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Biomedical subjects

L Martin

Publications and source records attributed to L Martin.

At least 397 records · Page 22Linked to original sources

Prehospital diagnosis and treatment of acute myocardial infarction: a north-south perspective. The Cincinnati Heart Project and the Nashville Prehospital TPA Trial.

Intravenous thrombolytic therapy improves left ventricular function and reduces mortality in patients with acute myocardial infarction (AMI). In European and Middle Eastern trials, prehospital delivery of thrombolytic agents by physician-directed mobile intensive care units has been successful. This report describes two independently conceived and performed trials that used cellular telephone transmission of 12-lead ECGs to deliver recombinant tissue plasminogen activator (r-tPA) in the field to patients with AMI. In the Nashville Prehospital TPA Trial, 85 patients with chest pain were evaluated in the field for possible administration of r-tPA over a 6-month period. Three of 85 patients (3.5%) were found to be actual candidates for r-tPA treatment in the field. In phase II (dry-run phase) of the Cincinnati Heart Project, 374 patients were evaluated in the field with 14 documented cases of AMI (3.7%) before r-tPA was placed in ambulances for administration by paramedics. In phase III (active with r-TPA in ambulances), over a 1-year period 103 patients were evaluated with six (5.8%) documented cases of AMI. Three of five r-tPA field treatment decisions by emergency physicians using transmitted 12-lead ECGs were accurate (60%). When patients in phases II and III were combined, only 20 of 477 total patients (4.2%) were documented to have AMI. A decline in paramedic skills was noted because of the infrequent administration of the thrombolytic agent. Combining the Nashville and Cincinnati experiences, only 27 of 562 total patients with chest pain (4.8%) were candidates for prehospital thrombolysis. We conclude that few patients evaluated in the prehospital setting are actual candidates for thrombolytic therapy. Substantial allocation of financial and human resources for prehospital delivery of intravenous thrombolytic therapy does not appear warranted.

Adolescent↗

Prolonged pumpless arteriovenous perfusion for carbon dioxide extraction.

A method of extracorporeal carbon dioxide extraction from the blood using an efficient microporous membrane oxygenator or membrane gas exchanger was evaluated during pumpless arteriovenous perfusions with a view to its application for partial respiratory support. The first study carried out in dogs revealed some increase in cardiac output, cardiac index, and cardiac work, although this increase was less than that normally expected from the added extracorporeal blood flow. In sheep during 3 to 7 days of continuous bypass, there was practically no hemolysis and relatively stable hemoglobin and hematocrit levels, and the platelet counts remained within safe levels. The maximum extracorporeal blood flow tended to decrease from a mean of 1.55 L/min on day 1 to 1.34 L/min on day 3 to 1.28 L/min on day 7. Carbon dioxide extraction remained efficient throughout the perfusion, but there was a minimal decrease from the first day (10.92 mmol/L) to the third day (8.46 mmol/L) at the higher blood carbon dioxide concentrations; it remained stable thereafter at 9.0 mmol/L.

Animals↗

Effects of female sex hormones on lipid metabolism in the uterine epithelium of the mouse.

1. The effects of oestrogen and progesterone on synthesis and composition of lipids in the uterine epithelium were studied. 2. Oestrogen treatment for up to 18 hr resulted in an increased incorporation of [14C]acetate into all classes of lipids, but particularly into cholesterol. 3. Progesterone treatment increased incorporation into all classes of lipids except cholesterol and completely inhibited the oestrogen-induced incorporation into cholesterol. We suggest that this may be the mechanism whereby progesterone blocks uterine epithelial cell proliferation. 4. Oestrogen increased incorporation into all classes of phospholipids, and progesterone pretreatment inhibited the marked oestrogen-induced incorporation into phosphatidylinositol. 5. Both oestrogen and progesterone, but particularly progesterone, increased the epithelial cell phospholipid to cholesterol ratio. 6. Oestrogen induced changes in epithelial phospholipid fatty acyl composition: particularly marked was a time related reduction in 20:4 which was inhibited by progesterone pretreatment to only a minor degree.

Acetates↗

A chemiluminescent immunoassay for urinary thromboxane B2.

Because of the vasoactive properties of thromboxane A2 and other related prostaglandins, much research has been conducted on drugs which alter their levels. Urinary levels of thromboxane B2 and 2,3-dinor thromboxane B2 (major urinary metabolite of thromboxane B2) are used as an indication of thromboxane production in-vivo. In order to accurately measure urinary TXB2 levels of subjects on investigative drugs which lower TXA2 and subsequently TXB2, a simple and sensitive analytical tool becomes necessary. We have thus developed a non-radioisotopic (chemiluminescent) assay for urinary TXB2. Sensitivity has been demonstrated to 5 pg/ml. The method correlates well with gas chromatography/mass spectrometry (the accepted reference method) even without column chromatographic purification prior to the conduct of the chemiluminescent assay (r = 0.96). In addition, we have demonstrated feasibility for a chemiluminescent assay to measure urinary 2,3-dinor TXB2.

Acridines↗

Technique for quantification of LTB4-induced changes in peripheral granulocyte counts in vivo in the rabbit.

A method to quantify leukotriene B4-(LTB4)-induced changes in peripheral granulocyte counts in the rabbit is described. Rabbits were surgically prepared with vascular access ports cannulating the right external jugular vein. This preparation made possible rapid, accurate, and repeated sampling of venous blood. Intravenous infusion of LTB4 (0.5-2 micrograms/mL) into the left marginal ear vein was found reproducibly to cause an initial, rapid (1-5 min) leukopenia (64%-100% reduction) followed by an extended (20-30 min) leukocytosis (121%-178% increase). Saline infusion for 30 min resulted in no changes in peripheral granulocyte number. The method described was sensitive and reproducible enough to allow evaluation of the LTB4 receptor antagonist, LY223982 (10 mg/kg, i.v.), which was shown to block both the leukopenia and the leukocytosis induced by LTB4 infusion.

Animals↗

The effect of lonidamine (LND) on radiation and thermal responses of human and rodent cell lines.

Rodent and human cells were tested for response to Lonidamine (LND) (1-(2,4 dichlorobenzyl) 1-indazol-3-carboxylic acid) combined with radiation or hyperthermia. Lonidamine exposure before, during, and after irradiation caused varying degrees of inhibition of potentially lethal damage (PLD) repair which was cell line dependent. In human glioma, melanoma, squamous cell carcinoma, and fibroblasts, LND exposure did not inhibit or only partially inhibited repair of potentially lethal damage. LND up to 100 micrograms/ml produced only a low level of toxicity in these cells and only slightly inhibited glucose consumption at the maximum concentration. In human glioma cells, LND treatment alone did not inhibit PLD repair, but when combined with hyperthermia treatment at moderate levels easily achievable in the clinic, there was complete inhibition of potentially lethal damage repair. These data suggest that LND effectiveness is cell type dependent. Combinations of LND, hyperthermia, and radiation may be effective in cancer therapy especially in tumors such as glioma in which repair of potentially lethal damage may be extensive.

Animals↗

Radial shortening osteotomy for treatment of Kienböck's disease.

Sixteen patients who had radial shortening osteotomy for treatment of Kienböck's disease were reviewed. Ulnar minus variance averaged 3.3 mm. All patients had conservative management that failed. Six were stage II, six were stage III, and four were stage IV. Average follow-up was 4.5 years. In all patients osteotomies united within 3 months. Thirteen patients were totally relieved of pain, and three had mild pain. Motion in the dorsal palmar plane improved, on average, 15 degrees. Grip strength increased 20% to 30% after the operation. Follow-up radiographs did not show continued collapse of carpal height or disease progression except in one patient. No radiographic evidence of degenerative changes at the distal radioulnar joint materialized. As a safe, reliable, and consistently successful method of managing Kienböck's disease, we strongly recommend radial shortening. Excluding the rare extended stage IV disease in which midcarpal arthritis with or without intercarpal instability is present, we have successfully applied this technique to all stages of Kienböck's disease. We recognize that further collapse and progression of disease may occur in stage III and IV disease, as was evident in one patient 5 years after osteotomy.

Adult↗

Effect of estradiol and progesterone on phosphatidylinositol metabolism in the uterine epithelium of the mouse.

The effect of estradiol and progesterone on uterine phosphatidylinositol (PtdIns) metabolism was examined in whole uteri and separated uterine luminal epithelium of ovariectomized mice. Incorporation of [3H]myo-inositol in vitro, into inositol-containing phospholipids extracted from whole uteri, increased in mice injected with estradiol, with maximal incorporation at 9-12 h. The breakdown of PtdIns to inositol polyphosphates was also stimulated in whole uteri by estrogen, with an abrupt increase between 6 and 9 h. Comparable increases in both processes occurred in the uterine epithelium after estrogen stimulation and were inhibited by progesterone pretreatment which by itself had little or no effect. These results suggest that PtdIns metabolism is involved in the stimulation of uterine epithelial cell proliferation by estrogens, and its inhibition by progesterone.

Animals↗

Effect of early ovariectomy and steroid hormone replacement of embryo transport, development and implantation in mice.

Bilateral ovariectomy on Day 1 of pregnancy increased abnormal embryo numbers on Day 4 and delayed passage of embryos to the uterus. Progestins given on Day 1 reversed these effects; given on Day 3 they reduced numbers of abnormal embryos, but did not restore normal transport. Oestrogen given alone after ovariectomy increased embryo loss, but restored preimplantation embryo development to normal when given on Day 3 after progestins on Day 1. The results suggested that both oestrogen and progesterone were necessary for normal preimplantation embryo development in vivo. However, although Day-1 progestins produced the greatest improvement in embryo transport and preimplantation development, they supported only low implantation rates compared with progestins starting on Day 3, and no progestin treatment returned implantation rates to normal. Sham ovariectomy on Day 1 also reduced implantation rate, suggesting that surgical stress of Day-1 ovariectomy had major adverse effects on embryo viability. This view was supported by experiments involving unilateral ovariectomy, which produced abnormalities in embryo transport, development and implantation, but only on the operated side. Furthermore, the major abnormality induced in embryo development by unilateral and bilateral ovariectomy, viz embryonic autolysis, was not increased in experiments in which pregnancy was blocked by non-surgical antagonism of progesterone. It is concluded that abnormalities in embryo development induced by early ovariectomy are not caused by a deficit of endogenous hormones, but result largely from effects of surgical trauma on oviduct function which can be reversed by treatment with exogenous hormones.

Animals↗

In vivo myometrial activity in the rat during the oestrous cycle: studies with a novel technique of video laparoscopy.

Previous techniques of recording myometrial activity in vivo gave limited information about the nature of contractions, and disrupted normal reproductive events. To overcome these drawbacks we developed a new in vivo method of video laparoscopy (VL). This involves positioning a laparoscope in the abdomen of anaesthetized rats to view the caudal ends of both uterine horns. Myometrial activity is recorded by video camera onto video tape. Myometrial contractions are classified according to the muscle layers involved, the interaction between layers and the direction of propagation. Experiments with intrauterine balloons and electromyography (EMG) in conscious and ketamine/xylazine anaesthetized rats showed that this anaesthetic does not have major effects on myometrial activity. To validate the VL method, recordings were obtained throughout the oestrous cycle and compared with results obtained with EMG in conscious rats. The frequency and pattern of activity were similar with both techniques although more information was obtained from VL. Frequency of contractions was highest in oestrus and dioestrus and lowest in pro-oestrus, when contractions occurred in groups separated by quiescent intervals. At all stages, longitudinal contractions propagating towards the cervix predominated. Circular muscle activity was only seen at oestrus and dioestrus; that at oestrus consisted of weak peristalses, that at dioestrus was more complex. A major advantage of VL is that it does not interfere with the course of the oestrous cycle, pseudopregnancy or early pregnancy.

Anesthesia↗

In vivo myometrial activity during early pregnancy and pseudopregnancy in the rat.

Video-laparoscopic studies in early pregnant and pseudopregnant rats showed large changes in frequency, direction of propagation and nature of myometrial contractions. Day 2 patterns of activity were essentially the same as in unmated animals at the equivalent stage of the cycle. From Days 3 to 5 there was a large increase in longitudinal and circular contractions propagating towards the oviduct, circular contractions making the greatest contribution. This circular activity may be important in retaining and spacing embryos. Circular contractions propagating towards the cervix showed smaller increases and there was a transient diminution in the frequency of longitudinal contractions in this direction on Day 5. In pregnant rats, the frequency of discrete contractions declined on Days 6-7. However, circular tone appeared to be increased and uteri showed dramatic twisting and curling, apparently due to resistance to the shortening imposed by longitudinal contractions. None of the major changes in activity appeared to be caused by embryos, because they were seen in pseudopregnant rats and, after embryo implantation, in both horns of unilaterally pregnant rats. The earliest divergence from the activity patterns of unmated rats occurred when progesterone levels first increased significantly above those of the undisturbed oestrous cycle, suggesting that progesterone has a major influence on myometrial activity. The complexity of the changes in activity raises questions about other regulatory factors, particularly in regard to coordination between the circular and longitudinal muscle layers. Anomalous results from pregnant, unilaterally pregnant, and pseudopregnant animals on Day 7 suggested that embryos exert systemic effects on myometrial activity.

Animals↗

Pace-maker activity in the myometrium of the oestrous rat: in vivo studies using video-laparoscopy.

Female rats had one oviduct, or the cranial tip of one or both uterine horns, lesioned by coagulation, or separated from the remainder of the uterus. After recovery and return to oestrous cycles, myometrial activity at oestrus was analysed by video-laparoscopy. Lesioning the oviduct had no effect on myometrial activity. Coagulating the cranial tip of one horn initially reduced the frequency of ipsilateral longitudinal contractions propagating caudally, but this returned to normal after 14 days. Separating the cranial tip of the uterus had permanent effects on myometrial activity. Separation of one tip reduced the frequency of ipsilateral longitudinal contractions propagating caudally, had no effect on ipsilateral contractions propagating cranially, but reduced the frequency of contralateral contractions propagating cranially. The effect of a lesion near one uterotubal junction on contractions originating contralaterally near the cervix results from communication between uterine horns at the cervical junction; arrival of a caudally propagating contraction in one horn frequently generates a cranially propagating contraction in the other. Separating both uterine tips reduced the frequency of longitudinal contractions propagating in both directions. We conclude that, at oestrus, most spontaneous myometrial contractions are generated by pace-makers in the cranial tip of each uterine horn. The pace-makers are close to the uterotubal junction and regenerate after destruction by coagulation. When their influence is permanently removed, new pace-makers do not develop in myometrium caudal to the lesion. We conclude that most myometrial cells do not exhibit spontaneous pace-maker activity in vivo.

Animals↗

Is the antiprogestin RU486 luteolytic in rats?

Subcutaneous injections of RU486 on Day 1, Day 4 or Days 3 and 4 of pregnancy in rats induced abortion of the embryo and transient vaginal cornification. Nevertheless, most corpora lutea appeared to be functional at autopsy on Day 12. The same treatments in pseudopregnant rats also produced transient vaginal cornification, but did not terminate pseudopregnancy. This suggests that transient antagonism of progesterone by RU486 does not terminate function of the corpus luteum in rats and that positive feedback by progesterone is not essential for continuing luteal function in rats.

Animals↗

Postcopulatory myometrial activity in the rat as seen by video-laparoscopy.

Myometrial activity was analysed by video-laparoscopy in unmated and mated oestrous female rats. In the former, most contractions propagated caudally and were predominantly longitudinal, with circular contractions limited to weak peristalsis. Mating had dramatic effects on activity, inducing a high frequency of strong peristaltic and non-peristaltic circular contractions propagating both cranially and caudally. Activity remained elevated for up to 10 h, decreasing to control levels as uterine contents were lost when the vaginal plug disintegrated. Mechanical stimulation of the cervix, sufficient to induce pseudopregnancy, increased the frequency of weak peristalsis but did not induce myometrial activity comparable to that seen after mating. Treatment of mated females with indomethacin returned myometrial activity towards control levels, suggesting that myometrial stimulation involved prostanoid production. After mating to intact males the uterus took on a characteristic blue colour suggestive of hypoxia. This too was abolished by indomethacin treatment. Removal of accessory reproductive glands from males showed that induction of myometrial activity and the colour change both required constituents from the vas deferens, seminal vesicles and coagulating glands. Males lacking seminal vesicles or coagulating glands were infertile. The prolonged myometrial activity and putative hypoxia induced by seminal constituents may be important in survival and selection of sperm.

Animals↗

Effects of medroxyprogesterone acetate (MPA) on myometrial activity in unmated rats: a study in vivo using video-laparoscopy.

Unmated female rats received medroxyprogesterone acetate (MPA) on the day of oestrus. Myometrial activity in vivo was quantified by video-laparoscopy 24-96 h later. Changes induced by MPA resembled those in early pregnancy/pseudopregnancy, but were not as extreme. There was a significant increase in circular contractions, followed by a decline, as in mated rats. Increases in circular contractions propagating caudally were as large as in mated rats, but increases in those propagating cranially were much smaller and qualitatively different. MPA induced only small increases in the frequency of longitudinal contractions propagating cranially, whereas large increases occurred in pregnancy/pseudopregnancy. We conclude that in early pregnancy/pseudopregnancy, increased circular activity is induced by rising progesterone levels. However, progesterone alone does not account for the increased contractions propagating cranially in mated rats. We suggest that these are induced by increased pacemaker activity in the region of the cervix, possibly activated by stimuli received during copulation.

Animals↗

Malignant combined nevus.

This report describes an example of combined nevus with malignant transformation. The clinical impression was blue nevus. Histologically, the lesion was composed of a cellular blue nevus in the reticular dermis and an overlying compound melanocytic nevus. The junctional component of the melanocytic nevus showed transition to malignant melanoma in situ. A review of the literature failed to find a precedent for the present case.

Cell Nucleus↗

Erythema elevatum diutinum mimicking porphyria cutanea tarda.

A case of erythema elevatum diutinum (EED) closely resembling porphyria cutanea tarda (PCT) is reported. The initial skin biopsies were suggestive for PCT but porphyrin levels in the urine, stool and plasma were normal. A further biopsy from an early cutaneous lesion showed a leucocytoclastic vasculitis with fibrinoid necrosis of the vessel walls.

Adult↗