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Biomedical subjects

M Jones

Publications and source records attributed to M Jones.

At least 793 records · Page 44Linked to original sources

The late prognosis after localized resection for fixed (discrete and tunnel) left ventricular outflow tract obstruction.

We studied the follow-up status of 56 patients after operation for fixed left ventricular outflow tract obstruction (LVOTO), 42 with discrete LVOTO consisting of an obstructing membranous ring in the left ventricular outflow tract (LVOT) and 14 with tunnel (diffuse) LVOTO. Forty-one of the 56 patients were available for long-term follow-up. Patients with discrete LVOTO fared better than patients with tunnel LVOTO postoperatively in their functional class status (discrete: 21 in Class I, five in Class II; tunnel: one in Class I, four in Class II; p less than 0.05), their LVOT peak systolic gradients (discrete: 22 +/- 4 mm Hg; tunnel: 98 +/- 23 mm Hg; p less than 0.02), their actuarially determined survival probabilities (discrete: 82% +/- 9% at 20 years; tunnel: 40% +/- 19% at 20 years; p less than 0.1), and their survival probabilities without an adverse event, i.e., (1) death, (2) reoperation, (3) residual gradient greater than 50 mm Hg, (4) significant aortic regurgitation, (5) bacterial endocarditis, or (6) complete heart block (discrete: 43% +/- 9% at 4 years, 36% +/- 9% at 10 years, and 15% +/- 9% at 20 years; tunnel: 0% at 4 years; p less than 0.02). Thus most patients who undergo operation for fixed LVOTO will survive late postoperatively; resection of the membrane is adequate for relief of LVOTO and for relief of symptoms in most patients with discrete LVOTO; the majority of patients with tunnel LVOTO who undergo only local resection will have an unsatisfactory operative result; most patients with discrete as well as tunnel LVOTO surviving operation will have clinically significant adverse events early or late postoperatively. This last observation dictates continuing long-term follow-up evaluations of patients operated upon for fixed LVOTO.

Adolescent↗

The effect of estrogen dose on postmenopausal bone loss.

In order to establish whether the favorable effect of estrogen therapy on postmenopausal bone loss was dose related, we measured sequential changes in the cortical diameters of the metacarpals by radiographic morphometry in 120 normal postmenopausal women who were being treated with ethinyl estradiol in doses ranging from 5 to 50 micrograms daily. There was a net loss of bone at doses below 15 micrograms per day and a net gain at doses of 25 micrograms per day and above. At doses between 15 and 25 micrograms daily, bone was neither gained nor lost. The loss of bone with the low doses was due to expansion of the medullary cavity that was unaccompanied by any change in total bone width. There was no change in bone volume with the intermediate doses because endosteal resorption of bone was offset by periosteal apposition. The net gain of bone with the higher doses occurred because endosteal resorption was totally inhibited but periosteal bone apposition continued. Thus, in postmenopausal women the reduction in the rate of cortical bone loss in response to estrogen therapy depends on the dose administered.

Adult↗

Formation of cartilage in bioprosthetic cardiac valves implanted in sheep: a morphologic study.

Foci of cartilage were found in 12 of 120 bioprostheses implanted in young sheep for 13 to 24 weeks, but in none of 47 bioprostheses implanted for less than 13 weeks. Cartilage was found more frequently (p less than 0.01) in bioprotheses implanted in the tricuspid position than in those implanted in the mitral position. In porcine aortic valvular bioprostheses, the cartilage was preferentially localized in the region of the muscle shelf; in pericardial bioprostheses, it occurred in the fibrous sheaths covering the cusps. In both instances, the cartilage was found to undergo calcification and was considered to be formed by metaplasia of connective tissue cells of host origin.

Animals↗

Hemodynamics, regional myocardial blood flow, and sarcoplasmic reticulum calcium uptake in right ventricular hypertrophy and failure.

Either right ventricular hypertrophy (RVH) or failure (RVF) was produced by pulmonary arterial banding in 47 piglets aged 3-6 weeks. When sufficient time was allowed to elapse after banding, RVH was present in 30 and had progressed to RVF in 17. These two groups were compared with 24 control, i.e., normal pigs (C). Animals with RVF differed from RVH and C animals by having reduced cardiac output and clinical signs of failure. Both RVH and RVF had significantly elevated right ventricular peak systolic pressures (RVS), weights (GMRV), and RV/LV systolic pressure ratios (these variables all increased greater than 100% compared with C). The RV (dP/dt)max correlated with RVS in C (r = 0.687, P less than 0.001), but this relationship was absent in RVH with higher RVS and GMRV. The RV (dP/dt)max correlated closely with RV blood flow/g per min in C (r = 0.638, P less than 0.01) and in RVH (r = 0.462, P less than 0.02). Calcium uptake by RV sarcoplasmic reticulum (SR) was diminished in RVH compared to C and further diminished in RVF (38%, P less than 0.001). Calcium uptake by LV SR also fell in RVF, suggesting that SR calcium uptake is merely a passive reflection of myocardial function. Our results also suggest that hemodynamic and subcellular changes seen in RVF may be detected during the compensated stage of RVH.

Animals↗

Lymphocyte enzyme activities in East African blacks: decrease in 5'nucleotidase and possible relation to immunosuppression.

Microanalysis of subcellular organelle marker enzymes was applied to cryopreserved lymphocytes (obtained and processed in the field) from East African blacks with moderate to severe malnutrition and subject to locally endemic parasitic and infectious diseases. An initial study demonstrated that activities of these enzymes, with the partial exception of catalase, were stable to cryopreservation. Cryopreserved and thawed lymphocyte specimens (1 to 3 X 10(6) viable cells) from 26 Africans and 20 Caucasian controls were studied. There was a highly significant decrease in 5'nucleotidase activity in these African subjects. Activity of another plasma membrane enzyme, gamma-glutamyl transferase, and of marker enzymes for other intracellular organelles, was not significantly different between the two groups, indicating that the nucleotidase alteration is highly specific. 5'Nucleotidase activity in a group of 17 East African blacks of high socio-economic status lay between the values obtained in the other two groups and was not significantly different from either. Further studies on 5'nucleotidase showed no evidence that the enzyme is functionally different in Africans. The differences in activity of this enzyme in Africans may reflect the known immuno-suppressive effects of infectious disease and malnutrition or may have a genetic basis which may in turn be associated with the pathogenesis of secondary immunodeficiency.

5'-Nucleotidase↗

Does secondary cardioplegia provide long-term recovery from ischemic injury?

Short-term experimental studies have indicated that initial reperfusion with blood cardioplegia may decrease ischemic injury after aortic occlusion; however, no long-term studies have been performed. We evaluated cardioplegic reperfusion in fifteen dogs, divided into three groups of five each. Group I underwent 2 hours of cardiopulmonary bypass at 37 degrees C. Group II underwent 2 hours of cardiopulmonary bypass, including 1 hour of ischemic arrest, at 25 degrees C. Group III was identical to Group II, but the hearts of the animals were initially reperfused with 500 ml of blood cardioplegia at 25 degrees C (K+ = 30 mEq/L). Stroke work index (SWI), left ventricular end-diastolic pressure (LVEDP), dp/dt max and maximal contractile element velocity (Vpm) were measured preoperatively, immediately after operation, 21 days postoperatively, immediately after operation, 21 days postoperatively and 120 days postoperatively. Compliance curves were evaluated using an intraventricular balloon at 120 days. Groups II and III had significant (p less than 0.05) elevations of LVEDP at all three postoperative measurements. The hearts of the Group III animals (cardioplegic reperfusion group) demonstrated significantly (p less than 0.05 to 0.01) better recovery of SWI immediately after operation (62% versus 39%), at 21 days (85% versus 69%), and at 120 days (81% versus 66%) than did those in Group II. However, groups II and III had decreased compliance at 120 days, compared with that of Group I, and also showed both gross and microscopic evidence of subendocardial necrosis and fibrosis. It is concluded that while initial reperfusion with blood cardioplegia appears to provide better preservation of ventricular function early after ischemic cardiac arrest, this technique does not prevent later deterioration of ventricular compliance. Moreover, it produces myocardial fibrosis.

Animals↗

Calcium fractions in serum of patients with thermal burns.

Total calcium measurement is less useful clinically than assay of the physiologically active fractions, free and ionized calcium. The latter were measured in burned patients by ultrafiltration and by ion-selective electrode. Hypocalcemia was observed in these patients but it was generally limited to low total calcium. On average, free or ionized calcium were in the normal range. Total and free calcium were weakly correlated with severity of burn injury suggesting a loss of several forms of calcium in severe burn injury. An algorithm was derived to allow calculation of free calcium from total calcium and albumin. Interpatient variables are important, however, so that the algorithm should not be substituted for actual assay of free and ionized calcium.

Burns↗

A double-blind crossover study of cinromide versus placebo in epileptic outpatients with partial seizures.

Cinromide was evaluated versus placebo as add-on therapy in a double-blind crossover study in epileptic outpatients with partial seizures at three sites. Four-week base lines were used before, between, and after the two 12-week treatment periods of the crossover. An operational definition was used to classify each partial seizure as Type A, B, or C. Doses of concurrent antiepileptic drugs were adjusted to maintain pretreatment therapeutic plasma levels. Doses of cinromide ranged from 1,200 to 4,800 mg/day, depending on patient response. Seven patients were withdrawn from the study because of adverse experiences (two receiving placebo and five receiving cinromide). Twenty-eight patients completed the entire 36-week study. A decrease in the average frequency of seizures/week was observed in 12 patients receiving cinromide and in 16 patients receiving placebo. The median frequencies with cinromide and placebo were 3.3 and 2.9 seizures/week, respectively (median initial base-line frequency 3.5 seizures/week for all 28 patients). Although patients were randomly assigned to receive either cinromide or placebo first, the median base-line seizure frequency was greater at the start of the first treatment period in the cinromide group (4.3 versus 2.5 seizures/week) and greater at the start of the second treatment period in the placebo group (3.8 versus 1.4). The median seizure frequency in each higher group decreased with treatment, whereas it increased in each of the lower groups. This study did not demonstrate a beneficial effect of cinromide over placebo for Type A, B, or C partial seizures. The data suggested the presence of an oscillation of seizure frequency in our population of epileptic patients having partial seizures, as well as a placebo effect. No significant carry-over effects were observed. Cinromide has previously been shown to have significant antiepileptic activity in various animal models of epilepsy. The lack of an antiepileptic response to cinromide in humans may have been due to factors other than species differences but indicates that a positive results of a drug in animal models is not the sole factor necessary to predict beneficial antiepileptic activity in humans.

Adolescent↗

Work in progress: the effect of heat on bleomycin cytotoxicity in vitro and on the accumulation of 57Co-bleomycin in heat-treated rat tumors.

The cytotoxic effects of the sequence and timing in combined hyperthermia and bleomycin treatment were tested in vitro using V79 Chinese hamster cells. The order of treatment was important; heat treatment followed by the administration of bleomycin yielded greater cytotoxicity than when the opposite order was used. To determine whether heat-treated tumors have an altered uptake of bleomycin, rat rhabdomyosarcoma (BA 1112) tumors were heated locally with RF current (43 degrees C, 90 min.), injected with 57Co-bleomycin, and imaged on a radioisotope camera. Results of tumor-to-background (T/B) ratio analysis indicate that (a) local hyperthermia (43 degrees C) does not appear to alter tumor uptake patterns of 57Co-bleomycin; and (b) intravenous and intraperitoneal injections produce similar T/B uptake ratios, typically between 2 and 3 at 120 minutes postinjection. In the BA 1112/WAG/Rij tumor system, local hyperthermia treatment does not seem to interfere with the subsequent accumulation of bleomycin in the tumor.

Animals↗

Detection of isolated mammary carcinoma cells in marrow of patients with primary breast cancer.

Single cells from mammary carcinoma infiltrating bone marrow can be detected in marrow aspirates using immunocytochemical stains for epithelial membrane antigen (EMA). This technique has been used to examine marrow aspirates taken from multiple sites from 24 patients at surgery for breast cancer. Ten of these patients had EMA-positive cells in their marrow, while 32 marrow samples from patients who did not have carcinoma were negative. These results have been combined with those obtained by taking aspirates from single sites from 47 breast patients without known skeletal deposits. Follow up showed that the patients with EMA-positive cells in their marrow developed bone metastases at a significantly faster rate.

Biopsy, Needle↗

On the treatment of migraine. Pharmacokinetic-pharmacodynamic relationships for a programmed release formulation of dihydroergotamine administered orally in the human.

With the combined pharmacokinetic-pharmacodynamic approach, the bioavailability and venoconstrictor effects of two DHE formulations (programmed release capsules and oral solution) have been compared after acute oral dose administrations in the healthy volunteer subjects. The bioavailability of DHE from programmed release capsules has been significantly greater than that shown by the oral solution. DHE capsules formulation has seemed to provide appropriate plasma concentrations for at least 10 h after administration. That may well account for its efficacy in the treatment of morning migraine.

Administration, Oral↗

Combined chloroquine/Fansidar-resistant falciparum malaria appears in East Africa.

The first two cases from East Africa of RII chloroquine- and Fansidar-resistant falciparum malaria are described. The first case occurred in a non-immune Swedish expatriate 2 weeks after arrival in Tanzania, and the second in a semi-immune Tanzanian soldier. Fansidar has not yet been marketed in Tanzania. The significance and etiology of the occurrence of combined chloroquine/Fansidar resistance in East Africa are discussed.

Adult↗

Hyperthermia and bleomycin schedules on V79 Chinese hamster cell cytotoxicity in vitro.

The effect of sequence and timing of hyperthermia (43 degrees) and bleomycin on Chinese hamster cells (V79) has been investigated. Hyperthermia preceding bleomycin treatment produced a greater cytotoxic effect than bleomycin treatment preceding hyperthermia. Furthermore, it appears that the combination of hyperthermia and bleomycin becomes less effective if the application of bleomycin is delayed. The enhancement of cytotoxicity with hyperthermia first may be related to the effect of heat on the intracellular bleomycin degradation ability and protein synthesis. V79 cells treated with a protein synthesis inhibitor, cycloheximide, before bleomycin (but not in the reversed sequence) also showed a markedly lower level of survival. As for hyperthermia treatment, pretreatment with cycloheximide did not change the uptake of bleomycin. These results suggest that hyperthermia and cycloheximide have increased the effectiveness of bleomycin and are consistent with the observation on chromosome damage induced by hyperthermia-bleomycin and cycloheximide-bleomycin treatments reported in the literature.

Animals↗

Pulmonary artery balloon counterpulsation for right ventricular failure. An experimental evaluation.

Right ventricular (RV) failure frequently occurs in patients undergoing correction of congenital cardiac defects, as well as in other clinical settings. RV hypertrophy was created in 10 neonatal lambs by pulmonary artery (PA) banding. Twelve months later RV hypertrophy was present (RV weight/body weight = 2.71 +/- 0.31 gm/kg); RV systolic pressures were elevated (65 +/- 9 mm Hg) and the average gradient across the PA band was 38 +/- 9 mm Hg. RV failure was produced in all animals by performing a right ventriculotomy. Four unassisted (control) animals died shortly after separation from bypass. Six experimental animals underwent pulmonary artery balloon counterpulsation (PABCP). A Dacron graft anastomosed to the proximal PA served as a reservoir for a 40 ml intra-aortic balloon pump system. PABCP effectively reversed RV failure, low cardiac output, and systemic arterial hypotension. Periods with PABCP on and off in each animal were compared. PABCP increased cardiac output from 1.45 +/- 0.16 to 2.03 +/- 0.13 L/min (p less than 0.0001) and increased aortic systolic pressure from 78 +/- 7 to 99 +/- 6 mm Hg (p less than 0.0004). PABCP produced a significant reduction in RV peak systolic pressure from 56 +/- 5 to 41 +/- 3 mm Hg (p less than 0.0001). PA peak pressure distal to the band increased from 31 +/- 2 to 40 +/- 1 mm Hg (p less than 0.0001). Right atrial pressure decreased from 14 +/- 1 to 11 +/- 1 mm Hg (p less than 0.0001) with PABCP, and RV end-diastolic pressure fell from 15 +/- 1 to 11 +/- 1 mm Hg (p less than 0.0001). RV stroke work index increased 49% from 0.081 +/- 0.011 to 0.121 +/- 0.017 gm X m/kg/beat (p less than 0.01), and RV systolic pressure time index decreased 38% from 1140 +/- 79 to 710 +/- 65 mm Hg sec/min (p less than 0.0001). Thus PABCP in the presence of RV dysfunction can produce substantial improvement in RV function and in overall cardiac function and may prove clinically useful in managing patients in refractory RV failure.

Animals↗

Comparison of approaches for augmenting the serologic response to the individually specific methylcholanthrene-induced sarcoma-Meth A: pretreatment with cyclophosphamide is most effective.

We have previously reported the production of antisera against a highly restricted antigen expressed on the BALB/c sarcoma Meth A. Because induction of the antibody required many vaccinations with irradiated and unirradiated Meth A cells over a prolonged period, we have investigated methods of improving the efficiency of producing Meth A antibody in BALB/c mice. Three general approaches were used: immunizing with irradiated Meth A cells mixed with adjuvants, immunizing with irradiated Meth A cells modified by treatment with chemicals, or administration of tumor cell vaccines in conjunction with low dose cyclophosphamide. These vaccine preparations were injected subcutaneously into groups of BALB/c mice five to six times at 2-wk intervals. Sera from all mice were screened for reactivity to Meth A by complement-dependent cytotoxicity, protein A, and mixed hemadsorption assays. Twenty-three vaccine preparations containing adjuvants or modified cells were tested in individual groups of mice. Mice in some groups receiving adjuvants and in all groups receiving modified cells produced antibody, but only after four to six vaccinations. In contrast, nine of the 14 mice immunized with irradiated Meth A cells (unmodified and without adjuvant) in conjunction with 10 or 100 mg/kg body weight of cyclophosphamide, and all nine of the mice receiving 25 mg/kg cyclophosphamide made Meth A antibodies after only one or two vaccinations. The titer of antibodies produced after one treatment with cyclophosphamide and irradiated Meth A cells was at least as high as that achieved after five or six vaccinations in our other trials. The specificity of these antibodies for the Meth A antigen was established by absorption analysis. We conclude that treatment with cyclophosphamide before vaccination is highly effective in augmenting the humoral immune response to the Meth A antigen.

Adjuvants, Immunologic↗