Citations

Increasingly more tests are being used to detect and characterize diabetic polyneuropathy, but their value in setting minimal criteria for the diagnosis of neuropathy and for staging severity remains inadequately studied. In 180 diabetics, we compared the percentage of patients with test abnormalities and associations among test results, evaluating neuropathic symptoms [neuropathy symptom score (NSS) and neuropathy scale of neuropathy symptom profile (NNSP)], deficits [neurologic disability score (NDS) and vibratory (VDT) and cooling (CDT) detection thresholds], or nerve dysfunction [nerve conduction (NC)]. The percentage of patients that were abnormal varied considerably depending on criteria for abnormality and the tests used. Abnormality (≥ 3 SD of 1 or more parameters) of NC of one or more of four nerves occurred in 80%, of two or more in 69%, of three or more in 46%, and of four in 21%. Similarly, for other tests, the rate of abnormality decreased with use of increasingly stringent criteria. Setting the criteria for abnormal NC at abnormality of two or more nerves, NSS at ≥ 1, NDS at > 6, NNSP at ≥ 97.5th percentile, and at ≥ 95th percentile for the other tests, NC was abnormal in 69%, NSS in 54%, NDS in 48%, NNSP in 47%, VDT in 44%, and CDT in 35%. Abnormality of any two or more of the six tests evaluated occurred in 64% of patients. We estimated that at least 16% of patients without abnormal NC (<2 abnormal nerves) had other findings indicative of neuropathy. By regression analysis, results of one test were in almost all cases associated with those of another test, but the association was not close enough to be predictive. Therefore, although NC provides objective and repeatable results, symptoms and deficits must be measured independently. Assuming no differences between groups of patients, the standardized and validated test (NNSP, VDT, or CDT) should provide the same results at different medical centers. By contrast, the results of NSS or NDS tests, with less standardized approaches and based on the judgment of physicians, might not provide the same results at different medical centers. Tests such as the ones described here may be used to define minimal criteria for the diagnosis of polyneuropathy and for staging its severity.

OBJECTIVE—To characterize potential differences in glycemic control, plasma lipid level, and weight in a cohort of patients previously treated with troglitazone (TROG) who were switched to either pioglitazone or rosiglitazone. RESEARCH DESIGN AND METHODS—After a 2-week washout from TROG, 186 patients were randomly assigned to receive either pioglitazone (PIO) or rosiglitazone (ROSI). Weight, HbA1c, and fasting lipid profile were documented before discontinuing TROG and at 4 months after starting either pioglitazone or rosiglitazone. Secondarily, the effect of concurrent medications on study outcomes was assessed. RESULTS—A total of 127 patients completed follow-up: 67 individuals in the PIO group (32 women, 35 men) and 60 individuals in the ROSI group (33 women, 27 men). There were no significant differences in gender mix, age, weight, fasting lipid profile, or HbA1c between the ROSI and PIO groups. After 4 months of randomized treatment, no change in HbA1c from baseline between or within groups was noted. Both groups experienced an equal and significant increase in weight from baseline of ∼2.0 kg. Thiazolidinedione and HMG-CoA reductase inhibitor therapy had significant and independent effects on lipid profile (P < 0.005). Significant improvements in lipid profile were noted in the PIO group (P < 0.01), whereas none were detected with conversion to ROSI. Specifically, the PIO group experienced an average decrease in total cholesterol of ∼20 mg/dl. CONCLUSIONS—Differing effects on lipid profile were apparent after random conversion from TROG to either PIO or ROSI, despite similar weight increase and glycemic control. The clinical significance of these differences remains to be determined, and further comparative research is warranted.

Fasting hypoglycemia, which persisted for 3 days after insulin treatment was stopped,occurred in a patient with non-insulin-dependent diabetes mellitus who had inappropriate plasma free-insulin levels (18–25 μU/ml) and extremely high antibody-bound insulin (>20,000 μU/ml) but normal counterregulatory hormone secretion and plasma C-peptide levels. The amount of antibody-bound insulin decreased in a biphasic pattern over13 mo of observation with an initial half-life of 35 days and a more gradual decrease with a half-life of 160 days. The number of high-affinity antibody binding sites was virtually identical to the amount of antibody-bound insulin in the patient's plasma. We conclude that the patient's fasting hyperinsulinemia and hypoglycemia were due to release of antibody-bound insulin.

Abstract Anal canal pressure gradient and ileal pouch motor activity were studied in continent and incontinent patients after ileal pouch-anal anastomosis. A multichannel microtransducer catheter was positioned in eight continent and eight incontinent patients 15 months or more after operation and 24-h ambulatory motor activity recorded. Resting anal pressures were significantly lower for incontinent patients during the day and night. The frequency of high-pressure waves was identical in both groups, but peak pressures were higher for incontinent patients. For continent patients, each high-pressure wave was accompanied by a rapid increase in anal canal pressure such that pressure in the pouch was always less than that in the anal canal. For incontinent patients this response was often absent. Incontinent patients had lower resting pressure, more prolonged anal canal relaxation, higher amplitude high-pressure waves and a non-responsive anal canal; the anal canal pressure gradient was therefore frequently reversed.

Abstract Covalent linkage of an antitumour antibody specific for a tumour cell surface antigen to an antilymphocyte antibody specific for the T lymphocyte receptor complex produces a heteroconjugated antibody that can activate and redirect cytotoxic T lymphocytes to lyse tumour cells. The ability of an antilymphocyte-antitumour heteroconjugate (500A2 × 96.5) to direct the lysis of murine melanoma cells by cultured murine lymphocytes was tested in vitro using a 4-h chromium release assay and in vivo with a tumour neutralization assay. In vitro, the addition of heteroconjugated antibody significantly increased tumour lysis by murine C3H/HeN lymphocytes (median specific lysis 82.7 per cent with lymphocytes plus heteroconjugate versus 9.5 per cent for lymphocytes alone, P < 0.001). In vivo, treatment with heteroconjugated antibody plus lymphocytes significantly reduced the development of pulmonary metastases after intravenous tumour administration (median number of pulmonary metastases 28.5 for combined treatment versus 250 for heteroconjugate or lymphocytes alone, P < 0.001).

Abstract Anal canal length, anal canal resting and squeeze pressures, ileal pouch capacity and pouch compliance were measured in 104 patients after ileal pouch—anal anastomosis but before ileostomy closure. The intention was to determine if such parameters were associated with late functional outcome after re-establishment of intestinal continuity. Functional outcome in terms of stool frequency (day and night), incontinence (day and night), perianal pad use, perianal skin irritation, and the use of constipating agents was assessed for all 104 patients 1 year or more (median 438 days) after ileostomy closure. A low mean anal sphincter resting pressure before ileostomy closure was associated with subsequent nocturnal incontinence (P < 0·05) and, to a lesser extent, the need to use constipating agents (P = 0·08). Pouch compliance if low before ileostomy closure was associated with an increased frequency of nocturnal stool frequency after 1 year (P < 0·05). Anal canal length, anal sphincter squeeze pressure and pouch capacity before ileostomy closure were not related to subsequent functional outcome in these patients.

Background and Purpose— Genetic factors influence risk for ischemic stroke and likely do so at multiple steps in the pathogenic process. Variants in genes related to inflammation contribute to risk of stroke. The purpose of this study was to confirm our earlier finding of an association between allele 2 of a variable number tandem repeat of the IL-1 receptor antagonist gene ( IL1RN ) and cerebrovascular disease. Methods— An association study of the variable number tandem repeat genotype with ischemic stroke and stroke subtypes was performed on samples from a North American study of affected sibling pairs concordant for ischemic stroke and 2 North American cohorts of prospectively ascertained ischemic stroke cases and unrelated controls. DNA analysis was performed on cases and controls, stratified by race. Results— After adjustment for age, sex, and stroke risk factors, the odds ratio for association of allele 2 and ischemic stroke was 2.80 (95% confidence interval, 1.29 to 6.11; P =0.03) for the white participants. The effect of allele 2 of IL1RN on stroke risk most closely fits a recessive genetic model ( P =0.009). For the smaller sample of nonwhite participants, the results were not significant. Conclusions— Allele 2 of IL1RN , present in nearly one-quarter of stroke patients, may contribute to genetic risk for ischemic stroke and confirm the previously identified association with cerebrovascular disease. These results are driven by the association in the white participants. Further exploration in a larger nonwhite sample is warranted.

Abstract The surgical management of locally recurrent rectal cancer may involve major procedures and is not for the faint-hearted. Nevertheless, such treatment is preferable to chemotherapy and radiotherapy; the latter will fail over a period of months during which the patient is likely to experience intractable pain. Radical surgery offers good palliation and a better quality of life. Survival is prolonged by such operations which may be curative in up to one-third of patients. Nevertheless, surgeons must be realistic in their assessment of and discussions with patients.