Emergency subtotal hepatectomy: a new concept for acetaminophen-induced acute liver failure: temporary hepatic support by auxiliary orthotopic liver transplantation enables long-term success

INTRODUCTION: Acetaminophen (paracetamol) overdose (AOD) has recently emerged as the leading cause of acute liver failure (ALF) in the United States, with an incidence approaching that seen in the United Kingdom. We describe a new way to treat AOD ALF patients fulfilling King's College criteria for "super-urgent" liver transplantation. METHODS: Beginning in June 1998, we have been piloting a clinical program of subtotal hepatectomy and auxiliary orthotopic liver transplantation (ALT) for AOD ALF. Our technique is based on the following principles: (1) subtotal hepatectomy; (2) auxiliary transplantation of a whole liver graft; (3) gradual withdrawal of immunosuppression after recovery. Results were compared with patients who had undergone an orthotopic liver transplantation (OLT) for AOD ALF in the same period. Quality of life comparisons were made using the SF36 questionnaire. RESULTS: Thirteen patients underwent this procedure between June 1998 and March 2005. Median survival is 68 months (range, 0-102 m). Actual survival data show that 9 of 13 patients are alive (69%) compared with 7 of 13 OLT patients (54%). One ALT patient required a retransplantation with an OLT due to hepatic vein thrombosis, and immunosuppression is therefore maintained. The other 8 surviving ALT patients are off immunosuppression. These 8 ALT patients have normal liver function and have a better quality of life compared with the 7 surviving OLT patients. CONCLUSION: Our results with this new technique are encouraging: 69% actual survival, no long-term immunosuppression requirement, and improved quality of life in the 62% successful cases.     

A controlled study of plasma exchange in the treatment of severe rheumatoid arthritis

To learn whether the removal of immune complexes from the circulation by plasma exchange could effect an improvement in disease activity in rheumatoid arthritis (RA) patients, we performed a controlled study of 20 patients with severe progressive disease which had not responded to previous therapy. Ten patients (Group 1) were hospitalized, continued on their regular antiinflammatory medication, and given a graded course of physiotherapy. A further 10 patients (Group 2) received the same treatment as the first group with the addition of a concurrent course of plasmapheresis. Clinical measurement of disease activity after treatment revealed little difference between the two groups with a statistically significant improvement in four measures in Group 1 and in five in Group 2. Laboratory studies suggested that the intensity of plasma exchange was sufficient to remove circulating immune complexes in these patients. Our results confirm that hospitalization in itself is of benefit in the treatment of acute exacerbations of rheumatoid arthritis. The marginal improvement achieved by the addition of plasma exchange in the management of these patients (despite the removal of circulating immune complexes) makes its short-term use of questionable value in the treatment of severe rheumatoid arthritis.     

Dopamine increases the efficacy of anticancer drugs in breast and colon cancer preclinical models.

PURPOSE: Because neurotransmitter dopamine inhibits vascular permeability factor/vascular endothelial growth factor (VEGF)-induced angiogenesis and as anti-VEGF agents act synergistically with anticancer drugs, we therefore investigated whether dopamine can increase the efficacies of these drugs. EXPERIMENTAL DESIGN: The effect of dopamine was investigated in human breast cancer-(MCF-7) and colon (HT29) cancer-bearing mice. Experimental groups received either dopamine or doxorubicin or dopamine plus doxorubicin in MCF-7 tumor-bearing mice, and either dopamine or 5-fluorouracil or dopamine plus 5-fluorouracil in HT29-bearing mice. Thereafter, tumor growth, angiogenesis, tumor cell apoptosis, life span, and the effect of dopamine on the growth and survival of tumor cells in vitro were determined. Finally, the effects of dopamine on tumor vascular permeability; on VEGF receptor-2, mitogen-activated protein kinase, and focal adhesion kinase phosphorylation; and also on the proliferation and migration of tumor endothelial cells were investigated. RESULTS: Dopamine, in combination with anticancer drugs, significantly inhibited tumor growth and increased the life span when compared with treatment with dopamine or anticancer drugs alone. Dopamine had no direct effects on the growth and survival of tumor cells. The antiangiogenic action of dopamine was mediated by inhibiting proliferation and migration of tumor endothelial cells through suppression of VEGF receptor-2, mitogen-activated protein kinase, and focal adhesion kinase phosphorylation. CONCLUSION: Our study shows that dopamine significantly enhances the efficacies of commonly used anticancer drugs and also indicates that an inexpensive drug like dopamine, which is being extensively used in the clinics, might have a role as an antiangiogenic agent for the treatment of breast and colon cancer.     

Role of plant metabolites in toxic liver injury

Aphanamixis polystachya is a traditional medicinal plant of the Meliaceae family in India. A crude ethanolic extract of the leaf of this plant shows a beneficial effect on toxic liver injury. Its antihepatotoxic activity was evaluated on carbon tetrachloride (CCl4)-induced liver injury in a rat model. The assessment of hepatoprotective activity was evaluated by measuring the activities of aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), alkaline phosphatase (ALP), acid phosphatase (ACP) and lactate dehydrogenase (LDH), serum total bilirubin and albumin and histology of the liver. The crude leaf extract significantly inhibits the enhanced ASAT, ALAT, ALP, ACP and LDH activities released from the CCl4-intoxicated animals. It also ameliorated the depressed value of serum albumin and the enhanced value of total bilirubin in plasma caused by CCl4 intoxication. The study showed that the crude ethanolic extract from A. polystachya leaves provided protection against acute carbon tetrachloride-induced liver damage.     

Endothelin receptor antagonists--an overview

In thirteen years since the appearance of Endothelin (ET) on the international scene, possibility of its involvement in a variety of diseases has attracted the attention of medicinal chemists in search of novel therapeutics for various cardiovascular diseases (CVDs). Discovery of pharmaceutical agents which either block the generation of ET from its precursor or antagonize its binding to cellular receptor, should not only provide means to assess the physiological role of ET, but lead to useful therapy for conditions associated with altered production or responsiveness to ET. In this review article, we have attempted to present in a classified format, the kaleidoscope of ET receptor antagonists that have emerged through structure activity relationship studies using the parent peptide as well as from screening of various compound libraries. By all indications, the variety and range of small molecules that are currently under investigation continues to open up newer opportunities and lures fresh groups of scientists into this research arena. Presently a number of these compounds are in the clinics, being evaluated for their beneficial effects in a range of human pathologies such as essential hypertension and chronic heart failure.     

The cost effectiveness of a nurse-led shared-care prostate assessment clinic

OBJECTIVE: Nurse-led prostate clinics (NPCs) have proved to be a highly effective method of assessing patients with lower urinary tract symptoms (LUTS) and most urology units now run such clinics. However, it was not known whether they are cost-effective and this analysis ansWers that question. PATIENTS AND METHODS: During one year, a trained urology nurse assessed 1,080 patients in our NPC following GP referral using a standard pro forma. Costs included those incurred for the salary of a grade D nurse at 30 min per patient, all investigations, indirect charges and overheads. This was compared to the cost of seeing all patients in clinic directly, either by a consultant, staff grade urologist or registrar. Of these 1,080 patients, 350 were sent back to their GPs after NPC assessment. RESULTS: The NPC cost of 44.25 pounds per patient compared favourably with an average medical out-patient clinic cost of 50.46 pounds per patient, yielding an actual annual saving of 6,706.80 pounds. Since a third of the patients assessed in the NPC were sent directly back to primary care, saving the cost of a medical follow-up appointment, the true savings in secondary care were 17,661.00 pounds (50.46 x 350pounds), giving a total annual saving of 24,367.80 pounds. CONCLUSIONS: A nurse-led shared-care prostate clinic is a cost effective, thorough and speedy method of assessing men presenting with suspected bladder outflow obstruction. The approach used has a wider generic, cost-benefit potential for the NHS.     

An interesting rare case of sirenomelia

In sirenomelia the caudal tissues of the foetus fail to develop because of the "stealing" of blood by a vitelline vascular shunt from the distal aorta during embryogenesis interfering with foetal development. A 25 years old 2nd gravida delivered one full term premature grossly asphyxiated baby at BS Medical College on 24-10-1998. The examination of the dead foetus revealed no genitalia, no anal nor urethral opening and having a single lower limb with the single thigh and rudimentary leg. Skiagram of the foetus corroborated it to be a case of syrenomelia.     

Evaluation of efficacy of nizer versus nimesulide tablets in otitis media

An evaluation of clinical efficacy of nizer versus nimesulide tablets was undertaken in 118 patients suffering from otitis media. Nizer demonstrated rapid and powerful analgesic and antipyretic effects compared to plain nimesulide, without additional side effects.