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Biomedical subjects

D J Smith

Publications and source records attributed to D J Smith.

At least 325 records · Page 18Linked to original sources

Alterations in serotonin binding sites after 5,7-dihydroxytryptamine treatment in the rat spinal cord.

The 5-HT1B subtype of serotonin (5-HT) receptor regulates the release of 5-HT in the rat spinal cord. In an attempt to confirm the presynaptic location of the 5-HT1B receptor, serotonergic nerves were destroyed neurochemically with 5,7-dihydroxytryptamine (5,7-DHT) administered intrathecally. At 3, 7 and 14 days post 5,7-DHT, competitive radioligand binding assays were performed using 2 nM [3H]5-HT and varying concentrations of trifluoromethylphenylpiperazine (TFMPP), a drug which interacts with 5-HT1B and 5-HT1A binding sites (affinity of 5-HT1B site greater than 5-HT1A site for TFMPP). The decrease in 5-HT1B sites that was expected was not observed at any time following the lesion. However, the binding capacity of the 5-HT1B site, as well as the 5-HT1A site, increased significantly by 7 and 14 days postlesion, respectively. Thus, it appears that an up-regulation of 5-HT1B sites occurred that may have obscured the ability to observe a reduction in a small population of sites located on the serotonergic nerve terminals.

5,7-Dihydroxytryptamine↗

Quantitation of N,N,N',N'-tetrakis (2-hydroxypropyl)-ethylenediamine in plasma by gas chromatography.

A wide-bore capillary gas chromatographic method with nitrogen-selective thermionic detection is described for the quantitative analysis of N,N,N',N'-tetrakis (2-hydroxypropyl)ethylenediamine (Quadrol) in plasma. N,N,N',N'-tetrakis (2-hydroxybutyl)ethylenediamine is used as an internal standard. Rat or human plasma samples (0.5 ml) are mixed with internal standard, adjusted to alkaline pH and subjected to a single extraction with dichloromethane. Quadrol recovery from plasma typically exceeds 90%. The method is linear over the range 1.0-50 micrograms/ml. The working detection limit is 0.5 microgram/ml and the analysis time is under 7 min. The procedure has been used to obtain plasma concentration versus time data for the evaluation of Quadrol pharmacokinetics in rats.

Animals↗

Removing broken needles and other foreign objects.

A needle or other foreign body that has penetrated the skin superficially can be located and removed fairly easily. If it is too deeply embedded to be palpated, it should be located by use of an image intensifier and two venipuncture needles. If this is unsuccessful, exploration and removal must be done in the operating room.

Foreign Bodies↗

Achievement of atomic resolution electron microscopy.

Atomic-level details are easily resolved in the latest generation of intermediate voltage electron microscopes, but structural information on the same scale can only be extracted under certain specific conditions. Some understanding of imaging theory, as well as an awareness of correct operating conditions, is required for reliable image interpretation. Several representative examples are chosen to illustrate the possibilities for atomic-resolution imaging of materials, and perspectives and outlook for the technique are briefly discussed.

Image Enhancement↗

Amplification of the isopenicillin N synthetase gene in a strain of Penicillium chrysogenum producing high levels of penicillin.

The isopenicillin N synthetase (IPNS) gene has been isolated from wild-type Penicillium chrysogenum and used as a probe to detect the equivalent gene on Southern blots of genomic DNA from a mutant producing high levels of penicillin. The IPNS gene in this strain is contained within a region of DNA of wild-type restriction pattern that extends for at least 39 kb and is present at between 8 and 16 copies. The steady state level of IPNS mRNA in the mutant producing high levels of penicillin is between 32- and 64-fold of that of the wild type, suggesting that the rate of transcription of some or all of the copies has been increased. In addition we have also shown that both the IPNS mRNA and enzyme is present throughout the growth phase in both strains under the culture conditions used. IPNS enzyme activity is greatly increased in the strain with the high penicillin titre.

Cloning, Molecular↗

Intracellular signals for developmental hemoglobin switching.

We have detected trans-acting factors that regulate developmental hemoglobin switching by fusing erythroid cells of different developmental programs. Adult erythroid cells of one anuran species, Xenopus laevis, were fused with tadpole erythroid cells of another frog, Rana catesbeiana. In a second set of experiments, dimethyl sulfoxide-induced murine erythroleukemia cells, which express only adult mouse globins, were fused with Rana tadpole erythroid cells, which express only embryonic and fetal-like globins. Adult Rana globin gene expression was detected in both sets of transient heterokaryons at 6 hr after fusion. Dot blots and Northern blots of total RNA from the heterokaryons contained material that reacted with an adult Rana alpha-globin probe; newly synthesized adult Rana hemoglobin tetramers were detected with native polyacrylamide gel electrophoresis. These results show that developmental stage-specific transacting factors for globin genes can function across vertebrate classes (mammalia to amphibia) and suggest that the mechanisms that regulate developmental hemoglobin switching are highly conserved.

Animals↗

A local serotonergic component involved in the spinal antinociceptive action of morphine.

Participation of opiate, serotonergic and noradrenergic components in the antinociceptive action of intrathecally administered morphine was evaluated by measuring the ability of subcutaneously administered doses of naloxone, methysergide and phentolamine to alter analgesia. Morphine produced a dose-dependent elevation of the tail-flick latency, due exclusively to local spinal actions. For example, 10 nmol of the drug, when administered intrathecally in rats with bilateral lesions of the dorsolateral funiculus, produced an increase in the tail-flick latency, that was similar to that observed in intact animals. Furthermore, morphine was ineffective when administered intracerebroventricularly into the fourth ventricle of intact rats. The spinal antinociceptive action of the opiate was antagonized by naloxone (ID50 = 0.035 mg/kg, s.c.) but was also significantly attenuated by methysergide (ID50 = 4.28 mg/kg, s.c.). Phentolamine was ineffective. Doses of methysergide that were most effective in reversing the spinal action of morphine also produced hyperalgesia when administered alone. On the other hand, when the dorsolateral funiculus was lesioned, the hyperalgesia was no longer observed, yet the antagonist remained effective against morphine. These data suggested that the doses of methysergide needed to antagonize the action of morphine were in the same range as those needed to block the synaptic actions of serotonin (5-HT) released from the tonically-acting, descending pain inhibitory nerves. The results demonstrate that local opiate, as well as serotonergic, mechanisms mediate the antinociceptive action of morphine in the spinal cord. The recruitment of a serotonergic component may be related to an action of opiates within the spinal cord, to cause the release of serotonin from the terminal fields of the spinipetal serotonergic nerves.

Analgesics↗

Uses and abuses of a biosynthetic dressing for partial skin thickness burns.

The following report reviews 851 applications of Biobrane on partial skin thickness burn wounds awaiting epithelialization. After the patients had been evaluated and resuscitated as needed, the burn wounds were cleansed and debrided. Those evaluated as shallow were treated with Biobrane application. Joint surfaces were splinted for immobilization. The wound was inspected at 24 and 48 h and if any fluid had accumulated it was aspirated and the wound was redressed. When the Biobrane was adherent, the wound was covered with a light dressing and joint immobilization was discontinued. Treatment with Biobrane dressing provided certain advantages over other topical wound care. As the dressing changes were performed less frequently outpatient care was possible, with a resultant decrease in both the length of hospital stay and the ultimate cost of burn care. Wound desiccation is prevented and pain is decreased. Accurate diagnosis of wound depth is crucial if Biobrane is to be used. Very deep wounds will not allow Biobrane adherence, neither will it occur if the wound has a high bacterial count. If joint surfaces are not splinted, the Biobrane will shear and not adhere to the wound. Convex and concave surfaces can be treated with Biobrane, which may need to be meshed.

Adolescent↗

Lipolytic response of bovine adipose tissue to alpha and beta adrenergic agents 30 days pre- and 120 days postpartum.

1. The beta adrenergic agonists isoproterenol and epinephrine stimulated in vitro lipolysis in adipose tissue removed from heifers 30 days pre- and 120 days postpartum. 2. Propranolol, a beta antagonist, blocked isoproterenol stimulated lipolysis pre- and postpartum. 3. Epinephrine co-incubated with propranolol resulted in a suppression of lipolysis similar to that produced by clonidine, an alpha agonist, both pre- and postpartum. 4. Bovine adipose tissue lipolysis was more responsive to isoproterenol and isoproterenol + propranolol at 120 days of lactation than 30 days prepartum. 5. Adipose tissue sensitivity to clonidine, epinephrine and epinephrine + propranolol did not differ 30 days pre- and 120 days postpartum.

Adipose Tissue↗

Effect of diltiazem and a prostaglandin derivative (PGBx) on platelet function during long-term storage.

Calcium is an intermediate messenger between platelet stimuli and platelet response. Published studies have shown that the decreased ability of platelets to control calcium flux during long-term storage leads to platelet senility. Platelet metabolism might be more efficient during storage if pharmacologic agents that limit calcium movement were incorporated into the platelet concentrate storage solution. This hypothesis was tested by storing platelets with the calcium channel blocker, diltiazem, or with a prostaglandin B1 derivative, PGBx. During a 15-day storage period, platelets incubated with either diltiazem or PGBx showed improved function, as measured by aggregation, as compared to control platelets. The PGBx -enhanced platelet function during storage was accompanied by a significant decrease in glucose and an increase in adenosine triphospate concentrations. Platelet function after storage with PGBx improved in spite of significantly lower pH levels of the platelet concentrates at all time points tested. These studies suggest that the maintenance of calcium ion homeostasis during long-term platelet storage is important to in vitro platelet function even if the Ca2+ balance is maintained at the expense of pH and the glucose concentrations.

Blood Preservation↗

Rotational muscle flaps: a new technique for covering infected vascular grafts.

Twenty-one patients with established localized infection of vascular bypass grafts were treated with aggressive debridement and rotational muscle flap coverage to control graft infection. There were six gram-positive, six gram-negative, four mixed, and three fungal graft infections. Graft material included Dacron, Gore-Tex (registered trademark of W. L. Gore Associates Inc., Elkton, Md.), Dacron and Gore-Tex in combination, and saphenous vein. Twenty of 21 patients had successful preservation of graft function, local wound healing, and control of infection. There were no amputations or deaths. The one failure was caused by incomplete debridement of an infected graft segment. Aggressive debridement and rotational muscle flap coverage is an effective means of treating locally infected vascular bypass grafts.

Adult↗

Hospital care of major burns.

The burn patient initially requires many of the same measures as any other trauma patient. Both depth and surface extent of the burn injury should be evaluated. Evaluation for smoke inhalation is important, since this is prevalent and life-threatening among burn victims. A treatment plan begins with a realistic appraisal of the probability of survival. Once goals of management have been established, treatment is aimed at both physiologic and aesthetic rehabilitation.

Burns↗

Cuts and scrapes of knees and elbows.

Knee and elbow injuries are seen frequently by the primary care physician and require prompt and careful treatment in order to prevent infection, preserve joint function, and avoid scarring. A thorough history and physical examination help to rule out more significant damage to the related joint, nerves, or tendons. Immobilization of the joint may be necessary to prevent dehiscence, and the patient should be instructed to return for further examination if signs of infection develop.

Debridement↗

Drug injection injuries of the upper extremity.

The increasing incidence of illicit intravenous drug abuse has reached epidemic proportions in western society. Although the accompanying infectious complications such as hepatitis and acquired immunodeficiency syndrome receive the most notoriety, injection injuries are causing an increasing number of problems. A retrospective review of patients requiring admission for acute or chronic drug injection injuries of the upper extremities was made at the Detroit Receiving Hospital from 1980 through 1985. The demographical, historical, physical, microbiological, and follow-up data were analyzed. The majority of the injuries involved subcutaneous injections into the hand with accompanying inflammatory or infectious complications. The bacteriological data revealed unique characteristics and did not reflect patterns expected from inoculation of normal skin flora. A treatment regimen based on the data is proposed.

Adult↗

The effect of endogenous skin bacteria on burn wound infection.

Burn wound sepsis can be due to exogenous or endogenous bacteria. When rare organisms cause infection, exogenous sources are implicated. This sets into motion hospital infection control team searches, which are both exhausting and harassing to patients and staff. This study examines the skin bacteria present at admission and the frequency of endogenous infection in burn patients. Sixty-two patients with burns up to 92% of the total body surface area underwent unburned skin bacterial surveillance on admission and at weekly intervals using RODAC contact plates. Burn wounds were biopsied for quantitative and qualitative analyses. Morphologically dissimilar colonies were isolated and identified using standard gram-positive and gram-negative identification strips (Analytab Products, Inc. [API]). On admission, the patients harbored Staphylococcus species, many of which were burn wound sepsis were infected with the same organisms cultured from their unburned skin on admission. A subset of patients (14) grew methicillin-resistant Staphylococcus aureus from their wounds or other sites. A comparison with admission isolates showed identical susceptibilities. These data suggest skin is an endogenous source of infection in the burned patient.

Bacteria↗

An analysis of 1,423 facial fractures in 788 patients at an urban trauma center.

The hospital records of all patients presenting to a large urban trauma center emergency department with facial fractures from 1980 through 1984 were reviewed retrospectively. There were 788 patients in the study group, averaging 1.8 fractures per patient for a total of 1,423 facial fractures. The study population had 638 (80.9%) males and 150 (19.1%) females. Racial mix was 71.6% black, 27.8% white, and 0.6% oriental. The most frequent fracture involved the zygoma (23.6%), followed by the orbital floor (21.4%), maxilla, mandible, and nasal bones. The most frequent etiology was assault with a blunt object or fist (70.1%) followed by motor vehicle accidents (13.5%), falls (9.3%), and gunshot wounds (6.1%). Initial diagnostic procedures included a facial X-ray series in 99.9%, tomograms in 43.1%, and CT studies in 8.1%. Surgical intervention was required in 61.2% of cases. Prosthetic materials were used in 8.5% of the cases. At our institution, personal assault was found to be the primary cause of both midface fractures and mandibular fractures.

Adult↗

In vitro and in vivo testing of a collagen sheet to support keratinocyte growth for use as a burn wound covering.

Neonatal Fischer 344 rat keratinocytes were cultured on a collagen sheet to create a 'quasi-skin.' The cells were grown in either control medium or a low-calcium supplemented medium to enhance proliferation. The rate of 3H-thymidine incorporation into DNA was assessed at days 3, 7, 10, and 20 to determine the effectiveness of the medium supplements. The cells grown in supplemented medium did have an elevated rate of incorporation. On days 7 and 14 post culture, the quasi-skin was used to cover full-thickness defects on the dorsum of adult male rats. The covered defects were biopsied 45 and 60 days postoperatively. Light microscopy showed the wounds to be completely re-epithelialized. Barr bodies were present at the wound site, confirming the presence of quasi-skin keratinocytes up to 60 days postoperatively.

Animals↗