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Biomedical subjects

R Hickey

Publications and source records attributed to R Hickey.

At least 19 recordsLinked to original sources
PubMed1992

A comparative study of 0.25% ropivacaine and 0.25% bupivacaine for brachial plexus block.

The present study compares the effectiveness of 0.25% ropivacaine and 0.25% bupivacaine in 44 patients receiving a subclavian perivascular brachial plexus block for upper extremity surgery. The patients were assigned to two equal groups in this randomized, double-blind study; one group received ropivacaine 0.25% (112.5 mg) and the other, bupivacaine 0.25% (112.5 mg), both without epinephrine. Onset times for analgesia and anesthesia in each of the C-5 through T-1 brachial plexus dermatomes did not differ significantly between the two groups. The mean onset time for analgesia ranged from 11.2 to 20.2 min, and the mean onset time for anesthesia ranged from 23.3 to 48.2 min. The onset of motor block differed only with respect to paresis in the hand, with bupivacaine demonstrating a shorter onset time than ropivacaine. The duration of sensory and motor block also was not significantly different between the two groups. The mean duration of analgesia ranged from 9.2 to 13.0 h, and the mean duration of anesthesia ranged from 5.0 to 10.2 h. Both groups required supplementation with peripheral nerve blocks or general anesthesia in a large number of cases, with 9 of the 22 patients in the bupivacaine group and 8 of the 22 patients in the ropivacaine group requiring supplementation to allow surgery to begin. In view of the frequent need for supplementation noted with both 0.25% ropivacaine and 0.25% bupivacaine, we do not recommend using the 0.25% concentrations of these local anesthetics to provide brachial plexus block.

Adult↗
PubMed1992

Helicase inhibition by anthracycline anticancer agents.

Helicases are essential to both DNA replication and transcription because they separate double-stranded DNA, preparing the single strands for replication or transcription. Because the anti-cancer anthracycline antibiotics stabilize double-stranded DNA primarily by their intercalative binding, we expected the intercalated antibiotics to interfere with helicase action. We examined anthracycline antibiotic effects on SV40 large T antigen helicase activity, using a duplex DNA helicase substrate of 32P-labeled 17-mer annealed to complementary M13mp19(+) circular single-stranded DNA. The T antigen helicase activity was potently inhibited by the anthracycline antibiotics. The T antigen helicase IC50 values for the anthracycline antibiotics were as follows: nogalamycin, 2 x 10(-7) M; daunorubicin, 4 x 10(-7) M; doxorubicin, 4 x 10(-7) M; idarubicin, 1.8 x 10(-6) M; 4'-epidoxorubicin, 2 x 10(-6) M; aclacinomycin, 4 x 10(-6) M; and menogaril, 6 x 10(-6) M. Partially purified helicases from HeLa cells and murine mammary carcinoma FM3A cells also were potently inhibited by doxorubicin, with IC50 values of 4 x 10(-7) M and 9 x 10(-7) M, respectively. Because the abundance, specificities, and types of helicases vary in the cell, this site of action for anthracycline antibiotics may help explain anthracycline potency, drug specificity for DNA or RNA inhibition, and some types of cellular resistance to these drugs.

Animals↗
PubMed1991

A dominant positive and negative selectable gene for use in mammalian cells.

We have constructed three different fusion genes containing the herpes simplex virus thymidine kinase (HSV tk) and the bacterial neomycin phosphotransferase (neo) genes. All three fusion genes utilize the HSV tk promoter but differ at the junction of their components. We have determined if the fusion genes are bifunctional by introducing them into mammalian cells and testing for function of the individual components. One of the fusion genes, TNFUS 69, produced a bicistronic message and a fusion protein that has TK and NEO protein functions. This and other fusion genes of a similar nature could serve as dominant positive and negative selectable markers in mammalian cells.

Amino Acid Sequence↗
PubMed1991

A comparison of ropivacaine 0.5% and bupivacaine 0.5% for brachial plexus block.

This study compared the effectiveness of 0.5% ropivacaine and 0.5% bupivacaine for brachial plexus block. Forty-eight patients received a subclavian perivascular brachial plexus block for upper-extremity surgery. One group (n = 24) received ropivacaine 0.5% (175 mg) and a second group (n = 24) received bupivacaine 0.5% (175 mg), both without epinephrine. Onset times for analgesia and anesthesia in each of the C5 through T1 brachial plexus dermatomes did not differ significantly between groups. Duration of analgesia and anesthesia was long (mean duration of analgesia, 13-14 h; mean duration of anesthesia, 9-11 h) and also did not differ significantly between groups. Motor block was profound, with shoulder paralysis as well as hand paresis developing in all of the patients in both groups. Two patients in each group required supplemental blocks before surgery. Ropivacaine 0.5% and bupivacaine 0.5% appeared equally effective in providing brachial plexus anesthesia.

Adult↗
PubMed1990

Evidence for DNA binding activity of numatrin (B23), a cell cycle-regulated nuclear matrix protein.

Stimulation of various cell types with growth factors is associated with a rapid induction in the synthesis of a nuclear matrix protein, termed 'numatrin' which was shown to be identical to the nucleolar protein B23. The abundance of numatrin was shown to be correlated with entry and progression through the S-phase. Thus, experiments were undertaken to examine whether numatrin also has DNA binding activity. Using whole nuclear extract, we showed that numatrin binds to both double-stranded (DS) DNA and to single-stranded (SS) DNA cellulose columns. Purified numatrin, which was extracted either under native conditions (in oligomeric form) or under urea conditions (in monomeric form), demonstrated significant binding to either [3H]DS-DNA or [3H]DS-DNA as shown by nitrocellulose filter binding assay. However, numatrin binding to DS-DNA was qualitatively and quantitatively different from its binding to SS-DNA. Thus, the binding of numatrin was several fold higher to DS-DNA as compared to SS-DNA. The binding to DS-DNA was reduced by 77% in the presence of 0.5 M NaCl, while the binding to SS-DNA was not affected under this condition. Furthermore, treatment of the native numatrin under conditions which caused monomerization of the protein resulted in a significant enhancement of numatrin binding to SS-DNA but did not affect the binding to DS-DNA. Following heparin-Sepharose chromatography purification (under native conditions), numatrin at picomole amounts showed significant binding to both DS-DNA and SS-DNA. Finally, numatrin was found to copurify with the complex of DNA polymerase alpha primase together with other proteins required for SV-40 in vitro replication activity. These results demonstrate that numatrin has DNA binding activity, and imply a possible role for numatrin/B23 in DNA-associated processes.

Blotting, Western↗
PubMed1990

Patterns of failure in anorectal melanoma. A guide to surgical therapy.

Anorectal melanoma is an aggressive tumor with a reported 5-year survival rate of 6%. Recommendations for local surgical therapy vary from local excision to abdominoperineal resection. Therapy, patterns of failure, and survival were retrospectively examined in 32 patients with anorectal melanoma. Twenty-six patients were treated surgically, 14 with abdominoperineal resection and 12 with local excision. Local recurrence occurred less frequently in patients undergoing abdominoperineal resection (4 [29%] of 14) compared with patients undergoing local excision (7 [58%] of 12) but developed concomitantly with distant or regional metastasis in all but 2 of the 11 patients whose operations failed locally. Inguinal nodal disease developed in 15 patients (47%). Pelvic nodal disease became apparent in only 2 patients (7%). There was no difference in overall survival between the two surgically treated groups (median survival, 19.5 months for patients treated with abdominoperineal resection vs 18.9 months for patients treated with local excision). Therefore, local excision is recommended when technically feasible since these patients eventually succumb to metastasis regardless of surgical therapy.

Anal Canal↗
PubMed1990

Brachial plexus block with a new local anaesthetic: 0.5 per cent ropivacaine.

A new local anaesthetic, ropivacaine hydrochloride, was used in a concentration of 0.5 per cent in 32 patients receiving a subclavian perivascular block for upper extremity surgery. One group (n = 15) received 0.5 per cent ropivacaine without epinephrine and a second group (n = 17) received 0.5 per cent ropivacaine with epinephrine in a concentration of 1:200,000. Anaesthesia was achieved in 87 per cent of the patients in both groups in all of the C5 through T1 brachial plexus dermatomes. Motor block was profound with 100 per cent of patients in both groups developing paresis at both the shoulder and hand and 100 per cent developing paralysis at the shoulder. There was a rapid initial onset of sensory block (a mean of less than four minutes for analgesia) with a prolonged duration (a mean of greater than 13 hr of analgesia). The addition of epinephrine did not significantly affect the quality or onset of sensory or motor block. The duration of sensory block was reduced by epinephrine at T1 for analgesia and at C7, C8, and T1 for anaesthesia. The duration of sensory block in the remaining brachial plexus dermatomes as well as the duration of motor block was not effected by epinephrine. There was no evidence of cardiovascular or central nervous system toxicity in either group with a mean dose of 2.5-2.6 mg.kg-1 ropivacaine.

Adult↗
PubMed1990

Plasma concentrations of ropivacaine given with or without epinephrine for brachial plexus block.

The purpose of this study was to determine the pharmacokinetic properties of the local anaesthetic ropivacaine used with or without epinephrine for brachial plexus block. Seventeen ASA physical status I or II adult patients undergoing elective orthopaedic surgery received a single injection of 33 ml ropivacaine for subclavian perivascular block and 5 ml to block the intercostobrachial nerve in the axilla. One group (n = 8) received 0.5 per cent ropivacaine without epinephrine (190 mg) and the other (n = 9) received 0.5 per cent ropivacaine with epinephrine 1:200,000 (190 mg). Plasma ropivacaine concentrations were measured from peripheral venous blood samples taken for 12 hr after drug administration. Ropivacaine base was determined in plasma using gas chromatography and a nitrogen-sensitive detector. The mean peak plasma concentration (Cmax) was 1.6 +/- 0.6 mg.L-1 and 1.3 +/- 0.4 mg.L-1 after administration of ropivacaine with and without epinephrine. The median time to peak plasma concentration (tmax) was 0.75 hr and 0.88 hr and the mean area under the plasma concentration curve AUC0-12h was 7.7 +/- 3.6 and 7.0 +/- 3.4 mg.l hr-1. The differences were not statistically significant. The terminal phase of the individual plasma concentration-time curves showed a varying and sometimes slow decline possibly indicating a sustained systemic uptake of ropivacaine from the brachial plexus. No central nervous system or cardiovascular symptoms attributed to systemic plasma concentrations of the drug were observed, with the dose (1.90-3.28 mg.kg-1) of ropivacaine used. It is concluded that the addition of epinephrine does not alter the pharmacokinetic properties of ropivacaine when used for subclavian perivascular brachial plexus block.

Adult↗
PubMed1989

Subclavian perivascular block: influence of location of paresthesia.

Subclavian perivascular block of the brachial plexus was used in 156 adult patients undergoing orthopedic hand and forearm surgery. The location of the elicited paresthesia prior to deposition of 30 ml of a solution containing 1% mepivacaine, 0.2% tetracaine and 1.200,000 epinephrine was recorded. Twenty minutes later the quality of the block in the distribution of the superior, middle and inferior trunks of the brachial plexus was evaluated. Anesthesia in each of the three trunks was compared with the three sites where the paresthesia was elicited (superior, middle, or inferior trunk). A middle trunk paresthesia was the most successful in producing surgical anesthesia of all three trunks. A superior trunk paresthesia was the paresthesia most often elicited. It resulted in a significantly lower incidence of inferior trunk anesthesia than did a middle or inferior trunk paresthesia. Complications included arterial puncture (25.6%), Horner's syndrome (64.1%), and recurrent laryngeal nerve block (1.3%), with no instances of symptomatic phrenic block or symptomatic pneumothorax.

Adult↗
PubMed1986

Regulation of a human cardiac actin gene introduced into rat L6 myoblasts suggests a defect in their myogenic program.

The rat myogenic cell line L6E9 induces skeletal but not cardiac alpha-actin mRNA upon fusion to form myotubes. However, when a human cardiac alpha-actin gene was introduced into L6E9 myoblasts, differentiation of the cells led to the accumulation of human gene transcripts in parallel with those derived from the endogenous skeletal alpha-actin gene. This result demonstrates that factors which direct rat myogenesis can regulate a muscle gene from another species and that the L6E9 cells may have a defect in their ability to activate endogenous cardiac actin gene expression.

Actins↗
PubMed1975

Anesthetic effects on ventilation in patients with chronic obstructive pulmonary disease.

The effects of 1.0 per cent end-tidal halothane-oxygen anesthesia on spontaneous ventilation, ventilatory deadspace, functional residual capacity (FRC), and alveolar-arterial oxygen difference (A-aD-O-2) were measured in patients with chronic obstructive pulmonary disease and in normal patients of similar age. results obtained were compared with values obtained preoperatively from the same patients. The following were measured: 1) ventilation and ventilatory deadspace, breathing room air and breathing 100 per cent oxygen; 2) functional residual capacity (FRC) and alveolar-arterial oxygen tension difference (A-aD-O-2); 3) forced expiratory volume in 1 second (FEV1.0); 4) ventilatory response to exogenous carbon dioxide. Findings indicated that ventilation is depressed more during halothane anesthesia in patients with emphysema than in normal patients and that the extent of depression is best related to a preoperative measurement of FEV1.0 (P less than 0.001, r = 0.86). The depression in alveolar ventilation results primarily from a reduction in tidal volume. A-aD-O-2 and ventilatory deadspace-to-tidal volume ratio are increaded and FRC decreased with anesthesia in patients with COPD, but the changes are no greater than those found in normal patients.

Anesthesia, Inhalation↗
PubMed1971

Pulmonary artery pressure and alveolar gas exchange in man during acclimatization to 12,470 ft.

Pulmonary hemodynamics and gas exchange were studied in four physicians during 72 hr acclimatization to 12,470 ft. Pulmonary catheters were left in three subjects for 72 hr. Resting mean pulmonary arterial pressure (PAP) rose progressively during the first 24 hr from 10.3 +/-1.0 to 21.1 +/-4.0 torr and remained at this level. During this same 24 hr period cardiac output increased from 7.1 +/-1.4 to 8.4 +/-2.0 liters/min and total pulmonary resistance rose from 122 +/-16 to 209 +/-40 dynes.sec/cm(-5). Excercise at 60 w after 24 hr of hypoxia increased PAP to 28.8 +/-5.1 torr and decreased total pulmonary resistance to 155 +/-25. Shunt fractions were 11 +/-3.8% after 24 hr at altitude and fell to 7 +/-0% after 72 hr. Alveolar to arterial O(2) difference (P(A-a)(O2)) breathing oxygen fell from 116 +/-10.8 to 92 +/-33.3 torr during the same period of acclimatization, whereas dead space to tidal volume ratio (V(D)/V(T)) rose from 33 +/-4.0% to 40 +/-5.3% and P(A-a)(O2) breathing ambient air rose from 8 +/-2.6 to 11 +/-3.0 torr. Inspiratory static lung compliance decreased significantly from a control of 176 +/-8 to 141 +/-8 ml/cm H(2)O after 72 hr of hypoxia. After 4-7 days at altitude, further deterioration in gas exchange was observed after a 5 mile, 1800 ft climb to the summit (14,255 ft) and return. P(A-a)(O2) on air rose from 2.5 +/-2.1 just before starting, to 16.3 +/-2.8 at the summit (rested), and was still 9.0 +/-2.2 several hours after returning. The O(2)-breathing values paralleled these, whereas dead space appeared to fall. We speculate that the hypoxic pulmonary hypertension which develops over 24 hr in some way may be responsible for a reduction of compliance and deterioration in oxygen exchange efficiency, possibly representing a sub-clinical form of pulmonary edema of high altitude. The increased alveolar to arterial O(2) difference induced by hypoxic exercise persists for several hours of hypoxic rest.

Acclimatization↗
PubMed1966

Frostbite.

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Chlorpromazine↗