Diabetic neuropathic foot ulcers and amputation

A neuropathic foot ulcer is a severe complication of diabetes that can result in a more severe complication, a lower extremity amputation. We conducted a cohort study of 24,616 individuals with a diabetic neuropathic foot ulcer treated within a multicenter wound care network. A total of 1653 (6.7%) individuals had an amputation and 46.3% of these amputations were of a toe or ray (minor amputation). In the more than 10-year follow-up period that we studied, the percentage of those who had an amputation varied between 5.6% and 8.4%. Of those who had an amputation, the percentage that had a minor amputation increased over time from 4.0% in the earliest years to more than 60% in the later years of observation. The single most important determinant of amputation was the observation of fascia, tendon, and bone at the initial assessment. In conclusion, about 7% of those with a diabetic neuropathic foot ulcer will have an amputation and in the past 10 years there has been a remarkable increase in the number of minor as compared to major amputations.     

Functional and structural characteristics of the glycosaminoglycans of the bladder luminal surface

The glycosaminoglycan layer of bladder has been proposed to play a crucial role in protecting the bladder from harmful substances in urine. Rats were partially cystectomized to determine whether bladder glycosaminoglycans are routinely eluted from the bladder surface in detectable quantities. Cystectomy produced no detectable qualitative or quantitative changes in excreted GAG thereby showing that most urinary glycosaminoglycan originates in the kidney and not from the bladder. Damaging the glycosaminoglycan layer by a dilute acid wash, however, leads to a consistent decrease in the output of urinary GAG which recovers to normal at the same rate as the layer regenerates. This suggests that the newly exposed sites tightly bind urinary GAG. We suggest that such binding may be a component of the normal physiological defense mechanism of the bladder. The bladder glycosaminoglycan layer was isolated, dilute acid being used to elute ionically-bound material and brief trypsinization to elute intercalated proteoglycans from the luminal surface. The GAG from the luminal surface, which was present at a density of one chain per 50 nm.2 of bladder surface, was quite different in composition from that isolated from the whole bladder.     

Optimal timing of a single dose of zoledronic acid to increase strength in rat fracture repair.

We hypothesized that ZA treatment would bolster fracture repair. In a rat model for closed fracture healing, a single dose of ZA at 0, 1, or 2 wk after fracture significantly increased BMC and strength of the healed fracture. Delaying the dose (1 or 2 wk after fracture) displayed superior results compared with dosing at the time of fracture. INTRODUCTION: Bisphosphonates are known to increase bone strength and thus the resistance to fracture by decreasing osteoclastic bone resorption. These properties may enable bisphosphonates to also increase the strength of fracture repair. Zoledronic acid (ZA) is a potent bisphosphonate with a high affinity for bone mineral, allowing bolus intravenous dosing in a range of indications. In this study, we examined the application of bolus dose ZA in endochondral fracture repair. MATERIALS AND METHODS: Carbon-14 labeled ZA was used in a closed rat fracture model. Rats were divided into five treatment groups (n = 25 per group): saline control, local ZA (0.01 mg/kg), and three systemic bolus ZA groups (0.1 mg/kg) with different administration times: at fracture, 1 wk after fracture, and 2 wk after fracture. Rats were killed 6 wk postoperatively. Postmortem analyses included radiography, QCT, microCT, biomechanical testing, scintillation counting, autoradiography, and histology. RESULTS: Single-dose systemic ZA administration significantly increased callus volume, callus BMC, and mechanical strength. Perioperative treatment increased mechanical strength by 30% compared with controls (p < 0.05). Administering the systemic dose at 1 or 2 wk after fracture further increased mechanical strength compared with controls by 44% and 50%, respectively (p < 0.05). No significant differences in mechanical parameters were seen with local injection at the dose studied. Autoradiographic analysis indicated that ZA binds significantly to bone that is present at the time of administration. ZA quantification indicated that delayed administration significantly increased the uptake efficiency in the callus. Histological and microCT analysis showed that ZA treated calluses had a distinctive internal structure consisting of an intricate network of retained trabecular bone. CONCLUSIONS: The timing of a single systemic dose of ZA plays an important role in the modulation of callus properties in this rat fracture model; delaying the single dose produces a larger and stronger callus.     

Recombinant erythropoietin improves exercise capacity in anemic hemodialysis patients

The objective of this study was to quantitate the improvement in exercise capacity produced in anemic chronic hemodialysis (HD) patients after correction of their anemia with recombinant human erythropoietin (rHuEPO). The maximal exercise capacity and quadriceps strength of 19 anemic HD patients was tested before and after correction of the anemia with rHuEPO. A progressive work exercise protocol (PWET) on a cycle ergometer was used to compare measurements of maximal oxygen uptake (VO2max), maximal heart rate, and subjective assessment of fatigue during the test. Measurements of quadriceps strength were performed before the cycle ergometer studies. At baseline, all patients had reduced VO2max (15.3 +/- 5.4 mL/kg/min) and maximal exercise heart rates (138.5 +/- 23.9 beats/min). rHuEPO increased the mean hematocrit from 21.2% to 35%, and this was associated with a 17% increase (P less than 0.0005) in the VO2max. At any specified work load, rHuEPO treatment decreased heart rate, minute ventilation, and the subjective perception of fatigue. Both isometric and isokinetic measurements of quadriceps strength were improved following administration of rHuEPO. The maximal exercise heart rate was decreased in comparison to the baseline measurements (P less than 0.04), suggesting that in contrast to normal subjects, HD patients stop exercise before oxygen transport limitations are reached. In this unselected group of chronic HD patients, rHuEPO produced clinically significant improvements in both aerobic exercise capacity and isometric and isokinetic quadriceps strength. The improvement in aerobic capacity was substantially less than would have been expected from the correction of a comparable degree of anemia in non-HD patients. None of the 19 treated patients attained the exercise performance level predicted for a sedentary normal subject.     

Obesity in youth and middle age and risk of colorectal cancer in men

To investigate an association between colon cancer and obesity during early adulthood—a potentially important period in the etiology of this disease—the authors assembled, by computer linkage, a population-based historical cohort of 52,539 men born between 1913 and 1927 residing in Hawaii (USA), for whom weight and height had been recorded in 1942–43 and 1972. Linkage of this cohort to the Hawaii Tumor Registry resulted in the identification of 737 incident cases of colorectal cancer for 1972–86. An average of 3.8 cancer-free controls were matched to each case on month and year of birth and ethnicity of the parents. A case-control analysis in each anatomic subsite of the large bowel revealed that both early and middle-age body mass increased the risk of sigmoid cancer in men in a dose-dependent fashion. The odds ratios (OR) for sigmoid cancer for the highest compared with the lowest tertiles of Quetelet index were: 2.1 (95 percent confidence interval [CI]=1.4–3.2) and 1.7 (CI=1.1–2.5), at ages 15–29 and in prediagnostic years, respectively. These associations were additive and idependent of socioeconomic status. Men who were above the median Quetelet index in 1942 and 1972 had an OR of 2.7 (CI=1.8–4.0), compared with those who were below the median in both periods. This study provides further evidence for an association of obesity with colon cancer in men and suggests that this association is limited to the sigmoid colon and may be related to both early and late events of colon carcinogenesis.The authors are with the Epidemiology Program, Cancer Research Center of Hawaii, University of Hawaii. Address correspondence to Dr Le Marchand, Epidemiology Program, Cancer Research Center of Hawaii, 1236 Lauhala Street, Suite 407, Honolulu, HI 96813, USA. This work was supported in part by Public Health Service grant 5-R29-CA44503 and contract NO1-CN-55424 from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services.