Mood response to levodopa infusion in early Parkinson's disease

Mood response to levodopa infusion was studied in 18 Parkinson's disease (PD) patients during the first year of levodopa therapy before and after 2-hour (1.0 mg/kg/h) levodopa infusions at baseline and 6- and 12-month follow-up. Mood elevation was greatest after a 2-day levodopa holiday at the 6- and 12-month assessments. Age, sex, duration and severity of PD, and ongoing oral levodopa dose did not correlate with mood response. Mood response in these patients differs from that seen in advanced patients, possibly because of sensitization to levodopa's mood effects.     

High-throughput assay for G2 checkpoint inhibitors and identification of the structurally novel compound isogranulatimide

Treatment of cancer cells lacking p53 function with G2 checkpoint inhibitors sensitizes them to the toxic effects of DNA damage and has been proposed as a strategy for cancer therapy. However, few inhibitors are known, and they have been found serendipitously. We report the development of a G2 checkpoint inhibition assay that is suitable for high-throughput screening and its application to a screen of 1300 natural extracts. We present the isolation of a new G2 checkpoint inhibitor, the structurally novel compound isogranulatimide. In combination with gamma-irradiation, isogranulatimide selectively kills MCF-7 cells lacking p53 function.     

The impact of antiretroviral therapy on AIDS survival observed in a province-wide drug treatment programme

Erythrocytosis is a relatively common complication of renal transplantation. Recent observations indicate that angiotensin-converting enzyme inhibitors correct renal transplant erythrocytosis. Other drugs to inhibit the renin-angiotensin system have been developed recently. The newest of these is losartan, a specific antagonist of the angiotensin II type I receptor. We report three patients in which the use of losartan controlled posttransplant erythrocytosis. Our findings suggest that losartan can be effective and safe in the treatment of posttransplant erythrocytosis.     

Identification of 2 allelic mutations of the gene of the phosphodiesterase beta subunit in a Spanish family with recessive autosomic retinitis pigmentosa

BACKGROUND: Retinitis pigmentosa (RP) is a group of inherited eye disorders that affect photoreceptor and pigment epithelial function. Mutations in different genes involved in the phototransduction process have been described in patients with autosomal recessive RP. PATIENTS AND METHODS: We examined the gene coding the beta subunit of the phosphodiesterase (PDEB) in a ARRP family with two affected sisters. SSCP (single stand conformational polymorphism) analysis of the coding region of the gene showed abnormal bands in two different exons. PCR products showing SSCP aberrant patterns were subsequently sequenced. RESULTS: The two affected sisters had inherited from their father a PDEB gene with a known mutation (Gln298X) and a rare variant and from their mother a PDEB gene with a new mutation: Asp600Asn. CONCLUSIONS: The nature of the mutations in the PDEB gene and their pattern of inheritance indicate that the lack of activity of the phosphodiesterase (PDE), a key enzyme in the visual phototransduction process, account for the RP phenotype in these patients.     

Stable phenotypic resistance of Candida species to amphotericin B conferred by preexposure to subinhibitory levels of azoles

The fungicidal activity of amphotericin B (AmB) was quantitated for several Candida species. Candida albicans and C. tropicalis were consistently susceptible to AmB, with less than 1% survivors after 6 h of exposure to AmB. C. parapsilosis and variants of C. lusitaniae and C. guilliermondii were the most resistant, demonstrating 50 to 90% survivors in this time period and as high as 1% survival after a 24-h exposure time. All Candida species were killed (<1% survivors) after 24 h of exposure to AmB. In contrast, overnight exposure to either fluconazole or itraconazole resulted in pronounced increases in resistance to subsequent exposures to AmB. Most dramatically, C. albicans was able to grow in AmB cultures after azole preexposure. Several other Candida species did not grow in AmB but showed little or no reduction in viability after up to 24 h in AmB. Depending on the growth conditions, Candida cells preexposed to azoles may retain AmB resistance for days after the azoles have been removed. If this in vitro antagonism applies to the clinical setting, treatment of patients with certain antifungal combinations may not be beneficial. The ability of some Candida isolates to survive transient exposures to AmB was not reflected in the in vitro susceptibility changes as measured by standard MIC assays. This finding should be considered in studies attempting to correlate patient outcome with in vitro susceptibilities of clinical fungal isolates. Patients who fail to respond to AmB may be infected with isolates that are classified as susceptible by standard in vitro assays but that may be resistant to transient antifungal exposures which may be more relevant in the clinical setting.     

The MIRD perspective 1999. Medical Internal Radiation Dose Committee

The MIRD schema is a general approach for medical internal radiation dosimetry. Although the schema has traditionally been used for organ dosimetry, it is also applicable to dosimetry at the suborgan, voxel, multicellular and cellular levels. The MIRD pamphlets that follow in this issue and in coming issues, as well as the recent monograph on cellular dosimetry, demonstrate the flexibility of this approach. Furthermore, these pamphlets provide new tools for radionuclide dosimetry applications, including the dynamic bladder model, S values for small structures within the brain (i.e., suborgan dosimetry), voxel S values for constructing three-dimensional dose distributions and dose-volume histograms and techniques for acquiring quantitative distribution and pharmacokinetic data.     

Solar retinopathy in a hospital-based primary care clinic

BACKGROUND: Most reports of solar retinopathy describe epidemics of patients who go to the eye doctor after viewing a solar eclipse. Rarely is it encountered by the primary eye care provider during a routine eye examination. METHODS: For 26 months, patients who went to the primary care eye clinic and found to have macular lesions consistent with solar retinopathy were identified from the total clinic population. These patients were documented in a coded log and fundus photographs were obtained (when possible). RESULTS: Twenty-six eyes of twenty patients (0.14% incidence) were determined to have macular lesions consistent with solar retinopathy. Visual acuity was 20/25 or better in 100% of the patients and 85% were 20/20. Patients were predominantly men (75%) of middle age (average age, 43 years; SD, 11 years) with a history relevant for solar retinopathy (80%)--consisting of sungazing, 60%; looking at welding light without eye protection, 15%; substance abuse, 15%; and psychiatric condition, 5%. Forty percent had solar lesions in both eyes. Amsler grid testing revealed a defect in only 20%, and macular threshold visual-field testing was normal in all the eyes tested. CONCLUSIONS: This is the first report to characterize solar retinopathy in a primary eye care population. Management includes correct differentiation from other macular disorders, acquisition of a careful detailed history, and provision of patient education regarding the dangers of sungazing.