Extensive Foot Research Articles

Progression and potential regression of glomerulosclerosis

illicit drugs. He had not noted any peri-orbital or leg edema, shortness of breath, chest pains, hematuria, or urinary symptoms. His only medication was fosinopril, 10 mg orally each day. The physical examination revealed a well-developed white male in no apparent distress. The blood pressure was 146/ 84 mm Hg; pulse, 84 beats/min; respiratory rate, 16 breaths/ min; temperature, 98.68F; weight, 215 lbs; and height, 599′′. The physical examination was unremarkable. Ultrasound tests showed an atrophic 3.4 cm echogenic right kidney, and a 12.6 cm left kidney with normal echogenicity. Laboratory evaluation revealed: serum glucose, 97 mg/dL; cholesterol, 137 mg/dL; triglycerides, 672 mg/dL; albumin, 4.1 g/dL; total protein, 7.4 g/dL; hematocrit, 46%; platelets, 361,000/mm; serum creatinine, 1.2 mg/dL; BUN, 15 mg/dL; and normal electrolytes. Creatinine clearance was 126 mL/min. An open renal biopsy disclosed early lesions of focal segCASE PRESENTATIONS mental glomerulosclerosis (FSGS) and glomerulomegaly, charPatient 1 acteristic of secondary FSGS (Fig. 1). The renal changes most A 13-year-old white boy was noted to have proteinuria, likely were related to his unilateral renal atrophy. He was 1 g/24 hr, eight years ago on a routine physical examination treated with a higher dose of the same ACE inhibitor. At latest for participation in school sports. The serum creatinine and follow-up nearly two years later, the serum creatinine was blood glucose levels were normal, and serologic tests were 1.2 mg/dL, and proteinuria was ,500 mg/24 hr. negative. Ultrasound examination demonstrated a very small, atrophic right kidney and hypertrophy and normal echogenicity Patient 2 of the left kidney. A diagnosis of solitary functioning kidney A 5-year-old white girl presented 17 years ago with an 8was made. month history of relapsing nephrotic syndrome. The first two The patient was treated with dietary protein restriction and episodes were steroid-sensitive, but subsequent relapses were an angiotensin-converting enzyme (ACE) inhibitor. At routine steroid-dependent, and she was admitted for renal biopsy. Labfollow-up at age 19, the proteinuria had increased to 3.7 g/24 oratory tests revealed normal serum creatinine (0.8 mg/dL), hr, and he was referred for further evaluation. The medical hypoalbuminemia (0.8 g/dL), proteinuria (2 g/24 hrs), negahistory was significant for a bilateral inguinal hernia repair at tive ASO titers, and normal complement levels. Physical exage 10 months, and a poorly documented history of vesicoureamination showed 31 edema, and her blood pressure was teral reflux as a child. The family history was significant for 120/70 mm Hg. microhematuria detected in the father three months prior to The renal biopsy showed no segmental sclerosis in the 23 this evaluation, a maternal grandmother with hypertension, glomeruli sampled. Immunofluorescence studies were negative, and a paternal grandfather with diabetes. There was no family and electron microscopy showed extensive foot process effacehistory of visual abnormalities or hearing loss. No hypertension ment. An initial diagnosis of minimal change disease was made. had been noted at regular follow-ups. The patient had gained Corticosteroid treatment was continued with no response even 25 pounds over the previous 18 months. A college student, he at a higher dose (40 mg daily). Addition of a six-week course worked part-time in an ice cream store. He had smoked for of chlorambucil resulted in remission (serum albumin, 4.3 g/dL; one month one year previously and did not drink alcohol or use proteinuria, 420 mg/24 hr). She remained in remission for 18 months and had a normal serum creatinine (0.3 mg/dL) when she was 7 years old. She then had a relapse following an upper

CD2AP is expressed with nephrin in developing podocytes and is found widely in mature kidney and elsewhere.

CD2-associated protein (CD2AP) is an adapter molecule that can bind to the cytoplasmic domain of nephrin, a component of the glomerular slit diaphragm. Mice lacking CD2AP exhibit a congenital nephrotic syndrome characterized by extensive foot process effacement, suggesting that CD2AP-nephrin interactions are critical to maintaining slit diaphragm function. We have examined the patterns of expression of both CD2AP and nephrin in developing mouse and human kidney. Both proteins were first detected in developing podocytes at the capillary loop stage of glomerulogenesis and eventually became concentrated near the glomerular basement membrane. CD2AP was also observed diffusely in collecting duct and apically in many cells of proximal and distal tubule. Kidneys from Cd2ap -/- mice initially exhibited normal nephrin localization, but as the mice aged and foot processes became effaced, nephrin disappeared. In laminin-beta(2) mutant mice exhibiting nephrotic syndrome, CD2AP in glomeruli was aberrantly localized in a primarily punctate pattern. Extensive extrarenal expression of CD2AP was observed in endothelial and epithelial cells, in many cases with a specific subcellular localization. Together, these results suggest that CD2AP is not only involved in maintaining the slit diaphragm but may also have a general role in maintaining specialized subcellular architecture. The severity of kidney disease in Cd2ap mutant mice may have eclipsed manifestation of defects in other tissues.

Pedal Bypass for Critical Limb Ischemia

This case panel discussion addresses some of the problems and judgment decisions required in a patient with extensive forefoot gangrene, a stenosis of the superficial femoral artery (SFA), and occlusions of all three leg arteries in the mid and upper leg. With extensive foot debridement to the trans-metatarsal level, balloon angioplasty of the SFA, and a vein bypass to the distal anterior tibial artery, a functional foot remnant was saved. The timing of the various procedures, technical details regarding them, and other issues are discussed.

Repair of high-energy-induced tissue defects of the dorsal foot by free muscle transfer and skin graft.

Various alternative methods have been used for repair of extensive dorsal foot defects due to high-energy-induced injuries. The authors reconstructed such defects with free muscle transfers and skin grafts in 9 male patients (average age, 21.7 years) between the years 1995 and 1998. Patients (right foot, 5; left foot, 4) presented with injuries due to military rifle gunshot (N = 4), mine explosion (N = 2), high-voltage electricity (N = 2), and traffic accident (N = 1). The patient injured in a traffic accident was treated with skin grafting only, and experienced osteomyelitis and skin breakdown. The other 8 patients were injured acutely and were hospitalized within 3 weeks of injury. After serial debridement of necrotic tissues, surgery was performed at an average of 6 weeks postinjury. Metatarsal bone defects of 5 cm in 3 patients were repaired by iliac (N = 2) and fibular (N = 1) bone grafts. Free muscle latissimus dorsi (N = 4) and rectus abdominis (N = 5) flaps were transferred microsurgically. The transferred muscle flaps were covered with split-thickness skin grafts. Mean operation duration was 5 hours 12 minutes. All flaps survived. The average area of soft-tissue defect repaired was 93 cm2 (range, 36-231 cm2). Average follow-up was 25 months. No symptoms of osteomyelitis and skin breakdown were encountered in the 8 acutely injured patients. Monofilament sensory tests revealed diminished protective sensation in 5 patients and absence of protective sensation in 4 patients. Partial resorption of bone grafts occurred in 2 patients. Thinning of the flaps was performed by tangential excision in 2 patients whose muscle flaps did not diminish in thickness. All patients were able to wear normal shoes. The authors suggest the use of free muscle transfer in reconstructing extensive soft-tissue defects of the dorsal foot.

Continuous sciatic nerve infusion: Expanded case report describing a new approach

Background and Objectives. Severe pain following extensive reconstructive foot surgery is difficult to manage effectively. Sciatic nerve block provides excellent analgesia for a limited duration. I wanted to determine an approach to sciatic nerve block enabling an infusion of a local anesthetic for a prolonged period without loss of efficacy due to catheter displacement. Methods. Seventy-six consecutive sciatic nerve catheter placements—in 73 patients undergoing reconstructive foot surgery—were performed by four different approaches. Soft epidural catheters were found to be unsatisfactory—both for placement and for prolonged infusion. A firmer catheter, also capable of “through the catheter” nerve stimulation, was developed and proved to be satisfactory on both counts. Traditional approaches proved satisfactory for identifying the nerve but were unsatisfactory for prolonged infusion. A unique “in line” approach was developed to enable the insertion of the catheter along the course of the sciatic nerve, thus maintaining position for prolonged infusions. Results. According to predetermined criteria for success, only 64% of placements using traditional epidural catheters were successful, whereas the firmer catheter with “through the catheter” nerve stimulation was successful in 95% of placements. Conclusions. The described “in line” technique of continuous sciatic nerve infusion of a local anesthetic solution gives prolonged and effective analgesia following foot surgery.

Postinfectious Glomerulonephritis

The AJKD Atlas of Renal Pathology presents a compilation of figures on a specific pathologic entity. You may download the figures to create your own personal, non-commercial library of images or to create slides for teaching purposes. The AJKD Atlas of Renal Pathology presents a compilation of figures on a specific pathologic entity. You may download the figures to create your own personal, non-commercial library of images or to create slides for teaching purposes. Fig 2Diffuse proliferative acute postinfectious glomerulonephritis with numerous PMNs with PAS-positive cytoplasm and endocapillary proliferation (periodic acid-Schiff; original magnification ×400).View Large Image Figure ViewerDownload Hi-res image Download (PPT) Fig 3The large number of PMNs typical of acute poststreptococcal glomerulonephritis is evident in this high-power silver stain. The glomerular basement membrane does not show splitting or spikes. There is endocapillary proliferation, ie, proliferation of endothelial and mesangial cells and infiltrating cells in addition to filling and distending capillary loops. The large number of PMNs is characteristic of postinfectious glomerulonephritis, with the prototype being poststreptococcal glomerulonephritis (Jones' silver stain; original magnification ×400).View Large Image Figure ViewerDownload Hi-res image Download (PPT) Fig 4Crescents may occasionally be found in diffuse proliferative acute postinfectious glomerulonephritis, particularly in those patients who undergo renal biopsy when spontaneous resolution does not occur. The crescent in this case has ruptured Bowman's capsule, and there is an intense lymphoplasmocytic interstitial infiltrate surrounding the glomerulus (Jones' silver stain; original magnification ×200).View Large Image Figure ViewerDownload Hi-res image Download (PPT) Fig 5aAcute postinfectious glomerulonephritis by immunofluorescence typically shows irregular capillary loop deposits staining for IgG, seen here, or C3, seen in Figure 6 (immunofluorescence with anti-IgG; original magnification ×400).View Large Image Figure ViewerDownload Hi-res image Download (PPT) Fig 5bThe garland pattern of immune complexes due to large subepithelial deposits in acute postinfectious glomerulonephritis is shown (immunofluorescence with anti-IgG; original magnification ×400).View Large Image Figure ViewerDownload Hi-res image Download (PPT) Fig 6The scattered capillary wall granular deposits in acute poststreptococcal glomerulonephritis also stain for complement (immunofluorescence with antibody to C3; original magnification ×400).View Large Image Figure ViewerDownload Hi-res image Download (PPT) Fig 7Large, subepithelial, hump-like scattered deposits in acute postinfectious glomerulonephritis. The deposits are irregularly spaced and frequently mottled, and they sit on top of the basement membrane with little, if any, basement membrane reaction (transmission electron micrograph; original magnification ×6,800).View Large Image Figure ViewerDownload Hi-res image Download (PPT) Fig 8Hump- or dome-shaped deposits in acute postinfectious glomerulonephritis with extensive foot process effacement and endocapillary proliferation (transmission electron micrograph; original magnification ×11,250).View Large Image Figure ViewerDownload Hi-res image Download (PPT) Fig 9In this case of acute postinfectious glomerulonephritis, only rare subepithelial deposits remain with occasional intramembranous deposits. At this later stage, the deposits may be found only in the notch area, ie, where the basement membrane reflects over the mesangium. Such deposits may indent the basement membrane as well as protrude above it, as shown (transmission electron micrograph; original magnification, ×17,125).View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Increased limb salvage by the use of unconventional foot amputations.

Limb salvage in the presence of ischemic foot necrosis requires revascularization followed by debridement or partial foot amputation. Necrosis extending beyond the toes and metatarsal heads may require the use of unconventional types of amputations. Over a 15-year period 2105 ischemic limbs were treated with infrainguinal revascularization. In 98 cases, extensive foot necrosis was than managed with amputations, including 59 modified Chopart, 14 Lisfranc, 17 Pirogoff and 8 Syme amputations. Patients were not allowed to bear weight for several days to weeks. Skin flap necrosis in 14 cases was managed successfully by debridement and skin grafting. Ambulation required the use of a "clamshell" prosthesis and foot spacer. The overall limb salvage rate in this group was 84% (82 of 98). In general, the modified Chopart amputation most frequently produced ambulatory limb salvage and is technically easier to perform than a Syme amputation. Patient satisfaction and long-term ambulatory function was highest with the modified Chopart. Ischemic foot necrosis extending beyond the limits of conventional transmetatarsal amputation need not be treated with major amputation. This requires the surgeon to be well versed in the use of less common types of partial foot amputations. Acceptable limb salvage and good functional results may be attained by the motivated patient and surgeon with the use of these procedures in the revascularized limb.

The dorsalis pedis bypass — Moderate success in difficult situations

Recent reports have documented excellent results for inframalleolar reconstructions. We reviewed our outcomes for dorsalis pedis bypass and report a more modest rate of success. We analyzed reasons for failure. Sixty-nine patients underwent 73 dorsalis pedis bypass procedures between 1984 and 1991. Seventy-eight percent of the patients were diabetics. Inflow was from the external iliac in 1, femoral in 35, popliteal in 34, and tibial in 3. The operative indication was gangrene in 57%, ulcer in 22%, and rest pain in 21%. Forty-six percent of limbs had foot infection, with six requiring minor amputation before the bypass and 24 requiring minor amputation after bypass. There was one perioperative death. Twenty-nine grafts failed over the course of the series. The primary patency rate at 2 years was 59.2%. The limb salvage rate was 73.5%. Of the 10 perioperative failures, four were due to continued foot infection, four to marginal vein quality, and two to skin necrosis of the bypass incisions. Graft failure occurred at 3 to 30 months in 10 of 14 patients who had deficient anterior arches, with segmental occlusion of the dorsalis pedis or its branches. Six of the 14 patients with extensive infections of the forefoot or extensive heel ulcers required amputation with patent bypasses. In dorsalis pedis bypass, failure to achieve limb salvage was more likely in patients with marginal vein quality, deficient anterior pedal arches, and extensive foot infection. In patients where the chance of failure appears to be unacceptably high, primary amputation should be considered.

Ultrastructural Alterations in the Sialic Acid Distribution in Minimal Change Disease and Membranous Glomerulonephritis

Kidney biopsy specimens from patients with minimal change disease and membranous glomerulonephritis were embedded in glycolmethacrylate and stained with phosphotungstic acid (PTA) at low pH. Biopsy specimens from patients without proteinuria served as a control. The PTA staining at low pH on glycolmethacrylate sections was used to study the changes in the sialic acid content of the lamina rara externa of the glomerular basement membrane. This method also gives a clear picture of the changes occurring at the epithelial cell coat and these alterations have implications on the distribution of the negative charges. In minimal change disease no alterations could be observed in the sialic acid content of the lamina rara externa. But the luminal epithelial cell coat showed obvious changes in conjunction with extensive foot process widening. In membranous glomerulonephritis with heavy deposits the staining of the lamina rara externa became almost completely negative and the foot process architecture was strongly affected. Obvious defects at the luminal epithelial cell coat, as observed in minimal change disease, were also found regularly. The alterations at the epithelial cell coat are tentatively related to the selective proteinuria reported in minimal change disease. In addition the non-selective proteinuria observed in non-minimal glomerulopathies, may find its origin in the absence of sialic acid molecules from the lamina rara externa.

Foot Reconstruction Using Free Microvascular Muscle Flaps with Skin Grafts

Free muscle flap transfer with skin graft coverage for extensive foot defects can be a successful form of foot reconstruction in well-selected patients who have overall normal foot innervation and deep pressure sensibility. Cutaneous sensibility does not appear to be necessary to maintain a functional or well-healed foot. The major reconstructive goal in plantar foot reconstruction is the restoration of weight-bearing during normal ambulation using regular foot apparel. Based on this reconstructive goal, the authors present their current approach in the reconstruction of extensive defects of the foot using free microvascular muscle flaps with skin grafts.

Topical oxygen therapy treatment of extensive leg and foot ulcers.

The authors present a study of 15 patients with extensive leg ulcers of at least a grade Ill out of five grades, who were treated with topical oxygen treatment. A 73.3% healing rate was obtained. Three patients required further amputation and one patient eventually died. Failures to heal were associated with severe ischemic diseases and tissue hypoxia. Management of severe wound infections of the limbs required multidisciplinary treatment, which included the use of high-pressure oxygen treatment.

Glomerulopathy does not increase renal susceptibility to acute ischemic injury.

To determine whether preexistent glomerular injury and the nephrotic syndrome increase renal susceptibility to ischemic renal injury, normal rats and rats with either experimental minimal-change disease (Adriamycin nephropathy) (AN) or membranous nephropathy (passive Heymann nephritis) (PHN) underwent renal functional and histologic studies under either basal conditions or 18 h after bilateral renal artery occlusion (over 30 min). Prior to renal ischemia AN and PHN rats had minimally depressed glomerular filtration rate (GFR), normal (AN) or increased (PHN) renal blood flow (RBF), heavy proteinuria, hypoalbuminemia, decreased urine sodium excretion, extensive glomerular foot process fusion, and intratubular hyalin cast formation. Losses of GFR in response to ischemia were comparable among the three groups of rats (controls, 0.29; AN, 0.28; PHN, 0.25 ml X min-1 X 100 g body wt-1) despite prevailing differences in postischemic hemodynamics. Neither light nor transmission electron microscopy showed any differences in the degree of ischemic renal injury. These results suggest that 1) glomerulopathy and the nephrotic syndrome do not significantly increase renal susceptibility to ischemic renal injury; 2) the syndrome of acute renal failure that occurs in patients with minimal-change glomerulopathy is not due to a marked susceptibility of these kidneys to clinically occult ischemic events; and 3) foot process fusion is probably not a pathophysiologically significant lesion in ischemic acute renal failure, as previously suggested.

Alterations in lung basement membrane during fetal growth and type 2 cell development

We studied basement membrane development in the late fetal and in the neonatal rat lung, from the 18th day of gestation (term = 22 days) through the 8th postnatal day, with particular emphasis on the gas-exchange region of the lung. In the periphery of the lung, as type 2 cells differentiate, the continuous basement membrane develops openings beneath these cells. Basal cytoplasmic foot processes extend through these discontinuities into the underlying interstitium, often approaching interstitial cells closely. These discontinuities and extensive foot processes are associated only with type 2 epithelial cells and not with either differentiated airway cells or with the type 1 alveolar lining cells derived from type 2 cells. The type 2 cell basement membrane discontinuities and penetrating foot processes are maximal in the perinatal period and decrease in the week after birth. The appearance of openings in type 2 cell basement membrane and changes in distribution, linear density, and ruthenium red staining of anionic sites suggest that the epithelial basement membrane undergoes continuous remodeling throughout development, particularly in association with type 2 cell differentiation and growth of lung surface area. Epithelial cell foot processes may interact with underlying interstitial cells and affect the coordination of lung surface growth with the development of its connective tissue framework.

Renal pathology of fetuses with congenital nephrotic syndrome of the Finnish type. 2. A qualitative and quantitative electron microscopic study.

A qualitative and quantitative transmission electron microscopic study was performed on kidneys of fetuses with congenital nephrotic syndrome of the Finnish type (CNF) and controls obtained from elective pregnancy terminations. The gestational age of the fetuses ranged from 16–22 weeks. A consistent qualitative change of CNF glomeruli was the nearly total loss of epithelial cell foot processes, with smudging of epithelial cytoplasm as broad masses on the glomerular basement membrane. Adjacent to the basement membrane there were increased amounts of fibrillar material in the epithelial cytoplasm. The number of pinocytic droplets was increased both in epithelial and endothelial cytoplasm and some of the capillary loops showed swelling of endothelial cells with poor fenestrations in cases of CNF. Mesangial hyperplasia was focally evident in the most mature CNF glomeruli with an increase of the mesangial matrix. A striking qualitative feature in CNF, only rarely seen in controls, was the occurrence of electron lucent vacuoles and heteromorphic residual bodies in the mesangial cell cytoplasm. The total thickness of the glomerular basement membrane was comparable in CNF and controls but the width of the lamina densa was significantly smaller in CNF than controls. Lamina rara interna of the basement membrane showed irregular widening with accumulation of coarse granular material. Reabsorption droplets of proximal tubular cytoplasm were significantly increased in CNF. With the dilatation of the tubule the droplets almost totally disappeared. Based on the results of the study it is suggested that the basic pathogenetic defect in CNF lies in faulty development of the lamina densa of the glomerular basement membrane and, secondary to this, various glomerular and tubular changes occur. In addition to evidence of extensive foot process fusion, mesangial cell cytoplasmic vacuoles represent a diagnostically important qualitative change in the glomeruli of fetal CNF.

THE ARMY SHOE AND MILD FOOT DISABILITIES

Extensive foot inspections were made of the soldiers who were trained during the latter half of 1917 and early part of 1918. These inspections were first made when the men were inducted into service and while the feet still showed the abnormal conditions that were present in civil life, and again before they were sent overseas. Comparison of the results of the two examinations disclosed that marked changes had occurred, and the experience of civil orthopedic practice is verified by these observations. These changes have been almost uniformly favorable to better function of the feet, and when unfavorable results have occurred, the reason has been readily traced. In endeavoring to account for the marked changes observed, there are two factors that stand out as most potent. First is the Army shoe and second is the increased personal care and interest in foot health on the part of the officers and