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Biomedical subjects

C Dowling

Publications and source records attributed to C Dowling.

12 recordsLinked to original sources

Cerebral monitoring devices: analysis of complications.

The use of indwelling cerebral monitoring devices (ICMDs) is common in the intensive care of neurosurgical patients. ICMDs are used to measure and treat intracranial pressure (ICP), temperature, blood flow and the microchemical environment. Intracranial hemorrhage (ICH) and infection are risks of ICMD use [4]. This study presents ICMD use at Detroit Receiving Hospital (DRH) from July 1993- March 1997. Analysis of complications associated with ICMD placement will test the hypothesis that complication rate depends upon type of ICMD used. A log of all patients having ICMDs at DRH has been kept since 1993. This log was used to identify complications of ICMD placement. Each case was reviewed and the following data obtained: diagnosis, patient age, initial Glasgow Coma Score, Glasgow Outcome Score, type of ICMD, number of ICMDs per patient, duration of implant and complication. Descriptive and non-parametric statistics were used to compare samples of interest. The following number of ICMDs were placed: 274 ventriculostomies, 229 Camino intra parenchymal ICP monitors, and 33 other ICMDs. Complications in these 536 cases include 21 infections, 15 ICHs, 1 granuloma and 1 persistent cerebrospinal fluid leak. Complication was analyzed as a function of ICMD type using Chi-Square test for independence. The rate of infection and ICH was significantly higher in the ventriculostomy group (p = 0.0001). These results support the hypothesis that complications of ICMD use are due to the type of device implanted. The determinants of ICMD complication is undoubtedly multifactorial. The clinician must consider the complication rate related to a particular ICMD among other factors when choosing to place an ICMD.

Brain Injuries

High resolution MRI of small joints: impact of spatial resolution on diagnostic performance and SNR.

This study focuses on the spatial resolution required for cartilage imaging. The purposes of this study were (I) to analyze the diagnostic performance in diagnosing artificially produced cartilage lesions in a small joint model using an optimized fat saturated three-dimensional gradient-echo sequence, (II) to relate the lesion size and depth as diagnosed in the magnetic resonance images with the corresponding pathologic findings and (III) to assess signal-to-noise (SNR) ratios for each of the protocols. Twenty-five artificial cartilage lesions were created in the knee joints of 10 rabbits. These specimens and seven specimens without lesions were imaged at 1.5 T using a three-dimensional gradient-echo sequence with varying slice thickness, field of view and matrix. A total of 404 corresponding images were selected, 50% with and 50% without cartilage lesions. Six radiologists scored all images according to five levels of confidence and receiver operating characteristic (ROC) analysis was performed. Lesion size and depth were compared to the corresponding pathological specimen sections. Additionally SNR ratios were calculated. ROC analysis of pooled data from all readers showed the highest area under the ROC curve for the sequence with the highest spatial resolution, while the diagnostic performance was significantly lower in the other sequences (p <0.01). Assessment of the lesion size and depth was correct in 45% and 40% respectively with the highest resolution and in 29% and 23% with the lowest resolution. SNR ratios decreased with increasing spatial resolution. In conclusion this study shows that increasing spatial resolution improves diagnostic performance in cartilage lesions, though SNR decreases substantially. Assessment of correct lesion size and depth still is limited.

Animals

Comparison of bupivacaine plus buprenorphine with bupivacaine alone by caudal blockade for post-operative pain relief after hip and knee arthroplasty.

In a double-blind, parallel group trial, 15 patients who were given a caudal injection of 1.8 mg kg-1 of bupivacaine after induction of anaesthesia, were compared with 15 patients in whom 7.2 mg kg-1 of buprenorphine was added to the same dose of bupivacaine, prior to knee or hip replacement surgery. The duration of analgesia was much longer (mean 606 min vs. 126 min P < 0.001) in those receiving added buprenorphine; mean morphine consumption in the first 24 h was halved (14 mg vs. 28 mg) and patient satisfaction greatly increased. There were no significant differences in the incidence of complications although the group which had added buprenorphine had a lower incidence of vomiting.

Aged

Two mutations in the beta-globin polyadenylylation signal reveal extended transcripts and new RNA polyadenylylation sites.

Two mutations in the beta-globin poly(A) signal were identified in Israeli patients with beta +-thalassemia by sequence analysis following PCR. One is a point mutation (AATAAA----AATAAG) and the other is a 5-base-pair deletion (AATAAA----A----). The mutant genes were used to investigate the function of the poly(A) signal in vivo and to evaluate the mechanism whereby these mutations lead to a thalassemic phenotype. Analysis of RNA derived from peripheral blood demonstrated the presence of elongated RNA species in patients carrying either mutation. Other aspects of RNA processing (initiation, splicing) were unimpaired. RNA obtained from the patients carrying the point mutation contained four discrete, extended RNA species, 1500-2900 nucleotides long, which were found to be polyadenylated. Some normal cleavage-polyadenylylation was also observed. The 5-base-pair deletion completely abolished cleavage at the normal site. This deletion mutation resulted in a phenotype of beta +-thalassemia, thus providing evidence that the extended mRNAs are translatable in vivo. Furthermore, additional transcripts, greater than 5 kilobases, presumably mRNA precursors, were found in all RNA samples, including those of nonthalassemic controls. The extended transcripts of the poly(A) mutants, together with the high molecular weight precursors, suggest that the human beta-globin gene transcription unit is significantly longer than previously recognized.

Base Sequence

Regulation of taurine transporter activity in LLC-PK1 cells: role of protein synthesis and protein kinase C activation.

Taurine transporter activity increases after exposure of cultured renal epithelial cells to taurine-free medium for 24 h and decreases after incubation in high (500 microM) taurine. This adaptive response mimics that observed in rat kidney after manipulation of dietary taurine. In order to elucidate potential mechanisms involved in the regulation of beta-amino acid transporter activity, the role of RNA transcription, protein synthesis, and protein import (trafficking), as well as protein kinase C activation, on the control of taurine transport was examined in the continuous proximally derived LLC-PK1 renal cell line. Inhibition of RNA transcription with actinomycin D did not alter the up-regulatory and down-regulatory adaptive responses. Inhibition of protein synthesis with cycloheximide prevented the increased taurine transport in response to taurine-free medium as well as the decrease in taurine transport after exposure to high taurine. Colchicine prevented the response to taurine-free medium but had no effect on the response to high-taurine medium. Exposure of confluent cell monolayers to the active phorbol esters, phorbol 12-myristate 13-acetate and phorbol 12,13 dibutyrate, resulted in a reduction in taurine uptake. The effect was seen within minutes of exposure but was not observed in the presence of the inactive phorbol 4-alpha. This inhibitory action was blocked by staurosporin, an inhibitor of protein kinase C (PKC). Treatment of cells with the diacylglycerol kinase inhibitor R59022, which results in increased intracellular diacylglycerol, a natural stimulant of PKC, also inhibited taurine uptake, providing further evidence for a specific effect of PKC activation.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiloride

Omental angiogenic lipid fraction and bone repair. An experimental study in the rat.

A lipid material extracted from the omentum has previously been shown to contain a potent angiogenetic activator (20), capable of creating intense vasoproliferation in traumatized tissues (19). This study was undertaken to analyze the efficacy of local administration of this omental lipid fraction on osseous vascularization and bone repair. An osteoperiosteal segmental femoral defect in the rat was replaced by a demineralized allogenic bone graft exposed to continuous local delivery of omental lipid via an implanted miniosmotic pump. Saline solution delivered in the same way served as a control. Neovascularization and bone formation in the transplant were quantitatively evaluated by means of dynamic radioisotopic bone imaging, radiographic photodensitometry, microangiography, and biomechanical testing. Compared with the control group, the omental lipid angiogenic fraction-treated specimens showed an 80% overall increase (p less than 0.001) in bone density as well as a twofold increase (p less than 0.001) in regional blood perfusion, maximal at 2 weeks following surgery. At 12 weeks, biomechanical testing demonstrated significantly higher union rate (p less than 0.05) and strength (p less than 0.01) in the treated specimens as compared with the controls. These data demonstrate that the omental lipid fraction factor has potent angiogenic properties that enhance bone blood perfusion and bone regeneration.

Absorptiometry, Photon

Penetration of ceftazidime into intracranial abscess.

The penetration of ceftazidime into intracranial abscess was investigated in nine patients receiving intravenous ceftazidime. Concentrations of antibiotic in pus were measured by a microbiological agar diffusion assay (12 samples) and high performance liquid chromatography (8 samples) at varying times following ceftazidime administration. Concentrations of ceftazidime varying between 2.7 and 27.0 mg/l were detected. The role of ceftazidime in the therapy of intra-cranial abscess of otogenic origin is discussed.

Adult

An initiator codon mutation in ornithine-delta-aminotransferase causing gyrate atrophy of the choroid and retina.

Gyrate atrophy of the choroid and retina (GA) is an autosomal recessive chorioretinal degeneration caused by deficiency of the mitochondrial matrix enzyme, ornithine-delta-aminotransferase (OAT). To study the molecular basis of the mutations causing GA, we cloned and sequenced the human OAT cDNA and determined the intron-exon arrangement of the structural gene. Using the cDNA template, we synthesized antisense RNA probes and performed RNase A protection experiments with RNA from four Lebanese GA patients. We found a probe-target mismatch at the 5' end of the first coding exon and amplified this region of the patients' genomic DNA using the polymerase chain reaction. Sequence analysis showed a G----A transition, changing the initiator ATG (methionine) codon to ATA. This mutation segregates with the GA allele in both pedigrees. Initiation of translation at the closest in-frame methionine codon would truncate OAT by 138 amino acids, eliminating the entire mitochondrial leader sequence and 113 amino acids of the mature peptide.

Choroid

Etiology of growth hormone deficiency in little, Ames, and Snell dwarf mice.

There are three recessive genes (little, Snell, and Ames) which cause dwarfism and GH deficiency in mice. These genes are nonallelic, and in the case of little mice, GH deficiency is isolated, while Snell and Ames dwarfs have deficiencies of GH as well as other anterior pituitary hormones. Previous reports in which restriction endonuclease analyses were used suggested that the GH genes are grossly intact in each of these types of dwarfs. In this report, ultrastructural studies of the anterior pituitary glands of little mice showed a deficiency or absence of secretory granules within somatotropes, while Snell and Ames dwarf pituitaries lacked identifiable somatotropes. Furthermore, there were deficiencies of GH precursor RNA and mRNA in total RNA from little pituitaries, while GH transcripts appeared to be absent in total RNA from Snell or Ames dwarf pituitaries. Thus, the primary defect in little mice may be in the production of GH transcripts, while GH deficiency in Snell and Ames dwarfs is probably due to defects other than alterations of the GH genes.

Animals