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Biomedical subjects

T McCarthy

Publications and source records attributed to T McCarthy.

At least 55 records · Page 3Linked to original sources

Voluntary activation of human quadriceps during and after isokinetic exercise.

The extent of voluntary activation in fresh and fatigued quadriceps muscles was investigated during isometric and isokinetic voluntary contractions at 20 and 150 degrees/s in 23 normal human subjects. The muscles were fatigued by a total of 4 min of maximal knee extension at an angular velocity of 85 degrees/s. Voluntary activation was determined by the superimposition of tetanic electrical stimulation at 100 Hz for 250 ms, initiated at a constant knee angle. The relationship between voluntary and stimulated force was similar to that found with the established twitch superimposition technique used on isometric contractions. In fresh muscle all the subjects showed full voluntary activation during isometric contractions. Some activation failure was seen in five subjects at 20 degrees/s [2.0 +/- 0.9 degrees (SE)] and in two subjects at 150 degrees/s (0.7 +/- 0.5). After fatigue all subjects showed some activation failure at 0 and 20 degrees/s (36.4 +/- 3.1 and 28.8 +/- 4.1 degrees, respectively), but only two showed any at 150 degrees/s (1.4 +/- 5.7). We conclude that brief high-intensity dynamic exercise can cause a considerable failure of voluntary activation. This failure was most marked during isometric and the lower-velocity isokinetic contractions. Thus a failure of voluntary activation may have greater functional significance than previous studies of isometric contractions have indicated.

Adult↗

Long-term contraception with the levonorgestrel 20 mcg/day (LNg 20) and the copper T 380Ag intrauterine devices: a five-year randomized study.

An intrauterine device, releasing approximately 20 micrograms/day of levonorgestrel (LNg 20), used by 1124 women, was studied in a randomized trial of five years duration in comparison with the Copper T, model TCu 380Agm in 1121 women. At five years, the gross cumulative pregnancy rate of 1.1 +/- 0.5 per 100 among users of the LNg 20 devices was not significantly different from the rate of 1.4 +/- 0.4 per 100 experienced by users of the Copper T 380Ag. The steroid-releasing IUD had significantly higher termination rates for expulsion and amenorrhea, a significantly lower termination rate for other menstrual problems and pain, and a lower continuation rate. The five-year continuation rate among women using the TCu 380Ag was 40.6 per 100 as compared with that of 33.0 per 100 among women randomized to the LNg 20 device (P less than .001). Terminations attributed to amenorrhea with the LNg device primarily account for differences in continuation. These two intrauterine devices are the most effective long-term, reversible IUDs yet reported in the literature. No other contraceptive methods have exhibited such low long-term pregnancy rates in randomized comparative trials.

Adolescent↗

Use of an intraaortic balloon pump as a pneumatic ventricular assist device controller.

Using a circulatory analogue, we investigated sequentially the performance of a dedicated ventricular assist device driver and an intraaortic balloon pump when driving a pneumatic ventricular assist device. Each drive device was compared under identical pumping conditions at rates of 40 to 120 cycles/min against two resistances. Our preliminary study showed that a modified intraaortic balloon pump could drive a pneumatic ventricular assist device as effectively as its dedicated driver. The necessary modifications to and possible further development of the intraaortic balloon in this role are discussed.

Assisted Circulation↗

Current concepts on the use of IUDs.

IUDs have been used in Singapore since the mid 1960's but acceptance of this contraceptive method has fluctuated widely as a result of misconceptions regarding possible complications. The current generation of copper bearing devices have pregnancy rates below 1 per 100 women per year and this rate falls further with continued use. New developments which hold promise include a device releasing 20 mcg levonorgestrel per day and a copper device without a plastic frame which may reduce menstrual blood loss and dysmenorrhoea. In addition to the well established contra-indications to use, a past history of pelvic inflammatory disease or ectopic pregnancy, promiscuity, nulliparity and age less than 25 are now considered relative contraindications.

Evaluation Studies as Topic↗

Isolation of growth factors from adult bovine bone.

Fetal rat calvariae synthesize transforming growth factor beta (TGF beta), beta 2 microglobulin (beta 2 m), and insulinlike growth factor I (IGF I), but, except for TGF beta, it is not known if these polypeptides are also present in adult bone tissue. Pulverized bovine bone, extracted with 0.5 N HCl and 4 M guanidine HCl and fractionated by gel filtration, was found to contain several biologically active components when tested for its effects on DNA synthesis in osteoblast-rich cell cultures. TGF beta, beta 2 m, and IGF I were identified and further purified using high performance liquid chromatography (HPLC). TGF beta, identified by a standard TGF beta bioassay or by immunoreactivity, was purified by muBondapak C18 and muBondapak CN reversed phase HPLC. beta 2 m, identified by immunoreactivity, required an additional fractionation step on a DEAE-HPLC column for complete purification. IGF I, identified by immunoreactivity, was purified by HPLC using a muBondapak C18 and a DEAE-HPLC column. Purified TGF beta, beta 2 m, and IGF I migrated as single bands on polyacrylamide gel electrophoresis with respective molecular masses of 24,000, 10,000, and 7,500. In conclusion, adult bone matrix, like fetal bone cultures, contains TGF beta, beta 2 m, and IGF I and these factors may play a role in adult skeletal remodeling.

Animals↗

Effects of basic fibroblast growth factor on bone formation in vitro.

Basic fibroblast growth factor (bFGF) was studied for its effects on bone formation in cultured rat calvariae. bFGF at 0.1-100 ng/ml stimulated [3H]thymidine incorporation into DNA by up to 4.4-fold. bFGF also increased the number of colcemid-induced metaphase arrested cells and the DNA content. Transient (24 h) treatment with bFGF enhanced [3H]-proline incorporation into collagen 24-48 h after the factor was removed; this effect was DNA synthesis dependent and blocked by hydroxyurea. The collagen stimulated by bFGF was type I, and this effect was observed primarily in the periosteum-free bone. In contrast, continuous treatment with bFGF for 24-96 h inhibited [3H]proline incorporation into type I collagen. bFGF did not alter collagen degradation. In conclusion, bFGF stimulates calvarial DNA synthesis, which causes an increased number of collagen-synthesizing cells, but bFGF has a direct inhibitory effect on collagen synthesis.

Animals↗

Isolation and characterization of insulin-like growth factor I (somatomedin-C) from cultures of fetal rat calvariae.

Cultured bones have been shown to secrete local regulators of bone remodeling, such as beta 2-microglobulin, transforming growth factor-beta, and insulin-like growth factor (IGF), but the IGF secreted has not been characterized. In the present study, IGF from medium conditioned by 21-day-old fetal rat calvariae was isolated and characterized. IGF was purified using dialysis, gel filtration, and reverse phase HPLC. Amino acid composition was compatible with that of IGF I (somatomedin-C), and amino-terminal sequence analysis revealed homology with IGF-I. The concentration of IGF-I in the calvarial culture medium was 1 nM and was suppressed by cycloheximide. Calvaria-derived rat IGF I at 20 nM stimulated DNA and collagen synthesis by 42% and 26%, respectively, in monolayer cultures of osteoblast-rich rat parietal bone cells. This study indicates that locally produced IGF-I regulates bone formation in cultures of 21-day-old fetal rat calvariae.

Amino Acid Sequence↗

Pentoxifylline inhibits granulocyte and platelet function, including granulocyte priming by platelet activating factor.

Pentoxifylline has been claimed to work a beneficial effect in arterial insufficiency by improving erythrocyte deformability and thus improving blood flow. A number of observations, including the drug concentrations required to work the red cell effect, suggested that this was not likely to be a complete explanation. We therefore examined the effect of pentoxifylline on several granulocyte and platelet functions. Pentoxifylline inhibited platelet aggregation in response to 4 mumol/L adenosine diphosphate; although statistically significant inhibition was seen at 1 mumol/L pentoxifylline, over 200 mumol/L was required for 50% inhibition. The adherence of unstimulated platelets to cultured endothelial cells was not strongly inhibited by pentoxifylline; however, the additional increment in adherence seen in the presence of thrombin was strongly inhibited (50% attenuative dose [AD50] = 18 mumol/L). Granulocyte aggregation in response to C5a was modestly inhibited (AD30 approximately equal to 8 mumol/L; AD50 greater than 1 mmol/L), and the adherence of unstimulated polymorphonuclear neutrophils (PMNs) to endothelium was uninhibited. The C5a-mediated augmentation of PMN adherence to endothelium was mildly inhibited (AD50 = 240 mumol/L). Inhibition of PMN chemotaxis to N-Formyl-methionyl-leucyl-phenylalanine (FMLP) or C5a (AD50 = 12 mumol/L) and inhibition of superoxide production in response to FMLP-cytochalasin B (AD50 = 24 mumol/L) were seen at more clinically credible concentrations. Perhaps most important, pentoxifylline blocked the ability of platelet activation factor to prime neutrophils for enhanced response to subsequent stimuli (AD50 approximately equal to 8 mumol/L; AD60 = 10 mumol/L when production was the indicator system); in vivo, this could broaden the drug's effect to include functions that it does not inhibit potently in a primary fashion. Although pentoxifylline is known to be a phosphodiesterase inhibitor, and we found it to elevate intracellular cyclic adenosine monophosphate in stimulated PMNs, we found it to be only marginally more potent than theophylline in this regard; therefore, the failure of theophylline to inhibit PMN priming suggests that this enzyme inhibition is not a complete explanation of the pharmacologic action of pentoxifylline. We suggest that the effects of pentoxifylline on platelet and granulocyte function are likely to contribute to the drug's clinical efficacy.

Blood Platelets↗

Interim 4-year results of a comparative study between the Nova T and the Multiload 250.

Eight-hundred patients recruited between September 1981 and December 1984 were admitted to a randomized prospective trial of the Nova T (NTCu200Ag) and Multiload 250 (MLCu250) IUDs. At the cut off date, 31 December 1986, 206 patients had completed the 4-year trial period, 379 had terminated before completion and 215 were in the fourth year of use. For the third and fourth years, the MLCu250 had a significantly lower accidental pregnancy rate (p less than 0.05).

China↗

A bone-derived growth factor isolated from rat calvariae is beta 2 microglobulin.

Rat calvariae are known to secrete a bone-derived growth factor (BDGF) that stimulates bone DNA and collagen synthesis. BDGF was purified from calvarial culture medium with dialysis, gel filtration and HPLC. Amino acid composition of BDGF was compatible with murine beta 2 microglobulin (beta 2 m), and amino terminal sequence analysis revealed identity with mature murine beta 2 m. This was confirmed by Western blot analysis using a polyclonal antibody to beta 2 m. Like BDGF, human beta 2 m stimulated bone DNA, collagen and noncollagen protein synthesis. Thus, BDGF, an autologous regulator of bone formation, is homologous to beta 2 m.

Amino Acid Sequence↗

Evaluation of a low dose of hepatitis B vaccine given within a childhood immunisation programme in Singapore.

The feasibility of introducing low dose (5 micrograms) hepatitis B (HB) virus vaccination at birth and again 1 and 2 months later as part of an existing primary immunisation programme of childhood, was assessed in 662 healthy newborn Singapore children. The vaccine (B-Hepavac, Menck, Sharp and Dohme) was given to three neonatal groups: those born to HB surface antigen (sAg)-negative mothers, HBsAg-positive/HBeAg-positive mothers and HBsAg-positive/HBeAg-negative mothers. A dose of 5 micrograms was compared in a randomised study with the more usual 10 micrograms dose given at the same intervals. Neonates born to HBsAg-positive/HBeAg-positive mothers were also given hepatitis B immunoglobulin (HBIg) at birth. The 5 microgram dose of vaccine was as immunogenic as the 10 microgram dose in all three groups of children studied. At 1 year, anti-HBsAg seroconversion among infants of antigen-negative mothers was 95.8% for the 5 microgram dose and 91.9% for the 10 microgram dose. Suppression of anti-HBsAg formation was not seen even when maternal anti-HBsAg was present or HBIg given. Among infants born to HBsAg-positive/HBeAg-positive mothers, passive plus active immunisation was 100% protective at doses of 5 micrograms and 10 micrograms vaccine in the newborns who were HBsAg-negative at 24 h. Seroconversion after both the 5 and 10 microgram doses of vaccine was reduced, however, to 88% in each group of infants who were already HBsAg-positive at 24 h of age. Overall, passive plus active immunisation as well as HB vaccine alone (5 micrograms dose), given within the existing but expanded primary immunisation programme of childhood, was effective in preventing infection and the chronic carrier state in newborns exposed to risk of HB virus infection during infancy.

Carrier State↗

Postabortion insertion of the Nova T and MLCu250: preliminary results of a comparative study.

This 4-year prospective randomized study is designed to compare the effectiveness and complication rates of the Nova T and MLCu250 inserted immediately postabortion. At the cut-off date (30 November 1983), all patients in the first cohort of 400 women had completed at least 12 months of use. At this stage of the trial, no significant differences had emerged between the two devices in any of the standard termination categories.

Abortion, Induced↗

Effect of benztropine on the diurnal prolactin responses to haloperidol.

Prolactin (PRL) responses to haloperidol were investigated at 0900 and 1800 h in six young healthy men under basal conditions and after benztropine mesylate administration. Haloperidol administration induced significantly higher PRL release during the evening compared to the morning. The anticholinergic drug, benztropine, potentiated the PRL responses to haloperidol both in the morning and in the evening. The possible mechanisms of these findings are discussed.

Adult↗

Effect of atropine on the diurnal PRL responses to TRH in normal subjects.

Prolactin (PRL) responses to TRH were investigated at 0900 and 1800 hr in six young healthy men under basal conditions and after atropine administration. TRH induced significantly higher PRL release during the evening administration compared to the morning. Atropine had no effect on basal PRL secretion. Unlike the reported influences of anticholinergic drugs on the diurnal PRL responses to other stimuli, atropine also had no effect on TRH-stimulated PRL release either in the morning or in the evening. These observations in part may be accounted for by the direct PRL-releasing effect of TRH (without neurotransmitter involvement).

Adult↗