Clinical assessment of near-infrared spectroscopy for noninvasive diabetes screening.

BACKGROUND: Current diabetes screening techniques comprise the fasting plasma glucose (FPG) and oral glucose tolerance tests. Both tests demand patient compliance, and neither test has ideal performance. Near-infrared (NIR) spectroscopy is a noninvasive means of interrogating characteristics of a sample and is evaluated as a novel screening method for type 2 diabetes. METHODS: One hundred fifty-four patients with and without type 2 diabetes were recruited. Their forearm skin was measured with the NIR spectroscopic system, and a capillary blood glucose measurement was also taken. Sixty-six patients returned for a second visit at a later date. A multivariate model, generated from a separate training study, was employed to produce a quantitative risk marker of disease for each NIR spectrum. Sensitivity and specificity (the probabilities that the NIR method will correctly identify a subject as having diabetes or as not having diabetes, respectively) were calculated. As the NIR method produces a continuous rather than categorical classification, various thresholds were evaluated to give several sensitivity and specificity pairs. Test reproducibility was also determined. RESULTS: At a false-positive rate of 70%, the NIR test had a sensitivity of 77.7%, which is comparable to the 77.3% sensitivity for the FPG test as reported for the Third National Health and Nutrition Examination Survey (NHANES III) study. The reproducibility of the NIR test was also similar to the FPG test (inter-day agreement rates of 84.2% and 79.2%, respectively). CONCLUSIONS: A noninvasive NIR spectroscopic measurement of the volar forearm was shown to have comparable performance characteristics with the FPG test. The source of the spectroscopic signal is still uncertain and is the subject of ongoing research.

Administration of pentoxifylline during allergen sensitization dissociates pulmonary allergic inflammation from airway hyperresponsiveness.

Asthma, a chronic inflammatory disease characterized by intermittent, reversible airflow obstruction and airway hyperresponsiveness (AHR), is classically characterized by an excess of Th2 cytokines (IL-13, IL-4) and depletion of Th1 cytokines (IFN-gamma, IL-12). Recent studies indicating an important role for Th1 immunity in the development of AHR with allergic inflammation suggest that Th1/Th2 balance may be important in determining the association of AHR with allergic inflammation. We hypothesized that administration of pentoxifylline (PTX), a phosphodiesterase inhibitor known to inhibit Th1 cytokine production, during allergen (OVA) sensitization and challenge would lead to attenuation of AHR in a murine model of allergic pulmonary inflammation. We found that PTX treatment led to attenuation of AHR when administered at the time of allergen sensitization without affecting other hallmarks of pulmonary allergic inflammation. Attenuation of AHR with PTX treatment was found in the presence of elevated bronchoalveolar lavage fluid levels of the Th2 cytokine IL-13 and decreased levels of the Th1 cytokine IFN-gamma. PTX treatment during allergen sensitization leads to a divergence of AHR and pulmonary inflammation following allergen challenge.

The suitability of ISO 9001 as a quality system for a medical illustration department.

The Medical illustration Department within Bradford Hospitals NHS Trust is typical of many such units in the UK that are facing increasing competition from the commercial sector and Private Finance Initiatives, and at the same time, being driven by NHS initiatives towards having a demonstrable quality system. It was considered that having a recognized quality management system would ensure that the service provided was more efficient and effective, improve quality, guard against competition, be an asset if the organization was benchmarked against others, and provide evidence of quality assurance to our customers. This paper summarizes the history of quality management, discusses a number of quality systems in the NHS in general, and in Bradford Hospitals NHS Trust in particular, and puts forward the reasons for choosing ISO9001. Finally, the process leading to accreditation is described.

Commentary: quality of alcohol, drug, and mental health services for American Indian children and adolescents.

American Indian children and adolescents suffer from a high prevalence of alcohol, drug, and mental (ADM) disorders. Unfortunately, the systems of services for these children and youth have never been able to address adequately their mental health needs. Thus, the revolutionary changes now taking place within these service systems, in particular the marked increase in the direct provision of services by Indian tribes and organizations, provides a unique opportunity to address these historical shortcomings. In this paper, we describe our existing knowledge concerning the quality of ADM services for American Indian children and adolescents and their critical sociodemographic, sociocultural, and epidemiologic contexts. We then consider the implications of these studies for improving the quality of care as well as its measurement and monitoring.

The Trust experience: eight years on.

In 1992 the author described her experience of working in a newly formed acute NHS Trust hospital. One of the key messages of the paper concerned the pace of radical changes experienced. Eight years on, the process of change has accelerated still further, and healthcare professionals working in the NHS face newer and tougher challenges with regard to funding, recognition and survival. This paper describes the author's personal view of developments so far.

Changes to the ocular biota with time in extended- and daily-wear disposable contact lens use.

Gram-negative bacteria may play a role in the etiology of certain soft contact lens (SCL)-related diseases. Contact lens (CL) wear may modify the normal ocular biota, providing a more favorable environment for potential pathogens. This study reports temporal changes in ocular biota in daily-wear (DW) and extended-wear (EW) disposable SCL use in experienced and neophyte wearers. Lid margin and bulbar conjunctival biota were sampled prior to CL fitting in 26 previous DW SCL users, 18 previous EW SCL users, and 26 neophytes. Wearers were fitted with an etafilcon A CL in one eye and a polymacon CL in the fellow eye. Lenses were worn on a daily basis by the 26 previous DW SCL wearers and on an EW basis by the remaining 44 subjects. The ocular biota was further sampled after 1, 3, 6, 9, and 12 months of wear. The ocular biota consisted of coagulase-negative staphylococci, Corynebacterium spp., Micrococcus spp., and Propionibacterium spp. Potential pathogens were rarely isolated at baseline. No significant trend of increasing ocular colonization was shown for extended CL wear. Lid and conjunctival colonization increased with DW SCL use (P < 0.001), although this increase occurred for nonpathogenic species only. Fewer potential pathogens were isolated from DW SCL than from EW SCL users (P < 0.05). The lid margin consistently showed greater colonization than the conjunctiva and may be a source of potential pathogens during CL wear. Hydrogel CL wear appears to modify the ocular biota. An increased number of commensal organisms were present in DW SCL use. EW SCL use altered the spectrum of organisms isolated. These alterations may suppress the normal ocular defense mechanisms and may be relevant in the pathogenesis of CL-related disease.

The procarcinogen hypothesis for bladder cancer: activities of individual drug metabolizing enzymes as risk factors.

Bladder cancer provides the most definitive example for an association between environmental agents and cancer. However, in the absence of industrial occupational exposure, the primary carcinogen is rarely identified, and the mechanisms involved in cancer formation are poorly understood. The environmental procarcinogen hypothesis of tumour pathogenesis proposes that many carcinogens require metabolic activation by drug metabolizing enzymes to form the proximate carcinogen. A balance of exposure to the carcinogen, the activity of the enzymes involved in either formation of proximate carcinogen, or production of non-toxic metabolites, will determine tumour risk. We have used mephenytoin, debrisoquine and dapsone as selective probes for the phenotypic measures of activity of CYP2C19, CYP2D6, and CYP3A4, respectively. Within subject reproducibility of phenotypic measures, and the lack of cross-inhibition when the three drugs are given in a concurrent cocktail, have been confirmed. We have applied the cocktail drug approach in two, non-overlapping series of cases with bladder cancer and matched controls. In both series, patients with aggressive bladder cancer (GIII histopathology) had a history of excess alcohol intake, an under-representation of poor metabolizers of debrisoquine, a significant mean reduction in dapsone recovery ratio, but no difference in mephenytoin phenotype. Collectively, these observations involving multiple routes of drug metabolism support the procarcinogen environmental hypothesis for bladder cancer and suggest that measurement of activity of selected individual drug metabolizing enzymes involved in the pathogenesis of this tumour can be used to identify subjects at high risk of developing bladder cancer.

Low activity of dapsone N-hydroxylation as a susceptibility risk factor in aggressive bladder cancer.

N-arylamines involved in the pathogenesis of bladder cancer, require metabolic activation via N-hydroxylation. The efficiency of in vivo N-hydroxylation of dapsone, a non-carcinogenic arylamine, may, therefore, provide a host susceptibility measure of risk of developing bladder cancer. To investigate this possibility, the dapsone recovery ratio, a phenotypic measure of the efficiency of dapsone hydroxylation, has been measured in a case control study in an urban UK population, comparing patients with aggressive bladder cancer (n = 33), non-aggressive bladder cancer (n = 60) and controls (n = 108). Dapsone recovery ratio in controls exhibited a unimodal distribution. Patients with aggressive bladder cancer had a similar distribution but significantly lower mean value (p < 0.005). Logistic regression analysis, controlling for sex, age, smoking habit and alcohol consumption confirmed a significant (p < 0.05) association between the dapsone recovery ratio and aggressive bladder cancer. Subjects in the lowest tertile of dapsone recovery ratio had a relative risk to 5.4-fold greater than subjects in the upper tertile (p < 0.009), and a trends test was significant (p < 0.001). There was no significant association between dapsone recovery ratio and non-aggressive bladder cancer. These results do not support the hypothesis that the drug metabolizing enzymes involved in dapsone N-hydroxylation are involved in causing bladder cancer. Instead, they suggest the opposite, the observation that low enzyme activity was associated with increased risk is consistent with this enzyme providing a detoxification mechanism for environmental procarcinogens.

The role of the nurse in the patient self-determination act.

The passage of the Patient Self-Determination Act (PSDA) in November 1990 marked an important step in assuring that individuals' choices regarding health care matters would be honored. This paper reports the results of a descriptive survey of hospitals and nursing homes about the role of the nurse in the implementation of the PSDA. Although exploratory, results of this survey indicate that nurses are assuming varied roles in carrying out the dictates of the PSDA. Differences between the role responsibilities of the nurse in a hospital and a nursing home are noted. It was concluded that community education about the PSDA is vital to its success and that nurses need to assume a more active role.

The Trust experience.

Since the introduction of 'The NHS and Community Care Act' in 1990, the National Health Service and the role of medical illustrators within it have undergone many changes. Following the new Act, a number of hospitals became National Health Service (NHS) Trusts in April 1991 with a second wave in April 1992. Whether the formation of NHS Trusts is regarded as an opportunity or a threat, it is estimated that most NHS hospitals in the UK will become Trusts within the next 5 years. Bradford hospitals were among the first to become a Trust and this article discusses the experience to date and offers hints as to how other departments might prepare for Trust status.

The ability to 4-hydroxylate debrisoquine is related to recurrence of bladder cancer.

Oxidative metabolism by cytochrome P450 enzymes is often involved in the activation of environmental procarcinogens. Debrisoquine, mephenytoin, and dapsone were used as in vivo probes for the activities of P4502D6, 2CMP, and 3A4, respectively, as well as dapsone for N-acetyltransferase, in order to assess the relationship between such activities and the relative risk of recurrence of bladder cancer. Urinary recovery ratios of debrisoquine and dapsone and the R/S ratio of mephenytoin were measured in an 0-8 h urine sample after simultaneous administration of debrisoquine (10 mg) and racemic mephenytoin (100 mg), and the administration of dapsone (100 mg) one week later, to patients undergoing local surgical resection of transitional cell bladder cancer of G-I, G-II, or G-III histopathology. In addition, plasma levels of dapsone and mono-acetyldapsone were determined in an 8 h plasma sample to determine the N-acetylation phenotype. Patients were followed for 3 years, to the time of tumour recurrence, or death. Three patients were lost to follow-up; of the remaining 95 patients, 55 had tumour recurrence. The debrisoquine recovery ratio was significantly greater in patients with recurrence than in individuals who remained disease-free. Among the 65 patients with non-aggressive (G-I and G-II) histopathology, two patients were lost to follow-up and 32 had tumour recurrence. In this subgroup, the debrisoquine recovery ratio was again found to be significantly greater in those individuals with tumour recurrence (p < 0.003).(ABSTRACT TRUNCATED AT 250 WORDS)

The disposition of dapsone in cirrhosis.

Acetylation and N-hydroxylation of dapsone were evaluated in drug-free, non-smoking, normal subjects and subjects with cirrhosis (n = 7 for each group) after oral administration of 100 mg dapsone. Acetylation was not correlated with oral dapsone clearance or reduced in cirrhosis (0.37 +/- 0.43 versus 0.52 +/- 0.32). Fractional metabolic clearance of dapsone to its hydroxylamine was associated with dapsone oral clearance (r = 0.96, p less than 0.001, n = 14). In patients with cirrhosis, liver disease was associated with a trend to reduction in oral clearance (22%) and metabolic clearance of dapsone (48%). Protein binding was minimally reduced by cirrhosis (73% +/- 1% versus 69% +/- 3% in patients with cirrhosis (p less than 0.02). The dapsone recovery ratio was validated as a phenotypic index of the metabolic clearance of dapsone (r = 0.74, p less than 0.05). In an extended comparison of 14 patients with cirrhosis to 70 control subjects, cirrhosis was associated with reductions of 28% in dapsone recovery ratio (p less than 0.001), and 37% in acetylation ratio (p less than 0.01). Neither dapsone recovery ratio nor acetylation ratio correlated with Pugh Score, conventional liver function tests, indocyanine green clearance, or phenotypic measures of S-mephenytoin hydroxylase or debrisoquin hydroxylase activity. We conclude that cirrhosis is associated with minor changes in dapsone disposition and that dosage modification is not required. In addition, there is evidence that cirrhosis has a selective influence on activity of individual isozymes of cytochrome P450.

Human liver microsomal N-hydroxylation of dapsone by cytochrome P-4503A4.

One of the major routes of elimination of dapsone (4,4'-diaminodiphenylsulfone) is by N-oxidation, to produce a hydroxylamine metabolite. The specific form of cytochrome P-450 (P-450) involved in this oxidation reaction was examined in human liver microsomal preparations previously characterized with respect to their content of several known P-450 enzymes. Among five preparations, the rank order of activity for dapsone hydroxylamine formation was most well correlated with the immunochemically determined level of P-4503A4 (r = 0.94, p less than 0.03). Moreover, inhibition of microsomal oxidation was observed with antibodies specific to P-4503A, with a maximum reduction of greater than 90%, but was not produced by antibodies specific to P-4501A2, P-4502CMP, or P-4502E1. Prior incubation of microsomes with gestodene (100 microM) or troleandomycin (20 microM), known selective mechanism-based inhibitors of P-4503A enzymes (in the presence of NADPH), led to 75% and 40% reductions in catalytic activity, respectively. In contrast, preincubation with increasing concentrations of alpha-naphthoflavone, a known activator of P-4503A4, increased dapsone N-hydroxylation in a concentration-dependent manner, with 5-fold activation being observed at 50 microM alpha-naphthoflavone. Finally, P-4503A4 isolated from human liver microsomes and cDNA-expressed P-4503A4 (in yeast) were both able to catalyze dapsone N-hydroxylation, with the latter preparation exhibiting a 3-fold activation in the presence of 100 microM alpha-naphthoflavone. Collectively, these findings demonstrate that N-oxidation of dapsone in human liver is predominantly mediated by P-4503A4, and they suggest that quantitative measurement of this metabolic pathway in vivo might serve as an index of the activity of this enzyme.

A photographically recorded assessment of enamel hypoplasia in fluoridated and non-fluoridated areas in England.

This study assesses the effect on enamel formation of the use of fluoride toothpaste in a fluoridated area. The prevalence of enamel hypoplasia in 251 9-10-year-old children born and raised in a fluoridated city (Birmingham) was compared with that in 319 similar children born and raised in a non-fluoridated city (Leeds). Observer bias was eliminated by the use of a new photographic technique, enabling colour slides of both groups to be assessed together in a random order. Scoring was done using both the Jackson-Al-Alousi (J-A) index, which is designed to record nonspecific hypoplasias and the Tooth Surface Index of Fluorosis (TSIF). Both were compared to the results from conventional clinical recording using the J-A index. The results showed that the photographic method was highly reproducible and more sensitive than conventional recording and showed a higher level of mild fluorosis in the fluoridated area. However, no evidence of an increase in the higher grades of fluorosis was found. It is concluded that the use of fluoride toothpaste by young children in fluoridated areas is unlikely to produce aesthetically unacceptable levels of enamel fluorosis.

Photographic technique for the recording of children's teeth for signs of enamel mottling.

A photographic method is described for recording children's teeth in large numbers on location. The essential features of the dental study were that the photography should be consistent, accurate, and fast, since the subjects were to be photographed at a rate of 45 children per hour. Details are given on how this was achieved including the technique and equipment used.