The Antigenicity of Normal and Leukemic Human Leukocytes

1. A leukoagglutinin was formed in the serum of a normal human subjectwho received 10 intravenous injections of blood from a single patient withchronic myelogenous leukemia over a period of 20 weeks.

2. Coincident with development of the leukoagglutinin, first detectable oneweek after the fifth injection of leukemic blood, the normal subject experiencedprogressively more severe febrile reactions to the infusions and exhibited acharacteristic pattern of leukocyte response—namely, an immediate transientleukopenia, followed by a leukocytosis which reached its peak around 3 hoursand subsided to normal within 12 hours.

3. During the early part of the investigation immature leukocytes, presumably from the leukemic donor, could be identified in the recipient’s circulationduring the first hour immediately following injection, but none could befound following the tenth infusion of leukemic blood.

4. The leukoagglutinin which appeared in response to the injections of bloodfrom the single leukemic donor was a typical iso-antibody, showing a broadpattern of reactivity against normal leukocytes from 127 of 129 donors, leukemicleukocytes from 5 of 5 patients with chronic myelocytic leukemia and 6 of 6patients with chronic lymphocytic leukemia. No reactivity was observed againstthe recipient’s own leukocytes, and little or no reactivity was demonstrableagainst the immature leukocytes from 3 patients with acute leukemia.

5. Eighteen months after the last injection of leukemic blood, restimulationof a leukocyte iso-agglutinin in the previously immunized recipient was provoked within one week of commencing a series of intravenous infusions ofblood from a single normal donor.

6. The volume of normal leukocytes employed for the restimulation was 1/10to 1/100 the volume of leukemic leukocytes employed for the primary immunization.

7. The concept of antibody excess was demonstrable in the sensitized recipient. No evidence of in vivo absorption of leukoagglutinin activity was observedafter transfusion of 500 ml. of blood from the normal donor. The severity ofthe recipient’s reaction to the transfused blood was clearly related to the doseof donor leukocytes administered, 0.47 billion cells causing no reaction but4.16 billion causing a moderately severe reaction.

8. Fifteen months after completion of the injections of normal blood, reexposure of the normal subject to injections of blood from a second leukemicdonor resulted in prompt restimulation of leukoagglutinin activity in therecipient’s serum.

9. The leukoagglutinin could be completely absorbed in vitro by incubationwith donor leukocytes.

10. The leukoagglutinin was concentrated in the gamma globulin fraction ofthe recipient’s plasma.

11. The recipient exhibited typical symptomatic reactions and transient hematologic changes following the infusions of leukemic blood.

12. It was possible to correlate the severity of the recipient’s clinical reactionsboth with the strength of the recipient’s leukoagglutinin, as well as with thedose of donor leukocytes transfused.

13. Serologic observations, plus the results of fractionated transfusion studies,indicated that the recipient’s transfusion reactions were related to sensitivityto the donor’s buffy coat (Part II), and more specificially to donor leukocytes(Part III), rather than to donor plasma, platelets or erythrocytes.

14. Sustained stimulation of the recipient’s white cell count as a result of theinjections of leukemic blood was not observed.

15. There has thus far been no evidence of transmission of leukemia to therecipient (now 6 years after the first course of injections of leukemic bloodand 2 years since completion of the present study).

Submitted on July 15, 1960 Accepted on November 20, 1960     

Periodontal Diseases and Dental Implants in Older Adults

Abstract: Older adults present special problems for the dentist trying to establish or reestablish esthetics. Periodontal diseases are of concern for this population since tooth loss from these widespread problems increases with age. In general, this loss occurs because of increased exposure time to pathogenic bacteria, not some change inherent in the body brought on by the aging process. The profession has begun to place more emphasis on systemic risk factors and their role in modifying periodontal inflammation. The current thinking is that bacteria are necessary to initiate and sustain periodontal diseases, but the clinical manifestation is dictated to a significant extent by systemic factors. Smoking, diabetes, and being positive for the interleukin-1 genotype predispose the patient to developing more severe disease. For those older adults who lose teeth, dental implants have emerged as reliable replacements, and concerns about placing these devices in patients who have lost teeth as a result of periodontitis appear to be largely unfounded.     

Inhibition of Leukotriene (SRS-A)-Mediated Acute Lung Anaphylaxis by Azelastine in Guinea Pigs

Azelastine hydrochloride, chemically known as 1(2H)-phthalazinone, 4-[(4-chlorophenyl)methyl]-2-(hexahydro-1-methyl-1H-azepine-4-yl)-, monohydrochloride, is a novel, orally effective, long-acting, antiallergic/antiasthmatic agent. The ability of azelastine and selected antiallergic drugs to inhibit SRS-A (leukotriene)-mediated acute lung anaphylaxis in guinea pigs (Konzett-Rossler method) was investigated. Azelastine and ketotifen were administered p.o. 2 and 24 h before antigen challenge; disodium cromoglycate (DSCG) was administered i.v. immediately before antigen challenge. The oral dose of azelastine required to inhibit leukotriene-mediated allergic bronchospasm by 50% (ID50: mg/kg) was 0.063 at 2 h and 0.120 at 24 h. Ketotifen at a dose of 0.05 to 10 mg/kg at 2 and 24 h, p.o., as well as DSCG at a dosage of 0.3 to 10 mg/kg at 0 min, i.v., produced weak, inconsistent and nondose-related antianaphylactic effects. Azelastine is an orally effective and long-acting inhibitor of in vivo synthesis and/or release of leukotrienes.     

Noradrenergic component in the vasoconstriction induced by 5-hydroxytryptamine in goat cerebral arteries

5-Hydroxytryptamine (5-HT) elicited dose-dependent increases in tension in the middle cerebral artery of the goat, which were significantly antagonized by lysergic acid diethylamide (LSD, 10(-8) M) and methysergide (10(-7) M). In the presence of phentolamine (10(-6) M), the dose-response curve to 5-HT was shifted to the right, the pA2 value for this antagonism was 6.52. Pretreatment of goats with reserpine (0.02 mg kg-1 day-1 for three days) or removal of both superior cervical ganglia 15 days before the experiment brought about a significant decrease in the vasoconstriction induced by doses of 5-HT higher than 10(-7) M. The remaining contraction produced by 5-HT in arterial segments from reserpinized or gangliectomized goats was further reduced in the presence of LSD. In addition, high concentrations of 5-HT induced tritium release from goat pial arteries preloaded with (-)-[3H]noradrenaline, 2 X 10(-7) M) which was significantly decreased in vessels from gangliectomized or reserpinized goats. These results in goat cerebral arteries indicate that in the contraction evoked by 5-HT there are two components. The first appears with low concentrations (up to 10(-7) M) in which 5-HT acts directly on 5-HT receptors. The second occurs at high doses (greater than 10(-7) M) in which 5-HT also acts indirectly on alpha-adrenoceptors by release of noradrenaline from noradrenergic nerve endings.     

Diagnosis of a Bleeding Meckel''s Diverticulum Using Radiopertechnetate

A case report of bleeding from a Meckel's diverticulum diagnosed by Tc99-m pertechnetate scanning is presented. The noninvasive advantage of this method justifies its early use as a diagnostic measure when a Meckel's diverticulum is suspected in the differential diagnosis of lower gastrointestinal bleeding.     

Tissue-factor coagulant activity of cultured human endothelial and smooth muscle cells and fibroblasts

The tissue-factor (thromboplastic) activity of cultured human endothelial cells and fibroblasts is low at time of transfer into fresh medium but increases 3-10 fold. Endothelial cells reach peak activity (400 U/10(5) cells) 5-8 hr after subculture. Activity in fibroblast cultures peaks (3000-12,000 U/10(5) cells) 7-12 hr after subculture. After attaining maximum activity, endothelial and fibroblast tissue- factor content decreases in a time course similar to other cells studied in this laboratory, approaching basal levels by 24-50 hr after subculture. If medium over fibroblasts is changed every 12 hr, activity can be sustained at the peak level for an additional day but cannot be maintained at a high level indefinitely. The kinetics of expression of smooth muscle cell tissue factor are markedly different from other cell types. There is always a pronounced lag (30 hr or more) before the activity increases, and then, in most cases, there is no subsequent decline in activity even though the cells are not refed or restimulated. The activity of each of these cell types is cryptic but becomes available after freeze-thaw disruption of cells.     

Emergency department utilization by adolescents in the United States

BACKGROUND: Adolescents in the United States have been shown to underutilize primary care services and therefore may rely heavily on emergency service. Although several small studies have explored local emergency services for youth, there are no published reports of adolescent utilization of emergency services on a national scale. Furthermore, emergency services data have not been aggregated according to the age subgroups used by the current guidelines for adolescent care. OBJECTIVE: To explore the utilization of emergency departments in the United States by early (11 to 14 years), middle (15 to 17 years), and late (18 to 21 years) adolescent subgroups. DESIGN: Secondary analysis of the emergency department component of the 1994 National Hospital Ambulatory Medical Care Survey. SETTING: Nationally representative sample of 418 emergency departments in the United States. PATIENTS: Approximately 26,547 visits by patients of all ages, representing 93.4 million total visits in 1994 and 14.8 million adolescent visits. OUTCOME MEASURES: Number of visits, health insurance, reasons for visits, urgency of visits, resulting diagnoses, and hospitalization rates. RESULTS: Adolescents accounted for 15.4% of the population and 15.8% of emergency department visits in 1994. Late adolescents were overrepresented in emergency department visits relative to their population proportion (6.8% of visits, 5.3% of population), whereas early adolescents were underrepresented (4.6% of visits, 5.9% of population). Lack of health insurance was more common among 11- to 21-year-olds (26.2%) than either children (13.6%) or adults (22.7%). By ages 18 to 21 years, 40.5% of male visits and 27.6% of female visits were uninsured. Injury-related visits were more common among adolescents (28.6%) than either children (23.1%) or adults (18.2%). Injury was the leading reason for visits among all adolescent age-sex subgroups (36.6% to 42.0% of male visits and 14.1% to 27.2% of female visits) except females aged 18 to 21 years for whom digestive reasons ranked first (18.8%). Injury was the leading diagnosis for all adolescent age-sex subgroups, with peaks at early adolescence of 61.6% for males and 45.8% for females. Across all adolescent age-sex subgroups, 3.1% to 5.3% of visits resulted in hospitalization, and 41.0% to 52.5% of visits were urgent. These rates did not differ from those of children but were lower than those of adults. CONCLUSIONS: Utilization of emergency departments increases and health insurance decreases during adolescence, suggesting that adolescents with inadequate health insurance may rely heavily on emergency departments for their health care needs. Most adolescent visits to emergency departments are not urgent and might be better treated through nonemergency, primary care sites.