PREDICT-GTN 1: Can we improve the FIGO scoring system in gestational trophoblastic neoplasia?

Gestational trophoblastic neoplasia (GTN) patients are treated according to the eight-variable International Federation of Gynaecology and Obstetrics (FIGO) scoring system, that aims to predict first-line single-agent chemotherapy resistance. FIGO is imperfect with one-third of low-risk patients developing disease resistance to first-line single-agent chemotherapy. We aimed to generate simplified models that improve upon FIGO. Logistic regression (LR) and multilayer perceptron (MLP) modelling (n = 4191) generated six models (M1-6). M1, all eight FIGO variables (scored data); M2, all eight FIGO variables (scored and raw data); M3, nonimaging variables (scored data); M4, nonimaging variables (scored and raw data); M5, imaging variables (scored data); and M6, pretreatment hCG (raw data) + imaging variables (scored data). Performance was compared to FIGO using true and false positive rates, positive and negative predictive values, diagnostic odds ratio, receiver operating characteristic (ROC) curves, Bland-Altman calibration plots, decision curve analysis and contingency tables. M1-6 were calibrated and outperformed FIGO on true positive rate and positive predictive value. Using LR and MLP, M1, M2 and M4 generated small improvements to the ROC curve and decision curve analysis. M3, M5 and M6 matched FIGO or performed less well. Compared to FIGO, most (excluding LR M4 and MLP M5) had significant discordance in patient classification (McNemar's test P < .05); 55-112 undertreated, 46-206 overtreated. Statistical modelling yielded only small gains over FIGO performance, arising through recategorisation of treatment-resistant patients, with a significant proportion of under/overtreatment as the available data have been used a priori to allocate primary chemotherapy. Streamlining FIGO should now be the focus.     

Pituitary abnormalities in eating disorders: further evidence from MRI studies

1. The frequent occurrence of hypothalamo-pituitary dysfunction in patients with eating disorders as well as prior reports that nutritional and endocrine status influence pituitary morphology, led us to hypothesize that pituitary size and shape may be altered in patients with eating disorders. 2. Magnetic resonance imaging (MRI) does not use ionizing radiation and is currently one of the most feasible modalities available to study the pituitary gland in vivo. Using MRI, we have previously reported in a preliminary study that female patients with eating disorders had significantly smaller pituitary glands than controls. In addition MRI excluded any pituitary mass lesions. 3. In this report, we confirm our previous MRI findings and provide further evidence of pituitary abnormalities in an expanded sample of eating disorder patients. Preliminary data on pituitary volume estimates from MRI scans are provided for a subset of patients and controls.     

PADGEM (GMP140) is a component of Weibel-Palade bodies of human endothelial cells

PADGEM protein (PADGEM), also known as GMP140, is a platelet alpha- granule membrane protein that is translocated to the external membrane after platelet activation. Although the biosynthesis of this protein was originally thought to be confined to megakaryocytes, the synthesis of PADGEM in endothelial cells was recently demonstrated (McEver et al: Blood 70:1974a, 1987). We now describe the subcellular localization of this protein in endothelial cells. Immunofluorescence staining of permeabilized human umbilical vein endothelial cells with KC4, a well characterized monoclonal antibody to PADGEM, showed positively stained elongated structures similar in distribution and shape to Weibel-Palade bodies. Their identity as Weibel-Palade bodies was confirmed by double label immunofluorescence using KC4 and a polyclonal antiserum to von Willebrand factor (vWf), a protein known to be specifically stored in these organelles. All Weibel-Palade bodies were found to contain PADGEM. In contrast to strong perinuclear staining produced with anti- vWf antibodies, no significant perinuclear staining was obtained with KC4, indicating that relatively little PADGEM is present in the endoplasmic reticulum and in the Golgi apparatus. In endothelial cells treated with secretagogues that stimulate vWf release the elongated structures positive for PADGEM disappeared, further identifying these structures as Weibel-Palade bodies. This observation extends the parallels between Weibel-Palade bodies and alpha-granules and suggests a possible functional association between vWf and PADGEM.     

Optic nerve glioma and the management of optic nerve tumours in the young.

Thirty-one patients presenting as orbital optic nerve glioma have been reviewed with maximum follow-up of 14 years. Sixteen of these patients have been reported on previously and further follow-up is provided. Sixteen patients had a stable clinical course with little change over a period of up to 13.5 years. Neurofibromatosis was relatively common in this group (11/16). Fifteen patients had progressive enlargement of the tumour; the incidence of neurofibromatosis in this group was low (4/15). Eleven of these patients were explored neurosurgically and the optic nerve totally excised in 10 of them. The proximal cut end was normal in six patients and the chiasm has apparently remained free of tumour in all of them. We suggest a method of management of primary optic nerve tumours, both meningiomas and gliomas, in young patients.     

Intraocular lens removal during penetrating keratoplasty for pseudophakic bullous keratopathy

Pseudophakic bullous keratopathy is now the most common reason for penetrating keratoplasty. In previous reports, the type of intraocular lens (IOL) most frequently encountered in these eyes was the iris plane IOL. The authors reviewed 27 cases of IOL removal during penetrating keratoplasty. Lenses were removed if they were dislocated or associated with iritis, recurrent hyphema, glaucoma, or persistent cystoid macular edema. The IOL encountered most often was the anterior chamber lens (in 22 eyes); closed thin loop, semiflexible or flexible anterior chamber lenses accounted for 19 of these. Iris plane lenses were removed from five eyes. No posterior chamber lenses were removed. Clear grafts were obtained in 24 of 27 cases (89%); visual acuity improved or remained the same in 24 cases, to 20/60 in 11 cases. The most common causes of poor postoperative vision were retinal disease (6/27 cases) and glaucoma (6/27 cases). The association between anterior chamber lenses and pseudophakic bullous keratopathy is probably the result of both the increase in use of these lenses and the documented propensity of the closed loop semiflexible anterior chamber lenses to cause complications.     

Altered excitatory and inhibitory amino acid receptor binding in hippocampus of patients with temporal lobe epilepsy.

We examined binding to excitatory amino acid and inhibitory amino acid receptors in frozen hippocampal sections prepared from surgical specimens resected from 8 individuals with medically refractory temporal lobe epilepsy. The excitatory receptors studied included N-methyl-D-aspartate (NMDA), strychnine-insensitive glycine, phencyclidine, and quisqualate. The inhibitory receptors studied were gamma-aminobutyric acid type A (GABAA) and benzodiazepine. Excitatory and inhibitory amino acid receptor binding were differentially altered in the patients with temporal lobe epilepsy in comparison to 8 age-comparable autopsy control subjects, and changes in receptor binding were regionally selective in four areas. Binding to phencyclidine receptors associated with the NMDA channel was reduced by 35 to 70% in all regions in the hippocampi of the patients. In contrast, binding to the NMDA recognition site and its associated glycine modulatory site was elevated by 20 to 110% in the cornu ammonis (CA) 1 area and dentate gyrus of the hippocampus of the patients. Binding to these sites was unaffected in area CA4. Binding to the quisqualate-type excitatory amino acid receptor was unchanged in all regions except the stratum lacunosum moleculare CA1, where it was increased by 63%. GABAA and benzodiazepine receptor binding was reduced by 20 to 60% in CA1 and CA4, but unchanged in dentate gyrus. The data indicate that excitatory and inhibitory amino acid receptors are altered in the hippocampus of patients with temporal lobe epilepsy.     

Just-in-Time Evidence-Based E-mail “Reminders” in Home Health Care: Impact on Patient Outcomes

OBJECTIVE: To assess the impact and cost-effectiveness of two information-based provider reminder interventions designed to improve self-care management and outcomes of heart failure (HF) patients. DATA SOURCES/STUDY SETTING: Interview and agency administrative data on 628 home care patients with a primary diagnosis of HF. STUDY DESIGN: Patients were treated by nurses randomly assigned to usual care or one of two intervention groups. The basic intervention was an e-mail to the patient's nurse highlighting six HF-specific clinical recommendations. The augmented intervention supplemented the initial nurse reminder with additional clinician and patient resources. DATA COLLECTION: Patient interviews were conducted 45 days post admission to measure self-management behaviors, HF-specific outcomes (Kansas City Cardiomyopathy Questionnaire-KCCQ), health-related quality of life (EuroQoL), and service use. PRINCIPAL FINDINGS: Both interventions improved the mean KCCQ summary score (15.3 and 12.9 percent, respectively) relative to usual care (p< or =.05). The basic intervention also yielded a higher EuroQoL score relative to usual care (p< or =.05). In addition, the interventions had a positive impact on medication knowledge, diet, and weight monitoring. The basic intervention was more cost-effective than the augmented intervention in improving clinical outcomes. CONCLUSIONS: This study demonstrates the positive impact of targeting evidence-based computer reminders to home health nurses to improve patient self-care behaviors, knowledge, and clinical outcomes. It also advances the field's limited understanding of the cost-effectiveness of selected strategies for translating research into practice.