Biomedical subjects
Publications and source records attributed to C Lynch.
Recently, much research interest has been directed to demonstrating a possible biological basis to obsessive compulsive disorder. In particular, dysregulation in brain serotonin is suggested to be important. Two cases are described in which fenfluramine, a presynaptic 5 HT-releasing agent and 5HT-reuptake inhibitor was used to augment clomipramine treatment for OCD.
This article describes the key elements of a three-year innovative project underway in Dublin, Ireland, which is applying the principles of supported employment. It covers the development of more integrated day services for adults with mental handicap, programme participants and activities, and key issues to be resolved in maintaining effective programmes of this kind.
The sensitivity and specificity of the polymerase chain reaction (PCR) for the detection of HIV-1 proviral DNA was determined in five laboratories with extensive experience in PCR testing. Five panels consisting of 105 HIV-1-seronegative specimens from regularly repeating blood donors with no risk factors for HIV infection and 99 HIV-1-seropositive and culture-positive specimens from a cohort of homosexual/bisexual men were sent under code to each laboratory. Amplification procedures and testing algorithms by which specimens were judged positive, negative, or indeterminate varied between laboratories. The average sensitivity for the five laboratories was 99.0%, with two laboratories achieving 100%. The average specificity was 94.7%, varying between 90.5 and 100%. The overall false-positive rate was 1.8%, the false-negative rate was 0.8%, and the indeterminate rate was 1.9%. Of 1,005 determinations made by the five laboratories, 32 (3.2%) were misclassifications. Most of the classification errors occurred in specimens from uninfected individuals and were distributed among the laboratories in such a way as to indicate laboratory error rather than the inherent reactivity of some samples. This emphasizes the need for standardization of PCR testing and caution in interpreting positive PCR reactions in HIV-1-seronegative persons.
A literature search identified eight articles containing data on both baldness and coronary artery disease (CAD). Three of these articles described case-control studies that showed a positive relationship between baldness and CAD when controlling for CAD risk factors. Three other case-control studies showed no such relationship, but these did not control for CAD risk factors. The results of two cohort studies were inconclusive. Insufficient data were available from these studies to analyze possible relationships between baldness and CAD risk factors themselves. Overall, the data reviewed suggest that a small risk of CAD due to baldness may exist, but this risk is smaller than that of well-known CAD risk factors such as smoking and hypertension. Future research should emphasize proper control for age and CAD risk factors.
This study examined in vitro myocardial depression by 50% N2O. Maximal isometric contractions of guinea pig right ventricular papillary muscles were studied in Tyrode's superfusate at 37 degrees C within a gas-tight chamber. Superfusate (pH at 7.45) and chamber were equilibrated with 95% O2/5% CO2. After control measurements in 95% O2, muscles were studied with 50% N2 and 50% N2O (45% O2/5% CO2) in random order with an intervening and final recovery in oxygen. Muscles were field stimulated after rest and at 0.1-3 Hz. At 37 degrees C, muscle performance deteriorated over time with exposure to reduced oxygen; therefore, identical experiments were performed at 30 degrees C in which no systematic deterioration occurred. Peak tension and maximum rate of tension development (dT/dtmax) were compared for each stimulation rate. At both temperatures, N2O caused a 10-15% depression of contractility as compared to that observed with nitrogen. In a second protocol, muscles were studied at 37 degrees C in 26 mM K+ Tyrode's solution with 0.10 microM isoproterenol to study enhanced contractions mediated by slow (Ca2(+)-channel-dependent) action potentials. Rested-state double stimulations were used (stimulus interval, 250-600 ms) resulting in a first rested-state contraction followed by a second contraction (C2) with rapid initial tension development. The muscles were exposed to nitrogen and N2O as in the force-frequency experiments and did not deteriorate over time. In this setting, N2O also caused a 10-15% depression of C2 contractility as compared with nitrogen. Another set of muscles was studied in 95% O2 to which 0.5% halothane or 1% isoflurane was added before exposure to nitrogen and N2O. The combined depressant action of N2O with either halothane or isoflurane did not differ from that predicted by the simple addition of independent effects; there was no evidence of synergism. Furthermore, N2O (50%) alone depressed dT/dtmax in a manner similar to that of 0.5% halothane and different from that of 1.0% isoflurane. Experiments conducted in iso-osmolar 40 mM Na+ Tyrode's solution, in which activator Ca2+ arose from the sarcoplasmic reticulum Ca2+, also showed greater depression by N2O than nitrogen. N2O (50%) is a myocardial depressant independent of concurrent hypoxic effects with a pattern and magnitude of contractile depression similar to that of 0.5% halothane.
Depression of rested state contractions (RSCs) and 0.1-0.25 Hz contractions by equianesthetic concentrations of isoflurane (2.5%), halothane (1.5%), and enflurane (3.5%) was studied in guinea pig papillary muscles in which tension development was enhanced by 0.1 microM isoproterenol. In a second series of experiments, an RSC was elicited, followed by a second contraction elicited with stimulus intervals of 300-600 ms. In both types of experiments, the results were similar. Halothane and enflurane depressed rapid initial tension development more than isoflurane. This initial tension development was also selectively depressed by 0.1 microM ryanodine, which specifically decreases Ca2+ release from the sarcoplasmic reticulum (SR). Isoflurane and also enflurane depressed a delayed and late peaking component of tension development, which was very prominent after rest and was depressed by 200 microM procaine or 500 microM benzocaine. Although isoflurane and enflurane were similar to the local anesthetics in depressing late tension, unlike the local anesthetics they prolonged the late phase of tension development as well. The late tension of the RSC is associated with Ca2+, which enters the rested myocyte on depolarization and may be transiently sequestered in the SR before release. Both early initial and late tension development are depressed to a similar degree by application of 10-20 nM nifedipine. These results emphasize the multiple differing actions of the volatile anesthetics on myocardial contractions, with halothane and isoflurane possessing distinct depressant characteristics.
Fifty-nine towns in Iowa with single source drinking water supplies were stratified on the basis of radium content in finished non-softened water to test the hypothesis of an association with total or acute myeloid leukemia. Fourteen towns had radium concentrations in drinking water exceeding the EPA safety limit of 5 picocuries per liter (pCi/L). A small increasing trend existed for total leukemia with increased radium content in drinking water that is in accordance with either the hypothesis of no effect or of a small effect.
The parents of 56 children who had received behavior therapy rated a number of variables, including the degree to which they viewed the therapeutic relationship versus the specific techniques used in treatment as important, the extent to which the child improved in therapy, and the child's present functioning. Therapists also provided ratings of clinical improvement. Even though parents gave the highest ratings for the importance of the relationship in therapy, the correlation between technique and clinical outcome was statistically significant while the correlations between the relationship and outcome was not. These statistical associations also held when therapists rated improvement. Also, therapists saw greater improvement in children than did the parents. Over-all, the results support the view that the relationship and techniques are interwoven and are both perceived as important factors in treatment.
A recent ecologic study has suggested a relationship between mortality from diabetes mellitus and levels of magnesium in drinking water. However, diabetes mortality rates were from aggregate data for the entire geographic area under study. The state of Iowa has data resources available to determine diabetes mortality rates for individuals on known water supplies in Iowa and magnesium levels for raw drinking water supplies. To determine the presence of this relationship in the state of Iowa, mortality rates from 1976 through 1985 for diabetes as an underlying cause of death and for major cardiovascular disease with diabetes as an ancillary cause of death were compared for individuals from towns in Iowa with populations of 1,000 to 10,000. At the stratification levels of magnesium in municipal drinking water used in this study, no significant differences were found in diabetes mortality rates.
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Adenosine is a well-known locally active vasodilator metabolite. A major role in blood flow regulation has been ascribed to adenosine. This investigation compared the dose-response curves to adenosine in the cremaster of spontaneously hypertensive rats (SHRs) with Wistar-Kyoto rats (WKYs) at an age when cardiac output and blood flow of the SHR have been shown to be increased (6 weeks). Each concentration (10(-5), 10(-4), and 10(-3) M) was injected retrograde through the femoral artery as a bolus of 100 microliters/sec and 300 microliters/3 sec. Changes in arteriolar diameter were recorded for 3 min. Continuous monitoring techniques enabled detection of differences between strains using an average of the 3-min response (DAVG) and the 3-min response pattern. In contrast, no interstrain differences were observed using the peak diameter response (DMAX). SHRs exhibited a reduced sensitivity to adenosine which was apparent in the dose-response curves based on DAVG with 3-sec injections (P less than 0.02). There was no difference with 1-sec injections. Analysis of the 3-min response pattern showed that SHRs also returned to control diameters faster than WKYs, except at the highest dose when vessels of both strains remained dilated. These results are consistent with the role of metabolic (vasodilator) autoregulation in hypertension. If extracellular adenosine is washed out in the SHR, intraarterial injections of the same concentration of adenosine would cause a reduced response in SHRs.
To clarify the mechanisms by which volatile anesthetics may depress myocardial contractility, the depressant effects of equivalent concentrations of isoflurane, enflurane and halothane were compared in rat and frog ventricular myocardium, preparations which differ markedly in excitation-contraction coupling. In Tyrode solution, right ventricular papillary muscles from rat exhibited very large, rapidly developing contractions after rest, with a subsequent negative force-frequency relation as the stimulation rate was increased to 0.1, 0.25, 0.5, 1, 2, and 3 Hz. The large contractions after rest and at 0.1 Hz were depressed by 0.75% halothane and 1.7% enflurane to about 60% of control, but less so by 1.3% isoflurane (approximately 0.8 MAC). Halothane at 1.5% was more depressant than 2.5% isoflurane at all stimulation rates, while 3.5% enflurane caused intermediate depression (approximately 1.6 MAC). Contractions in frog ventricular strips were studied in Ringer solution following rest and at stimulation rates of 0.1, 0.25, 0.5, and 1 Hz, in the absence and presence of equivalent anesthetic concentrations. At 0.1 to 1 Hz, isoflurane was less depressant than equivalent concentrations of halothane. Enflurane (1.7%) was less depressant than 0.75% halothane at 0.1 and 0.25 Hz; 3.5% enflurane was more depressant than 2.5% isoflurane at 1 Hz. Anesthetic effects on sustained contractures were also studied in frog ventricular strips that were superfused for 4-5 min with 40, 60, 80, and 100 mM K Ringer solution. Contractures induced by 80 and 100 mM K solution were depressed more by halothane (to 60% of control) than by isoflurane or enflurane (approximately 85% of control). However, only enflurane depressed the contractions at 1 Hz more than the sustained contractures in 100 mM K Ringer. The Ca2+ for activating contractions in rat ventricle is derived largely from the sarcoplasmic reticulum, the intracellular Ca2+ accumulation and release organelle. In contrast, Ca2+ for activating contractions in the frog ventricle originates primarily from the external medium. These results suggest that halothane is more potent than isoflurane in reducing the amount of Ca2+ rapidly released from the sarcoplasmic reticulum (as observed in rat), as well as in depressing entry of extracellular Ca2+ to activate myofibrils (as in frog). Enflurane appears to have intermediate potency with actions distinct from halothane and isoflurane. The greater potency of halothane may also be due in part to greater direct depression of actin-myosin ATPase.
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