Treatment of Wegener's granulomatosis.
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Biomedical subjects
Publications and source records attributed to P Mason.
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Ovulation was successfully induced with luteinising hormone releasing hormone in 28 women with hypothalamic amenorrhoea who had failed to respond to treatment with clomiphene. Luteinising hormone releasing hormone was administered in a pulsatile manner with miniaturised automatic infusion systems. The rate of ovarian follicular maturation, as monitored by serial pelvic ultrasonography, was similar to that observed in spontaneous cycles. Endocrine assessment by serial measurement of gonadotrophin, oestradiol, and progesterone concentrations showed hormone concentrations to be within the normal range. Intravenous treatment was required in only two patients, the remainder responding satisfactorily to subcutaneous infusion. All patients conceived within six cycles of treatment, and only one multiple pregnancy occurred.
Amiloride (75 mg daily) and spironolactone (300 mg daily) were given to five normal subjects for 7 days in order to compare metabolic effects at maximal doses. Blood pressure, body weight, Na+ and K+ balance, and plasma concentrations of Na+, K+, active and total renin, angiotensin II, aldosterone, 11-deoxycorticosterone (DOC), 18-hydroxydeoxycorticosterone (18-OH DOC), corticosterone (B), 18-hydroxycorticosterone (18-OH B) and cortisol were measured before and on each day of treatment. Natriuresis and K+ retention were significantly greater with amiloride. Plasma K+ increased from 4.1 +/- 0.2 to 4.9 +/- 0.2 mmol/l (mean +/- s.d.) on amiloride and from 4.0 +/- 0.2 to 4.4 +/- 0.2 mmol/l with spironolactone. Stimulation of renin, angiotensin II, aldosterone and 18-OH B occurred with both drugs but was greater with amiloride in each case. A transient decrease in systolic and diastolic blood pressure was observed after 2 days of spironolactone treatment but not with amiloride. The slope of the regression of aldosterone on angiotensin II during spironolactone treatment was less than that with amiloride, consistent with partial blockade of aldosterone synthesis by spironolactone. These data suggest that the maximum metabolic effects of amiloride exceed those of spironolactone.
Cooling and drying of the intrapulmonary airways have been shown to be important stimuli for the development of bronchospasm induced by exercise and isocapnic cold air hyperventilation. It has also been suggested that alpha-adrenergic receptor activity is increased at lower temperatures. To evaluate the role of alpha-adrenergic activity in the development of bronchoconstriction during airway cooling, we examined the effects of alpha-adrenergic blockade with phentolamine on bronchospasm induced by exercise and isocapnic cold air hyperventilation in 8 asthmatics. Exercise consisted of 6 min of steady-state exercise at 90% predicted maximal heart rate breathing compressed air at 0% humidity and 21 +/- 1 degrees C (mean +/- SD). During baseline exercise studies, FEV1 fell 41.6 +/- 15.8%, but only 12.8 +/- 8.5% during alpha-adrenergic blockade (p less than 0.001). Isocapnic cold air challenge consisted of breathing compressed cold air (0% humidity, -17 +/- 4 degrees C) for 3-min periods, with stepwise increases in minute ventilation (Ve) until the FEV1 fell at least 20%. During baseline cold air challenges, FEV1 fell 20% (PD20 FEV1) at a Ve of 48.8 +/- 21 L/min. However, during alpha-adrenergic blockade 6 asthmatics were able to achieve much higher levels of VE (86.6 +/- 22.7 L/min) before FEV1 fell 20% (p less than 0.01), and 2 asthmatics did not decrease their FEV1 by 20%, despite reaching maximal levels of ventilation of 132 and 108 L/min, respectively. Alpha-adrenergic blockade did not affect airways responses to histamine or ragweed antigen (p greater than 0.1).(ABSTRACT TRUNCATED AT 250 WORDS)
A selection of pulsatile infusion devices suitable for administering LHRH are described. The principles of operation and control options of the different pumps are explained, including the new compact direct-drive syringe pump. The relative merits of these infusion systems are discussed and it is concluded that size, ease of use and range of application are paramount.
An evaluation was made of the role of the outer membrane of Haemophilus influenzae type b as a permeability barrier against beta-lactam antibiotics. Sonic extracts of H. influenzae containing beta-lactamase were assayed for the rates of hydrolysis of benzylpenicillin, ampicillin, cloxacillin, cephacetrile, cefazolin, cefamandole, cephalothin, cephaloridine, cephaloglycin, and cefaclor. Benzylpenicillin was hydrolyzed most rapidly, whereas cephacetrile, cephaloridine, and cephaloglycin were the poorest substrates for the beta-lactamase. The hydrolysis of these ten beta-lactams by intact cells was also determined; it was necessary to stabilize the cells with MgCl2 to prevent lysis and thereby to maintain the beta-lactamase in the periplasm. Calculations were made of the concentration of the antibiotics which had accumulated in the periplasm. The transmembrane permeability coefficient, C, was determined for the ten beta-lactam antibiotics. All of the compounds tested were able to diffuse across the outer membrane of H. influenzae type b very efficiently. The values of the permeability coefficient were compared with the partition coefficients of the antibiotics in a two-phase isobutanol/water mixture. For a ten-fold increase in hydrophobicity, there was a ten-fold decrease in the permeability coefficient. The outer membrane of haemophilus was not an effective barrier against the penetration of penicillins or cephalosporins. The activity of these compounds could be attributed either to their low hydrolysis by beta-lactamase or to the high affinity of binding to their sensitive targets.
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A receptor protein in the outer membrane of Escherichia coli K-12 is required for the binding of ferrichrome-iron at the cell surface and for the transport of iron from this complex into the cell. This protein of Mr 78,000 is the product of the fhuA (previously called tonA) gene, located at 3.5 min on the E. coli chromosome. We cloned the fhuA gene into plasmid p343, a high-copy-number cosmid derived from pBR322. An 8.5-kilobase pair fragment of E. coli chromosomal DNA, generated by hydrolysis with the restriction endonuclease HindIII, was found to have conferred the FhuA+ phenotype to E. coli P8, which lacks the ferrichrome-iron receptor. A partial physical map of this recombinant plasmid pPM18 was established by determining the restriction endonuclease sites for BglII, EcoRI, PstI, PvuII, SmaI, and XhoI. The fhuA gene was localized to a 3.5-kilobase pair fragment of DNA whose extremities were defined by the restriction sites PstI-PvuII. A 7.5-fold enhancement of the rate of transport of iron from the ferrichrome complex was measured for cells which contained pPM18 as compared to wild-type E. coli K-12. Overproduction of the FhuA protein was detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of outer membrane proteins of the recombinant plasmid-containing strain. Proteins encoded by the subcloned DNA fragments were identified by [35S]methionine labeling of maxicells of E. coli CSR603, which contained recombinant plasmids; only one polypeptide chain, the presumptive fhuA gene product, was detected.
In asthmatics, alpha-adrenergic blockage with oral phentolamine partially or completely blocked bronchospasm after maximal exercise challenge. Bronchial reactivity to isocapnic hyperventilation with conditioned cold air was also reduced. However, non-specific airways reactivity to inhaled histamine did not change. Therefore, exercise and cold induced bronchospasm in asthma may be partially mediated by alpha adrenergic neural mechanisms perhaps through sensitization of alpha receptors during airway cooling.
Using an optical diffraction technique, the series elasticity of frog striated muscle fibres was investigated. One source of series elasticity was located in the cross-bridges during the application of either quick stretches or releases of muscle fibres. Evidence is presented here for a second component attributable to a small population of slowly activated sarcomeres. The size of the second component was progressively reduced until it virtually disappeared at a sarcomere length of 3 microns. A third component appears to reside in the thick filaments. Calculation of the elastic energy in the muscle fibres enabled an identification of the source of the energy to be made in terms of the components of the series elasticity. Evidence is presented of a short-range elastic component present in resting fibres.
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A screening test to measure nonspecific airways reactivity was developed and compared to a standard methacholine inhalation challenge in 13 asthmatic patients and ten normal control subjects. The screening challenge consisted of one deep breath, then four breaths of a 5 mg/ml methacholine solution followed by one and four breaths of 25 mg/ml of methacholine. Subjects with a history of wheezing received the 5 mg/ml of methacholine first while those without a history of asthma began the challenge at the 25 mg/ml methacholine concentration. Spirometric test were employed and the challenge was terminated when FEV1 fell 20 percent from baseline. The standard methacholine challenge used a dosimeter and all subjects took five breaths of saline solution followed by seven increasing concentrations of methacholine. Dose response curves were constructed and the provocation dose of methacholine that caused a 20 percent fall in FEV1 was calculated for each protocol. Results of the screening methacholine challenge correlated with those obtained from the more lengthy standard protocol (r = 0.94), and correctly identified levels of airways reactivity in asthmatic patients and normal subjects. The abbreviated protocol was rapid (6-12 min), safe, and inexpensive. Since the equipment is readily available and easy to transport, it could be used at sites outside the hospital as a screening test for nonspecific airways reactivity.
Previous studies are in conflict over the effect of infusing mixed fibrinogen-fibrin degradation products on fibrinogen synthesis, as determined by changes in fibrinogen concentration or by incorporation of labeled amino acids into fibrinogen. We have injected purified homologous fragments D1 and E into rats and measured their fibrinogen and albumin synthetic rates by the [14C]carbonate technique, a method that provides quantitative estimates of hepatic secretory protein synthesis. Fibrinogen fractional synthetic rates were increased 2.5 times in animals injected with fragment D1, compared with saline-injected controls. No increase were observed in fragment E-injected animals. Neither fragment produced changes in albumin synthesis. Fragment D increased plasma fibrinogen concentration, but did not raise plasma haptoglobin levels. These results suggest that fragment D is a regulator of fibrinogen synthesis.
Pulse-propagation measurements on a muscle stimulated into tetanus show that the stiffness develops earlier and starts later than the tension. It is concluded that the myosin heads which moves towards the actin filaments during excitation become mechanically attached to them.
Four methods (radioimmunoassay, electroimmunoassay, laser nephelometry and kinetic immunoturbidimetry) have been evaluated for the measurement of proteins with pregnancy-specific beta1 glycoprotein immunoreactivity. The influence of two maternal plasma proteins with different electrophoretic mobilities (alpha2 and beta1) but with similar antigenic determinants has been assessed in each assay system. The radioimmunoassay method, which utilises a homogeneous preparation of pregnancy-specific beta1 glycoprotein for the preparation of iodinated tracer, and the kinetic immunoturbidimetric assay which measures antigen-antibody complex formation over the first minute of the reaction, were both considerably more specific for the beta1 component of pregnancy specific beta1 glycoprotein immunoreactivity than the laser nephelometric or electroimmunoassay methods.
Typical Cogan syndrome (CS) is a disease of young adults consisting of flares of interstitial keratitis (IK) and sudden onset of Ménière-like attacks. The prognosis of typical CS is excellent with life-threatening aortic insufficiency (AI) developing in only 10% of reported cases. Serious systemic necrotizing vasculitis (SNV) rarely, if ever, complicates typical CS. Atypical S (vestibuloauditory dysfunction with types of inflammatory eye disease other than IK) frequently overlaps other defined rheumatologic syndromes, is associated with vasculitis in 21% of cases, and carries a less favorable prognosis than typical CS. Topical ocular corticosteroids can usually control IK, and a short trial of systemic corticosteroids is warranted as soon as possible after the onset of hearing loss. SNV should be treated initially with prednisone and may also require the administration of cytotoxic agents, while aortitis and AI can be controlled with the administration of prednisone and surgical replacement of the aortic valve.
Laser diffraction and tension measurements from frog muscle during isometric tetanus reveal that the sarcomeres contract more rapidly than tension develops.
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