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Biomedical subjects

M A Simon

Publications and source records attributed to M A Simon.

At least 55 records · Page 3Linked to original sources
PubMed1998

Comparison of the effects and disposition kinetics of articaine and lidocaine in 20 patients undergoing intravenous regional anaesthesia during day case surgery.

The aim of this investigation was to assess the effects and disposition kinetics of the local anaesthetic drugs (+/-) articaine and lidocaine during intravenous regional anaesthesia (IVRA). The mean onset time of surgical analgesia of articaine was 2.5 +/- 1.1 min and that of lidocaine 11.2 +/- 5.1 min (p = 0.0006). None of the patients exhibited objective symptoms of toxicity, either local or systemic, during injection of articaine or lidocaine, nor were there any subjective complaints. No changes in blood pressure, heart rate or oxygen saturation were observed with these local anesthetics at any time during the procedure, nor after deflation of the tourniquet. After releasing the tourniquet, articaine appears in the blood and is rapidly eliminated with a t1/2 alpha of 5 +/- 3 min and a t1/2 beta of 59 +/- 39 min due to hydrolysis. Lidocaine is rapidly and biexponentially eliminated with similar half-lives of t1/2 alpha of 4 +/- 2 min and a t1/2 beta of 79 +/- 31 min. Total body clearance of articaine (8.9 +/- 3.5 L/min) is ten times greater than that of lidocaine (0.9 +/- 0.4 L/min; p = 0.0005). We concluded that both (+/-) articaine and lidocaine are suitable and safe agents for IVRA with rapid onset of good surgical anaesthesia. Articaine is a racemic mixture, which is nowadays considered as less favourable. After releasing the tourniquet, articaine is eliminated with a t1/2 beta of 60 min and lidocaine with a t1/2 beta of 80 min. Quicker onset and shorter elimination time favours (+/-) articaine over lidocaine for IVRA in day case settings so that patients treated with articaine will be 'drug free' more quickly than those who receive lidocaine. Faster elimination and more rapid onset are important advantages for articaine in IVRA for day-case procedures.

Adult↗
PubMed1998

Disposition of lignocaine for intravenous regional anaesthesia during day-case surgery.

Lignocaine is a suitable and safe agent for intravenous regional anaesthesia (IVRA) with rapid onset of good surgical anaesthesia. The onset time of the local anaesthetic action of lignocaine was 11.2 +/- 5.1 min. Satisfactory surgical conditions, evidenced by good sensory blockade were achieved within 20 min, and no additional analgesics were required. There was no trend towards a fixed sequence, radial, median and ulnar in the development of sensory blockade. No patient exhibited objective symptoms of toxicity, either local or systemic, after release of the tourniquet, nor were there any subjective complaints. No changes in blood pressure, heart rate or oxygen saturation were observed at any time during the procedure, or after deflation of the tourniquet. After releasing the tourniquet lignocaine is rapidly and biexponentially eliminated, with a t1/2a of 4.3 +/- 2.1 min and a t1/2 beta of 79.1 +/- 31.2 min. Total body clearance was 0.86 +/- 0.39 L min-1. Eight patients showed rapid release of lignocaine from the exsanguinated area. In two patients the systemic plasma concentration of lignocaine increased more slowly than in the remaining eight. This can be explained by a greater degree of lignocaine absorbtion in the tissues of the arm. Pharmacokinetic constants after rapid and slow absorption were calculated.

Adult↗
PubMed1998

Disabled is a putative adaptor protein that functions during signaling by the sevenless receptor tyrosine kinase.

DRK, the Drosophila homolog of the SH2-SH3 domain adaptor protein Grb2, is required during signaling by the sevenless receptor tyrosine kinase (SEV). One role of DRK is to provide a link between activated SEV and the Ras1 activator SOS. We have investigated the possibility that DRK performs other functions by identifying additional DRK-binding proteins. We show that the phosphotyrosine-binding (PTB) domain-containing protein Disabled (DAB) binds to the DRK SH3 domains. DAB is expressed in the ommatidial clusters, and loss of DAB function disrupts ommatidial development. Moreover, reduction of DAB function attenuates signaling by a constitutively activated SEV. Our biochemical analysis suggests that DAB binds SEV directly via its PTB domain, becomes tyrosine phosphorylated upon SEV activation, and then serves as an adaptor protein for SH2 domain-containing proteins. Taken together, these results indicate that DAB is a novel component of the SEV signaling pathway.

Animals↗
PubMed1998

Src64 is required for ovarian ring canal morphogenesis during Drosophila oogenesis.

The Src family of protein tyrosine kinases have been implicated as important regulators of cellular proliferation, differentiation and function. In order to understand further the role of Src family kinases, we have generated loss-of-function mutations in Src64, one of two Src family kinases known in Drosophila melanogaster. Animals with reduced Src64 function develop normally and are fully viable. However, Src64 female flies have reduced fertility, which is associated with the incomplete transfer of cytoplasm from nurse cells to the developing oocyte. Analysis of Src64 egg chambers showed defects in the ring canals that interconnect the oocyte and its 15 associated nurse cells. Src64 ring canals fail to accumulate the high levels of tyrosine phosphorylation that are normally present. Despite the reduced tyrosine phosphorylation, known ring canal components such as filamentous actin, a ring canal-specific product of the hu-li tai shao gene, and the kelch protein localize properly. However, Src64 ring canals are reduced in size and frequently degenerate. These results indicate that Src64 is required for the proper growth and stability of the ovarian ring canals.

Animals↗
PubMed1997

mirror encodes a novel PBX-class homeoprotein that functions in the definition of the dorsal-ventral border in the Drosophila eye.

The Drosophila eye is composed of dorsal and ventral mirror-image fields of opposite chiral forms of ommatidia. The boundary between these fields is known as the equator. We describe a novel gene, mirror (mrr), which is expressed in the dorsal half of the eye and plays a key role in forming the equator. Ectopic equators can be generated by juxtaposing mrr expressing and nonexpressing cells, and the path of the normal equator can be altered by changing the domain of mrr expression. These observations suggest that mrr is a key component in defining the dorsal-ventral boundary of tissue polarity in the eye. In addition, loss of mrr function leads to embryonic lethality and segmental defects, and its expression pattern suggests that it may also act to define segmental borders. Mirror is a member of the class of homeoproteins defined by the human proto-oncogene PBX1. mrr is similar to the Iroquois genes ara and caup and is located adjacent to them in this recently described homeotic cluster.

Amino Acid Sequence↗
PubMed1997

Regional metabolism of articaine in 10 patients undergoing intravenous regional anaesthesia during day case surgery.

AIMS: To study the pharmacokinetics of articaine and its metabolite articainic acid, in patients undergoing intravenous regional anaesthesia. METHODS: Ten patients (three male, seven female, ASA class 1-2), scheduled for surgery of the hand or forearm were included in the study. Articaine (40 ml, 0.5% solution (200 mg) was injected over 30 s. In total fifteen arterial blood samples were taken; one before injection and then at 10 min intervals, starting 10 min after completion of injection, until the tourniquet was released; thereafter blood samples were drawn at intervals of 1, 5, 10, 15, 20, 25, 30, 45, 60, 75 and 90 min. The tourniquet was released 30 min after completing the injection. RESULTS: During tourniquet application and regional analgesia of 30 min duration, 55% of articaine was hydrolysed by plasma (20%) and tissue (35%) esterase activity to the metabolite articainic acid. After releasing the tourniquet, articaine and its metabolite appeared in the blood; articaine was rapidly eliminated with a t1/2z of approximately 60 min. The plasma concentration of the metabolite articainic acid was the sum of the amount formed during IVRA (55%) and the amount formed after tourniquet release (45%). CONCLUSIONS: Articaine is a safe agent for intravenous regional anaesthesia (IVRA) with rapid onset of good surgical anaesthesia. During tourniquet application and regional analgesia, 55% of the administered dose is already hydrolysed, thus reducing the chance of side effects after tourniquet release.

Anesthesia, Intravenous↗
PubMed1997

A curriculum for the ideal orthopaedic residency. Academic Orthopaedic Society.

The Academic Orthopaedic Society met in April 1994 to discuss manpower issues in orthopaedics. The members developed an approach using the Delphi system to define and obtain consensus on the characteristics of the ideal residency. Six categories of educational attributes were included: General; Clinical Management; Skills and Technical Aspects; Rehabilitation; Basic Science and Research; and Educational Environment. The following year a questionnaire was sent to more than 125 programs in an attempt to have residents and staff anonymously self score their residencies according to the standards defined by the Delphi panels. The results obtained from the 745 responders from 73 programs validate effectively the characteristics of the ideal program and also show the variation among the programs.

Clinical Competence↗
PubMed1997

Bone allografts are immunogenic and may preclude subsequent organ transplants.

The authors report a case of a 41-year-old woman with diabetes and chronic renal failure in whom antihuman leukocyte antigen antibodies developed after she received a frozen bone allograft that limited her access to organ donors. The patient had a chondrosarcoma of the right distal femur. A wide resection with segmental total knee arthroplasty was followed by a revision using a composite bone allograft prosthesis. After revision, broadly reactive lymphocytotoxic antibodies developed in the patient. The patient's panel reactive antibody level rose from 28% to a peak of 70%. Panel reactive antibody expresses the percentage of a panel of human leukocyte antigen type T lymphocytes from 40 individuals (representative of all human leukocyte antigen Class I histocompatibility antigens) to which antihuman leukocyte antigen Class I lymphocytotoxic antibodies have developed in the recipient as measured by the antiglobulin crossmatch method. The specificity of the patient's primary antibody is found in 45% of donors available in Illinois since 1988 (N = 1606). Because a positive crossmatch precludes kidney and pancreas transplantation, at least 45% of cadaver organ donors were excluded from use for this patient. This is an unusual case that focuses on the potential impact of bone allografts in patients who may need subsequent organ transplantation.

Adult↗
PubMed1997

Comparison of the disposition kinetics of lidocaine and (+/-)prilocaine in 20 patients undergoing intravenous regional anaesthesia during day case surgery.

OBJECTIVE: The aim of this investigation was to compare the pharmacokinetics of lidocaine and prilocaine in two groups of 10 patients undergoing intravenous regional anaesthesia. METHOD: The study had a randomized design. The patients were allocated to one of the two groups of 10. Each group received either lidocaine (200 mg = 0.855 mM) or prilocaine (Citanest, 200 mg = 0.909 mM), injected intravenously over a period of 30 s. Onset of the surgical analgesia was defined as the period from the end of the injection of the local anaesthetic to the loss of pinprick sensation in the distribution of all three nerves. RESULTS: The mean onset time of surgical analgesia of lidocaine was 11.2 +/- 5.1 min and that of prilocaine was 10.9 +/- 6.0 min. After releasing the tourniquet, lidocaine is bi-exponentially eliminated with a t1/2 alpha of 4.3 +/- 2.1 min and a t1/2 beta of 79.1 +/- 31.2 min. Total body clearance was 0.86 +/- 0.39 litres/min. Prilocaine is rapidly and bi-exponentially eliminated with a t1/2 alpha of 3.0 +/- 1.6 min and a t1/2 beta of 29.9 +/- 15.7 min. The total body clearance of prilocaine is higher than that of lidocaine, 4.15 +/- 1.31 vs. 0.86 +/- 0.39 litres/min, respectively (P = 0.0007). Both compounds show comparable volumes of distribution (Vd, Vss and V beta) and a comparable t1/2 alpha (4.3 +/- 2.1 vs. 3.0 +/- 1.6 min; P = 0.1780). The t1/2 beta for the two compounds were different (P = 0031); 79.1 +/- 31.2 min for lidocaine and 29.9 +/- 15.7 min for prilocaine. The mean residence time (MRT) of lidocaine (193 +/- 233 min) also differed significantly from that of prilocaine (33.4 +/- 19.9 min; P = 0.0022). CONCLUSION: Lidocaine is preferred for relatively long procedures and prilocaine for short procedures.

Adult↗
PubMed1997

A malignant astrocytoma containing simian virus 40 DNA in a macaque infected with simian immunodeficiency virus.

Polyomaviruses have proven oncogenicity in nonhost experimental animals; however, studies concerning the association between human brain tumors and simian and human polyomaviruses have yielded inconclusive results. We examined the relationship of SV40 to a malignant astrocytoma found in the right frontal lobe of a pigtail macaque (Macaca nemestrina) infected with simian immunodeficiency virus (SIV). Consistent with the histologic diagnosis, the tumor was immunoreactive with antibodies to S-100 protein, vimentin, and glial fibrillary acidic protein, but negative for neurofilament protein, synaptophysin, neuron-specific enolase, and chromogranin A. At the time of SIV inoculation, the animal was seropositive for SV40. Polymerase chain reaction assay of tumor DNA, but not normal brain DNA, yielded a 300 base-pair fragment corresponding to the carboxy-terminal coding region (C-terminus) of the large T antigen gene of SV40, suggesting an association with the tumor.

Animals↗
PubMed1997

Induction of AIDS by simian immunodeficiency virus lacking NF-kappaB and SP1 binding elements.

Rhesus monkeys (Macaca mulatta) were infected with five strains of simian immunodeficiency virus (SIV) derived from SIVmac239 containing deletions (delta) or substitutions (subst) in NF-kappaB and Sp1 binding sites. We have shown previously that mutations in these regions still allow efficient SIVmac replication in primary lymphoid cell cultures (P. O. Ilyinskii and R. C. Desrosiers, J. Virol. 70:3118-3126, 1996). Two animals were inoculated intravenously with each mutant strain of SIVmac239: delta NFkappaB, delta Sp1234, delta NFkappaB delta Sp1234, substSp12, and substSp1234. All but one of the infected animals showed an early spike in plasma antigenemia, maintained high virus burdens, and had significant changes in lymphoid tissues, and six died with AIDS within the first 60 weeks of infection. One of the animals infected with the SIV strain delta NFkappaB delta Sp1234 showed lower levels of plasma antigenemia and lower virus burdens; the other animal infected with this same mutant strain died with AIDS 17 weeks after inoculation. No consistent novel mutations or reversions were detected in proviral sequences derived from the animals infected with the deletion mutants and the substSp12 mutant by 20 weeks postinfection. Point-mutated sequences were partially deleted in both animals infected with the substSp1234 strain. These results indicate that the NF-kappaB and Sp1 binding sites are not essential for the induction of AIDS by SIVmac239. They also provide indirect evidence for the importance of a novel enhancer element in the U3 region of the SIVmac long terminal repeat that is located immediately upstream of the NF-kappaB binding site within the C-terminal region of the nef coding sequence.

Animals↗
PubMed1997

Oncological outcomes of operative treatment of subcutaneous soft-tissue sarcomas of the extremities.

We reviewed the cases of sixty-two patients who had had a subcutaneous sarcoma to determine the effect of tumor and treatment-related variables on the rates of survival and local recurrence. Fifty-nine (95 per cent) of the patients had had an operation at another hospital before being referred to us. Twenty-nine (47 per cent) of the sixty-two tumors were high-grade, forty-two (68 per cent) were small (five centimeters or less), and thirty (48 per cent) were malignant fibrous histiocytomas. We followed a treatment strategy that consisted of repeat excision with the goal of obtaining wide margins. Excluding thirteen patients who had had a palpable local recurrence at the time of presentation, twenty (49 per cent) of forty-one patients who had had a marginal excision at another hospital had microscopic residual tumor on repeat excision. At a median of fifty-six months after the repeat excision, fifty (81 per cent) of the sixty-two patients had been continuously disease-free, one had no evidence of disease, eight had died of the disease, and three had died of other causes. The five-year rate of disease-free survival was 85 per cent (fifty-three of sixty-two patients). There were three local recurrences, all in patients who had had a marginal resection. No recurrences were noted in patients who had had a wide local excision of the tumor or of the previous operative field. Multivariate analysis revealed that a large tumor (greater than five centimeters), a marginal excision, and adjuvant radiation therapy were associated with a worse prognosis. Excellent rates of survival for patients who have a subcutaneous sarcoma, including those who have a large or high-grade tumor and those who have residual tumor following a previous operation, can be obtained with carefully planned operative treatment alone. We recommend operative excision or repeat excision with wide margins because of the high prevalence of residual tumor. Size is the most important tumor-related factor, and the operative margin is the most important treatment-related factor. The additional value of adjuvant radiation therapy remains unproved.

Adolescent↗
PubMed1997

Reconstruction of the lower extremity after ablative resection for cancer.

Limb-sparing surgery for cancer of the lower extremity has ushered the development of composite, one-stage reconstructions that employ a combination of autologous tissues, bone allografts, and endoprosthetic devices. The success of these efforts in preserving limb function has been generally good, yet the ultimate level of function is less than normal. Microsurgery has assumed a progressively greater role in the reconstruction of composite defects and allows much latitude in the surgical planning and in the management of delayed complications. Although patients who opt for limb salvage reconstructions frequently require more operative procedures and have longer hospitalizations than patients undergoing primary amputation, their functional outcome surpasses that of the amputation group and thus justifies the surgical effort.

Humans↗
PubMed1996

Daughter of sevenless is a substrate of the phosphotyrosine phosphatase Corkscrew and functions during sevenless signaling.

The SH2 domain-containing phosphotyrosine phosphatase Corkscrew (CSW) is an essential component of the signaling pathway initiated by the activation of the sevenless receptor tyrosine kinase (SEV) during Drosophila eye development. We have used genetic and biochemical approaches to identify a substrate for CSW. Expression of a catalytically inactive CSW was used to trap CSW in a complex with a 115 kDa tyrosine-phosphorylated substrate. This substrate was purified and identified as the product of the daughter of sevenless (dos) gene. Mutations of dos were identified in a screen for dominant mutations which enhance the phenotype caused by overexpression of inactive CSW during photoreceptor development. Analysis of dos mutations indicates that DOS is a positive component of the SEV signaling pathway and suggests that DOS dephosphorylation by CSW may be a key event during signaling by SEV.

Amino Acid Sequence↗
PubMed1996

Plasticizer-level study of poly(vinyl chloride) ion-selective membranes.

Highly plasticized poly(vinyl chloride) (PVC) membranes (200 per hundred resin [phr]) form the basis of one class of ion-selective electrodes (ISEs). In previous work on the mechanical properties of membranes, the optimal ratio of plasticizer level employed to minimal level required for complete plasticization (phr(exp)/phrmin) was found to be 2.0. The current study was designed to determine whether this ratio is necessary or sufficient for proper ISE function. Dynamic mechanical analysis (DMA) was used to examine the effects of five plasticizers on the dynamic mechanical properties of membranes at three frequencies (110, 11.0, and 1.1 Hz) as a function of temperature (-100 degrees C to +100 degrees C); dioctyl sebacate (DOS), epoxidized propylene glycol dioleate (PGDO), ortho-nitrophenyl octyl ether (o-NPOE), epoxidized soybean oil (ESO), and epoxidized linseed oil (ELO). The glass transition temperature of PVC, which was found to be +77.1 degrees C at 11.0 Hz, was depressed by the addition of 200 phr of each plasticizer from a high of -1.4 degrees C (PGDO at 110 Hz) to a low of -70.2 degrees C (DOS at 1.1 Hz). DMA and electromotive-force (EMF) measurements on membranes plasticized with o-NPOE through a range of phr(exp)/phrmin from 0.5 to 9.3 indicated that a "transition window" occurs between phr(exp)/phrmin of 2.0 and 3.3 in which the membranes change from minimally plasticized polymer films to predictable ion-selective membranes, coinciding with the optimal mechanical properties observed previously. Based on dynamic mechanical properties and EMF response data, the optimal phr(exp)/phrmin++ ratios for membranes as a function of plasticizer were proposed: 0.8 for ESO and ELO, 1.3 for PGDO, 1.7 for DOS, and 3.0 for o-NPOE.

Elasticity↗