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Biomedical subjects

M E Thompson

Publications and source records attributed to M E Thompson.

At least 55 records · Page 3Linked to original sources

Characterization of monoclonal antibodies against ovine prolactin: suitability for use in immunocytochemical analysis of rat prolactin.

The aim of this study was to identify a monoclonal antibody (MAb) suitable for use in the immunocytochemical localization of prolactin in rat tissues. We took advantage of the conservation of certain amino acid sequences in prolactin among species by examining the crossreactivity patterns of five MAb, originally generated to ovine prolactin, with rat prolactin by enzyme-linked immunoassay (ELISA), Western blot analysis, and immunocytochemistry. Two of five antibodies (17D9 and 6F11) showed reactivity with 100 ng of immobilized rat prolactin (NIH RP-3) by ELISA, 6F11 reacting more strongly than 17D9. Only 6F11 reacted with prolactin in lysates of GH4C1 rat pituitary tumor cells by Western blot analysis. When we examined the crossreactivity of the MAb with rat prolactin in monolayer cultures of GH4C1 cells by indirect immunofluorescence, we found that both 17D9 and 6F11 reacted strongly with the cultures. The distribution of staining with 17D9 or 6F11 was coincident with staining with a polyclonal antiserum to rat prolactin. Preabsorption of the antibodies with a 20-fold excess of purified rat prolactin abolished the staining of GH4C1 cell cultures with either antibody. Therefore, we have selected from a series of MAb raised to ovine prolactin two antibodies (17D9 and 6F11) that react specifically with rat prolactin in immunocytochemical studies, whereas 6F11 also reacts strongly with rat prolactin by ELISA and Western blot analysis.

Animals↗

Sensory integrative processing in delinquent-prone and non-delinquent-prone adolescents.

The purposes of this study were to obtain a preliminary description of the sensory integrative and practic abilities of 114 non-delinquent-prone adolescents aged 12 through 18 years and to compare their performances with those of 12 delinquent-prone adolescents with learning problems. Ten of the 17 subtests of the Sensory Integration and Praxis Tests (SIPT) (Ayres, 1989) as well as the Finger Posture Imitation Test (Druker, 1980) and the MacQuarrie Test for Mechanical Ability (MacQuarrie, 1925/1953) were administered to both groups. It was hypothesized that performance on some tests would correlate with age in the non-delinquent-prone adolescents. It was also hypothesized that some delinquent-prone adolescents with learning problems would perform significantly worse on the tests of sensory integrative and practic abilities than would the non-delinquent-prone adolescents. A data analysis indicated that performance on the praxis tests, Manual Form Perception, Graphesthesia, and Bilateral Motor Coordination showed a significant age correlation. The results of this study indicated a difference between the two groups, and it was concluded that the delinquent-prone group performed more poorly on all of the praxis-related tests and on the absolute values of the tests of Postrotary Nystagmus, Standing and Walking Balance, and Bilateral Motor Coordination. Some of the vestibular- and praxis-related tests, therefore, may still provide useful information on children older than 8 years of age.

Adolescent↗

Hypertension, creatinine, and plasma renin activity in heart transplant recipients.

Development of de novo hypertension in a large proportion of orthotopic heart transplant recipients receiving cyclosporine has previously been reported. This hypertension is characterized by a persistence of increased peripheral resistance, sodium retention, and loss of nocturnal decline in BP. Vascular nephropathy with plasma renin activity (PRA) elevation from cyclosporine (CsA) may also be major factor in the progress of hypertension. To investigate this hypothesis, observations of BP, creatinine (Cr), and PRA were made in 144 heart transplant recipients followed for up to four and a half years. Median Cr was 133 mumol/l. Average diastolic BP and mean PRA values were significantly higher in patients with Cr greater than or equal to the median. Cr and PRA were significantly correlated (r = 0.4; P less than 0.001) in recipients with Cr greater than or equal to 133 mumols/l but not in those with Cr less than 133 mumols/l. In a selected subsample of heart transplant recipients with repeated Cr and PRA values, Cr and PRA appeared to increase longitudinally after transplant. These data are derived from a case series of patients managed on a variety of antihypertensive agents (excluding ACE inhibitors) needed to control the persistent hypertension.

Antihypertensive Agents↗

Hypertension following orthotopic cardiac transplantation.

It seems established that hypertension, to some degree, is a frequent consequence of cardiac transplantation. The hypertension occurs de novo and is not related to whether hypertension was present in association with the heart disease that led to the need for transplantation. The etiology of this hypertension is multifactorial and varies depending on the time that has ensued after transplantation. Acutely, it is primarily a problem related to intravascular volume expansion and persistently increased systemic vascular resistance. Although it may be modest in severity, it seems to be particularly resistant to therapy with most antihypertensive drugs. Moreover, the total "hyperbaric impact" of the hypertension is rendered greater because the blood pressure and heart rate in these patients with denervated hearts fails to show the usual 10 to 15 percent fall when recumbent/asleep at night, which occurs in normotensive individuals and in most with hypertension of other etiologies. The major factor in the persistence of the hypertension through the later stages post-transplantation appears to be the cyclosporine that is used as an immunosuppressive. Although cyclosporine has been the major contributor to reduced rejection in these individuals, and to their increasingly prolonged survival, it inevitably produces slowly progressive impairment of renal function. The damage to the kidney is reflected both in tubular as well as glomerular and vascular damage, with a steady fall in glomerular filtration and a rise in creatinine. From our studies it appears that the renal alterations are associated with a gradual rise in plasma renin activity and angiotensin II, which perhaps further damages the kidney and causes persistence of the increased systemic vascular resistance. The use of lower doses of cyclosporine during the ischemic phase in the kidney that immediately follows surgery and of reduced doses over time, often with azathioprine added, seems to minimize the renal damage, or at least to stabilize it and to slow progression of the renal dysfunction and hypertension. Treatment of the hypertension with conventional drugs has definite but limited value. Diuretics and vasodilators have been the mainstay of our approach during the early phases of the hypertension but our recent data indicate that ACE inhibitors may become relatively specific in management during the later phases of the post-transplantation period as PRA levels rise in response to vascular damage by cyclosporine. ACE inhibitors have inherent dangers that require careful monitoring.(ABSTRACT TRUNCATED AT 400 WORDS)

Cyclosporins↗

Responses of nucleus ambiguus neurons to arterial pressure manipulations.

Nearly 69% of nucleus ambiguus neurons in the anesthetized, artificially respired dog responded to nonpharmacological manipulations of arterial pressure (AP). All were active at resting AP, most responded robustly to increased AP, and of these, about half showed activity modulated by the respiratory cycle. Other AP-sensitive neurons fired only during the inspiratory or expiratory phase of the pump-driven respiratory cycle, and were inhibited by increased AP and excited by decreased AP.

Action Potentials↗

Gout in the heart transplant recipient: physiologic puzzle and therapeutic challenge.

PURPOSE: Hyperuricemia and gouty arthritis have been associated with cyclosporine use in renal transplant recipients. Patients requiring heart or heart-lung transplantation may have additional risk factors for the development of gout, yet it has not previously been described in this population. We share herein our clinical experience with gouty arthritis in six heart transplant recipients. PATIENTS AND METHODS: During a one-year period, six hospitalized male heart transplant patients were seen in consultation for gouty arthritis. Five were subsequently followed for gout as outpatients; the sixth died within six months. Management included trials of nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine, allopurinol, and intra-articular steroid injections, as well as attempts to minimize cyclosporine nephrotoxicity. RESULTS: Three patients had gout in remission at time of transplant surgery, and three others developed gout for the first time two to 45 months after transplantation. Following transplant surgery, both pre-existing and new-onset gout appeared to exhibit an accelerated course, with unusually rapid development of chronic polyarticular disease and tophi in four of the five patients followed for more than six months. Peak serum uric acid levels ranged from 11.0 mg/dL to 16.5 mg/dL. NSAIDs produced reversible renal insufficiency in four patients. Gout-related infections occurred in three patients, one of whom died. CONCLUSION: Acute gouty arthritis may occur in the heart transplant recipient despite concomitant use of immunosuppressive drugs. Cyclosporine, with its attendant hypertension and nephrotoxicity, appears to be the major risk factor for hyperuricemia in this setting, leading to the accelerated development of tophi and chronic polyarthritis. Management is complicated by the patients' renal insufficiency and propensity to infection, as well as by interaction with transplant-related medications. Prevention of hyperuricemia by minimizing cyclosporine nephrotoxicity appears to be the best management strategy, with judicious use of allopurinol for those patients in whom this preventive approach fails.

Adult↗

Prehospital providers' AIDS knowledge and attitudes.

Of the 110 career and volunteer prehospital care providers surveyed from two Maryland counties, about 20 percent were concerned about dealing with AIDS patients, including 24 percent who have considered leaving EMS due to the risk of HIV infection.

Acquired Immunodeficiency Syndrome↗

Summation of baroreflex and classically conditioned heart rate responses in dogs.

Following instrumentation with pneumatic cuffs around the inferior vena cava and the descending aorta, dogs were studied either following differential classical conditioning or in a control state. The cuffs functioned to raise and lower blood pressure for the construction of baroreflex curves for heart rate. Conditioned dogs received 8 trials each day with each CS+ (tone paired with flank shock) and CS- (a different tone without shock). Curves were constructed from cuff inflations timed to coincide with the maximum conditioned heart rate response. These curves were constructed from data acquired during infusion of saline, methyl atropine, or propranolol. Comparison of these curves revealed that the CS+ shifted the curves toward higher heart rates while the CS- curve was shifted toward lower heart rates without a change in gain. The amount of shift was comparable to that of the conditioned heart rate response. This suggested that the responses were independent and additive. Neither propranolol nor atropine eliminated this separation between the curves induced by the conditioning. These observations lead us to conclude that classically conditioned stress and baroreceptor stimulation exert independent control over heart rate that are mediated by both sympathetic and parasympathetic influences.

Animals↗

Patient selection and results of cardiac transplantation in patients with cardiomyopathy.

Cardiac transplantation for the treatment of end-stage congestive heart failure has been shown to be of benefit regardless of the etiology. With few exceptions, the evaluation of patients with end-stage heart failure is the same, regardless of the etiology. In those with cardiomyopathy not as a result of CAD, special attention must be given to exclude secondary causes of cardiomyopathy such as amyloidosis, hemochromatosis, and sarcoidosis, as well as generalized systemic illnesses that may also involve the heart, either secondary or hereditary, because special consideration must be given to these patients on a case-by-case basis to determine that there is no general systemic involvement of the illness that would preclude satisfactory rehabilitation after transplantation. Before cardiac transplantation becomes widely available, there must be a greater number of donor hearts, the lack of which now severely limits the number of transplants performed in comparison with the estimated need.66 Additionally, more effective and specific immunosuppressive agents must be identified in order to reduce the incidence of rejection, infection, and accelerated atherosclerosis that now limits the longevity of transplant recipients. Furthermore, the ideal immunosuppressive agent should be associated with fewer side effects than those currently available. The emotional and economic burdens placed on the patient, the family, and society must be balanced against the benefits generated by the procedure. Despite these limitations, cardiac transplantation continues to offer hope for the terminally ill patient, which must be tempered by an understanding of the real limitations of transplantation.

Adolescent↗

Temporary use of the Jarvik-7 total artificial heart before transplantation.

Between October 24, 1985, and July 31, 1986, the Jarvik-7 total artificial heart was implanted into six moribund patients in an attempt to test its potential as a bridge from almost certain death to cardiac transplantation. Four of these patients are now well and at home after implantation of the device and subsequent cardiac transplantation. Before transplantation, one patient died with sepsis and multiorgan failure that preceded implantation of the artificial heart. Another patient died with acute rejection 60 days after cardiac transplantation. Fifty-two days of total mechanical support with the artificial heart were accumulated in these six patients, and although the device worked flawlessly and no clinically apparent thromboembolic events occurred, each artificial heart contained areas of macroscopic aggregations of platelets and thrombi. The results of this trial indicate that in properly selected cases, direct benefit to the patient can be obtained when the Jarvik-7 artificial heart is used as a bridge to transplantation.

Adult↗

Effects of high intensity ultrasound on inorganic solids.

Ultrasonic irradiation dramatically affects the reactivity of a variety of inorganic solids. We have found, for example, large increases in the rates of intercalation of a wide range of compounds into various layered inorganic solids (such as ZrS2, V2O5, TaS2 and MoO3. High intensity ultrasound also enhances the heterogeneous catalysis of alkene hydrogenation by Ni powders. Scanning electron microscopy reveals that ultrasound has multiple effects on the morphology and surface characteristics of inorganic solids, creating substantial surface damage, increasing surface areas significantly and causing increased particle aggregation.

Chemical Phenomena↗

Recordings from arterial pressure-sensitive units in the awake dog.

Recordings were made from units in or near nucleus ambiguus (NA) in the awake, drug-free dog while arterial pressure (AP) was increased and decreased nonpharmacologically by inflating occlusion cuffs that had been placed around the descending aorta and inferior vena cava, respectively. Units were recorded differentially through floating fine-wire electrodes that extended from vertically movable cannulas in a chronically implanted microdrive. Fifty-three percent of units recorded in or near NA were excited by increased AP, but were unresponsive to decreased AP. The remaining units were unresponsive to increased or decreased AP. About 25% of AP-sensitive units had activity patterns related to the cardiac cycle. AP-sensitive, cardiac cycle related units located in NA displayed several of the properties previously demonstrated for antidromically identified preganglionic parasympathetic cardiac motoneurons involved in baroreflex control of heart rate and rhythm. Recording from such neurons in the awake, neurologically intact, drug-free dog permits the fullest and most natural expression of neuro-cardiologic interactions and will allow the investigation of behavioral influences on autonomic and cardiovascular function.

Action Potentials↗

Heart-lung transplantation: lessons learned and future hopes.

Since March, 1982, 33 patients have undergone cardiopulmonary transplantation. Nineteen were discharged from the hospital following the operation, and 16 continue to do well. Eight patients have survived 1 year, 5 patients 2 years, and 1 patient 3 years. Often survival has been influenced most by the selection of candidates, as no patient who had undergone a previous sternotomy survived (3 of 3). All 7 early (between 30 and 72 days) and 3 late (145 to 466 days) deaths were related to infection. Methods for ex vivo preservation of the heart-lung bloc have included storage at 4 degrees C, cardiopulmonary bypass and profound hypothermia, and autoperfusion of the heart-lung bloc. The last technique is original and currently is preferred for distant procurement. Because dehiscence of the tracheal anastomosis has occurred in 3 patients, a sutured line is now encircled with a wrap of omentum. Isolated rejection of the lung is frequent in the first three weeks following operation and has been controlled with methylprednisolone. Late survivors have shown a mild restrictive lung disorder that has not progressed between 6 and 24 months. Bronchoalveolar lavage has been useful for diagnosing infection and providing insight into the immunobiology of the transplanted lung. Although mortality and morbidity have been high, the experiences gained through this series will likely result in an improved outlook for future recipients.

Adolescent↗

Early and late forms of cyclosporine nephrotoxicity: studies in cardiac transplant recipients.

To characterize the two forms of cyclosporine nephrotoxicity, we examined renal function in the immediate and late postoperative periods after cardiac transplantation. Moderate azotemia occurred during the first postoperative week in 58% of 43 cyclosporine-treated recipients, but in only 34% of 41 azathioprine-treated recipients, and 4% of 25 patients undergoing cardiopulmonary bypass for nontransplant surgery (both P less than .01 v cyclosporine). Acute renal failure developed in an additional 12% of the cyclosporine-treated group. Late postoperative renal dysfunction also occurred with a high prevalence. Life-table analysis indicated that at 6 months 55%, at 12 months 17%, at 24 months 4%, and at 36 months no cyclosporine-treated recipients retained normal renal function. Three renal biopsies performed in subjects with late nephrotoxicity demonstrated prominent interstitial fibrosis. Although one patient subsequently required chronic dialysis, reduction of cyclosporine dosage from a mean of 5.3 +/- 0.7 mg/kg/d to a mean of 2.3 +/- 0.3 mg/kg/d 9 to 21 months after transplantation with concurrent initiation of azathioprine therapy to prevent rejection led to an improvement of renal function in the five patients so treated. These data indicate that there are two distinct forms of cyclosporine nephrotoxicity. Although both occur with high prevalence, the early form does not appear to be a specific risk factor for the late form.

Acute Kidney Injury↗