Making and reading microarrays.

There are a variety of options for making microarrays and obtaining microarray data. Here, we describe the building and use of two microarray facilities in academic settings. In addition to specifying technical detail, we comment on the advantages and disadvantages of components and approaches, and provide a protocol for hybridization. The fact that we are now making and using microarrays to answer biological questions demonstrates that the technology can be implemented in a university environment.

Motor neuron pathology in experimental autoimmune encephalomyelitis: studies in THY1-YFP transgenic mice.

Using adult male C57BL/6 mice that express a yellow fluorescent protein transgene in their motor neurons, we induced experimental autoimmune encephalomyelitis (EAE) by immunization with myelin oligodendrocyte glycoprotein peptide 35-55 (MOG peptide) in complete Freund's adjuvant (CFA). Control mice of the same transgenic strain received CFA without MOG peptide. Early in the course of their illness, the EAE mice showed lumbosacral spinal cord inflammation, demyelination and axonal fragmentation. By 14 weeks post-MOG peptide, these abnormalities were much less prominent, but the mice remained weak and, as in patients with progressive multiple sclerosis, spinal cord atrophy had developed. There was no significant loss of lumbar spinal cord motor neurons in the MOG peptide-EAE mice. However, early in the course of the illness, motor neuron dendrites were disrupted and motor neuron expression of hypophosphorylated neurofilament-H (hypoP-NF-H) immunoreactivity was diminished. By 14 weeks post-MOG peptide, hypoP-NF-H expression had returned to normal, but motor neuron dendritic abnormalities persisted and motor neuron perikaryal atrophy had appeared. We hypothesize that these motor neuron abnormalities contribute to weakness in this form of EAE and speculate that similar motor neuron abnormalities are present in patients with progressive multiple sclerosis.

GenMapDB: a database of mapped human BAC clones.

GenMapDB (http://genomics.med.upenn.edu/genmapdb) is a repository of human bacterial artificial chromosome (BAC) clones mapped by our laboratory to sequence-tagged site markers. Currently, GenMapDB contains over 3000 mapped clones that span 19 chromosomes, chromosomes 2, 4, 5, 9-22, X and Y. This database provides positional information about human BAC clones from the RPCI-11 human male BAC library. It also contains restriction fragment analysis data and end sequences of the clones. GenMapDB is freely available to the public. The main purpose of GenMapDB is to organize the mapping data and to allow the research community to search for mapped BAC clones that can be used in gene mapping studies and chromosomal mutation analysis projects.

A decision support framework for sustainable urban water planning and management in new urban areas.

The paper discusses issues of decision support within the context of sustainable development and more specifically sustainable water cycle management to provide a context and a rationale for the decision support approach adopted within an on-going U.K. EPSRC-funded project, WaND. The paper proposes a set-up for a flexible, upgradeable, efficient and modular decision support framework and associated tools. Furthermore, the paper presents early prototypes of three decision support tools developed within the proposed framework including initial results for one of them.

Economic burden of pneumonia in an employed population.

OBJECTIVE: To estimate the overall economic burden of pneumonia from an employer perspective. METHODS: The annual, per capita cost of pneumonia was determined for beneficiaries of a major employer by analyzing medical, pharmaceutical, and disability claims data. The incremental costs of 4036 patients with a diagnosis of pneumonia identified in a health claims database of a national Fortune 100 company were compared with a 10% random sample of beneficiaries in the employer overall population. RESULTS: Total annual, per capita, employer costs were approximately 5 times higher for patients with pneumonia ($11 544) than among typical beneficiaries in the employer overall population ($2368). The increases in costs were for all components (eg, medical care, prescription drug, disability, and particularly for inpatient services). A small proportion (10%) of pneumonia patients (almost all of whom were hospitalized) accounted for most (59%) of the costs. CONCLUSIONS: Patients with pneumonia present an important financial burden to employers. These patients use more medical care services, particularly inpatient services, than the average beneficiary in the employer overall population. In addition to direct health care costs related to medical utilization and the use of prescription drugs, indirect costs due to disability and absenteeism also contribute to the high cost of pneumonia to an employer.

Evaluation of a hypertension screening programme in Independence, Belize.

This study assesses the effectiveness of a hypertension-screening programme in Independence, Belize. Forty-nine of the 101 patients screened were found to have elevated blood pressure readings and were advised to seek medical care. Four months later, interviews with 35 of the 49 patients from the hypertensive group revealed that 85.7% of the patients had sought medical care. Women, elderly patients and patients with a previous history of hypertension were more likely than men, younger patients and those without a history of hypertension to seek follow-up medical care. The screening programme successfully directed a high proportion of patients with elevated blood pressure to seek appropriate medical care.

Comparative effects of neonatal exposure of male rats to potent and weak (environmental) estrogens on spermatogenesis at puberty and the relationship to adult testis size and fertility: evidence for stimulatory effects of low estrogen levels.

This study investigated whether neonatal exposure of male rats to estrogenic compounds altered pubertal spermatogenesis (days 18 and 25) and whether the changes observed resulted in long-term changes in testis size, mating, or fertility (days 90-100). Rats were treated neonatally with a range of doses (0.01-10 microg) of diethylstilbestrol (DES; administered on alternate days from days 2-12), a high dose of octylphenol (OP; 2 mg administered daily from days 2-12) or bisphenol A (Bis-A; 0.5 mg administered daily from days 2-12), or vehicle, while maintained on a standard soy-containing diet. The effect on the same parameters of rearing control animals on a soy-free diet was also assessed as was the effect of administering such animals genistein (4 mg/kg/day daily from days 2-18). Testis weight, seminiferous tubule lumen formation, the germ cell apoptotic index (apoptotic/viable germ cell nuclear volume), and spermatocyte nuclear volume per unit Sertoli cell nuclear volume were used to characterize pubertal spermatogenesis. Compared with (soy-fed) controls, DES administration caused dose-dependent retardation of pubertal spermatogenesis on day 18, as evidenced by decreases in testis weight, lumen formation, and spermatocyte nuclear volume per unit Sertoli cell and elevation of the germ cell apoptotic index. However, the two lowest doses of DES (0.1 and 0.01 microg) significantly increased spermatocyte nuclear volume per unit Sertoli cell. Similarly, treatment with either OP or Bis-A significantly advanced this and some of the other aspects of pubertal spermatogenesis. Maintenance of control animals on a soy-free diet also significantly advanced lumen formation and spermatocyte nuclear volume per unit Sertoli cell compared with controls fed a soy-containing diet. Administration of genistein reversed the stimulatory effects of a soy-free diet and significantly retarded most measures of pubertal spermatogenesis. In general, plasma FSH levels in the treatment groups changed in parallel to the spermatogenic changes (reduced when pubertal spermatogenesis retarded, increased when pubertal spermatogenesis advanced). By day 25, although the changes in FSH levels largely persisted, all of the stimulatory effects on spermatogenesis seen on day 18 in the various treatment groups were no longer evident. In adulthood, testis weight was decreased dose dependently in rats treated neonatally with DES, but only the lowest dose group (0.01 microg) showed evidence of mating (3 of 6) and normal fertility (3 litters). Animals treated neonatally with OP or Bis-A had normal or increased (Bis-A) testis weights and exhibited reasonably normal mating/fertility. Animals fed a soy-free diet had significantly larger testes than controls fed a soy-containing diet, and this difference was confirmed in a much larger study of more than 24 litters, which also showed a significant decrease in plasma FSH levels and a significant increase in body weight in the males kept on a soy-free diet. Neonatal treatment with genistein did not alter adult testis weight, and although most males exhibited normal mating and fertility, a minority did not mate or were infertile. It is concluded that 1) neonatal exposure of rats to low levels of estrogens can advance the first wave of spermatogenesis at puberty, although it is unclear whether this is due to direct effects of the estrogen or to associated elevation of FSH levels; 2) the effect of high doses of OP and Bis-A on these processes is essentially benign; and 3) the presence or absence of soy or genistein in the diet has significant short-term (pubertal spermatogenesis) and long-term (body weight, testis size, FSH levels, and possibly mating) effects on males.

Gonadotropin-releasing hormone receptor in the teleost Haplochromis burtoni: structure, location, and function.

GnRH acts via GnRH receptors (GnRH-R) in the pituitary to cause the release of gonadotropins that regulate vertebrate reproduction. In the teleost fish, Haplochromis burtoni, reproduction is socially regulated through the hypothalamus-pituitary-gonadal axis, making the pituitary GnRH-R a likely site of action for this control. As a first step toward understanding the role of GnRH-R in the social control of reproduction, we cloned and sequenced candidate GnRH-R complementary DNAs from H. burtoni tissue. We isolated a complementary DNA that predicts a peptide encoding a G protein-coupled receptor that shows highest overall identity to other fish type I GnRH-R (goldfish IA and IB and African catfish). Functional testing of the expressed protein in vitro confirmed high affinity binding of multiple forms of GNRH: Localization of GnRH-R messenger RNA using RT-PCR revealed that it is widely distributed in the brain and retina as well as elsewhere in the body. Taken together, these data suggest that this H. burtoni GnRH receptor probably interacts in vivo with all three forms of GNRH:

Permanent effects of neonatal estrogen exposure in rats on reproductive hormone levels, Sertoli cell number, and the efficiency of spermatogenesis in adulthood.

This study aimed to identify the mechanism(s) for impairment of spermatogenesis in adulthood in rats treated neonatally with estrogens. Rats were treated (days 2-12) with 10, 1, or 0.1 microg diethylstilbestrol (DES), 10 microg ethinyl estradiol (EE), 10 mg/kg of a GnRH antagonist (GnRHa), or vehicle and killed in adulthood. DES/EE caused dose-dependent reductions in testis weight, total germ cell volume per testis, and Sertoli cell volume per testis. Sertoli cell number at 18 days of age in DES-treated rats was reduced dose dependently. GnRHa treatment caused changes in these parameters similar to those in rats treated with 10 microg DES. Plasma FSH levels were elevated (P < 0.001) to similar levels in all treatment groups regardless of differences in Sertoli cell number and levels of inhibin B; the latter reflected Sertoli cell number, but levels were disproportionately reduced in animals treated with high doses of DES/EE. Neonatal estrogen treatment, but not GnRHa, caused dose-dependent reductions (40-80%) in plasma testosterone levels in adulthood, but did not alter LH levels. Preliminary evidence suggests that the decrease in testosterone levels in estrogen-treated rats is not due to reduced Leydig cell volume per testis. GnRHa-treated rats exhibited a significant increase in germ cell volume per Sertoli cell and a reduction in germ cell apoptosis, probably because of the raised FSH levels. Despite similar raised FSH levels, rats treated with DES (10 or 1 microg) or EE (10 microg) had reduced germ cell volume/Sertoli cell and increased germ cell apoptosis, especially when compared with GnRHa-treated animals. The latter changes were associated with an increase in lumen size per testis, indicative of impaired fluid resorption from the efferent ducts, resulting in fluid accumulation in the testis. Rats treated neonatally with 0.1 microg DES showed reduced germ cell apoptosis comparable to that in GnRHa-treated animals. The changes in apoptotic rate among treatment groups occurred across all stages of the spermatogenic cycle. It is concluded that 1) neonatal estrogen treatment results in dose-dependent alterations in Sertoli cell numbers, germ cell volume, efficiency of spermatogenesis, and germ cell apoptosis in adulthood; 2) the relatively poor spermatogenesis in estrogen-treated animals is most likely due to altered testis fluid dynamics and/or altered Sertoli cell function; 3) as indicated by FSH (LH) and testosterone levels, the hypothalamic-pituitary axis and Leydig cells are probably more sensitive than the Sertoli cells to reprogramming by estrogens neonatally; and 4) elevated FSH levels in adulthood may improve the efficiency of spermatogenesis.

Effect of chronic administration of an aromatase inhibitor to adult male rats on pituitary and testicular function and fertility.

The aim of the present study was to evaluate the effects of the administration of a potent non-steroidal aromatase inhibitor, anastrozole, on male reproductive function in adult rats. As anastrozole was to be administered via the drinking water, a preliminary study was undertaken in female rats and showed that this route of administration was effective in causing a major decrease in uterine weight (P<0.02). In an initial study in male adult rats, anastrozole (100 mg/l or 400 mg/l) was administered via the drinking water for a period of 9 weeks. Treatment with either dose resulted in a significant increase ( approximately 10%) in testis weight and increase in plasma FSH concentrations (P<0.01) throughout the 9 weeks. Mating was altered in both groups of anastrozole-treated rats, as they failed to produce copulatory plugs. Histological evaluation of the testes from anastrozole-treated rats revealed that spermatogenesis was grossly normal. In a more detailed study, adult rats were treated with 200 mg/l anastrozole via the drinking water for periods ranging from 2 weeks to 1 year. Plasma FSH and testosterone concentrations were increased significantly (P<0.001) during the first 19 weeks of treatment. However, LH concentrations were increased only at 19 weeks (P<0.001) in anastrozole-treated rats, and this coincided with a further increase in circulating and intratesticular testosterone concentrations (P<0.05). No consistent change in inhibin-B concentrations was observed during the study. Suppression of plasma oestradiol concentrations could not be demonstrated in anastrozole-treated animals, but oestradiol concentrations in testicular interstitial fluid were reduced by 18% (P<0.01). Mating was again inhibited by anastrozole treatment, but could be restored by s.c. injection of oestrogen, enabling demonstration that rats treated for 10 weeks or 9 months were still fertile. Testis weight was increased by 19% and 6% after treatment for 19 weeks and 1 year, respectively. Body weight was significantly decreased (P<0.01) by 19 weeks of anastrozole treatment; after 1 year the animals appeared to have less fat as indicated by a 27% decrease in the weight of the gonadal fat pad. The majority of anastrozole-treated animals had testes with normal spermatogenesis but, occasionally, seminiferous tubules showed abnormal loss of germ cells or contained only Sertoli cells. Ten percent of anastrozole-treated animals had testes that appeared to contain only Sertoli cells, and one rat had 'giant' testes in which the tubule lumens were severely dilated. Morphometric analysis of the normal testes at 19 weeks showed no difference in the number of Sertoli cells or germ cells, or the percentage volumes of the seminiferous epithelium, tubule lumens and interstitium between control and anastrozole-treated rats. On the basis of the present findings, oestrogen appears to be involved in the regulation of FSH secretion and testosterone production, and is also essential for normal mating behaviour in male rats. Furthermore, these data suggest that the brain and the hypothalamo-pituitary axis are considerably more susceptible than is the testis to the effects of an aromatase inhibitor. Anastrozole treatment has resulted in a model of brain oestrogen insufficiency.

Modulation of gene expression by androgen and oestrogens in the testis and prostate of the adult rat following androgen withdrawal.

Androgens are important for the structural and functional integrity of the testis and the prostate and this may in part be mediated by the aromatisation of testosterone to oestradiol. The aim of the present study was to establish an in vivo model that would allow the identification of genes, the expression of which was regulated acutely by androgen and/or oestrogen in the male reproductive system. In rats in which the Leydig cells were ablated by administration of ethane dimethane sulfonate (EDS) 6 days earlier, testosterone esters (T) were administered from day 0 (To), and additional animals were administered either T, 17beta-oestradiol benzoate (EB) or diethylstilbestrol (DES) for 1 or 4 h on day 6 after EDS-treatment. Nuclear immunoexpression of the androgen receptor (AR) was reduced or absent from the testis but unaffected in the ventral prostate following these treatments. ERbeta immunoexpression in these tissues was unchanged. Northern blot analysis showed that EB and DES as well as T administration 4 h earlier could modulate mRNA expression of two androgen-responsive genes, C3 and SGP-2, in the prostate. The co-administration of T or EB with the AR antagonist, flutamide, or with the ER antagonist, ICI 182,780 (ICI), did not block the suppression of SGP-2 mRNA expression by T or EB. In contrast, the upregulation of C3 mRNA expression by T was successfully antagonised by both flutamide and by ICI. A preliminary evaluation of the expression of three Sertoli cell and five germ cell mRNAs revealed that their expression was not steroid regulated. Our results support the hypothesis that the action of testosterone in the male reproductive system may in part be mediated by its conversion to oestradiol. This in vivo model should prove of value in future studies to identify androgen and oestrogen regulated genes in the male reproductive system.

The effect of d-amphetamine on operant behaviour maintained under variable-interval schedules of reinforcement.

Dose-response curves were obtained for the effects of d-amphetamine sulphate (0.1-3.2 mg/kg) on the operant performance of rats in variable-interval 4-min and variable-interval 20-min schedules of reinforcement. Response rates maintained under variable-interval 4-min were suppressed in a dose-dependent manner. Response rates maintained under variable-interval 20-min schedules tended to be elevated by low doses and suppressed by higher doses. The degree of response rate suppression was greater in the case of the variable-interval 4-min schedule. The results are consistent with the previously reported effect of d-amphetamine on the values of the two constants of Herrnstein's (1970) equation: the drug reduces the reinforcement frequency needed to maintain the half-maximum response rates (KH) and lowers the maximum response rate (Rmax) (Bradshaw et al. 1981 b). It is suggested that the effects of d-amphetamine on operant performance may involve two processes: an enhancement of motivation and a reduction of the capacity to respond.

Attenuation by pimozide of the suppressant effect of d-amphetamine on operant behaviour.

The interaction between pimozide (a selective D2-dopamine receptor antagonist) and d-amphetamine on the operant performance of rats maintained under variable-interval schedules of positive reinforcement was examined. In Experiment 1, eight rats responded under variable-interval 30-s and variable-interval 300-s. Pimozide (0.0625, 0.125, 0.25, 0.5 mg/kg) suppressed performance maintained under both schedules in a dose-dependent manner, the degrees of suppression being equivalent in the two schedules. In Experiment 2, 12 rats responded under the same schedules. d-Amphetamine (0.1-3.2 mg/kg) suppressed performance under both schedules, the degree of suppression being somewhat greater in the case of variable-interval 30-s. Pre-treatment with pimozide (0.0625, 0.125 mg/kg) significantly attenuated the suppressant effect of d-amphetamine under both schedules. It is suggested that D2-dopamine receptors may be involved in mediating the suppressant effect of d-amphetamine on operant behaviour.

Effect of 6-hydroxydopamine-induced lesions of the dorsal noradrenergic bundle on steady-state operant behaviour.

The possible role of the dorsal noradrenergic bundle (DNAB) in the maintenance of operant behaviour by positive reinforcement was examined using a quantitative behavioural paradigm based on Herrnstein's (1970) equation which defines a hyperbolic relationship between steady-state response rate and reinforcement frequency in variable-interval schedules. Twelve rats received bilateral injections of 6-hydroxydopamine (4 micrograms/2 microliters) into the DNAB; ten rats received sham injections. The rats were trained to steady state in a series of six variable-interval schedules of sucrose reinforcement affording reinforcement frequencies of 8-350 reinforcers per hour. Herrnstein's equation was fitted to the data obtained from each rat and to the averaged data obtained from the two groups. The values of both Rmax (the parameter of the equation expressing the theoretical maximum response rate) and KH (the parameter expressing the reinforcement frequency needed to maintain the half-maximal response rate) were significantly higher in the DNAB-lesioned group than in the sham-lesioned group. At the end of the behavioural experiment the rats were sacrificed for determination of catecholamine levels in the brain by high-performance liquid chromatography. The levels of noradrenaline in the neocortex and hippocampus of the DNAB-lesioned rats were approximately 10% of those of the sham-lesioned rats. The results indicate that destruction of the DNAB reduced the "value" of the reinforcer without impairing the animals' capacity to respond.

DSP4 alters the effect of d-amphetamine on variable-interval performance: analysis in terms of Herrnstein's equation.

The effect of d-amphetamine (0.1-3.2 mg/kg) on performance in variable-interval 1-min and variable-interval 12-min schedules of positive reinforcement was examined in ten rats treated with the selective noradrenaline neurotoxin DSP4 and 12 control rats. In the control group d-amphetamine had a dose-dependent suppressant effect on response rates maintained under variable-interval 1-min; under variable-interval 12-min, response rates were increased by low doses and suppressed by higher doses of the drug. In the case of both schedules, lower doses of d-amphetamine were more suppressant and higher doses less suppressant in the DSP4-treated group than in the control group. The levels of noradrenaline in the parietal cortex, hippocampus and cerebellum (determined by high-performance liquid chromatography) were reduced to approximately 15% of control levels in the DSP4-treated rats. The results indicate that treatment with DSP4 attenuated both the facilitatory and the suppressant effects of d-amphetamine on variable-interval performance. A formal model couched in terms of Herrnstein's (1970) equation is put forward to account for these results. It is suggested that the noradrenergic pathways emanating from the locus caeruleus are involved in both the facilitatory and suppressant effects of d-amphetamine on operant behaviour.

The effect of pimozide on variable-interval performance: a test of the 'anhedonia' hypothesis of the mode of action of neuroleptics.

A quantitative behavioural test system based on Herrnstein's (1970) equation was used to test a prediction derived from the "anhedonia" hypothesis of neuroleptic action, that pimozide should increase the value of the behavioural parameter KH (the reinforcement frequency needed to maintain the half-maximal response rate in variable-interval schedules). On the basis of theoretical considerations, it was shown that the equation implies that a drug which exerts such an effect on KH must have a more profound suppressant effect on performance maintained by low reinforcement frequencies than on performance maintained by high reinforcement frequencies. Fifteen rats were trained under variable-interval 10-s and variable-interval 100-s schedules, and the effect of pimozide (0.125, 0.25, 0.33, and 0.5 mg/kg) was tested on performance maintained under both schedules in a dose-dependent manner, and there was no tendency for the drug to exert a greater effect on performance maintained under the lower reinforcement frequency. These results do not provide any evidence that the effect of pimozide on variable-interval performance is due to an "anti-hedonic effect"; rather, they are compatible with the hypothesis that pimozide impairs the capacity to respond.

DSP4 and Herrnstein's equation: further evidence for a role of noradrenaline in the maintenance of operant behaviour by positive reinforcement.

The effect of the selective noradrenaline neurotoxin DSP4 on steady-state operant behaviour was examined using a quantitative behavioural paradigm based on Herrnstein's (1970) equation, which defines a hyperbolic relationship between steady-state response rate and reinforcement frequency in variable-interval schedules. Eleven rats received injections of DSP4 (two doses of 50 mg/kg, intraperitoneally), and 12 rats received injections of the vehicle alone. The rats were trained to steady state in a series of six variable-interval schedules of sucrose reinforcement, affording scheduled reinforcement frequencies of 4-360 reinforcers per hour. Herrnstein's equation was fitted to the data obtained from each rat and to the averaged data obtained from the two groups. The value of KH (the parameter expressing the reinforcement frequency needed to maintain the half-maximal response rate) was higher in the DSP4-treated rats than in the control rats; the value of Rmax (the parameter expressing the maximum response rate) did not differ significantly between the two groups. At the end of the behavioural experiment the rats were sacrificed for determination of the concentrations of catecholamines in the brain by high-performance liquid chromatography. The levels of noradrenaline in the parietal cortex, hippocampus and cerebellum of the DSP4-treated rats were less than 20% of those of the control rats. The results provide further evidence that central noradrenergic neurones are involved in the maintenance of operant behaviour by positive reinforcement.

The effect of pentobarbitone on variable-interval performance: analysis in terms of Herrnstein's equation.

Six rats were exposed to a series of variable-interval schedules of reinforcement, each schedule specifying a different reinforcement frequency. The effects of two doses of pentobarbitone (24.16 and 40.27 mumol/kg) upon performance maintained under each schedule were examined. The data were analyzed in terms of the goodness of fit of Herrnstein's (1970) equation. Under control conditions (no injection or injection of vehicle alone) response rate was an increasing negatively accelerated function of reinforcement frequency, the data obtained from each rat conforming closely to Herrnstein's equation. In the presence of pentobarbitone there was a reduction in the value of Rmax (the theoretical maximum response rate) in all six rats. The effect of pentobarbitone upon the value of KH (the reinforcement frequency needed to obtain the half-maximal response rate) differed between animals, the value being increased in some rats and decreased in others. This was shown to reflect a systematic relationship between the baseline value of KH and the change in KH produced by pentobarbitone, high baseline values being associated with reductions, and low baseline values with elevations, in the presence of the drug. The data were also analyzed using conventional rate-dependency analysis. In some animals there was a tendency for lower response rates to be suppressed to a greater degree than higher rates, while the reverse was true in other animals. In general, rate-dependency functions provided poor descriptions of the data obtained from individual subjects.

Cis-platinum chemotherapy for ocular basal cell carcinoma.

We have used intravenous cis-platinum chemotherapy in the treatment of three patients with basal cell carcinoma of the lid extending into the orbit. Cis-platinum chemotherapy caused a reduction in tumour size and thereby delayed surgery in all cases. It allowed for local resection in one case, appeared to delay a patient's exenteration in a second case, and was used prior to radiotherapy in a third case. While not curative, cis-platinum may be useful as an adjuvant to decrease tumour mass prior to local excision and for patients who refuse or must delay exenteration.

Psychological status of diabetic people with or without lower limb disability.

The aim of this study was to compare the quality of life between diabetic people with chronic foot ulceration or lower limb amputation and diabetic controls. Each participant was interviewed using the Psychosocial Adjustment to Illness Scale, the Hospital Anxiety and Depression (HAD) scale, a specifically designed foot questionnaire and a quality of life ladder. Thirteen diabetic unilateral lower limb amputees (DA) were matched for age and sex with 13 unilateral diabetic patients with chronic foot ulceration (DU). Twenty six age- and sex-matched diabetic people with no history of foot ulceration were the controls (DC). Significantly poorer psychosocial adjustments to illness were found in DU and DA compared to diabetic controls (both P < 0.05). DU were also significantly more depressed than the DC (P < 0.05) using the HAD scale. The quality of life ladder revealed that DU were significantly more dissatisfied with their personal lives than DC (P < 0.05). Finally, the foot questionnaire showed that DU had a significantly more negative attitude towards their feet than DC and DA (P < 0.05). This study showed that the psychological status of mobile amputees was better than that of the diabetic foot ulcer patients but not as good as diabetic controls.