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Biomedical subjects

J H Young

Publications and source records attributed to J H Young.

At least 19 recordsLinked to original sources

DAE (daunorubicin, Ara-C, and etoposide) and intermediate dose Ara-C for remission induction and consolidation treatment of adult patients with acute myeloid leukemia.

Fifty-one patients (age 18-73 years) with acute myeloid leukemia were treated with daunorubicin, cytarabine, and etoposide in an age-adjusted protocol, with patients older than 50 receiving fewer days of therapy. Complete remission (CR) occurred in 66% of the patients (34 of 51 patients). Patients 50 years of age and younger achieved a 74% CR rate (23 of 31 patients) compared to a 55% CR rate (11 of 20 patients) in older patients. Of the 34 complete responders, 11 (32%) refused consolidation therapy and received traditional Chinese herbal medicine. All of these 11 patients relapsed after a short remission duration (median, 3.8 months) and died. The median remission duration and median overall survival of 23 complete responders receiving at least two courses of consolidation therapy were 10.1 and 19.8 months, respectively. The actuarial 3-year disease-free survival for these 23 complete responders was 21 +/- 9%. Myelosuppression was the major toxicity, and nonhematological side effects were acceptable. The regimen appeared to have acceptable toxicity, and its efficacy was comparable with that of standard regimens with long-term maintenance therapy.

Acute Disease

Ketoconazole and high-dose methylprednisolone predisposing to cyclosporine-induced seizures: report of 3 cases.

Three consecutive cases of severe aplastic anemia undergoing immunosuppressive therapy with cyclosporin A (CyA) and high-dose methylprednisolone (HDMP) developed grand mal seizures after receiving ketoconazole treatment. All the seizures were reversed after transient discontinuation of those drugs. To our knowledge, it has not been reported as yet that the combination of ketoconazole and HDMP may considerably increase the risk of CyA-induced seizure. We would advise that ketoconazole and HDMP not be taken concomitantly with CyA treatment, and whenever ketoconazole therapy is needed, CyA be started with as small a dose as possible.

Adolescent

Subunit stoichiometry of retinal rod cGMP phosphodiesterase.

The cyclic GMP phosphodiesterase of the retinal rod is composed of three distinct types of polypeptides: alpha (90 kDa), beta (86 kDa), and gamma (10 kDa). The gamma subunit has been shown to inhibit phosphodiesterase activity associated with alpha and beta. To investigate the subunit stoichiometry of the retinal phosphodiesterase, we have developed a panel of monoclonal and peptide antibodies that recognize individual phosphodiesterase subunits. By quantitative and immunochemical analysis of the purified subunits, we have shown that each phosphodiesterase molecule contains one copy each of alpha and beta subunit and two copies of gamma subunit. Moreover, gamma can be chemically cross-linked to both alpha and beta, but not to itself, suggesting that alpha and beta may each bind one gamma. The phosphodiesterase is fully activated when both copies of gamma were removed by proteolysis with trypsin. Upon recombination of the purified gamma subunit with the trypsin-activated phosphodiesterase containing alpha beta, the alpha beta gamma 2 stoichiometry is once again restored, with concomitant total inhibition of activity. Our results suggest that at least two activated transducin molecules are required to fully activate one molecule of phosphodiesterase in retinal rods.

3',5'-Cyclic-GMP Phosphodiesterases

Effect of hsien-ho-t'sao (Agrimonia pilosa) on experimental thrombosis in mice.

The water extract of Hsien-Ho-T'sao (HHT) prolonged the tail bleeding time in conscious mice. This antihemostatic effect was dose-dependent and exhibited a biphasic pattern; i.e. its activity declined at doses higher than 0.5 mg/kg. the prolonged bleeding time persisted for at least 12 hr and maximal effect was observed at 3 hr after the oral administration of HHT 500 mg/kg. HHT was effective in preventing ADP-induced acute pulmonary thromboembolic death in mice, while aspirin and indomethacin had no effect on this model. HHT, like aspirin and indomethacin, also reduced the mortality in collagen- and sodium arachidonate-induced thromboembolic death. All three drugs caused no significant protection in endotoxin shock. HHT was found to suppress platelet aggregation markedly, but little effect on blood coagulation. In conclusion, HHT was proved to be effective in the treatment of acute pulmonary thromboembolism, and this effect was mainly due to its antiplatelet action.

Animals

Efficacy and tolerance of a fixed ratio combination of hydrochlorothiazide, amiloride and timolol, taken before or after food, in the treatment of hypertension.

An open study was carried out in general practice to assess the efficacy and tolerance of a fixed ratio combination of hydrochlorothiazide (25 mg), amiloride (2.5 mg) and timolol (10 mg) in the treatment of patients with mild to moderate hypertension, and to determine if there were any differences in response when medication was taken before or after food. A total of 663 patients was studied and received 1 to 2 tablets once daily for a period of 12 weeks; 322 patients took their medication before and 341 after food. The results showed that there were similar significant reductions in systolic and diastolic blood pressure and in heart rate in both groups, over half of the patients being controlled (less than 90 mmHg diastolic) after 2 weeks and 80% by the end of the study period. Relatively few adverse effects were reported and the incidence during treatment was less than that recorded on entry to the study. There was no evidence to suggest that the timing of drug intake in relation to food had any effect on the efficacy or tolerance of the combination.

Adult

Acute leukemia with megakaryocytic differentiation: a study of 12 cases identified immunocytochemically.

Acute leukemia with megakaryocytic differentiation has been an uncommonly recognized disorder. We used specific monoclonal and polyclonal antibody reagents (HP1-1D antibody and anti-factor VIII antibody, respectively) and an immunocytochemical staining technique to identify the megakaryocytic nature of the leukemic cells of 12 patients who presented with acute leukemia. The leukemic cells of our patients demonstrated the presence of one or both of these platelet- and megakaryocyte-related antigens, but were negative for all of the commonly employed cytochemical and immunocytochemical staining reactions, except for diffuse acid phosphatase activity and granular PAS positivity. Morphologically, the leukemic cells varied in size from 10 to 40 microns in diameter, frequently had cytoplasmic budding, and contained occasional vacuoles and/or peroxidase-negative azurophilic granules. Five patients presented with syndromes of acute myelofibrosis, and seven patients had otherwise unclassifiable acute leukemias, including three patients who had secondary leukemias. Diffuse reticulin myelofibrosis was present in all cases in which it was sought. Chromosomal abnormalities of leukemic cells were found in five cases. Two patients had deficiencies of plasma coagulation factor V. Study of one patient revealed significant platelet dysfunction. When cytoreductive chemotherapy of leukemia was attempted, the observed response was generally poor, with the exceptions of one patient who has remained in complete remission following treatment with etoposide (VP-16) and a second patient who attained remission following bone marrow transplantation. These cases of acute megakaryoblastic leukemia represented from 3.6% to 9.3% of all acute leukemia cases diagnosed concomitantly in our institution. Acute leukemia with megakaryocytic differentiation may occur more frequently than previously recognized, may present with differing syndromic features, and can be identified by the use of specific antibody reagents and relatively simple immunocytochemical techniques.

Acute Disease

Comparison of a fixed ratio combination of hydrochlorothiazide, amiloride and timolol ('Moducren') given once versus twice daily in mild to moderate hypertension.

An open, multi-centre study was carried out in general practice to compare the efficacy and tolerance of antihypertensive therapy with once-daily and twice-daily dosage of a fixed ratio combination of hydrochlorothiazide (25 mg), amiloride (2.5 mg) and timolol (10 mg). A total of 604 patients with mild to moderate hypertension were treated over a period of 12 weeks with either 1 to 2 tablets once-daily (294 patients) or 1/2 to 1 tablet twice-daily (310 patients). The results showed that there was a significant reduction in systolic and diastolic blood pressures in both groups after only 2-weeks' therapy and the overall reduction after 12 weeks was 31/19 mmHg, with 57% of patients being adequately controlled on the equivalent of 1 tablet per day, whether taken once daily or in divided doses. Forty-six (8%) patients withdrew from the study because of drug-related symptoms, mainly central nervous system in origin. Overall, treatment with either regimen was considered suitable and acceptable by over 80% of patients and doctors.

Adult

'Osmosin' in general practice: preliminary report of a double-blind study in the treatment of osteoarthritis.

'Osmosin' (105 mg sodium indomethacin trihydrate) has been studied in a double-blind general practice trial of patients with osteoarthritis of the hip at a dose of 1 tablet in the morning and matching placebo at night versus 1 tablet twice daily. To date, 223 patients have completed the study, 113 in the lower dose and 110 in the higher dose group. In the preliminary analysis, the overall trend at 4 weeks favoured the higher dose in effectiveness and this group appeared to respond more rapidly. The incidence of side-effects was similar in both groups, but there were fewer drop-outs due to side-effects in the group receiving 'Osmosin' once daily. The preliminary results indicate that the response to 'Osmosin' is time-dependent as well as dose-dependent and, therefore, rather than increasing the dose early, it is probably preferable to initiate therapy with 1 'Osmosin' daily and review at 1 month the need to increase the dose to 1 'Osmosin' twice daily.

Adult