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Biomedical subjects

R M Rosenberg

Publications and source records attributed to R M Rosenberg.

15 recordsLinked to original sources
PubMed1990

Multicentre, double-blind comparison of terfenadine and cetirizine in patients with seasonal allergic rhinitis.

This double-blind, multicentre study was designed to compare the efficacy and tolerability of terfenadine 120 mg with cetirizine 10 mg, each taken once daily, in the treatment of seasonal allergic rhinitis. Two hundred and eighty-five patients were recruited to the study by nine general practice centres in the south of England during the 1989 hay-fever season. Symptom severity was assessed daily by the patient and before and after the one-week treatment period by the investigator. At the second clinic visit both patient and investigator assessed the overall response to treatment. The two treatment groups were well matched for all demographic variables and baseline symptom scores. Improvement in all seven symptoms (nasal congestion, sneezing, rhinorrhoea, itching nose, itching eyes, watery eyes and red eyes) and overall response to treatment were similar in both treatment groups. Adverse events were mainly of mild to moderate severity and were reported by 14 patients on terfenadine and 21 patients treated with cetirizine (p = 0.317). This study confirmed terfenadine's role as the treatment of choice in hayfever. A single 120 mg dose in the morning effectively reduced symptoms by 43 to 70 per cent of baseline values, with an acceptably low incidence of side effects. Cetirizine at a single dose of 10 mg displayed equal efficacy in controlling hayfever symptoms but, in common with other studies, had a significantly greater incidence of drowsiness (p = 0.046).

Adult↗
PubMed1990

Treatment of seasonal allergic rhinitis: a comparison of a combination tablet of terfenadine and pseudoephedrine with the individual ingredients.

This single-centre, double-blind, parallel randomised study of one week's duration compared terfenadine 40 mg, pseudoephedrine 60 mg and a combination of the two (40 mg/60 mg) given three times a day in the management of hayfever. Of 88 known hayfever sufferers recruited during the 1988 season 86 were evaluable for efficacy. Demographic data were similar, but some significant differences in baseline symptom values made direct comparison of post-treatment scores difficult to interpret. Nevertheless, comparisons of improvements from baseline show that all three treatments provide good control of the individual seven symptoms (nasal block, sneezing, runny nose, itchy nose, watery eyes, red eyes, itchy eyes). Terfenadine provided a statistically greater improvement in mean total symptom score than pseudoephedrine alone. Overall assessments favoured terfenadine and the combination, and rhinoscopy examination showed a trend in favour of terfenadine alone. Adverse events were recorded more frequently in the combination group: 45% of patients versus 21% in the terfenadine group and 26% in the pseudoephedrine group. In this group of patients, terfenadine, pseudoephedrine or a combination provide good relief of hayfever symptoms, including nasal block, with terfenadine and the combination being preferred to pseudoephedrine in the treatment of this condition. However, the combination can be expected to cause a greater incidence of side-effects.

Adolescent↗
PubMed1990

A comparative study of terfenadine at two dose levels in the management of hayfever.

One hundred and twenty patients with hayfever were enrolled in a single-centre, double-blind crossover study designed to compare the efficacy and safety of terfenadine at doses of 60 mg bd and 120 mg bd. A two-week placebo run-in period was followed by the two treatment periods, each lasting two weeks. Assessments of hayfever symptoms were made daily by patients and at each clinic visit by the investigator. Adverse events were recorded at the end of each treatment period. At the end of the study both investigator and patient rated the overall efficacy and the patient recorded treatment preference. The data were examined by analysis of variance (ANOVA) for treatment, period and crossover effects. Pollen counts were recorded for the duration of the study. Seventy-four patients completed the study, the majority of withdrawals occurring during the placebo phase. There was no significant difference in symptom relief between the two doses of terfenadine. The number of adverse events, including drowsiness, was similar for the two treatments and for placebo. Mean and peak pollen counts both correlated well with symptom severity. These data show that terfenadine 60 mg bd is an adequate dose for the treatment of hayfever symptoms.

Adult↗
PubMed1989

Indicator assay for amino acid decarboxylases.

Indicator assays have been devised for glutamate decarboxylase and arginine decarboxylase as models for a general procedure for amino acid decarboxylases. Since the decarboxylation results in the absorption of a proton in the pH range of maximum enzymatic activity, the change in absorbance of an acid-base indicator can be used to follow the progress of the reaction. For glutamate decarboxylase, the substrate was used as the buffer, and 1-1'-diethyl-2-2'-cyanine iodide was used as the indicator. For arginine decarboxylase, acetate was used as the buffer, and bromcresol green was used as the indicator. The change in absorption with extent of reaction is linear if the indicator pK is equal to the buffer pK.

Acid-Base Equilibrium↗
PubMed1989

Triiodothyronine alters the cornification of cultured human keratinocytes.

Scaly skin occurs in 80-90% of patients who are hypothyroid, the pathogenesis of which is unknown. Since thyroid hormone (T3) affects growth and differentiation in other organs, we examined the effects of its absence on keratinocytes in vitro. Human neonatal foreskin keratinocytes were cultivated and second passage cells were switched to T3-depleted (-T3) medium at 50% confluence. Cells maintained in the -T3 medium demonstrated increased (1.5 fold) levels of the cross-linking enzyme transglutaminase and increased (1.5 fold) formation of cornified envelopes, when compared to keratinocytes maintained in medium containing physiologic levels (2 X 10(-9)M) of T3. Additionally, in the -T3 cultures, the level of the protease plasminogen activator (PA), an enzyme implicated in the process of shedding of cornified cells, was decreased 70-80% of that measured in +T3 media. Absence of T3 from keratinocyte culture-medium increased both the level of the enzyme responsible for cross-linking cornified envelope precursors and the rate of envelope formation in cultured cells. The decreased levels of PA observed in the -T3 cultures could result in decreased shedding of cornified cells. These alterations in the process of keratinocyte differentiation may explain the clinically observed scaliness associated with hypothyroidism in humans. The molecular mechanism by which T3 alters keratinocyte cornification is not yet known.

Cell Differentiation↗
PubMed1986

Abnormal lipogenesis in thyroid hormone-deficient epidermis.

Striking skin changes can accompany hypothyroidism, among them a scaly ichthyosis. The pathogenesis of these disorders is unknown. Since altered sterol metabolism has been associated with other scaling dermatoses, we tested the hypothesis that altered epidermal lipogenesis may accompany hypothyroidism and induce the observed scaling. Thyroidectomized (TX) rats were sacrificed 53 days postthyroidectomy, and the rate of incorporation of the radiolabeled precursor, [14C]acetate, into epidermal lipids was determined. Approximately 2-fold decreases in incorporation of precursor into both polar and neutral lipids were observed in the TX epidermis; the most significant decreases, however, were in the neutral lipids, particularly the sterol and sterol-ester moieties. Total cholesterol pool size was also reduced in the TX epidermis. Similar decreases in sterol biosynthesis were noted in human keratinocytes cultivated in medium devoid of thyroid hormone. These findings demonstrate that lipid metabolism, and notably sterol synthesis, is altered in epidermal keratinocytes deprived of thyroid hormone, and suggest that, as in other scaling disorders, this abnormal sterologenesis may lead to the clinically observed ichthyosis that can accompany hypothyroidism.

Animals↗
PubMed1985

Aspartate beta-decarboxylase from Alcaligenes faecalis: carbon-13 kinetic isotope effect and deuterium exchange experiments.

We have measured the 13C kinetic isotope effect at pH 4.0, 5.0, 6.0, and 6.5 and in D2O at pD 5.0 and the rate of D-H exchange of the alpha and beta protons of aspartic acid in D2O at pD 5.0 for the reaction catalyzed by the enzyme aspartate beta-decarboxylase from Alcaligenes faecalis. The 13C kinetic isotope effect, with a value of 1.0099 +/- 0.0002 at pH 5.0, is less than the intrinsic isotope effect for the decarboxylation step, indicating that the decarboxylation step is not entirely rate limiting. We have been able to estimate probable values of the relative free energies of the transition states of the enzymatic reaction up to and including the decarboxylation step from the 13C kinetic isotope effect and the rate of D-H exchange of alpha-H. The pH dependence of the kinetic isotope effect reflects the pKa of the pyridine nitrogen of the coenzyme pyridoxal 5'-phosphate but not that of the imine nitrogen. A mechanism is proposed for the exchange of aspartate beta-H that is consistent with the stereochemistry suggested earlier.

Alcaligenes↗
PubMed1975

A mechanism for the electrocardiogram response to left ventricular hypertrophy and acute ischemia.

A proposed mechanism for explaining the electrocardiographic response in left ventricular hypertrophy and in subendocardial and epicardial acute ischemia was incorporated in a mathematical model of electrical heart activity. The model of hypertrophy was simply an increase in cell size, and the principal effect on the computer-generated 12-lead electrocardiograms (ECGs) was an increase in R-wave amplitude and ventricular activation time and a flattening or polarity reversal of the T wave. The model of acute ischemia was a reduction between plateau and resting potential of the transmembrane action potential. The principal effect on the computer-generated 12-lead ECGs was an S-T segment displacement up or down depending on the location of the lesion. This shift was linearly proportional to the severity of the ischemia, i.e., the reduction in electrical activity of the ischemic cell, and for a lesion of given severity the S-T segment shift was a measure of the area, not the volume, of ischemic tissue. Therefore, this model suggests that a direct correlation does not necessarily exist between volume-measuring tests such as serum enzyme values in the case of necrosis and S-T segment shifts.

Computers↗
PubMed1975

Stimulation of pathologic electrocardiograms: the role of Durrer layers in the normal, the hypertrophied and the ischemic heart.

A mechanism is described which explains the electrocardiographic manifestations of cellular hypertrophy and acute ischemia. This mechanism arises from neighboring cells having different transmembrane action potentials, and it has been called the "contiguity effect". The contiguity effect of adjacent "Durrer layers" (defined in the paper) gives rise to the T-wave distortions in hypertrophy and is also responsible for the polarity of the normal T-wave. This mechanism has been incorporated in a computer model of electrical heart activity which generates high fidelity 12-lead electrocardiograms. It is shown that the increase in R-wave amplitude and in ventricular activation time, and the flattening and/or polarity reversal of the T-wave in hypertrophy is due to an increase in the size of myocardial cells, and the S-T segment shift in acute ischemia is produced by the contiguity effect between normal and ischemic cells. For a lesion of given size, the S-T segment shift is linearly proportional to the "severity"; i.e., the reduction in electrical activity, of ischemic cells, and fora lesion of given severity, the S-T segment shift is a measure of the area, not the volume, of ischemic tissue. Therefore, a direct correlation does not necessarily exist between volume measuring tests (such as serum enzyme values in the case of necrosis) and S-T segment shifts in acute ischemia.

Cardiomegaly↗
PubMed1968

Proton magnetic resonance of proteins fully deuterated except for 1H-leucine side chains.

The fully deuterated proteins C-phycocyanin, C-phycoerythrin, and cytochrome c have been obtained by biosynthesis with the leucine side chains, and only the leucine side chains, of normal ((1)H) isotopic composition. In these (isotopic hybrid) proteins, proton magnetic resonance analysis shows that the (1)H-leucine side chains are in a variety of environments. During protein biosynthesis, the alpha hydrogen of leucine is exchanged with a hydrogen ((2)H) from the aqueous medium.

Cytochromes↗