A phase I/II dose escalation study of carboplatin in the treatment of newly diagnosed patients with advanced ovarian cancer receiving paclitaxel

The objective of this study was to determine the maximum tolerated dose of carboplatin when administered with paclitaxel in previously untreated patients with ovarian cancer. Patients were treated with paclitaxel at 225 mg/m2 for 3 hours followed by carboplatin at an area under the curve (AUC) of 6, 7, 8, or 9 every 3 weeks. Granulocyte colony-stimulating factor was added if needed to maintain dose intensity before dose reductions were used for grade 4 hematologic toxicity or febrile neutropenia. Twenty-two patients were enrolled in the study. At the AUC 6 level, five of six patients finished all six cycles. At the AUC 7 level, four of five patients completed six cycles, although three required dose reductions for toxicity. At the AUC 8 level, all four patients completed six cycles and two required dose reductions. The AUC 9 level was not well tolerated. Only four of seven patients completed six cycles. Neutropenia was common, and transient thrombocytopenia was more severe and required dose reduction, especially in later cycles. An AUC of 8 is the maximum tolerated dose of carboplatin in combination with paclitaxel at 225 mg/m2 for 3 hours.     

Sentinels and signposts: The epidemiology and significance of the oral manifestations of HIV disease

A large number of studies attest to the frequency of oral disease in those with HIV infection. Most show that hairy leukoplakia and pseudomembranous candidiasis are the commonest lesions in those with HIV infection and AIDS, with higher prevalence and incidence rates correlating with falling CD4 counts and disease progression. HIV-infected individuals with oral candidiasis or hairy leukoplakia progress to AIDS more rapidly than matched controls without these lesions. Oral candidiasis and hairy leukoplakia increase with time since seroconversion. On the other hand, parotid enlargement in children appears to be associated with slower progression to AIDS. As a consequence of these and other observations, oral lesions are widely included in natural history studies, staging and classification schemes for HIV infection. In addition to their role in the diagnosis of HIV infection and as indicators of the progression of HIV disease, oral lesions are used as clinical correlates of CD4 counts and as criteria for entry into clinical trials.     

Close correspondence between quantitative- and molecular-genetic divergence times for Neandertals and modern humans

Recent research has shown that genetic drift may have produced many cranial differences between Neandertals and modern humans. If this is the case, then it should be possible to estimate population genetic parameters from Neandertal and modern human cranial measurements in a manner analogous to how estimates are made from DNA sequences. Building on previous work in evolutionary quantitative genetics and on microsatellites, we present a divergence time estimator for neutrally evolving morphological measurements. We then apply this estimator to 37 standard cranial measurements collected on 2,524 modern humans from 30 globally distributed populations and 20 Neandertal specimens. We calculate that the lineages leading to Neandertals and modern humans split approximately 311,000 (95% C.I.: 182,000 to 466,000) or 435,000 (95% C.I.: 308,000 to 592,000) years ago, depending on assumptions about changes in within-population variation. These dates are quite similar to those recently derived from ancient Neandertal and extant human DNA sequences. Close correspondence between cranial and DNA-sequence results implies that both datasets largely, although not necessarily exclusively, reflect neutral divergence, causing them to track population history or phylogeny rather than the action of diversifying natural selection. The cranial dataset covers only aspects of cranial anatomy that can be readily quantified with standard osteometric tools, so future research will be needed to determine whether these results are representative. Nonetheless, for the measurements we consider here, we find no conflict between molecules and morphology.     

Relationship between visual field loss and contrast threshold elevation in glaucoma

Background  

There is a considerable body of literature which indicates that contrast thresholds for the detection of sinusoidal grating patterns are abnormally high in glaucoma, though just how these elevations are related to the location of visual field loss remains unknown. Our aim, therefore, has been to determine the relationship between contrast threshold elevation and visual field loss in corresponding regions of the peripheral visual field in glaucoma patients.     

Natural history of Hartnup disease

Hartnup disease was diagnosed in 12 children and 3 of their 15 sibs in the course of routine urine screening of 6-week-old infants in New South Wales. These children were followed for up to 8 years, during which time there were only two clinical episodes which might be ascribed to Hartnup disease. The mental development of all the children was normal. 10 had height centiles less than the midparent height centiles, while 4 had centiles equal to or above the midparent centiles. The study shows that in children with Hartnup disease in Australia symptoms are very uncommon. Mental development is normal, and heights are possibly slightly below that expected. Hartnup disease has an incidence of approximately 1 in 33 000 in New South Wales.     

Poststroke restless legs syndrome and lesion location: anatomical considerations

Several case studies have reported on restless legs syndrome (RLS) associated with stroke. In this study, we investigated the prevalence and the lesion topography of poststroke RLS. There were 137 patients with ischemic stroke included in this study. The diagnosis of RLS was made 1 month after the index stroke using the criteria established by the International RLS Study Group. All patients enrolled underwent magnetic resonance imaging within 7 days of the onset of the stroke. The prevalence of stroke-related RLS was calculated, and the topography of the associated ischemic lesions was analyzed. Among 137 patients, 17 patients (12.4%) were diagnosed with RLS after a stroke. Stroke-related RLS was found in 10 out of 33 patients with a basal ganglia/corona radiata infarct (30.3%), 1 out of 8 patients with an internal capsular infarct (12.5%), and 1 out of 7 patients with a thalamic infarct (14.3%). In addition, one out of 54 with a cortical lesion with/without subcortical involvement (1.9%), and 4 out of 18 patients with a pontine lesion (22.2%) had RLS. The analysis of the lesions in the cortical and subcortical group showed only 1 patient in the cortical group had stroke-related RLS, whereas 16 in the subcortical group had stroke-related RLS. The results of this study suggest that lesions of the subcortical brain areas such as the pyramidal tract and the basal ganglia-brainstem axis, which are involved in motor functions and sleep-wake cycles, may lead to RLS symptoms in patients after an ischemic stroke.     

A new name (Pneumocystis jiroveci) for Pneumocystis from humans

The disease known as Pneumocystis carinii pneumonia (PCP) is a major cause of illness and death in persons with impaired immune systems. While the genus Pneumocystis has been known to science for nearly a century, understanding of its members remained rudimentary until DNA analysis showed its extensive diversity. Pneumocystis organisms from different host species have very different DNA sequences, indicating multiple species. In recognition of its genetic and functional distinctness, the organism that causes human PCP is now named Pneumocystis jiroveci Frenkel 1999. Changing the organism's name does not preclude the use of the acronym PCP because it can be read "Pneumocystis pneumonia." DNA sequence variation exists among samples of P. jiroveci, a feature that allows reexamination of the relationships between host and pathogen. Instead of lifelong latency, transient colonization may be the rule.