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Biomedical subjects

R Snyder

Publications and source records attributed to R Snyder.

At least 73 records · Page 4Linked to original sources
PubMed1991

Effects of intraocular irrigants on the preserved human corneal endothelium.

Either a simple balanced salt solution (BSS) or a bicarbonate-buffered, glutathione-containing commercial irrigant (BSS Plus, Alcon Laboratories, Fort Worth, Texas, U.S.A.) may be used during the vitrectomy portion of a corneal transplant procedure. To simulate the conditions present in the anterior chamber during the first few hours after vitrectomy and grafting, we performed in vitro perfusions of stored human corneas using each irrigant and measured corneal thickness over a 3-hour period. Irrespective of the preservation medium used (McCarey Kaufman, Chondroin Sulfate or Dexsol, all from Chiron Ophthalmics, Irvine, California) or duration of storage (2 or 4 days), corneas irrigated with BSS Plus exhibited significantly (p less than .05) decreased thickness compared with their paired mates irrigated with BSS. In ultrastructural studies performed on postperfusion corneas, there was a tendency toward improved surface morphology in the in vitro BSS Plus-perfused tissue. This study shows that in vitro corneal thickness after preservation is significantly irrigant dependent, with BSS Plus providing the essential ingredients to promote the corneal endothelial pump function.

Corneal Edema↗
PubMed1991

Blood antibodies and uncrossmatched type O blood.

The immediate transfusion of uncrossmatched type O blood in the initial resuscitation of the trauma victim remains controversial. To examine difficulties in crossmatching blood for later transfusions after use of uncrossmatched type O blood, we undertook a prospective 23-month study at a level I trauma center. One hundred thirty-five severely injured patients received uncrossmatched type O blood during the study period. Sixty-one patients (45%) died and 76 patients (56%) underwent emergent operation. There were no major transfusion reactions. Six patients had blood antigen-antibodies present on admission, and such antibodies developed in three patients during hospitalization. We conclude that uncrossmatched type O blood may be used safely in the exsanguinating patient, but blood antigen-antibodies, which may complicate later crossmatching, can develop after its use.

ABO Blood-Group System↗
PubMed1990

Nucleotide specificity for the bidirectional transport of membrane-bounded organelles in isolated axoplasm.

Video microscopy of isolated axoplasm from the squid giant axon permits correlated quantitative analyses of membrane-bounded organelle transport both in the intact axoplasm and along individual microtubules. As a result, the effects of experimental manipulations on both anterograde and retrograde movements of membrane-bounded organelles can be evaluated under nearly physiological conditions. Since anterograde and retrograde fast axonal transport are similar but distinct cellular processes, a systematic biochemical analysis is important for a further understanding of the molecular mechanisms for each. In this series of experiments, we employed isolated axoplasm of the squid to define the nucleoside triphosphate specificity for bidirectional organelle motility in the axon. Perfusion of axoplasm with 2-20 mM ATP preserved optimal vesicle velocities in both the anterograde and retrograde directions. Organelle velocities decreased to less than 50% of optimal values when the axoplasm was perfused with 10-20 mM UTP, GTP, ITP, or CTP with simultaneous depletion of endogenous ATP with hexokinase. Under the same conditions, TTP and ATP-gamma-S were unable to support significant levels of transport. None of the NTPs tested had a differential effect on anterograde vs. retrograde movement of vesicles. Surprisingly, several inconsistencies were revealed when a comparison was made between these results and nucleoside triphosphate specificities that have been reported for putative organelle motors by using in vitro assays. These data may be used in conjunction with data from well-defined in vitro assays to develop models for the molecular mechanisms of axonal transport.

Animals↗
PubMed1990

Synthesis and characterization of deoxyguanosine-benzoquinone adducts.

Benzene expresses its carcinogenic potential in humans largely in the form of acute leukemia. Because an understanding of the formation of DNA adducts by benzene metabolites may help to explain the etiological role they play in benzene-induced bone marrow disease, we have synthesized, isolated and characterized adducts formed by the reaction of deoxyguanosine with hydroquinone and p-benzoquinone, two toxic metabolites of benzene. [3H]Deoxyguanosine and [14C]hydroquinone reacted in neutral aqueous buffer containing iron to form two dual-labeled products, which were separated using HPLC. When p-benzoquinone was substituted for hydroquinone, the same adducts were formed in the absence of added iron. The ultraviolet and fluorescence spectra of the less polar adduct, called Adduct 2, were distinctly different from the spectra of the starting materials. NMR and mass spectrometry suggested a compound with a mass of 357 with the p-benzoquinone moiety bound to the N-1 and N2 positions of deoxyguanosine. Based on these data it is proposed that Adduct 2 is (3'OH)benzetheno(1,N2)deoxyguanosine. The more polar product, Adduct 1, was found to have a unique ultraviolet spectrum but did not appear to be fluorescent. Both adducts were observed after calf thymus DNA was incubated with hydroquinone and digested to its constituent nucleosides.

Animals↗
PubMed1990

Ascending aortic dissection in weight lifters with cystic medial degeneration.

We report 4 cases of ascending aortic dissection in patients with long histories of weight lifting. In 2 of the patients, the initial symptoms of dissection developed while they were lifting weights. Two patients had a history of hypertension and 2 had previously used anabolic steroids. All 4 were successfully treated surgically. Histopathology showed aortic medial changes in all 4. We believe that the hemodynamic stresses of weight lifting, namely, a rapid increase in systemic arterial blood pressure without a decrease in total peripheral vascular resistance, in combination with aortic medial degeneration may have contributed to the development of the aortic dissection.

Adult↗
PubMed1990

Interactive inhibition of erythroid 59Fe utilization by benzene metabolites in female mice.

Using radioiron uptake into erythrocytes as a measure of hematopoiesis, it was demonstrated that benzene inhibited bone marrow function in female mice. Hydroquinone was marginally effective, but the inhibition occurred only at the highest dose tested (100 mg/kg). The combination of phenol and hydroquinone was more effective in reducing erythrocyte production than either chemical given alone. Catechol given alone was not inhibitory but when phenol was added to catechol, erythropoiesis was suppressed, as observed for the phenol and hydroquinone combination. It appears that benzene toxicity may be the result of cooperative inhibitory effects produced by its metabolites.

Animals↗
PubMed1990

Oncogenes, malignant transformation, and modern medicine.

During the past decade there have been remarkable strides in the understanding of the basic mechanism of cancer. It is now clear that there is a set of genes, known as oncogenes, that can cause cells to become malignant if their expression is altered, either by mutation or overexpression. The products of these genes include growth factors, growth factor receptors, signal tranduction proteins, and DNA binding proteins. The normal cellular counterparts of these genes play very important roles in the regulation of growth and proliferation by normal cells. Another set of genes, anti-oncogenes, also play an important role in preventing abnormal cell proliferation. The remarkable explosion of understanding of the pathophysiology of malignancy has led to a common unifying concept of malignant transformation that applies to all tumors. It is likely that these new insights will lead to improved and more specific treatments for malignant disease in the next decade.

Animals↗
PubMed1990

Effective salvage chemotherapy with etoposide, dactinomycin, and methotrexate in refractory germ cell cancer. Australasian Germ Cell Trial Group.

Fifty-one patients with advanced germ cell malignancy who had either failed to achieve complete remission with initial cisplatin, vinblastine, and bleomycin chemotherapy or who had relapsed after complete response (CR) to this therapy and then proven refractory on retreatment, were treated with etoposide (75 mg/m2 for 3 days), dactinomycin (1 mg/m2 day 1), and methotrexate (30 mg/m2 day 1) (EAM) every 3 weeks. Courses were continued until maximum response without empirical limit, and if complete remission was achieved, two courses of consolidation therapy were given before cessation of treatment. Thirteen patients (25%) were complete responders with residual masses containing fibrosis or benign teratoma being subsequently resected in seven patients. Two patients had persisting viable carcinoma within residual masses that were completely resected, leaving no evidence of disease (NED); the combined CR plus NED rate was 29%. The only pretreatment factor significantly influencing this response rate was tumor volume. Toxicities were moderate, with leukopenia being observed in 28% of patients, but it was severe in only 2%. There was one death from septicemia. Severe nausea and vomiting occurred in only 9% of patients and treatment-related stomatitis was observed in 42%. All patients achieving CR plus NED have been followed for a minimum of 5 years and no relapses have occurred, suggesting that these patients are cured. Unlike other regimens of salvage chemotherapy, this treatment program did not contain cisplatin and it is contended that a completely noncrossresistant drug regimen based on etoposide provides the opportunity to further improve the curability of patients with advanced germ cell cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

An in vivo study of benzene metabolite DNA adduct formation in liver of male New Zealand rabbits.

Rabbits were treated with benzene (586 mg/kg/b.i.d./4 days) after which DNA was isolated from liver and analyzed for adduct formation using the [32P] post-labeling method of Randerath and coworkers (Randerath et al. 1981; Reddy et al. 1984, 1986, 1987). Liver 500 g and 9000 g fractions were analyzed for adducts. There appeared to be several adducts in both the 500 g and 9000 g fractions observed on radioautographs of cellulose-TLC plates. Several adducts were also observed when the 9000 g fraction was studied using HPLC.

Animals↗
PubMed1989

Dose intensity and outcome with combination chemotherapy for germ cell carcinoma. Australasian Germ Cell Trial Group.

Two hundred and fifty-three patients with advanced stage germ cell carcinoma received induction chemotherapy with vinblastine, bleomycin and cisplatin, sometimes with subsequent surgical resection of residual masses. Overall, 191 patients (76%) achieved complete remission or no evidence of disease after surgery (CR + NED). With 64 months median follow-up only 24 patients have relapsed (13%) and 68% of all patients treated are long-term survivors and 84% of patients entering CR + NED are alive. Toxicity with this chemotherapy was considerable, including seven deaths from leukopenia and septicaemia and eight deaths from bleomycin lung toxicity. Dose reductions or omissions of the drug from the treatment programme was necessary with cisplatin in 8% of patients, with vinblastine in 37% and with bleomycin in 35% of patients. Analysis of these alterations in dose intensity for each drug revealed that initial treatment response and subsequent survival were not compromised by reductions in intended doses of drug administered for either vinblastine or bleomycin. Too few patients had dose reductions of cisplatin for meaningful analysis. This apparent lack of major dose-response effect for either vinblastine or bleomycin in the present treatment programme for germ cell carcinoma has prompted the initiation of a randomized study to determine whether deletion of bleomycin from treatment for patients with good prognostic pretreatment characteristics improves the therapeutic index of this very successful therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Acute toxicity and urinary excretion of diphenyldiselenide.

The acute toxicity of diphenyldiselenide (DPDS) in the male Swiss mouse was found to be enhanced by pretreatment with phenobarbital of SKF-525A. DPDS decreased hepatic glutathione content by 50% at 1 h after administration. Following administration of 14C-DPDS, labelled metabolites were found in urine but not in bile or feces. Analysis of the urinary metabolites of 14C-DPDS showed that selenium-containing metabolites elute from a DEAE-Sephadex column in two fractions: the first has not been chemically characterized, while the second peak contained the glucuronide conjugates of C6H4(OH)SeH and C6H5SeH. Virtually all of the administered selenium is excreted within 5 days, while only about 36% of the 14C is excreted in the same time period. This discrepancy indicates metabolic scission of the carbon-selenium bond.

Animals↗
PubMed1989

Studies on the mechanism of benzene toxicity.

Using the 59Fe uptake method of Lee et al. it was shown that erythropoiesis in female mice was inhibited following IP administration of benzene, hydroquinone, p-benzoquinone, and muconaldehyde. Toluene protected against the effects of benzene. Coadministration of phenol plus either hydroquinone or catechol resulted in greatly increased toxicity. The combination of metabolites most effective in reducing iron uptake was hydroquinone plus muconaldehyde. We have also shown that treating animals with benzene leads to the formation of adducts of bone marrow DNA as measured by the 32P-postlabeling technique.

Aldehydes↗
PubMed1989

Activation of bone marrow phagocytes following benzene treatment of mice.

Techniques in flow cytometry/cell sorting were used to characterize the effects of benzene and its metabolites on subpopulations of bone marrow cells. Treatment of male Balb/c mice with benzene (880 mg/kg) or a combination of its metabolites, hydroquinone and phenol (50 mg/kg), resulted in a 30 to 40% decrease in bone marrow cellularity. Flow cytometric analysis revealed two subpopulations of bone marrow cells that could be distinguished by their size and density or granularity. The larger, more dense subpopulation was found to consist predominantly of macrophages and granulocytes as determined by monoclonal antibody binding and by cell sorting. Benzene treatment had no selective cytotoxic effects on subpopulations of bone marrow cells. To determine if benzene treatment activated bone marrow phagocytes, we quantified production of hydrogen peroxide by these cells using the fluorescent indicator dye, 2',7'-dichlorofluorescein diacetate. We found that macrophages and granulocytes from bone marrow of treated mice produced 50% more hydrogen peroxide in response to the phorbol ester, 12-O-tetradecanoyl-phorbol-13-acetate than did cells from control animals. It is hypothesized that phagocyte activation and production of cytotoxic reactive oxygen intermediates may contribute to hematotoxicity induced by benzene.

Animals↗
PubMed1989

Mortality patterns among a Native American population in New York State.

This study investigated patterns of mortality among a Native American tribe, the Seneca Nation of Indians (SNI). The names of 962 tribal members reported to have died in New York State between 1955 and the end of 1984 were identified through a review of tribal roll books maintained by the Seneca Nation. Positive matches were obtained for 796 (83%) of these individuals using New York State mortality files for the period under investigation. Standardized Proportionate Mortality Ratios (PMR) were computed for major causes of death based on cause-specific mortality patterns in the New York State population for each sex during the same time period. Significantly elevated risks of mortality were observed for all infectious diseases, tuberculosis, diabetes mellitus, cirrhosis, and accidents. Depressed mortality ratios were noted for deaths due to all cancers combined, and for cancers of the lung, pancreas, breast, and lymphatic/hematopoietic cancers. Changes in mortality risks over time were also observed.

Cause of Death↗
PubMed1988

Comparison of functional outcome of total hip arthroplasties involving four surgical approaches.

One hundred thirty-seven total hip arthroplasty patients had a follow-up evaluation consisting of an orthopaedic physical evaluation, isokinetic strength testing, and collection of demographic and surgical information from medical records. The intraoperative variables of surgical time and blood loss and the functional outcome status of the subjects, as demonstrated by D'Aubigne--Postel ratings and isokinetic strength tests, were compared for various trochanteric management techniques: no osteotomy; complete Charnley-type osteotomy; sharp abductor release; and a wafer technique, in which a wafer of bone was osteotomized from the trochanter to release the abductors. A comparison of the mean values for the variables indicated that the wafer and sharp techniques were superior to the complete and no osteotomy techniques. The wafer technique resulted in statistically significant superior isokinetic strength measured in adduction, flexion, and extension. Surgical time was significantly greater in the complete osteotomy cases and blood loss was least in the wafer cases, although these differences were not significant.

Femur↗