Brain abscess in the 1980s

Brain abscess was reviewed in 24 patients admitted to University Hospital, Nottingham over a period of 3 years. Chronic ear infection was the most common predisposing factor, but in 11 patients the focus of infection remained unknown. CT scanning, carried out in all patients, was negative in one patient with clinical signs of meningitis. Polymicrobial and anaerobic infections were common. Actinomyces species were isolated in mixed culture from seven patients; in five the abscess was located in the cerebellum. Therapy was most often a combination of surgical drainage and antimicrobial therapy with beta-lactam agents and metronidazole. Evidence suggests that cefotaxime may offer a suitable alternative to chloramphenicol and benzylpenicillin in the treatment of brain abscess.     

Regulation of hematopoietic cell function by protein tyrosine kinase-encoding oncogenes, a review.

Tyrosine phosphorylation of proteins by protein tyrosine kinases (PTKs) is an important mechanism in the regulation of various cellular processes such as proliferation, differentiation, and transformation. Accumulating data implicate PTKs as essential intermediates in the transduction of extracellular signals to the interior of the cell. This review summarizes the mechanism of action of PTKs from the major subclasses and the involvement of PTK-encoding oncogenes in the regulation of hematopoietic cell function.     

Phase IB study of doxorubicin in combination with the multidrug resistance reversing agent S9788 in advanced colorectal and renal cell cancer.

S9788 is a new triazineaminopiperidine derivate capable of reversing multidrug resistance (MDR) in cells resistant to chemotherapeutic agents such as doxorubicin. It does not belong to a known class of MDR revertants, but its action involves the binding of P-glycoprotein. Thirty-eight evaluable patients with advanced colorectal or renal cell cancer were treated with doxorubicin alone (16 patients) followed after disease progression with combination treatment of doxorubicin plus S9788 (12 patients) or upfront with the combination of doxorubicin plus S9788 (22 patients). S9788 was given i.v. as a loading dose of 56 mg m-2 over 30 min followed by doxorubicin given at 50 mg m-2 as a bolus infusion. Thereafter, a 2-h infusion of S9788 was administered at escalating doses ranging from 24 to 120 mg m-2 in subsequent cohorts of 4-10 patients. Pharmacokinetic analysis demonstrated that concentrations of S9788 that are known to reverse MDR in vitro were achieved in patients at non-toxic doses. Compared with treatment with doxorubicin alone, treatment with the combination of doxorubicin and S9788 produced a significant increase in the occurrence of WHO grade 3-4 granulocytopenia. Treatment with S9788 was cardiotoxic as it caused a dose-dependent and reversible increase in corrected QT intervals as well as clinically non-significant arrhythmias on 24- or 48-h Holter recordings. Although clinically relevant cardiac toxicities did not occur, the study was terminated as higher doses of S9788 may increase the risk of severe cardiac arrhythmias. Twenty-nine patients treated with S9788 plus doxorubicin were evaluable for response, and one patient, who progressed after treatment with doxorubicin alone, achieved a partial response. We conclude that S9788 administered at the doses and schedule used in this study results in relevant plasma concentrations in humans and can safely be administered in combination with doxorubicin.     

Chromosomal radiosensitivity of breast cancer with a CHEK2 mutation

Recently, multiple studies have shown that a sequence variant in CHEK2 (CHEK2 1100delC) plays a role in the susceptibility to breast cancer. This mutation should confer about a twofold increased breast cancer risk in women and a 10-fold increased risk in men. Because the CHEK2 gene plays a critical role in DNA damage repair and the CHEK2 1100delC variant confers susceptibility to breast cancer, we investigated if patients carrying the CHEK2 1100delC mutation are characterized by an enhanced chromosomal radiosensitivity. To this end, familial breast cancer patients, sporadic breast cancer patients, and healthy women, considered in our previously studied to determine their chromosomal radiosensitivity with the G2 and G0-MN assay, were all tested in present study for the presence of the CHEK2 1100delC variant. The 1100delC variant was detected in none of the 100 healthy individuals, in 1 of 100 (1%) unselected breast cancer patients and in 3 of 78 (3.8%) breast cancer patients with a family history of breast cancer. The breast cancer patients with the CHEK2 1100delC genotype had a mean radiation-induced yield of chromatid breaks that was not significantly different from that of the healthy control group. Although the mean yield of micronuclei (MN) was significantly higher compared to the healthy control group, this higher mean MN yield was due to a single patient who had a very high number of MN compared to the parallel control. Our data suggest that breast cancer patients with a CHEK2 1100delC mutation are in general not characterized by a distinct enhanced chromosomal radiosensitivity. These conclusions are, however, very preliminary, because of the small numbers of CHEK2 1100delC breast cancer patients studied.     

Flexible neuroendoscopic treatment of suprasellar arachnoid cysts

Endoscopic treatment of suprasellar arachnoid cysts is now the treatment of choice. By marsupializing the roof of the cyst the condition can be cured. The perceived necessity to open both the roof and the floor is called into question by this paper. Three cases of suprasellar arachnoid cyst are described all of which have had successful marsupialisation of the cysts by flexible neuroendoscopy Flexible neuroendoscopic marsupialization of the cyst by widely opening the cyst roof only is described. This is compared with the other techniques, and also the endoscopic technique involving opening both the roof and the floor of the cyst, a more difficult and potentially dangerous method. Successful treatment of this condition is achieved by marsupialization of only the roof of the cyst. This is a much safer procedure, and has resulted in a resolution of signs and symptoms in the cases described followed-up between 24 and 28 months from the procedure.     

Third ventricular cysts and membranes unsuspected on conventional CT and MRI

Three cases are presented of symptomatic cysts or membranes within the third ventricle interfering with CSF flow and presenting as non-communicating triventricular hydrocephalus. None was visible on conventional CT or MRI, two being discovered at neuroendoscopy and one only with a specific MRI sequence designed to show CSF partitioning.