Biomedical subjects
C McDonald
Publications and source records attributed to C McDonald.
Comparison of two techniques for targeting the production of monoclonal antibodies against particular antigens.
We have compared the efficacy of two methods for enhancing the probability of producing monoclonal antibodies against particular target antigens in a complex mixture. These methods use two tissue extracts, one extract that contains (A) and one extract that does not contain (B) the target antigen(s) of interest. In the chemical immunosuppression approach, cyclophosphamide is used to suppress the mouse's response to common antigens in extract B before injection of extract A containing the target antigens. In the tolerization approach, neonatal mice are tolerized against the common antigens in extract B before injection of extract A containing the target antigens. Although small numbers of animals were used in this initial comparison, immunodot assays clearly indicate that the cyclophosphamide immunosuppression method yields significantly more monoclonal antibodies specific for the target antigen-containing extract A than does the tolerization method.
Small intestinal function and dietary status in dermatitis herpetiformis.
Small intestinal morphology and function were assessed in 82 patients with dermatitis herpetiformis, 51 of whom were taking a normal diet and 31 a gluten free diet. Methods used were histopathological evaluation of jejunal mucosal biopsy specimens, quantitation of intraepithelial lymphocytes, cellobiose/mannitol permeability test, tissue disaccharidase values, serum antigliadin antibodies, and formal assessment of dietary gluten content by a dietician. There was no correlation between dietary gluten intake and the degree of enteropathy in the 51 patients taking a normal diet, whereas biopsy specimens were normal in 24 of the 31 patients on a gluten free diet, all previously having been abnormal. Eighteen patients on gluten containing diets had normal jejunal histology and in seven of these all tests of small intestinal morphology and function were entirely normal. Intestinal permeability was abnormal and serum antigliadin antibodies were present in most patients with enteropathy. Studies of acid secretion in seven patients showed that hypochlorhydria or achlorhydria did not lead to abnormal permeability in the absence of enteropathy. This study shows that a combination of objective tests of small intestinal architecture and function will detect abnormalities in most dermatitis herpetiformis patients, including some with histologically normal jejunal biopsy specimens. Nevertheless there is a small group in whom all conventional intestinal investigations are entirely normal.
Primitive reflexes in Alzheimer's disease.
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Linear kinematics of the men's 110-m and women's 100-m hurdles races.
Twenty-three male and nine female hurdlers were filmed using three-dimensional methods during competition at the 1988 United States Olympic Trials. An entire four-step cycle was analyzed, including the clearances of the men's fifth hurdle and the women's fourth hurdle. The results showed an increase in vertical velocity and a decrease in forward horizontal velocity during the takeoff of the hurdle step. The forward velocity was recovered mainly in the second support phase after the hurdle. The downward motion of the center of mass (c.m.) was not stopped until the second support phase after the hurdle clearance. The peak of the c.m. parabola was almost directly over the hurdle in the men, and 0.30 m before the hurdle in the women. It was shown that the women used a parabola with a larger margin over the top of the hurdle than the men: A lower parabola would shorten the hurdle step, and would require the lengthening of the three interhurdle steps. It would also make the duration of the airborne phase too short, which would not give the legs enough time to prepare for landing after the execution of their motions over the hurdle. Therefore, women should not be coached to imitate the men's hurdle clearance technique.
Angular momentum in the men's 110-m and women's 100-m hurdles races.
Twenty-three male and nine female hurdlers were filmed using three-dimensional methods at the 1988 United States Olympic Trials. With respect to the athletes, the X, Y, and Z axes pointed to the right, forward, and upward, respectively. During hurdle clearance, the X component of angular momentum was negative (clockwise rotation in a view from the right). Early in the airborne phase, it was associated with the motion of the trail leg. The downward motion of the lead leg was produced mainly by transfer of angular momentum from the trail leg, rather than by the lifting of the head-trunk. The Y component of angular momentum was negative (counterclockwise in a back view of a hurdler taking off from the right foot). It was necessary for the abduction of the trail leg. When this abduction slowed down, the angular momentum was taken up by the lowering (and slight adduction) of the left leg and elevation of the right elbow. The hurdle clearance required a positive Z component of angular momentum (counterclockwise in an overhead view): The clockwise angular momentum of the right arm as it swept backward was not enough to compensate for the larger counterclockwise angular momentum required for the forward motion of the trail leg. Our improved understanding of the rotations involved in hurdling will be useful for the correction of technique defects in individual athletes.
Intravenous or inhaled pentamidine for treating Pneumocystis carinii pneumonia in AIDS. A randomized trial.
OBJECTIVE: To evaluate the efficacy and toxicity of aerosolized pentamidine and of reduced-dose intravenous pentamidine for the treatment of mild to moderate Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN: Randomized open study with serial pulmonary function testing and measurement of pentamidine concentrations in plasma and bronchoalveolar lavage fluid. PATIENTS: Of 44 men and 1 woman with a mild to moderate first episode of P. carinii pneumonia (Pao2 greater than or equal to 7.3 kPa [55 mm Hg]), 23 received aerosolized pentamidine and 22, intravenous pentamidine. INTERVENTIONS: Pentamidine isethionate, 600 mg by inhalation using a Respirgard II nebulizer (Marquest Medical Products, Inc., Englewood, Colorado) or 3 mg/kg body weight intravenously, administered once daily for 2 to 3 weeks. MEASUREMENTS AND MAIN RESULTS: The planned 60-patient study was stopped after 45 patients had been enrolled. The rates (aerosolized compared with intravenous pentamidine) of initial failure, early recrudescence of symptoms, and relapse were 12% and 19% (difference, 7%; 99% confidence interval [CI], - 23% to 37%; P = 0.67), 35% and 0% (difference, 35%; CI, 13% to 58%; P = 0.02), and 24% and 0% (difference, 24%; CI, 4% to 49%; P = 0.03). The rates (aerosolized compared with intravenous pentamidine) of major toxicity were 0% (0 of 17 patients) and 10% (2 of 21 patients) (difference 10%; CI, -1% to 29%; P = 0.24). The mean (+/- SD) pentamidine concentration in bronchoalveolar lavage fluid for patients receiving aerosolized pentamidine was 96.6 +/- 65.1 ng/mL compared with 14.4 +/- 17.7 ng/mL for patients receiving intravenous treatment. Trough concentrations of pentamidine in plasma increased from 0 to 25.4 +/- 16.4, 56.5 +/- 26.1, and 61.1 +/- 56.0 ng/mL at the end of weeks 1, 2, and 3 of intravenous therapy, respectively. CONCLUSIONS: The data suggest that reduced-dose intravenous pentamidine was more effective than aerosolized pentamidine for treating mild to moderate P. carinii pneumonia. Systemic absorption during aerosolized therapy was minimal; daily doses of intravenous pentamidine resulted in increased accumulation of pentamidine in plasma.
Stability of solutions of histamine acid phosphate after sterilization by heating in an autoclave.
Histamine acid phosphate (HAP) solutions are used in tests for asthma and also as positive controls in general allergenic testing. Previously these solutions have been sterilized, if at all, by filtration, thus limiting the shelf-life of the preparation and introducing some degree of uncertainty in their use. It is shown here that HAP solutions can be sterilized successfully by heating in an autoclave with little degradation and that subsequent storage of autoclaved solutions indicates a minimum shelf-life of 4 months.
Screening plasma donors for high-titre antibody to cytomegalovirus using a latex agglutination test.
Cytomegalovirus (CMV) can cause severe morbidity in immunosuppressed patients. Regional transfusion centres in the UK are required to supply high-titre anti-CMV plasma to the Blood Products Laboratory (BPL), now called 'Bio-Products Laboratory', for the production of specific intravenous immunoglobulin at the Protein Fractionation Centre in Scotland. For this purpose, 703 plasmapheresis donors were screened by a modified latex agglutination test to assess their suitability as donors with high-titre anti-CMV. CMV antibodies were found in 48% of the donors. Seropositivity increased with age ranging from 33% in the 20- to 29-year age group to 57% in the 40-49 age group, although the 50-59 age group showed a slight decline to 53%. In all age ranges except the 40-49 group, seropositivity was highest in the female population. With the latex test, 14% of the total donors screened had a titre greater than or equal to 1 in 64, 7% greater than or equal to 1 in 128 and 4.2% greater than or equal to 1 in 256. Samples from 18 donors with titres greater than or equal to 1 in 128 were sent to BPL and all samples were found to have a sufficiently high titre for the production of CMV immune plasma. For BPL the 'cut-off' level for CMV immune plasma is a titre greater than or equal to 1 in 64 by complement fixation. Since the establishment of a panel of donors with high-titre anti-CMV plasma, more than 10 kg of plasma are dispatched monthly from our centre to BPL.
A comparison of geriatric day hospitals in Fife.
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Cytomegalovirus in blood from blood donors.
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Mesothelioma in railroad workers.
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Ovarian hormone-induced short-latency maternal behavior in ovariectomized virgin Long-Evans rats.
Two ovarian hormone regimens reported to induce rapid-onset maternal behavior (MB) in maternally naive virgin, ovariectomized Sprague-Dawley (SD) albino rats (R. S. Bridges, 1984, Endocrinology 114, 930-940; A. L. Giordano, 1987, Doctoral Dissertation, Rutgers University, Newark, NJ) were assessed in Long-Evans (LE) hooded rats, a strain which tends to be less maternally responsive in various situations dissociated from parturition. The combination of sufficiently high and long-lasting treatments with estradiol (E, 10-mm Silastic capsule, sc, on Day 1) and progesterone (P, 3 x 30-mm Silastic capsules, Days 3-13) resulted in a mean MB onset latency (after pup presentation on Day 14) of 1.8 days. In contrast, no-hormone or P-only controls had latencies of about 5.5 days. However, the E + P combination was completely ineffective if the E capsule was withdrawn along with the P capsules, unlike the case for SD rats. Also in contrast to the albinos, E alone was ineffective, while E treatment following P withdrawal was only partially effective. The most efficacious regimen, which included a P treatment (injections of 4 mg/day, Days 3-12 or 3-15) known to maintain pregnancy in ovariectomized rats, resulted in mean latencies of less than or equal to 1 day; 39% overall displayed MB rapidly, i.e., retrieval within 15 min of exposure to pups and crouching by 3 hr, and 89% became maternal by the next day. With this regimen, neither duration of 4 mg/day P treatment (10 or 13 days) nor hysterectomy 2 days before testing affected MB latencies. Thus, the essential features of the previously reported ovarian hormone regimens for induction of short-latency MB are efficacious in LE rats, but the hormonal requirements in this strain seem to be more precise. Factors which might contribute to an even higher percentage maternal on the first day of pup exposure are considered.
The stability of amoxycillin sodium in normal saline and glucose (5%) solutions in the liquid and frozen states.
The stability of a 1% w/v solution of amoxycillin sodium in normal saline and in glucose (5%) solutions was examined in the liquid and frozen states over the temperature range -26-60 degrees C. It was found that under all conditions amoxycillin sodium was much less stable in glucose (5%) solution. Freezing the solutions markedly reduced amoxycillin sodium stability. Maximum degradation rates in the frozen state occurred over the temperature range -7.5 degrees C to -6.5 degrees C in normal saline and at -8.9 degrees C in glucose (5%) solutions. For example, in normal saline the liquid state t90 (time for the concentration to decrease to 90% of its initial value) at 0 degree C of 252 h, was reduced to 8 h at -6.5 degrees C and increased to 14 h at -19.2 degrees C. In glucose (5%) solution comparative values of 12.5 h at 0 degree C, 2.5 h at -6.5 degrees C and 8.4 h at -19.2 degrees C were found. Amoxycillin sodium is very unstable in these solutions even at -26 degrees C. Maximum stability of the solutions examined in this study was at 0 degree C in normal saline and at -26 degrees C in glucose (5%) where the t90 value was 25.5 h.
A three-dimensional analysis of angular momentum in the hammer throw.
Eight hammer throwers were studied using three-dimensional cinematography. The local term of angular momentum of each thrower (HTL) followed a wide conical path, while the remote term (HTR) and the hammer angular momentum (HH) followed much narrower conical paths. HT, the sum of HTL and HTR, followed a conical path similar to that of HTL, although with smaller amplitude. HH was half of a cycle out of phase with HT. It was also larger but followed a narrower conical path. As a result, the conical paths of HH and HT counteracted each other, and HS, the total angular momentum vector of the thrower-hammer system, had little conical motion. The paths of the angular momentum vectors, the trunk tilt, and the height of the hammer plane relative to the system center of mass were interrelated. Some throwers kept the hammer plane high and the trunk tilting back in all the turns; other throwers kept the hammer plane low and the trunk tilting forward in the early turns, but the hammer plane rose in their late turns and the trunk tilted back. Two theories were proposed to explain why the athletes who had forward trunk tilt in the early turns tilted backward in the final part of the throw.
Enprofylline in chronic asthma.
A double-blind crossover study has been performed in 14 patients with moderately severe chronic asthma to compare the bronchodilator efficacy of two dosage regimens of intravenous enprofylline (high dose = 2 mg/kg bolus and 1 mg/kg/hour infusion; low dose = 1 mg/kg bolus and 500 micrograms/kg/hour infusion) with aminophylline (5 mg/kg/bolus and 500 micrograms/kg/hour infusion) and placebo. The bolus injections were given over 20 minutes and infusion over 160 minutes. Twelve subjects completed the study. High dose enprofylline was more effective than aminophylline in increasing PEF (P = 0.008) and FEV1 (P = 0.004). Low dose enprofylline and aminophylline were of similar efficacy. Side-effects, notably headaches and nausea, were more common with enprofylline; three out of 14 subjects receiving the high dose regimen developed severe nausea. The plasma enprofylline levels achieved with the high dose regimen were greater than anticipated. Further studies are required in acute severe asthma to clarify the therapeutic role of intravenous enprofylline and the most appropriate dosage regimen.
Contraceptive use in the chronically ill adolescent female.
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