FK506 in combination with methotrexate for the prevention of graft- versus-host disease after marrow transplantation from matched unrelated donors

The safety and potential efficacy of FK506 in combination with a short course of methotrexate (MTX) for the prevention of acute graft-versus- host disease (GVHD) after marrow transplantation from HLA-matched unrelated donors was evaluated in a single-arm Phase II study conducted at two centers. Forty-three patients, 15 to 54 (median 41) years of age, were transplanted for hematologic malignancies. Thirty-seven of 43 evaluable patients had evidence of sustained marrow engraftment. Five patients died before day 17 after transplantation. The median time to an absolute neutrophil count of > 0.5 x 10(5)/L was 21 (range, 14 to 30) days. Nephrotoxicity (serum creatinine concentration > 2 mg/dL or doubling of baseline) occurred in 32 patients (74% cumulative incidence during the first 100 days after transplant). Other adverse effects included hypertension (n = 27), hyperglycemia (n = 27), neurotoxicity (n = 9) and thrombotic thrombocytopenic purpura (n = 2). Severe veno- occlusive disease of the liver occurred in 9 (21%) of the 43 patients. Eighteen patients (42%) developed grades II to IV acute GVHD and five (12%) developed grades III to IV acute GVHD. Twelve of 25 evaluable patients developed extensive chronic GVHD within 1 year of marrow transplantation resulting in an estimate of the probability of developing this complication of 48%. The cumulative incidence of transplant-related mortality during the first 100 days was 37%. Kaplan- Meier estimates of disease-free survival at 2 years for good-risk, poor- risk, and all patients were 65%, 4%, and 32%, respectively. FK506 in combination with a short course of MTX appears active in preventing acute GVHD after marrow transplantation from unrelated donors. Further studies comparing the combination of FK506 and MTX with cyclosporine and MTX for the prevention of acute GVHD are warranted.     

Evaluation of the anticonvulsant and muscle relaxant effects of the methanol root bark extracts of Annona senegalensis

ObjectiveTo investigate the potentials of the root bark of Annona (A.) senegalensis in the control of seizure and related hypnotic and motor incoordination effects in mice using experimental models.MethodsThe methanol extract (ME) of the root bark of A. senegalensis was studied in mice using pentylenetetrazole (PTZ) induced convulsions, phenobarbitone induced sleeping time and motor coordination test on rota-rod performance. Acute toxicity and lethality (LD₅₀) test as well as phytochemical analysis were also carried out.ResultsThe extract (200, 400, 800 mg/kg) exhibited a non-dose dependent significant (P <0.05) delay in the onset of both tonic and clonic phases of seizure induced by PTZ (60 mg/kg, s.c.) as well as offered a 100% protection (200 mg/kg) in mice from PTZ induced seizures. The extract significantly (P <0.05) decreased the latency and increased the duration of phenobarbitone induced sleeping time. At 200 mg/kg, the extract exhibited a significant (P <0.05) motor incoordination. The acute toxicity test revealed an oral LD₅₀ of 1 296 mg/kg, while the phytochemical studies showed the presence of alkaloids, resins, glycosides, carbohydrate, reducing sugar, flavonoids, terpenoids, saponins and tannins.ConclusionThe extract of A. senegalensis possessed anticonvulsant activity with pronounced hypnotic and muscle relaxant effects.     

Intriguing issues of EGFR targeting in head and neck cancer

We have read the recent comprehensive review by Cruz et al.[1] regarding the targeting of receptor tyrosine kinases andtheir therapeutic perspectives in head and neck squamous cellcarcinomas (HNSCC). The major focus of this report was epidermalgrowth factor receptor (EGFR) biology and targeting. However,we feel     

Atrial natriuretic peptide in the diagnosis of patent ductus arteriosus

The aim of this study was to measure plasma atrial natriuretic peptide in preterm infants with a patent ductus arteriosus before and after closure with indomethacin. Atrial natriuretic peptide was measured in 28 preterm infants with clinical and echocardiographic evidence of a patent ductus arteriosus and in eight preterm infants who did not develop clinical evidence of a patent ductus arteriosus. Plasma concentration of atrial natriuretic peptide was measured by radioimmunoassay. In 18 infants the patent ductus arteriosus closed after one course of indomethacin; atrial natriuretic peptide levels decreased from median 1240 pg/ml (range 201-5483 pg/ml) to 266 pg/ml (range 62-1108 pg/ml). In four infants the patent ductus arteriosus closed after two courses of indomethacin and two infants had surgical ligation after indomethacin treatment failed. The patent ductus arteriosus closed spontaneously in four infants (atrial natriuretic peptide median level 152 pg/ml, range 61-495 pg/ml). In the eight infants without patent ductus arteriosus, atrial natriuretic peptide level was median 224 pg/ml (range 38-876 pg/ml). Measurement of plasma atrial natriuretic peptide concentration has a role in predicting when indomethacin treatment is indicated.     

Visual function-specific perimetry for indirect comparison of different ganglion cell populations in glaucoma

PURPOSE: To compare short-wavelength automated perimetry, frequency-doubling technology perimetry, and motion-automated perimetry, each of which assesses different aspects of visual function, in eyes with glaucomatous optic neuropathy and ocular hypertension. METHODS: One hundred thirty-six eyes from 136 subjects were evaluated with all three tests as well as with standard automated perimetry. Fields were not used in the classification of study groups to prevent bias, because the major purpose of the study was to evaluate each field type relative to the others. Seventy-one of the 136 eyes had glaucomatous optic neuropathy, 37 had ocular hypertension, and 28 served as age-matched normal control eyes. Glaucomatous optic neuropathy was defined by assessment of stereophotographs. Criteria were asymmetrical cupping, the presence of rim thinning, notching, excavation, or nerve fiber layer defect. Ocular hypertensive eyes had intraocular pressure of 23 mm Hg or more on at least two occasions and normal-appearing optic disc stereophotographs. Criteria for abnormality on each visual field test were selected to approximate a specificity of 90% in the normal eyes. Thresholds for each of the four tests were compared, to determine the percentage that were abnormal within each patient group and to assess the agreement among test results for abnormality, location, and extent of visual field deficit. RESULTS: Each test identified a subset of the eyes with glaucomatous optic neuropathy as abnormal: 46% with standard perimetry, 61% with short-wavelength automated perimetry, 70% with frequency-doubling perimetry, and 52% with motion-automated perimetry. In the ocular hypertensive eyes, standard perimetry was abnormal in 5%, short wavelength in 22%, frequency doubling in 46%, and motion in 30%. Fifty-four percent (38/71) of eyes with glaucomatous optic neuropathy were normal on standard fields. However, 90% were identified by at least one of the specific visual function tests. Combining tests improved sensitivity with slight reductions in specificity. The agreement in at least one quadrant, when a defect was present with more than one test, was very high at 92% to 97%. More extensive deficits were shown by frequency-doubling perimetry followed by short-wavelength automated perimetry, then motion-automated perimetry, and last, standard perimetry. However, there were significant individual differences in which test of any given pairing was more extensively affected. Only 30% (11/37) of the ocular hypertensive eyes showed no deficits at all compared with 71% (20/28) of the control eyes (P < 0.001). CONCLUSIONS: For detection of functional loss standard visual field testing is not optimum; a combination of two or more tests may improve detection of functional loss in these eyes; in an individual, the same retinal location is damaged, regardless of visual function under test; glaucomatous optic neuropathy identified on stereophotographs may precede currently measurable function loss in some eyes; conversely, function loss with specific tests may precede detection of abnormality by stereophotograph review; and short-wavelength automated perimetry, frequency-doubling perimetry, and motion-automated perimetry continue to show promise as early indicators of function loss in glaucoma.     

Progression of visual field loss in untreated glaucoma patients and glaucoma suspects in St. Lucia,West Indies

PURPOSE: A 1986-1987 survey found 8.8% prevalence of open-angle glaucoma in the black population of St. Lucia, West Indies. This follow-up study assessed visual field loss progression in untreated glaucoma patients and glaucoma suspects 10 years later. DESIGN: Cohort study. METHODS: Subjects were 205 glaucoma patients and suspects; 1987 data included age, sex, visual acuity, and visual fields measured by automated threshold perimetry (Humphrey C 30-2 test), and 1997 data included intraocular pressure, visual acuity, and visual fields measured by the same test. Exclusion criteria included field unreliability, field improvement due to vision improvement, nonglaucomatous vision deterioration, glaucoma treatment since 1988, and scoring of a visual field as end stage in 1987. Visual fields were scored by algorithms for the Advanced Glaucoma Intervention Study (AGIS) and Collaborative Initial Glaucoma Treatment Study (CIGTS). RESULTS: By AGIS criteria, 55% of 146 right eyes and 52% of 141 left eyes showed progression of visual field loss. In linear regressions, progression severity was unassociated with sex, intraocular pressure, or baseline visual field score, but was positively associated with age (P <.001, right; P =.002, left). The cumulative probability of reaching end stage in 10 years in at least one eye was approximately 16% by AGIS criteria. By CIGTS criteria, 73% of 146 right eyes and 72% of 141 left eyes progressed. CONCLUSIONS: These data provide a unique opportunity to study progression of untreated glaucoma. The percentage of eyes showing visual field loss progression and the percentage reaching end stage were considerably higher than in studies of visual field progression in treated eyes.