and thyroparathyroidectomized dogs fed a normal diet. In normal dogs when 1,25(OH)2D3 increased the plasma calcium within the normal range (2.9-3.1 mmol/L) there was no significant increase in plasma 45Ca. In thyroparathyroidectomized dogs, oral or intravenous 1,25(OH)2D3 increased the low blood calcium to a normal level (1.8-2.9 mmol/L) without significantly increasing plasma 45Ca. In normal and thyroparathyroidectomized dogs, any 1,25(OH)2D3-induced increase in plasma calcium above the normal range was associated with a significant increase in 45Ca, indicating mobilization of bone calcium. Intravenous administration of 1,25(OH)2D3 in the normal or thyroparathyroidectomized dogs had a much larger effect than oral doses in mobilizing bone 45Ca when inducing a similar level of hypercalcemia. The major physiological effect of 1,25(OH)2D3 in the low or normal range of plasma calcium is on intestinal absorption of calcium without a significant effect on mobilizing bone calcium. The pharmacological effect of 1,25(OH)2D3 in vivo is to mobilize bone calcium as well as dietary calcium into blood.

Administration, Oral↗

Effects of parathyroid hormone on puppies during development of Ca and vitamin D deficiency.

The acute effects of parathyroid extract (PTE) were studied repeatedly in young dogs (prelabeled with 45Ca and [3H]tetracycline) during the development of calcium (Ca) and vitamin D deficiency. Blood Ca and radioactivity changes were monitored sequentially after subcutaneous PTE, injected seven times over 63 days. In control dogs, all sequential responses to acute PTE challenges were constant in both magnitude of increase and time at which maximum response occurred over the entire experiment. Under chronic Ca and D deficiency, plasma 25-hydroxyvitamin D in experimental dogs decreased continuously to very low levels at 63 days, whereas 1,25-dihydroxyvitamin D initially increased to a maximum at 32 days and thereafter decreased. In response to an acute challenge of PTE, dogs on the deficient diet for 3 and 10 days showed a greater response of blood Ca and 45Ca than the controls but subsequently showed a smaller response than controls after 49 and 63 days on the deficient diet. Compared with control dogs, the time of maximal response of blood Ca and 45Ca to PTE occurred much earlier in dogs that were on the deficient diet for 35-63 days. The blood [3H]tetracycline response (index of bone resorption) to exogenous PTE in the deficient dogs, however, was constant and similar to that of the control dogs during the entire period. The data suggest that the bone resorption response to PTE was normal in Ca- and D-deficient puppies with hypocalcemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Phase I trial of misonidazole (NSC#261037) plus cyclophosphamide in solid tumors.

Misonidazole, a hypoxic cell sensitizer, enhances the antitumor effects of cyclophosphamide in preclinical studies. Several studies also showed increased cytotoxicity for normal tissues. We undertook a phase I study of this combination. The regimen consisted of oral administration of misonidazole at one of two dose levels, 1 g/m2 and 2 g/m2, followed by an intravenous (IV) injection of cyclophosphamide four hours later. The cycle was repeated every twenty-one days. The dose of misonidazole remained constant for each regimen, but the dose of cyclophosphamide ranged from 0.4 g/m2 to 1.3 g/m2. Thirty-eight trials in 35 patients with advanced solid tumors were considered evaluable. Dose-limiting toxicity was granulocytopenia at 1 g/m2 of cyclophosphamide without significant thrombocytopenia or anemia. Peripheral neuropathy was negligible. Two patients received cumulative doses of 8 and 16 g/m2 of misonidazole without neurotoxicity. One patient developed hemorrhagic cystitis. Nausea and vomiting was mild to moderate. Possible evidence of tumor stabilization was seen in three patients, and one patient had a mixed response. The mean serum half-life for misonidazole was 11.3 hours (range, 8.4 to 20.0) and for cyclophosphamide 8.3 hours (range, 3.2 to 15.5), both within the previously reported ranges. In conclusion, it appears that this combination is well tolerated and that misonidazole does not significantly potentiate myelotoxicity caused by cyclophosphamide or alter its pharmacokinetics. The recommended starting doses for misonidazole and cyclophosphamide in phase II trials using this schedule of administration should be 2 g/m2 and 1 g/m2, respectively, with escalation for cyclophosphamide to individual tolerance.

Adult↗

Iatrogenic superior vena cava syndrome. A new entity.

Four patients with cancer developed superior vena cava syndrome following placement of a central venous catheter (Broviac or Hickman catheter) without evidence of mediastinal tumoral involvement. Diagnostic and therapeutic considerations are discussed.

Adult↗

Liposome-mediated transfer of macromolecules into flagellated cell envelopes from bacteria.

We have studied the interaction between flagellated cell envelopes from Escherichia coli and liposomes. Oligolamellar liposomes of ca. 0.45-micron diameter, composed of azolectin, phosphatidylserine, and cholesterol at a molar ratio of 7:1:2, were prepared by freezing and thawing and subsequent extrusion through polycarbonate filters. These liposomes exhibited high entrapment capacity and low leakiness. Liposome-cell envelope interaction was monitored flow cytometrically in a fluorescence-activated cell sorter with a fluorescent aqueous space marker and by a filtration assay with radiolabels for the lipid phase and the liposomal aqueous space. Maximal association of liposomes with the envelopes was observed in both assays after ca. 25 min at 30 degrees C. After such period of time, it seems that up to 200 liposomes (depending on the liposome to envelope ratio) were associated with a single cell envelope, as calculated from the radiotracer studies. Fluorometric measurements of the transfer of liposomal contents and the intermixing of membrane lipids indicated that at least 20% of the envelope-associated liposomes had delivered their content into the envelopes, possibly by fusion. Electron microscopic observations confirmed the transfer of liposome-encapsulated ferritin molecules into the cell envelopes. Our data suggest that liposomal carriers might be employed to deliver cytoplasmic, chemotaxis-related macromolecules into bacterial cell envelopes.

Animals↗

Collagen dynamics of partial small bowel obstruction.

The response of intestinal collagen to obstruction and stress was studied in the rat. Partial small bowel obstructions were created. Preobstruction collagen was measured by injection of tritium labeled proline. New collagen formation after obstruction occurred was followed by injection of carbon-14 labeled proline. At 3 weeks, collagen fractions were identified. Throughout the study, preexisting preobstruction intestinal collagen was metabolically stable with no breakdown or remodeling demonstrable. New collagen formation was rapid and occurred to the largest degree close to the obstruction.

Animals↗