Permeation of nickel through human skin in vitro—effect of vehicles

The effect of the vehicle on the permeation rate of nickel ions through excised human skin was evaluated. Different hydrogels were compared with the standard patch test in petrolatum. A hydroxypropyl methylcellulose gel seemed to be the most promising alternative to petrolatum. It gave high bioavailability of the nickel and had good film forming properties leaving the nickel spread across the skin surface as a thin film without microscopically detectable crystals. The content of nickel in the various skin layers after cutaneous application was determined, and nickel was found to accumulate in the epidermis, probably due to epidermal binding. A significant amount of nickel was found also in the dermis. Occlusion and application of higher nickel concentrations increased the transport rate and must be considered in patch testing using this hydrogel. We conclude that nickel permeation is highly dependent of the choice of vehicle and the vehicle should, therefore, be an important consideration in patch testing with nickel.     

Childbirth Stress An Immunologic Study

The study examined salivary immunoglobulin A (IgA) concentrations during pregnancy and at parturition. A significant drop in salivary IgA (p less than 0.001) occurred at parturition. State anxiety appeared to account for some of the variance in IgA concentration during pregnancy and at childbirth. Mothers who had very low or undetectable IgA concentrations when they gave birth had increased incidences of postpartum complications, and their infants had more illnesses during the first six weeks postpartum.     

An evaluation of freestanding alcoholism treatment for Medicare recipients

The Health Care Financing Administration (HCFA) and the National Institute on Alcohol Abuse and Alcoholism (NIAAA) conducted a demonstration between 1982 and 1985 to test the feasibility of providing payments for alcoholism treatment services to Medicare and Medicaid recipients in specially selected freestanding facilities. This study of the Medicare part of the demonstration answers two questions: do freestanding facilities save money for Medicare and do their patients have lower health care utilization following imitation of treatment than patients treated in hospital-bated facilities? The statistical methodology is a logit and cluster approach. The analysis begins with a logistic regression model to predict the probability of patients seeking alcoholism treatment in either the demonstration (freestanding facility) or hospital-based cohort. The statistically significant variables from logit analysis are then used to form clusters. The health expenditure of freestanding and hospital patients are compared within homogeneous clusters. This study shows that the number of admissions, the average length of stay, and the average monthly health expenditures following the start of treatment are lower for the group treated in the freestanding facilities. The conclusion is that for some persons with alcohol problems, treatment in freestanding facilities is less costly and leads to lower subsequent health care utilization than treatment in hospitals.     

TUBERCULOSIS INCIDENCE AMONG CHINESE CLINIC CHILDREN

Beginning January l, 1940, a routine intradermal tuberculin test of 0.01 mg was given to our clinic children. This change from the previous 0.1 mg suggests the present as an opportune time to collect results of our former measure, the records of which were published(1) in 1937. The present report therefore brings up-to-date additional data on the subject, covering much of the period from March 1928 to January l, 1940. During these two recent years,     

New Method for Imaging Innervation of the Renal Preglomerular Vasculature. Alterations in Hypertensive Rats

Objective : To develop a new method for viewing adrenergic innervation along renal preglomerular vessels; to assess nerve densities and vascular lesions along arcuate arteries (ArcA), arcuate arterial branches (ArcB), and interlobular arteries (ILA) in spontaneously hypertensive rats (SHR) and in angiotensin II (AngII) and in N^G‐nitro‐l ‐arginine methyl ester (l ‐NAME) hypertensive rats. Methods : Preglomerular vasculatures were isolated after HCl maceration and were immunostained against synaptophysin, a membrane protein of synaptic vesicles. Lesions were stained with Sudan black. Longitudinal nerve densities and relative frequencies of ArcA, ArcB, and ILA endowed with sudanophilic lesions were assessed separately. Results : Synaptophysin immunostaining revealed the vascular neural plexus. Nerves were adrenergic, as the plexus was destroyed by treatment with 6‐hydroxy dopamine. Vascular lesions were not seen in SHR, and increased nerve density was observed along ArcA and ILA. In l ‐NAME‐ and AngII‐hypertensive rats, vascular lesions affected predominantly ArcB and ILA, and nerve density was reduced by 12% and 28% (ArcA), 37% and 31% (ArcB), and by 55% and 34% (ILA), respectively, versus normotensive controls. Endothelin‐1 receptor blockade did not affect AngII‐induced hypertension but prevented both lesion development and reduction of density of the vascular neural plexus. Conclusions : The method we have devised provides a direct en face view of the vascular adrenergic innervation of isolated preglomerular vasculature. Measurements in hypertensive rat models suggest a link between vascular lesions and reduction in nerve density in hypertension. Endothelin‐1 likely plays a key role in mediating both vascular injury and altered vascular nerve density in hypertension.     

Time trends of cardiovascular mortality and post-menopausal hormone use in Finland

The purpose of this paper was to study the relationship of post-menopausalhormone therapy to cardiovascular mortality by time trend analysis.Mortality and incidence figures by age and sex in 1970–1993in Finland were obtained from published and unpublished statisticsand the extent of hormone therapy use by age from previous nationwidesurveys. Percent changes in mortality were calculated for differentage groups and time periods (1970–1976, 1977–1987and 1988–1993, chosen by the extent of hormone use). Atheoretical reduction in mortality among 50–54 and 55–59year old women was calculated by using the time trends amongmen and older women (60–64 years) as the bases and bymultiplying the proportion of users by four hypothetical estimates(100, 50, 30, and 0% of benefit among users). The actual reductionin ischaemic heart disease and total cardiovascular mortalityin the age groups with highest post-menopausal hormone use wasnot larger than in other female age groups or among men. Until1987, the actual mortality of 50–54 and 55–59 yearold women was lower than that predicted from both the data ofolder women and men and from the assumed benefits of hormonetherapy. In the last time period the actual mortality was relativelynearer the predicted mortality both among 50–54 and 55–59year old women. This time trend analysis does not support theclaim that post-menopausal hormone therapy notably preventscardiovascular mortality.     

Solution synthesis of antigenic and inhibiting peptides of the human renin prosegment-2

The [Tyr⁴⁰]preprorenin (40–50) peptide methyl ester, an undecapeptide related to the human renin prosegment, has been synthesized using a stepwise strategy with hydrogenolisable protections on the side chains. The final deprotection was very difficult as observed by ¹ H NMR and reversed phase HPLC. 2D ¹ H NMR spectroscopy of the purified peptide allowed the assignment of all protons.     

Quinidine reduces biliary clearance of digoxin in man

Quinidine is known to reduce the renal clearance of digoxin, but this effect does not completely explain the influence of quinidine on the total clearance of digoxin. We therefore studied the effect of quinidine administration on biliary clearance of digoxin in five patients with atrial fibrillation. Biliary clearance of digoxin under steady state conditions before and during treatment with quinidine was investigated using a duodenal-marker-perfusion technique. Quinidine caused an average 42% (range 21-65%, P less than 0.02) reduction of the measured biliary clearance of digoxin. We conclude that the biliary effect adds to the previously demonstrated inhibitory effect of quinidine on the renal clearance of digoxin and helps to explain the decrease in total clearance of the drug. This is the first demonstration in man of a pharmacokinetic drug interaction at the level of biliary excretion.     

Very high doses of valsartan provide renoprotection independently of blood pressure in a type 2 diabetic nephropathy rat model

Aim:   Angiotensin II type 1 receptor blockers (ARB) retard the progression of hypertensive diabetic kidney disease. Clinical evidence suggests that the dose of ARB required to correct hypertension is suboptimal for renoprotection evaluated by proteinuria. No systematic, prospective study has yet evaluated separately the effect of increasing doses of ARB on blood pressure and proteinuria.
Methods:   Over a period of 8 weeks, the effect of seven constant doses of an ARB, valsartan (4–160 mg/kg per day), on blood pressure and proteinuria taken as a surrogate marker of nephropathy in a hypertensive, type 2 diabetic rat model, the spontaneously hypertensive/NIH-corpulent rat (SHR/NDmcr-cp), was assessed. In this spontaneously hypertensive rat strain, a genetic mutation in the leptin receptor gene is associated with hyperphagia leading to obesity with metabolic syndrome and eventually to nephropathy.
Results:   No additional blood pressure lowering was observed above 120 mg/kg per day of valsartan, suggesting that a dose of 80–120 mg/kg per day had a maximal effect. Nevertheless, higher doses of valsartan further reduced proteinuria in a dose-dependent fashion suggesting the absence of a maximal dose. Obesity, hyperglycaemia and hypercholesterolaemia were unaffected but hypertriglyceridaemia was partially corrected at various ARB doses.
Conclusion:   ARB improve renoprotection at doses above those required for a maximal effect on blood pressure. The mechanism of the renoprotection obtained at high doses of ARB is yet to be elucidated.