A novel palladium-catalyzed synthesis of phenanthrenes from ortho-substituted aryl iodides and diphenyl- or alkylphenylacetylenes.

[reaction--see text] 1,5-Selectively disubstituted 9,10-diphenyl- or alkylphenylphenanthrenes are obtained by reaction of ortho-substituted aryl iodides and diphenyl- or alkylphenylacetylenes in the presence of palladium and norbornene as catalysts. The reaction outcome is controlled by the steric effect exerted by the ortho substituent in the aryl iodide.

Randomized, double-blind trial comparing indinavir alone, zidovudine alone and indinavir plus zidovudine in antiretroviral therapy-naive HIV-infected individuals with CD4 cell counts between 50 and 250/mm3.

Treatment with indinavir has been shown to result in marked decreases in viral load and increases in CD4 cell counts in HIV-infected individuals. A randomized double-blind study to evaluate the efficacy of indinavir alone (800 mg q8h), zidovidine alone (200 mg q8h) or the combination was performed to evaluate progression to AIDS. 996 antiretroviral therapy-naive patients with CD4 cell counts of 50-250/mm3 were allocated to treatment. During the trial the protocol was amended to add lamivudine to the zidovudine-containing arms. The primary endpoint was time to development of an AIDS-defining illness or death. The study was terminated after a protocol-defined interim analysis demonstrated highly significant reductions in progression to a clinical event in the indinavir-containing arms, compared to the zidovudine arm (p<0. 0001). Over a median follow-up of 52 weeks (up to 99 weeks), percent reductions in hazards for the indinavir plus zidovudine and indinavir groups compared to the zidovudine group were 70% and 61%, respectively. Significant reductions in HIV RNA and increases in CD4 cell counts were also seen in the indinavir-containing groups compared to the zidovudine group. Improvement in both CD4 cell count and HIV RNA were associated with reduced risk of disease progression. All three regimens were generally well tolerated.

Comparison of conventional culture and PCR methods for the detection of Legionella pneumophila in water.

A comparative assessment of conventional culture and nucleic acid techniques in the detection of Legionella pneumophila in seeded tap water samples was performed, using bacterial concentrations ranging from 994 to 0.015 cfu ml-1. Different filtration and centrifugation protocols were evaluated. The results permitted the development of a tentative algorithm for the detection of legionellae in tap water. Samples should first be analysed using PCR methods. In the event of quantitative data and bacterial strains for epidemiologic typing being required, the same sample, or a greater volume of the sample, if positive with PCR, can be re-tested by filtration through polycarbonate membranes followed by plating a homogenate of the filter. If samples are found to be negative with PCR, they can be re-analysed in greater volumes by filtration through polycarbonate membranes followed by direct placing of the filter on culture media, to allow detection of very low numbers of bacteria. This protocol should be validated in the field before it can be routinely implemented.

Prospective study of tetanus-induced acute renal dysfunction: role of adrenergic overactivity.

To assess the mechanisms related to tetanus-induced acute renal failure (ARF), 30 patients with tetanus had their renal function prospectively studied and factors possibly related to renal changes were evaluated during four weeks of hospitalization. Fifty percent of these patients had a glomerular filtration rate (GFR) < or = 50 ml/min in the first or second week of hospitalization (Group I) and 50% had a GFR > 50 ml/min throughout the entire hospitalization period (Group II). Age, gender, tetanus incubation time and tetanus onset time, hospitalization time, use of nephrotoxic drugs, need for mechanical ventilation with intermittent positive pressure, and presence of systemic infection were similar in both groups. None of the patients presented with oliguria. Autonomic nervous system (ANS) overactivity, characterized by intense variations in systolic and diastolic blood pressure, by increased heart rate and elevated urinary metanephrine excretion, was higher in Group I compared with Group II. Plasma renin activity, serum creatinephosphokinase levels, and myoglobinuria were not significantly different between the two groups. These results strongly suggest that tetanus-induced ARF has a high prevalence, is characterized by early onset, and is probably related to ANS overactivity.

Clinical and pathological features in hydrocarbon-induced parkinsonism.

A neuropathological examination was performed on a patient with parkinsonism induced by prolonged exposure to a mixture of aliphatic hydrocarbons, mainly n-hexane and halogenated compounds. The patient developed a rapid-course disease that progressed even after withdrawal from the toxic exposure. Pathological examination and immunohistochemical analysis of the brain revealed severe and widespread dopaminergic neuronal loss, associated with severe gliosis, in the substantia nigra, and almost complete loss of tyrosine hydroxylase immunostaining in the striatum. No Lewy bodies were detected. Neuronal loss was also observed in the periaqueductal gray matter, locus ceruleus, and pedunculopontine nucleus. These changes, combined with the moderate anemia due to marrow suppression, and the mild axonal neuropathy observed in vivo, are suggestive of a hydrocarbon toxic insult.

Stereotactic radiosurgery of pituitary adenomas.

The first gamma knife (GK) treatment of a pituitary adenoma in 1967 was meant as an alternative to the primitive surgical approaches that prevailed at the time, with consequent unsatisfactory results. Surprisingly, pituitary adenomas still account for only 7.8% of the 27,000 cases treated in GK centers worldwide. Transnasosphenoidal surgery has greatly improved and surgeons are reluctant to give up a relatively safe and effective operative technique. Radiosurgery is not currently vying to be the primary method of "surgery", but has a definite role following failed pituitary surgery and for tumors that extend into the cavernous sinus. Of 300 patients treated in our GK service, 30 had pituitary adenomas and most had undergone surgery. To date, we have not noted any side effects in the pituitary group. Published information is also reviewed and divided, where possible, into the pre-computed tomography (CT) era and the era of CT-magnetic resonance imaging (MRI). Growth hormone (GH)-secreting adenomas and prolactinomas tend to be larger and cannot be treated with the high doses successful against corticotropin (ACTH)-secreting tumors in Cushing's disease. Radiation fall-off is steep in GK radiosurgery, with the 20% isodose curve being only millimeters away from the point of maximal radiation. The effective dose has mostly been decided on the basis of maintaining safe levels at the sensitive perisellar neural structures. The safety of GK treatment (with no mortality and no permanent morbidity) is compared with other radiosurgical techniques. Good patient response owes much to the cumulative experience of GK pioneers and also to recent advances in images and computers that have enabled increasingly precise stereotaxic targeting and dose planning.

Pre-targeted immunodetection in glioma patients: tumour localization and single-photon emission tomography imaging of [99mTc]PnAO-biotin.

The imaging of cerebral gliomas with radiolabelled monoclonal antibodies (MoAbs) has been previously reported. However, previous studies have been hampered by the drawback of a low tumour to non-tumour ratio. In order to overcome this problem we have developed a three-step pre-targeting method using the avidin-biotin system. The rationale of this technique consists in vivo labelling of biotinylated MoAbs targeted onto tumour deposits, when most of the unbound antibodies have been cleared from the bloodstream as avidin-bound complexes. The anti-tenascin MoAb BC2, specific for the majority of gliomas, was biotinylated and 1 mg was administered i.v. in 20 patients with histologically documented cerebral lesions. After 24-36 h, 5 mg avidin was injected i.v. followed 24 h later by a third i.v. injection of 0.2 mg PnAO-biotin labelled with 15-20 mCi technetium-99m. No evidence of toxicity was observed. Whole-body biodistribution was measured at 20 min, 3 h and 5 h post-injection. [99mTc]PnAO-biotin had a fast blood clearance and was primarily excreted through the biliary system. A dedicated single-photon emission tomography system was used to acquire brain tomographic images 1-2 h after the administration of [99mTc]PnAO-biotin. Tumours were detected in 15/18 glioma patients with a tumour to non-tumour ratio of up 14:1. This three-step method, based on the sequential administration of anti-tenascin MoAb BC2, avidin and [99mTc]PnAO-biotin, can support computed tomography or magnetic resonance imaging for the diagnosis and follow-up of patients with glioma. Further studies are required to evaluate the potential of this technique for therapeutic application.

Human lagochilascariasis treated successfully with ivermectin: a case report.

A 15 year old male patient was diagnosed as being infected with the nematode Lagochilascaris minor, presenting as abscesses over the left mastoid region, and invading the temporal bone, mastoid sinuses and possibly the CNS. Surgical drainage and administration of cambendazole and levamisole led to improvement, followed by an early relapse and poor tolerance to the antihelminthic drugs. Repeated doses of ivermectin (an animal preparation) were used for the first time to treat this condition and resulted in complete remission of signs of infection, maintained for 15 months after the end of drug therapy, indicating cure of the disease.

[Patterns of antimicrobial resistance in gram-negative bacilli isolated from patients in intensive care units]. / Padrões de resistência a antimicrobianos em bacilos gram-negativos isolados de pacientes em unidade de terapia intensiva.

Minimal inhibitory concentration test with 16 antibiotics was performed for 435 stains of Gram negative bacilli, isolated from patients in intensive care units of five large hospitals. The results were analysed as to provide in vitro sensitivity patterns, as well as cross resistance between the tested drugs. The most frequent species were Pseudomonas aeruginosa, E. coli, Klebsiella spp., Enterobacter ssp., and Acinetobacter calcoaceticu, accounting for more than 80% of all isolates. Best figures were seen with ciprofloxacin and imipenem, with 805 of sensitive strains or more; third generation cephalosporins, aminoglycosides and aztreonam had overall sensitivity rates ranging from 58 to 73%. There was marked cross resistance between ceftazidime and other beta-lactam antibiotics, except for imipenem. These results bear implications regarding the establishment of empirical therapy in critical patients.

[Complications during preoperative embolization in intracranial meningioma]. / Complicanza in corso di embolizzazione pre-operatoria di meningioma intracranico.

We report a rare case of meningioma of the parieto-occipital convexity accompanied by hemorrhage in the tumor and in the subdural space that occurred while pre-operative embolization was being applied. The patient, a 48 year old woman, presented sudden headache and, in a few minutes, comatose status and decerebrate rigidity. A quick diagnosis with CT-scan of acute intratumoral and subdural hemorrhage and a rapid intervention on the patient led to complete recovery. The possible reason for the hemorrhage is the sudden change in blood pressure of pathologic small vessels triggered by embolization.

[Postoperative tetanus: report of a case and prophylaxis]. / Tétano pós-cirúrgico: descrição de caso e profilaxia.

We describe a case of a patient presenting tetanus after mastectomy with postoperative complications. Risk factors and prophylaxis of this disease after surgery are discussed, emphasizing the need for vaccine protection and evaluation of all patients before any kind of surgical procedure.

Percutaneous selective thermorhizotomy in the treatment of "essential" trigeminal neuralgia. The importance of lesion selectivity.

Results following percutaneous thermorhizotomy for trigeminal neuralgia are described in 111 patients. Recurrences and side effects are more frequent whenever selectivity of the surgical lesion has been imperfect (exceeding the original pain area and causing marked hypoesthesia), and less frequent in the cases with strictly selective lesion.

Neuronal generators of the visual evoked potentials: intracerebral recording in awake humans.

Flash and pattern reversal visual evoked potentials were recorded in awake patients undergoing stereotactic procedures for severe dyskinetic disorders resistant to medical treatment. The nucleus ventralis lateralis thalami was reached via an occipital approach. VEPs were recorded on the scalp at the entrance of the intracerebral electrode, and serially from sites at different depths. A polarity reversal of the surface recorded wave form took place as the intracerebral electrode was advanced beneath the surface cortical layers. As concerns F-VEPs, most of the scalp activity mirrored the potentials recorded down to the depth of 70-65 mm from the thalamus. The largest amplitude of intracerebral F-VEPs was obtained from recording sites at 50-70 mm from the thalamus, i.e., in the depth of the calcarine fissure. A negative wave, peaking around 47-50 msec, became evident in recording sites at 30-40 mm from the thalamus but vanished as the electrode was advanced farther. In only one patient could we record a small negative wave, peaking at 33 msec, in the vicinity of the corpus geniculatum externum. Furthermore, the oscillatory activity recorded from the scalp appeared to be generated in the cortical layers. PR-VEPs also underwent polarity reversal as the electrode traversed the cortex. PR-VEPs disappeared more superficially than F-VEPs. No PR-evoked activity could be recorded in the vicinity of the corpus geniculatum externum. We conclude that slow and fast components of VEPs recorded from the scalp are entirely generated in cortical layers.