Hereditary Long QT Syndrome Associated with Cardiac Conduction System Disease

This report describes the cardiac conduction abnormalities, detected by invasive electrophysiological study, in two identical siblings with symptomatic congenital long QT syndrome. Both patients had evidence of intra-Hisian conduction delay in response to programmed atrial stimulation and pacing induced infranodal block was seen in one of the two patients. The response of the observed conduction delay to autonomic interventions is described. The observed electrophysiologic abnormalities are consistent with previously reported pathological findings and document the association of functional conduction system disease with congenital QT prolongation.     

Pharmacodynamic and Pharmacokinetic Studies in Rats of S-8-(2-Furyl)- and R-8-Phenyl-2-(di-n-Propylamino)Tetralin,Two Novel 5-HT1A Receptor Agonists In-vitro with Different Properties In-vivo

R- and S-8-(2-Furyl)- and R- and S-8-phenyl-2-(di-n-propylamino)tetralins (R- and S-LY-55 and R- and S-LY-49, respectively), novel enantiopure dipropylaminotetralins, have been screened as 5-HT_1A receptor ligands. All had nanomolar affinities for 5-HT_1A receptors and fully inhibited forskolin-stimulated adenylyl cyclase in-vitro (i.e. the four compounds appeared to be 5-HT_1A agonists). It was also found that the enantiomers of LY-55 behaved as typical 5-HT_1A receptor agonists in rats in-vivo by inducing a typical behavioural 5-HT syndrome, hypothermia and a decrease in 5-HT synthesis and turnover, indicating effects both on postsynaptic 5-HT_1A receptors and somatodendritic 5-HT_1A autoreceptors. In contrast, R- and S-LY-49 did not cause any 5-HT_1A receptor-related effects in-vivo except for a partial inhibition of 5-HT synthesis after high doses. The 5-HT_1A receptor antagonist WAY-100635 was shown to attenuate the R-LY-49-induced inhibition of 5-HT synthesis, indicating the compound to be a weak agonist at somatodendritic 5-HT_1A autoreceptors. R-LY-49 at a high dose and with a long pre-treatment time interval inhibited the hypothermic and behavioural effects, but not the inhibition of 5-HT synthesis induced by the 5-HT_1A receptor agonist R-8-hydroxy-(dipropylamino)tetralin (R-8-OH-DPAT). Taken together, these findings seem to indicate, that R-LY-49 is a weak partial agonist at 5-HT_1A receptors. A comparative pharmacokinetic study showed that the enantiomers of LY-55 entered the brain rapidly after subcutaneous administration and reached peak brain tissue/plasma concentration ratios within 15–30 min of injection, whereas the brain concentrations of R-LY-49 increased slowly, reaching a relatively low peak brain tissue/plasma concentration ratio 90 min after injection despite their similar lipophilicity. The differences between the pharmacological activity of the two compounds in-vivo seem to be explained by their different abilities to cross the blood-brain barrier, and a weak agonistic activity of R-LY-49 on 5-HT_1A receptors, both pre- and postsynaptically, compared with S-LY-55. Further studies are, however, needed for a deeper understanding of these differences.     

Pacemaker Lead Fracture Due to Twiddler's Syndrome

The authors report a case of pacemaker twiddler's syndrome that led to lead fracture and loss of consciousness. The role of chest X rays in the diagnosis of pacemaker twiddler's syndrome as well as the management of the syndrome is discussed.     

Comparative Sensitivity of Eight- and 24-hour Bile Acid Breath Tests and Schilling Test in Ileopathies

The conventional eight-hour bile acid breath test ("acute measurements"), was compared with a modified, extended, 24-hour breath test ("ratio measurements") and the Schilling test to assess relative sensitivity in detecting ileal dysfunction. Sixty-four patients with ileopathies were studied. The presence or absence of bile acid malabsorption was documented by fecal excretion studies of bile acid labels. The sensitivity of the "acute measurements" in the breath test was not significantly different from that of the "ratio measurements" in the ileopathies, regardless of whether or not bile acid malabsorption was present. The "acute measurements" were positive in 49 (77%), the "ratio measurements" in 54 (84%) and the Schilling test in 49 (77%) of the patients. In about 30%, bile acid breath test and Schilling test were not positive in the same patient. A combination of "acute measurements" (breath test) and Schilling test increased the percentage of cases with at least one positive test to 91%. The results of the study show: 1. The sensitivity of the bile acid breath test does not increase if ¹⁴CO₂ measurements are carried out beyond eight hours. 2. Although the breath test and Schilling test are of similar sensitivity in ileopathies, they are frequently not positive in the same patient. Therefore, it would be clinically useful to combine both tests in order to increase the likelihood of diagnosing ileal dysfunction.     

Diagnostic Specificity of Sucrose Hemolysis Test for Paroxysmal Nocturnal Hemoglobinuria

The diagnostic specificity of the various modifications of the sucrose hemolysis test for PNH was examined in detail. In whole blood screening tests thegreatest specificity was achieved using citrated or oxalated blood and roomtemperature incubation (23°). Defibrinated whole blood should not be usedsince "false positive" hemolysis may occur in blood disorders other than PNH.Mechanisms were suggested for this phenomenon. The validity of the confirmatory sucrose hemolysis test employing normal serum was further reported.Because of the clear, colorless character of serum-sucrose mixtures, an insignificant degree of hemolysis (i.e., less than 5%) is more readily visible thanin other PNH hemolytic tests employing undiluted serum. Definitive instructions and criteria for interpretation were given for both the whole bloodscreening test and the confirmatory sucrose hemolysis test.

Submitted on June 18, 1969 Accepted on December 8, 1969     

Trisomy 3 in marginal zone B-cell lymphoma: a study based on cytogenetic analysis and fluorescence in situ hybridization

Trisomy 3 represents the most frequent and consistent chromosomal abnormality characterizing the recently defined entity marginal zone B-cell lymphoma (MZBCL). By cytogenetic analysis and/or fluorescence in situ hybridization (FISH) on interphase nuclei we found an increased copy number of chromosome 3 in 22/36 (61%) successfully analysed cases, including 8/12 cases with extranodal MZBCL, 8/13 cases with nodal MZBCL, and 6/11 patients with splenic MZBCL. Sensitivity of interphase cytogenetics was somewhat higher than that of conventional cytogenetic investigation. Structural chromosomal changes involving at least one chromosome 3 were seen in 11/20 cases with an increased copy number of chromosome 3: +del(3)(p13) was demonstrated in three cases, and was the sole chromosomal abnormality in one of them; +i(3)(q10) was seen in two other patients; and rearrangements involving various breakpoints on the long arm of chromosome 3 were found in the remaining cases. FISH on metaphase spreads confirmed these structural abnormalities and additionally showed two unexpected translocations involving chromosome 3. We conclude that: (1) trisomy 3 occurs in a high proportion of extranodal, nodal and splenic MZBCL; (2) FISH on interphase nuclei is an additional and sensitive tool in detecting an increased copy number of chromosome 3 in MZBCL; (3) additional structural abnormalities involving the long arm of chromosome 3 are frequent but non-recurrent and are perhaps secondary changes; and (4) abnormalities such as +del(3)(p13) and +i(3)(q10) suggest that genes located on the long arm of chromosome 3 are of particular importance in the pathogenesis of MZBCL.     

Ultrasound‐Guided Venous Access for Pacemakers and Defibrillators

Ultrasound‐Guided Lead Placement . Introduction: Ultrasound guidance is widely recommended to reduce the risk of complications during central venous catheter placement. However, ultrasound guidance is not commonly utilized for implanting leads for cardiac rhythm management devices. Methods and Results: We describe our technique of ultrasound‐guided pacemaker implantation, including a novel pull‐through technique that allows percutaneous guidewire insertion prior to the first incision. We review the literature and recent advances in ultrasound imaging technology that may facilitate the adoption of ultrasound guidance. Conclusions: Ultrasound guidance provides a safe and rapid technique for extrathoracic subclavian or axillary venous lead placement. (J Cardiovasc Electrophysiol, Vol. 24, pp. 370‐374, March 2013)     

Experimental Pathological Studies on the Nature and Rôle of Bacterial Allergy.

It is now well known that while the body is acquiring an active immunity to bacteria during infection, the tissues ordinarily become hypersensitive to the protein of the infecting microorganisms. When this hypersensitiveness has appeared, the tissues will be locally damaged and killed by amounts of the bacterial protein which are harmless to the normal body, and disturbing constitutional symptoms and even death may occur when amounts of the protein which would be harmless to the normal body find their way into the blood stream of the hypersensitive one. By the side of this hypersusceptibility of the tissues to the protein of the infecting bacteria there is also developed a heightened resistance to the growth of the bacteria, and their spread through the tissues and into the blood stream is markedly inhibited. The state of hypersusceptibility to the bacterial protein is ordinarily spoken of as allergy; the ability of the body to inhibit the growth and the invasion of the bacteria, and to neutralize the toxins which they may produce, constitutes acquired immunity.     

Disseminated testicular cancer with bulky disease: results of a phase-II study with cisplatin ultra high dose/VP-16/bleomycin

This is a preliminary analysis of the AIO-Testicular Tumour Study Group trial in patients with disseminated bulky testicular cancer. Treatment plan: cisplatin 35 mg/m2 days 1-5, VP-16 120 mg/m2 days 1-5 (two daily divided doses), bleomycin 15 mg/m2 days 1, 8, 15. Of 98 patients at present evaluable 63% had complete remission or have no evidence of disease (CR/NED), 30% had partial remission (PR) and 7% had no change or progressive disease (NC/P). Relapse-free survival is 93% for the CR/NED group after a median follow up of 2.2 years: the overall survival for the entire patient population is 70%. Toxicity included predominantly granulocytopenic fever and infection with septicaemia, thrombocytopenia, nausea, vomiting, neurotoxicity and lung toxicity, with 7% fatal toxicity. A prospective randomized trial is warranted to evaluate the apparent superior activity of ultra high dose cisplatin in combination with VP-16 and bleomycin.