The inflammatory milieu and the insulin like growth factor axis in children with inflammatory bowel disease following recombinant human growth hormone treatment.

It is unclear whether recombinant human growth hormone (rhGH) in inflammatory bowel disease (IBD) alters cytokine profile. The objective of this study is to evaluate changes in cytokines and systemic markers of the insulin growth factor axis following 6 months of rhGH treatment in children with IBD. In a six-month randomised control trial in children with IBD treated with rhGH at 0.067 mg/kg/day and controls (11 in each group), we measured pro-, anti-inflammatory cytokines and systemic markers of the IGF axis (total IGF-1, free IGF-1, total IGFBP-3, ALS, IGFBP-2) at baseline (T+0), and six months (T+6). Results expressed as median (range). In the rhGH group, TNFα was 3.1pg/ml (2.9, 100.6) and 3.6pg/ml (3.1, 5.3) at T+0 and T+6, respectively (p=0.85), whereas in the controls this was 3.3pg/ ml (2.7, 4.0) and 3.1pg/m l (2.7, 4.7), respectively (p=0.79). In the rhGH group, IL1ß was 18.0pg/ml (5.0,716.7) and 18.0pg/ml (1.7, 52.2) at T+0 and T+6 respectively(p=0.90), whereas in the controls this was 19.8pg/ml (4.1, 27.1) and 19.1pg/ml (2.4,77.3), respectively (p=0.65). None of the twenty-eight other cytokines analysed was different at T+6 in either group. Despite increase in total IGF1 in the rhGH group (p=0.03), free IGF1, IGFBP3, ALS and IGFBP2 did not change in either group at T+6. Percentage change in IGFBP3, was significantly associated with percentage change in IL2 (r=0.77, p=0.009) and IL4 (r=0.58, p=0.01). Percentage change in ALS was significantly associated with percentage change in IL2 (r=0.90, p less than 0.0001) and IL4 (r=0.63, p=0.04). Although changes in markers of the GH/IGF-1 axis do show an association with cytokines (IL-2, IL-4) in pediatric IBD, six months of rhGH treatment was not associated with any significant changes in levels of a range of pro and anti-inflammatory cytokine. Careful evaluation of disease process is required in future trials of rhGH in paediatric IBD.

Complex interventions for preventing diabetic foot ulceration.

BACKGROUND: Ulceration of the feet, which can lead to the amputation of feet and legs, is a major problem for people with diabetes mellitus, and can cause substantial economic burden. Single preventive strategies have not been shown to reduce the incidence of foot ulceration to a significant extent. Therefore, in clinical practice, preventive interventions directed at patients, healthcare providers and/or the structure of health care are often combined (complex interventions). OBJECTIVES: To assess the effectiveness of complex interventions in the prevention of foot ulcers in people with diabetes mellitus compared with single interventions, usual care or alternative complex interventions. A complex intervention is defined as an integrated care approach, combining two or more prevention strategies on at least two different levels of care: the patient, the healthcare provider and/or the structure of health care. SEARCH METHODS: For the second update we searched the Cochrane Wounds Group Specialised Register (searched 22 May 2015), The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2015, Issue 4), The Database of Abstracts of Reviews of Effects (DARE) (The Cochrane Library 2015, Issue 4), The Health Technology Assessment Database (HTA) (The Cochrane Library 2015, Issue 4), The NHS Economic Evaluation Database (NHS EED) (The Cochrane Library 2015, Issue 4), Ovid MEDLINE (1946 to 22 May 2015), Ovid MEDLINE (In-Process & Other Non-Indexed Citations 21 May, 2015), Ovid EMBASE (1974 to 21 May, 2015) and EBSCO CINAHL (1982 to 22 May, 2015). SELECTION CRITERIA: Prospective randomised controlled trials (RCTs) which compared the effectiveness of combinations of preventive strategies, not solely patient education, for the prevention of foot ulcers in people with diabetes mellitus, with single interventions, usual care or alternative complex interventions. DATA COLLECTION AND ANALYSIS: Two review authors were assigned to independently select studies, to extract study data and to assess risk of bias of included studies, using predefined criteria. MAIN RESULTS: Only six RCTs met the criteria for inclusion. The study characteristics differed substantially in terms of healthcare settings, the nature of the interventions studied and outcome measures reported. In three studies that compared the effect of an education-centred complex intervention with usual care or written instructions, only little evidence of benefit was found. Three studies compared the effect of more intensive and comprehensive complex interventions with usual care. One study found a significant and cost-effective reduction, one of lower extremity amputations (RR 0.30, 95% CI 0.31 to 0.71). One other study found a significant reduction of both amputation and foot ulcers. The last study reported improvement of patients' self care behaviour. All six included RCTs were at high risk of bias, with hardly any of the predefined quality assessment criteria met. AUTHORS' CONCLUSIONS: There is no high-quality research evidence evaluating complex interventions for preventing diabetic foot ulceration and insufficient evidence of benefit.

Patient education for preventing diabetic foot ulceration.

BACKGROUND: Ulceration of the feet, which can result in loss of limbs and even death, is one of the major health problems for people with diabetes mellitus. OBJECTIVES: To assess the effects of patient education on the prevention of foot ulcers in patients with diabetes mellitus. SEARCH METHODS: We searched The Cochrane Wounds Group Specialised Register (searched 03 September 2014); The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 8). SELECTION CRITERIA: Prospective randomised controlled trials (RCTs) that evaluated educational programmes for preventing foot ulcers in people with diabetes mellitus. DATA COLLECTION AND ANALYSIS: Two review authors independently undertook data extraction and assessment of risk of bias. Primary end points were foot ulceration or ulcer recurrence and amputation. MAIN RESULTS: Of the 12 RCTs included, the effect of patient education on primary end points was reported in only five. Pooling of outcome data was precluded by marked, mainly clinical, heterogeneity. One of the RCTs showed reduced incidence of foot ulceration (risk ratio (RR) 0.31, 95% confidence interval (CI) 0.14 to 0.66) and amputation (RR 0.33, 95% CI 0.15 to 0.76) during one-year follow-up of diabetes patients at high risk of foot ulceration after a one-hour group education session. However, one similar study, with lower risk of bias, did not confirm this finding (RR amputation 0.98, 95% CI 0.41 to 2.34; RR ulceration 1.00, 95% CI 0.70 to 1.44). Three other studies, also did not demonstrate any effect of education on the primary end points, but were most likely underpowered. Patients' foot care knowledge was improved in the short term in five of eight RCTs in which this outcome was assessed, as was patients' self-reported self-care behaviour in the short term in seven of nine RCTs. Callus, nail problems and fungal infections improved in only one of five RCTs. Only one of the included RCTs was at low risk of bias. AUTHORS' CONCLUSIONS: In some trials, foot care knowledge and self reported patient behaviour seem to be positively influenced by education in the short term. Yet, based on the only two sufficiently powered studies reporting the effect of patient education on primary end points, we conclude that there is insufficient robust evidence that limited patient education alone is effective in achieving clinically relevant reductions in ulcer and amputation incidence.

A preliminary trial of the effect of recombinant human growth hormone on short-term linear growth and glucose homeostasis in children with Crohn's disease.

BACKGROUND: It is unclear whether recombinant human growth hormone (rhGH) improves linear growth in children with Crohn's disease (CD). AIMS: To investigate the effects of rhGH on height velocity (HV) and glucose homeostasis over a 6-month period. DESIGN AND SETTING: Randomized controlled trial in two tertiary children's hospitals in 22 children with inflammatory bowel disease amongst whom 21 had CD. Duration of disease from diagnosis and number of acute relapses requiring either exclusive enteral nutrition or therapeutic dose of oral prednisolone were similar in the treatment and control groups. INTERVENTION: Either rhGH (0·067 mg/kg per day) as daily subcutaneous injections (rhGH group; n, 11) or no rhGH, (Ctrl; n, 11) for 6 months. MAIN OUTCOME MEASURE: Percentage change in HV after 6 months in the two groups. Auxology, puberty, skeletal age, disease factors, treatment and glucose homeostasis were also assessed. RESULTS: Median HV increased from 4·5 (range, 0·6, 8·9) at baseline to 10·8 (6·1, 15·0) cm/year at 6 month (P = 0·003) in the rhGH group, whereas in the Ctrl group, it was 3·8 (1·4, 6·7) and 3·5 cm/year (2·0, 9·6), respectively (P = 0·58). Median percentage increase in HV after 6 months in the rhGH group was 140% (16·7, 916·7) compared with 17·4% (-42·1%, 97·7%) in the Ctrl group (P < 0·001). There were no significant differences in disease activity and proinflammatory cytokines at baseline and 6 months in both groups and change in bone age for chronological age was also similar in the two groups. In the rhGH group, fasting insulin increased from 4·0 (2·0, 11·0) to 7·0 mU/l (2·0, 16·0) (P = 0·02), whereas in the Ctrl group, it was 3·0 (1·2, 12·7) and 3·8 mU/l (2·1, 7·0) (P = 0·72), respectively. CONCLUSIONS: Although this pilot trial shows that rhGH can improve short-term linear growth in children with CD, the clinical efficacy of this therapy needs to be further studied in longer-term studies of growth, glucose homeostasis and disease status.

Patient education for preventing diabetic foot ulceration.

BACKGROUND: Ulceration of the feet, which can result in loss of limbs and even death, is one of the major health problems for people with diabetes mellitus. OBJECTIVES: To assess the effects of patient education on the prevention of foot ulcers in patients with diabetes mellitus. SEARCH STRATEGY: Eligible studies were identified by searching the Cochrane Wounds Group Specialised Register (22 December 2009), the Cochrane Central Register of Controlled Trials (Cochrane Library 2009 Issue 4 ), Ovid MEDLINE (1950 to November Week 3 2009), Ovid MEDLINE In-Process & Other Non-Indexed Citations (Searched 22/12/09), Ovid EMBASE (1980 to 2009 Week 51) and EBSCO CINAHL (1982 to December 22 2009). SELECTION CRITERIA: Prospective randomised controlled trials (RCTs) which evaluated educational programmes for preventing foot ulcers in people with diabetes mellitus. There was no restriction on language of the publications. DATA COLLECTION AND ANALYSIS: Two review authors independently undertook data extraction and assessment of risk of bias. Primary end-points were foot ulceration or ulcer recurrence and amputation. MAIN RESULTS: Eleven RCTs were included. Three studies described the effect of foot care education as part of general diabetes education compared with usual care. Two studies examined the effect of foot care education tailored to educational needs compared with no intervention. Finally, six studies described the effect of intensive compared with brief educational interventions. Pooling of outcome data was precluded by marked, mainly clinical, heterogeneity. Four RCTs assessed the effect of patient education on primary end-points: foot ulceration and amputations. One of these studies reported a statistically significant benefit of one hour group education after one year of follow-up in people with diabetes who were at high risk for foot ulceration; RR amputation 0.33 (95% CI 0.15 to 0.76); RR ulceration 0.31 (95% CI 0.14 to 0.66), however this study was at high risk of bias and may have overestimated the effect due to a unit of analysis error. One similar, but methodologically superior study did not confirm this finding; RR amputation 0.98 (95% CI 0.41 to 2.34); RR ulceration 1.00 (95% CI 0.70 to 1.44). The other two studies did not detect any effect of education on ulcer incidence or amputation but were underpowered. Patients' foot care knowledge was improved in the short term in five of eight RCTs in which this outcome was assessed, as was patients' self reported self care behaviour in the short term in seven of nine RCTs. The effects on callus, nail problems and fungal infections were described in five of the included studies, of which only two reported temporary improvements after an educational intervention.Only one of the included RCTs was considered to be at low risk of bias. AUTHORS' CONCLUSIONS: Most of the RCTs included in this review are at high or unclear risk of bias. In some trials, foot care knowledge and self reported patient behaviour seem to be positively influenced by education in the short term. This, however, must be viewed with caution. The ultimate goal of educational interventions is preventing foot ulceration and amputation but only four RCTs reported these outcomes and only two reported sufficient data to examine this. Based on these two studies, we conclude that there is insufficient robust evidence that limited patient education alone is effective in achieving clinically relevant reductions in ulcer and amputation incidence.Future research should focus on evaluating the effect of more comprehensive and/or intensive prevention strategies which may also include patient education (complex interventions).

Complex interventions for preventing diabetic foot ulceration.

BACKGROUND: Ulceration of the feet, which can lead to the amputation of feet and legs, is a major problem for people with diabetes mellitus, and can cause substantial economic burden. Single preventive strategies have not been shown to reduce the incidence of foot ulceration to a significant extent. Therefore, in clinical practice, preventive interventions directed at patients, health care providers and/or the structure of health care are often combined (complex interventions). OBJECTIVES: To assess the effectiveness of complex interventions on the prevention of foot ulcers in people with diabetes mellitus compared with single interventions, usual care or alternative complex interventions. A complex intervention is defined as an integrated care approach, combining two or more prevention strategies on at least two different levels of care: the patient, the healthcare provider and/or the structure of healthcare. SEARCH STRATEGY: Eligible studies were identified by searching the Cochrane Wounds Group Specialised Register (28/05/09), the Cochrane Central Register of Controlled Trials (CENTRAL, 28 May 2009), Ovid MEDLINE (1950 to May Week 3 2009), Ovid EMBASE (1980 to 2009 Week 21) and EBSCO CINAHL (1982 to May Week 4 2009). SELECTION CRITERIA: Prospective randomised controlled trials (RCTs) which compared the effectiveness of combinations of preventive strategies, not solely patient education, for the prevention of foot ulcers in people with diabetes mellitus, with single interventions, usual care or alternative complex interventions. DATA COLLECTION AND ANALYSIS: Two review authors were assigned to independently select studies, to extract study data and to assess risk of bias of included studies, using predefined criteria. MAIN RESULTS: Only five RCTs met the criteria for inclusion. The study characteristics differed substantially in terms of health care settings, the nature of the interventions studied and outcome measures reported. In three studies that compared the effect of an education centred complex intervention with usual care or written instructions only, little evidence of benefit was found. Two studies compared the effect of more intensive and comprehensive complex interventions with usual care. One of these reported improvement of patients' self care behaviour. In the other study a significant and cost-effective reduction of lower extremity amputations (RR 0.30 (95% CI 0.13 to 0.71)) was achieved. All five included RCTs were at high risk of bias; with hardly any of the predefined quality assessment criteria met. AUTHORS' CONCLUSIONS: There is no high quality research evidence evaluating complex interventions for preventing diabetic foot ulceration and insufficient evidence of benefit.

Biochemical severity of thyroid ectopia in congenital hypothyroidism demonstrates sexual dimorphism.

BACKGROUND: A recent study suggested that sexual dimorphism affects initial thyroid function in congenital hypothyroidism (CH) but differs according to aetiology of CH. AIMS: To determine if sexual dimorphism was associated with biochemical severity of CH and its aetiology in our large British population. METHODS: We examined retrospectively the initial thyroid function tests of 140 infants diagnosed with CH from screening. All infants underwent Tc-pertechnetate radionuclide scans at diagnosis to establish the aetiology of CH prior to commencement of treatment. Patients were classified into athyreosis, ectopia and presumed dyshormonogenesis on the basis of thyroid scans. A comparison of males and females were made within the three aetiological groups for gestational age, birth weight, initial dose of levothyroxine (LT4), screening TSH, confirmatory plasma thyroxine (T4), confirmatory plasma TSH and age of TSH suppression. RESULTS: There was no significant difference between sexes for gestation, birth weight and initial treatment dose in all aetiological subgroups. In thyroid ectopia, screening TSH and confirmatory plasma TSH were significantly higher in females compared with males (P < 0.01), while confirmatory plasma T4 were significantly lower in females (P < 0.05). No difference was detected between males and females in athyreosis and dyshormonogenesis subgroups for screening TSH, confirmatory plasma TSH and total T4. CONCLUSION: Sexual dimorphism influenced the biochemical severity of thyroid ectopia in congenital hypothyroidism in our British population. However, this effect was not apparent in patients with athyreosis or dyshormonogenesis. Further advances in the molecular genetics of CH are essential to evaluate this phenomenon further.

Discomfort in nursing home patients with severe dementia in whom artificial nutrition and hydration is forgone.

BACKGROUND: While there is debate about whether it may be better to forgo than to initiate artificial nutrition and hydration (ANH) in nursing home patients with severe dementia, the consequences of forgoing ANH in these patients, in particular their discomfort, have not yet been investigated. METHODS: In this prospective, longitudinal, observational study of 178 patients in Dutch nursing homes, discomfort was measured at all measurement times according to the observational Discomfort Scale-Dementia of Alzheimer Type. Furthermore, at all measurement times, plausible determinants of discomfort were registered. Data were analyzed with the statistical technique of generalized estimated equations. RESULTS: Decisions to forgo ANH were made most often in severely demented, female patients with an acute illness as the most important diagnosis at that time. The mean level of discomfort was highest at the time of the decision and decreased in the days thereafter. There were substantial differences in level of discomfort between patients. Dyspnea, restlessness, and physicians' observations of pain and dehydration were associated with higher levels of discomfort. Furthermore, patients who were awake had higher levels of observed discomfort than patients who were asleep. CONCLUSIONS: Forgoing ANH in patients with severe dementia who scarcely or no longer eat or drink seems, in general, not to be associated with high levels of discomfort. The individual differences emphasize the need for constant attention for possible discomfort.

Pubertal growth in young adult survivors of childhood leukemia.

PURPOSE: To determine the effect of cranial irradiation (18 Gy and 24 Gy) on pubertal growth in young adult survivors of childhood acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: Final height (FH) and pubertal growth were retrospectively examined in 142 young adult survivors of childhood ALL. All were in first remission and had received either 18 or 24 Gy of cranial irradiation. Eighty-four children (48 girls) were treated with 24 Gy and 58 (35 girls) with 18 Gy. None had received either testicular or spinal irradiation. Timing and duration of puberty were studied in 110 patients. RESULTS: Significant reduction in height standard deviation score (SDS) from diagnosis to FH was seen in both sexes and in both dose groups. In girls, in both dose groups, mean age at peak height velocity (PHV) and mean age at menarche occurred significantly earlier than in the normal population. In boys, there was a normal timing of PHV. The amplitude of PHV was significantly reduced in both sexes and in both dose groups. Parameters of pubertal duration (PHV to menarche, PHV to FH, and menarche to FH) were not significantly different from normal population values. CONCLUSION: In conclusion, puberty occurred early in girls, but not in boys. Amplitude of PHV was reduced in both sexes, with no reduction in the duration of puberty. It is likely that disturbances of both timing and quality of growth during puberty contribute to the loss of standing height and body disproportion seen in these children.

Patient education for preventing diabetic foot ulceration. A systematic review.

OBJECTIVE: Ulceration of the feet, which can result in loss of limbs and death, is a major health problem for people with diabetes mellitus. The objective of this review is to assess the effectiveness of patient education to prevent diabetic foot ulcers. RESEARCH DESIGN AND METHODS: We conducted a systematic review of randomized controlled trials (RCTs) that evaluated educational programmes for the prevention of foot ulcers in people with diabetes mellitus. We used standard search methods of the Cochrane "Wounds Groups". Two reviewers working independently extracted data and assessed study quality. RESULTS: The methodologic quality of the 8 included RCTs was poor. The internal validity score (range 0-10) of individual RCTs ranged from 2 to 4. Four trials compared the effect of intensive with brief educational interventions; 2 of these reported clinical endpoints. One study involving high-risk patients reported a reduction in ulcer incidence (OR 0.28, 95% confidence interval [CI] 0.13-0.59) and amputation rate (OR 0.32, 95% CI 0.14-0.71) after 1 year. The other RCT did not find an effect after 7 years of follow-up. Two trials showed that participants' foot care knowledge significantly improved with education. In one trial, foot care knowledge was significantly worse at 6 months, although foot care behavior improved significantly. One RCT, that compared patient foot care education as part of a general diabetes education program to usual care, showed no reduction in the risk of foot ulceration. In one RCT, patient education as part of a complex intervention targeted at both people with diabetes and doctors reduced the prevalence of serious foot lesions at 1 year (OR 0.41, 95% CI 0.16-1.00) and improved foot care behavior. Evidence from two RCTs comparing the effect of patient-tailored education in addition to usual care was conflicting. SUMMARY: Evidence, limited by poor methodologic quality and conflicting results, suggests that patient education may have positive but short-lived effects on foot care knowledge and behavior of patients and may reduce foot ulceration and amputations, especially in high-risk patients. High-quality randomized controlled trials are needed to establish the efficacy of patient education to prevent diabetic foot ulcerations.

Comorbidity of somatic chronic diseases and decline in physical functioning:; the Longitudinal Aging Study Amsterdam.

OBJECTIVE: To assess the association of decline in physical functioning with number of chronic diseases and with specific comorbidity in different index diseases. METHODS: A longitudinal design was employed using data from 2,497 older adults participating in the Longitudinal Aging Study Amsterdam. Logistic regression analyses were used to determine influence of chronic diseases on change in physical functioning, operationalized using the Edwards-Nunnally index. RESULTS: Decline in physical functioning was associated with number of chronic diseases (adjusted ORs from 1.58 for 1, to 4.05 for > or =3 diseases). Comorbidity of chronic nonspecific lung disease and malignancies had the strongest exacerbating influence on decline. An exacerbating effect was also found for arthritis in subjects with diabetes or malignancies and for stroke in subjects with chronic nonspecific lung disease or malignancies. A weaker effect than expected was observed for diabetes in subjects with stroke, malignancies, cardiac disease, or peripheral atherosclerosis. CONCLUSION: Comorbidities involving chronic diseases that share etiologic factors or pathophysiologic mechanisms appear to have a weaker negative influence on decline in physical functioning than expected. Results indicate that combinations of diseases that both influence physical functioning, but through different mechanisms (locomotor symptoms vs. decreased endurance capacity) may be more detrimental than other combinations.

The longitudinal relation between chronic diseases and depression in older persons in the community: the Longitudinal Aging Study Amsterdam.

OBJECTIVE: The purposes of this study were to examine the differences in influence of various chronic diseases on depressive symptomatology over time and to determine whether there were differences in such influence depending on physical limitations and time of onset of disease. STUDY DESIGN AND SETTING: Data for this study were obtained from the Longitudinal Aging Study Amsterdam. Two thousand two hundred eighty-eight respondents (age 55-85) were included and followed for a maximum of 6 years. Depressive symptoms (using the CES-D scale), the presence of seven frequently occurring chronic diseases, physical limitations, and sociodemographic variables were assessed by structured interviews. Generalized estimating equation models were estimated for each disease and compared with each other. RESULTS: Lung disease, arthritis, cardiac disease, and cancer were all positively associated with increased depressive symptoms over time. Stroke was associated with depressive symptoms, but these associations were not found when adjusted for physical limitations. For atherosclerosis and diabetes mellitus only weak or no associations with depressive symptoms were found. Recent onset of disease resulted in less strong associations for in cancer, lung disease, and arthritis. CONCLUSION: The results demonstrate that the level of depressive symptoms varies across type of chronic disease. In cardiac disease, arthritis, cancer, and lung disease increased depressive symptoms could not be attributed to physical limitations, but in stroke the association found with depressive symptoms was to a large extent attributable to physical limitations.

Tumor oncogenic expression in malignant effusions as a possible method to enhance cytologic diagnostic sensitivity. An immunocytochemical study of 87 cases.

The diagnostic ability of cytological preparations can be hampered by specimen inadequacy and the presence of representative cells, which may result in a diagnostic accuracy of only 70%. An immunocytochemical battery (ICC), which included anti-p53, anti-c-erbB-2, and B72.3 MoAbs, was used to enhance sensitivity in 87 specimens of body effusions. Thirty-six cases were positive for malignancy using conventional cytology. Forty cases were negative and 11 cases were inconclusive or had an equivocal diagnosis. Sensitivity was 65%, and there was a negative predictive value (NPV) of 62%. p53 was expressed in 50 cases (56%, sensitivity = 83%, NPV = 73%), and B72.3 MoAb was positive in 36 cases (37%, sensitivity = 66%, NPV = 64%). Forty-eight cases (56%) displayed reactivity with anti-c-erbB-2 (sensitivity = 75%, NPV = 63%). The authors concluded that application of an ICC panel of anti-p53, B72.3 and c-erbB-2 to complement conventional cytology increases sensitivity to 98% (P < .0005) with an NPV of 96% (P = .001).

Comparative study between cytology and dot-ELISA for early detection of bladder cancer.

Schistosomiasis remains one of the major public health problems of the tropics. Conservative estimates place the number of infected individuals at about 200 millions. In Egypt, carcinoma of the urinary bladder associated with schistosomiasis is the foremost oncologic problem, because of its high frequency and the late presentation of cases. A newly developed monoclonal antibody CK1K10 to keratinized grade 1 squamous cell carcinoma was used in a dot enzyme-linked immunosorbent assay (Dot ELISA) to test urine samples of 118 patients with bladder carcinoma, 291 patients with genitourinary pathology other than bladder carcinoma, in addition to 550 healthy controls. The overall sensitivity of the dot ELISA was 90% among 118 patients with bladder carcinoma. Twenty-seven of 33 transitional cell carcinoma cases (82%), 68 of the 71 squamous cell carcinoma cases (96%), 7 of 10 undifferentiated tumors cases (70%), and 4 of 4 adenocarcinoma were positive with this assay. The specificity was 90% in our sample population. A comparative study of diagnosis by cytology and dot ELISA was carried out in 57 patients with bladder carcinoma. Dot ELISA was found to be superior as a screening tool for high risk groups (P < .001 using chi-square test). Cytology detected 21% of transitional cell carcinoma, 68% of squamous cell carcinoma, 50% of adenocarcinoma, and 86% of undifferentiated tumors. The dot ELISA assay should be useful for screening high-risk groups because it does not require sophisticated equipment, is noninvasive, does not require highly trained staff, and can be performed in less than 30 minutes.

PREVENTION OF CISPLATIN-INDUCED NEPHROTOXICITY BY METHIMAZOLE.

Nephrotoxicity is a dose-limiting factor in the use of cisplatin against solid tumours. Methimazole, an antithyroid drug containing a free SH group, has a nephroprotective potential against chemically-induced nephrotoxicity. We tried to explore the nephrotoxic effect of the experimentally therapeutic dose of cisplatin (7 mg kg(-1), i.p.), particularly on the nuclear level of kidney cells in male albino rats, as well as the possible protective effect of methimazole. Furthermore, the drug interaction regarding the oncolytic effect of cisplatin was examined in Ehrlich ascites carcinoma (EAC)-bearing mice. A single dose of cisplatin caused kidney damage, 6 days after injection, manifested by 219% increase in serum creatinine, 384% increase in blood urea nitrogen and 170% increase in kidney content of lipid peroxides. Kidney DNA showed clear fragmentations detected by gel electrophoresis. However, kidney reduced glutathione was unchanged at that time period. Histological examination of kidney confirmed the toxic effect of cisplatin. Methimazole (40 mg kg(-1), i.p., 30 min before cisplatin injection) significantly protected the kidney from the nephrotoxic effect of cisplatin as judged from the biochemical parameters investigated as well as the histopathological examination. On the other hand, the survival data in EAC-bearing mice treated with both drugs indicated the persistence of an effective cytotoxic action. This study points to a promising use of this combination and necessitates further experimental and clinical studies. 2000 Academic Press@p$hr Copyright 2000 Academic Press.

Breast conservative surgery: is it appropriate for locally advanced breast cancer following downstaging by neoadjuvant chemotherapy? A pathological assessment.

The application of breast conserving surgery to down-staged cases with locally advanced breast cancer (LABC) after neoadjuvant chemotherapy (NACT) is still a controversial issue with a variable incidence of locoregional failures. In this study, the response of LABC to NACT was assessed pathologically and the eligible candidates for breast conserving surgery were identified retrospectively. The efficacy of preoperative clinical examination and mammography in detecting these pathological changes were also evaluated. The study included 41 LABC cases. They received NACT (FAC) and were then subjected to a mastectomy. The cases were examined clinically and by mammography before starting treatment and immediately before surgery. Residual tumours in the mastectomy specimens were correlated with the pretreatment and preoperative clinical and mammographic findings in order to assess the efficacy of these tools for detection of NACT-induced changes. After 3 cycles of NACT, 78% of women showed an objective response. However, only 25% of them would have been eligible for breast conserving surgery. The remaining responders had an increased incidence of either multifocality and or peritumoural in situ carcinoma. Both clinical examination and mammography were inadequate for detection of these chemotherapy-induced changes and hence for selecting suitable candidates for breast conservation. This study has shown that tumour regression by NACT is probably induced by a process of tumour segmentation and is associated with an increased incidence of ductal in situ lesions in the original tumour bearing area.

A new surgical strategy for breast conservation in locally advanced breast cancer that achieves a good locoregional control rate: preliminary report.

The scope of breast conserving surgery has recently expanded to include locally advanced breast cancer (LABC) patients who are downstaged following neoadjuvant chemotherapy (NACT). However, the efficacy of this approach in achieving adequate locoregional control of disease is in doubt. Some reports have attributed the failure to the association of NACT-induced tumour downstaging which can leave multifocal in situ and invasive lesions around the main tumour mass. In the present study, in order to eradicate all possible tumour satellites, a very wide local excision that included the whole original tumour-bearing area was performed regardless of the expected wide defect. This defect was then immediately reconstructed by an ipsilateral pedicled latissimus dorsi myocutaneous (LDM) flap. The study included 26 patients with LABC without evidence of primary tumour-multicentricity. Tumours were downstaged following NACT. The early cosmetic outcome was good in the majority of cases. Early complications were minimal. Twenty-two patients had a mean follow up period of 30.2 (range 7-50) months. In those evaluable cases, locoregional control of the disease was excellent (100%) but distant metastases occurred in seven cases (31.8%).

Quality of care for patients with type 2 diabetes mellitus in the Netherlands and the United States: a comparison of two quality improvement programs.

OBJECTIVE: To assess differences in diabetes care and patient outcomes by comparing two multifaceted quality improvement programs in two different countries, and to increase knowledge of effective elements of such programs. STUDY SETTING: Primary care in the ExtraMural Clinic (EMC) of the Department of General Practice of the Vrije Universiteit in Amsterdam, the Netherlands, and the Group Health Cooperative (GHC), a group-model health maintenance organization (HMO) in western Washington State in the United States. Data were collected from 1992 to 1997. STUDY DESIGN: In this observational study two diabetes cohorts in which a quality improvement program was implemented were compared. Both programs included a medical record system, clinical practice guidelines, physician educational meetings, audit, and feedback. Only the Dutch program (EMC) included guidelines on the structure of diabetes care and a recall system. Only the GHC program included educational outreach visits, formation of multidisciplinary teams, and patient self-management support. DATA COLLECTION: Included were 379 EMC patients, and 2,119 GHC patients with type 2 diabetes mellitus. Main process outcomes were: annual number of diabetes visits, and number of HbA1c and blood lipid measurements. Main patient outcomes were HbA1c and blood lipid levels. Multilevel analysis was used to adjust for dependency between repeated observations within one patient and for clustering of patients within general practices. PRINCIPAL FINDINGS: In the EMC process outcomes and glycemic control improved more than at GHC, however, GHC had better baseline measures. There were no differences between programs on blood lipid control. During follow-up, intensification of pharmacotherapy was noted at both sites. Differences noted between programs were in line with differences in diabetes guidelines. CONCLUSIONS: Following implementation of guidelines and organizational improvement efforts, change occurred primarily in the process outcomes, rather than in the patient outcomes. Although much effort was put into improving process and patient outcomes, both complex programs still showed only moderate effects.

Chronic diseases and depression: the modifying role of psychosocial resources.

Psychosocial coping resources have been found to protect against depressive symptoms in people with and without chronic diseases. It has not been established, however, whether these resources have the same effects across patients with different diseases. Therefore, the aim of the study was to estimate the direct and buffer effects of psychosocial resources on depression, and to examine whether these effects are different for various chronic diseases. Data were obtained from the Longitudinal Aging Study Amsterdam. In all, 2288 community-dwelling respondents (age 55-85) were included and followed for a maximum of 6 years. Depressive symptoms (using the Center for Epidemiologic Studies-Depression scale), the presence of seven frequently occurring chronic diseases, social support and personal coping resources, physical functioning and sociodemographic variables were assessed by structured interviews. Generalized estimating equation models were estimated for each disease, social support and personal coping resources. All resources, except social network size, showed a direct effect on depressive symptoms regardless of the presence of chronic diseases. Having a partner, high self-esteem, mastery, self-efficacy and feeling less lonely additionally buffered the negative effect of some, but not all, specific chronic diseases. Unexpectedly, in patients with cardiac disease, none of the psychosocial resources exerted a buffer effect on depressive symptoms. For instrumental and emotional support only direct (unfavorable) effects and no buffer effects could be observed. In conclusion, our study provides evidence that buffer effects of psychosocial resources are different across various chronic diseases. This suggests that interventions to enhance specific resources may ameliorate depressive symptoms in specific chronic patients groups.

Concepts of self-rated health: specifying the gender difference in mortality risk.

PURPOSE: This study addresses the question of how the relation between self-rated health (SRH) and mortality differs between genders. In addition to the general question, four specific concepts of SRH are distinguished: SRH in comparison with age peers, SRH in comparison with one's own health 10 years ago, and current and future health perceptions. For these concepts, the gender-specific risks of mortality were evaluated for a short and a longer follow-up period. DESIGN AND METHODS: Baseline and mortality data from the Longitudinal Aging Study Amsterdam (N = 1917, initial ages 55-85 years) were used. Mortality risks were evaluated in Cox regression models at 3 and 7.5 years of follow-up, both adjusted for age and for sociodemographic characteristics, indicators of functional and mental health, lifestyle, and social involvement. All SRH measures were scaled from 1 (positive) to 5 (negative). RESULTS: Baseline correlations between SRH concepts were similar for men and women. After 3 years, 12% of the men and 7% of the women had died; after 7.5 years, these percentages were 27 and 15, respectively. In fully adjusted models, current health perceptions predicted 3-year mortality in men (risk ratio of 1.33). At 7.5 years, mortality in men was predicted by current health perceptions and by SRH compared with age peers (risk ratios of 1.25 and 1.23, respectively). In women, no SRH concept predicted either 3-year or 7.5-year mortality. IMPLICATIONS: SRH was a predictor of mortality only in men, not in women. The gender difference showed most clearly at longer follow-up, in the SRH concept "comparison with age peers."