Biomedical subjects
S Johnston
Publications and source records attributed to S Johnston.
Cadmium effects on bone metabolism: accelerated resorption in ovariectomized, aged beagles.
The purpose of this study was to evaluate, in an animal whose skeleton is comparable to humans, the combined effects of estrogen depletion and Cd exposure on bone resorption by monitoring skeletal release of 45Ca and to determine whether Cd-induced bone resorption occurred independent of osteotropic hormone changes and renal dysfunction. Cd exposure following ovariectomy or sham surgery was for 7 months: 1 month by oral ingestion of capsules (1, 5, 15, 50 ppm) and 6 months via drinking water (15 ppm). Serum and fecal 45Ca were increased at 1 week following ovariectomy (OV) (54 +/- 9% and 122 +/- 40%, respectively), but this response was attenuated by 2 weeks. Five of seven exposed dogs had increased serum and fecal 45Ca during the 50-ppm Cd capsule period (15-40% and 15-190%, respectively). Serum 45Ca levels in OV/+Cd dogs showed a significant and consistent increase within 1 week of initiating each of three separate Cd.H2O exposure cycles. Blood Cd levels increased over time from 2 to 15 micrograms/l, coinciding with the elevated serum 45Ca concentrations. No correlation was observed between serum 45Ca increases and parathyroid hormone, 1,25-(OH)2-vitamin D, or calcitonin. No effects of ovariectomy and/or Cd were observed in total serum Ca, calciotropic hormone concentrations, serum or urinary phosphorus and creatinine, creatinine clearance, or urinary specific gravity. Urinary Cd concentrations ranged from 7 to 50 micrograms/l in exposed dogs but were not detectable in nonexposed dogs. Urinary protein concentrations showed no differences between groups. Cd increased bone resorption (skeletal 45Ca release) in ovariectomized and sham-operated dogs without renal dysfunction or calciotropic hormone interaction. Based on our results, Cd is an exogenous factor which exacerbates bone mineral loss in postmenopausal osteoporosis.
Acute hypoxemic respiratory failure in infants and children: clinical and pathologic characteristics.
OBJECTIVE: To examine the clinical and pathologic features of acute hypoxemic respiratory failure in children. DESIGN: Retrospective review of medical records and pathologic material during a 44-month period. SETTING: Multidisciplinary pediatric ICU. PATIENTS AND METHODS: With the assistance of a computerized database, the medical records of 2,254 pediatric ICU admissions were evaluated to identify children with respiratory failure. Children with acute hypoxemic respiratory failure who met the following definition were selected for inclusion: a) PaO2 less than 75 torr (less than 10.0 kPa) with an FIO2 of greater than 0.5; b) diffuse bilateral infiltrates on chest radiograph; and c) exclusion of cardiogenic pulmonary edema clinically or by pulmonary artery catheterization. Patients were excluded if they did not receive tracheal intubation and assisted ventilation. The medical records were reviewed for demographic, clinical, and physiologic information. Pathologic findings from autopsy or lung biopsy were also reviewed. Patients were placed in one of six groups based on their underlying disorder. In addition, the presence of neutropenia, septic shock, or a history of bone marrow transplantation was noted as a coexisting condition. MAIN RESULTS: A total of 100 acute hypoxemic respiratory failure patients were identified (4.4% of all 2,254 pediatric ICU admissions; 50 male, 50 female). Mean age was 6.0 +/- 5.4 (SD) yrs (range 1 month to 18 yrs). The overall mortality rate was 72%. The mortality rate was not affected by the underlying disorder, but it was higher in the presence of septic shock (80% vs. 58%; odds ratio 2.8), neutropenia (88% vs. 64%; odds ratio 4.0), and bone marrow transplantation (95% vs. 66%; odds ratio 10.4). When multivariate regression analysis was performed using all coexisting conditions, human immunodeficiency virus status, and patient gender, only a history of bone marrow transplantation and gender appeared to affect outcome. Oxygenation ratio (PaO2/FIO2), alveolar-arterial oxygen tension difference, duration of exposure to high levels of oxygen, and airway pressure measurements indicated more severe derangement of pulmonary function in those patients who died. Cardiac function was similar in survivors and nonsurvivors. Respiratory failure occurred in 32 children with severe neutropenia (mean absolute neutrophil count 55 +/- 101 cells/mm3), including 16 children with an absolute neutrophil count of 0. Pulmonary tissue from 37 children was studied. Diffuse alveolar damage was observed in 24%; morphologic evidence of infectious pneumonitis was encountered in an additional 41%. CONCLUSIONS: Children with acute hypoxemic respiratory failure represent a heterogeneous subset of patients. In our group of patients, infectious pneumonitis was more commonly encountered than diffuse alveolar damage. The mortality rate of children with acute hypoxemic respiratory failure has not improved since 1980.
Cardiopulmonary, anesthetic, and postanesthetic effects of intravenous infusions of propofol in greyhounds and non-greyhounds.
The cardiopulmonary, anesthetic, and postanesthetic effects of an IV infusion of the hypnotic agent propofol were assessed in 6 Greyhounds and 7 non-Greyhounds. After IM injection of acetylpromazine and atropine, a bolus injection of propofol sufficient to allow endotracheal intubation (mean +/- SEM = 4.0 +/- 0.3 mg/kg of body weight in Greyhounds; 3.2 +/- 0.1 mg/kg in non-Greyhounds) was administered, followed by continuous infusion at a rate of 0.4 mg/kg/min for 60 minutes, during which time dogs breathed 100% oxygen. In 23% of all dogs (3 of 13), apnea developed after initial bolus administration of propofol. Arterial blood pressure was well maintained in all dogs, but heart and respiratory rates were decreased significantly (P less than 0.05) during the infusion in Greyhounds. In Greyhounds, mild respiratory acidosis developed after 45 minutes, whereas arterial carbon dioxide tension was increased at all times after propofol administration in non-Greyhounds. In all dogs, PCV and total plasma proteins were unaffected by propofol. Rectal temperature decreased during treatment. Muscle tremors were observed in approximately 50% of dogs (in 3 of 6 Greyhounds and 3 of 7 non-Greyhounds) during and after infusion of propofol. Non-Greyhounds lifted their heads, assumed sternal recumbency, and stood 10 +/- 1, 15 +/- 3, and 28 +/- 5 minutes, respectively, after the end of the infusion; in Greyhounds, the corresponding times were 36 +/- 4, 43 +/- 6, and 63 +/- 7 minutes.
A system for the quality audit of treatment dose delivery in radiotherapy.
Treatment planning is a process requiring the cooperation of a number of different staff groups. The possibility for error is well recognised and quality control procedures are necessary to ensure that the chances of errors in planning leading to incorrect treatments are as low as possible. An audit system is described which is based on the calculation of the dose delivered to the patient using the parameters set for treatment as input data. The calculated dose is compared with the prescribed dose and errors greater than a defined limit are flagged. During a period of 19 months during which this audit procedure has been operating a total of 14 errors in excess of 5% were discovered and corrected, this is approximately 0.5% of the total number of plans checked.
Neuroendocrine regulation of growth hormone secretion in sheep. IV. Central and peripheral cholecystokinin.
The result of alterations in the levels of CCK, in the blood and in the cerebrospinal fluid, on the functioning of the growth hormone axis has been examined in sheep. Male Coopworth sheep of about 40 kg liveweight were given various doses of CCK either intracerebroventricularly (icv) or intravenously (iv). Other similar sheep were given various doses of a CCK antagonist (loxiglumide) by the same routes. Bolus iv administration of either 35 micrograms or 200 micrograms of CCK had no effect on plasma GH levels. When given icv, however, CCK resulted in a marked (P less than 0.01) prolonged depression in plasma GH levels. The decrease in GH secretion could be partially attenuated by concurrent administration of loxiglumide, but was completely unaffected by concurrent administration of antisomatostatin serum icv. Loxiglumide alone had no effect on plasma GH levels when given at up to 200 micrograms icv, but intravenous administration of 8 mg of the CCK antagonist resulted in an increase in plasma GH concentrations (P less than 0.05). Plasma levels of somatostatin, glucose and cortisol were unaffected by both icv and iv administration of CCK. These results show that CCK can have a strong GH-inhibiting effect in the brain. Furthermore, this effect seems to be independent of hypothalamic somatostatin, suggesting another GH-inhibiting system exists.
Management of adipsia by a behavioural modification technique.
Adipsia combined with diabetes insipidus after hypothalamic damage may produce major difficulties in clinical management. If there is an associated memory impairment it may be impossible to teach self-regulation of fluid balance, necessitating long-term hospital supervision. The successful use of a behaviour modification technique to achieve independent drinking and allow discharge from hospital into the community is described in a patient with adipsia, diabetes insipidus and memory impairment resulting from the removal of a craniopharyngioma.
[The efficacy of nutritional intervention in patients diagnosed with AIDS. A study].
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Isolation of measles virus in primary rhesus monkey cells from a child with acute interstitial pneumonia who cytologically had giant-cell pneumonia without a rash.
The isolation of measles virus in primary Rhesus monkey kidney cells (PRMK) in patients with documented giant-cell pneumonia who have presented without a rash is limited. The diagnosis usually is made by cytologic examination of nasal or bronchial secretions in which characteristic multinucleated giant cells with intranuclear and intracytoplasmic inclusion bodies are observed. The diagnosis of giant-cell pneumonia has been associated with measles virus but not exclusively. Canine distemper, herpes group viruses, and parainfluenza infections have been associated with these cells. In addition, vitamin A deficiency also has been cytologically associated with multinucleated giant cells. The authors describe the isolation of measles virus from bronchial washing and sputum in PRMK cells at 4 days from an 11-year-old child with acute interstitial pneumonia who was in remission for acute lymphocytic leukemia. Classic cytopathologic effect (CPE) consisting of syncytial and hole formation on the PRMK monolayer was apparent. In addition, a foamy appearance of the monolayer was noted in an otherwise clean lot of monkey cells. Confirmatory testing with measles antibody of the infected areas of the monolayer by indirect immunofluorescence (IFA) was positive for measles antigen and negative for mumps, parainfluenza (types I, II, and III) and influenza A and B virus. Serologic studies for measles antibody revealed an IFA IgG titer of greater than 1:10,240, and an IgM titer of 1:128. Cytologic examination of the same bronchial fluid revealed the typical giant cells with characteristic inclusions associated with measles virus. Because this disease usually is severe, and often fatal, prompt recognition of this virus is essential, not only to the patient, who can be treated with immunoglobulin and/or antiviral therapy, but also to prevent the spread of the virus to other patients and medical personnel. These findings also support direct evidence for the etiologic role of measles virus in giant-cell pneumonia that has been detected either histologically or cytologically and in tissue culture at autopsy.
The influence of microwave radiation on transdermal delivery systems.
It has been alleged that the exposure of a transdermal delivery system to leakage of microwave radiation from a domestic microwave oven can result in the user receiving a second-degree burn in the area of the patch. Several transdermal delivery systems were exposed to microwave radiation from an Electro Medical Supplies Microtron 200 microwave diathermy unit. Temperature rises of up to 2.2 degrees C were recorded at a maximum power density of 800 W/m2. These temperature rises were considered insignificant compared to that required to produce a burn. The exposure of transdermal delivery systems to a microwave diathermy field or lower level leakage radiation from a microwave oven is unlikely to cause direct thermal injury to the wearer.
Comparison of a serum replacement (Omni Serum) and fetal bovine serum in cell cultures used to isolate herpes simplex virus from clinical specimens.
Traditionally, fetal bovine serum (FBS) has been the principal component in media used in the growth and maintenance of cell cultures. Recent shortages have affected the cost and availability of FBS to clinical laboratories. Furthermore, lot-to-lot variability can affect cell culture performance and growth. We evaluated a commercially available serum replacement (Omni Serum; Advanced Biotechnologies Inc., Columbia, Md.) for use in the growth of cell cultures and for use in maintenance media used for the isolation of herpes simplex virus from clinical specimens. Cells (rhabdomyosarcoma and mink lung) raised on 5% Omni Serum grew as well as those grown on 10% FBS. The sensitivity of the Omni-raised cells to herpes simplex virus that had been isolated from 111 clinical specimens was equal to that of the cells raised and maintained with FBS. Cells grown with 10% FBS and maintained with 2% Omni Serum displayed the same sensitivity and integrity in tubes (rhabdomyosarcoma and mink lung) and vials (MRC-5 cells) as cells grown with 10% FBS and maintained with 5% FBS. This study indicates that Omni Serum is an acceptable substitute for FBS in maintenance media for cell culture tubes and vials used for viral isolation from clinical specimens.
Respiratory muscle incoordination in stuttering speech.
We investigated the role of respiratory muscle incoordination during stuttering by measuring esophageal, gastric, and transdiaphragmatic pressures to obtain subglottic pressure (Psg) and indices of diaphragmatic, rib cage, and abdominal muscle contraction during speech in normal volunteers and in severe stutterers. We found in contrast to the relatively constant subglottic pressure during normal conversational speech that speech in stutterers was characterized by failure to control Psg because of contraction of the diaphragm, rib cage, and abdominal muscles singly or in various combinations. As a result, Psg varied substantially and sometimes chaotically from too high to too low, rendering normal speech impossible. During periods of fluency, Psg was much better controlled. We conclude that incoordination of the respiratory muscles is a major problem in stuttering, resulting in failure to control the pressure difference across the vocal cords. It is unclear if this is a primary abnormality or is a secondary response to a primary abnormality elsewhere.
Selection and characterization of ricin toxin A-chain mutations in Saccharomyces cerevisiae.
A DNA sequence encoding the A chain of ricin toxin (RTA) from the castor bean plant, Ricinus communis, was placed under GAL1 promoter control and transformed into Saccharomyces cerevisiae. Induction of expression of RTA was lethal. This lethality was the basis for a selection of mutations in RTA which inactivated the toxin. A number of mutant alleles which encoded cross-reactive material were sequenced. Eight of the first nine mutant RTAs studied showed single-amino-acid changes involving residues located in the proposed active-site cleft.
Is viewing television harmful to actinic reticuloid patients?
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Prophylactic parenteral antibiotics in clean neurosurgical procedures: a review.
Clean surgical procedures carry a risk of postoperative wound infection that is less than 5% in most hospitals. The use of prophylactic antibiotic agents in clean neurosurgical cases is controversial, and the neurosurgical literature through 1980 contains no controlled clinical trials to study its effectiveness in such cases. A report of 1732 consecutive procedures without a single postoperative wound infection in patients receiving systemic gentamicin, vancomycin, and streptomycin irrigation fluids is often quoted by neurosurgeons; however, these results have not yet been duplicated by others. Since 1980, there have been several controlled trials that support the use in clean neurosurgical cases of prophylactic antibiotics, including the vancomycin/gentamicin/streptomycin regimen and the first-generation cephalosporins. A report in 1986 of 1602 cases without a primary wound infection supports the use of a single perioperative dose of cefazolin. A review of causative organisms in postoperative wound infections demonstrates the preponderance of Gram-positive pathogens. Therefore, when antibiotic prophylaxis is indicated, adequate Gram-positive bacterial coverage, including protection against Staphylococcus infection, is required. With consideration of the present data, the cost of antibiotic therapy, and the danger of drug toxicity, a short perioperative regimen of cefazolin as prophylaxis is preferred in clean neurosurgical cases.
[Nutritional status. Its evaluation].
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Prognostic factors in breast cancer: immunohistochemical staining for SP1 and NCRC 11 related to survival, tumour epidermal growth factor receptor and oestrogen receptor status.
It has been proposed that intense immunohistochemical staining using the monoclonal antibody NCRC 11 is indicative of a better prognosis in breast cancer, and that expression of pregnancy specific glycoprotein (SP1) and epidermal growth factor receptors (EGFR) are poor prognosis indicators. In order to evaluate the significance of staining for NCRC 11 to prognosis and to these other variables, we studied two series of breast cancer patients. In one series (n = 93), staining with NCRC 11 and for SP1 was correlated with prognosis: in neither case was there any overall relationship between staining and survival. However, when the patients were stratified by tumour histological (Bloom's) grade, SP1 expression was associated with a poorer prognosis in grade II tumours (p less than 0.025). In a further series (n = 94), NCRC 11 staining was carried out and fresh tumour samples were assayed biochemically for oestrogen receptor (OER) and EGFR. NCRC 11 showed a negative correlation with EGFR status (p = less than 0.05) but no significant association with OER status. Thus despite our demonstration of a negative correlation with an indicator of poorer prognosis, we were unable to demonstrate any direct relationship between staining with NCRC 11 and survival.
Follow up study of sexually transmitted disease (STD), sexual practice and human immunodeficiency virus (HIV) serology in homosexual men attending an STD clinic.
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