Spillover of avian haemosporidian parasites (Haemosporidia: Plasmodium) and death of captive psittacine species.

CASE REPORT: During February 2014, a yellow-tailed black cockatoo (Calyptorhynchus funereus) and glossy black cockatoo (C. lathami) housed in aviaries on a property in Wamuran, Queensland, were submitted for postmortem. Histopathology and molecular diagnostics demonstrated the presence of Plasmodium sp. infection. The Plasmodium isolate identified has previously only been reported as infecting a healthy wild rufous fantail (Rhipidura rufifrons) in Australia. CONCLUSION: To the authors' knowledge, these are the first reported cases of Plasmodium in Calyptorhynchus. We hypothesised that the maintenance of these two cockatoo species in ground level aviaries in a low-altitude geographic zone resulted in exposure of birds to mosquito vectors of endemic avian Plasmodium. Black cockatoos roost and forage in the mid to high canopy of forests in the wild, outside the likely spatiotemporal distribution of relevant haemosporidian vectors. It is therefore likely that these birds had immunological naivety and susceptibility to infection with Plasmodium circulating in wild passerines.

Cervical spine clearance in the elderly: do elderly patients get a bad deal?

OBJECTIVE: To investigate whether elderly patients, presenting following trauma and requiring immobilisation and imaging of the cervical spine, require increased use of CT and spend longer immobilised when compared to the younger population. METHODS: A retrospective chart review was undertaken of 35 adults aged 18-65 years, and 32 adults over 65 years, requiring cervical spine imaging following trauma. RESULTS: 1 of the 35 younger patients, and 16 of the 32 elderly patients, underwent CT. Elderly patients spent 1:05 h longer immobilised (p<0.005). CONCLUSIONS: Half of the elderly patients underwent CT, and they were immobilised for significantly longer than younger patients. Measures should be adopted to facilitate early diagnosis and mitigate complications of prolonged immobilisation in elderly patients with neck trauma.

Detection of the circulating antigens CAA and CCA in a group of Dutch travellers with acute schistosomiasis.

Detection of circulating anodic antigen (CAA) and circulating cathodic antigen (CCA) in serum and urine is a highly specific and sensitive alternative for the diagnosis of schistosome infections in endemic areas. However, it is not known how soon after the onset of infection these antigens can be detected in humans. Neither has there been much research on the detection of these antigens in individuals normally living in non-endemic areas. We studied the kinetics of CAA and CCA in serum and urine of a group of 28 Dutch tourists, shortly after accidental exposure to a Schistosoma infection during a visit to Mali. Twenty-seven were found to be positive for Schistosoma eggs and/or specific antibodies. From each individual, 1-4 serum samples were tested for circulating antigen level, 4-15 weeks after exposure, and urine samples were also tested from 22 subjects. CAA and CCA levels were quantified by monoclonal antibody-based ELISAs and TRIFMAs. In serum, 23 individuals (85%) were positive at least once for one or both antigens, but titres were generally very low. CAA and CCA could be detected 5 and 6 weeks after exposure, respectively. Urines were all found to be negative. Almost all cases were negative at 7 months' follow-up.

Modulation of multidrug resistance with dexniguldipine hydrochloride (B8509-035) in the CC531 rat colon carcinoma model.

The chemosensitizing potency of dexniguldipine hydrochloride (B8509-035) on epidoxorubicin was assessed in a multidrug-resistant (MDR) tumour model, the intrinsic MDR rat colon carcinoma CC531. In vitro in the sulphorhodamine B cell-viability assay the cytotoxicity of epidoxorubicin was increased approximately 15-fold by co-incubation with 50 ng/ml dexniguldipine. In vivo concentrations of dexniguldipine 5 h after a single oral dose of 30 mg/kg were 72 (+/- 19 SD) ng/ml in plasma and 925 (+/- 495 SD) ng/g in tumour tissue. Levels of the metabolite of dexniguldipine, M-1, which has the same chemosensitizing potential, were 26 (+/- 6 SD) ng/ml and 289 (+/- 127 SD) ng/g respectively. The efficacy of treatment with 6 mg/kg epidoxorubicin applied intravenously combined with 30 mg kg-1 day-1 dexniguldipine administered orally for 3 days prior to epidoxorubicin injection was evaluated on tumours grown under the renal capsule. Dexniguldipine alone did not show antitumour effects in vivo. Dexniguldipine modestly, but consistently, potentiated the tumour-growth-inhibiting effect of epidoxorubicin, reaching statistical significance in two out of four experiments. In conclusion, these experiments show that dexniguldipine has potency as an MDR reverter in vitro and in vivo in this solid MDR tumour model.

Non-selective digital subtraction angiography in comparison with selective conventional angiography in the diagnosis of carotid artery disease.

In the recent past, non-selective arterial digital subtraction angiography (NSDSA) seemed a less invasive alternative to conventional filmscreen angiography (CFA) in the diagnosis of carotid artery disease. NSDSA obviated the need for selective catheterization with its associated risks but yet took advantage of the DSA method. However, this technique has not found general application although there are no reports that formally assess the (dis)advantages of NSDSA. The aim of our study was to compare the reliability of NSDSA with CFA in evaluation of carotid bifurcations in patients with transient ischemic attacks or partial stroke by reviewing prospectively collected data. Over a 2-year period, 40 patients (upper age limit 65 years) underwent both NSDSA and CFA. Bilateral NSDSA was performed in all 40 patients (80 bifurcations). Bilateral CFA was performed in 27 patients whereas unilateral CFA was carried out in 13 patients (67 bifurcations). Inter- and intra-observer variability for the degree of stenosis was determined by calculation of kappa-values for a 4-point and a 2-point scale. The proportion of interpretable studies was significantly lower in NSDSA. The inter- and intra-observer agreement was on average better in CFA examinations, though the difference was only statistically significant for the inter-observer agreement. The results of our study indicate that images obtained with NSDSA give less reliable information about carotid artery disease than images obtained with CFA. This is in accordance with the fact that NSDSA now seems an abandoned technique.

Systemic effects of inhalational methyl bromide poisoning: a study of nine cases occupationally exposed due to inadvertent spread during fumigation.

Systemic methyl bromide (CH3Br) poisoning with signs and symptoms of varying severity developed in nine greenhouse workers after acute inhalational exposure on two consecutive days. Measurements of CH3Br, carried out at the site within hours after the accident, suggest that exposure on the second day may have been in excess of 200 ppm (800 mg/m3) CH3Br. All workers were admitted for observation. Seven of them were discharged after an uneventful overnight observation and residual symptoms, if any, subsided within three weeks of the accident. Two patients needed intensive care for several weeks because of severe reactive myoclonus and tonic-clonic generalised convulsions. These conditions were unresponsive to repeated doses of diazepam, clonazepam, and diphenylhydantoin but could be suppressed effectively by induction of a thiopental coma that had to be continued for three weeks. In some of the patients prior subchronic exposure to CH3Br, as shown by their occupational histories and high serum bromide (Br-) concentrations, is likely to have been a factor contributing to the severity of their symptoms. A direct association between serum Br- concentrations and the severity of neurological symptoms, however, seemed to be absent. An on site investigation into the circumstances leading to the accident showed the presence of an empty and out of use drainage system that covered both sections of the greenhouse. This was probably the most important factor contributing to the rapid and inadvertent spread of CH3Br.

Chemotherapy as treatment of choice in extrapulmonary undifferentiated small cell carcinomas.

Extrapulmonary undifferentiated small cell carcinomas, especially those arising in the upper aerodigestive tract, form a group of neoplasms with a clinical behavior which resembles small cell carcinoma of the lung. In 11 patients treated by combination chemotherapy an objective response rate of 82% was achieved for a median duration of 8+ months. Median survival for all patients was 12 months. Long-term survival was observed in those patients with limited disease who achieved a complete response after chemotherapy followed by radiotherapy.

Pharmacokinetics and toxicity of mitomycin C in rodents, given alone, in combination, or after induction of microsomal drug metabolism.

The pharmacokinetics of mitomycin (MMC) was studied in Wistar rats. Up to five half-lives, the plasma concentration-time curve was biphasic. The AUC changed linearly with increasing doses between 0.5 and 7.5 mg/kg, which corresponds to 0.2 and 3 times the LD50 value in rats. Most of the drug was metabolized, and only 1%-2% and 10%-15% of the dose was eliminated unchanged by biliary and urinary excretion, respectively. The AUC of MMC at the LD50 is slightly less than that reported for the human MTD. Inoculation of MMC together with 5-fluorouracil and doxorubicin did not change the terminal half-life of MMC but decreased the total body clearance and the volume of distribution. The lack of significant influence of phenobarbital and 3-methylcholanthrene pretreatment on the terminal elimination half-life suggests that microsomal drug-metabolizing enzymes inducible by these compounds do not play a decisive role in the in vivo biotransformation of MMC.

Cyclophosphamide versus ifosfamide: final report of a randomized phase II trial in adult soft tissue sarcomas.

Ifosfamide (IFOS) 5 g/m2 and its parent analog Cyclophosphamide (CYCLO) 1.5 g/m2 were studied in a randomized phase II study, accruing 171 patients with advanced soft tissue sarcoma. Both drugs were administered as 24 hr infusions, every 3 weeks, with comcomitant Mesna 400 mg/m2 i.v. bolus 4 hourly X 9 doses. Twenty-four patients were ineligible and 12 were not evaluable. The groups were well matched for age, previous chemotherapy (42% of the total) or radiotherapy, the presence of distant metastases and performance status, but there were more females (59% vs. 45%) in the IFOS arm. Among the 68 evaluable patients receiving IFOS, there were 2 CR, 10 PR (overall response 18%), 27 SD and 29 PD. For CYCLO, the corresponding results in 67 patients were 1 CR, 4 PR (overall response 8%), 23 SD and 39 PD. Using the chi-square test the P values for response rate and linear trend were 0.13 and 0.04 respectively. Response rates were higher for females (20% vs. 5%, P = 0.01) and patients who had not received previous chemotherapy (19% vs. 4%, P = 0.01). Fourteen of the 17 responses came from a group of 43 females, who had not received previous chemotherapy, for whom the overall response rate was 37.5%. Remissions were noted in only 4 histological subtypes (centrally reviewed material), i.e., 5 of 17 synovial sarcomas, 7 of 13 mixed mesodermal sarcomas and 2 of 7 fibrosarcomas. One of the 31 leiomyosarcomas responded to Cyclophosphamide. Durations of response did not differ significantly between the 2 arms--median 26, range 10-81+ weeks. Leucopenia was significantly more severe on CYCLO, particularly in patients who had received previous chemotherapy (P = 0.007). Serious infections occurred in approx. 7% of patients with no difference between the two drugs, although there was one toxic death on CYCLO. Nausea and vomiting were significantly worse on IFOS and alopecia, related in extent to dose, was seen in both arms. Other side-effects, such as hematuria or rises in serum creatinine and encephalopathy, were infrequent and mild. A higher response rate with less myelosuppression suggests that IFOS may have advantages over CYCLO in combination therapy.

Mitomycin C-induced renal toxicity, a dose-dependent side effect?

Mitomycin C (MMC) has been known to be nephrotoxic since 1971. Whether this side effect was dose-dependent is unknown, while data on incidence are scanty. The presently-reported prospective study was initiated with the objective to obtain more data on these subjects. Forty-four patients treated with MMC entered the study, 37 were evaluable. All patients were subjected to extensive serial laboratory tests to study renal function and to detect hemolysis or coagulation disorders. The results were evaluated per cumulative dose level. One patient developed a lethal hemolytic uremic syndrome after 40 mg/m2 MMC. None of the laboratory tests predicted this side effect. None of the other patients developed renal toxicity, while all laboratory tests remained within normal ranges. All available literature on this subject was also reviewed. Based on the results of the present study, as well as on the literature review, it is concluded that MMC-related renal toxicity is a dose-dependent side effect, occurring at cumulative dose levels of 30 mg/m2 or more. The incidence is likely to be less than 10%. Predictive laboratory test could not be indicated.

The cold pressor test during radionuclide ventriculography: a feasibility study in cancer patients.

To monitor the use of cardiotoxic drugs, adequate assessment of myocardial function is required. Although serial radionuclide left ventricular ejection fraction (EF) studies allow a simple and rapid assessment of the myocardial function without risk or discomfort to the patient, they appear not to be sensitive enough. Determination of the EF during cold application may be more sensitive. In this study we tested the feasibility of the cold pressor test (CPT) in relation to EF determination in 23 cancer patients. Only minor side effects were recorded. The response of heart rate to cold was similar to the response reported in healthy volunteers and patients with coronary artery disease. In selected cases EF determination during CPT appeared to be more sensitive than EF at rest. EFCPT may be an attractive alternative for EFexercise in cancer patients who cannot perform enough exercise to stress cardiac function adequately, but for a more definite conclusion a prospective comparative study is required.

Neuroepithelioma (neuroblastoma) arising in an adult. A case report.

Cytogenetic studies on neuroblastomas arising in children have revealed consistent abnormalities of the short arm of chromosome number 1. Partly because of the rare occurrence of neuroblastomas in adults, extensive cytogenetic studies in this group of patients have not been performed. We report a case of a neuroepithelioma (neuroblastoma) arising in a 50-year-old male patient. On chromosome analysis of a metastasis, a stemline with karyotype 47,XY, +der1 (1 qter---1 cen::1q21---1 qter) was identified. The possible consequences of this result and those of results previously reported in the literature are discussed.

Recovery from mitomycin C-induced hemolytic uremic syndrome. A case report.

Mitomycin C (MMC) is a cytotoxic agent that may induce a hemolytic uremic syndrome (HUS) with severe renal insufficiency. Of all reported patients with terminal renal failure only two survived with chronic hemodialysis. A patient with advanced gastric cancer in complete remission, who developed MMC-induced HUS, is reported; hemodialysis was necessary because of oliguria. Hemolysis subsided, and after addition of captopril renal function recovered partially. The patient is alive 6 months after discontinuation of hemodialysis. Recently she developed brain metastases. Symptoms of hemolysis did not recur. The pathogenesis and treatment of HUS are discussed.