The Influence of Race and Phenotype on the Erythrocyte D Antigen Studied by I131--labeled Anti--D

A method for the preparation of I¹³¹-labeled anti-D eluates (I^[unknown] anti-D)specific for the D antigen by adsorption and elution from intact D positivered cells is presented. A standard D antigen reference system for the quantitative comparison of the red cell D antigen from various donors was developedon the basis of kinetic studies of the effect of pH, temperature and antigenconcentration on the I^[unknown] anti-D reaction with the D antigen. The red cell Dantigen determinations of the blood from 33 Negro and 102 Caucasiandonors showed wide monomodal frequency distributions which indicate aheterogeneity of quantitative D antigen reactivity consistent with previousserologic and I¹³¹-labeled anti-D studies. The average red cell D antigenreactivity of the 20 probable D homozygote and 14 established D hemizygoteCaucasian donors was similar to the D antigen reactivity of the 102 randomCaucasian donors. The red cell D antigen reactivity was strongly depressedby the C antigen (or C gene) in Caucasian bloods and enhanced by the Eantigen (or E gene) in Negro bloods. The E antigen (or E gene) may alsohave enhanced the D antigen reactivity in red cells from Caucasian donors,but the difference in D zygosity provides an alternative explanation for theresults. The marked influence on red cell D antigen reactivity in the presenceof the C and E antigen may well have obscured any lesser influence of Dzygosity.

Accepted on December 6, 1962     

Efficacy of a nicotine nasal spray in smoking cessation: a placebo-controlled, double-blind trial

Laboratory trials have demonstrated the efficacy of nicotine replacement in smoking cessation bur absolute success races are low. For many, nicotine gum is hard to use and transdermal nicotine is slow-acting and passive. A new, faster-acting nicotine nasal spray (NNS) can provide easily self-administered relief from cigarette withdrawal. The NNS was tested for safely and efficacy in smoking cessation. Two hundred and fifty-five smokers were randomized to NNS or a piperine placebo. Drug use was limited to 8–32 doses/day for 6 months. Subjects were tested while smoking and at post-cessation daily (week 1) with follow-up at weeks 2, 3, 6 and at 3 months, 6 months and 1 year. Continuous abstinence analyses (CO ≤8 ppm.; no slips) showed that NNS significantly enhanced success rates over placebo overall (p < 0.001) and at all test intervals. Differences at key intervals between active and placebo were: 63% vs. 40% (day 5), 51% vs. 30% (week 3), 43% vs. 20% (6 weeks), 34% vs. 13% (3 months), 25% vs. 10% (6 months) and 18% vs. 8% (1 year). Side effects were common but tolerable. Cotinine measures showed that replacement of nicotine approximated 30% of smoking levels. Hazard functions revealed relapse risks peaked at day 1, day 5 and 3 weeks for strict abstinence. It is concluded NNS is safe, efficacious and a viable alternative treatment for smoking cessation.     

Abnormal Automaticity as Mechanism of Atrial Tachycardia in the Human Heart—Electrophysiologic and Histologic Correlation:

Abnormal Automaticity in Human Atrium, introduction: A 32-year-old woman was operated upon because of drug refractory atrial tachycardia.
Methods and Results: Electrophysiologic study was performed prior to operation. During surgery, epicardial mapping of the electrical activity of the left atrium was performed. The left atrial appendage was resected and studied in a tissue bath. Thereafter, histologic examination was performed. Polarity of the P wave in the surface ECG suggested that the tachycardia originated high in the left atrium. Epicardial mapping disclosed earliest activation in the apex of the left atrial appendage. Intracellular recordings from surgical specimen made at the site of origin, which was marked during surgery, revealed cells with phase 4 depolarization at cycle lengths ranging from 360 to 540 msec. Exit block prevented spread of activation from the spontaneously firing cells to surrounding tissue. Histology showed that spontaneous activity arose in an area with abnormal cells-characterized by an amorphous, pale eosinophilic staining cytoplasm and absence of nuclei-surrounded by normal myocytes.
Conclusion: The observations indicate that the mechanism of the atrial tachycardia was based on abnormal automaticity in an area consisting of a conglomeration of normal and abnormal myocytes.     

Arteriovenous Malformation of the Stomach

Of the multitude of sources capable of producing massive hemorrhage from the gastrointestinal tract, one of the rarest forms is arteriovenous malformation (AVM) of the stomach. The typical patient is a middle-aged male who presents with recurrent painless massive hematemesis and an unremarkable past medical history. Until recently the diagnostic work-up has often presented a dilemma, with the lesion rarely being confirmed prior to laparotomy. The patient whom we have encountertd with AVM of the stomach confirms our belief in the use of visceral angiography as a vital tool in the diagnosis of obscure gastrointestinal bleeding. We present this case as one which is unusual in its diagnostic work-up, therapeutic approach and pathologic findings.     

Elevation of gastric pH heals peptic oesophagitis - A role for omeprazole

The aim of this study was to investigate the hypothesis that the prolonged and substantial elevation of gastric pH which can be achieved with the antisecretory agent omeprazole will result in healing of peptic oesophagitis. Eight patients with erosive or ulcerative peptic oesophagitis were treated with omeprazole (30 mg daily) for 8 weeks. Complete healing occurred in seven patients after 8 weeks of omeprazole therapy. Only a small area of residual ulceration persisted in one unhealed patient. Heartburn resolved within the first 2 weeks of therapy in all but one patient. Specific food intolerances also were eliminated in most cases. Post-prandial oesophageal pH monitoring during omeprazole administration showed abolition of acid reflux episodes (pH < 4). This effect appeared to be due solely to the antisecretory effect of omeprazole, since motility measurements demonstrated a continued high frequency of reflux while concurrent gastric pH monitoring showed sustained elevation of gastric pH above 4. These results support the hypothesis that a prolonged and potent inhibition of gastric acid secretion renders refluxed gastric juice sufficiently innocuous to allow healing of severe peptic oesophagitis.     

Intranasal immunization with yeast-expressed 19 kD carboxyl-terminal fragment of Plasmodium yoelii merozoite surface protein-1 (yMSP119) induces protective immunity to blood stage malaria infection in mice

Variable protection against malaria blood-stage infection has been demonstrated in mice following parenteral immunization with the highly conserved 19 kD carboxylterminal fragment of the merozoite surface protein-1 (MSP1₁₉) using CFA/IFA and other adjuvants. Here we show that intranasal immunization of BALB/C mice with yeast expressed Plasmodium yoelii MSP1₁₉ plus a mixture of native and recombinant cholera toxin B subunit, could induce serum MSP1₁₉-specific antibodies at titres ranging from 20 000 to 2 560 000. The Ig subclass responses were predominantly G1 and G2b. Intranasal immunization led to protection following challenge (peak parasitaemia < 1%) in mice with the highest MSP1₁₉-specific titre (≥ 640 000). In two of the three protected mice, a peak parasitaemia of 0.1%–1% was followed by a boost of the antibody response whereas one of the three protected mice did not boost its antibody response after a peak parasitaemia of 0.02%. In unprotected mice, antibody levels rose, then fell, following the detection of parasites in the peripheral blood. CD4⁺ T cell-depletion abrogated the ability of the mice to boost their antibody response following challenge. These data demonstrate the potential for intranasal immunization with MSP1₁₉ to protect against malaria .     

Mature liver stages of cloned Plasmodium falciparum share epitopes with proteins from sporozoites and asexual blood stages

The liver merozoites of malaria parasites are of paramount importance, as they initiate the parasite invasion of red blood cells and start the cycle associated with the clinical features of malaria. Investigating liver merozoite antigen is difficult because of the lack of a rodent model of human malaria. In addition, only a low proportion of cells are obtained in vivo, the parasites from Cebus and Aotus monkeys are immature, and in-vitro experiments with liver cells are often confounded by contamination with the natural mosquito flora copurified with the sporozoites used for seeding the liver cultures. In our study, mature liver schizonts were shown to possess many of the antigenic determinants recognized by MoAbs and sera specific for defined sporozoite and blood-stage antigens. We employed an immunofluorescence procedure based on evaluating parasites in cryosections prepared from infected chimpanzee liver. Sufficient numbers of sectioned parasites were evaluated with each antibody to assure the reproducibility of the results, and the fixation procedure used was sufficiently non-destructive to parasite antigens so that clear differences between reactions of specific antibodies and negative controls were observed. Our evidence for sharing of epitopes by liver merozoites and sporozoites or by liver merozoites and asexual blood-stage parasites raises the possibility that immune responses elicited against sporozoites or asexual stage antigens being considered as vaccine candidates may also act against this important, little-studied stage of the parasite.     

THE NATURE OF ARTHRITIS PAIN

A modified version of the McGill Pain Questionnaire in visualanalogue format was used to evaluate the sensory, affectiveand evaluative intensities of pain experienced by 40 patientswith rheumatoid arthritis and 20 patients with degenerativearthritis. The affective component of the pain was found tobe more intense than the sensory component in all patients indicatingthe importance of emotional factors in the pain experience.The sensory aspects of the pain were more complex than the affectiveones reflecting the varied sources and combinations of somaticpathology. There were no significant differences found in theoverall pain experience between rheumatoid and degenerativearthritis. No differences were noted in the evaluative categoryof pain. Overall pain intensity increased with disease durationin both rheumatoid and degenerative arthritis. The relationshipof affective and sensory components of the pain experience didnot alter with duration of disease. KEY WORDS: Arthritis, Pain