Effects of High-Frequency Atrial Pacing in Atypical Atrial Flutter and Atrial Fibrillation

Atypical atrial flutter has, hitherto, been relatively refractory totermination by rapid atrial pacing. High-frequency pacing (HFP) in theatrium, for termination of atrial flutter or atrial fibrillation (AF), andthe electrophysiologic effects related to it have not been examined. Weexamined the clinical efficacy, safety, and electrophysiologic mechanisms ofHFP using 50-Hz bursts at 10 mA applied at the high right atrium in patientswith atypical atrial flutter (group 1) or AF (group 2), using a prospectiverandomized study protocol. Four burst durations (500, 1000, 2000, and 4000ms) were applied at the high right atrium repetitively in random sequence in22 patients with spontaneous atrial flutter or AF. Local and distant rightand left atrial electrogram recordings were analyzed during and after HFP.HFP resulted in local and distant right and left atrial electrogramacceleration in 8 of 10 patients (80%) in group 1 but caused lessfrequent local atrial electrogram acceleration (6 of 12 patients) and nodistant atrial electrogram effects in group 2 (p < .05 versus group 1).The HFP protocol was effective in arrhythmia termination in 6 of 10patients in group 1 but in no patient in group 2 (p < .05 versus group1). Standard HFP protocol applied at the high right atrium can frequentlyalter atrial activation in both atria and can terminate atypical atrialflutter. Efficacy in AF is limited, probably due to limitedelectrophysiologic actions beyond the local pacing site.     

Indapamide-induced hyponatremia or the syndrome of inappropriate antidiuretic hormone secretion: a case report

We report a case of an apparently well-documented indapamide-induced hyponatremia. The initial diagnosis was made on the basis of dechallenge and rechallenge performed on two occasions. Further course of the disease, which proved inconsistent with our expectations, prompted us to look for another aetiology leading to the final diagnosis of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) complicated by indapamide treatment.     

Melatonin enhances antioxidant action of α‐tocopherol and ascorbate against NADPH‐ and iron‐dependent lipid peroxidation in human placental mitochondria

Abstract: Human placental mitochondria might be a significant source of NADPH‐ and iron‐dependent production of reactive oxygen species (ROS). Preeclampsia is believed to be a consequence of overproduction of ROS in human placenta. The experimental results presented here show that melatonin inhibits NADPH‐ and iron‐dependent lipid peroxidation of human placental mitochondria in a concentration‐dependent manner. At 1.5 mm concentration, melatonin suppressed this process nearly completely. Melatonin does not influence significantly the iron oxidation at this conditions, indicating that free radical scavenging rather than metal‐chelating phenomenon is the basis of its antioxidant action. The fact of inhibition of lipid peroxidation by melatonin at conditions excluding iron participation also supports this hypothesis. Elucidation of the nature of common interaction among melatonin, ascorbate, and α‐tocopherol in human placental mitochondria was the main aim of this study. In presence of 90 μm ascorbate, the inhibition of lipid peroxidation by melatonin was strong and had a feature of synergistic interaction. At presence of 30 μm ascorbate, which stimulated lipid peroxidation, melatonin caused a loss of pro‐oxidant effect of ascorbate. While the interaction of melatonin with ascorbate indicated synergism, the joint action of melatonin and α‐tocopherol was additive. When all three antioxidants were applied together, the strongest inhibition of lipid peroxidation was observed. The experimental results presented here indicated that melatonin could be considered as an effective component of antioxidant treatment of preeclampsia, allowing the use of reduced doses of vitamin C and E owing to elevated efficiency of their antioxidant activity in placenta when used in combination.     

Tubulointerstitial nephritis with uveitis: clinico-pathological and immunological study

A 10-year-old boy was evaluated for fever, weight loss, uveitis, normocytic, normochromic anemia, renal insufficiency, and hypergammaglobulinemia of 8 weeks' duration. Infectious and neoplastic causes of fever were excluded. A renal biopsy performed in the 4th week of disease revealed diffuse plasmocytic interstitial nephritis. No treatment was prescribed and the patient was transferred to another hospital. Because clinical symptoms and renal insufficiency were still present, in the 8th week of disease a second biopsy was performed, which showed lympho-monocytic interstitial nephritis. At the same time, phenotypic analysis of peripheral blood mononuclear cells was carried out, revealing a significantly decreased number of CD3(+), CD4(+), and CD3(+)/CD8(+) cells, increased non-T CD3(-)/CD8(+) and CD56(+) NK cells, and decreased "na?ve" (CD45RA(+)/CD4(+)) and memory (CD45RO(+)/CD8(+)) T lymphocytes. A 6-month course of oral prednisone was prescribed. Clinical symptoms and laboratory findings quickly returned to normal values. After 13 days of corticosteroid therapy, a second phenotypic analysis of peripheral blood mononuclear cells was performed, which revealed normalization of CD3(+), CD4(+), and CD3(+)/CD8(+) cells as well as proportions of non-T CD8(+) and CD56(+) NK lymphocytes, "na?ve" and memory cells. This case shows spontaneous evolution of tubulointerstitial infiltrates from plasmacytic to lympho-monocytic, profound disturbances of the immunological system, and the beneficial effect of corticosteroids on both the clinical course and immunological disturbances.     

Comparative evaluation of safety and efficacy of pamidronate and zoledronic acid in multiple myeloma patients (single center experience)

Osteolytic bone destruction, caused by the aberrant production and activation of osteoclasts, results in significant morbidity for patients with multiple myeloma (MM). Pamidronate [(3-amino-1-hydroxypropylidene)-1,1-bis-phosphonate] inhibits osteoclastic activity and reduces bone resorption. A potency of zoledronic acid (2-[imidazol-1-yl]-1-hydroxyethylidene-1,1-bisphosphonic acid, a new third generation bisphosphonate, as inhibitor of resorption was 850-fold greater than pamidronate, as was shown in preclinical models of bone resorption. Randomized, double-blind study was conducted to compare the efficacy and safety of zoledronic acid and pamidronate for treating myeloma bone disease. Since March 1999 the efficacy and safety of pamidronate and zoledronic acid is evaluated in MM patients all receiving anti-myeloma chemotherapy acc. to VMCP/VBAP alternating regimen. Nine patients with stage III myeloma and osteolytic lesions (3 female, 6 male, median age 57 years, range 52-67, with monoclonal protein: IgG-7, IgA-2) were randomly assigned (1:1:1 ratio) to treatment with either 4 or 8 mg of zoledronic acid via 15-minute intravenous infusion or 90 mg of pamidronate via 2-hour intravenous infusion every 3 to 4 weeks for 12 months. All patients have received 500 mg of calcium supplements and 500 IU of vit.D, orally, once daily, for the duration of administration of study medication. In extension phase of the study (June 2000-April 2002) patients did not received bisphosphonates. In 7 patients 18 cycles of assessed treatment was administered to each of them and one patient received 16 cycles. One patient died after receiving of 12 pamidronate therapy cycles at 11 month of the trial duration (and at 49 month since MM diagnosis and anti-tumour treatment). The patient's death occurred during the progression of plasma cell proliferation due to acute left ventricle cardiac failure. During the 12-month-period of bisphosphonate treatment skeletal related events (SRE) and progression of osteolysis occurred with the same frequency in 3 treatment groups. One patient experienced spinal cord compression and received radiation to bone and 2 patients experienced vertebral fracture. Time from study entry to the first SRE was 304 days in pamidronate and 366 and 392 days in 4 and 8 mg zoledronic acid group, respectively. The skeletal morbidity rate was identical in all treatment groups. Single hypocalcemic events occurred in 2 patients, mild hypertransaminasemia was observed in 3, worsening of renal function parameters in 2 patients (transient in one of them). Muscular pain and fever up to 39 degrees C (transient and self-limiting "flu-like" symptoms) occurred in 6 patients after several or some dozens of hours from study drug administration. Adverse events were similar in nature and frequency with zoledronic acid and pamidronate and were experienced by a similar proportion of patients in each treatment group. Median time of patient's observation duration after completing of administered treatment with zoledronic acid and pamidronate amounts to 20 months. At present actual median survival time of analysed patients since MM diagnosis is 42 months, since the beginning of treatment with pamidronate and zoledronic acid--33 months, and since completing treatment--20 months and is similar in 3 treatment groups. As was shown in our single center study in MM patients the safety and efficacy of pamidronate 90 mg and zoledronic acid 4 mg and 8 mg in monthly i.v. infusion are comparable. Thus the recommended dosage of zoledronic acid is 4 mg administered as a 15 minute i.v. infusion at intervals of 3 to 4 weeks.     

Some aspects of arsenic toxicity and carcinogenicity in living organism with special regard to its influence on cardiovascular system,blood and bone marrow

This paper gathers data on the most current aspects of arsenic action, especially its influence on the cardiovascular system, blood and bone marrow. A potential carcinogenic mechanism of arsenic is also discussed. Arsenic is a potent toxicant that may exist in several valencies and in a number of inorganic and organic forms. Most cases of arsenic-induced toxicity in humans are due to exposure to inorganic arsenic, and there is an extensive database on the human health effects of common arsenic oxides and oxyacids. Exposure of humans living near hazardous waste sites may involve inhalation of arsenic dusts in the air, ingestion of arsenic in water, food or soil, or dermal contact with contaminated soil or water. The exposure to arsenic via the inhalation route is responsible for the increased risk of lung cancer, although respiratory irritation, nausea and skin effects may also occur. The oral route of exposure to arsenic predominates in the general population. The most common effects of arsenic ingestion are gastrointestinal irritation, peripheral neuropathy, vascular lesions, anemia, skin diseases, including skin cancer and other cancers of the internal organs like bladder, kidney, liver or lung. Relatively little information is available on the effects of direct dermal contact with inorganic arsenicals, but several studies indicate local irritation and dermatitis as the major ones.     

Restoration of human beta-globin gene expression in murine and human IVS2-654 thalassemic erythroid cells by free uptake of antisense oligonucleotides

Correct human beta-globin mRNA has been restored in erythroid cells from transgenic mice carrying the human gene with beta-globin IVS2-654 splice mutation and from thalassemia patients with the IVS2-654/beta(E) genotype. This was accomplished in a dose- and time-dependent manner by free uptake of morpholino oligonucleotide antisense to the aberrant splice site at position 652 of intron 2 in beta-globin pre-mRNA. Under optimal conditions of oligonucleotide uptake, the maximal levels of correct human beta-globin mRNA and hemoglobin A in patients' erythroid cells were 77 and 54%, respectively. These levels of correction were equal to, if not higher than, those obtained by syringe loading of the oligonucleotide into the cells. Comparison of splicing correction results with the cellular uptake of fluorescein-labeled oligonucleotide indicated that the levels of mRNA and hemoglobin A correlate well with the nuclear localization of the oligonucleotide and the degree of erythroid differentiation of cultured cells. Similar but not as pronounced results were obtained after the oligonucleotide treatment of bone marrow cells from IVS2-654 mouse. The effectiveness of the free antisense morpholino oligonucleotide in restoration of correct splicing of IVS2-654 pre-mRNA in cultured erythropoietic cells from transgenic mice and thalassemic patients suggests the applicability of this or similar compounds in in vivo experiments and possibly in treatment of thalassemia.     

Acute cervical epidural hematoma as a complication of anterior cervical C5-C6 diskectomy. A case report

A 32 year-old woman with cervico-brachial pain and progressive neurological disorders was admitted to the Department and Clinic of Neurosurgery and Neurotraumatology of the K. Marcinkowski University of Medical Sciences in Poznań. Neurological examination revealed right hemiparesis with muscular atrophy in the right upper limb, progressing in the past 3 months. MRI demonstrated relatively large herniations of C4-C5 and C5-C6 discs with spinal and nerve compressions. A surgery was carried out. Discectomy of C4-C5 and C5-C6 discs was performed using the anterior vertebral approach. After the removal of C4-C5 and C5-C6 discs and C5 vertebral body a fragment of the iliac bone strut was wedged between C4 and C6 vertebral bodies. The bone graft was fixed to C4 and C6 vertebral bodies with a titanium plate. Within 6 hours after the surgery the patient developed a complete loss of motor functions in the upper and lower limbs. MRI scan of the cervical spine showed a huge anterior epidural hematoma compressing the spinal cord. An emergency re-operation and removal of the hematoma was performed by the anterior approach. A complete neurological recovery followed during the first 24 postoperative hours.     

Post-traumatic unilateral atlanto-axial rotatory subluxation in an adult

This retrospective single-patient case report deals with a rare form of spinal trauma, i.e. atlantoaxial rotatory subluxation. The authors present a review of the literature including a classification of rotatory atlantoaxial subluxation types proposed by Fielding, and describe their own experience with treatment of this condition. A case is reported of a 29-year-old woman with a history of head contusion in a car accident. Immediately after the trauma she had the following symptoms: torticollis and neck pain with decreased cervical motion. Atlantoaxial rotatory subluxation of the right C1-C2 articulation was diagnosed by plain radiographs and CT. The patient was treated surgically by an open reduction, unilateral screw fixation of the right CI-C2 articulation (according to Magerl) and posterior C1-C2 wiring with graft. The normal atlantoaxial relation was restored with disappearance of torticollis. At follow-up certain limitation of neck movements due to C1-C2 stabilization persisted. No complications were noted. The patient remains neurologically intact and has radiographic documentation of fusion.     

Single fibers of skeletal muscle as a novel graft for cell transplantation to the heart

OBJECTIVE: Skeletal myoblast transplantation is a promising alternative to treat heart failure. A single fiber, the minimal functional unit of skeletal muscle, retains skeletal myoblasts beneath the basal lamina. When surrounding muscle is injured, myoblasts migrate from the fiber into the damaged area to regenerate muscle. We hypothesized that such isolated fibers could be used as an efficient vehicle to deliver myoblasts into damaged myocardium, resulting in improved cardiac function. METHODS: Living single fibers of rat skeletal muscle were isolated, and their behavior was characterized in vitro. Single fibers were injected into the myocardium (at 4 sites, each receiving a single fiber) of rats in 2 models of heart failure induced either by means of doxorubicin administration or left coronary artery occlusion. RESULTS: Skeletal myoblasts dissociated from an isolated single fiber, proliferated, and differentiated into multinucleated myotubes in vitro. Within 3 days after grafting in vivo, original fibers provided putative myoblasts and disappeared. At 4 weeks, discrete loci consisting of several multinucleated myotubes were observed. Furthermore, single-fiber transplantation significantly improved cardiac function compared with the control treatment in either doxorubicin-treated hearts (maximum dP/dt, 4013.9 +/- 96.1 vs 3603.1 +/- 102.3 mm Hg/s; minimum dP/dt, -2313.7 +/- 75.1 vs. -2057.1 +/- 52.4 mm Hg/s) or ischemic hearts (maximum dP/dt, 3905.6 +/- 103.0 vs 3572.6 +/- 109.7 mm Hg/s; minimum dP/dt, -2336.1 +/- 69.7 vs -2106.4 +/- 74.2 mm Hg/s). CONCLUSION: Single-fiber transplantation acts as a vehicle for delivering putative skeletal myoblasts that appear to differentiate into myotubes within the myocardium. This was associated with improved function of failing hearts, suggesting its efficacy as a novel graft for cellular cardiomyoplasty.