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Biomedical subjects

D C Johnson

Publications and source records attributed to D C Johnson.

At least 127 records · Page 7Linked to original sources
PubMed1989

Wheezing on maximal forced exhalation in the diagnosis of atypical asthma. Lack of sensitivity and specificity.

STUDY OBJECTIVE: To determine whether wheezing on maximal forced exhalation is a predictor of asthma in persons with normal or nearly normal baseline spirometry. DESIGN: Prospective study of patients referred for methacholine challenge testing. SETTING: Pulmonary function laboratory at a hospital. PATIENTS: Forty-four patients referred for methacholine challenge testing because of the clinical suspicion of cough variant or otherwise difficult to diagnose asthma, with normal or nearly normal baseline spirometry and without wheezing on routine lung auscultation during quiet breathing. INTERVENTIONS: We listened for wheezing on maximal forced exhalation. Wheezing was defined as a continuous sound with a musical quality. Methacholine challenge testing was done. The concentration of methacholine required to produce a 20% fall in baseline FEV1 (PC20) of less than 8 mg/mL was considered a positive test for asthma. MEASUREMENTS AND MAIN RESULTS: Wheezing was present on maximal forced exhalation in 8 of 14 patients with a positive methacholine challenge test (sensitivity = 57%) and absent in 11 of 30 patients with a negative test (specificity = 37%). Furthermore, wheezing on maximal forced exhalation was present in 13 of 27 patients with a PC20 greater than 16 mg/mL and absent in 2 of 7 with a PC20 less than 4 mg/mL. CONCLUSIONS: Wheezing on maximal forced exhalation is neither sensitive nor specific for airway hyperreactivity.

Adult↗
PubMed1989

Protection of mice against lethal challenge with herpes simplex virus by vaccination with an adenovirus vector expressing HSV glycoprotein B.

Increasing attention has been focused on the use of recombinant mammalian viruses as potential vaccines. Recombinant human adenoviruses are one of the more promising vaccine vectors because they can be easily constructed and because live adenovirus vaccines have been administered orally to large numbers of military recruits without adverse reactions. In order to examine the efficacy of human adenoviruses as vaccines we have studied the immunity induced by a recombinant adenovirus vector, AdgB2, which induces high level expression of herpes simplex virus (HSV) glycoprotein B (gB) in human and murine cells. Mice inoculated with AdgB2 produced antibodies specific for gB which neutralized HSV in the presence of complement. Although mice inoculated with AdgB2 showed no ill-effects after AdgB2 inoculation and we were unable to detect replication of human adenoviruses in mice, the mice were protected from a lethal challenge with HSV after a single inoculation with AdgB2.

Adenoviruses, Human↗
PubMed1989

Surgical therapy for atrial tachycardia in adults.

Eighteen adult patients with atrial tachycardia refractory to treatment with a mean of four drugs underwent attempted surgical cure. Atrial tachycardia originated in the right atrium in 17 patients and the left atrium in 1 patient. Tachycardia could be reproducibly induced and terminated by atrial extrastimuli or atrial pacing in 8 patients (44%). Resection of the arrhythmogenic area was performed in 16 patients (89%), and an isolation procedure was performed in 1 patient. In seven cases (39%), the area of isolation or excision included the sinoatrial node. One patient underwent His bundle section because the arrhythmogenic region was too close to the atrioventricular (AV) conduction system to enable resection. The mean duration of clinical follow-up was 56 +/- 34 months. Clinical tachycardia recurred in five patients (28%), but in two patients it did not recur until greater than 1 year after surgery. A permanent pacemaker was implanted in 3 (18%) of the 17 patients whose His-Purkinje system was left intact. One other patient had required permanent pacing before surgery. Only one of the seven patients undergoing sinoatrial node resection or isolation required permanent pacing for symptomatic bradycardia. Apart from the requirement for permanent pacing, no significant complications occurred. Surgical therapy for atrial tachycardia is a safe procedure, but the rate of cure appears to be less than that of supraventricular tachycardias associated with accessory AV connections. Excision or isolation of the sinoatrial node does not necessitate permanent pacing in most patients.

Adolescent↗
PubMed1989

Surgery for supraventricular tachycardia (SVT).

All forms of supraventricular tachycardia (SVT) are now potentially curable by surgery and we believe that patients should be offered surgery as an initial therapeutic option. At Westmead Hospital, 311 patients have undergone surgery for SVT, 13 having AV node ablation, a procedure now rarely performed, and 298 have had attempts at curative surgery. One hundred and ninety-nine patients were diagnosed primarily as having a Wolff-Parkinson-White syndrome (WPW) and 139 had free wall or anterior septal connections with a clinical cure rate of 98.0%. The failures were entirely due to unrecognised posterior septal connections. Sixty patients had primarily posterior septal connections with a clinical cure rate of 96%. Atrioventricular junctional re-entry tachycardia may now be cured, probably by dividing an extra nodal His-to-atrial connection. Seventy-eight patients have undergone surgery with a clinical cure rate of 92%. Fifteen patients with right atrial tachycardias, 4 patients with nodo-ventricular fibres and 2 with incessant AV tachycardia have undergone surgery. The overall clinical cure rate for all patients is 95% and 92% at late electro-physiological study (EPS).

Adolescent↗
PubMed1989

Report of four cases of aneurysm complicating patch aortoplasty for repair of coarctation of the aorta.

Patch aortoplastry, used almost routinely in the period 1972-86, except in infants in the operative treatment of coarctation of aorta, is sometimes complicated by late formation of true or false aneurysms. This complication, which seems likely to increase with longer follow-up, calls into question the advisability of patch aortoplasty except when it has specific advantages. Other surgical techniques such as subclavian flap angioplasty in infants and young children or radical excision with end-to-end anastomosis may be preferable where there is no anatomical contraindication. In any case, lifelong yearly review of postoperative patients should include chest X-ray and further investigation by computerized tomography scanning or other suitable imaging of those with suspicious findings.

Adolescent↗
PubMed1989

Effects of hypercapnia on brain pHi and phosphate metabolite regulation by 31P-NMR.

The ability of brain cells to regulate intracellular pH (pHi) and several phosphate metabolites was evaluated during 1 h of hypercapnia (inspiratory CO2 fraction of 0.10 and 0.05) in anesthetized rats by 31P high-field (145.6 MHz) nuclear magnetic resonance spectroscopy. Body temperature was maintained at 37 +/- 0.5 degrees C. Fully relaxed spectra were obtained for controls and 30-50 min after CO2 loading and CO2 withdrawal. Spectra were taken serially every 2.5 min after gas mixtures were changed. Brain pHi decreased 0.10 +/- 0.02 units [7.06 +/- 0.01 (SE)] to 6.96 +/- 0.01 (P less than 0.001) after 30-50 min of 10% CO2 breathing, and arterial pH decreased 0.24 +/- 0.01 units. Brain pHi decreased by 0.045 +/- 0.01 units (7.05 +/- 0.01 to 7.01 +/- 0.01, P less than 0.05) during 5% CO2 breathing. Brain pHi returned to control values after 30-50 min of CO2 washout in both groups. In three of six animals breathing 10% CO2, there was an undershoot in brain pHi by 0.07-0.09 units between 2.5 and 20 min of hypercapnia. Three animals exhibited an overshoot in pHi by 0.06-0.11 units between 7.5 and 17.5 min during CO2 washout. Phosphocreatine-to-Pi and Pi-to-beta-ATP ratios changed during hypercapnia and returned to base line after withdrawal of CO2. The findings of a smaller brain pHi change than arterial pH change and undershoots and overshoots in pHi support the view that pHi regulation involves active processes such as transmembrane ion transport.

Adenosine Triphosphate↗
PubMed1989

CSF acidosis augments ventilation through cholinergic mechanisms.

Ventilation is influenced by the acid-base status of the brain extracellular fluids (ECF). CO2 may affect ventilation independent of changes in H+. Whether the acidic condition directly alters neuronal firing or indirectly alters neuronal firing through changes in endogenous neurotransmitters remains unclear. In this work, ventriculocisternal perfusion (VCP) was used in anesthetized (pentobarbital sodium, 30 mg/kg) spontaneously breathing dogs to study the ventilatory effects of acetylcholine (ACh), eucapnic acidic (pH approximately 7.0) cerebrospinal fluid (CSF), and hypercapnic acidic (pH approximately 7.1) CSF in the absence and presence of atropine (ATR). Each animal served as its own control. Base line was defined during VCP with control mock CSF (pH approximately 7.4). With ATR (4.8 mM) there was an insignificant downward trend in minute ventilation (VE). ACh (6.6 mM) increased VE 53% (n = 12, P less than 0.01), eucapnic acidic CSF increased VE 41% (n = 12, P less than 0.01), and hypercapnic acidic CSF increased VE 47% (n = 6, P less than 0.01). These positive effects on ventilation were not seen in the presence of ATR. This suggests that acidic brain ECF activates ventilatory neurons through muscarinic cholinergic mechanisms. Higher concentrations of ACh increased ventilation in a concentration-dependent manner. Higher concentrations of ATR decreased ventilation progressively, resulting in apnea. The results suggest that ACh plays a significant role in the central augmentation of ventilation when the brain ECF is made acidic by either increasing CSF PCO2 or decreasing CSF bicarbonate.

Acetylcholine↗
PubMed1989

Effects of hypothermia on rat brain pHi and phosphate metabolite regulation by 31P-NMR.

The effects of arterial alphastat regulation on brain intracellular pH (pHi) and several phosphate metabolites were assessed in anesthetized rats during hypothermia (28.6 +/- 0.2 degrees C) and normothermia (36.2 +/- 0.2 degrees C) by using 31P high-field (8.5 T) nuclear magnetic resonance (NMR). There were significant differences in pHi and metabolite ratios at the two temperatures under conditions of equal minute ventilation. During hypothermia, the brain pHi was 0.09 U higher, the phosphocreatine-to-inorganic phosphate (PCR/Pi) ratio 49% larger, and Pi-to-ATP 20% lower than at normothermia. These changes were fully reversible on warming the animal. The change in brain pHi/temperature was -0.011U/degrees C (95% confidence interval -0.007 to -0.016). The brain's ability to regulate its pHi and phosphate metabolism during hypercapnic acid-base stress was studied by using 10% CO2 ventilation. Hypothermic rats showed a larger fall in brain pHi (0.145 +/- 0.01 U, 7.15-7.01) with 10% CO2 than normothermic rats (0.10 +/- 0.02 U, 7.06-6.96). Similarly ventilated rats had a larger fall in arterial pH with 10% CO2 at hypothermia (0.36 +/- 0.04 U) than normothermia (0.24 +/- 0.01 U), so the delta brain pH/delta arterial pH was the same at both temperatures. The brain PCr-to-Pi ratio decreased approximately 20% during 10% CO2 breathing in both hypothermic and normothermic animals. Brain pHi and metabolite ratios returned to base line 30-50 min after CO2 washout in both groups. In summary, lowering body temperature while maintaining constant ventilation leads to changes in brain pHi and metabolites.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Increased activity of ovarian thecal cytochrome P450(17 alpha) in the hamster induced by endogenous LH.

The in vivo regulatory action of LH on the ovarian androgen synthesizing enzyme cytochrome P450(17 alpha) (17 alpha-hydroxylase/C17,20-lyase) was studied in cyclic golden hamsters. Immunohistochemical studies using anti-porcine testicular cytochrome P450(17 alpha) antibody indicated that the enzyme was limited to thecal cells. Transient removal of the negative feedback action of endogenous steroids by use of aminoglutethimide phosphate produced an increase in endogenous gonadotropins. A single dose (30 mg) of aminoglutethimide on days 1, 2 or 3 of the estrous cycle (day 1 = estrus), increased serum levels of LH, but only for about 12 h. Increases in enzyme activities, which persisted for at least 24 h, followed. Two doses of aminoglutethimide, 12 h-apart, maintained elevated levels of serum LH for about 36 h, and enzyme activities for at least 48 h. However, when the drug was given after the pre-ovulatory surge of LH on proestrus, and again on the morning of estrus, neither serum LH nor enzyme activity levels increased within 24 h. Induced increases in enzyme activity had no effect upon ovulation rate, as determined by the number of oviductal eggs present on the morning of estrus. The results demonstrate clearly a close correlation between serum concentrations of LH and ovarian androgen synthesizing enzyme activity.

Aminoglutethimide↗
PubMed1989

Comparison of early and late dimensions and arrhythmogenicity of cryolesions in the normothermic canine heart.

Little is known about myocardial cryoablation at normothermia and the effect of cryoprobe head size and duration of freeze on final lesion volume. In the present study, cryolesions were created with a carbon dioxide cryoprobe with two head sizes (cylindrical head 6 mm diameter and large circular head 18 mm diameter) in the normothermic canine heart during cardiopulmonary bypass. The duration of freeze (exposure time) varied from 2 to 3 or 4 minutes and the effects on immediate and chronic lesion size were evaluated. Lesions produced by epicardial exposures were compared with intramyocardial lesions created by placing the cylindrical head in a 6 mm stab incision. A minimum of four lesions were created in each dog. Lesion size was evaluated at 0 minutes (iceball) and 24 hours (two dogs), 7 days (one dog), or 4 weeks (five dogs). Iceball diameter was approximately 5 mm larger than chronic lesion diameter regardless of head size or exposure time. Prolongation of exposure time from 2 to 3 minutes resulted in significant increases in the volume of epicardial lesions (cylindrical head: 280 +/- 100 mm3 versus 740 +/- 200 mm3, p = 0.001; circular head: 1200 +/- 100 mm3 versus 2300 +/- 500 mm3, p = 0.007) because of increases in diameter and depth. No further increase in lesion size was observed when exposure time was prolonged from 3 to 4 minutes. A 3-minute intramyocardial exposure with the cylindrical head placed in a stab incision enabled production of transmural lesions (16 +/- 2 mm deep). Two and 4 weeks postoperatively, dogs underwent electrophysiologic study from the right and left ventricular apices. No animals had inducible ventricular tachycardia despite the heterogeneous configuration of the multiple cryolesions. In conclusion, it is possible to produce rapid and predictable ablation of clinically useful volumes of myocardium during normothermic bypass with the use of currently available equipment. Under these conditions, an exposure time of 3 minutes is optimal for a liquid carbon dioxide cryoprobe. Cryolesions should be overlapped by at least 2.5 mm to produce continuous areas of ablation. Multiple cryolesions do not form a chronic substrate for ventricular tachycardia.

Animals↗
PubMed1988

Multiple estrogenic action of O,P'-DDT: initiation and maintenance of pregnancy in the rat.

The estrogenic action of O,P'-DDT has been known for many years. The majority of studies have used immature or ovariectomized adult rats to demonstrate estrogenic responses that require interaction with an intranuclear receptor and genic expression. However, evidence is accumulating that not all estrogenic effects are mediated by such a receptor; initiation of implantation being one such effect. The present study examined the ability of O,P'-DDT to initiate embryo implantation in the progesterone-primed uterus of a hypophysectomized adult rat. Not only did O,P'-DDT initiate implantation, it also maintained pregnancy for at least 3 days. However, when administered at the time of mating or early after fertilization, the same dosage caused loss of pre-implantation embryos. The results are consistent with the interpretation that O,P'-DDT has multiple estrogenic actions that may involve more than 1 kind of receptor.

Animals↗
PubMed1988

Management of oesophageal cancer at Westmead Hospital from 1979-1985.

The aim of this study was to evaluate the various treatment options, including radiotherapy, surgery and chemotherapy, when all patients with carcinoma of the oesophagus were assessed and managed by the same team. From December 1, 1979 to December 31, 1985, 144 patients with carcinoma of the oesophagus were referred to Westmead Hospital. Eighty-five patients were men, 59 patients were women and the median age was 63 years. Twenty-five patients were at stage I, 75 patients were at stage II, 24 patients were at stage III and 20 patients were at stage IV of oesophageal cancer. Forty-two patients underwent surgical resection. Fifty patients underwent radical radiotherapy, 30 patients underwent palliative radiotherapy and 22 patients underwent palliative intubation. The operative mortality of those patients who underwent surgery was zero. The treatment mortality of those who underwent radical radiotherapy was 6%, and for those who underwent palliative radiotherapy, was 16.7%. The mortality after intubation was 12.5%. The prevalence of benign strictures was 7.5% after surgery, 33% after radical radiotherapy and 8% after palliative radiotherapy. The prevalence of malignant strictures (recurrent disease) was 2.5% after surgery, 21% after radical radiotherapy and 20% after palliative radiotherapy. The median survival after surgery was 12 months; that after radical radiotherapy, 12 months; that after palliative radiotherapy, six months; and that after intubation, 3.5 months. Where all patients with carcinoma of the oesophagus were managed by a team approach the treatment mortality was low but the long-term survival remained poor.

Adenocarcinoma↗
PubMed1988

Antiviral drugs for common respiratory diseases. What's here, what's to come.

Progress is being made in the development of drugs for the prevention and treatment of viral respiratory infections. Two drugs currently available to clinicians are amantadine (Symmetral) and ribavirin (Virazole). Oral amantadine is effective for both treatment and prevention of uncomplicated influenza A infections. Although vaccination continues as the mainstay of influenza prevention, amantadine is useful for unvaccinated patients if complications are likely. When used for treatment, it must be started within the first 48 hours of illness. Ribavirin appears to be safe for treatment of respiratory syncytial virus infections in nonintubated infants. It must be delivered by aerosol in a hospital setting. Patients at risk for complications should be given the drug as early as possible in the course of the disease. Efficacy has yet to be proven in intubated patients, but the drug is probably safe to use with proper supervision. On the horizon are rimantadine and the interferons. Rimantadine is similar to amantadine in its action and indications for use and has a lower incidence of side effects. The interferons have not been the hoped-for panacea for viral respiratory infections but may be useful in a nasal spray for the prevention of colds caused by rhinovirus.

Adult↗
PubMed1988

Loss of ovarian 17 alpha-hydroxylase/C17,20-lyase activity induced by human chorionic gonadotropin is correlated with in vivo substrate availability.

Administration of human chorionic gonadotropin (hCG) to hypophysectomized immature rats caused a rapid reduction in ovarian microsomal 17 alpha-hydroxylase/C17,20-lyase activity (cytochrome P450(17 alpha] with a concomitant large increase in serum progesterone (P4) level. Pretreatment with cycloheximide (Cyclo) or aminoglutethimide (Ag) prevented these effects of hCG, while Actinomycin D (Act-D) or Azastene, an inhibitor of 3-hydroxysteroid dehydrogenase, were ineffective. In ovaries with enzyme activity increased by 48 h exposure to pregnant mare's serum gonadotropin, hCG also caused a large decrease in enzyme activity but only after a lag period of about 2 h: P4 levels were increased simultaneously. Administration of Cyclo. or puromycin (Puro) caused a loss of enzyme activity without changing P4 levels, but both inhibitors prevented some of the loss of activity and rise in P4 induced by hCG. AG and Act D completely inhibited the enzyme reducing action of hCG, as well as the increase in P4 synthesis, in these animals. P4 applied directly onto one ovary of an animal given hCG plus AG reduced enzyme activity by 69%. The results are consistent with the interpretation that increased substrate concentration is one of but not the only important factor in loss of hydroxylase/lyase activity induced by a sudden large increase in luteinizing hormone activity.

Aminoglutethimide↗
PubMed1988

Abundant expression of herpes simplex virus glycoprotein gB using an adenovirus vector.

Herpes simplex virus type 1 (HSV-1) glycoprotein B (gB) is a major component of infected cell membranes and virion envelopes. Glycoprotein B is known to be essential for entry of viruses into cells and may play important roles in virus-induced cell fusion and other alterations in cell morphology. In order to study the biochemical and immunological properties of gB in isolation from other HSV-1 polypeptides we have constructed human adenovirus vectors capable of expressing high levels of gB. The gB gene was coupled to the SV40 early promoter and inserted into the E3 region of two adenovirus vectors, one in which the E1 region was deleted (AdgB-1) and another which contained E1 sequences (AdgB-2). In AdgB-1 the orientation of the chimeric gB-SV40 gene was right to left, i.e., opposite to the direction of late and E3 mRNA transcription, whereas in AdgB-2 the orientation was left to right. Human 293 cells which express E1 functions supported replication of AdgB-1 and gB was expressed in these cells but not in mouse cells and only at very low levels in human cells other than 293. Replication of AdgB-2 was not limited to 293 cells and the virus was able to induce synthesis of gB at levels equal to or higher than those expressed in HSV-1-infected human or mouse cells. Microscopic examination of AdgB-2-infected cells revealed extensive vacuolization in a manner completely uncharacteristic of adenovirus-infected cells, and fluorescent antibody staining indicated that gB was not only present at the cell surface but also concentrated in the cytoplasmic vacuoles.

Adenoviridae↗