Goth migration induced changes in the matrilineal genetic structure of the central-east European population.

For years, the issues related to the origin of the Goths and their early migrations in the Iron Age have been a matter of hot debate among archaeologists. Unfortunately, the lack of new independent data has precluded the evaluation of the existing hypothesis. To overcome this problem, we initiated systematic studies of the populations inhabiting the contemporary territory of Poland during the Iron Age. Here, we present an analysis of mitochondrial DNA isolated from 27 individuals (collectively called the Mas-VBIA group) excavated from an Iron Age cemetery (dated to the 2nd-4th century A.D.) attributed to Goths and located near Maslomecz, eastern Poland. We found that Mas-VBIA has similar genetic diversity to present-day Asian populations and higher diversity than that of contemporary Europeans. Our studies revealed close genetic links between the Mas-VBIA and two other Iron Age populations from the Jutland peninsula and from Kowalewko, located in western Poland. We disclosed the genetic connection between the Mas-VBIA and ancient Pontic-Caspian steppe groups. Similar connections were absent in the chronologically earlier Kowalewko and Jutland peninsula populations. The collected results seem to be consistent with the historical narrative that assumed that the Goths originated in southern Scandinavia; then, at least part of the Goth population moved south through the territory of contemporary Poland towards the Black Sea region, where they mixed with local populations and formed the Chernyakhov culture. Finally, a fraction of the Chernyakhov population returned to the southeast region of present-day Poland and established the archaeological formation called the "Maslomecz group".

Does MRSA affect patient outcomes in the elderly? A retrospective pilot study.

We retrospectively studied admissions to our geriatric acute assessment and rehabilitation ward over a one-year period, to identify those with Methicillin-resistant Staphylococcus aureus (MRSA) and determine whether this affected outcomes. Two hundred and thirty eight admissions of 204 patients were analysed and 9.8% of patients were MRSA positive. Demographics did not differ between MRSA positive and negative patients. Respiratory co-morbidity was more common in MRSA positive patients. Rates of functional decline did not differ between the two groups. Those colonized or infected by MRSA had a significantly longer stay (51.4 vs. 32.2 days, P=0.03), perhaps due to isolation and limited rehabilitation. The virulence of MRSA may be less in these patients, therefore isolation may be inappropriate and counter-productive.

Cognitive effects of anticonvulsant monotherapy in elderly patients: a placebo-controlled study.

Old age is recognized to be the commonest time in life to develop epilepsy. There is a perception that older patients are more sensitive to the deleterious cognitive effects of antiepileptic drugs (AEDs). Elderly patients (median age 70 years, range 60-88 years) taking anticonvulsant monotherapy (10 carbamazepine [CBZ], 8 sodium valproate [VPA], 5 phenytoin [PHT]) took an extra dose of their usual medication (200mg CBZ, 500mg VPA, 100mg PHT) and matched placebo each for a month in random order. The concentrations of AEDs were higher after 7 and 28 days of active treatment compared with placebo (7 days: CBZ 9.5 vs. 7.8 mg L(-1), p < 0.05; VPA 97 vs. 64 mg L(-1), p < 0.05; PHT 13 vs. 11 mg L(-1), p < 0.05; 28 days: CBZ 9.4 vs. 7.7 mg L(-1); p < 0.01, VPA 85 vs. 60 mg L(-1), p < 0.05; PHT 16 vs. 13 mg L(-1), p < 0.05). Despite these increases in concentration, there were no significant changes in attention, reaction time, finger tapping, memory, side-effect scale or sedation scoring during the active phases compared with placebo phases for the three drugs analysed together and separately. Elderly patients taking standard AEDs as monotherapy did not develop cognitive impairment when the dose was modestly increased within the target range for each drug.

Management of seizures in the elderly: a survey of UK geriatricians.

The incidence and prevalence of epilepsy increase substantially with old age. Despite this, the investigation and management of this patient population remains a grey area. Four hundred and eleven (53%) consultant geriatricians responded to a questionnaire exploring their approach to seizures in the elderly in order to establish an overview of current clinical practice. Between one and five patients presenting with seizures, predominantly aged between 75-85 years, were reviewed monthly. Seventy per cent of geriatricians undertook to investigate the patients themselves with biochemical and haematological profiles performed by most. Electroencephalography and computerized tomographic scanning were routinely requested by a quarter of responders. Only 58% would themselves initiate therapy with antiepileptic drugs, with 16% of consultants starting treatment following the first seizure, 59% after a second and 5% after a third. Phenytoin was first choice for generalized tonic-clonic seizures with carbamazepine preferred for partial seizures. If good control was not obtained, 67% would substitute another first line drug, while 27% would add in a second. Less than 3% would use the new anticonvulsants lamotrigine or vigabatrin. Sixty per cent monitored anticonvulsant concentrations in patients with poor control or suspected toxicity. A wide variability was seen in the current approach to seizures in the elderly, which reflects a lack of established practice. Epilepsy clinics for the elderly would encourage structured research into the many unanswered questions affecting the care of older people with seizures.

Deliberate overdose with the novel anticonvulsant tiagabine.

Tiagabine is a novel antiepileptic drug which acts by decreasing gamma aminobutyric acid uptake in astrocytes and neurones. Here the first case of deliberate overdose with this compound in a patient on concomitant phenytoin is reported. On admission to hospital his conscious level deteriorated to grade III coma. No changes in the electrocardiogram were noted. Recovery from the initial effects was rapid, and there were no sequelae. Plasma levels of tiagabine (3.1 micrograms/ml) 4 hours after ingestion were 30 times higher than at typical steady state during therapeutic dosing. The effects of poisoning with current first-line antiepileptic drugs are reviewed. The newer agents, particularly those with greater biochemical specificity, may be safer in overdose than the more established anticonvulsants.

Vigabatrin and lamotrigine in refractory epilepsy.

Epilepsy arises from an imbalance of inhibitory and excitatory influences in the brain. Vigabatrin (VIG) decreases the breakdown of the inhibitory neurotransmitter gamma-aminobutyric acid, whereas lamotrigine (LTG) reduces presynaptic excitatory amino acid release. 22 patients with refractory epilepsy, treated with an anticonvulsant regimen containing VIG, entered a balanced, double blind, placebo controlled, crossover trial of additional LTG. Treatment periods of 12 weeks (25 mg, 50 mg, 100 mg LTG twice daily for four weeks at each dose, and matched placebo) were followed by wash out intervals of four weeks. 14 of the 20 patients completing the study improved, resulting in a significant fall in seizure days and numbers. Analysis of seizure type confirmed a beneficial effect on partial and secondary generalised tonic-clonic seizures. At the highest LTG dose (200 mg daily) there was a median fall of 37% in seizure count with nine (45%) patients reporting > 50% reduction. Three of these patients were seizure free during this month of treatment. Side effects were minimal throughout the study. Concentrations of other antiepileptic drugs, including those of carbamazepine 10,11-epoxide, were not modified by LTG. This study suggests a substantial efficacy for a regimen containing VIG and LTG. Combinations of drugs with complementary modes of action may provide a rational pharmacological approach to the management of refractory epilepsy.

Physiological changes due to age. Implications for cardiovascular drug therapy.

Cardiovascular disease is the single largest cause of death in the elderly. Many of the published studies concerning the physiology and pharmacology of the aging cardiovascular system are seriously flawed. Problems include failure to measure the drug bioavailability and the selection of subjects with overt or subclinical disease. With exercise, the rise in heart rate is inversely proportional to age and maximum heart rate is reduced. Baroreceptor reflex activity appears to decline with age. Cardiac output is maintained in the elderly, with a slower heart rate and a greater stroke volume than in the young. Plasma noradrenaline (norepinephrine) levels increase in the elderly but there is no change in the sensitivity of the vasoconstrictor alpha 1-adrenoceptor. There is evidence for a decline in the activity of the vasodilator beta 2-adrenoceptor with age. It is difficult to make general rules about the effect of aging on the disposition and elimination of drugs. Each drug must be tested separately.

Biological variation of urinary N-acetyl-beta-D-glucosaminidase: practical and clinical implications.

The analytical, within-subject, and between-subject components of variation of N-acetyl-beta-D-glucosaminidase (NAG) were estimated from duplicate assays of 10 timed first morning and 10 untimed urine specimens collected from each of 15 ostensibly healthy individuals. Results were expressed in terms of activity, NAG/creatinine ratio, and excretion rate. Current analytical methods can achieve desirable performance standards. NAG has little individuality, and conventional population-based reference intervals are therefore useful. In view of the practicability and relatively low within-subject variation, for routine clinical purposes we prefer assay of NAG in first morning urine, expressing the results in terms of activity. Using the results of assays of different specimens, we found that the correlation between urinary albumin and NAG varied considerably, owing to the large intrinsic variability of both analytes; this might explain previous conflicting results.

The basic and advanced cardiopulmonary resuscitation skills of trained hospital nursing staff.

The cardiopulmonary resuscitation skills of 105 trained hospital nurses were tested. Both basic and, for the first time in the UK, advanced skills were examined; basic skills were assessed by practical evaluation with a standard manikin and advanced knowledge by multiple choice questionnaire. No nurse adequately performed all four practical skills tested. Knowledge of the ventilatory aspects of resuscitation, defibrillation and advanced technique and drug management were also found to be poor. The findings add further support to adequate training of nurses in resuscitation skills. We describe a solution to overcome the heavy demands of such teaching and suggest that the same model be applied to the training of medical staff in resuscitation skills.

Central venous catheterization and fatal air embolism.

Central venous catheterization is an established procedure in medical, surgical and anaesthetic practice. However, the procedure is not without hazard. One complication that may be life-threatening is air embolism. This article considers the causes of air embolism related to central venous catheterization, its treatment and methods of prevention.