Identification of physical and psychosocial problems associated with diabetic nephropathy using the International Classification of Functioning,Disability and Health Core Set for Diabetes Mellitus

Background

We previously demonstrated validation of the Comprehensive International Classification of Functioning, Disability and Health Core Set for Diabetes Mellitus (ICF-CS for DM) in patients with diabetic nephropathy (DMN). The objective of the present study was to identify differences in experience of physical and psychosocial problems between DMN patients with and without hemodialysis (HD), and diabetes patients without nephropathy using the ICF-CS for DM.

Methods

A total of 302 diabetes outpatients (men, 68 %; mean age, 62 years) were interviewed using four components of the ICF-CS for DM including “Body functions”, “Body structures”, “Activities and participation”, and “Environmental factors”.

Results

The mean number of categories in which difficulty was experienced in the four components was significantly greater in DMN patients with HD followed by DMN patients without HD, and diabetes patients without nephropathy (23.9 vs. 18.0 vs. 13.1, respectively). Multivariate logistic regression models revealed that, compared with diabetes patients without nephropathy, diabetes patients with nephropathy were more likely to have difficulty with physical problems and social activities and participation. Among DMN patients, dialysis patients were found to have larger numbers of problems, and face difficulty with employment status after adjusting for sex, age, type, and duration of diabetes.

Conclusion

The results of this study using the ICF-CS for DM identified the areas for improvement among physical and psychosocial problems in DMN patients with and without HD in contrast to diabetes patients without nephropathy.

     

Oral administration of itraconazole solution has superior efficacy in experimental oral and oesophageal candidiasis in mice than its intragastric administration

OBJECTIVE: The therapeutic activities of cyclodextrin-associated itraconazole oral solution (itraconazole OS) by two administration routes in experimental oral and oesophageal candidiasis in mice were examined and compared. METHODS: Using experimental oral and oesophageal candidiasis models in ICR mice, we investigated the efficacy of oral and intragastric administration of itraconazole OS and checked the concentration of itraconazole and its metabolite hydroxyitraconazole (OH-itraconazole) in tongues or oesophagus tissue after administration of itraconazole OS. RESULTS: Oral administration of itraconazole OS at doses of 0.8, 4.0 or 20 mg/kg/day clearly decreased the number of viable Candida albicans cells in the oral cavity of mice with oral candidiasis in a dose-dependent manner at 3 days after infection. Intragastric administration of itraconazole OS at doses of 4 and 20 mg/kg/day once a day were also effective but to a lesser degree than that of oral administration. In the oesophageal candidiasis model, oral administration of itraconazole OS displayed superior therapeutic efficacy to the intragastric route. In coincidence with the greater efficacy, itraconazole was detected in lesional tissues after oral administration of itraconazole OS. CONCLUSIONS: Oral administration of itraconazole OS displayed therapeutic efficacy against murine oral and oesophageal candidiasis superior to that achieved by intragastric administration. This can be explained by there being higher concentrations of itraconazole in tongues or oesophagus tissues after administration of the suspension by the oral route.     

Comparative effects of topiroxostat and febuxostat on arterial properties in hypertensive patients with hyperuricemia

Elevated serum uric acid is a cardiovascular risk factor in patients with hypertension, even when blood pressure (BP) is well controlled. Xanthine oxidoreductase inhibitors (XORi) reduce serum uric acid levels and have several other potential effects. This multicenter, randomized, open‐label study compared the effects of two XORi, topiroxostat and febuxostat, on arterial stiffness, uric acid levels, and BP in hypertensive patients with hyperuricemia. Patients received topiroxostat 40–160 mg/day or febuxostat 10–60 mg/day, titrated to maintain serum uric acid <6 mg/dl, for 24 weeks. The primary endpoint was change in the cardio‐ankle vascular index (CAVI) from baseline to 24 weeks. There were no significant changes in CAVI from baseline to 24 weeks (from 9.13 to 9.16 [feboxustat] and 8.98 to 9.01 [topiroxostat]). Compared with baseline, there were significant reductions in serum uric acid (–2.9 and –2.5 mg/dl; both p < 0.001) and morning home systolic BP (–3.6 and –5.1 mm Hg; both p < 0.01) after 24 weeks'' treatment with febuxostat and topiroxostat. BP decreased to the greatest extent in the subgroup of patients with uncontrolled blood pressure at baseline. Topiroxostat, but not febuxostat, significantly decreased plasma xanthine oxidoreductase activity versus baseline. The urinary albumin‐creatinine ratio (UACR) decreased significantly from baseline to 24 weeks with topiroxostat (–20.8%; p = 0.021), but not febuxostat (–8.8%; p = 0.362). In conclusion, neither topiroxostat nor febuxostat had any significant effects on arterial stiffness over 24 weeks'' treatment.     

A combination of fludarabine,half-dose cyclophosphamide,and anti-thymocyte globulin is an effective conditioning regimen before allogeneic stem cell transplantation for aplastic anemia

Conditioning regimens consisting of reduced-dose cyclophosphamide (CY) and fludarabine (FDR) have been investigated for use in allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with aplastic anemia to reduce the toxicities associated with CY. However, the ideal dose of CY has not been identified. In addition, little information is available regarding donor cell chimerism after allo-HSCT with these regimens. Therefore, we retrospectively analyzed 13 patients who underwent allo-HSCT with half-dose CY (100 mg/kg in total), FDR, and anti-thymocyte globulin at total doses of 2.5–10 mg/kg at our center. All the patients except one, who died due to encephalopathy on day 20, achieved neutrophil engraftment a median of 18.5 days after HSCT with complete donor-type chimerism. Two patients who received a graft from an HLA-matched donor subsequently developed mixed chimerism (MC) associated with transfusion-dependent cytopenia. One became transfusion-independent after donor lymphocyte infusion, but continues to exhibit MC. The other regained complete donor-type chimerism after the cessation of cyclosporine, but remains transfusion-dependent. These findings suggest that a conditioning regimen with half-dose CY and FDR is effective for achieving neutrophil engraftment and complete donor-type chimerism. However, subsequent MC may be observed, especially after HLA-matched HSCT.     

ETIOLOGY OF YELLOW FEVER : XII. CHEMOTHERAPY VERSUS SEROTHERAPY IN EXPERIMENTAL INFECTION WITH LEPTOSPIRA ICTEROIDES.

In several series of experiments guinea pigs were variously infected with different amounts of Leptospira icteroides, either in the form of culture, organ emulsion from infected guinea pigs, or a mixture of both. The infecting materials were of different grades of virulence; in some series the amount given was near a single lethal dose, in others a subminimum lethal dose was given, i.e. causing mild infection with recovery in the majority of animals, and in still others the animals were injected with at least 50 minimum lethal doses of a mixture of a culture and a highly virulent organ emulsion from a guinea pig. The animals were inoculated intraperitoneally, and within about 30 minutes each was injected subcutaneously with a different amount of salvarsan or neosalvarsan. The amounts injected were in most series 0.0005, 0.001, 0.002, 0.005, 0.01, 0.02, and 0.03 gm. per 350 to 450 gm. of body weight, and in one series, in addition to this dosage, 0.00005,0.0001, and 0.0002 gm. were also tried. Among the guinea pigs treated either with salvarsan or with neosalvarsan there were more recoveries than among the controls, but they were not in strict proportion to the amounts of the drugs injected. In the experiments with 50 minimum lethal doses of the infecting material there were several recoveries among those which received 0.001 to 0.002 to 0.003 gm., but all passed through a typical infection with all its symptoms. It is extremely doubtful, therefore, whether salvarsan or neosalvarsan mitigated the severity of the infection. The fact is noteworthy that in the same series of experiments the guinea pigs receiving 0.00005 and 0.0001 gm., or thereabout, of salvarsan died 1 to 2 days sooner than the controls, which died in 6 to 7 days. This suggests a possible earlier injury of the kidneys by the drugs, giving the leptospiras an easier and earlier access to, and localization in this organ. The inefficacy or dubious therapeutic value of salvarsan and neosalvarsan against the experimental icteroides infection of guinea pigs presents a close analogy to the observations already made by several investigators with Leptospira icterohæmorrhagiæ. Several series of test-tube experiments were also made to determine the direct effect of salvarsan and neosalvarsan on Leptospira icteroides cultures. It was found, the injurious effect of alkalinity being eliminated, that the leptospiras remain motile for at least I hour in a concentration weaker than 1:10,000 of salvarsan or 1:1,000 of neosalvarsan. But they become gradually sluggish and succumb to the effect of the drugs at the end of 18 to 24 hours. The highest dilution which killed the leptospira in 18 hours was somewhere near 1:200,000. When added to a culture medium, salvarsan and neosalvarsan both suppressed the growth of icteroides when their concentration in the medium was 1:200,000. Hence these two drugs are highly poisonous for Leptospira icteroides. The serums derived from rabbits which received 0.05 gm. of salvarsan or neosalvarsan per kilo of body weight 1 hour before bleeding proved to be very different from a normal rabbit serum in their behavior toward Leptospira icteroides. In the salvarsanized or neosalvarsanized serums the leptospiras remained active for at least 1 hour but appeared somewhat sluggish at the end of 18 hours, and were all dead and degenerated when examined after 48 hours. On the other hand, the leptospiras mixed with normal rabbit serum lived well and multiplied during the same period of time and under otherwise identical conditions (at 28°C.) To these tubes another portion of culture was added to determine whether or not a rapidly detrimental toxic substance had appeared in the drugged serum while standing for 72 hours, but the organisms remained still active at the end of 1 hour, 24 hours being required to kill them. In another experiment the salvarsanized and neosalvarsanized serums, together with normal serum as a control, were first left standing for 72 hours, after which period a rich culture of icteroides was introduced. The organisms remained uninfluenced for 1 hour in all the serums, but at the end of 24 hours many of those in the drugged serums were dead, and none was left alive at the end of 48 hours. In normal serum they steadily increased in numbers and were all active. It is evident, then, that salvarsan or neosalvarsan introduced intravenously into the body of the rabbit is present in some form in the blood serum drawn at the end of 1 hour. The substance present in such serum has a slowly operating injurious effect upon Leptospira icteroides. The action of the drugs seems to be slower after passage through the animal body than before. If this phenomenon were to take place also in the infected body injected with these drugs, it is obvious that in a rapidly evolving infectious disease like yellow fever the progress of the infection will be too rapid to allow the drugs to exert their beneficial effect upon the course of the disease. In direct contrast to the behavior of salvarsan and neosalvarsan in vivo and in vitro, anti-icteroides immune horse serum in a dose of 0.0001 cc., or 1 cc. of a 1:10,000 dilution, protected guinea pigs from an infection with at least 5,000 minimum lethal doses of icteroides when injected simultaneously, but the same serum failed to exert any injurious effect upon the organism when mixed in vitro in a concentration weaker than 1:2,000. A rapid disintegration resulted with a concentration of 1:20 and almost complete agglutination and degeneration in 1:200. The contrast between chemotherapy, as carried out with salvarsan and neosalvarsan, and serotherapy demonstrated with an immune serum is apparently of considerable practical significance.     

IMMUNOLOGICAL STUDIES WITH A STRAIN OF LEPTOSPIRA ISOLATED FROM A CASE OF YELLOW FEVER IN MERIDA,YUCATAN

Identification of the leptospira isolated from a case of yellow fever in Merida was accomplished by means of an anti-icteroides immune serum prepared in a horse with several Guayaquil strains of Leptospira icteroides. The immune serum showed a protective action of high titer against the Merida strain, thus establishing its efficacy as a therapeutic agent against this strain. Polyvalent anti-icteroides immune serum prepared in the horse or monovalent anti-icteroides immune serums prepared in the rabbit had a definite devitalizing action upon the Merida strain, while immune serums similarly prepared with strains of icterohœmorrhagiœ had no perceptible effect upon the Merida strain. Serums from yellow fever convalescents in Merida gave a positive Pfeiffer reaction with the Merida strain of Leptospira icteroides. The reactions between the Guayaquil strains (Nos. 1 and 5) and two of these serums from convalescents varied from definitely positive to doubtful, owing probably to the diminution of active immune principles in the serums during the prolonged and unfavorable conditions of their transportation.     

FURTHER STUDY ON THE CULTURAL CONDITIONS OF LEPTOSPIRA (SPIROCH?TA) ICTEROH?MORRHAGI?

1. The presence of suitable animal or human serum is essential for the cultivation of Leptospira icterohæmorrhagiæ. 2. The nutrient value of serum is considerably reduced by heating to 60°C. for 30 minutes and is destroyed by boiling (100°C). Filtration through a Berkefeld filter does not diminish the nutrient value of the serum. 3. The cultural value of different animal sera varies considerably. It is entirely absent from the sera of the rat and the pig. The sera of the rabbit, horse, and goat are better suited for the growth of the organism than those of the guinea pig, sheep, donkey, or calf. Human serum is suitable, but not ascitic fluid. 4. Fresh or heated emulsions of the liver, kidney, heart muscle, or testicle of the normal guinea pig or rabbit have no cultural value for the organism. The same may be said of both the white and yolk of the hen''s egg. 5. A luxuriant growth takes place in a medium of Ringer''s solution to which more than 10 per cent of normal rabbit serum is added. There is only moderate growth with 5 per cent of serum, and none when less than 2 per cent is present. The use of an undiluted serum offers no advantage over a diluted one, provided the latter contains at least 10 per cent of serum. In the case of certain animal sera dilution seems to make them more suitable for cultivation purposes, owing perhaps to its reduction of their inherent alkalinity. 6. The tonicity of the culture medium has but little influence upon the growth and morphology of the organism. A medium containing distilled water as diluent or one containing 8 per cent sodium chloride seems to give identical results. The viability of the organism was greatest in a medium in which Ringer''s solution or isotonic salt solution was used as diluent. 7. The reaction of the medium is an important factor in the cultivation of the organism, which thrives most vigorously in a medium of which the reaction is slightly alkaline, not exceeding that of the serum. If the reaction is neutral, the growth is meager, and the culture is short lived. When the reaction of a medium becomes alkaline by the addition of a small amount of sodium hydroxide, or faintly acid by the addition of a little hydrochloric acid, no growth can take place. 8. Leptospira icterohæmorrhagiæ is an obligatory aerobe. Any hindrance to the access of oxygen constitutes an unfavorable factor in obtaining a culture. 9. The addition of carbohydrates to media has no perceptible effect upon the growth or morphology of the organism. The reaction of the media is not modified by their presence. 10. Leptospira icterohæmorrhagiæ grows at any temperature between 37° and 10°C., the optimum zone being 30–37°C. Growth proceeds more rapidly at 37°C. than at 30° or at 25°, but the cultures remain viable much longer at the latter temperatures. No growth takes place at 42°C. 11. Three different media are described for the cultivation of freshly isolated strains. After prolonged cultivation on these media a strain may be readily cultivated in a serum diluted with Ringer''s or isotonic salt solution.     

ETIOLOGY OF OROYA FEVER : XVI. VERRUGA IN THE DOG AND THE DONKEY

In the experiments here reported, definite verruga lesions, in which the presence of Bartonella bacilliformis was established by culture or by passage to rhesus monkeys, were produced in a dog and in a donkey by inoculation of cultures or monkey passage strains. The reaction induced in these animals was entirely local, however; blood cultures were sterile. Histologically, the lesions produced were similar to those obtained in monkeys by inoculation of Bartonella bacilliformis, except for the presence of a marked polynuclear leucocytic exudate. In another donkey a lesion histologically suggestive of verruga was produced, while in one donkey and a horse the results of inoculation were negative or indefinite. The intravenous injection of a filtrate or of heat-killed cultures of Bartonella bacilliformis into two donkeys was followed by the appearance of large, soft, subcutaneous swellings, on various parts of the body, not resembling in any way verruga lesions.