Localized Kaposi''s sarcoma in a patient with pemphigus vulgaris

We report the case of a patient with a 13-year history of pemphigus vulgaris (PV) treated with immunosuppressive agents, prednisone and mycophenolate mofetil who had developed lesions of Kaposi's sarcoma (KS) on a sole plaque of PV that had been previously treated with intralesional injections of steroids. The lesions were surgically removed and polymerase chain reaction (PCR) demonstrated human herpesvirus-8 (HHV-8) DNA. There were neither recurrences nor later dissemination of KS following gradual decrease of the immunosuppressive therapy. We suggest that the treatment with intralesional steroids may have influenced the local reactivation of a latent infection of the virus, determining the appearance of this localized KS.     

Toxic cardiomyopathy: the effect of antipsychotic-antidepressant drugs and calcium on myocardial protein degradation and structural integrity

In the nonrecirculating isolated perfused rat heart it has recently been described that basal myocardial protein degradation is suppressed by 30% within 5 min of maximal beta-adrenergic receptor occupancy under 5 X 10(-7) M isoproterenol (Lockwood, 1985, Biochem. J. 231, 299-308). This adrenergic-controlled proteolytic process presumably contributes to the well-known normal coordination of myocardial protein mass with functional demand. It is presently reported that elevated intracellular calcium is among the messengers that somehow suppress protein degradation. Acute elevation of extracellular calcium to a maximal concentration of 9.0 mM mimicked the simultaneous effects of isoproterenol on increasing inotropy and decreasing protein degradation, although this concentration was eventually lethal. Conversely, infusion of trifluoperazine (TFP), a calmodulin-blocking antipsychotic drug, caused stimulation of protein degradation above basal levels within 5 min. The stimulation of degradation by 30-60% was transient at 5 X 10(-7) M and returned to the control level in 5-10 min. However, TFP produced massive irreversible release of amino acid peptides and proteins at 10(-5) M within 30 min, followed by grossly observable cell structural disruption and cell separation. The degradative stimulation caused by TFP was potentiated by lowering the normal 2.5-mM extracellular Ca2+ concentration to 1.25 mM. Trifluoperazine at 10(-5) M caused longitudinal separation of myofibrils by disrupting lateral attachments between adjacent Z lines, leading to a loss of lateral myofibrillar registry followed by myofibrillar degeneration. Spot desmosomes were disrupted, leading to lateral cell separation; however, the fascia adherens region of the intercalated disks remained intact and cells maintained end-to-end attachment. Perfusion under the low extracellular Ca2+ concentration of 0.1 mM for 0.5 hr caused separation of the fascia adherens region and spot desmosomes of the intercalated disks as well as disruption of cytoplasmic myofibrils and other changes. Although the structural disorganization caused by perfusion with low (0.1 mM) Ca2+ were similar to those caused by TFP, cells also lost end to end attachment under low Ca2+. Amitriptyline (10(-5) M), thioridazine (10(-5) M), and calmidazolium (10(-6) M) stimulated protein degradation and caused structural damage. It is speculated that the above Ca2+-related phenomena describe the mechanism of the well-known toxic cardiomyopathy resulting from overdoses of some of the antipsychotic-antidepressant drugs.(ABSTRACT TRUNCATED AT 400 WORDS)     

Flerobuterol: a potential antidepressant drug related to β-adrenergic agonists. Experimental profile in mice

The potential antidepressant effect of flerobuterol (dl-(fluoro-2 phenyl)-1 t-butylamino-2 ethanol), a new drug related to beta-adrenoceptor agonists, was evaluated and compared with imipramine and salbutamol using classical psychopharmacological tests in mice. Like imipramine and salbutamol, flerobuterol (0.5-32 mg kg-1, ip) fully prevented apomorphine (16 mg kg-1, sc)- and partly reversed reserpine- and oxotremorine-induced hypothermia. At higher doses (16-32 mg kg-1), flerobuterol enhanced the toxic effects of yohimbine. Unlike imipramine, flerobuterol and salbutamol did not reduce immobility duration in the behavioural despair test. Salbutamol and flerobuterol decreased locomotor activity. Flerobuterol did not induce mydriasis, did not prevent oxotremorine-induced tremors or salivary and lacrimal gland secretion and did not reduce reserpine-induced palpebral ptosis. Propranolol (8 mg kg-1, ip) but not alpha-methyl-paratyrosine (75 mg kg-1, ip) prevented the flerobuterol-induced antagonism of apomorphine-induced hypothermia. Our results suggest that flerobuterol demonstrates potential antidepressant activity, which could be related to beta-adrenoceptor activation in mice.     

Retrospective review of pemetrexed with or without platinum in malignant mesothelioma: The Australian 'Special Access Scheme' experience

Background: Pemetrexed and cisplatin have recently been shown to significantly improve survival compared with cisplatin alone. However, there are only limited data reflecting teaching hospital experience outside a clinical trial. Pemetrexed has only been available in Australia on a restricted basis since 2002. We reviewed our experience of patients treated on the Australian ‘Special Access Scheme’ at three major thoracic oncology units. Methods: Charts were reviewed for all patients enrolled on the scheme. Data was extracted on age, World Health Organization (WHO) performance status, histology, prior therapy, time from diagnosis to starting pemetrexed, chemotherapy (pemetrexed alone or with a platinum), cycle number, response rate, actuarial progression‐free and overall survival. Doses were cisplatin 75 mg/m² or carboplatin AUC = 5 and pemetrexed 500 mg/m² every 21 days. Results: 52 patients (32 male and 20 female) were reviewed. Median age was 58 years and 88% were WHO 0–1. Histology included 54% epithelial, 17% biphasic (epithelial and sarcomatoid) and 21% undefined. The median time from diagnosis to administration of pemetrexed was 145 days. Sixty‐five percent had minimal surgical intervention with video assisted thoracoscopy, pleurodesis and biopsy, while 19% had received prior palliative radiation. Seventy‐one percent were chemotherapy naïve, the remaining 29% having received previous platinum and/or gemcitabine regimens. Twenty‐three percent had pemetrexed alone, 35% in combination with carboplatin and 42% with cisplatin. The median number of cycles was 4 (range 1–13). The response rate was 33%. No toxicity was observed in 20% grade 3–4 toxicity in 10% (majority nausea/vomiting). The median progression‐free and overall survival times from starting pemetrexed were 184 days and 298 days, respectively. Conclusions: Pemetrexed‐based regimens are safe and effective in a community setting in malignant mesothelioma.     

Benign intracranial hypertension and recombinant growth hormone therapy in Australia and New Zealand

Benign intracranial hypertension (BIH) is reported in three children from Australia and one from New Zealand, who were being treated with recombinant human growth hormone (rhGH). Three males and one female, aged between 10.5 and 14.2 y, developed intracranial hypertension within 2 weeks to 3 months of starting treatment. A national database, OZGROW, has been prospectively collecting data on all 3332 children treated with rhGH in Australia and New Zealand from January 1986 to 1996. The incidence of BIH in children treated with growth hormone (GH) is small, 1.2 per 1000 cases overall, but appears to be greater with biochemical GHD (<10IUml ^-1), i.e. 6.5/1000 (3 in 465 cases), relative risk 18.4, 95% confidence interval 1.9-176.1, than in all other children on the database. The incidence in patients with Turner's syndrome was 2.3/1000 (1 in 428 cases). No cases in patients with partial GHD (10–20 IUml ^-1) or chronic renal failure were identified. Possible causative mechanisms are discussed. The authors'practice is now to start GH replacement at less than the usual recommended dose of 14IUm-² week^-1 in those children considered to be at high risk of developing BIH. Ophthalmological evaluation is recommended for children before and during the first few months following commencement of rhGH therapy and is mandatory in the event of peripheral or facial oedema, persistent headaches, vomiting or visual symptoms. The absence of papilledema does not exclude the diagnosis.     

Identification of a Klebsiella pneumoniae strain associated with nosocomial urinary tract infection.

To differentiate between relapse of infection and reinfection of the urinary tract due to Klebsiella pneumoniae, 33 K. pneumoniae isolates collected from 20 patients with spinal cord injury (SCI) over 2 years were typed by genomic fingerprinting by repetitive-element PCR. Clinical isolates obtained from the same patients with recurrent episodes of urinary tract infection (UTI) revealed identical genomic fingerprints indicating relapse of UTI due to K. pneumoniae, despite appropriate antibiotic therapy. Seventeen isolates obtained from 8 of the 20 SCI patients shared a common genotype, termed RD6. Among non-SCI patients residing in other nursing units, the RD6 genotype was found in 5 of 10 patients with K. pneumoniae UTI but in only 1 of 20 patients with K. pneumoniae infection that did not involve the urinary tract, suggesting a strong association of this genotype with UTI. All RD6 isolates exhibited strong adherence (> or =50 adherent bacteria per cell) to HEp-2 cells, whereas other K. pneumoniae isolates generally did not adhere to or adhered very weakly to HEp-2 cells (< or =5 adherent bacteria per cell). Adherence was inhibited either by 4% D-mannose or by anti-type 1 fimbrial rabbit serum. These results suggest that the capacity of K. pneumoniae RD6 isolates to cause UTI may be mediated by its striking adherence to mammalian cells.