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PubMed1981

Titration of integrated simian virus 40 DNA sequences, using highly radioactive, single-stranded DNA probes.

Nick-translated simian virus 40 (SV40) [32P]DNA fragments (greater than 2 X 10(8) cpm/micrograms) were resolved into early- and late-strand nucleic acid sequences by hybridization with asymmetric SV40 complementary RNA. Both single-stranded DNA fractions contained less than 0.5% self-complementary sequences; both included [32P]-DNA sequences that derived from all regions of the SV40 genome. In contrast to asymmetric SV40 complementary RNA, both single-stranded [32P]DNAs annealed to viral [3H]DNA at a rate characteristic of SV40 DNA reassociation. Kinetics of reassociation between the single-stranded [32P]DNAs indicated that the two fractions contain greater than 90% of the total nucleotide sequences comprising the SV40 genome. These preparations were used as hybridization probes to detect small amounts of viral DNA integrated into the chromosomes of Chinese hamster cells transformed by SV40. Under the conditions used for hybridization titrations in solution (i.e., 10- to 50-fold excess of radioactive probe), as little as 1 pg of integrated SV40 DNA sequence was assayed quantitatively. Among the transformed cells analyzed, three clones contained approximately one viral genome equivalent of SV40 DNA per diploid cell DNA complement; three other clones contained between 1.2 and 1.6 viral genome equivalents of SV40 DNA; and one clone contained somewhat more than two viral genome equivalents of SV40 DNA. Preliminary restriction endonuclease maps of the integrated SV40 DNAs indicated that four clones contained viral DNA sequences located at a single, clone-specific chromosomal site. In three clones, the SV40 DNA sequences were located at two distinct chromosomal sites.

Animals↗

PubMed1989

Development and characterization of an Fv-1-sensitive retrovirus-packaging system: single-hit titration kinetics observed in restrictive cells.

We have constructed an RNA-packaging-deficient mutant of N-tropic murine leukemia virus WN1802N by removal of 330 nucleotides located between the upstream long terminal repeat and the start of the gag gene region. Transfection into mink CCL64 cells produced a cell line capable of packaging retrovirus vectors into ecotropic, Fv-1 N-tropic virions. Using retrovirus vectors that confer resistance to the antibiotic G418, we demonstrated that the magnitude of restriction in BALB/3T3 and SIM.R cells (both Fv-1b/b) and in RFM/3T3 cells (Fv-1nr/nr) is approximately 100-fold compared with that in AKR or NIH 3T3 cells (both Fv-1n/n). Furthermore, titration kinetics were single hit in restrictive cells. Colonies of antibiotic-resistant cells recovered after infection of genotypically restrictive cultures were phenotypically restrictive when reinfected, ruling out selection of stably nonrestrictive subpopulations. These results suggest that the ability to infect some fraction of cells in a genotypically restrictive culture does not require specific abrogation and that multihit kinetics may not be an essential feature of Fv-1 restriction.

Animals↗

PubMed1972

Amniotomy and oral prostaglandin E 2 titration for induction of labour.

The efficacy of oral prostaglandin E(2) used on a titration basis in association with amniotomy for the induction of labour was investigated in a series of 50 patients. Induction was successful in 29 out of 32 primigravid and 17 out of 18 multigravid patients. The mean induction-delivery intervals in successful cases were 10(1/2) and 6 hours respectively. There were no significant effects on the fetuses.

Administration, Oral↗

PubMed1979

Self-titration by cigarette smokers.

An 11-week crossover study was carried out in which 12 subjects smoked high-nicotine (1.84 mg standard yield) and low-nicotine (0.6 mg) cigarettes after an initial period of smoking their usual brands with a medium-nicotine yield (mean 1.4 mg). Plasma and urine nicotine concentrations, carboxyhaemoglobin (COHb) concentration, puffing behaviour, 24-hour cigarette consumption, and butt nicotine content were measured. The changes in plasma nicotine and blood COHb concentrations showed that the smokers compensated for about two-thirds of the difference in standard yields when switched to either high- or low-nicotine cigarettes. Thus, compared with the medium-nicotine brand, the intake of nicotine and carbon monoxide was only about 10% higher when subjects smoked the high-nicotine cigarettes, which had a standard yield 30-40% higher than the medium brands; and only about 15% lower when they smoked the low-nicotine cigarettes, which had a standard yield about 50% lower than the medium brands. But nicotine content and urine nicotine concentrations followed a similar pattern. Changes in puffing behaviour and in 24-hour cigarette consumption were only slight.The results show clear evidence of both upward and downward self-titration of nicotine and carbon monoxide (and tar) intakes when smokers change to cigarettes with standard yields that differ over the range studied.

Adult↗

PubMed1983

Treatment of angina pectoris with nifedipine: importance of dose titration.

The effects of different doses of nifedipine on frequency of angina and objective measurements of myocardial ischaemia during exercise were studied in 10 patients with stable angina pectoris. In a single blind trial over nine weeks patients received one week's treatment each with placebo, nifedipine 10 mg, 20 mg, 30 mg, 40 mg, 30 mg, 20 mg, 10 mg, then placebo three times a day. The response to the different doses of nifedipine was highly variable. On exercising, three patients achieved a consistent improvement in workload attained before onset of ST segment depression and maximum ST depression during exercise testing during all active phases. Four patients improved with 10 mg three times a day but deteriorated at higher doses. In two patients there was no objective or subjective improvement with any dose of the drug, while in one patient anginal frequency increased and there was objective deterioration during exercise testing at doses above 10 mg three times a day. Thus a dose of nifedipine that is beneficial in one patient may have minimal or opposite effects in another. These results indicate the importance of careful titration of doses for individual patients if the maximum benefit from nifedipine is to be obtained in patients with exertional angina.

Adult↗

PubMed1997

Titrated intravenous opioids from the same syringe: an infection risk?

OBJECTIVE: (1) To compare the rate of contamination of syringes prepared under laminar flow conditions in pharmacy with those prepared by nurses in the emergency department; (2) to determine whether the time elapsed since preparation or number of doses given affected the contamination rate; (3) to determine whether any adverse effects resulted from bacterially contaminated drugs. METHODS: Prospective, blinded trial exploring the effect of method of preparation, time since preparation, and number of doses given on contamination rates and infective adverse events associated with bacterially contaminated specimens. RESULTS: The rate of bacterial contamination was 12% (95% confidence interval 6% to 18%). There was no difference in contamination rate in respect of method of preparation, number of doses given, or time since preparation. No infective complications were identified. CONCLUSIONS: Abandonment of titrated intravenous opioids is not justified by the results. However, there is concern about the use of this technique of pain control for immunocompromised patients and those with prosthetic heart valves.

Analgesia↗

PubMed1975

Prednisone for chronic active liver disease: dose titration, standard dose, and combination with azathioprine compared.

Among 120 consecutive patients with chronic active liver disease (CALD) randomized to different treatments, those receiving maintenance doses of prednisone 20 mg daily (Pred), prednisone in doses given on alternate days and titrated to secure resolution of clinical and biochemical abnormalities (Pred-Titrad), or a combination of prednisone 10 mg and azathioprine 50 mg daily (Comb) survived and underwent resolution of clinical and biochemical features of disease more often than a control group receiving placebo or azathioprine 100 mg daily. Histological remission occurred significantly more often with Pred and Comb than with other regimens. Major side-effects of therapy were commoner with Pred than with Comb or Pred-Titrad, which did not differ. We conclude that Comb is the initial treatment of choice for CALD, since clinical, biochemical, and histological resolution of disease activity occurs as often as with Pred, whereas early side-effects are significantly less frequent.

Adolescent↗

PubMed1983

Simultaneous measurement of gastric acid and duodenal alkali secretion by in situ titration in health and disease.

We have devised a technique for simultaneously measuring the acid secretion into the stomach and alkali into the duodenum by in situ titration using a modification of the technique of Fordtran and Walsh. Using this technique, the results of acid and alkali secretion measured simultaneously were identical with those obtained using the conventional aspiration method on separate days. In response to stimulation with pentagastrin acid output was 17.2 +/- 1.4 vs 15.4 +/- 1.9 mmol/h and alkali response with secretin was 16.0 +/- 0.8 vs 14.4 +/- 1.5 mmol/h. The response to food was measured in 10 control subjects, 10 patients with duodenal ulcer, and 10 patients with pancreatitis. In controls, the acid and alkaline secretion were similar (15.8 +/- 1.7 vs 18.2 +/- 1.3 mmol/h), in patients with duodenal ulcer acid secretion was significantly greater than alkaline secretion (31.9 +/- 2.2 vs 21.9 +/- 1.7 mmol/h), and in patients with pancreatitis the alkali secretion was significantly less than acid (19.8 +/- 1.9 mmol/h acid vs 11.4 +/- 0.6 mmol/h alkali). It can, therefore, be concluded that in response to food the patients with duodenal ulcer are significant hypersecretors of acid (DU acid greater than DU alkali output) and patients with pancreatitis are significant hyposecretors of alkali (pancreatitis-alkaline output less than acid output) and normal subjects secrete equal amounts of acid and alkali.

Alkalies↗

PubMed1966

Automatic technique for titration of influenza virus haemagglutination inhibitors.

An automatic method, utilizing the AutoAnalyzer, for titration of influenza virus haemagglutination inhibitors is described. The titres obtained compare favourably with those obtained by densitometric methods. So far, the technique has not proved superior to the densitometric methods in either speed of operation or in reproducibility but various developments are suggested to effect this.

Autoanalysis↗

PubMed1972

A comparison of the TRCII and latex-particle tests for the titration of FR-antigen.

The great convenience of a method using a suspension of antibody-coated latex particles for the titration of fibrinogen-related antigens over the tanned red cell haemaglutination immunoassay (TRCHII test) of Merskey, Lalezari, and Johnson (1969) has been demonstrated. The usefulness of Ca-Ancrod for the defibrination of heparinized plasma is presented here.

Animals↗

PubMed1986

Importance of anticomplement immunofluorescence antibody titration for diagnosing varicella-zoster virus infection in Bell's palsy.

Anticomplement Immunofluorescence was used for antibody titration against varicella-zoster virus (VZV) in 43 patients with peripheral facial palsy. Nine of 31 patients (29%) with Bell's palsy and eight of 12 patients (75%) with Ramsey-Hunt syndrome had anticomplement immunofluorescence antibody titres of greater than or equal to 1/10. On the other hand, none of 14 patients with herpes simplex virus (HSV) infection and 51 healthy adults showed anticomplement immunofluorescence antibody titres of greater than or equal to 1/10. The anticomplement immunofluorescence antibody titre in two patients with Ramsey-Hunt syndrome increased later and decreased sooner than the indirect immunofluorescence antibody titre, becoming undetectable at 66 and 104 days, respectively, after onset of the disease. There was no cross reaction between anti-VZV and anti-HSV antibodies in the patients who showed a positive antibody rise for VZV. As the acute stage of VZV infection is obscure in the patients with peripheral facial palsy without herpes the screening of anticomplement immunofluorescence antibody to VZV at titres greater than or equal to 1/10 may be useful for the diagnosis of VZV infection in patients with peripheral facial palsy.

Adult↗

PubMed1996

Titrated total intravenous anaesthesia (TIVA) in war.

In the Rama mobile war hospital, intravenous (i.v.) anaesthesia was used in 78 patients undergoing surgical procedures lasting 4-25 min. Boluses of thiopentone (Group 1), propofol (Group 2), propofol + alfentanyl (Group 3), and ketamine + midazolam (Group 4) were used. Induction of anaesthesia, resulted in a mean blood pressure decreased about 15%. Apnoea of more than 20 sec was observed in Group 3, but no naloxone was required. Recovery was rapid enabling patients to maintain their own airway. The use therefore of titrated anaesthetics in war is considered acceptable.

Adult↗

PubMed1990

Long-term suppression of severe recurrent genital herpes simplex infections with oral acyclovir: a dose-titration study.

Twenty immunocompetent patients, four females and 16 males, with severe recurrent genital herpes (median number of recurrences the previous year 16, range (8-24] entered an open continuous long-term suppressive treatment with oral acyclovir (ACV) for 12 months. The study included a dose-titration schedule: (ACV, 200 mg x 4/1-3 months, ACV, 400 mg x 2/4-6 months, ACV, 200 mg x 2/7-9 months, and ACV, 400 mg x 1/10-12 months). Patients with recurrences on steps two and three received an alternative dose of ACV, 200 mg x 3. Otherwise patients entered the previous dose-step. Five (20%) of patients were completely free of symptoms (recurrences and abortive lesions) during the four dose-reduction periods. A further nine patients (50%) could be dose-reduced to 200 mg x 3 without symptoms. Isolates from three patients showed a decrease in virus sensitivity after ceasing treatment. In conclusion, 14/20 of treated patients could be dose reduced to 200 mg x 2-3 without selection of HSV strains showing clinically important decreases in sensitivity towards ACV.

Acyclovir↗

PubMed1975

Titration study of guaiacol oxidation by horseradish peroxidase.

Titration of guaiacol by hydrogen peroxide in the presence of a catalytic amount of horseradish peroxidase shows that the reduction of hydrogen peroxide proceeds by the abstraction of two electrons from a guaiacol molecule. In the same way, it can be demonstrated that 0.5 mol of guaiacol can reduce, at low temperature, 1 mol of peroxidase compound I to compound II. Moreover, the reaction between equal amounts of compound I and guaiacol at low temperature produces the native enzyme. A reaction scheme is proposed which postulates that two electrons are transferred from guaiacol to compound I giving ferriperoxidase and oxidized guaiacol with the intermediary formation of compound II. The direct two-electron transfer from guaiacol to compound I without a dismutation of product free radicals must be considered as an exception to the general mechanism involving a single-electron transfer.

Electron Transport↗

PubMed1984

Effects of saline infusion on titratable acid generation and ammonia secretion.

Short-term hyperchloremic metabolic acidosis can decrease sodium reabsorption by the superficial proximal tubule (PT), increase tubular fluid flow rate, and stimulate aldosterone release. We studied the effects of increased tubular fluid delivery (graded saline infusion) and mineralocorticosteroid administration on tubular fluid pH (TFpH), titratable acid (TA) generation, and ammonium (NH+4) secretion by superficial proximal and distal tubules (DT) of acidotic, phosphate-loaded rats. The TFpH was 6.4 +/- 0.1 at the late proximal tubule (LP); it was unaltered at the early (ED) or late distal tubule (LD), but urine pH (UpH) was 1 unit lower. The major fraction of TA or NH+4 was formed in the superficial PT. There was no net TA generation by the superficial DT even during supplemental mineralocorticosteroid and increased Pi delivery during saline infusion. TA excretion was increased only slightly by saline infusion in acidotic rats despite increased buffer delivery (caused by decreased Pi reabsorption, primarily in the loop segment) because this was offset by a rise in UpH. Ammonia was secreted into tubular fluid in the superficial PT and DT; there was loss of NH+4 in the loop segment and addition after the LD. Saline infusion did not modify TFpH in the PT or DT but increased NH+4 secretion by the DT in direct proportion to tubular fluid flow. DOCA administration increased the addition of NH+4 between the LD and the urine. In conclusion 1) the superficial PT is of major importance for acidification, generation of TA, and secretion of NH+4 in short-term metabolic acidosis. 2) The superficial DT does not generate TA even during dramatically high rates of buffer delivery and mineralocorticosteroid administration. 3) Excretion of NH+4 is increased by saline infusion, which leads to flow-dependent NH+4 secretion by the superficial DT. 4) Chronic administration of DOCA stimulates NH+4 secretion predominantly in the terminal or deep nephrons.

Acidosis, Renal Tubular↗

PubMed1982

Instrumentation simultaneously measuring VCO2 and VO2 in humans using titration methods.

An instrument has been developed for the simultaneous measurement of carbon dioxide excretion (VCO2) and oxygen uptake (VO2). This instrument, the Nutrimeter, gives these breath-averaged measurements continuously without having to determine respiratory flow rate, perform timed spirometric gas collections, or determine absolute CO2 or O2 concentrations. It can be used on ventilated or nonventilated patients in long- and short-term studies. VO2 is determined via the replenishment technique. VCO2 is determined via a new technique, absorption-titration, described here. Bench test results of VCO2 measurements show a standard error of the estimate (SEE) +/- 0.591% of full scale (500 ml/min) and maximum single point error (MSPE) of +/- 3.54% over a 100--350 ml/min range. VO2 measurements show SEE +/- 0.518% of full scale (1,000 ml/min) and MSPE +/- 2.42% over a 100--450 ml/min range. In 31 human clinical trials the Nutrimeter was compared with the open-circuit spirometric collection and micro-Scholander analysis technique. VCO2 measurements show SEE +/- 2.208% and MSPE +/- 10.57% over 135--315 ml/min. VO2 measurements show SEE +/- 1.134% of full scale and MSPE +/- 9.54% over 170--360 ml/min. Response time is 60 s optimally for step changes in VO2 (0--90% of steady-state value), 90 s for VCO2.

Calorimetry↗

PubMed2004

Titration of hepatitis C virus in chimpanzees for determining the copy number required for transmission.

OBJECTIVE: To determine the copy number of hepatitis C virus (HCV) RNA, determined by nucleic acid amplification test (NAT) for screening blood units in Japan, that can transmit infection to chimpanzees. METHODS: Fresh-frozen plasma with markers of HCV infection, as well as inocula pedigreed from 1 of them, were evaluated for the infectious activity in chimpanzees. RESULTS: One unit each (273-282 ml) of fresh-frozen plasma from 2 blood donors or a pool from 13 donors to make a unit, which contained high-titered antibody to HCV but without HCV RNA detectable by NAT, did not infect any of 3 chimpanzees. Two chimpanzees were infected, however, when they were inoculated with 1 ml of serum from a blood donor in the 'window period' of HCV infection and containing 7.0 x 10(6) copies/ml of HCV RNA. The preacute phase serum from 1 of them harvested 7 weeks after the inoculation was titrated in 2 chimpanzees, and an inoculum containing approximately 2 x 10(1) copies of HCV RNA could transmit infection to both of them. CONCLUSION: Approximately 20 copies of HCV can transmit infection to recipients, which needs to be taken into consideration in planning the screening of blood units for HCV RNA by NAT. Although the sensitivity of present NAT could be improved further, there would be a limit of it in detecting a low-level HCV RNA in the window period of donors with the infectious capacity in recipients.

Animals↗

PubMed1988

Fractional reduction of somatostatin concentration interacted with rat growth hormone releasing hormone to titrate the magnitude of pulsatile growth hormone and prolactin release in perifusion.

Growth hormone (GH) pulses in vivo are associated with increased hypothalamic portal growth hormone releasing hormone (GH-RH) concentration and can be prevented by GH-RH antisera. GH pulses are also associated with prior reduction of portal somatostatin (SRIF) concentrations, although SRIF antisera do not abolish GH pulses. In vitro, pulses of GH-RH as well as SRIF withdrawal are followed by pulses of GH release; the presence of GH-RH enhances post-SRIF GH release. We asked four questions: (1) During combined GHRH-SRIF exposure in vitro, must SRIF withdrawal be complete to produce a pulse of GH release, or is there a threshold diminution of SRIF which permits it? (2) When pulsatile GH release does occur, is it an all-or-none phenomenon, or is it titratable by fractional reduction of SRIF? (3) Does varying the GH-RH concentration while administering SRIF systematically alter GH release in response to fractional SRIF reduction? (4) Given a small but distinct effect of GH-RH on release of stored prolactin (PRL) in this system, does fractional SRIF reduction alter PRL release in parallel? Rat pituitary tissue whose hormone stores had been prelabeled with tritium was perifused for 120 min in combined 25 nM SRIF and 3 or 10 nM rat GH-RH (rGH-RH). Then, while maintaining rGH-RH concentrations, the SRIF concentration was left unchanged (control) or was reduced to 20, 15, 10, 5, or 0 nM for 60 min. Release of stored rGH and rPRL was assessed by immunoprecipitation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗