Biomedical subjects

K Karpinski

Publications and source records attributed to K Karpinski.

At least 19 recordsLinked to original sources

PubMed1995

Toxicodynamics and toxicokinetics of amikacin in the guinea pig cochlea.

An extensive overview of the relationship between cochlear toxicity and amikacin blood concentrations in the guinea pig is provided which should assist in the clinical application of this class of antibiotic. A data set previously used to relate the incidence of amikacin ototoxicity to dosing rates and blood concentrations was re-examined to assess the toxicodynamics of amikacin in terms of decibels of hearing loss across dosing rate, hearing frequency and time following drug exposure. Animals in this data set had received continuously i.v. infused amikacin over an 8-fold range of dosing rates. Preliminary analysis indicated that the data were consistent with a sigmoid relationship between hearing loss (decibels) and area under the amikacin plasma concentration vs time curve cumulated over the entire course of drug administration (cAUC). The sigmoid model was therefore used as the backbone of a far more comprehensive toxicodynamic model which described all the data with a single equation. Testing with this model showed that the cAUC required to produce half-maximum hearing loss (cAUC-1/2) was related to dosing rate (P < 0.01), to hearing frequency (P < 0.00001), and to post-drug interval (P < 0.00001). Maximum hearing loss (difference between upper and lower sigmoid asymptotes) was less than total and was significantly related to frequency (P < 0.00001). No effects could be detected on the sigmoid slope. Further modelling of the significant effects detected by the comprehensive toxicodynamic model was done to determine if they could be described by simple relationships or by biologically relevant sub-models. Modelling of maximum hearing loss (postulated to represent loss of mainly outer hair cell function) indicated that this parameter was constant at about 61 decibels for 2-12 kHz and linearly decreased with log frequency for frequencies > 12 kHz. Modelling of cAUC-1/2 on frequency indicated that there was a strong inverse linear relationship to log frequency. Modelling of cAUC-1/2 on post-drug interval indicated that delayed ototoxicity continued at progressively slower rates for at least 56 days after drug administration had ceased. Modelling of cAUC-1/2 on dosing rate showed an increased requirement for drug as the dosing rate decreased. However, cAUC-1/2 changed no more than 20% across the range of dosing rates compared to the 8-fold difference in mean steady-state plasma concentrations, suggesting that plasma concentration is not a primary determinant of ototoxicity. A toxicokinetic model was developed which explained the dosing rate effect on cAUC-1/2 very successfully.(ABSTRACT TRUNCATED AT 400 WORDS)

Amikacin↗

PubMed1993

Toxicological consequences of Aroclor 1254 ingestion by female rhesus (Macaca mulatta) monkeys. Part 1A. Prebreeding phase: clinical health findings.

A group of 80 menstruating rhesus (Macaca mulatta) monkeys, with an average estimated age of 11.1 +/- 4.1 yr SD, were first randomly allocated to four similar test rooms (20 monkeys/room) and then randomly allocated to one of the five dose groups (four females/dose group/room). Each day, the females self-ingested capsules containing doses of 0, 5, 20, 40 or 80 micrograms Aroclor 1254/kg body weight. After 25 months of daily dosing, approximately 90% of the treated females attained a qualitative pharmacokinetic steady state with respect to the concentration of polychlorinated biphenyl in their adipose tissue. The test monkeys were monitored daily for health and menstrual status, as well as feed and water consumption. On a weekly basis, each female's body weight was determined and a detailed clinical examination was conducted. Minor treatment effects included a slight, but not statistically significant, decrease in feed and water consumption as well as a decreased feed conversion ratio and a slight increase in the duration of menses. Statistically significant, dose-related treatment effects included inflammation and/or prominence of the tarsal (Meibomian) glands, eye exudate, and various finger and toe nail changes. These results were found at doses lower than those previously reported for non-human primates.

Animal Feed↗

PubMed1993

Toxicological consequences of Aroclor 1254 ingestion by female rhesus (Macaca mulatta) monkeys. Part 1B. Prebreeding phase: clinical and analytical laboratory findings.

A group of 80 menstruating rhesus (Macaca mulatta) monkeys, with an average estimated age of 11.1 +/- 4.1 yr SD were first randomly allocated to four similar test rooms (20 monkeys/room), and then randomly allocated to one of five dose groups (four females/dose group/room). Each day, the monkeys self-ingested capsules containing doses of 0, 5, 20, 40 or 80 micrograms Aroclor 1254/kg body weight. After 25 months of daily dosing, approximately 90% of the treated females attained a qualitative pharmacokinetic steady state with respect to the concentration of polychlorinated biphenyl (PCB) in their adipose tissue. Subsequently, oestrogen and progesterone concentrations in serum were determined for one complete oestrous cycle and various immunological tests were conducted, while the monkeys continued to receive their daily dose of PCB. During the prebreeding phase of the study, blood for clinical and analytical monitoring including haematology, serum biochemistry, serum hydrocortisone, serum proteins (alpha 1, alpha 2, beta and gamma-globulins), serum immunoglobulins (A, G and M) and thyroid variables (thyroxine/triiodothyronine (T3) uptake ratio, percentage T3 uptake and free thyroxine index), were obtained monthly, as were specimens to ascertain the concentration of PCB in the blood, adipose tissue and faeces. Major findings among treated monkeys included the following: changes in haematology (decreased erythrocyte count, haematocrit, reticulocyte count, and mean platelet volume), serum biochemistry (decreased cholesterol and total bilirubin), immunotoxicity (decreased antibody production to sheep red blood cells and alterations in the percentage of T helper and T suppressor cells) and pathology (the number of regions of sebaceous gland lobules per unit of histological length was significantly reduced). These effects were observed at PCB doses lower than those previously reported for non-human primates.

Adipose Tissue↗

PubMed1992

Genetic characterization of Sabin types 1 and 3 poliovaccine virus following serial passage in the human intestinal tract.

Poliovirus isolates types 1 and 3 were obtained from five and seven successive passages respectively, in infants who had been fed monovalent OPV in two separate clinical trials conducted in 1960. The purpose of these trials was to answer the question how much the vaccine virus would revert to its original neurovirulent phenotype following multiplication in the intestinal tract. Human passages were performed either by contact exposure or by feeding the excreted virus while the infants were maintained in isolation. Several virus isolates were obtained at each passage level. Infants participating in both studies showed no symptoms of disease. Antigenic studies (McBride, van Wezel) and protein analysis (PAGE) of the isolates, reported earlier from this laboratory, had shown that the isolates remained vaccine-like, although isolates from the later passages revealed some differences. Monkey neurovirulence test results showed that for both types 1 and 3 viruses the loss of attenuation of the vaccine strain upon passage was gradual, although the loss was faster for type 3. Examination of the oligonucleotide maps demonstrated that the oligonucleotide configuration of the isolates remained the same as for the vaccine strain but there was an increase of individual spot differences with increasing passage. The nucleotide sequence analysis of selected regions of the virus genomes revealed that there was no change from a G to A in nucleotide 480 of type 1 isolates; however, nucleotide 476 changed from a U to an A in type 1 passages 3, 4 and 5. Conversely, for type 3 the change of nucleotide 472 from a U to a C changed at the early first passage (4 days following administration of OPV), and remained a C in the six following passages; type 3 nucleotide 2034 did not change in the first passage from a U to a C, but it became a C in all further passages tested. The nucleotide changes mentioned for both virus types remained stable in successive passages. However, there was another nucleotide change for type 3 from a U to a C at position 1973 only for passages 5 and 6 which reverted to a U for passages 7L and 7LL. Study of selected human passage virus strains could further contribute to the identification of the critical nucleotides that are responsible for the attenuation of these two polio types of vaccine viruses.

Base Sequence↗

PubMed1991

Disposition kinetics and dosage regimen of vitamin E administered intramuscularly to sheep.

Three experiments were conducted to estimate the effects of single intramuscular (IM) administrations of vitamin E on blood plasma and tissue concentrations of alpha-tocopherol in sheep. In Expt 1, plasma kinetics of alpha-tocopherol in sheep (n 30) were investigated following IM administration of three doses (ten sheep/dose) of DL-alpha-tocopheryl acetate, (20, 40 and 60 mg/kg live weight). Plasma profiles of alpha-tocopherol consisted of a lag phase followed by an apparent first-order absorption and elimination phase. The rate of absorption and elimination, as well as the lag phase, were independent of the dose, but the extent of absorption was directly proportional to dose. In Expt 2 (eighteen experimental and five control sheep), the animals were injected as in Expt 1 and were killed at 0, 80 and 176 h. Increases in alpha-tocopherol levels in organs were much higher than in plasma. Some tissues such as liver, spleen, lung and adrenal appeared to exhibit rapid absorption and elimination phases. The amount absorbed was proportional to the dose administered. Other organs such as heart, kidney and pancreas had a slow elimination rate. In Expt 3, D-alpha-tocopherol was injected IM into ten sheep at either 604 mg or 1208 mg. The mean hepatic alpha-tocopherol concentrations in both groups rose rapidly and after 4 weeks of dosing its concentrations were higher than the predosing levels. The increase in hepatic tocopherol concentrations were higher following 1208 mg dosing than 604 mg D-alpha-tocopherol. No simple relationship existed between plasma and hepatic alpha-tocopherol concentrations. This suggests a difference in body mechanisms controlling vitamin E in blood and liver.

Animals↗

PubMed1991

Bioavailability of vitamin E in sheep administered intramuscularly with D-alpha-tocopherol.

Two groups of five wethers each (40-50 kg body weight) were used. All were dosed intramuscularly (gluteus) with D-alpha-tocopherol. Five randomly selected sheep received a dose of 900 IU while the other five received 1800 IU. Doses were administered at 0, 6 and 14 days and at 7 day intervals for an additional 6 weeks. Plasma and liver samples were taken at various times. Single exponential equations provided good characterization of the multiple dose trough D-alpha-tocopherol concentrations in plasma and liver. There was a significant dose-response relationship for maximum concentration, area under the plasma curve and levels of hepatic alpha-tocopherol. These levels were proportional to the D-alpha-tocopherol dose given.

Animals↗

PubMed1991

Quantitation of serum immunoglobulins G, M, and A in the rhesus monkey (M. mulatta) using human monospecific antisera in the enzyme-linked immunosorbent assay: developmental aspects.

Using human monospecific antisera, several parameters have been optimized for the micro-ELISA "sandwich" technique used in the quantitative measurement of total serum IgG, IgM and IgA levels in rhesus monkeys. Representation of the optical density as a four-parameter logistic function provided excellent fits of the data over a wide choice of dilutions of human antisera used for coating the ELISA plates and for the peroxidase-conjugated antisera used in the system. The micro-ELISA "sandwich" technique was shown to be specific, reliable, sensitive, and economical for use in the routine measurement of total serum IgG, IgM and IgA levels in the rhesus monkey.

Animals↗

PubMed1990

Effect of fenoldopam in dogs with spontaneous renal insufficiency.

Fenoldopam administration orally or i.v. resulted in significant increases in paraaminohippuric acid (PAH) clearance in both four control dogs and four dogs with chronic renal failure. Oral fenoldopam resulted in significant plasma levels of fenoldopam sulfate metabolites. One metabolite, fenoldopam-8-sulfate, a potential inhibitor of organic anion transport, did not depress renal cortical slice accumulation of PAH. The data therefore indicate that in dogs with chronic renal failure, PAH clearance after fenoldopam administration is a reliable measure of renal plasma flow, and fenoldopam can result in an increase in renal plasma flow.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1990

A pilot study on the effects of Aroclor 1254 ingestion by rhesus and cynomolgus monkeys as a model for human ingestion of PCBs.

A pilot study using female cynomolgus (Macaca fascicularis) and female rhesus (Macaca mulatta) monkeys was conducted to study the effects of chronic ingestion of polychlorinated biphenyls (PCBs). Four control and four treated monkeys of each species received an apple juice-gelatin mixture containing 0 and 280 micrograms Aroclor 1254/kg body weight/day, respectively, 5 days/wk. The cynomolgus monkeys, which were mature monkeys with a poor breeding history, were treated for approximately 55 wk, while the rhesus monkeys, which were just attaining sexual maturity, were treated for approximately 120 wk. After 38 wk on test, the treated and control rhesus monkeys were mated with untreated males. The clinical signs resulting from the Aroclor 1254 ingestion were similar for both species, and the time of onset after initiation of treatment was not appreciably different between the two species. Several treatment and interspecies differences were found with regard to the haematological and serum biochemistry parameters monitored, but age differences between the two species may have contributed to these findings. Periodic analysis of adipose tissue, blood and faecal specimens for PCBs suggested that the rhesus monkey retained more of the ingested PCB than did the cynomolgus monkey. Following mating, all of the treated rhesus monkeys aborted within 30-60 days after becoming pregnant, while all of the control monkeys had viable offspring.

Abortion, Spontaneous↗

PubMed1990

Monitoring vitamin E pools in sheep tissue and plasma after intravenous dosing of radiotocopherol.

The fate of radiotocopherol was studied in plasma and tissues of sheep at various intervals after injection of single intravenous doses of 3H-labelled D-alpha-tocopherol. Plasma samples were taken at regular intervals after dosing and selected tissues were taken from all sheep after slaughter and assayed for radioactivity and D-alpha-tocopherol. Sheep were killed in groups of five at 24, 72, 96, 272 and 432 h post-dosing. Plasma profiles were characterized as a sum of three exponential terms. A principal component analysis of tissue concentrations was carried out to identify tissues with parallel profiles of log (disintegrations/min per microgram) over time. Five groups of tissues with distinct uptake and elimination processes were identified. The D-alpha-tocopherol in the liver and heart appeared to be consistent with the post-distributive kinetics of a highly perfused shallow compartment, while lung kinetics appeared to reflect a non-linear kinetic process. The third group, which included the spleen, neck brachiocephalicus muscle and pancreas, had depletion rates parallel to those of plasma for 24-272 h, but slower decreases than plasma over 272-432 h. Hip gluteus muscle and kidney comprised a fourth group, with depletion parallel to plasma rates for 24-96 h but progressively slower than plasma decreases over 96-272 h. Adrenal kinetics resembled the fourth group, but had a more rapid decrease in specific activities over 24-72 h.

Animals↗

PubMed1990

Pharmacology of SK&F R-105058 and R-106114, N-ethyl carbamate ester prodrugs of fenoldopam.

The pharmacology of SK&F R-105058 and SK&F R-106114, N-ethyl carbamate ester prodrugs of fenoldopam, was evaluated in pentobarbital-anesthetized dogs. The selective dopamine 1 (DA1) antagonist, SCH 23390, significantly attenuated the renal vasodilator effects of SK&F R-82526, the active enantiomer of fenoldopam. This dose of SCH 23390 also significantly attenuated the increase in renal blood flow and decrease in renal vascular resistance induced by the administration of either SK&F R-106114 or SK&F R-105058. The cholinesterase inhibitor, physostigmine, at a dose that significantly enhanced the renal effects of acetylcholine, did not alter the in vivo renal vasodilator effects of SK&F R-105058 or prevent conversion of SK&F R-105058 to fenoldopam. Thus, these data indicate that the renal vasodilator activity of fenoldopam prodrugs involves activation of DA1 receptors and that, unlike other carbamate ester prodrugs, conversion to the parent compound is unlikely to involve cholinesterase.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1990

Identification of fenoldopam prodrugs with prolonged renal vasodilator activity.

Fenoldopam (SK&F 82526) is a short-acting selective dopamine-1 agonist in clinical trials for the treatment of hypertension, congestive heart failure and renal failure. In the present study, we tested various N-ethyl carbamate esters of fenoldopam in the conscious dog instrumented with a femoral arterial Vascular-Access-Port and a renal artery flow probe. Oral administration of SK&F R-82526 at 1 and 3 mumol/kg resulted in transient (30-60 min) dose-dependent increases in plasma fenoldopam levels and renal blood flow. Administration of the 7,8-bis-N-ethyl carbamate ester of R-fenoldopam (SK&F R-106114) and the 4',7,8-tris-N-ethyl carbamate ester of R-fenoldopam (SK&F R-105058) at 1, 3 and 10 mumol/kg p.o. also resulted in dose-dependent increases in plasma fenoldopam levels and renal blood flow; however, both parameters remained elevated for at least 4 hr. Intravenous administration of SK&F R-105058 also resulted in sustained plasma fenoldopam levels and increases in renal blood flow, indicating that slow absorption was not the cause of the sustained effect. The present study indicates that N-ethyl carbamate esters of fenoldopam are fenoldopam prodrugs which result in sustained increases in renal blood flow and plasma fenoldopam levels.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1989

Short-term effects of butylated hydroxytoluene on the Wistar rat liver, urinary bladder and thyroid gland.

Long-term feeding of butylated hydroxytoluene (BHT) to rats and mice has been linked to the enhancement of the incidence of liver tumors. It is shown in this paper that in the liver, urinary bladder and thyroid of the male Wistar rat, feeding the highest tolerated doses of BHT for 30 days does not lead to detectable increases in [3H]thymidine labeling. On the other hand, treatment of rats with 0.5% dietary BHT leads to a time-limited increase in liver cell [3H]thymidine labeling that subsided to control values within 8 days. This increase in [3H]thymidine labeling in the liver is accompanied by an unexpectedly large increase in the mitotic index. These results are discussed in the light of the behavior of certain rodent liver tumorigens.

Animals↗

PubMed1989

The effect of long-term feeding of Aroclor 1254 to female rhesus monkeys on their polychlorinated biphenyl tissue levels.

The result of feeding Aroclor 1254 to female Rhesus monkeys at doses of 0, 5, 20, 40 and 80 micrograms/kg body weight/day for a period of 37 months was measured in terms of polychlorinated biphenyl (PCB) levels in blood, adipose tissue, and feces. PCB concentrations in whole blood increased more rapidly during the first 10 months of the study than in the remaining 27 months for all dose groups. On a blood-lipid basis, however, another rapid increase in PCB levels was observed after 27 months of dosing, which could not be explained on the basis of an overall decrease in blood-lipid levels. Concentrations in adipose tissue and adipose fat increased continuously during the 37 months of dosing. These observations were reflected in the ratio profiles of PCB levels in blood/PCB levels in adipose tissue, which remained relatively static between the 2nd and 27th month of continuous feeding. Expressing the data in terms of relative concentrations (concentration/dose) suggests that bio-accumulation or retention of PCBs may be dose-dependent, particularly for adipose tissue, with the higher relative concentrations of the lowest dose group significantly (p less than 0.001) different from all other dose groups. Similarly, the limited feces data available suggests a dose-dependent PCB absorption. The distribution of PCB peaks in the gas chromatographic elution pattern of all analyzed substrates showed considerable deviation from that of administered Aroclor 1254. Only minor changes in the percent distribution pattern were observed between dose groups.

Adipose Tissue↗

PubMed1989

Providing vitamin D to confined sheep by oral supplementation vs ultraviolet irradiation.

Serial vitamin D3 (D3) and 25-hydroxyvitamin D3 (25 OH D3) concentrations of plasma were measured in confined, shorn sheep that had either been supplemented with vitamin D3 (50 micrograms/d) or exposed daily to ultraviolet irradiation (UVI). In the sheep administered D3 orally, plasma D3 increased continuously until d 35. This was followed by small fluctuations of the plasma D3 concentrations until a plateau was reached after 56 d of supplementation (.94 ng/ml plasma). Plasma 25 OH D3 concentrations increased continuously and plateaued between d 65 to 75 at about 21 ng/ml plasma. In the UVI sheep, plasma D3 and 25 OH D3 concentrations increased continuously for the first 49 d, then plateaued at 2.03 ng D3 and 29.6 ng 25 OH D3/ml. When a plateau was reached in plasma 25 OH D3 concentrations in both treatment groups, a 3H-labeled tracer dose of 25 OH D3 was given i.v., and disappearance of the 3H-labeled 25 OH D3 was followed. The UVI group had a faster decline in specific activities during the first exponential phase but a slower decline during the prolonged terminal elimination phase. These differences are reflected in the intercompartmental transfer rates. Our data indicate that UVI is as effective as oral vitamin D3 supplementation for improving vitamin D status of confined sheep.

Animals↗

PubMed1988

A carcinogenesis reversibility study of the effects of butylated hydroxyanisole on the forestomach and urinary bladder in male Fischer 344 rats.

A reversibility study was initiated to determine if the length of feeding with 2% butylated hydroxyanisole (BHA) altered the incidence of forestomach lesions observed after a 24-month observation period. Groups of male Fischer 344 rats were fed 2% BHA for 0, 3, 6, 12, and 24 months and then the basal diet for the completion of the 24-month experimental period. Subgroups were serially sacrificed for histopathological examination and [methyl-3H]thymidine radioautography at the time when each group of animals was transferred to the basal diet and also at 15 months. The results showed that except for carcinomas and some epithelial downgrowths, cellular proliferation, measured by radioautography in the epithelium lining the greater and the lesser curvature of the forestomach, remained dependent on the continuous presence of 2% BHA for, at least, 12 months. Superficial hyperplasias, inflammatory lesions and many of the papillomas regressed after cessation of treatment at 12 months. The epithelial downgrowths did not appear to enlarge after the BHA was withdrawn. The squamous cell carcinomas occurred in almost identical yields whether the rats were fed 2% BHA for 12 months and then returned to the basal diet for 12 months or received 2% BHA continuously for 24 months. It is shown here that at several times, 2% BHA stimulated the [methyl-3H]thymidine labelling index of the transitional epithelium of the urinary bladder and that at 3 months the no observed effect level was greater than 0.5% BHA. The significance of the studies on the forestomach and bladder epithelia are discussed. It is concluded that the lesions induced by BHA are most unlikely to be relevant to humans exposed to much lower levels of BHA.

Administration, Oral↗

PubMed1988

Experience in Canada with the new revised monkey neurovirulence test for oral poliovirus vaccine.

Nine years of experience in our laboratory, using more than 1500 cynomolgus monkeys in 138 tests, has shown that the new neurovirulence test (NVT) adopted by the World Health Organization (WHO) for live, oral monovalent vaccine of each poliovirus type, was a reproducible and sensitive assay likely to ensure the safety of this vaccine in humans. Our findings were the following: (1) when the test vaccine and the appropriate homotypic reference vaccine were tested in a single group of monkeys, the concurrent use of the reference vaccine considerably increased the reproducibility of the NVT; (2) in the assessment of the degree of attenuation of each lot of vaccine, the use of 12 monkeys for types 1 and 2 vaccines and 20 monkeys for type 3 vaccine (inoculated intraspinally each for reference and test vaccine) was satisfactory; (3) the virus dose used per monkey (10(5.6) to 10(6.6) pfu per monkey) was found not to be critical, i.e. the lower virus dose yielded mean lesion scores in the central nervous system of monkeys at least as high or higher than the tenfold higher virus dose; (4) the statistical analysis of our data showed that the old intrathalamic (IT) assay was considerably less sensitive than the new intraspinal (IS) assay, i.e., a test vaccine with a twofold increase in monkey neurovirulence would have a 41% chance of failing in the IT test (using 30 monkeys per vaccine), while this chance increased to 99% in the WHO IS assay (using 12 or 20 monkeys per vaccine). Since the introduction of the WHO NVT in Canada, the laboratory findings in monkeys were confirmed by vaccine experience in humans; the number of vaccine-associated paralytic poliomyelitis cases in the population showed a further decline.

Animals↗

PubMed1988

Variability in caffeine consumption from coffee and tea: possible significance for epidemiological studies.

Five surveys, using a previously developed high-performance liquid chromatography procedure to measure caffeine concentrations, indicated great variations in the concentrations of caffeine in tea and coffee. In the study of beverages prepared at home, data on caffeine concentrations in 58 samples of tea and coffee, volumes of cups, and numbers of cups consumed/day, indicated that the range of caffeine intakes for the women participating was 49-1022 mg/day. There were considerable day-to-day variations in caffeine contents in coffee samples from some commercial coffee shops. When 17 samples of five national brands of instant coffee were made into beverages in the laboratory, variations in caffeine concentrations between lots were small but between brands were significant. A considerable range of caffeine concentrations was also found when 12 samples of coffee prepared at work by different individuals using the same jar of instant coffee were analysed. Analysis of tea samples prepared in the laboratory indicated that steeping time had an important influence on resulting caffeine and theobromine concentrations. People preparing their own beverages were found to drink more liquid than the volume offered commerically. The mean caffeine 'contents' of home-made coffee and of coffee prepared by individuals at work were 79.4 and 81.7 mg/cup respectively, indicating a mean intake of approximately 80 mg caffeine/cup. When this amount (80 mg/cup) was used to estimate daily intakes of caffeine from coffee, on the basis of the number of reported cups/day, and the values obtained were compared with the amounts actually consumed by individuals, the potential for misrepresentation of individual consumption became obvious. For example, for subjects consuming three cups of coffee, only 25% would have been correctly categorized in the expected range for the daily intake of caffeine, 39% would have been overestimated and 36% underestimated for the amount of caffeine consumed. These variations in caffeine concentrations and in the volume of coffee consumed have frequently been ignored in examinations of the possible relationship between coffee consumption and various health problems, and this could perhaps partly explain some conflicting results seen in epidemiological studies.

Adult↗