Long-term results of a double perfusion schedule using high dose hyperthermia and melphalan sequentially in extensive melanoma of the lower limb

The aim of this study was to assess the results of an isolated limb perfusion (ILP) schedule with high dose hyperthermia (42-43 degrees C) and melphalan, applied sequentially in patients with advanced melanoma of the limbs. Seventeen patients with extensive recurrent or bulky melanoma of a limb were treated with hyperthermic femoral ILP (42-43 degrees C) without drugs followed by normothermic (37-38 degrees C) ILP with melphalan. Eleven patients (65%) had a complete response. Three patients (27%) had limb recurrences after 5, 6 and 18 months, respectively. The 5 year limb recurrence-free interval for patients with a complete response was 63%. Limb toxicity was mild; pressure-related blistering and transient sensory disturbances occurred after the hyperthermic ILP, and 88% of the patients had a grade II reaction (mild erythema and oedema) after the second ILP. This sequential ILP schedule resulted in a high complete response rate and a low limb-recurrence rate in patients with extensive, recurrent melanoma of the limbs at the cost of only mild toxicity. This regimen could be an alternative to ILP with tumour necrosis factor-alpha and melphalan.     

Management of hypertension

Presently, many drugs are available for the treatment of patients with high blood pressure. Although there are several theoretical arguments favouring one particular type of drug over the other, prospective clinical trials have failed to show major differences between drug classes in terms of overall prognosis. A possible exception in this regard may be the development of diabetes mellitus which seems to occur less frequently with ACE inhibitors, AT1 receptor blockers and calcium entry blockers than with diuretics. The choice of the antihypertensive drug regimen should take certain patient characteristics into account, notably comorbid conditions. However, despite theoretical considerations concerning initial therapy many patients will end up using two or more medications.     

The effect of warfarin on the pharmacokinetics and pharmacodynamics of napsagatran in healthy male volunteers

OBJECTIVE: The effect of oral warfarin on the pharmacokinetics and pharmacodynamics of the synthetic direct thrombin inhibitor napsagatran was investigated. METHODS: In an open, randomised, two-way crossover study, 12 healthy male volunteers were infused napsagatran (80 micrograms/min) for 48 h. Each subject was administered 25 mg warfarin (Coumadin) at the start of the infusion in either the first or second treatment period. Sampling was performed regularly over the treatment period and 24 h thereafter for measurement of plasma levels of napsagatran, activated partial thromboplastin time (APTT) and prothrombin time (PT). RESULTS: The pharmacokinetic parameters of napsagatran were not significantly influenced by co-administration of warfarin. Napsagatran administration was followed by increases in APTT and PT. Co-administration of warfarin increased the AUEC (area under the effect curve) calculated for the period 0-48 h (corrected for baseline) for APTT by 45% (95% CI: 28-65%) and for PT by 438% (95% CI: 272-678%) compared to the treatment with napsagatran alone. CONCLUSION: Warfarin has no effect on the pharmacokinetics of napsagatran, but has a marked influence on the pharmacodynamic parameters (APTT, PT) of napsagatran. In clinical practice, this interaction between the two compounds should be taken into account. The PT cannot be used to monitor the effect of oral anticoagulants during the switch from this group of direct thrombin inhibitors to full oral anticoagulant therapy.     

Occupational stress in naval personnel

Introduction: Increased stress levels have been reported and it has been implicated for mental illness amongst service personnel. However no study has been reported among Indian naval sailors.