Intronic sequence motifs of HLA-DQB1 are shared between humans, apes and old world monkeys, but a retroviral LTR element (DQLTR3) is human specific

Long terminal repeats (LTRs) of the human endogenous retrovirus K (HERV-K) family have been found at several sites within the human genome, of which one is located in the vicinity of HLA-DQB1. Since this DQLTR3 is only present on some haplotypes, we performed a linkage analysis in 130 Caucasian families. In order to date the integration event we also investigated the presence of this DQLTR3 in apes and Old World monkeys. Additionally, we sequenced the adjacent region of DQLTR3-positive and -negative haplotypes in humans, apes and old world monkeys to elucidate their evolution. Linkage analysis revealed a differential integration of DQLTR3 on specific HLA-DQ haploypes: there was a high frequency of this LTR on haplotypes containing HLA-DQB1*0302 (0.96) and a moderate frequency on HLA-DQB1*0402 (0.78), HLA-DQB1*0303 (0.44), HLA-DQB1*0502 (0.38) and HLA-DQB1*0301 (0.35). HLA-DQB1*0201 (0.18), HLA-DQB1*0503 (0.15), HLA-DQB1*0603 (0.15), HLA-DQB1*0602 (0.04), HLA-DQB1*0501 (0.03) and HLA-DQB1*0604 were rarely positive or devoid of DQLTR3. In apes and Old World primates there was no DQLTR3 rendering it a human specific insertion. Sequence analysis of the adjacent region showed two different motifs in humans corresponding to either presence or absence of DQLTR3. Two different motifs were observed within three sequences of Macaca mulatta: One motif is closely related to the sequence from Macaca nemestrina and Macaca fascicularis whereas the other sequence is more closely related with that of Papio papio and Cercopithecus aethiops. Therefore the analysis of retroviral elements as well as intronic sequences of MHC-DQB1 could help to clarify the evolution of this gene region as well the phylogenic relationship between humans, apes and Old World monkeys.     

Aminoglycoside-associated hypomagnesaemia in children with cystic fibrosis

Hypomagnesaemia in children with cystic fibrosis (CF) is under-recognized. We report a child with CF who developed significant hypomagnesaemia following intravenous (i.v.) treatment with aminoglycosides for exacerbations of Pseudomonas aeruginosa infection. Three additional cases have also been observed. Investigations in two patients have revealed excessive renal loss of magnesium. It is postulated that renal tubular damage secondary to the cumulative effects of repeated courses of aminoglycosides resulted in hypomagnesaemia, and we suggest screening for this problem by monitoring serum magnesium regularly in all patients with CF receiving multiple courses of aminoglycosides.     

EBV-specific antibodies in patients with nasopharyngeal cancer and tonsillar cancer. Follow-up of over 4 years

26 NPC patients and 47 TC patients were investigated clinically, and in the sera of these patients EBV-specific antibodies were determined. No relapse occurred in 11 patients with NPC and in 17 patients with TC during the period of 4 years. In addition to the determination of antibodies we looked for EBNA in 3 undifferentiated NPC and 4 undifferentiated TC, and for EBV-DNA in 2 of these NPC and one of these TC. The 3 NPC and 4 TC tested for EBNA showed this antigen in the cells. 2 NPC and 1 TC showed EBV-DNA with in situ hybridization technique. In the blot hybridization according to Southern the Eco R 1 fragment of both NPC was identical with the Eco R 1 fragment of the positive control of P 3 HR 1 cells. The 15 NPC-patients with tumour (4 with primary NPC, 11 with relapse) in the observation period showed higher IgA-VCA titres than the NPC patients free of relapse during this time. Subsequent to therapy, IgG-VCA titres decreased. Most of the NPC-patients with tumour during the time of testing mentioned before had IgA-VCA once or several times. Most of half of these patients had IgA-EA, but there was no patient without relapse. IgA-VCA increase and the presence of IgA-EA may be the first sign of a relapse. Thus, intensive research into this phenomenon will be required. No remarkable difference could be found in EBV-specific antibody patterns between TC patients without relapse and TC patients with tumour progression or relapse.     

Thrombosis at venous insertion sites after inferior vena caval filter placement

Color Doppler flow imaging or compression ultrasound (US) was used to prospectively determine frequency of thrombosis at 54 venous insertion sites (47 in common femoral veins, seven in right internal jugular veins) after percutaneous placement of Greenfield filters for interruption of the inferior vena cava. Fifty-one filters were successfully placed in 51 patients with a dilator set or a balloon angioplasty catheter. Nine focal thrombi were detected in the common femoral vein (19%) and one in the right internal jugular vein (14%). Use of dilators induced eight thrombi (24%), compared with two (10%) from balloon catheters. The left common femoral vein had a high frequency of thrombosis, regardless of dilation technique (five of nine). Of nine patients with acute common femoral vein thrombosis, four became symptomatic within 10 days after the procedure. Patients may remain asymptomatic or have delayed symptoms; thus, US is valuable for determining patients at risk of thrombosis of the common femoral vein.     

High-frequency oscillations of ictal muscle activity and epileptogenic discharges on intracranial EEG in a temporal lobe epilepsy patient.

OBJECTIVE: During seizures, intracranial EEG electrodes can record ictal muscle movements. Our purpose was to differentiate the high-frequency oscillations (HFOs) of extracranial muscle contractions from those of intracranial epileptogenic discharges. METHODS: Using intracranial video-EEG (IVEEG), we recorded seizures in a 17-year-old boy with left mesial-temporal lobe epilepsy. We used multiple band frequency analysis (MBFA) to differentiate extracranial HFOs of craniofacial muscle activities from intracranial HFOs recorded ictally and interictally. RESULTS: During 11 seizures, IVEEG showed low-amplitude fast waves ( approximately 60Hz) starting at the left mesial-temporal electrodes. Ictal facial grimacing projected low-amplitude ( approximately 20muV) fast waves ( approximately 160Hz) on inferior lateral-temporal electrodes. Interictal chewing projected medium-amplitude ( approximately 100muV) fast waves ( approximately 140Hz) correlating to mouth movements. MBFA topographic power spectrograms revealed a sustained, consistent ictal fast-frequency band from electrodes in the seizure-onset zone and randomly scattered HFOs without a specific frequency band from ictal and interictal extracranial muscle contractions. CONCLUSIONS: MBFA power spectrograms differentiated randomly scattered muscle HFOs without a specific frequency band at electrodes close to temporal muscles from ictal epileptic HFOs with a sustained, fast-frequency band in the seizure-onset zone. SIGNIFICANCE: The pattern and distribution of frequency power spectrograms of extracranial HFOs differ from those of intracranial HFOs.     

Estimation of a common odds ratio in paired-cluster randomization designs

We develop two estimators of a common odds ratio psi for designs in which the investigator randomly assigns each of two clusters to interventions within strata. The estimators rely on an empirical adjustment for clustering to provide improved estimators of psi relative to the standard Woolf and Mantel-Haenszel estimators, respectively. The results of a simulation study show that the suggested adjustment improves the accuracy of both of these well-known estimators under conditions likely to arise in practice. We find the clustered Woolf estimator as particularly effective in terms of mean squared error reduction. We also discuss interval estimation.     

Calcium and citrate excretion by patients with calculi and healthy probands during induced acidosis

Acidosis induced increase in renal calcium excretion and decrease in renal citrate excretion was produced by means of ammonium chloride load in 15 patients with recurrent oxalate lithiasis and in 15 control subjects. The expected increase in the calcium citrate relationship in urine is more marked and more lasting in stone patients. Stone formers obviously respond to an acidotic metabolic situation by a more clear relative decrease in citrate excretion, in addition to more intensive calcium excretion, which is known. A certain individual sensitivity of renal tubular mechanisms is discussed with regard to acid base changes.     

Influence of atorvastatin versus simvastatin on fibrinogen and other hemorheological parameters in patients with severe hypercholesterolemia treated with regular low-density lipoprotein immunoadsorption apheresis.

Low-density lipoprotein (LDL) apheresis is a treatment option in patients with coronary artery disease and elevated LDL cholesterol concentrations if maximal drug therapy fails to achieve adequate LDL cholesterol reduction. This therapy is more effective when combined with strong lipid-lowering drugs, such as atorvastatin. However, conflicting data have been published concerning the effect of atorvastatin on fibrinogen concentration. Therefore, we investigated the effect of atorvastatin compared to simvastatin on fibrinogen concentration and other hemorheological parameters in patients treated by weekly LDL apheresis. Hemorheological parameters were, studied twice in 9 patients (4 female, 5 male, 54.0+/-8.9 years) with coronary artery disease treated by weekly LDL immunoadsorption, once during concomitant simvastatin therapy (40 mg daily) and once during atorvastatin therapy (40 mg daily). Fibrinogen concentration, plasma and blood viscosity at different shear rates, parameters of red cell aggregation at stasis and shear rate 3/s, and erythrocyte filterability were determined 7 days after the last LDL apheresis after each drug had been given for a minimum for 8 weeks. Fibrinogen concentration did not show any statistically significant difference during therapy with atorvastatin (3.09+/-0.36 g/L) compared to simvastatin (3.13+/-0.77 g/L). Plasma and blood viscosity as well as erythrocyte filterability were also unchanged. The increase in red cell aggregation at stasis during atorvastatin treatment (5.82+/-1.00 U versus 4.89+/-0.48 U during simvastatin; p < 0.05) was inversely correlated with a lower high-density liprotein (HDL) cholesterol concentration (1.17+/-0.21 mmol/L versus 1.31+/-0.30 mmol/L during simvastatin; p < 0.05). LDL cholesterol showed a strong trend to lower concentrations during atorvastatin (4.14+/-0.61 mmol/L versus 4.56+/-0.66 mmol/L during simvastatin; p = 0.07), despite a reduced plasma volume treated (3,547+/-1,239 ml during atorvastatin versus 3,888+/-1,206 mL during simvastatin; p < 0.05). In conclusion, fibrinogen concentration and other hemorheological parameters were unchanged during atorvastatin compared to simvastatin therapy with the exception of a higher red cell aggregation at stasis. Therefore, with respect to hemorheology, we conclude that atorvastatin should not be withheld from hypercholesterolemic patients regularly treated with LDL immunoadsorption.