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Biomedical subjects

D Martin

Publications and source records attributed to D Martin.

At least 613 records · Page 34Linked to original sources

Kindling, prenatal exposure to ethanol and postnatal development selectively alter responses of hippocampal pyramidal cells to NMDA.

Our studies suggest that treatments, such as kindling and exposure to ethanol in utero, which produce irreversible pathological changes in brain function also selectively alter neuronal responses to NMDA. We have identified increases in agonist potency, which may result from enhanced NMDA receptor expression, as well as both positive and negative modifications of Mg2+ regulation. There is no proof as yet that NMDA receptor plasticity accounts for the kindling phenomenon, for the cognitive deficits associated with fetal exposure to ethanol or for developmental events. However, all the effects we obtained are in the appropriate direction. The same functional parameters altered by kindling and prenatal exposure to ethanol are also modified during the normal development of the brain. It is tempting to speculate that these pathological stimuli produce their effects through the same mechanisms that would normally be activated by developmental signals.

Animals↗

Effects and interactions of 17 beta-estradiol, T3 and 1,25(OH)2D3 on cultured osteoblasts from mature rats.

Osteoporosis being frequently associated with hyperthyroidism and, mostly after menopause, with deficiency in estrogens, we tried to elucidate the interactions of estrogens and triiodothyronine (T3) with calcitriol by using cultured osteoblast-like cells obtained from mature rat bone. The tested parameters included [3H]thymidine incorporation, evaluation of the alkaline phosphatase activity of the cell layer and osteocalcin production in the culture medium. At physiological concentrations, 17 beta-estradiol and T3 stimulated alkaline phosphatase activity, did not enhance osteocalcin production and slightly inhibited [3H]thymidine incorporation. At higher concentrations, 17 beta-estradiol decreased the alkaline phosphatase and osteocalcin response to calcitriol whereas T3, although decreasing alkaline phosphatase activity, markedly increased the osteocalcin secretion elicited by calcitriol. These observations emphasize the complex physiology of osteoblasts and confirm different behaviors of alkaline phosphatase and of osteocalcin as markers of bone turnover.

Alkaline Phosphatase↗

Regulation of glutamate and aspartate release from the Schaffer collaterals and other projections of CA3 hippocampal pyramidal cells.

Excitatory synaptic transmission in the CNS can be modulated by endogenous substances and metabolic states that alter release of the transmitter, usually glutamate and/or aspartate. To explore this issue, we have studied the release of endogenous glutamate and aspartate from synaptic terminals of the CA3-derived Schaffer collateral, commissural and ipsilateral associational fibers in slices of hippocampal area CA1. These terminals release glutamate and aspartate in about a 5:1 ratio. The release process is modulated by adenosine, by the transmitters themselves and by nerve terminal metabolism. Adenosine inhibits the release of both amino acids by acting upon an A1 receptor. The transmitters, once released, can regulate their further release by acting upon both an NMDA and a non-NMDA (quisqualate/kainate) receptor. Activation of the NMDA receptor enhances the release of both glutamate and aspartate, whereas activation of the non-NMDA receptor depresses the release of aspartate only. Superfusion of CA1 slices with a glucose-deficient medium increases the release of both amino acids and reduces the glutamate/aspartate ratio. These results have implications for the regulation of excitatory synaptic transmission in the CA1 area and for the mechanism of hypoglycemic damage to CA1 pyramidal cells.

Adenosine↗

Four case studies: high-dose epinephrine in cardiac arrest.

Animal and human studies have suggested that higher doses of epinephrine than currently recommended may improve resuscitation rates after prolonged cardiac arrest. Because of our failure to resuscitate four patients with the standard American Heart Association protocol for cardiac arrest, we used a larger dose of epinephrine in an attempt to enhance resuscitative efforts. All patients required CPR and had nonperfusing rhythms for at least 20 minutes. The four patients received from 0.12 to 0.22 mg/kg epinephrine. Within five minutes of high-dose epinephrine, all four patients developed perfusing rhythms with maximum systolic blood pressures ranging from 134 to 220 mm Hg. Cardiac dysrhythmias did not occur after these doses of epinephrine. Only one of four patients had ECG evidence of an acute myocardial infarction. In this patient, the history suggested that the myocardial infarction was a primary event, not the consequence of epinephrine. All four patients sustained severe brain injury leading to their demise. This injury was probably due to prolonged cardiopulmonary arrest and global brain ischemia. Pharmacologic and potential pathophysiologic mechanisms of high-dose epinephrine are reviewed.

Adult↗

Gastrointestinal hormone responses to meals before and after gastric bypass and vertical banded gastroplasty.

The purpose of the study was to examine the gastrointestinal hormone responses to meals in morbidly obese patients before and after Roux-en-Y gastric bypass (GBP; n = 9) or vertical banded gastroplasty (VBG; n = 7). On consecutive days before and after operation, we measured changes in peripheral blood levels of glucose, insulin, enteroglucagon, serotonin, vasoactive intestinal polypeptide (VIP), and cholecystokinin (CCK) in response to a standardized glucose or protein-fat meal. The percentage of excess weight lost at 6 months after operation was 66.3% +/- 4% and 41.8% +/- 5% for GBP and VBG, respectively (p less than 0.01). The 3-hour integrated glucose response to a glucose meal decreased from 145.3 +/- 33.7 to 75.8 +/- 15.7 g min/L (p less than 0.02) after GBP. This was associated with a decrease in 3-hour integrated insulin response from 22.8 +/- 8.2 to 10.5 +/- 4.9 mU min/L. Vertical banded gastroplasty patients had lesser reductions of hyperglycemia and hyperinsulinemia. Neither the CCK, serotonin, nor VIP responses to meals were altered by either operation. The 3-hour integrated enteroglucagon response to glucose increased markedly in GBP patients after operation from 11.8 +/- 6 to 133.4 +/- 38 nmol min/mL (p less than 0.02). This increase in enteroglucagon occurred at the same time as development of dumping symptoms, which occurred exclusively in GBP patients after glucose but not protein. We conclude that (1) GBP surgery for morbid obesity results in amelioration of glucose intolerance and hyperinsulinemia, (2) CCK does not mediate an endocrine satiety effect of surgery, (3) GBP is associated with an exaggerated enteroglucagon response to glucose, and (4) enteroglucagon appears to be a marker of the dumping syndrome in GBP patients.

Adult↗

Revised implantation procedure for programmable automatic implantable cardioverter defibrillator: don't discard the magnet.

The newest implantable defibrillator (Ventak 1550 AICD) introduces radiofrequency telemetric communication that obviates the need for activation and deactivation of the device by a magnet during implantation. We present three of our first ten cases of implantation in which difficulties in intraoperative sensing would have been undetected without use of the magnet for audible evaluation of sensing. Based on this experience, we recommend a revised implantation protocol in which audible confirmation of sensing for 30 to 60 seconds by means of a sterile magnet is performed twice (with a pacemaker, if present in DOO or VOO mode): at the time of system test before induction of arrhythmia with testing cables connected to permit recording of rate, morphology, and ECG interpretation channel signals; and after final connection of the leads to the AICD. This simple additional maneuver is a powerful troubleshooting tool during implantation that permits prompt identification of sensing problems.

Adult↗

Antigenic relationships among the porin proteins of encapsulated Haemophilus influenzae clones.

Monoclonal antibodies (Mabs) specific for Haemophilus influenzae were generated to identify antigenic determinants shared among encapsulated H. influenzae clones. Sixteen MAbs reacted by Western immunoblot with a protein of an approximate molecular size of 40 kilodaltons corresponding to the P2 major outer membrane protein (porin). These MAbs also reacted with purified and recombinant H. influenzae porin. Fourteen of the MAbs recognized cell surface-exposed epitopes, and two of the MAbs, P2-16 and P2-17, identified epitopes that are not present or are not accessible on the cell surface. The reactivity spectrum of the MAb panel was studied by dot immunoassay against 32 serologically nontypeable and 119 encapsulated H. influenzae strains recovered worldwide, representing the major serotype a, b, and d clone families. MAbs P2-4 and P2-6 recognized only serotype b clones assigned to primary phylogenetic division I. These clones account for more than 99% of all invasive episodes worldwide. MAbs P2-3, P2-8, and P2-11 reacted with division I serotype b isolates and also identified all genetically allied strains expressing serotype a and d polysaccharide capsules. In contrast, none of the 16 MAbs reacted with genetically divergent serotype a or b clones assigned to primary phylogenetic division II. These results demonstrate that, in general, the patterns of P2 protein surface epitope exposure are cognate with genetic lineages of encapsulated H. influenzae strains and support the hypothesis that the population structure of encapsulated H. influenzae is predominantly clonal.

Antibodies, Monoclonal↗

CT of malignant anal canal tumors.

Radiation therapy of malignant neoplasms of the anal canal has promising results in the majority of patients if the disease is limited at initial diagnosis. Computed tomography (CT), especially when performed with contrast material injected intravenously, is valuable in the pre- and posttreatment assessment of the anorectal musculature and perirectal nodes. The authors review the anatomy of the anorectal area and their experience with CT evaluation of anal canal cancer in a series of 26 patients. They also discuss their experience with treatment of this cancer in a series of 48 patients.

Anal Canal↗

Fundamental properties of local anesthetics. II. Measured octanol:buffer partition coefficients and pKa values of clinically used drugs.

Because local anesthetic molecules interact with ion channel proteins embedded in membranes to effect impulse blockade, and because their clinical potency often depends on both vascular absorption and distribution into the tissue surrounding the site of deposition, the ability to partition into these various compartments is an important determinant of local anesthetic action. Therefore, the hydrophobic nature of local anesthetics used clinically was characterized by the octanol:buffer partition coefficients of their charged (P+) and neutral (Po) species. This was accomplished by previously described optical methods in which direct spectrophotometric measurement of both the pH-dependent distribution coefficient (Q) and of the ionization permit calculation of the pKa and partition coefficients. The rates of alkaline hydrolysis of ester-linked molecules also were measured to assess potential interference of such hydrolysis with the physicochemical assays. Results indicate that the hydrophobicity of a local anesthetic is increased by manipulation of the molecular structure at three sites: (a) the aromatic ring; (b) the intermediate linking group; and (c) the tertiary amine. Po for the agents studied was 10(3)-10(5) times greater than P+. Although there is no systematic relationship between hydrophobicity and pKa, the latter is greater with ester-linked (pKa = 8.59-9.30) than with amide-linked (pKa = 7.92-8.21) local anesthetics. All of the charged species, with the exception of bupivacaine, selectively partition into the aqueous environment (P+ less than 1.0). The temperature dependence of partitioning of the local anesthetics, measured at 25 and 36 degrees C, indicates an entropy-driven hydrophobic uptake. Solutions buffered with bicarbonate and including 5% CO2 showed the same local anesthetic partitioning as that of CO2-free solutions, suggesting that potentiation of impulse blockade by CO2 is not due to increased membrane uptake. Correlations of physicochemical properties of local anesthetics with potencies on isolated nerve confirm that the more potent local anesthetics have greater octanol:buffer partition coefficients, and that the ester-linked local anesthetics are more potent than their amide-linked counterparts having the same hydrophobicities. The correlations of structure with potency also suggest that the extracellular protonated species may contribute to impulse blockade.

Anesthetics, Local↗

Access to information by patients.

Patient records should be accessible to patients and/or parents or guardians. Hospitals should not be included in broad access to information legislation. Patient access should be included in the Public Hospital Act and in the Mental Health Act. Consistent, clear standards for the release/access of information must be established. Patients should have the right to correct records or include their disagreement. The Public Hospitals Act and the Mental Health Act should be consistent.

Canada↗

[The submental island skin flap. A surgical protocol. Prospects of use].

The authors report their use of a previously undescribed skin flap situated in the submental region and vascularised by the submental artery derived from the facial artery. It is possible to raise flaps as large as 11 cm X 6 cm with an identical colour to that of the face. The pedicle flap can reach any part of the homolateral oral cavity or the lower 2/3 of the homolateral side of the face (with the exception of the nasal region). The free flap, using a good calibre pedicle (including facial arteries and veins, may be as long as 7 cm and appears to be extremely reliable. It is also possible to use a distal or composite pedicle taking a segment of the internal basilar margin. The donor site scar dissimulated under the mandible is perfectly acceptable.

Arteries↗

[Spontaneous dissection of the internal carotid artery. Apropos of 7 cases and a review of the literature].

Since 1978, the authors have observed 7 cases of dissecting aneurysm in the internal carotid artery. Symptoms were severe headache and subsequent neurologic deficit in young persons (3 women, 4 men; mean age 35 years). The underlying pathology was spontaneous dissection of the cervical internal carotid artery, with surgical confirmation in 3 cases and typical angiographic patterns in all cases. Spontaneous dissection of the cervical internal carotid artery is being increasingly recognized as a cause of cerebral ischemia in young adults. Moreover this clinicopathologic event is more common than had previously been supposed. The etiology remains unclear, except in 15% of cases in which dystrophy of the media (Marfan's syndrome) is in cause. No history of cervical trauma can be found. Typical clinical features consist in ipsilateral headache preceding an abrupt neurologic deficit in a 40-year-old person. An incomplete Horner syndrome (oculosympathetic paresis without facial anhidrosis) associated with facial pain and numbness is pathognomonic, but the majority of dissections are less typical. The typical angiographic pattern is an elongated regular stenosis of the high cervical internal carotid artery, 2 cm above the non-involved bulbus ("string sign"). The dissection may modify to a tapered occlusion above the point of origin of the internal carotid artery. The natural course is spontaneous resolution of the stricture, without relapse. Optimal management is non-operative since medical treatment has proved to be efficient. These cases confirm the benign course and overall good prognosis of spontaneous dissections of the internal carotid artery which are not as rare as the scarcity of reports might indicate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Combination radiotherapy and chemotherapy in cancer of the pancreas. Review of the literature and prospects].

Overall prognosis of pancreatic adenocarcinoma is still very poor with median survival around 10 months after radical surgery in operable patients, or after full-dose radiation therapy in non-surgical candidates. In metastatic disease, multidrug chemotherapy regimens give a response rate of around 30% with median survival of 10 months. Random trials conducted by the GITSG in inoperable cases have shown improved results for chemoradiation with 5-FU for radiotherapy alone and a doubling of median survival with a 1-year survival of 40% vs 10%. Incorporation of Adriamycin in these combined modality protocols does not improve the results in terms of survival. Chemoradiation also shows improved results compared with chemotherapy alone. In patients amenable to radical surgery, adjuvant post-operative treatment with chemoradiation gave superior results over surgery alone with a doubling of median survival and a significant improvement of a two-year survival rate (42% versus 15%). Intra-operative radiation therapy leads to better local control but without a significant improvement in survival. With a better understanding of radio-chemotherapy interactions and mechanisms of radiosensitization through continuous infusion of fluorouracil and/or cisplatinum, these encouraging results should be confirmed within the next few years.

Adenocarcinoma↗

[Epidural hematoma of the posterior cranial fossa].

The use of CT scans has entirely modified the prognosis of epidural hematomas of the posterior cranial fossa. The analysis of a personal series of 20 cases diagnosed and treated over a 10 year period, that is 6.5% of E.D.H. cases seen in this hospital, has enabled us: to propose an anatomical study regrouping the different topographic forms observed in the literature as well as in the present series. to check the deceptive radiological appearance of these hematomas. The main sign remains the existence of a cranial fracture at the level of the occipital bone. Repeated CT scans should attempt to localize this lesion. In 15% of our cases, the lesion was only detected on the second CT scan. to recommend a simple and rapid surgical procedure in the ventral decubitus position, which does not involve the foramen magnum approach. This is performed away from the occipital junction of the venous sinus. to underline the progressive decrease in the mortality rate (10%) and the good subsequent prognosis of these apparently serious forms which have left no sequelae.

Adolescent↗