[Functional characteristics of pharmacy services related to home care in a certain suburban area].

In order to clarify functional characteristics of pharmacy services related to home care in a suburban area, a questionnaire survey regarding home-care services was conducted for all 75 pharmacies belonged to T-City Pharmaceutical Association. The following services were investigated; A) prescription (medication guidance for patients and their families, provision of drug information to patients, management of the patient's drug history, dispensing, advice to physicians, inquiries, management of prescriptions for home infusion services); B) supply (sales of items such as over-the-counter [OTC] drugs [commercially available drugs that do not require a physician's prescription], display and catalogue sales of nursing items); C) consultation (consultation on home care, holding events such as health education programs); D) management (guidance for drug management by home visit); and E) information exchange (information exchange with other medical professionals and social workers). The results of the present study were as follows. (1) The following services were considered important and therefore regularly performed; A) prescription: medication guidance for patients and their families, provision drug information to patients, management of the patient's drug history, dispensing, advice to physicians, inquiries; and B) supply: sales of items such as OTC drugs. (2) The following services were considered important, but not sufficiently regularly performed; B) supply: display and catalogue sales of nursing items; C) consultation: consultation on home care, holding events such as health education programs; D) management: guidance for drug management by home visits; and E) information exchange. (3) On factor analysis, among home care-related pharmacy services, display and catalogue sales of nursing items as well as consultation on home care were present in the same factor group as contained sales of items such as OTC drugs, which showed a high accomplishment rate. Guidance for drug management by home visits and information exchange with other social workers were present in the same factor group as contained information exchange with other medical professionals, which showed a relatively low accomplishment rate. In summary, home care-related pharmacy services were found to be associated with information exchange and supply/consultation functions. This suggests that to improve home care-related services in pharmacies, information exchange among health, medical practices, and social welfare-associated professionals, not previously promoted, should be stimulated and supported.

Toxicokinetics of intravenous fluoride in rats with renal damage caused by high-dose fluoride exposure.

Fluoride (F) complexes are used in some fields of industry and medicine. F excretion mainly depends on kidney function. Urinary F concentration is measured to monitor the health of workers exposed to F. The toxicokinetics of F were studied by analyzing plasma concentration of F after intravenous injection of 2.86, 5.71 and 8.57 mg/kg into male Wistar rats. A dose-response relationship was recognized between these F doses and renal tissue injury. Blood samples were removed at 0, 10, 20, and 30 min, and after 1, 2, 3, 4, 5, and 6 h after injection. Plasma concentration-vs-time profiles were evaluated by a nonlinear least-squares method for fitting data to polyexponential equations and calculation of relevant pharmacokinetic parameters. Results indicated that a two-compartment model could describe the elimination of F from plasma. The beta rate constant, total plasma clearance (C1) and first-order rate constants (K21, Kel) decreased, and the half-time of the beta-phase (t1/2beta) was significantly prolonged with increasing dose. The kidney is the main target organ for F toxicity. Acute exposure to high doses of F damages renal tissue and causes renal dysfunction. The C1 of F is mainly dependent on renal F excretion. Since severe kidney damage markedly affected the toxicokinetics of F and decreased its elimination, other nephrotoxic indicators and measurement of plasma F concentration are necessary for monitoring high-dose F exposure.

Successful treatments of lung injury and skin burn due to hydrofluoric acid exposure.

Recent growth in the electronics and chemical industries has brought about a progressive increase in the use of hydrofluoric acid (HF), along with the concomitant risk of acute poisoning among HF workers. We report severe cases of inhalation exposure and skin injury which were successfully treated by administering a 5% calcium gluconate solution with a nebulizer and applying 2.5% calcium gluconate jelly, respectively. Case 1: A 52-year old worker used HF for surface treatment after welding stainless steel, and was hospitalized with rapid onset of severe dyspnea. On admission to the critical care medical center he had widespread wheezing and crackles in his lungs. Chest radiograph showed a fine diffuse veiling over both lower pulmonary fields. Severe hypocalcemia with high concentrations of F in serum and urine were disclosed. He was immediately given 5% calcium gluconate solution by intermittent positive-pressure breathing (IPPB), utilizing a nebulizer. On the 21st hospital day, chest film and CT scan did not demonstrate any abnormality. He was discharged very much improved on the 22nd hospital day. Case 2: A 35-year old worker at an electronics factory was admitted to his local hospital with severe skin burn on his face and neck after exposure to 100% HF. Treatment began with immediate copious washing with water for 20 min. Calcium gluconate 2.5% gel (HF burn jelly) was applied to the area as a first-aid measure. Persistent high concentrations of serum and urinary F were disclosed for 2 weeks. After treatment with applications of HF burn jelly, he was confirmed as being completely recovered. The present cases and a review of published data suggest that an adequate method of emergency treatment for accidental HF poisoning is necessary.

Pharmacokinetics and effects after intravenous administration of high-dose boron to rat.

Boron (B) compounds have been widely used in the chemical industry, agriculture, and environmental science. The kinetics and toxicity of B were studied by analyzing several serum and urine parameters after a single intravenous injection of sodium tetraborate solution (B: 85.7 mg/kg) in Wistar male rats. Blood samples were removed at 0, 1, 2, 4, and 6 h after injection. The serum parameters studied included: B, Na, Ca, K, P, Mg, gamma-GTP, AST, ALT, BUN, Cr, CK, LDH and ALD. Plasma concentration-time profiles of B were evaluated by a nonlinear least-squares method for fitting data to polyexponential equations and calculation of relevant pharmacokinetic parameters. Urine samples were collected from the bladder following infusion. The urinary parameters that were studied included urine volume and excretion of B, Cr and NAG. Results indicated that a two-compartment model could describe the elimination of B from plasma after intravenous administration. Urine volume significantly increased. A diuretic effect of B was noted.

Usefulness of the assessment of urinary enzyme leakage in monitoring acute fluoride nephrotoxicity.

A single oral dose of sodium fluoride (NaF) in aqueous solution was given to male Wistar rats. Twenty-four-hour urine samples were collected and examined to evaluate fluoride-induced acute renal damage. The following parameters were measured in 24-h urine: urine volume and urinary excretion of fluoride, N-acetyl-beta-d-glucosaminidase (NAG), alpha-glutathione-S-transferase (alpha-GST), and creatinine (CR). Fluoride exposure produced specific, dose-dependent changes of these parameters. Significant increases of fluoride and fluoride-induced polyuria were observed. NAG as specific marker of proximal convoluted tubule (PCT) function showed a significant increase when the lowest dose of fluoride was administered. At this minimal dose, alpha-GST, a specific marker for the S3 segment, did not show a significant increase but presented the strongest relationship (r = 0. 83) to fluoride dose. No significant changes were measured for CR excretion, which showed a low correlation coefficient (r = 0.36) to administered fluoride. The specific differences in the increase pattern of these parameters show that the PCT is more susceptible to damage by low-dose fluoride than the S3 segment or the glomerulus. We concluded that both NAG and alpha-GST are useful for the diagnosis of fluoride-induced acute nephrotoxicity. Proper evaluation of these urinary indices may be of help to establish the site and extent of kidney injury in acute fluoride toxicity.

Urinary lithium: distribution shape, reference values, and evaluation of exposure by inductively coupled plasma argon-emission spectrometry.

Inductively coupled plasma argon-emission spectrometry (ICPAES) was used to evaluate the lithium content of undiluted urine samples. The method can be performed with 1 mL of urine in a single tube using a routine ICPAES analysis for rapid and convenient assessment of lithium exposure in humans. Urine samples obtained from male workers (n = 86) who had not been exposed to lithium were used for the determination of this element by ICPAES. The obtained concentrations were corrected using a specific gravity of 1.024. The particular frequency distribution resulted in a log-normal distribution diagram for anatomical spread. Geometric mean value for urinary lithium in the nonexposed male workers was 23.5 microg/L, and the confidence interval from a log-normal distribution was 11.0 to 50.5 microg/L. Taking into consideration a short biological half-life and the massive urine excretion of lithium, urinary lithium was considered to be a useful index for monitoring of exposure. Calibration curves obtained for lithium standards had good sensitivity and linearity. Good reproducibility was assessed by lithium addition to urine samples. It was concluded that the obtained lithium reference values would be useful for the early diagnosis of lithium intoxication or in the assessment of the degree of exposure to lithium in subjects at risk.

Study on urine boron reference values of Japanese men: use of confidence intervals as an indicator of exposure to boron compounds.

A simple and rapid method for the determination of urine boron by inductively-coupled plasma argon emission spectrometry (ICPAES) has been developed to establish boron exposure guidelines. After 11-fold dilution in 18.25 M omega cm ultra-pure water and vigorous shaking, urine may be directly injected into the spectrometer, providing accurate and reproducible results. We report the results obtained with urine samples obtained from a group of male Japanese electronic workers (n = 102) who had not been exposed to boron; boron concentrations were corrected with use of a specific gravity of 1.024 g/ml. The frequency distribution resulted in a log-normal distribution diagram for anatomical spread. The geometric mean values for urine boron in the non-exposed workers was 798.0 micrograms/l, while the confidence interval (C.I.) was between 398.1 and 1599.6 micrograms/l. Taking into consideration the short biological half-life of boron and its major excretion route via urine, urine was considered to be a suitable means for monitoring of exposure to this element. We conclude that the guidelines established by determining boron reference values are useful for the protection of individuals exposed to boron in their working environments.

Serum and urinary boron levels in rats after single administration of sodium tetraborate.

The pharmacokinetics of boron was studied in rats by administering a 1 ml oral dose of sodium tetraborate solution to several groups of rats (n=20) at eleven different dose levels ranging from 0 to 0.4 mg/100 g body weight as boron. Twenty-four-hour urine samples were collected after boron administration. After 24 h the average urinary recovery rate for this element was 99.6+/-7.9. The relationship between boron dose and excretion was linear (r=0.999) with a regression coefficient of 0.954. This result suggests that the oral bioavailability (F) of boron was complete. Another group of rats (n=10) was given a single oral injection of 2 ml of sodium tetraborate solution containing 0.4 mg of boron/100 g body wt. The serum decay of boron was followed and found to be monophasic. The data were interpreted according to a one-compartment open model. The appropriate pharmacokinetic parameters were estimated as follows: absorption half-life, t1/2a=0.608+/-0.432 h; elimination half-life, t1/2=4.64+/-1.19 h; volume of distribution, Vd = 142.0+/-30.2 ml/100 g body wt.; total clearance, Ctot=0.359+/-0.0285 ml/min per 100 g body wt. The maximum boron concentration in serum after administration (Cmax) was 2.13+/-0.270 mg/l, and the time needed to reach this maximum concentration (Tmax) was 1.76+/-0.887 h. Our results suggest that orally administered boric acid is rapidly and completely absorbed from the gastrointestinal tract into the blood stream. Boric acid in the intravascular space does not have a strong affinity to serum proteins, and rapidly diffuses to the extravascular space in proportion to blood flow without massive accumulation or binding in tissues. The main route of boron excretion from the body is via glomerular filtration. It may be inferred that there is partial tubular resorption at low plasma levels. The animal model is proposed as a useful tool to approach the problem of environmental or industrial exposure to boron or in cases of accidental acute boron intoxication.

Urinary biomarkers monitoring for experimental fluoride nephrotoxicity.

An excess of sodium fluoride (135 mg F/kg body weight) was given in a single oral dose to male Wistar rats. Effects were investigated of fluoride-induced acute kidney intoxication on the time-dependent variations of urine volume. Also, of urinary fluoride ion (F-), alpha-glutathione-S-transferase (alpha-GST), N-acetyl-beta-D-glucosaminidase (NAG), and creatinine (CR) concentrations. Fluoride administration strongly affects these urinary biochemical indices. Of the several biomarkers studied, alpha-GST is particularly useful as marker of S3 proximal tubule damage. We found that alpha-GST shows the strongest and more durable changes as a result of the large dose of F- given to the experimental animals. Our results suggest that the toxic effect of F- on the kidney may be more pronounced in the proximal tubule than the glomeruli region, and that the disorder of the proximal tubule is more serious in the S3 segment than S1 or S2 segment. Alpha-GST proved to be a useful marker for the early detection and long-term observation of proximal renal tubular injury resulting from F- intoxication. The animal model should help to establish guidelines for the treatment of industrial workers suffering from acute renal failure resulting from accidental exposure to fluoride.

[The effects of a day service center on the physical and mental condition and lifestyle of the disabled elderly living at home].

This study investigated the effects of a day service center on the physical and mental condition of the disabled elderly living at home, and clarified the factors which related to physical and mental effects after using the day service center. Sixty-nine male and 141 female subjects (mean age: 79.5 years) were studied by questionnaire. Among males, the characteristics of "having a spouse" and "dementia" occurred with significantly greater frequency than among female subjects, while the prevalence of "more advanced age" and "three-generation household" were significantly higher among females than males. The enjoyments at the center for the elderly were baths and/or meals, and meeting and talking with staff members, volunteers and other elders using the day service center. The survey found that the day service center helped to improve the physical and mental conditions such as cleanliness and cheerfulness. The main factors related to physical and mental effects after using the day service center were age distribution, household composition, degree of dementia and manner of bathing at the center. From the results obtained, it was concluded that the day service center provides the opportunity to improve actual living conditions and promote the welfare of the disabled elderly living at home.

Urine, serum and hair monitoring of hydrofluoric acid workers.

To define the relationship between fluoride (F) concentration in the serum, urine and hair of workers and the concentration of hydrofluoric acid (HF) in the work environment, pre- and postshift serum and urine samples of 142 HF exposed workers and 237 unexposed workers were examined. Hair specimens were also collected for the determination of F. To determine whether external contamination influences hair analysis, the control hair samples were kept in the work environment for one week. The pre-exposure levels in serum and urinary F in HF workers were higher (P < 0.01) than the control values. This suggests that F excretion from the body continues for at least 12 hours. The postshift serum and urinary F concentrations of these workers were significantly higher (P < 0.01) than the preshift concentrations. The levels of F in the hair of HF workers were also higher than in the control subjects. The concentrations of F in postshift serum and urine, and hair were in good correlation to each other. There was a linear relationship between mean serum and urinary F concentrations and HF concentration in the workplace. A mean F concentration of 82.3 micrograms/l in serum and 4 mg/l in urine with a lower fiducial limit (95%, P = 0.05) of 57.9 micrograms/l in serum and 2 mg in urine were estimated to correspond to an atmospheric HF concentration of 3 ppm, which is the maximum allowable concentration recommended by Japan Association of Industrial Health and also the threshold limit value suggested by American Conference of Governmental Industrial Hygienists.(ABSTRACT TRUNCATED AT 250 WORDS)

An experimental study on the treatment of hydrofluoric acid burns.

A 20% solution of hydrofluoric acid (HF) was applied to the skin of rats and a biomedical observation of the tissues and sera was made. Flushing with running water was effective for HF burns. By applying 2.5% calcium gluconate jelly, concentrations of fluoride in the urine and the tissues surrounding the injured region were reduced. Thus, the results proved that irrigation with running water and jelly applications were evaluated as the most effective therapy among various methods tested for HF burns.

Serum fluoride as an indicator of occupational hydrofluoric acid exposure.

To define the relationship between ionic fluoride concentration in the serum of workers and the amount of hydrofluoric acid (HF) in the work environment, pre-and postshift serum and urine samples of 142 HF workers and 270 unexposed workers were examined. The maximum and minimum concentrations of HF in the air in each workshop varied from the mean by less than 30%. The preexposure levels of serum and urinary fluoride in HF workers were higher (P < 0.001) than the control values. This suggests that fluoride excretion from the body continues for at least 12h. The postshift serum and urinary fluoride concentrations of these workers were significantly higher (P < 0.001) than the preshift concentrations. A good correlation (r = 0.64) was obtained between postshift serum fluoride and postshift urine fluoride. There was a linear relationship between mean serum fluoride concentration and HF concentration in the workshop. A mean fluoride concentration of 82.3 micrograms/l with a lower fiducial limit (95%, P = 0.05) of 57.9 micrograms/l was estimated to correspond to an atmospheric HF concentration of 3 ppm. This is the maximum allowable environmental concentration recommended by the Japanese Association of Industrial Health, and it is also the threshold limit value suggested by the American Conference of Governmental Industrial Hygienists. The results demonstrate that exposure to HF can be monitored by determining the serum fluoride concentration.

An experimental study on mandibular movement and osteoporosis.

In order to clarify the relationship between mandibular movement and osteoporosis, the authors secured the temporo-mandibular joints of 8-week-old rats to immobilize their jaws; then conducted histologic studies chronologically, up to the fifth week. After three weeks, an expansion of the marrow cavity and a reduction of the trabecular were observed in the mandibular process and mandibular fossa. During the fifth week, an osteoporosis-like state was clearly observed. Further, an irregularity in the form of mandibular process was recognized, as well as a remarkable disturbance caused by cartilaginous ossification of the articular cartilage of the condyle.

Serum and urinary N-acetyl-beta-D-glucosaminidase activity among the inhabitants of a rural area in Japan--the effect of age and hypertension.

In this paper, the normal values, distribution, and variations in serum and urinary activities of the lysosomal enzyme, N-acetyl-beta-D-glucosaminidase (NAG), were estimated in a rural area of Japan. The frequency distribution of NAG activities both in the serum and urine of 1,152 males and females (aged 35 to 87), living in a rural area of Gifu Prefecture in Japan, showed an approximately log-normal distribution. Geometric mean values (with S.D. ranges) in healthy subjects (876 males and females) were 12.61 U/l (9.56-16.63) for serum NAG and 8.05 U/l (4.03-16.07) for urinary NAG. There was no significant difference between those of males and females. Serum and urinary NAG activities increased with advancing ages, and these NAG activities in hypertensive subjects were higher than those in normotensives. Since the serum and urinary levels of several commonly measured cytosolic chemicals were within normal limits, the above results could not be ascribed to tissue necrosis. Thus, the estimation of serum and urinary NAG could be a useful indicator discriminating the essential hypertensive patients from the normal subjects.