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Biomedical subjects

C Martin

Publications and source records attributed to C Martin.

At least 379 records · Page 21Linked to original sources

Cardiac hypertrophy in chronically anemic fetal sheep: Increased vascularization is associated with increased myocardial expression of vascular endothelial growth factor and hypoxia-inducible factor 1.

OBJECTIVE: Our purpose was to determine whether the increase in fetal cardiac mass and cardiac output in chronic anemia is accompanied by changes in capillary density or size or changes in levels of vascular endothelial growth factor and hypoxia-inducible factor 1, a basic helix-loop-helix transcription factor that has previously been shown to activate vascular endothelial growth factor gene transcription when cultured cells are subjected to hypoxia. STUDY DESIGN: Anemia was induced in near-term ovine fetuses by daily isovolemic hemorrhage. In five fetuses the heart was arrested in diastole, isolated, and fixed at physiologic pressures with adenosine-paraformaldehyde, and morphometric measurements of capillaries were made. In six fetuses cardiac expression of vascular endothelial growth factor and hypoxia-inducible factor 1 protein was detected by Western analysis and vascular endothelial growth factor messenger ribonucleic acid by Northern blot analysis. Eleven age-matched fetuses served as controls. RESULTS: The anemic fetuses compared with controls had a lower hematocrit (14.8% +/- 0.7% vs 35.3% +/- 1.5%) and a greater heart-to-body weight ratio (10.5 +/- 1.1 vs 7.7 +/- 0.5 gm/kg). The minimal capillary diameter was increased and the intercapillary distance was decreased in both right and left ventricles of anemic fetuses compared with controls. Vascular endothelial growth factor protein was increased 4.5-fold, vascular endothelial growth factor messenger ribonucleic acid 3.2-fold, and hypoxia-inducible factor 1alpha protein 3.8-fold in ventricular tissue from anemic fetuses. CONCLUSIONS: In chronic fetal anemia cardiac hypertrophy is accompanied by anatomic changes in myocardial capillary morphometry along with induction of hypoxia-inducible factor 1 and vascular endothelial growth factor. These results provide evidence for a pathway by which anemia-hypoxia may stimulate myocardial vascularization.

Anemia↗

Inorganic phosphate content and free energy change of ATP hydrolysis in regional short-term hibernating myocardium.

OBJECTIVE: Short-term myocardial hibernation is characterized by an adaptation of contractile function to the reduced blood flow, the recovery of creatine phosphate content and lactate balance back towards normal, whereas ATP content remains reduced at a constant level. We examined the hypothesis that, despite the absence of ATP recovery, the short-term hibernating myocardium regains an energetic balance. METHODS: An enzymatic method was modified for the measurement of inorganic phosphate (Pi) in transmural myocardial drill biopsies (about 5 mg). In 12 anaesthetized swine, moderate ischemia was induced by reduction of coronary inflow into the cannulated left anterior descending coronary artery to decrease regional myocardial function (sonomicrometry) by 50%. RESULTS: The development of short-term hibernation was verified by the recovery of creatine phosphate content, the persistence of inotropic reserve in response to dobutamine and the absence of necrosis (triphenyl tetrazolium chloride). At 5-min ischemia, Pi was increased from 3.6 +/- 0.3 (SD) to 8.1 +/- 1.1 mumol/gwet wt (p < 0.05). The free energy of ATP hydrolysis (delta GATP) was decreased from -57.8 +/- 0.8 to -52.2 +/- 1.4 kJ/mol (p < 0.05). The relationships between function and Pi (r = -0.81) and delta GATP (r = -0.83), respectively, during control and at 5-min ischemia became invalid at 90-min ischemia, as myocardial blood flow and function remained reduced at a constant level, but Pi decreased back to 4.9 +/- 0.9 mumol/g (p < 0.05 vs. control and 5-min ischemia), and delta GATP fully recovered back to -57.2 +/- 1.3 kJ/mol (p < 0.05 vs. 5-min ischemia). CONCLUSIONS: In short-term hibernating myocardium, myocardial inorganic phosphate content recovers partially and the free energy change of ATP hydrolysis returns to control values. Contractile function remains reduced by mechanisms other than an energetic deficit.

Adenosine Triphosphate↗

Quality of perioperative antibiotic administration by French anaesthetists.

Antibiotics are the most prescribed drugs in hospitals in France and approximately one-third of prescriptions are for antimicrobial prophylaxis. Although the principles of prophylaxis have been defined over the years, there is still widespread misuse of antimicrobials for that purpose. The aim of this survey was to determine whether prescription of prophylactic antibiotics by French anaesthetists complies with the French Guidelines on Surgical Antibiotic Prophylaxis. Information was sought concerning the agent(s) recommended, the timing of the first dose and the duration of prescription. A total of 1473 French anaesthetists was studied. For the great majority (93%), the first antibiotic dose is administered at time of induction of anaesthesia, as recommended by the guidelines. First- and second-generation cephalosporins are frequently selected, as well as co-amoxiclav. In contrast to the guidelines, third-generation cephalosporins (3GCs) are widely prescribed in digestive and urological surgery and quinolones in urological surgery. Duration of prescription is limited to 48 h by most anaesthetists (94%), however there is a strong tendency to prescribe prophylaxis for longer periods in the immunocompromised and patients undergoing major surgery. This survey indicates discrepancies between the French Guidelines on Surgical Antibiotic Prophylaxis and the current practice of French anaesthetists. Major concerns are the use of antibiotics such as 3GCs or fluoroquinolones and prescription for periods exceeding 48 h. In conclusion, compliance with guidelines for prophylactic antimicrobial administration should be more strict in surgical patients.

Anesthesiology↗

Large surface of cultured human epithelium obtained on a dermal matrix based on live fibroblast-containing fibrin gels.

The aim of this study was to develop a new keratinocyte culture system on a dermal equivalent suitable for skin wound closure. Our dermal matrix is based on a fibrin gel from plasma cryoprecipitate containing live human fibroblast (from human foreskin). Keratinocytes obtained from primary culture according to the Rheinwald and Green method, were seeded on the gel at different seeding ratios. In all cases, the keratinocytes plated on the dermal equivalent grew to confluence and stratified epithelium was obtained within 10-15 days in culture. Early expression of basal membrane proteins was detected by immunostaining with laminin and type IV collagen antibodies. Cell proliferation was detected both in the epidermal layer and in the fibroblast embedded in the gel as assessed by BrdU incorporation. Detachment of composite cultures from dishes or flasks is a simple and quick procedure without the need for dispase treatment. Grafting of composite cultures to nude mice gave rise to an orderly stratified, orthokeratinized epithelium resembling human epidermis. A number of advantages including a large expansion factor without the need of 3T3 feeder layer, the availability of fibrin/plasma cryoprecipitate from blood banks and the versatile manipulation of composite cultures suggest that this system could be suitable for the definitive coverage of severely burned patients.

Adult↗

Partial cloning and differential expression of ryanodine receptor/calcium-release channel genes in human tissues including the hippocampus and cerebellum.

Cellular Ca2+ signalling is an important factor in the control of neuronal metabolism and electrical activity. Although the roles of Ca2+-release channels are well established for skeletal and cardiac muscle, less is known about their expression and roles in the central nervous system, especially in the human brain. We have isolated partial complementary DNAs derived from the human ryanodine receptor Ca2+-release channel genes (ryr1, ryr2 and ryr3), and examined their expression in the human hippocampus and cerebellum. For comparison, we have included in our analysis an inositol trisphosphate Ca2+-release channel type I complementary RNA probe. All four messenger RNAs show widespread distribution in the human hippocampus, where ryr2 is the most abundant isoform, and all four are expressed in the human cerebellum. However, striking differences were seen between ryr and inositol trisphosphate Ca2+-release channel type I complementary RNA expression in the cerebellum, with inositol trisphosphate Ca2+-release channel type I messenger RNA being largely restricted to, and very highly expressed, in Purkinje cells, whereas ryr1, ryr2 and ryr3 were all expressed predominantly in the granular layer. The widespread expression of ryr isoforms in the human hippocampus and cerebellum suggests that ryanodine receptor proteins may have a central role in Ca2+ signalling and Ca2+ homeostasis in the human central nervous system. These may include roles in fundamental processes like synaptic plasticity. Furthermore, these Ca2+-release channels may be involved in pathogenic processes such as excitotoxicity, where excessive rises in intracellular Ca2+ concentration mediate neuronal cell death.

Aged↗

Diagnostic value of the multifrequency tympanometry in active rheumatoid arthritis.

We carried out a functional evaluation of the malleus-incus and incus-stapes joints in 37 patients with rheumatoid arthritis using multifrequency tympanometry. As a reference point, we calculated the resonance point using two different methods, and the results obtained were classified into two groups according to the phase of the disease: active, with clinical affection of the joint and with no medication; and inactive, asymptomatic. The results were compared with previously published criteria indicating normality, which underlined a significant correlation in the analysis of the resonance point between both groups, and which determined the value of multifrequency tympanometry in that stage and reactivation of the rheumatoid arthritis in active phase.

Acoustic Impedance Tests↗

[Lethal portal venous gas after cardiopulmonary arrest].

We report the case of a 51-year-old patient admitted after a transient cardiorespiratory arrest. The abdominal CT scan revealed the presence of hepatic portal venous gas. At laparotomy, a diffuse mesenteric ischaemia was diagnosed. The patient died from multiple organ failure in the subsequent hours. Necrotic bowel is associated with hepatic portal venous gas in 50% of the cases and the current mortality rate is 85%. Gas originates either through intestinal transmucosal passage, either by intraportal bacterial gas production, or through both mechanisms.

Embolism, Air↗

[Survey of 39 South East Group hospital centers on the practice of antibiotic prophylaxis in surgery].

A survey was carried out in 39 hospitals regarding the prescribing of perioperative antibiotics. The day of the survey, hospital pharmacists collected information on prescription patterns of antibiotics and, for 3 days, the duration of their administration. A total of 1,131 cases were surveyed, originating from digestive surgery (20%), orthopaedics (31%), gynaecology (15%), ophthalmic surgery (15%), and others (19%). Duration of surgery was 72 +/- 68 min. For all types of surgeries, antibiotics not recommended by the French consensus conference were prescribed. Third generation cephalosporins were used in 17% of patients in gynaecological surgery. In 20% of cases, antibiotics were administered at an inappropriate time: 9.5% after the beginning of surgery, 8% at the time of pre-medication, and 2.5% the day before surgery. Administration exceeded 48 hours in 10% of the cases. In conclusion, special attention should be paid to limit the prescription of third generation cephalosporins, to inject antibiotic at the induction of anaesthesia and to reduce the duration of their administration.

Antibiotic Prophylaxis↗

Presenting symptoms in patients referred to a multidisciplinary clinic for bone metastases.

Symptom control is the goal of palliative irradiation. Approximately 1 month is required before symptomatic relief is accomplished with radiotherapy. However, many patients with cancer-related pain do not receive adequate analgesics, and opioids are often not prescribed until patients fail to respond to palliative irradiation. The presenting symptoms of 108 patients who were referred to a multidisciplinary clinic for bone metastases were evaluated with the Wisconsin Brief Pain Inventory (BPI). This validated instrument evaluates the severity of pain using a 0-10 scale; 10 represents the worst pain imaginable. The population comprised 65 men (60%) and 43 women whose ages ranged from 33 years to 81 years; median age was 55 years, and 69% of patients were less than 65 years of age. Despite the presence of metastatic disease, 21% of patients were working full-time outside the home, and 6% were employed part-time outside the home; 13% were homemakers. Only 17 patients (16%) were unemployed. The time since diagnosis ranged from 2 weeks to 23 years; the median time since diagnosis was 22 months, and 30% of patients had been diagnosed with the past 6 months. Pain was a presenting symptom in 74% (N = 80) of patients at diagnosis. At its worst, the pain was rated as severe (levels 7-10) by 78% and intolerable (level 10) in 22% of the patients in the 24 hr prior to the clinic appointment. On average, the pain was rated moderate to severe (levels 4-10) in 79% and severe in 23% of patients. Only 45% of patients experienced good relief from the prescribed analgesics, and 23% of patients indicated that the prescribed analgesics were ineffective. This survey demonstrates that bone metastases incur significant pain that is often undertreated with analgesics before antineoplastic therapy is administered.

Adult↗

Cellular differentiation in the shoot epidermis.

The recent advances in defining genes involved in shoot epidermal cell differentiation are impressive, especially the characterisation of genes involved in cellular patterning. The additional influences of environment and hormones on cellular patterning have recently been emphasised, and important connections have been made to changes in vegetative and reproductive growth phases. Despite these advances the cellular basis for differentiation remains less well defined, but now genetic and cell biological analysis from yeast may provide important models on which to develop further understanding.

Arabidopsis↗

The moderating effect of self-esteem in reaction to voice: converging evidence from five studies.

It has been posited that high self-esteem persons (high SEs) are more confident than low self-esteem persons (low SEs) of their capability to provide meaningful input in a decision process. If this is so, then high SEs should be more influenced by their perceived level of voice, relative to low SEs. Survey data from 4 field studies showed that voice was more positively related to various dependent variables among high SEs than low SEs. In Study 5, the authors experimentally manipulated voice as well as participants' beliefs about their capability to provide meaningful input. As expected, voice had a greater impact on the reactions of participants who were led to believe that they were more capable of providing meaningful input. Theoretical implications are discussed.

Adolescent↗

Two bZIP proteins from Antirrhinum flowers preferentially bind a hybrid C-box/G-box motif and help to define a new sub-family of bZIP transcription factors.

Two genes encoding bZIP proteins are expressed in flowers of Antirrhinum majus, predominantly in vascular tissues, carpels and anthers. The sequences of cDNA clones encoding these proteins show them to belong to a distinct sub-family of bZIP proteins which also includes LIP19 from rice and MLIPI5 and OBF1 from maize. The sub-family is characterized by the inclusion of very small proteins consisting of essentially a basic domain and a long leucine zipper. Members also have a conserved upstream open reading frame (uORF) in their 5' leader sequences, implying a common mode of post-transcriptional control. In vitro, the Antirrinum bZIP proteins preferentially bind to a novel hybrid C-box/G-box motif which is found in the promoters of some plant histone genes and of some nuclear-encoded genes with plastidial protein products. Expression of the bZIP proteins in transgenic tobacco under control of the CaMV 35S promoter supports the view that they can regulate expression of genes which contain the preferred target motif within their regulatory sequences, although both enhancement and repression of transcript levels of target genes were observed, indicating that the bZIP proteins probably interact with other factors to modulate transcription in different ways, as has been observed for the small MAF family of bZIP proteins in vertebrates.

Amino Acid Sequence↗

Towards functional characterisation of the members of the R2R3-MYB gene family from Arabidopsis thaliana.

Transcription factors containing a conserved DNA-binding domain similar to that of the proto-oncogene c-myb have been identified in nearly all eukaryotes. MYB-related proteins from plants generally contain two related helix-turn-helix motifs, the R2 and R3 repeats. It was estimated that Arabidopsis thaliana contains more than 100 R2R3-MYB genes. The few cases where functional data are available suggest an important role of these genes in the regulation of secondary metabolism, the control of cell shape, disease resistance, and hormone responses. To determine the full regulatory potential of this large family of regulatory genes, a systematic search for the function of all genes of this family was initiated. Sequence data for more than 90 different A. thaliana R2R3-MYB genes have been obtained. Sequence comparison revealed conserved amino acid motifs shared by subgroups of R2R3-MYB genes in addition to the characteristic DNA-binding domain. No significant clustering of the genes was detected, although they are not uniformly distributed throughout the A. thaliana genome.

Amino Acid Sequence↗

Radiotherapy residents' knowledge of and attitudes toward management of cancer pain.

PURPOSE: To evaluate the fund of knowledge of and attitudes toward cancer pain management of radiotherapy residents across the nation. METHODS: Radiotherapy (XRT) residents who had completed at least a year of training were surveyed by questionnaire. Residents (n = 10) from a training program who had been given instructional resources in cancer pain management skills were compared with residents from across the nation (n = 61). A validated survey used in national Cancer Pain Initiative Role Model Programs was administered by mail. The survey contained 30 questions that evaluated attitude alone (A), knowledge alone (K), and how attitude affects the application of knowledge (A/K). RESULTS: The residents from the training program scored significantly higher in K (p < 0.005) and A/K (p < 0.04) than did the residents across the nation. No difference in scores evaluating A were detected (p = 0.26). Compared with the baseline knowledge of physicians in practice who had attended a workshop on cancer pain management, the national XRT residents had significantly lower scores in A (p < 0.006) and K (p < 0.001); however, no difference was found in A/K scores. After the workshop, the physicians in practice had significant gains in cancer pain management skills (p < 0.006). When the post-instruction survey was compared with the national XRT resident scores, there were marked differences in A (p < 0.00001), K (p < 0.00001) and A/K (p < 0.01). CONCLUSIONS: XRT residents in the United States are empathetic, but knowledge of cancer pain management is lacking. Instruction in the principles of cancer pain management can make a profound difference in knowledge and attitude. There is a need to recognize cancer pain management as a significant aspect of radiotherapeutic practice.

Attitude of Health Personnel↗

Segregation of a missense mutation in the microtubule-associated protein tau gene with familial frontotemporal dementia and parkinsonism.

Frontotemporal dementia and parkinsonism (FTDP) is the second most common cause of neurodegenerative dementia after Alzheimer's disease. Recently, several kindreds with an autosomal dominant form of FTDP have been reported and in some families the pathological locus was mapped to a 2 cM interval on 17q21-22. The MAPT gene, located on 17q21 and coding for the human microtubule-associated protein tau, is a strong candidate gene, since tau-positive neuronal inclusions have been observed in brains from some FTDP patients. Direct sequencing of the MAPT exonic sequences in 21 French FTDP families revealed in six index cases the same missense mutation in exon 10 resulting in a Pro-->Leu change at amino acid 301. Co-segregation of this mutation with the disease was demonstrated by restriction fragment analysis in two families for which several affected relatives were available. The Pro301Leu mutation was not observed in either 50 unrelated French controls or in 11 patients with sporadic frontotemporal dementia. This mutation, which occurs in the second microtubule-binding domain of the MAPT protein, is likely to have a drastic functional consequence. The observation of this mutation in several FTDP families might suggest that disruption of binding of MAPT protein to the microtubule is a key event in the pathogenesis of FTDP.

Adult↗