Coronary atherosclerosis in cardiac transplant patients treated with total lymphoid irradiation.

BACKGROUND: Multiple episodes of rejection following cardiac transplantation have been associated with an increased incidence of coronary atherosclerosis. Total lymphoid irradiation (TLI) has been shown to be a successful treatment for persistent allograft rejection, but its effect on coronary arterial disease has yet to be evaluated. METHODS: From 1987 to 1999, 40 patients required TLI for persistent or recurrent allograft rejection following heart transplantation. Each patient's (Group 1, n = 31) post-transplant coronary angiograms were examined and compared with those of a control group (Group 2, (n = 32) matched for time of transplantation. Degree of coronary stenosis was assessed on a 6-point scale. All patients received induction therapy (rabbit anti-thymocyte globulin or OKT3) and standard triple immunosuppressive therapy. TLI (80 cGy x 10 fractions) was used for the treatment of recurrent or persistent rejection on the basis of clinical indications. Actuarial survival, number and treatment of rejection episodes, and severity of coronary artery disease were compared in each group. RESULTS: Recipient gender, age, race and cytomegalovirus (CMV) status at time of transplant, along with donor gender, CMV status and graft ischemia time, were similar in both groups. Group 1 donor age was younger than that of Group 2 (22.2 +/- 11.2 vs 31.5 +/- 13.6 years, p = 0.004), and the indication for surgery in Group 1 patients was more likely to be ischemic heart disease (15 of 31 vs 6 of 32, p = 0.02). Mean follow-up was 5.7 +/- 3.5 years in Group 1 vs 6.9 +/- 3.8 in Group 2 (p = NS). Group 1 had more rejection episodes (4.4 +/- 2.2 vs 2.3 +/- 2.0, p = 0.0002) and more steroid treatments (9.78 +/- 4.0 g vs 5.14 +/- 4.7 g, p < 0.0001), but less coronary artery disease compared with Group 2 (p = 0.035). CONCLUSIONS: Despite multiple episodes of rejection, patients treated with TLI after cardiac transplant appear to develop less coronary atherosclerosis than appropriately matched controls.     

Inverted duplication of the distal short arm of chromosome 3 associated with lobar holoprosencephaly and lumbosacral meningomyelocele

A fetus with lobar holoprosencephaly and lumbosacral meningomyelocele associated with duplication of the short arm of chromosome 3 is reported. The anomalies were detected on fetal ultrasound at 20 weeks' gestation and the autopsy findings correlated well with the prenatal findings. The fetal karyotype was 46,XY,der(3)del(3)(p26) dup(3)(p26p21.3). The association of holoprosencephaly with duplication 3p is well known, but to the best of our knowledge this is the first reported association of meningomyelocele with 3p duplication. These findings suggest that a gene or genes with a crucial role in central nervous system development are located on the short arm of chromosome 3.     

Localization,structure and polymorphism of two paralogous <Emphasis Type="Italic">Xenopus laevis</Emphasis> mitochondrial malate dehydrogenase genes

Two paralogous mitochondrial malate dehydrogenase 2 (Mdh2) genes of Xenopus laevis have been cloned and sequenced, revealing 95% identity. Fluorescence in-situ hybridization (FISH) combined with tyramide amplification discriminates both genes; Mdh2a was localized into chromosome q3 and Mdh2b into chromosome q8. One kb cDNA probes detect both genes with 85% accuracy. The remaining signals were on the paralogous counterpart. Introns interrupt coding sequences at the same nucleotide as defined for mouse. Restriction polymorphism has been detected in the first intron of Mdh2a, while the individual variability in intron 6 of Mdh2b gene is represented by an insertion of incomplete retrotransposon L1Xl. Rates of nucleotide substitutions indicate that both genes are under similar evolutionary constraints. X. laevis Mdh2 genes can be used as markers for physical mapping and linkage analysis.     

Cardiovascular response to peak voluntary exercise in males with cervical spinal cord injury

Context/Objective: Traumatic damage to the cervical spinal cord is usually associated with a disruption of the autonomic nervous system (ANS) and impaired cardiovascular control both during and following exercise. The magnitude of the cardiovascular dysfunction remains unclear. The aim of the current study was to compare cardiovascular responses to peak voluntary exercise in individuals with tetraplegia and able-bodied participants.

Design: A case-control study.

Subjects: Twenty males with cervical spinal cord injury (SCI) as the Tetra group and 27 able-bodied males as the Control group were included in the study.

Outcome Measures: Blood pressure (BP) response one minute after the peak exercise, peak heart rate (HR_peak), and peak oxygen consumption (VO_2peak) on an arm crank ergometer were measured. In the second part of the study, 17 individuals of the Control group completed the Tetra group's workload protocol with the same parameters recorded.

Results: There was no increase in BP in response to the exercise in the Tetra group. Able-bodied individuals exhibited significantly increased post-exercise systolic BP after the maximal graded exercise test (123±16%) and after completion of the Tetra group's workload protocol (114±11%) as compared to pre-exercise. The Tetra group VO_2peak was 59% and the HR_peak was 73% of the Control group VO_2peak and HR_peak, respectively.

Conclusions: BP did not increase following maximal arm crank exercise in males with a cervical SCI unlike the increases observed in the Control group. Some males in the Tetra group appeared to be at risk of severe hypotension following high intensity exercise, which can limit the ability to progressive increase and maintain high intensity exercise.     

Exposure?response modelling for empagliflozin,a sodium glucose cotransporter 2 (SGLT2) inhibitor,in patients with type 2 diabetes

Aims

To provide model-based clinical development decision support including dose selection guidance for empagliflozin, an orally administered sodium glucose cotransporter 2 inhibitor, through developed exposure−response (E−R) models for efficacy and tolerability in patients with type 2 diabetes mellitus (T2DM).

Methods

Five randomized, placebo-controlled, multiple oral dose studies of empagliflozin in patients with T2DM (n = 974; 1–100 mg once daily, duration ≤12 weeks) were used to develop E−R models for efficacy (glycosylated haemoglobin [HbA_1c], fasting plasma glucose [FPG] and urinary glucose excretion). Two studies (n = 748, 12 weeks) were used to evaluate tolerability E−R.

Results

The efficacy model predicted maximal decreases in FPG and HbA_1c of 16% and 0.6%, respectively, assuming a baseline FPG concentration of 8 mm (144 mg dl⁻¹) and 10–25 mg every day empagliflozin targeted 80–90% of these maximums. Increases in exposure had no effect on incidence rates of hypoglycaemia (n = 4), urinary tract infection (n = 17) or genital/vulvovaginal-related (n = 16) events, although low prevalence rates may have precluded more accurate evaluation.

Conclusions

E−R analyses indicated that 10 and 25 mg once daily empagliflozin doses achieved near maximal glucose lowering efficacy.     

Ischemic stroke and dose adjustment of oral Factor Xa inhibitors in patients with atrial fibrillation

Journal of Neurology - Oral Factor Xa inhibitors for the prevention of stroke in atrial fibrillation require dose adjustment based on certain clinical criteria, but the off-label use of the reduced...     

Massive right atrial myxoma presenting with syncope

A 65-year-old man presented to the emergency room following an episode of syncope. His vital signs and physical examination were unremarkable. A chest X-ray and an ECG were also normal. He was admitted to the hospital for further work-up. A computed tomography scan of his brain did not reveal any evidence of stroke, hemorrhage, or mass effect. A transesophageal echocardiogram, however, revealed tricuspid regurgitation and a right atrial mass with finger-like projections, which appeared to originate from the tricuspid valve. Left heart catheterization was performed, showing a 99% proximal right coronary artery stenosis. The patient was scheduled to undergo atrial mass resection, tricuspid valve annuloplasty, and coronary bypass. During the procedure, a large myxoma was found to be adherent to the right side of the atrial septum, adjacent to the fossa ovalis. The mass was friable and was attached to the endocardium by a pedicle. Following resection of the atrial mass and tricuspid valve annuloplasty, a single saphenous vein graft bypass to the right coronary artery was performed. The patient's postoperative course was unremarkable and he was discharged home on postoperative day 6.     

Mental disorders in a female patient with probable Creutzfeldt-Jakob disease

The paper presents an overview of the current knowledge about the etiology, classification of Creutzfeldt-Jakob disease, abnormalities in the results of the EEG, MR and laboratory examinations in patients with this disease. The diagnostic value of the CSF examination for presence of protein 14-3-3 is underlined. The article is based on both Polish and foreign literature, describing mainly the diagnostics of CJD. The case of a female patient with dementia, mental disorders and neurological symptoms in the course of probable CJD, who was hospitalized at the Psychogeriatric Department of the Neuropsychiatric Hospital in Lublin is described.     

Successful treatment of esophageal cancer with transhiatal esophagectomy after heart transplantation

A 55-year-old heart transplant recipient with reflux esophagitis presented for routine endoscopic surveillance of an area of Barrett's metaplasia initially seen 3 years previously. Esophagogastroduodenoscopy revealed adenocarcinoma at 33 cm from the incisors. The preoperative clinical stage was T₁N₀M₀ by endoscopic ultrasound. Transhiatal esophagectomy was performed with R0 resection of the cancer, and the patient recovered uneventfully. Pathologic examination confirmed esophageal adenocarcinoma (T₁N₀M₀) in Barrett's mucosa. The patient is doing well, and has no evidence of disease after 18 months.