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Biomedical subjects

T Oh

Publications and source records attributed to T Oh.

At least 19 recordsLinked to original sources

Thermodynamics of the reconstitution of tuna cytochrome c from two peptide fragments.

Two peptide fragments from tuna cytochrome c (cyt c), N-fragment (residues 1-44 containing the heme) and C-fragment (residues 45-103), combine to form a 1:1 fragment complex. This was clearly proved by ion-spray mass spectrometry. It was found from CD and NMR spectra that the structure of the fragment complex formed is similar to that of an intact cyt c, although each isolated fragment itself is unstructured. Binding constants and enthalpies upon the complex formation were directly observed by isothermal titration calorimetry. Thermodynamic parameters (deltaG(o)b, deltaHb, deltaS(o)b, and deltaC(b)p)) associated with the complex formation were determined at various pHs and temperatures. DeltaHb was found to be almost independent of pH values. The change in heat capacity accompanying the complex formation (deltaC(b)p) was directly determined from the temperature dependence of deltaHb. In addition, the change in heat capacity and enthalpy upon tuna cyt c unfolding were determined by differential scanning calorimetry. Thermodynamic parameters for the unfolding/dissociation process of the fragment complex were compared with those for cyt c unfolding at pH 3.9 and 303 K. In a comparison of two unfolding processes, the heat capacity change of each was very close to the other, while both the unfolding enthalpy and entropy of the fragment complex were larger than those of tuna cyt c. These thermodynamic data suggest that the internal interactions between polar groups (hydrogen bonding) and nonpolar groups (van der Waals interactions) are preserved in the fragment complex as well as in the native state of cyt c.

Animals

In-vitro and in-vivo antibacterial activities of CS-834, a new oral carbapenem.

We evaluated the in-vitro and in-vivo antibacterial activities of R-95867 and CS-834, a new oral carbapenem which is an ester-type prodrug of R-95867. Against Gram-positive bacteria, R-95867 was as active or two to 256 times more active than cefpodoxime, cefdinir, cefditoren and ofloxacin, while its activity was similar to or two to eight times lower than that of imipenem. Against most Gram-negative bacteria it was as active or two to 1024 times more active than the other compounds tested. Against Helicobacter pylori it was two to 64 times more active than orally active anti-H. pylori agents, i.e. amoxycillin, clarithromycin and lansoprazole. It also showed potent bactericidal activity against Staphylococcus aureus and Escherichia coli. R-95867 induced a spherical form in E. coli and showed high affinity for PBP 2 in E. coli. Against systemic infections in mice caused by various bacteria, CS-834 showed an excellent protective effect and its in-vivo efficacy correlated well with the in-vitro activity of R-95867. These results suggest that CS-834 may be effective in the therapy of various bacterial infections.

Administration, Oral

Gastric adenocarcinoma in patients 40 years of age or younger.

BACKGROUND: Gastric adenocarcinoma is considered a disease of the middle aged and elderly and has been infrequently reported in patients under 40 years of age. The purpose of this study was to determine the proportion of young patients diagnosed with gastric adenocarcinoma and to compare the demographic, clinical and pathologic features of younger and older patients with gastric adenocarcinoma. METHODS: A retrospective cohort study using tumor registry records of all patients with gastric adenocarcinoma diagnosed from 1982 through 1996 at a public teaching hospital. Demographic, clinical, and pathologic comparisons were made between patients younger than 41 years of age and race- and sex-matched older patients with gastric adenocarcinoma. RESULTS: Thirty of 203 (15%) cases of gastric adenocarcinoma were diagnosed in patients less than 41 years (range 23 to 40). Male to female ratio was 1:1. Young patients were more likely to be black (33% versus 17%, P = 0.04) Both younger and older patients presented with advanced disease, with nearly half of each group having metastases. Twelve of 29 (41%) younger patients were operated on without a histologic diagnosis of gastric adenocarcinoma in contrast to only 1 older patient (P < 0.001). One of 30 (3%) young patients is alive 39 months following gastrectomy. Twenty patients died and the remaining 9 were lost to follow-up, all with known residual or recurrent disease. Six-month survival of young patients (23%) was less than older patients (42%) (P = 0.14). Young patients were more likely to have diffuse histology (80% versus 55%, P = 0.12). Overt infection with Helicobacter pylori was uncommon in both groups. CONCLUSIONS: Young patients accounted for an unusually high proportion of patients with gastric adenocarcinoma diagnosed at our public teaching hospital. Young patients were significantly more likely to be black and less likely to have an accurate preoperative histologic diagnosis. Both young and older patients presented with advanced disease and had poor survival. Young patients were more likely to have diffuse histology and had poorer 6-month survival, suggesting a more aggressive variety of the disease in this group.

Adenocarcinoma

Poststreptococcal glomerulonephritis with the nephrotic range of proteinuria.

In order to characterize the clinical features in poststreptococcal glomerulonephritis (PSGN) in relation to the range of proteinuria, 27 patients with PSGN were divided into 3 groups according to the amount of urinary protein excretion; Group I: with proteinuria over 3.5 g/day (n = 8), Group II: with proteinuria between 1.0 and 3.4 g/day (n = 9) and Group III: with proteinuria less than 1.0 g/day (n = 10). Bed-rest was ordered until proteinuria decreased to less than 1.0 g/day. The serum creatinine levels in Group I were significantly higher than in Group III both on admission and at discharge, although the duration of hospitalization was longer in the former than in the latter group. Furthermore, the durations of proteinuria and hypocomplementaemia were longer in the former than in the latter. In addition, the former showed a higher systolic blood pressure and a greater expanded extracellular fluid volume expressed as body weight change during hospitalization. However, none of the patients in this study demonstrated any persistent proteinuria or renal function impairment. In conclusion, bed-rest in the acute phase of PSGN might improve the short-term prognosis of PSGN.

Adult

Use of i.v. cimetidine, ranitidine, and famotidine in 40 hospitals.

The drug experiences of 1200 patients receiving i.v. histamine H2-receptor antagonists were studied. Forty hospitals in five southeastern states participated in a drug-use evaluation (DUE). In addition to supplying background information, a pharmacist at each hospital used a standardized form to perform a concurrent review of 30 consecutive adult patients who had been started on i.v. cimetidine, ranitidine, or famotidine. In addition to the patient's age and the prescriber's medical specialty, specific DUE criteria included the reason given in the medical record for use; dosage regimen and adjustments made on the basis of the patient's renal function; other GI drugs taken concurrently; pharmacist intervention; simultaneous use of oral medications; occurrence of adverse events; H2-antagonist use with specified drug products known to affect serum drug concentrations of one or both medications; and use of gastric pH monitoring. Therapy with i.v. H2 antagonists was usually started by internal medicine specialists or surgeons, and most of the evaluated patients received such therapy for prevention of stress-related mucosal damage. According to estimated creatinine clearance, 34% of patients were in need of dosage adjustments, but such adjustments were made in only 49% of these. Forty percent of patients began therapy while taking at least one medication orally, and almost one fourth of patients were receiving an additional drug for the treatment of an acid-peptic or related indication. The occurrence of adverse events was similar for the three H2 antagonists studied. The findings identify several problematic areas in the way H2 antagonists are used in clinical practice.

Adolescent

Effect of synthetic prostaglandin E1 analog (ornoprostil) on gastric emptying and pancreatic polypeptide release after solid-meal ingestion in man.

The effect of orally administered ornoprostil, 17S,20-dimethyl-6-oxoprostaglandin E1 methyl ester, on gastric emptying and on pancreatic polypeptide (PP) release after solid meal ingestion, was investigated in man. A radionuclide technique was used to measure gastric emptying of eight healthy volunteers. In addition, four parameters [SI (starting index): the lag time in the start of emptying; K value: the emptying rate; T1/2: the half emptying time; 120 min RR: the percent retention at 120 min] were determined for evaluation. Also, the PP response was analyzed according to two parameters: IPPRSI the integrated PP response for periods up to SI, and IPPR120, the integrated PP response for 120 min. The results demonstrated that 5 micrograms of orally administered ornoprostil significantly reduced the gastric emptying rate of solid meal (T1/2 and 120 min RR, P less than 0.05). However, ornoprostil affected neither the basal PP concentrations nor the cephalic phase of PP secretion which was determined as IPPRSI. This thus suggests that ornoprostil affects the gastric motor function without interfering with the vagal-cholinergic pathway to the stomach.

Adult

Comprehensive therapeutic interchange program in a community hospital.

The implementation of a comprehensive therapeutic interchange program is described. The need to reduce the number of telephone calls to physicians about nonformulary drug orders, reduce drug costs, and maximize the effectiveness of drug therapy prompted the development of an automatic therapeutic interchange program at a 273-bed nonteaching community hospital. Pharmacists and physicians agreed that a telephone call to discuss every nonformulary drug order was unnecessary. The pharmacy department presented the automatic interchange program to the pharmacy and therapeutics committee. The program was reviewed by the committee, the hospital attorney, and medical staff members and was instituted in 1986 for drug products, such as vitamins and antacids, for which interchanges are noncontroversial. A newsletter describing the program was distributed, and inservice education sessions were held. A reminder was placed on order forms that an interchange for nonformulary drugs would be made unless the nonformulary agent was deemed "medically necessary" by the physician. In such cases, the physician is contacted to discuss the therapeutic alternative. As acceptance of the program and cost efficiencies were demonstrated, more controversial agents were phased in during subsequent years. It was difficult to obtain approval to add some agents, such as third-generation cephalosporins, to the program, but noncompliance and confusion have been minimal. An automatic therapeutic interchange program has worked well at this institution since 1986.

Florida

Implementing therapeutic interchange of intravenous famotidine for cimetidine and ranitidine.

The steps taken to implement a therapeutic interchange program for i.v. histamine H2-receptor antagonists and to determine the potential cost savings are described. A literature review conducted by pharmacists at a 273-bed nonteaching community hospital showed that i.v. famotidine was as safe and effective as i.v. cimetidine or ranitidine and that it was feasible to add famotidine to total parenteral nutrition (TPN) solutions. Because of famotidine's cost advantage, it was proposed that i.v. famotidine be used in place of specific dosage regimens of i.v. ranitidine or cimetidine and in TPN solutions ordered for patients receiving concurrent H2-antagonist therapy. The approval of the hospital attorney and hospital gastroenterologists was secured, and a formal proposal was submitted. The pharmacy department distributed a memorandum describing the advantages of famotidine, conducted inservice education sessions, and sought the compliance of physicians by placing reminders on order forms and patient charts and by contacting physicians directly. The program was implemented in May 1989. During the first three months, only one physician insisted that patients receive i.v. ranitidine rather than famotidine. It was projected that the interchange of i.v. famotidine for cimetidine or ranitidine would result in a total savings of $37,565 during the first year due to reductions in the cost of drugs, supplies, and nursing labor. The acceptance of a therapeutic interchange program for H2 antagonists was excellent, and the projected savings are substantial.

Cimetidine