Antigenic variation in Giardia lamblia: cellular and humoral immune response in a mouse model

Neonatal mice (CR:NIH:S) were infected with a cloned human isolate of Giardia lamblia (GS/M-83-H7) and the surface antigens of the intestinal trophozoites, as well as the cellular and humoral immune responses, were analysed during the course of infection. Infections in mice peaked 2-3 weeks after inoculation and were self-cured by day 42 post-infection (p.i.). The proportion of trophozoites expressing the Mr 72,000 surface antigen of the initial inoculum had decreased by day 12 and approached zero by day 22 p.i., similar to infections in humans. The predominant parasite-specific humoral response was an IgM- and IgG-isotype directed to the original Mr 72,000 surface antigen as well as other antigens. T-lymphocytes (predominantly LY4(CD4)+) isolated from Peyer's patches 12 days p.i. and later showed a significant proliferative response to Giardia lamblia antigens. Spleen and lymph node cells showed no lymphoproliferative response. T-cell blot analysis revealed the presence of dominant T-cell epitopes in the areas of Mr 200,000-75,000 and less than 50,000 polypeptides. No response was demonstrated in the Mr 72,000 region (migration site of the major surface antigen), suggesting T-cell dependent mechanisms are most likely not responsible for the surface antigen switch which occurred during the course of infection. This model infection can be used to study the role of immunological mechanisms in Giardia lamblia variant antigen switching and in the control of infections.     

The Occurrence of Lymphoma in Patients with Long-standing Hyperthyroidism

1) Six patients have been presented who, subsequent to long-standinghyperthyroidism, developed a lymphoma (one lymphoblastic lymphosarcoma,one Hodgkin’s disease, one giant follicular lymphoma, and three lymphocyticlymphosarcoma or leukemia).

2) Experimental evidence suggests that hyperthyroidism stimulates andhypothyroidism inhibits lymphoid structures, and hyperthyroidism promotestumor growth in animals. The mechanism of this action is not clear.

3) Three additional cases of hyperthyroidism followed by the developmentof a lymphoma were found in the literature.

4) It is suggested that prolonged hyperthyroidism may be a contributoryfactor in the development of lymphomas or allied disorders in man.

Submitted on July 30, 1962 Accepted on October 17, 1962     

Leukokinetic Studies. VII. Morphology of the Bone Marrow and Blood of Dogs Given Vinblastine Sulfate

The effect of a single injection of vinblastine sulfate was studied in 50mongrel dogs. Nine of 34 dogs given 0.2 mg./Kg. of VLB died with gastrointestinal toxicity and the mortality rate increased as the dosage of VLB wasincreased. The morphologic pattern of leukocyte suppression and recovery inthe bone marrow and blood was studied in detail in surviving animals.

The cells of the bone marrow were markedly affected by VLB. Within 4hours there was an increase in the number of cells in metaphase and, by day1, virtually all proliferating leukocytes and erythrocytes had disappeared. Anorderly repopulation of the bone marrow followed.

The neutrophils, eosinophils, lymphocytes and monocytes of the blood wereall markedly altered in concentration after VLB. Each type of cell first decreased to abnormally small numbers and then increased to abnormally largenumbers in the blood. The curve of disappearance from and reappearance inthe blood differed for each cell type.

The changes in blood neutrophil number and morphology were correlatedwith changes in the blood neutrophil precursor cells of the marrow. The following conclusions were reached concerning the neutrophils and the assumptions implicit to these conclusions were detailed.

1. In the dog, the marrow contains enough post-mitotic granulocytes toreplace those lost from the blood for at least 3 to 4 days.

2. The release of mature neutrophils from the bone marrow is a functionof the rate at which blood neutrophils are lost and proceeds normally evenwhen the marrow granulocyte reserve is partially depleted.

Submitted on March 27, 1963 Accepted on August 20, 1963     

Safety and Effectiveness of Transvenous Lead Extraction in Octogenarians

Transvenous Lead Extraction . Introduction: As the population ages, the number of elderly patients with implantable cardiac devices referred for transvenous lead extraction will dramatically increase in Western countries. The safety and effectiveness of lead extraction in elderly patients has not been well evaluated. We report the safety and effectiveness of transvenous lead extraction in octogenarians. Methods and Results: From January 2005 to January 2011, we reviewed data from consecutive patients ≥ 80 years referred to our institutions for transvenous lead extraction because of cardiac device infection or lead malfunction. Clinical characteristics, procedural features, and periprocedural major and minor complications were compared between octogenarians and younger patients. Out of 849 patients undergoing lead extraction in the participating institutions during the study period, 150 (18%) patients were octogenarians (mean age 84 years; range 80–96; 64% males). A significantly higher percentage of octogenarians presented with chronic renal failure (55% vs 26%; P < 0.001), history of malignancy (22% vs 6%; P < 0.001), and chronic obstructive pulmonary disease (46% vs 19%; P < 0.001). Complete lead extraction rates were similar in the 2 age groups (97% in octogenarians vs 96% in patients <80 years; P = 0.39). Periprocedural death occurred in 2 (1.3%) patients ≥80 years and in 5 (0.72%) patients <80 years (P = 0.45 for comparison). No differences in terms of other periprocedural major and minor complications were found between the 2 age groups. Conclusion: Despite presenting with a significantly higher rate of comorbidities, transvenous lead extraction can be performed safely and successfully in octogenarians. (J Cardiovasc Electrophysiol, Vol. 23 pp. 1103‐1108, October 2012)     

Phrenic Nerve Stimulation for Central Ventilatory Failure with Bipolar and Four-Pole Electrode Systems

A multi-channel phrenic nerve stimulator developed in Tampere has been implanted into seven patients with C2-tetraplegia and into three patients with central sleep apneas. Six bipolar cuff electrodes were implanted bilaterally into the neck. Two four-pole cuff and 14 four-pole noncuff electrodes were used in seven patients and to replace one bipolar electrode. Four-pole electrodes were implanted within the thorax. Seven patients achieved total independence from conventional ventilators within 4 months of implantation, and one for 18 hours each day. Two patients died 12 days and 3 months after implantation and two patients after having achieved independence from mechanical ventilators from causes unrelated to the stimulators. Reoperations were necessary because of dislocation of receivers, electrodes, electrode lesions, nerve injuries, and technical failures in seven patients. Most of the problems appeared in two patients with obesity and in three patients with very thin phrenic nerves. Single unit prototypes failed technically more frequently than units of prototype serial fabrication. New electrode design, progress in the manufacture of receivers, and improved implantation technique should help to diminish failures in future.     

Hemodynamic Responses to Rapid Pacing: A Model for Tachycardia Differentiation

The hemodynamic responses to rapid atrial and ventricular pacing were examined in 10 closed-chest anesthetized dogs in an attempt to distinguish hemodynamically stable from unstable tachycardias. Pressure monitoring catheters were placed in the femoral artery, right atrium, and right ventricle to measure mean arterial pressure, mean right atrial pressure, and mean right ventricular pressure at baseline heart rate and after rapid high right atrial and right ventricular apex pacing. Pressures recorded during rapid pacing (average of the pressures at 30 and 60 seconds of pacing) at pacing rates of 180, 250, and 280/minute were compared to those recorded initially at baseline heart rates. Rapid right ventricular apex pacing resulted in significant increases in mean right atrial pressure (from 6 ± 1 mmHg (mean ± standard error) to 12 ± 1 mmHg, a 100% increase, P < 0.001) and mean right ventricular pressure (from 11 ±1 mmHg to 16 ± 1 mmHg, a 45% increase, p < 0.02) with marked hemodynamic compromise (mean arterial pressure decreased from 85 ± 6 mmHg to 50 ± 6 mmHg, a 41% decrease, P < 0.01). These parameters remained stable (no statistically significant difference from baseline) during high right atrial pacing. In half of the dogs high right atrial pacing at rates 250 resulted in atrioventricular Wenckebach. Thus, it is concluded that mean right atrial pressure and mean right ventricular pressure may be useful in distinguishing hemodynamically significant tachycardias, and in the future design of antitachycardia devices.     

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.