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Biomedical subjects

R F Martin

Publications and source records attributed to R F Martin.

At least 37 records · Page 2Linked to original sources
PubMed1997

The acute abdomen. An overview and algorithms.

The diagnosis and management of the patient with an acute abdomen remains one of the most difficult challenges for the surgeon. A thorough understanding of the anatomy and physiology of the abdomen are essential to properly generate a differential diagnosis and to formulate a treatment plan. While recent advances in technology can be extremely helpful in certain situations, they cannot replace a physician's clinical judgment based upon a good history and physical examination. This article provides a general overview of the evaluation of the patient with an acute abdomen. It will also suggest algorithms to consider in the diagnosis and treatment of these patients.

Abdomen↗
PubMed1997

The acute abdomen in the critically ill patient.

The critically ill patient with an acute abdomen represents a great challenge for the surgeon. The physiologic derangement that is associated with the critically ill state both fuels and is fueled by acute abdominal processes. Improvements in critical care and cardiopulmonary bypass technique have allowed for a group of patients to evolve that are susceptible to the complications of prolonged flow states. This article focuses on the abdominal consequences of support of the critically ill patient, as well as, the diagnostic and therapeutic options that are available to treat these patients.

Abdomen↗
PubMed1996

Long-term results of pylorus-preserving pancreatoduodenectomy for chronic pancreatitis.

OBJECTIVE: To assess the long-term outcome of patients following pylorus-preserving pancreatoduodenectomy (PPPD) for chronic pancreatitis. DESIGN: Retrospective study with mean follow-up of 63 months (range, 1 month to 13.7 years). SETTING: Tertiary referral hospital. PATIENTS: Records of all patients who underwent PPPD for chronic pancreatitis at Lahey Clinic were reviewed. All patients who were alive were contacted by telephone. In cases where patients had died, information was gathered from family members and hospital records. RESULTS: Forty-five patients underwent PPPD for disabling chronic pancreatitis. The mean preoperative duration of pain was 50 months, with 32 patients (70%) requiring daily narcotics. In one patient resection of the portal vein was required. One patient died within 30 days of the operation. Forty-one patients (92%) had improvement of pain at 5 years. The mean pain score (on a scale of 0 to 10) was 9.2 preoperatively and 1.5, 0.8, 1.1, and 1.1 at 6 months, 1 year, 2 years, and 5 years, respectively. Thirty-three patients (74%) had a postoperative weight gain to an average of 92% of their pre-illness weight. New-onset diabetes occurred in six patients (14%) by 6 months and in 21 patients (46%) by 5 years. Hypoglycemia was the cause of death in one patient who underwent total pancreatectomy. Four patients died of causes unrelated to PPPD. Marginal ulcers occurred in five patients (10%). Nine patients required late operations. CONCLUSIONS: In selected patients, resection of the head of the pancreas achieves long-term pain improvement in over 90% of cases. The early development of diabetes mellitus is infrequent, but over longer follow-up periods it reaches prevalence rates similar to those described in patients who have not undergone resection. Weight gain in this group was superior to that previously reported for our patients who underwent "standard Whipple" operation for chronic pancreatitis.

Adult↗
PubMed1996

A stereotaxic template atlas of the macaque brain for digital imaging and quantitative neuroanatomy.

A stereotaxic brain atlas of the longtailed macaque (Macaca fascicularis) is presented in a format suitable for use as a template atlas of the macaque brain. It includes most of the brain segmented to show the boundaries of landmark structures such that every point in the brain can be represented by a unique set of coordinates in three-dimensional space and ascribed unambiguously to one and only one primary structure. More than 400 structures are represented, including 360 volumetric structures, which constitute the substance of the brain, and 50 superficial features. To facilitate use with ventriculography, magnetic resonance imaging, and other noninvasive imaging techniques, the stereotaxic space is referenced to internal landmarks, viz., the anterior commissure and posterior commissure; the center of the anterior commissure at the midline is the origin of the stereotaxic axes. Reference of stereotaxis to this bicommissural space facilitates structural comparison with human brain atlases, which are commonly referenced to the biocommissural line. It also facilitates comparison of brains of different nonhuman primate species by providing a template brain against which to compare size and internal variability. Thirty-three coronal sections at 1-mm intervals from the spinomedullary junction to the rostral extreme of the caudate nucleus show most structures of the hindbrain, midbrain, and subcortical forebrain. Separately, four side views and 16 coronal sections show cortical structures. Structures are represented by outlines of their boundaries and labeled according to NeuroNames, a systematic English nomenclature of human and nonhuman primate neuroanatomy. Abbreviations are based on a protocol designed to facilitate cross-species comparisons. Instructions are provided for: (1) locating sites from the Template Atlas in the conventional stereotaxic space of an experimental animal, (2) locating sites identified by conventional stereotaxis in the Template Atlas, and (3) using the Template Atlas to collate, compare, and display image information (e.g., labeled cells, recording sites, stimulation sites, lesions) from multiple animals.

Animals↗
PubMed1996

DNA strand breakage by 125I-decay in a synthetic oligodeoxynucleotide--1. Fragment distribution and evaluation of DMSO protection effect.

A double stranded oligodeoxynucleotide containing a single 125I-dC in a defined location was used to investigate DNA strand breakage resulting from 125I decay. Samples of a 41 bp oligodeoxynucleotide were incubated in 20 mM phosphate buffer (PB), or PB plus 2 M dimethylsulphoxide (DMSO), at 4 degrees C during 18-20 days. The 32P-5'-end labelled DNA fragments produced by 125I decays were separated on denaturing polyacrylamide gels, and the 32P activity in each fragment was determined by scintillation counting after elution of fragments from gel. Most of the breaks, around 90%, occurred within 4-5 nucleotides of the 125I-dC, but DNA breaks were detected up to 16 nucleotides from the decay site. The 125I-dC was located at the 21st nucleotide from the 32P-5'-end label, and since 32P was not detected in fragments longer than 20 nucleotides, it was assumed that all 125I decay events produce at least one break in the 125I-labelled DNA strand. The results show a considerable protection effect of DMSO on DNA breaks at sites >5-6 nucleotides from the 125I location. The probability of breaks in this region was decreased with DMSO by a factor of 2 to 8-fold, suggesting significant role for radical-mediated DNA breaks at the more distant sites. However, the total protection effect of DMSO is rather small: 1.1, because of the small contribution of breakage at distant sites to the total yield.

Base Sequence↗
PubMed1996

DNA strand breakage by 125I-decay in a synthetic oligodeoxynucleotide--2. Quantitative analysis of fragment distribution.

The DNA breakage produced by decay of 125I in a double-stranded 41 bp oligodeoxynucleotide was investigated by DNA sequencing gel analysis. Use of both 5'- and 3'-end 32P labelling of the 125I containing strand provided the single-stranded breakage pattern at either side of the 125I-dC. The asymmetric pattern of breakage relative to the 125I-labelled nucleotide enabled deconvolution of two components of breakage. One of them declines very quickly with nucleotide number from 125I-dC and dominates within 4-5 nucleotides. We assume this component to be associated with neutralisation of charged Te atom resulted from decay, or/and with radiation damage to an initial target other than the deoxyribosyl moiety--probably the bases. The second component depends on the geometrical distance between the 125I atom and deoxyribosyl atoms. These two components are responsible for breakage under conditions limiting radical mediated damage, namely in the presence of 2M dimethylsulphoxide. The third component, associated with radical-mediated damage, contributes to the total breakage during incubation in 20 mM phosphate buffer alone, and under these incubation conditions dominates the breakage beyond 8-9 nucleotides from 125I-dC. The estimated average numbers of single-stranded breaks produced in the 125I-containing strand by each mechanism in 41-mer oligodeoxynucleotide with 125I-dC at 21st position are respectively 2.33, 0.98 and 0.63.

DNA↗
PubMed1996

Modelling of Auger-induced DNA damage by incorporated 125I.

We have analyzed a newly available high resolution and precision repeat of the original Martin and Haseltine experiment which includes the influence of DMSO on the results. The new model includes the production and diffusion of radical species and .OH radical attack on DNA as well as the direct hits. Calculations of single-strand breaks use individual Auger electron along with the tracks of electrons and radical species superimposed on an atomistic model of B-DNA. Comparison of the preliminary calculations with the experiment supports the earlier choice of data for the amount of energy required to produce a single-strand break, i.e. 17.5 eV. In a separate simulation we found that an average of less than two ionizations inducing a single-strand break gave the best fit to experimental data. Direct hits were found to be predominantly occurring at short range while the damage by .OH radicals was mainly of the long-range type.

DNA, Single-Stranded↗
PubMed1996

Noninvasive detection of Helicobacter pylori infection in clinical practice: the 13C urea breath test.

OBJECTIVES: To validate the 13C urea breath test for the detection of Helicobacter pylori infection both before and after treatment. METHODS: 13C urea breath tests with 125-mg and 250-mg doses were carried out on each of 60 infected and 60 noninfected subjects. Results were compared with histological examination of gastric biopsies to establish detection limits. The best cut-off point was used in a clinical trial of the efficacy of the breath test in duodenal ulcer patients before and after antimicrobial therapy. The incremental increase (percentage, delta over baseline in U of delta/mil) in respiratory 13CO2 abundance was associated with histological evidence of H.pylori. Outpatient, tertiary care medical center, and secondary and primary care facilities were included. One hundred twenty healthy asymptomatic subjects and 465 patients with duodenal ulcer disease were studied. The test kit assessed repeatability of breath sample collection and storage and stability of stored samples. Test performance was analyzed by comparison of 125-mg and 250-mg 13C urea with measurements at 30 and 40 min postdose. The test was used to diagnose active H.pylori infection and gauge success of antimicrobial therapy. RESULTS: The test kit results were highly reproducible. The cut-off values were higher with 250-mg compared with 125-mg doses of 13C urea and 40 min compared with 30 min. Using a 125-mg 13C urea and test detection limit of 2.4% at 30 min, the accuracy was 94.8 (95% confidence interval = 92-97%) before antimicrobial therapy and 95.4% (95% confidence interval = 91-98%) after. An increase of 2.4% in the abundance of breath 13CO2 measured 30 min after a 125-mg dose of 13C urea reliably indicated the presence of active H.pylori infection either before or after antimicrobial therapy. The 13C urea breath test provides a simple and reliable and noninvasive method of assessing H.pylori status.

Anti-Bacterial Agents↗
PubMed1996

Radioprotection by DNA ligands.

Molecular studies on the mechanism of radioprotection by Hoechst 33342 have suggested that radioprotective activity might be improved by addition of electron-donating substituents to the ligand. This paper reports the results of experiments with proamine, in which the ethoxy group of Hoechst 33342 has been replaced with a dimethylamino group. Clonogenic survival studies with V79 cells confirmed the expectation of increased radioprotective activity of proamine. Also, proamine is less cytotoxic than Hoechst 33342, which further improves the extent of achievable radioprotection. The more general features of DNA-binding radioprotectors are also discussed in terms of their potential use in cancer radiotherapy. In particular it is proposed that the limited penetration of the compounds through cell layers might enable delivery to epithelial tissues by topical application, with limited access to the tumour via systemic uptake. In this context, the question of whether sufficient concentrations of such radioprotectors can be achieved in vivo has been addressed by experiments with the mouse lung model. In control animals, the ED50 for lethal loss of respiratory function at 16 weeks after irradiation was 19 Gy (single dose). Intravenous injection of Hoechst 33342 before irradiation extended the ED50 to 23 Gy.

Animals↗
PubMed1995

Combined modality treatment of symptomatic pancreatic ductal lithiasis.

OBJECTIVE: To assess the efficacy and safety of the removal of pancreatic duct stones by a combined modality approach in patients with pancreatic ductal lithiasis and recurrent abdominal pain. DESIGN: Retrospective review with a mean follow-up of 19 months (range, 1 to 56 months). SETTING: A tertiary care, private community hospital with a university affiliation. PATIENTS: The records of patients who presented to the hospital or who were referred with recurrent abdominal pain and who were demonstrated to have pancreatic ductal lithiasis between 1989 and 1994 were reviewed. Patients were assessed by their clinical response to pancreatic duct stone extraction by a variety of therapeutic interventions. RESULTS: Fifteen patients were included in the study. One patient was excluded from analysis because of a concurrent choledochocele. Two patients required operative decompression and stone extraction for endoscopically inaccessible stones. Six patients were treated with endoscopic management alone, and six were treated with a combination of extracorporeal shock wave lithotripsy and endoscopic stone retrieval. Twelve patients had complete clearance of the pancreatic duct. One patient had a stone that was not removed, but adequate pancreatic ductal decompression was achieved. The remaining patient had incomplete clearance of pancreatic stone fragments following extracorporeal shock wave lithotripsy but had adequate ductal drainage. No patient has required further therapy or hospitalization for abdominal pain. No complications occurred as a result of any intervention in this study. CONCLUSIONS: A multidisciplinary combined modality approach is a safe and effective method for extracting pancreatic duct stones in symptomatic patients. Stone extraction and reestablishment of adequate ductal drainage appear to relieve symptoms in some patients.

Abdominal Pain↗
PubMed1995

NeuroNames Brain Hierarchy.

The NeuroNames Brain Hierarchy is a structured system of neuroanatomical terminology that provides a comprehensive representation of virtually all human and nonhuman primate brain structures that are identifiable either grossly or in Niss1-stained histological sections. This system was devised for computer applications to address deficiencies in the brain terminology presented in Nomina Anatomica. English terms are listed for 783 structures in nine levels of hierarchical ranking. Abbreviations are provided for all superficial and primary volumetric structures. The substructures that constitute the total volume of every superstructure are identified. Superficial features of the brain are clearly distinguished from internal, volumetric brain structures. Structures found solely in either humans or macaques are identified. The purpose of the NeuroNames Brain Hierarchy is to bring greater standardization to the neuroanatomical terminology used by scientific investigators, clinicians, and students. This effort is consistent with the goals of the Unified Medical Language System program of the National Library of Medicine. It is hoped that the systematic construction of the NeuroNames Brain Hierarchy will facilitate use of the most widely accepted definitions of classical neuroanatomy in quantitative computerized neuroimaging applications. It should provide an accurate structural framework against which to reference the many other kinds of neuroanatomical information that are acquired by modern imaging, mapping, and histological labeling techniques.

Animals↗
PubMed1994

Comparative studies of UV-induced DNA cleavage by structural isomers of an iodinated DNA ligand.

PURPOSE: To evaluate the importance of the position of the halogen atom in iodinated DNA-binding bibenzimidazoles, with respect to sensitization of UV-A-induced DNA breakage. METHODS AND MATERIALS: Three analogues of iodoHoechst 33258, denoted ortho-, meta- and paraiodoHoechst, according to the site of iodine substitution, were synthesized. Plasmid DNA (pBR322) was used to assay UV-A-induced DNA single-strand breaks (ssbs). The location of the sites of strand breakage was determined by DNA sequencing gel analysis, using a 32P-endlabelled oligoDNA with a single binding site for the ligands. RESULTS: A clear trend in decreasing activity of sensitization of UV-induced DNA ssbs was established: ortho- > meta-, para- > iodoHoechst 33258. The sequencing gel studies showed that orthoiodoHoechst was distinct from the other three compounds, with respect to the sites of DNA strand breakage and the chemistry of the cleavage reaction. CONCLUSION: The position of iodine substitution in iodinated bibenzimidazoles determines the location of the carbon-centered radical on the ligand in the minor groove of DNA. DNA strand cleavage is mediated by abstraction of a nearby deoxyribosyl H-atom. Hence, the position of the radical species determines: which deoxyribosyl group is attacked (i.e., site of cleavage relative to the ligand binding site); which H-atom is abstracted, more specifically which of the five deoxyribosyl carbons is involved (i.e., the chemistry of the cleavage reaction), and the stereochemistry of the transition state for the H-atom abstraction (and hence the efficiency or extent of strand breakage). The ortho-compound represents the best example to date of iodinated DNA ligands designed as potential radiation sensitizers, as an extension of the well-established sensitization by halogenated DNA precursors.

Base Sequence↗
PubMed1994

Ultraviolet light-induced cleavage of DNA in the presence of iodoHoechst 33258: the sequence specificity of the reaction.

IodoHoechst 33258 sensitizes DNA to cleavage by near ultraviolet light (UV-A). Following an earlier study which showed that the UV-induced cleavage is at discrete locations corresponding to the ligand binding sites, this paper reports a more extensive analysis of the sequence specificity of cleavage. The experiments involved use of double-stranded DNA synthesised on primed M13 templates. Analysis of cleavage in a 280bp sequence in M13mp18 and a 310bp sequence in three M13mp9 clones ('alpha-32', 'alpha-82' and 'alpha-22') derived from human alpha-DNA, showed that for all of the twenty-nine strong and very strong damage sites, cleavage was at the 3' end of a run of three or more consecutive AT base pairs. The extent of cleavage was higher for sites with consecutive Ts than for consecutive As, and greatest for the sequence cTTTTca. Comparison of three closely-related alpha-DNA clones enabled assessment of single bp changes and essentially confirmed the results of detailed analysis of binding cleavage sites in mp18 and alpha-32. Decreasing the input ratio of iodoHoechst/per bp DNA from 0.13 to 0.013 altered the sequence specificity, and sites possessing only three consecutive AT bps were generally not cleaved. The contributions of both the strength of ligand binding and the efficiency of photolytic cleavage to the overall extent of cleavage by UV/iodoHoechst are discussed, in view of the potential utility of the ligand as a probe of DNA conformation.

Bacteriophage M13↗
PubMed1994

Comparative studies of UV-induced DNA cleavage by analogues of iodoHoechst 33258.

Following the earlier demonstration that iodo-Hoechst 33258 sensitizes DNA and cells to UVA, presumably mediated by formation of a carbon-centred radical on the ligand upon dehalogenation, three isomeric analogues of iodo-Hoechst 33258 have now been studied. The isomers differ in the location of the iodine atom in the phenyl ring of the ligand, relative to the site of attachment of the bibenzimidazole moiety, and are accordingly denoted ortho-, meta- and para-iodoHoechst. Comparison of the ligands with respect to induction of DNA ssb in pBR322 DNA revealed a wide range of activity; (D37's vary by a factor of 37), decreasing in the order: ortho- > meta- and para- > iodoHoechst 33258. Preliminary dehalogenation studies suggest that the higher activity of the ortho isomer results more from increased cross-section for dehalogenation than from increased efficiency of strand breakage per dehalogenation event. However, the chemistry of strand breakage by the ortho-isomer is distinctive, and tentatively assigned to initial attack at the 1'-deoxyribosyl carbon; the other two isomers, like iodo-Hoechst 33258, attack the 5'-carbon. The results are discussed in terms of the spectrum of DNA strand breakage chemistry associated with ionizing radiation, and the potential of DNA strand breaking agents such as the iodoHoechst compounds to study the chemical and biological consequences of the different subclasses of initial DNA damage.

Base Sequence↗
PubMed1994

Bile duct injuries. Spectrum, mechanisms of injury, and their prevention.

Bile duct injuries remain a relatively uncommon but potentially devastating complication of both open procedures and laparoscopic procedures. They may present immediately after a given operation or take years to be recognized. Despite the best intentions of the surgeon, many of these injuries are imminently preventable. Recent advances in laparoscopic procedures have served to remind us of lessons learned from the prelaparoscopic era with respect to injuries of the bile ducts. To conduct any operation safely on or near the biliary system, the surgeon should be familiar with the anatomy and its variations, the nature of the pathologic processes that may enhance the likelihood of causing harm, and, most important, his or her own limitations and the limitations of the system with which he or she has to work.

Bile Ducts↗
PubMed1992

Symptomatic choledochoceles in adults. Endoscopic retrograde cholangiopancreatography recognition and management.

During a 2-year interval, we identified 10 patients with symptoms of pancreaticobiliary disorders and small choledochoceles by endoscopic retrograde cholangiopancreatography. Patients ranged from 36 to 89 years of age. Eight were female. Seven presented with recurrent, acute pancreatitis, two presented with biliary colic, and one presented with cholangitis. Dilated common bile ducts were seen in four patients, and no other biliary lesions were demonstrated in any patients. Five patients were shown to have normal gallbladders by ultrasonographic or computed tomographic criteria. Choledochoceles were identified endoscopically as a bulge above or involving the ampulla. Diagnosis was confirmed by cholangiography. All patients underwent successful unroofing of the choledochocele and sphincterotomy of the common bile duct. One pancreatic sphincterotomy was performed for pancreatic ductal obstruction. We encountered no complications. Hospital stays ranged from 1 to 4 days. Follow-up intervals ranged from 2 to 20 months. At this time, no patients have had any recurrence of symptoms, and none has required rehospitalization or surgery.

Adult↗
PubMed1992

DNA ligands as radiomodifiers: studies with minor-groove binding bibenzimidazoles.

An iodinated bibenzimidazole, iodoHoechst 33258, was previously reported to markedly sensitize DNA and cells to UV-A, exemplifying the potential of iodinated DNA ligands as radiosensitizers, a rational extension of sensitization by halogenated pyrimidines. However, unlike the latter sensitizers, iodoHoechst 33258 is not a sensitizer of ionizing radiation, presumably due to the innate radioprotective properties of the uniodinated ligand. Experiments with purified DNA show that both Hoechst 33258 and Hoechst 33342 decrease the yield the radiation-induced DNA strand breakage. The ligands bind at discrete sites in the minor groove of DNA, and analysis on DNA sequencing gels show pronounced protection at the ligand binding sites, as well as more generalized protection. The extent of protection of strand breakage on plasmid DNA and the fact that it persists in the presence of 0.5 M NaCl (which prevents low affinity ionic binding between the high affinity sites) suggests that the protective effects of bound ligand are not confined to the high affinity binding sites in the minor groove. The mechanisms of this generalized protection is unknown, but there is some evidence indicating that the H-atom donation from the ligand may account for the site-specific protection. The extent of protection is much diminished, but still evident, in the presence of 100 mM mannitol, a known hydroxyl radical scavenger, indicating that some of the protective effects might relate to DNA damage mediated by direct action. Further evaluation of the mechanisms of protection should enable development of both more active radioprotectors and, by elimination of the radioprotective features from halogenated DNA ligands, more effective radiosensitizers.

Benzimidazoles↗