Surgical resection for gastrointestinal metastatic melanoma

AIM: Metastases of melanoma are frequent. On the gastro-intestinal tract, commonest localizations are small bowel, stomach and colon. Surgical treatment of digestive metastases from melanoma is not well known and its value is still debated. PATIENTS AND METHODS: Medical records of 10 patients (six female and four male) operated for metastatic melanoma to gastro-intestinal tract were reviewed to determine results of surgery. RESULTS: Gastro-intestinal metastases were symptomatic in eight patients (abdominal pain in three, bowel obstruction in three, abdominal mass and obstructive jaundice in one each). Two patients had anemia. Diagnosis has been suggested by imaging in seven patients and endoscopy in three. All patients were operated on by laparotomy for resection of metastases located on small bowel in four patients, gallbladder in two, stomach in two and colon in two. Complete resection suppressed symptoms in nine cases. In one patient, resection was incomplete but provided satisfying symptomatic relief. One patient died at day 3; in other patients, median survival was 18 months (range: 3-120). CONCLUSION: In a patient with previous history of melanoma, digestive symptoms indicate morphological explorations due to suspicion of metastases to gastro-intestinal tract. Surgical treatment of these metastases is usually palliative but, in some cases, allows long-term survival.     

Decrease in left ventricular ejection time on digital arterial waveform during simulated hypovolemia in normal humans

BACKGROUND: Left ventricular ejection time (LVET) measured in central arteries is modified during hypovolemia. We compared modifications of the pulse wave in a central artery (carotid) and in a peripheral artery (digital) during central hypovolemia induced by lower body negative pressure (LBNP) in conscious volunteers. METHODS: Hypovolemia was simulated with progressive LBNP (baseline, -10, -20, and -30 mm Hg) in nine young healthy volunteers. The carotid arterial pressure waveform was recorded using a Millar tonometric method. The digital pulse wave was measured with a volume-clamp method (Finapres) and the stroke volume with a thoracic impedance method (Biomed). RESULTS: Mean arterial pressure did not change during LBNP. Compared with baseline values, heart rate increased significantly at the -30 mm Hg level (68 +/- 13 beats/min vs. 59 +/- 11 beats/min), and stroke volume decreased as soon as -10 mm Hg was achieved (113 +/- 41 mL vs. 127 +/- 35 mL). Both carotid and digital LVET decreased significantly at the -10 mm Hg level (337 +/- 26 and 339 +/- 24 ms vs. 360 +/- 35 and 361 +/- 24 ms, respectively). CONCLUSION: Peripheral LVET could reflect variation of central LVET during LBNP and be a reliable noninvasive parameter for monitoring hypovolemia.     

Renal insufficiency and mortality from acute coronary syndromes

Background

Although there is accumulating evidence that renal insufficiency is an independent risk factor for mortality after acute myocardial infarction (AMI), it is not known whether renal dysfunction is associated with an increased mortality rate after a broad range of acute coronary syndromes, including unstable angina.

Methods

We examined consecutive patients from 24 Veterans Affairs hospitals with confirmed AMI or unstable angina between March 1998 and February 1999, who were categorized into groups according to estimated glomerular filtration rate (GFR). Multivariable regression was used to assess the independent association between GFR and the 7-month mortality rate, adjusting for differences in patient characteristics and treatment.

Results

Of the 2706 patients, 436 (16%) had normal renal function (GFR >90 mL/min/1.73 m²), 1169 (43%) had mild renal insufficiency (GFR 60-89 mL/min/1.73 m²), 864 (32%) had moderate renal insufficiency (GFR 30-59 mL/min/1.73 m²), and 237 (9%) had severe renal insufficiency (GFR <30 mL/min/1.73 m²). Patients with renal insufficiency were less likely to undergo coronary angiography or to receive aspirin or β-blockers at discharge. In multivariable models, renal insufficiency was associated with a higher odds of death (mild renal insufficiency: odds ratio [OR] = 1.76; 95% CI, 0.93-3.33; moderate renal insufficiency: OR = 2.72; 95% CI, 1.43-5.15; and severe renal insufficiency: OR = 6.18; 95% CI, 3.09-12.36; all compared with normal renal function). The associations between renal insufficiency and mortality rate were similar in both the AMI and unstable angina subgroups (P value for interaction = .45).

Conclusions

Renal insufficiency is common and is associated with higher risks for death in patients with a broad range of ACS at presentation. Future efforts should be dedicated to determining whether more aggressive treatment will optimize outcomes in this patient population.     

Presynaptic dopaminergic dysfunction in schizophrenia: a positron emission tomographic [18F]fluorodopa study

CONTEXT: The dopamine overactivity hypothesis of schizophrenia remains one of the most influential theories of the pathophysiology of the illness. Radiotracer brain imaging studies are now directly testing aspects of the overactivity hypothesis. OBJECTIVE: To assess presynaptic dopaminergic function in a large cohort of patients with schizophrenia by means of [18F]fluorodopa uptake and a high-sensitivity 3-dimensional positron emission tomograph. We predicted elevations in striatal [18F]fluorodopa uptake and reductions in prefrontal cortical [18F]fluorodopa uptake in patients with schizophrenia. DESIGN: Case-control study. SETTING: Research institute investigation recruiting hospital outpatients. PATIENTS: Sixteen male medicated hospital outpatients with a DSM-IV diagnosis of schizophrenia (mean age, 38 years) and 12 age-matched male volunteers free of psychiatric and neurologic illness. INTERVENTION: [18F]fluorodopa positron emission tomographic scanning. MAIN OUTDOME MEASURE: [18F]fluorodopa uptake constant Ki measured with statistical parametric mapping and region-of-interest analyses. RESULTS: Statistical parametric mapping (P<.05 corrected) and region-of-interest analyses (P<.01) showed increased [18F]fluorodopa uptake, confined primarily to the ventral striatum in patients with schizophrenia. No reductions in prefrontal cortical [18F]fluorodopa uptake Ki were seen in the statistical parametric mapping and region-of-interest analyses, although dorsal anterior cingulate [18F]fluorodopa Ki correlated with performance on the Stroop Color-Word Test in both groups. CONCLUSIONS: As in studies in unmedicated patients, presynaptic striatal dopamine dysfunction is present in medicated schizophrenic patients, adding further in vivo support for dopamine overactivity in the illness.     

Primary diffuse leptomeningeal sarcoma with rhabdomyoblastic differentiation. A case report and immunohistochemical study

Primary meningeal neoplasias are rare, and their diffuse growth within the subarachnoid space may simulate inflammatory processes or metastatic neoplastic dissemination. We report here the case of a boy with an 18-day history of fever and progressive neurological deterioration. While in the hospital, the patient showed neurological deterioration and did not respond to antituberculosis treatment. His cerebrospinal fluid (CSF) cytology disclosed an elevated white blood cell count accompanied by a mildly elevated protein level and a slightly decreased glucose level. The child died, and pathology revealed that his meningeal process was a sarcoma. The immunophenotype of the neoplastic cells showed expression of a sarcomeric actin marker, characterizing rhabdomyoblastic differentiation of the cells that occupied the subarachnoid space and invaded superficially the encephalon. Rhabdomyoblastic differentiation in leptomeningeal diffuse primary sarcoma (LDPS) is an aspect rarely observed in this malignant meningeal neoplasia, with few reported cases. The present case is the first reported in the Portuguese literature and the fifth reported in the English literature.     

Preliminary characterisation of an in vitro paradigm for the study of the delayed effects of organophosphorus compounds: hen embryo brain spheroids

Organophosphate induced delayed neuropathy (OPIDN) has been studied extensively but the mechanisms of toxicity remain unclear. It is generally accepted that the inhibition and ageing (dealkylation) of the B-esterase neuropathy target esterase (NTE) is integral to axonal loss. At present, the only way of detecting compounds that induce OPIDN is the hen test, an animal model. In this study, we preliminary validated hen embryo brain spheroids (HEBS) for the study of organophosphate (OP) toxicity. Hen brain spheroids have been characterised previously, although they have never been fully optimised for OP testing. We optimised the levels of acetylcholine esterase (AChE) and neuropathy target esterase by adapting the culture technique and using chemically defined media. Spheroid cultures were maintained for 35 days and viability and enzyme levels were monitored over this time. Levels of AChE and NTE in this system remained stable over the 35 day period. Using transmission electron microscopy, we have shown synaptogenesis within HEBS earlier than previously suggested in spheroid culture. These studies indicate that HEBS may be useful for the study of OP-induced toxicity and that the long-term stability of the cultures makes it an ideal candidate for studying OPIDN.     

Prolonged schedule of temozolomide (Temodal) plus liposomal doxorubicin (Caelyx) in advanced solid cancers

Temozolomide (Temodal) is an oral imidazotetrazine. Increased temozolomide exposure and subsequent depletion of O-alkylguanine alkyltransferase may improve the activity of temozolomide. The rationale for investigating temozolomide plus Caelyx is based on their antitumor activity, their formulation and no significant overlapping toxicities. We conducted a study of a prolonged schedule of temozolomide (orally on days 1-7 and 15-21) plus Caelyx (day 1) every 28 days. Twenty-one patients (melanoma n=10, sarcoma n=7 and other n=4) were assigned to four dose levels (DL; temozolomide+Caelyx, mg/m): DL1: 100+30 (n=3 patients), DL2: 100+40 (n=6 patients), DL3: 125+40 (n=6 patients) and DL4: 150+40 (n=6 patients). Dose-limiting toxicities were noted after 2 or more cycles in one patient at DL3 (stomatitis) and one patient at DL4 (grade 4 ANC >/=7 days). Treatment delays and/or dose reductions (due to hematological toxicity) were necessary in five of six patients receiving DL4 compared with one of six patients at DL3, and one patient at DL1 and 2. Thus, the recommended dose was temozolomide 125 mg/m (daily for 7 days every other week) plus Caelyx 40 mg/m (day 1 every 4 weeks). Other toxicities were mild. Antitumor activity was observed in eight patients, including one complete response (melanoma), three partial responses (one melanoma, two sarcomas) and four patients with stable disease (three melanomas, one Ewing), with a duration lasting from 14 to 135+weeks. Two melanoma patients showed tumor stabilization in non-irradiated cerebral lesions. This schedule of temozolomide allowed higher dose intensity (1750 mg/m in 4 weeks) compared to the standard 5-day regimen (1000 mg/m in the same amount of time).     

Antileishmanial activity of a linalool-rich essential oil from Croton cajucara

The in vitro leishmanicidal effects of a linalool-rich essential oil from the leaves of Croton cajucara against Leishmania amazonensis were investigated. Morphological changes in L. amazonensis promastigotes treated with 15 ng of essential oil per ml were observed by transmission electron microscopy; leishmanial nuclear and kinetoplast chromatin destruction, followed by cell lysis, was observed within 1 h. Pretreatment of mouse peritoneal macrophages with 15 ng of essential oil per ml reduced by 50% the interaction between these macrophages and L. amazonensis, with a concomitant increase by 220% in the level of nitric oxide production by the infected macrophages. Treatment of preinfected macrophages with 15 ng of essential oil per ml reduced by 50% the interaction between these cells and the parasites, which led to a 60% increase in the amount of nitric oxide produced by the preinfected macrophages. These results provide new perspectives on the development of drugs with activities against Leishmania, as linalool-rich essential oil is a strikingly potent leishmanicidal plant extract (50% lethal doses, 8.3 ng/ml for promastigotes and 8.7 ng/ml for amastigotes) which inhibited the growth of L. amazonensis promastigotes at very low concentrations (MIC, 85.0 pg/ml) and which presented no cytotoxic effects against mammalian cells.     

Enhancement of aerobic microbial degradation of polychlorinated biphenyl in soil microcosms

This article reports the results of various biodegradation experiments on polychlorinated biphenyl (PCB)-contaminated sandy soil employing a mixed culture of acclimatized bacteria. Following the optimization of different variables without chemical pretreatment, the elimination rate achieved of Aroclor 1242 in slurry-phase reactors was 61% after four months of treatment, with the presence of biphenyl as cosubstrate being the most important factor affecting PCB biodegradation. The biodegradation occurred as a first-order process, and it proved most effective in respect to dichlorinated biphenyls (100% removal), followed by trichlorinated (92%) and tetrachlorinated biphenyls (24%). The results also showed that the degradability of PCBs in soil may be enhanced by an advanced oxidation pretreatment (Fenton reaction), producing almost 100% elimination of PCBs at the end of the integrated chemical-biological process and 72% mineralization of the intermediates generated during the chemical pretreatment.     

Ecoparasitoses and public health in Brazil: challenges for control

Parasitic skin diseases such as scabies, pediculosis, tungiasis, and cutaneous larva migrans are hyperendemic in the numerous poor communities in Brazil and are commonly associated with considerable morbidity. However, programs to control ectoparasites are non-existent in the country's public health system. Due to neglect of these diseases by the population itself and health care professionals, the diseases' highly contagious characteristics, and lack of effective treatment and/or presence of animal reservoirs together with a complex life cycle, effective control of ectoparasites is an enormous public health challenge. This article discusses potential measures to control parasitic skin diseases in affected communities, based on mass treatment, health education, and (when applicable) eradication of animal reservoirs.