[Ultrastructural localization of protein-4 binding insulin-like growth factors in cow follicles].
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Biomedical subjects
Publications and source records attributed to D G Armstrong.
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The aim of this study is to compare the effectiveness of total contact casts based on wound location in groups of patients with diabetes mellitus with neuropathic ulcerations under the forefoot and patients with midfoot ulcerations associated with acute Charcot's arthropathy. Twenty-five consecutive diabetic patients with Meggitt-Wagner grade I neuropathic foot ulceration (NU) and 22 consecutive diabetic patients with neuropathic ulceration and acute Charcot's arthropathy (CU) were selected for study. Larger wounds took longer to heal in both the CU (p < 0.0001) and NU groups (p < 0.0001). Duration of ulcer prior to treatment also was significantly associated with increased healing time in both groups (p = 0.008 NU, p = 0.03 CU). The CU group had larger wounds (10.3 +/- 4.6 vs 7.7 +/- 4.0 cm2, p = 0.04) but took significantly less time to heal (28.4 +/- 13.0 vs 38.8 +/- 21.3 days, p = 0.04) than did subjects with neuropathic ulcerations only. The NU group had their ulcers present for a significantly longer period of time prior to contact casting (88.5 +/- 98.3 vs 17.7 +/- 12.9 days, p = 0.001). In this study, subjects with ulcerations secondary to acute Charcot fractures healed more rapidly than in previous reports with healing times of forefoot neuropathic ulcers similar to previous studies. Every patient's ulcer healed. There were no cast-related ulcerations, infections, or hospitalizations. Concerns regarding the safety of total contact casts to treat well-vascularized superficial forefoot and midfoot plantar wounds appear to be unfounded.
The aim of this longitudinal study was to report on the clinical characteristics and treatment course of acute Charcot's arthropathy at a tertiary care diabetic foot clinic. Fifty-five diabetic subjects, with a mean age of 58.6 +/- 8.5 years, were studied. All patients were treated with serial total contact casting until quiescence. Following casting and before transfer to prescription footwear, patients were eased into unprotected weightbearing via a removable cast walker. This cohort was followed for their entire treatment course and for a mean 92.6 +/- 33.7 weeks following return to shoes. Pain was the most frequent presenting complaint in these otherwise insensate patients (76%). The mean duration of casting was 18.5 +/- 10.6 weeks. Patients returned to footwear in a mean 28.3 +/- 14.5 weeks. Nine per cent of the population had bilateral arthropathy. These subjects were casted significantly longer than the unilateral group (p < 0.02). Surgery was performed on 25 % of patients, with approximately two-thirds of these procedures involving plantar exostectomies and one-third fusions of affected joints. Patients receiving surgery remained casted significantly longer than non-surgical patients (p < 0.05). Additionally, men were casted longer than women (p < 0.008). Acute Charcot's arthropathy requires prompt, uncompromising reduction in weightbearing stress. Our data show that the ambulatory total contact cast is very effective for this. Regardless of the specific treatment method instituted, it is imperative that appropriate and aggressive treatment be undertaken immediately following diagnosis to help prevent progression to a profoundly debilitating, limb-threatening deformity.
PURPOSE: We are unaware of any report in the medical literature that has discussed risk factors for both mortality and discharge disposition following lower extremity amputation (LEA). Our aim was to report risk factors associated with in-hospital mortality and the need for institutional care in diabetics with LEAs. PATIENTS AND METHODS: We abstracted data for every hospitalization for a LEA from January 1 to December 31, 1993 in six metropolitan statistical areas in South Texas. Amputation level was categorized as foot, leg, or thigh. Discharge status categories were: home, nursing home, rehabilitation facility, and death. We used the Kaplan scale of cogent comorbidities to determine the relationship of 12 disease categories and their association with discharge status. RESULTS: There were 1,043 LEAs in South Texas in 1993. Although only 2.3% of the population was admitted from an institutional care facility, over 25% were discharged to one. Of the total population, 18.5% were discharged to a nursing home and 7.0% to a rehabilitation facility, and 5.1% died within the period of hospitalization. We performed a univariate analysis. Factors with a P <0.25 were included in a stepwise logistic regression analysis with an alpha of 0.05. High level (leg or thigh) amputation, peripheral vascular disease, male gender, and absence of advanced locomotor impairment were associated with discharge to a rehabilitation facility. For discharge to a nursing home, significant associations were found with: female gender, advanced age (>65 years), single marital status, high level amputation, and advanced cerebrovascular disease and locomotor impairment. Death following LEA was strongly associated with female gender, high level amputation, advanced renal disease, anemia, and congestive heart failure. CONCLUSION: A significant number of patients either die or require long-term care following a diabetes-related LEA, thus further adding to the burden of this sequela. Several clinical parameters are significantly associated with discharge status after this procedure. More prospective clinical research is needed to verify the associations and to clarify their application in practice.
The aim of this study was to identify the age adjusted and level specific mortality rate in African-Americans, Hispanics and non-Hispanic whites (NHW) during the perioperative period following a lower extremity amputation. We identified amputation data obtained from the Office of Statewide Planning and Development in California for 1991 from ICD-9-CM codes 84.11-84.18 and diabetes mellitus from any 250 related code. Amputations were categorized as foot (84.11-84.12), leg (84.13-84.16) or thigh (84.17-84.18). Death was coded under discharge status. Age adjusted and level specific mortality rates per 1000 amputees were calculated for each race/ethnic group. The age adjusted mortality was highest for African-Americans (41.39) compared to Hispanics (19.69) and NHW's (34.98). Mortality was consistently more frequent for proximal amputations. We conclude that mortality rates for persons with diabetes hospitalized for an amputation varied by race, gender and level of amputation. Higher prevalence or severity of risk factors may explain the excess mortality observed in African-Americans.
BACKGROUND AND PURPOSE: The purpose of this study was to compare skin temperatures in patients with asymptomatic peripheral sensory neuropathy, patients with neuropathic ulcers, and patients with Charcot's arthropathy using the contralateral limb as a control. SUBJECTS: On a retrospective basis, patients with diabetes (N = 143) were divided into three groups: patients with asymptomatic sensory neuropathy (n = 78), patients with neuropathic foot ulcers (n = 44), and patients with neuropathic fractures (Charcot's arthropathy) (n = 21). METHODS: We evaluated the subjects' skin temperatures with a portable hand-held infrared skin temperature probe at the time pathology was initially identified and at subsequent clinical visits for an average of 22.1 months (SD = 6.4). Skin temperatures of the contralateral foot were measured as a control. RESULTS: There were differences in skin temperature between the affected foot and the contralateral (i.e., nonaffected) foot among the patients with Characot's arthropathy (8.3 degrees F) and the patients with neuropathic ulcers (5.6 degrees F), with no difference identified among the patients with asymptomatic sensory neuropathy. Five patients with neuropathic ulcers experienced reulceration a mean of 12.2 months (SD = 6.4) after initial healing, with a corresponding increase in skin temperature. (89.6 degrees +/- 1.2 degrees F versus 82.5 degrees +/- 2.9 degrees F) at the clinic visit immediately preceding reinjury. CONCLUSION AND DISCUSSION: The data suggest that monitoring of the corresponding contralateral foot site may provide clinical information before other clinical signs of injury can be identified.
We reviewed the hospital course of 77 diabetic and 69 nondiabetic subjects who had incision, drainage, and exploration of infected puncture wounds of the foot. Diabetics were 5 times more likely to have multiple operations and 46 times more likely to have a lower extremity amputation than nondiabetics. The interval from injury to surgery was significantly longer in diabetics than nondiabetics. Total lymphocyte count and hemoglobin, hematocrit, and albumin values were significantly lower in diabetics than in nondiabetics. Diabetic amputees had higher prevalences of nonpalpable pulses, nephropathy, neuropathy, and osteomyelitis as compared with diabetic nonamputees. The neuropathic diabetic foot is not protected by pain. When combined with other comorbid factors, this may increase morbidity associated with puncture wounds of the foot.
Folliculogenesis is associated with the development of a group of follicles at various stages of maturation from which a species-specific number of follicles are selected for continued growth. These selected follicles, after being exposed to the requisite hormonal environment, ovulate in response to the preovulatory gonadotrophin surge. Follicular dominance is the mechanism by which the selected follicle(s) undergoes rapid development in an environment where growth and development of other follicles, recruited at a similar time, are suppressed. These processes are controlled by the interaction of endocrine signals and locally produced ovarian growth factors. The response of the two major follicular cell types, granulosa and theca cells, to gonadotrophins is regulated by the local production of growth factors. Mechanisms controlling growth factor action occupy a central role in the regulation of folliculogenesis. In this review, we highlight the influence of the extracellular matrix in this process by describing its involvement in regulating the activity of components of the insulin-like growth factor system, transforming growth factor beta superfamily, fibroblast growth factors and the epidermal growth factor/transforming growth factor alpha family. In addition, some recent studies on the role of protein factors produced by the dominant follicle in maintaining dominance and inhibiting the growth of subordinate follicles are described.
Insulin-like growth factor-binding protein (IGFBP) extraction protocols were tested for their efficacy in removing IGFBPs from bovine plasma and bovine granulosa cell culture medium compared with standard acid exclusion chromatography. Traditional extraction methods, acidification, Sep-Pak, ethanol:acetone:acetic acid (EAA) and EAA-cryoprecipitation (EAA-C), failed to remove all the IGFBPs from both granulosa cell culture medium and plasma. However, EAA and EAA-C treatment of plasma samples did give values similar to those obtained by acid exclusion HPLC, when corrected for extraction efficiency. There was an inverse relationship between insulin-like growth factor-I (IGF-I) concentration in plasma samples, as measured using HPLC chromatography, and IGF-I concentration after EAA extraction. Furthermore, the interference caused by residual IGFBPs differed between samples taken from animals given various treatment that altered peripheral IGF-I concentrations. As for plasma samples, EAA was the most effective extraction method for culture media, but residual IGFBPs caused an overestimation of IGF-I concentrations. In culture media, but not plasma, it was possible to block the interference of IGFBPs in the IGF-I assay, in both extracted and non-extracted culture samples, by the addition of excess IGF-II. Using this assay procedure, no IGF-I production by bovine granulosa cells was detected. This was confirmed by HPLC acid chromatography. It is concluded that HPLC extraction is needed for the accurate measurement of peripheral IGF-I concentrations. For granulosa cell culture media it is possible to measure IGF-I concentration in non-extracted samples if the IGFBPs are blocked by adding IGF-II. Using either this assay, or after HPLC acid chromatography, no IGF-I was detected in culture media, suggesting that IGF-I is not produced by non-luteinised bovine granulosa cells.
OBJECTIVE: To compare the effectiveness of therapeutic, comfort, and athletic shoes with and without viscoelastic insoles. RESEARCH DESIGN AND METHODS: We compared pressure reduction at ulcer sites under the hallux (n = 10), first metatarsal (n = 10), and lesser metatarsals (n = 12), using extra-depth, athletic, and comfort shoes with and without viscoelastic insoles. A rubber-soled canvas oxford was used to establish baseline pressure values. RESULTS: When used in conjunction with a viscoelastic insole, all shoe types reduced mean peak plantar pressure better than their non-insoled counterparts (P < 0.05). Consistently, comfort shoes reduced pressure significantly better than both the cross trainers and extra-depth shoes for ulcers under the first and lesser metatarsals (P < 0.05). For each shoe type, the addition of the viscoelastic insole provided a significant reduction in mean peak pressure (P < 0.05). Compared with stock insoles, viscoelastic insoles reduced pressures an additional 5.4-20.1% at ulcer sites. The same trend was also observed at regions of the foot not associated with an ulceration. CONCLUSIONS: When used in conjunction with a viscoelastic insole, both the comfort and athletic cross-trainer shoes studied were as, if not more, effective than commonly prescribed therapeutic shoes in reducing mean peak first and lesser metatarsal pressures. Furthermore, comfort shoes were as effective as therapeutic shoes in reducing pressure under the great toe. Both of these shoe types may be viable options to prevent the development or recurrence of foot ulcers.
The authors compare the level of foot amputation by age, prevalence of arterial disease as a precipitating factor, gender, and ethnicity in persons with diabetes mellitus. Medical records were abstracted for each hospitalization for a lower extremity amputation from January 1 to December 31, 1993, in six metropolitan statistical areas in south Texas. Amputation level was defined by ICD-9-CM codes and were categorized as foot, leg, and thigh amputations. Foot-level amputations were further subcategorized as hallux or first ray, middle, fifth, multiple digit or ray, and midfoot amputations. Only the highest amputation level for each individual was used in the analysis. Of 1,043 subjects undergoing a lower extremity amputation in south Texas in the year 1993, 477 received their amputation at the level of the foot. African-Americans requiring a foot-level amputation were at significantly higher risk to undergo a midfoot-level amputation than was the rest of the population. Nearly 40% of all subjects undergoing a foot-level amputation had a previous history of amputation. However, nearly 40% of subjects undergoing foot amputations had not been diagnosed either before or during admission with peripheral arterial occlusive disease, suggesting a causal pathway dependent primarily on neuropathy. This implies that better screening of diabetic patients with appropriate risk-directed treatment at the primary care level may significantly impact the large number of preventable diabetes-related lower extremity amputations.
OBJECTIVE: To evaluate the standard of evaluation and treatment of the infected diabetic foot ulceration at a 551-bed university teaching institution. DESIGN: A retrospective review of a 4-year consecutive sample (1991-1994). POPULATION: Two hundred fifty-five patients who were admitted to a hospital for care of an infected diabetic foot ulceration. Patients were subdivided into the following 4 dichotomous variables: (1) whether the patient underwent a lower-extremity amputation, (2) whether the patient was admitted once or multiple times, (3) whether the patient underwent intraoperative debridement, and (4) whether the patient was admitted to medical or surgical services. RESULTS: All groups that were evaluated had undergone a less than adequate foot examination. Of the admitted patients, 31.4% did not have their pedal pulses documented; 59.7% of the admitted patients were not evaluated for the presence or absence of protective sensation. Nearly 90% of the wounds were not evaluated for involvement of underlying structures, and foot radiographs were not performed in 32.9% of the patients. There were more blood cultures ordered (62.0%) than wound cultures (51.4%). CONCLUSION: The results of this study highlight the need for a systematic, detailed lower-extremity examination for every diabetic patient who is admitted to a hospital, particularly those who are admitted with a primary diagnosis that involves a foot complication.
The aim of this longitudinal study was to report on the clinical characteristics and treatment course of acute Charcot's arthropathy at a tertiary care diabetic foot clinic. Fifty-five diabetic subjects, with a mean age of 58.6 +/- 8.5 years, were studied. All patients were treated with serial total contact casting until quiescence. Following casting and before transfer to prescription footwear, patients were eased into unprotected weightbearing via a removable cast walker. This cohort was followed for their entire treatment course and for a mean 92.6 +/- 33.7 weeks following return to shoes. Pain was the most frequent presenting complaint in these otherwise insensate patients (76%). The mean duration of casting was 18.5 +/- 10.6 weeks. Patients returned to footwear in a mean 28.3 +/- 14.5 weeks. Nine per cent of the population had bilateral arthropathy. These subjects were casted significantly longer than the unilateral group (p < 0.02). Surgery was performed on 25% of patients, with approximately two-thirds of these procedures involving plantar exostectomies and one-third fusions of affected joints. Patients receiving surgery remained casted significantly longer than non-surgical patients (p < 0.05). Additionally, men were casted longer than women (p < 0.008). Acute Charcot's arthropathy requires prompt, uncompromising reduction in weightbearing stress. Our data show that the ambulatory total contact cast is very effective for this. Regardless of the specific treatment method instituted, it is imperative that appropriate and aggressive treatment be undertaken immediately following diagnosis to help prevent progression to a profoundly debilitating, limb-threatening deformity.
We reviewed the hospital course of 77 diabetic and 69 nondiabetic subjects who had incision, drainage, and exploration of infected puncture wounds of the foot. Diabetics were 5 times more likely to have multiple operations and 46 times more likely to have a lower extremity amputation than nondiabetics. The interval from injury to surgery was significantly longer in diabetics than nondiabetics. Total lymphocyte count and hemoglobin, hematocrit, and albumin values were significantly lower in diabetics than in nondiabetics. Diabetic amputees had higher prevalences of nonpalpable pulses, nephropathy, neuropathy, and osteomyelitia as compared with diabetic nonamputees. The neuropathic diabetic foot is not protected by pain. When combined with other comorbid factors, this may increase morbidity associated with puncture wounds of the foot.
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We report on the prevalence of osteomyelitis, the prevalence of soft tissue infections, and the type and number of pathogens encountered in bone and soft tissue infections caused by puncture wounds in children. In addition, we seek to establish whether shoe gear plays a role in the flora in infected puncture wounds and if laboratory indices are indicative of the presence of infection. The group consisted of 44 nondiabetic children admitted to hospital for puncture wounds of the foot. Cultures were positive for osteomyelitis in 7 patients (16%), all involving the forefoot (P < .04). The most common pathogen in soft tissue infections was Staphylococcus aureus. The most common pathogen in osteomyelitis was Pseudomonas aeruginosa. There was no significant difference in the prevalence of osteomyelitis and soft tissue infection based on footwear. There were no cases of osteomyelitis encountered among barefoot children (P < .04). In 10 cases (83%), P aeruginosa infection (both soft tissue and bone) occurred while the patients were wearing tennis shoes (P < .04). In this study, the leukocyte count (normal in 29 patients [66%]), erythrocyte sedimentation rate (normal in 28 patients [64%]), and temperature (normal in 44 patients [95%]) did not have any predictive value in differentiating soft tissue infection from osteomyelitis in children.
Foot ulcers in persons with diabetes are one of the most common precursors to lower extremity amputation. Appropriate care of the diabetic foot ulceration requires a clear, descriptive classification system that may be used to direct appropriate therapy and possibly predict outcome. Ideally, this system would be used by all participants in a multidisciplinary limb salvage team. We describe a clinical classification system for diabetic foot wounds that evaluates wound depth, the presence of infection, and peripheral arterial occlusive disease in every category of the wound assessment. The goal of this system is to improve communication, leading to a less complex, more predictable treatment course, and, ultimately an improved result.
The purpose of this study was to describe the use of skin temperature assessment in diabetics with acute Charcot's arthropathy to monitor resolution of inflammation longitudinally throughout the course of treatment and to predict development of neuropathic ulcers. Thirty-nine diabetic subjects presenting with acute Charcot's arthropathy received thermometric monitoring throughout their treatment course. Subjects were treated with a standard protocol involving total contact casting, removable cast walkers, and progression to therapeutic shoes. There was a steady decrease in temperatures during the casting regimen. After temperature gradients normalized, subjects were progressed to custom therapeutic shoe gear and insoles and were followed for a mean 22.6 +/- 7.1 months. Following quiescence, 8% returned during the follow-up period with a new-onset neuropathic ulceration. Temperature gradients during taken the visit prior to ulceration were significantly higher in this group than for the rest of the population. Elevated temperatures were strongly correlated with the location of arthropathy. Temperatures decreased in a predictable manner as acute arthropathy resolved. Additionally, increased temperature gradients may be predictive of future ulceration.