Does timolol modify retinal hemodynamics in patients with normal pressure glaucoma?]

In 31 patients with normal-pressure glaucoma, retinal blood flow, diameter of the retinal vessels and velocity were measured with 2-point fluorometry and automatic measurement of the diameters before and after administration of 0.5% timolol over 2 weeks. After timolol therapy the tension was significantly decreased (before therapy: 18.26 +/- 2.50; after therapy: 15.61 +/- 2.56 mm Hg, P < or = 0.01). The arterial and venous diameters and blood flow were nearly unchanged, but a slight increase in the arterial and venous velocity was noted. We conclude that timolol does not significantly influence the retinal hemodynamics in patients with normal-pressure glaucoma.     

Buoyant density characterization of neoplastic cell populations in patients with chronic B-lymphocytic leukemia

Leukemic cells from a series of patients with chronic B-lymphocytic leukemia (CLL) were analyzed for their buoyant density on discontinuous Percoll gradients. The density profile varied markedly between different patients and also between samples from different body compartments within the same patient. A good correlation was observed between buoyant density and maturation stage of the leukemic clones as judged by Ig-expression and their reactivity with a panel of monoclonal antibodies. Phorbol-ester-induced changes in the leukemic cells were found to be accompanied by a general decrease in their buoyant density. No correlation between density and clinical parameters such as cell counts, clinical stage and survival could be noted. Buoyant density characterization of leukemic B-cell populations is seen as a useful, rapid and simple marker of compartmentalization within the B-lymphocyte maturation spectrum but its clinical relevance remains to be established.     

Trimethoprim-sulfamethoxazole versus pentamidine for Pneumocystis carinii pneumonia in AIDS patients: results of a large prospective randomized treatment trial.

OBJECTIVE: To compare the clinical efficacy and safety of trimethoprim-sulfamethoxazole (TMP-SMX) with pentamidine in the therapy of Pneumocystis carinii pneumonia (PCP) in patients with AIDS. PATIENTS, PARTICIPANTS: TMP-SMX (TMP, 20 mg/kg/day plus SMX, 100 mg/kg/day) was compared with pentamidine (4 mg/kg/day), both administered intravenously for 21 days in a prospective randomized treatment trial of 163 patients diagnosed with PCP between November 1984 and May 1988. RESULTS: Ninety-two evaluable patients received TMP-SMX as initial therapy; 68 received pentamidine. Failure to complete therapy was common. Of those receiving TMP-SMX, 39 (42%) required change in therapy because of failure to respond, and an additional 31 (34%) because of drug toxicity. This compared with 27 (40%; P = 0.733) and 17 (25%; P = 0.235), respectively, in the pentamidine-treated group. The overall survival rates were similar in the two groups, 62 out of 92 (67%) initially administered TMP-SMX versus 50 out of 68 (74%) initially administered pentamidine (P = 0.402). The survival rates for patients requiring a change in therapy because of failure to respond was 46% (18 out of 39) for the TMP-SMX group compared with 56% (15 out of 27) for the pentamidine group. When a change in therapy was made because of toxicity, survival rates were 97% (30 out of 31) for those receiving TMP-SMX versus 94% (16 out of 17) for those receiving pentamidine. CONCLUSION: TMP-SMX and pentamidine are of equivalent efficacy as initial therapies for PCP in patients with AIDS.     

Reversibility of dilated cardiomyopathy by low-dose oral roxithromycin in a patient with chronic lyme-borreliosis

It has been shown earlier that dilated cardiomyopathy can be associated withBorrelia burgdorferi infection.Here the authors present a case: a fifty-nine-year-old man who presented with dyspnea, oligoarthritis, paresthesia in both hands, and acrodermatitis chronica atrophicans. Upon further cardiologic exploration by cardiac catheterization and two-dimensional echocardiography (volume-length-area method), the patient exhibited an ejection fraction (EF) of 49%. Serology revealed IgG ELISA positive and IIFT 1:64 positive forB. burgdorferi. The patient received 2 × 150 mg roxithromycin orally for six weeks. Upon a second examination after termination of treatment (three months later), the patient presented with negativeB. burgdorferi serology and normal EF (70%). While cardiac manifestations thus apparently vanished, other symptoms persisted.This case may give new insight into mechanisms of action of macrolides againstB. burgdorferi (a field where information is inherently scant). One may, however, argue that in a well-perfused organ like the heart, tissue-activity of roxithromycin may suffice in order to unfold its activity againstB. burgdorferi.     

Construction and validation of a Parkinson's disease mutation genotyping array for the Parkin gene.

Parkin mutations account for the majority of familial and sporadic early onset Parkinson's disease (EOPD) cases with a known genetic association. More than 100 mutations have been described in the Parkin gene that includes homozygous, compound heterozygous, and single heterozygous mutations. We have designed a Parkin mutation genotyping array (gene chip) that includes published Parkin sequence variants and allows their simultaneous detection. The chip was validated by screening 85 PD cases and 47 controls previously tested for Parkin mutations. Similar genotyping microarrays have been developed for other genetically heterogeneous diseases including age-related macular degeneration. Here, we show the utility of a genotyping array for Parkinson's disease by analysis of 60 subjects from the Genetic Epidemiology of Parkinson Disease (GEPD) study that includes 15 early-onset PD case probands and 45 relatives.     

Plasma pharmacokinetics of high-dose oral busulfan in children and adults undergoing bone marrow transplantation

Abstract: We have analyzed the plasma pharmacokinetics of busulfan in 272 patients receiving high-dose oral busulfan and intravenous cyclophosphamide in conjunction with allogeneic or autologous bone marrow transplantation. The patients ranged in age from 2 months to 59 yr (mean 10, median 12 yr) and had the following diagnoses: thalassemia or sickle cell anemia (n = 74); leukemia or myelodysplasia (n = 112); inborn errors of metabolism (n = 41) or immunodeficiency (n = 45). Plasma specimens were collected following the first dose for each patient which ranged from 1 to 4 mg/kg (mean ± SD, 1.21 ± 0.41, median 1.15). Busulfan was quantitated using ultraviolet absorbance detection after derivatization and HPLC separation. Pharmacokinetic parameters were derived by modeling the raw data to fit first-order single compartment kinetics. The kinetic parameters showed wide interpatient variability independent of age and diagnosis. There was a statistically significant correlation of age with the following parameters: area under the curve (AUC); maximal concentration; minimum concentration; clearance; volume of distribution and absorption half-time. The coefficients of determination (i.e. correlation coefficient squared) were low ranging from 0.04 to 0.12 implying only a small part (i.e. 4–12%) of the variance was explained by age. Although busulfan pharmacokinetics are age-related most of the variability is not explained by age or diagnosis.