Association of diabetic foot ulcer and death in a population-based cohort from the United Kingdom.

AIMS: The presence of diabetic foot ulcers is strongly associated with an increased risk of death. In this study, we investigate whether the effects of diabetes-associated complications can explain the apparent relationship between diabetic foot ulcers and death. METHODS: We analysed data from 414 523 people with diabetes enrolled in practices associated with The Health Improvement Network in the United Kingdom. Our methods were designed to control for potential confounders in order to isolate the relationship between diabetic foot ulcers and death. Using proportional hazards models and the area under the receiver operator curve, we evaluated the effects of diabetic foot ulcers and the covariates on death. RESULTS: Among the patients, 20 737 developed diabetic foot ulcers; 5.0% of people with new ulcers died within 12 months of their first foot ulcer visit and 42.2% of people with foot ulcers died within 5 years. After controlling for major known complications of diabetes that might influence mortality, the correlation between diabetic foot ulcers and death remained strong with a fully adjusted hazard ratio of 2.48 (95% confidence interval: 2.43, 2.54). Geographic variance existed but was not spatially associated. CONCLUSIONS: Diabetic foot ulcers are linked to an increased risk of death. This cannot be explained by other common risk factors. These results suggest that either there are major unknown risk factors associated with both diabetic foot ulcers and death, or that diabetic foot ulceration itself is a serious threat, which seems unlikely. A diabetic foot ulcer should be seen as a major warning sign for mortality, necessitating closer medical follow-up.

The Effects of Exercise on Dopamine Neurotransmission in Parkinson's Disease: Targeting Neuroplasticity to Modulate Basal Ganglia Circuitry.

Animal studies have been instrumental in providing evidence for exercise-induced neuroplasticity of corticostriatal circuits that are profoundly affected in Parkinson's disease. Exercise has been implicated in modulating dopamine and glutamate neurotransmission, altering synaptogenesis, and increasing cerebral blood flow. In addition, recent evidence supports that the type of exercise may have regional effects on brain circuitry, with skilled exercise differentially affecting frontal-striatal related circuits to a greater degree than pure aerobic exercise. Neuroplasticity in models of dopamine depletion will be reviewed with a focus on the influence of exercise on the dorsal lateral striatum and prefrontal related circuitry underlying motor and cognitive impairment in PD. Although clearly more research is needed to address major gaps in our knowledge, we hypothesize that the potential effects of exercise on inducing neuroplasticity in a circuit specific manner may occur through synergistic mechanisms that include the coupling of an increasing neuronal metabolic demand and increased blood flow. Elucidation of these mechanisms may provide important new targets for facilitating brain repair and modifying the course of disease in PD.

Diagnosis of pancreas rejection: cystoscopic transduodenal versus percutaneous computed tomography scan-guided biopsy.

BACKGROUND: The most common cause of graft failure after technically successful pancreas transplants is rejection. Laboratory parameters for detecting pancreas graft rejection are not consistently reliable and can lead to unnecessary antirejection treatment. Histopathologic evaluation is the gold standard in the differential diagnosis of pancreas graft dysfunction. Four biopsy techniques have been described: cystoscopic transduodenal (CB), percutaneous computed tomography scan-guided (PB), open, and laparoscopic biopsy. METHODS: We studied the two most common techniques, CB and PB, in pancreas transplant recipients with presumed rejection. Group 1 comprised 103 attempts at CB in 82 recipients (53 men, 29 women) with bladder-drained (BD) pancreas transplants, at 1 to 80 (median, 14) months after transplant. Group 2 comprised 93 attempts at PB in 68 recipients (41 men, 27 women), at 0.5 to 64 (median, 14) months after transplant. RESULTS: In group 1, of 103 attempts at CB, adequate tissue was obtained in 90 (87%): pancreas alone in 23 (22%), pancreas + duodenum in 35 (34%), duodenum alone in 32 (31%). Of the 58 pancreas biopsies, 23 (40%) showed acute rejection. Of the 67 duodenal biopsies, 16 (24%) showed acute rejection. Complications of CB included macrohematuria in 4 recipients (4%) and microhematuria in 32 (31%). We noted no biopsy-related pancreatitis. The mean cost of CB was $2561+/-246. In group 2, of 93 attempts at PB, adequate tissue (all pancreas) was obtained in 67 (72%); of these, 29 (43%) showed acute rejection. Of 23 inaccessible pancreases, 9 (39%) underwent CB; pancreatic tissue was obtained in four (45%), and results were consistent with rejection in all four. Complications of PB included biopsy-related pancreatitis (serum amylase > or = 25%) in five (7%) recipients, macrohematuria in one (1%), and abdominal hemorrhage in two (3%). The mean cost of PB was $1038+/-78. (1) CB and PB prevented unnecessary antirejection treatment in 44% of our recipients with successful biopsies; (2) CB had a higher success rate for obtaining tissue (including duodenal specimens) and a lower rate of major complications; (3) PB was easier and cheaper, did not require general anesthesia, and was performed as an outpatient procedure. CONCLUSIONS: We conclude that PB should become the biopsy technique of choice in recipients with presumed pancreas graft rejection. If PB fails, recipients with bladder-drained pancreas transplants should undergo CB. If CB fails, or in recipients with enteric-drained or duct-injected pancreas transplants, a laparoscopic or open biopsy should be considered.

CT-guided percutaneous biopsy of pancreas transplants.

PURPOSE: To evaluate the safety and efficacy of computed tomography (CT)-guided percutaneous needle biopsy in pancreas transplantation patients with graft dysfunction. MATERIALS AND METHODS: Sixty-three CT-guided core biopsies of 42 pancreas grafts were performed with 18-gauge needles over a 38-month period. All but one of the transplants were bladder-drained allografts. An average of 2.25 passes (range, 1-4) per allograft were made, and tissue was immediately processed for histopathologic examination. Fifteen patients (19% of biopsy referrals) could not undergo biopsy because a safe approach was not available. RESULTS: Of the 63 biopsy specimens, 57(90%) were adequate for histopathologic diagnosis, which was normal or no specific abnormality in 14, acute rejection in 20, chronic rejection in one, chronic rejection with cytomegalovirus inclusion bodies in one, acute or chronic pancreatitis in 13, chronic pancreatitis with cytomegalovirus inclusion bodies in one, and miscellaneous in seven. Three specimens contained no pancreatic tissue, and three were insufficient for diagnosis. Minor complications included a transient rise in serum amylase levels in four patients (6%) and transient mild hematuria in one patient (1%). The only major complication (substantial hemorrhage) occurred in two cases (3%). CONCLUSION: CT-guided percutaneous needle biopsy is a safe, alternative method for obtaining tissue in pancreas transplantation patients with graft dysfunction. It may obviate cystoscopic biopsy for bladder-drained grafts or open biopsy in duct-injected or enteric-drained grafts.

Masses simulating gynecologic diseases at CT and MR imaging.

The majority of pelvic masses in women arise from the reproductive tract. However, diseases of gastrointestinal origin (ruptured appendix, diverticular abscess, perforated rectosigmoid carcinoma), neurogenic origin (ganglioneuromas), primary extraperitoneal origin (presacral teratoma, soft-tissue sarcoma), and other miscellaneous disorders also occur in the pelvis and can be mistaken for gynecologic disease. Although determining the site of origin of a pelvic disease process can be difficult, several imaging signs can help differentiate an intra- from an extraperitoneal mass. These signs include displacement of the pelvic ureter, effacement or encasement of external iliac vessels, effacement of pelvic sidewall musculature, and displacement of the rectum. Depending on its exact location, an extraperitoneal mass can displace the pelvic ureter medially or anteriorly (compared with the lateral or posterolateral displacement caused by an ovarian mass), encase and obliterate the external iliac vessels, efface and compress the external iliac vein, abut and eventually efface the obturator internus muscle, or displace the rectum anteriorly or anterolaterally. Familiarity with these disease processes and the above imaging signs will facilitate accurate diagnosis and triage for treatment.

Biology of a brain metastasis.

The appearance of a brain metastasis is generally regarded as an ominous event in the progression of many solid tumors because it usually means that the patient will have reduced quality and length of survival. It is important to study the biology of brain metastasis because present treatments are principally palliative and new approaches to diagnosis and treatment are clearly needed.

Progesterone and estrogen are potential mediators of gastric slow-wave dysrhythmias in nausea of pregnancy.

Women in pregnancy experience nausea, which correlates with gastric slow-wave rhythm disruption. Mediators of these dysrhythmias were explored. To quantitate slow-wave disruption, eight pregnant women with first-trimester nausea underwent electrogastrography after a 250-kcal meal. Results were compared with nonpregnant women with nausea during a prior pregnancy who received estradiol and/or progesterone to levels of the first trimester of pregnancy. Five pregnant women exhibited dysrhythmias, with increases in combined recording time in tachygastria plus bradygastria, as well as decreases in the percentage of electrogastrography signal power in the normal 3 cycle/min range (cpm), compared with nonpregnant women (P<0.05). Estradiol did not evoke dysrhythmias in nonpregnant women; however, progesterone induced increases in recording time in bradygastria plus tachygastria and increases in bradygastric signal power with corresponding decreases in signal power in the 3-cpm range (P<0.05). With estradiol and progesterone coadministration, an additive effect was observed at 3.3 +/- 0.8 h, with increased recording time in bradygastria alone and in bradygastria plus tachygastria with corresponding increases in bradygastric signal power and decreases in power in the 3-cpm range (P<0.05). In conclusion, women with nausea of pregnancy exhibit slow-wave rhythm disruption. Similar dysrhythmias are evoked in nonpregnant women by progesterone alone or in combination with estradiol in doses that reproduce levels in pregnancy. Thus gastric dysrhythmias in pregnancy may be due to a combination of elevated progesterone and estrogen levels.

MRI of cerebellopontine angle choroid plexus papilloma.

We present a cerebellopontine angle choroid plexus papilloma that originated from the tuft of choroid plexus of the fourth ventricle protruding from the foramen of Luschka. MRI and CT did not establish the diagnosis, but the tumor was shown histopathologically to be a choroid plexus papilloma. Distinct features of the tumor on MRI are described and the differential diagnosis of other cerebellopontine angle tumors is discussed.

PET and SPECT imaging for stereotactic localization.

Stereotactic localization using PET and SPECT has been used together with the Leksell stereotactic frame and the other imaging tools routinely provided to Gamma Knife radiosurgery sites. The accuracy of the measurements has been confirmed with CT and MR using a Radiation Analog Dosimetry phantom. The activity of the radionuclide solution placed in the tubes of Elekta Radiosurgery's MR imaging box is somewhat critical because the window levels chosen for the scan will affect the apparent size of the lesion. A technique is presented to resolve areas of activity more than about 12-14 mm apart, and it may prove useful in targeting epileptogenic sites in patients with medically intractable epilepsy.

Thallium-avid cerebral radiation necrosis.

Thallium imaging has been proposed as a noninvasive method to distinguish recurrent tumor from cerebral radiation necrosis in patients who have undergone radiation therapy. Previous reports have supported the intuitive hypothesis that metabolically active tumor tissue would accumulate Tl-201 to a much higher degree than nonviable necrotic tissue. A case of biopsy-proven cerebral radiation necrosis is presented demonstrating a degree of Tl-201 avidity previously thought to be diagnostic of recurrent tumor. Based on this finding, it is concluded that a high degree of Tl-201 uptake does not exclude the diagnosis of cerebral radiation necrosis.

CT anatomy of the female pelvis: a second look.

Computed tomography (CT) remains a valuable technique in the assessment of the female pelvis. The CT appearance of the normal ligamentous, vascular, and visceral anatomy of the female pelvis can be confusing. Newer high-resolution CT scanners combined with mechanical intravenous contrast medium injectors and thinner sections have substantially improved the imaging of female genital tract anatomy. In addition to the cardinal, uterosacral, and round ligaments, the ovaries and their ligamentous attachments, as well as the blood supply to the female internal organs, can now be visualized. Inferior-to-superior image acquisition following bolus administration of intravenous contrast material with an angiographic injector facilitates precise identification of the uterine artery and its relationship to the pelvic ureter and the vascular plexus supplying the vagina, ovaries, and uterine body. Ideally, familiarity with variations in the CT appearance of normal female pelvic anatomy will enable more accurate evaluation of pelvic abnormalities.

Ground-glass opacity of the lung parenchyma: a guide to analysis with high-resolution CT.

Ground-glass opacity is a frequent but nonspecific finding on high-resolution CT scans of the lung parenchyma. The underlying abnormality is diverse; any condition that decreases the air content of the lung parenchyma without totally obliterating the alveoli can produce ground-glass opacity. These processes are not visible on high-resolution CT scans. However, in specific clinical settings, the information provided by high-resolution CT is considerable when the anatomic distribution and associated structural changes to the lung parenchyma are analyzed. This pictorial essay illustrates the pathologic basis of ground-glass opacity and provides a guide to the differential diagnosis of the disorders that can produce this appearance.

Coronary artery aneurysm formation following directional coronary atherectomy.

Directional coronary atherectomy has recently become available to treat coronary stenosis by excision and removal of tissue. The optimal depth of resection by this method has not been determined and complications have occurred. This report describes the formation of a coronary aneurysm at an atherectomy site in an asymptomatic patient, a finding not reported previously.

Computed tomography of gynecologic neoplasms.

Both CT and MR imaging have had a major impact on gynecologic oncologic imaging, and new technology and imaging techniques are still being introduced. CT maintains a role in gynecologic pelvic cancer imaging because of cost-effectiveness, high spatial resolution, fast examination time, and wide availability. CT is particularly advantageous for lymph node metastasis screening and guided-biopsy of metastases and recurrent tumor. CT currently is recommended for primary staging of ovarian cancer and advanced cancers of the cervix and endometrium, detection of persistent and metastatic gestational trophoblastic disease, and evaluation of recurrent gynecologic pelvic cancers.

Carotid and vertebral artery injury in survivors of atlanto-occipital dislocation: case reports and literature review.

Atlanto-occipital dislocation (AOD) usually results in immediate death from transection of the upper cervical spinal cord near the spinomedullary junction. However, over the last several decades increasing numbers of AOD survivors have been identified. Although many of these patients initially demonstrate profound neurologic deficits, a number who survive have regained most or all neurologic functions, indicating that they did not suffer mechanical disruption of the spinal cord at the time of AOD. In the survivors, a growing body of evidence indicates that many of the initial neurologic deficits are related to vascular injury to the carotid or vertebral arteries and their branches. We recently encountered three AOD survivors with no evidence of mechanical injury to the spinal cord in which angiography demonstrated vascular injury to the internal carotid artery in the form of vasospasm in one case and to the vertebral arteries in the forms of focal stenosis at the site of dural penetration, focal stenosis and distal vasospasm, and focal stenosis with distal intimal flap and dissection in one case each. Autopsy after one of the three died after cardiac arrest demonstrated diffuse infarction of the cerebrum, cerebellum, midbrain, brainstem, and upper cervical spinal cord without evidence of mechanical laceration or transection of the spinal cord. Recovery of neurologic function in two cases following prompt immobilization and angiography suggests that neurologic deficits secondary to vascular injury are potentially reversible.

The effect of dibutyryl camp (dBcAMP) on morphological differentiation, growth and invasion in vitro of a hamster brain-tumor cell line: a comparative study of dBcAMP effects in 2- and 3-dimensional cultures.

The use of agents that stimulate cancer cells to differentiate is proposed as a potential approach to the treatment of malignancy. To evaluate the effects of a differentiation inducer on morphology, growth and invasion in vitro of brain-tumor cells, a diffusely invasive hamster glial cell line (CxT3C15) was treated with ImM dibutyryl cyclic adenosine monophosphate (dBcAMP). The efficacy of dBcAMP was tested in monolayer cultures, 3-dimensional static cultures (i.e., spheroids) and confrontation cultures with an embryonic chick heart. CxT3C15 cells exhibited increased numbers of long cellular processes (morphological differentiation) following treatment of monolayer cultures with ImM dBcAMP. One mM dBcAMP also altered the macroscopic and ultrastructural morphology of CxT3C15 grown as spheroids. These alterations were: (i) a fast transition of rough to smooth morphology macroscopically, and (ii) fading of the cell borders concomitant with the disappearance of cell-membrane excrescences, as seen by scanning electron microscopy. Exponential growth of CxT3C15 in monolayers was not changed following treatment with ImM dBcAMP. Treatment of CxT3C15 spheroids with the same dose of dBcAMP caused a reduction of relative volume increase (30-40%). Invasion of CxT3C15 in an embryonic chick heart in vitro was not altered after addition (prior to or at the time of co-culture) of ImM dBcAMP to the co-cultures. These results indicate that invasion of CxT3C15 is not necessarily linked to morphological differentiation or moderated by reduced proliferation.

Split-thickness skin grafting of the myelomeningocele defect: a subset at risk for late ulceration.

The appropriate method and timing of the management of the myelomeningocele defect have prompted considerable discussion. Use of split-thickness skin grafts acutely has accomplished wound closure with low morbidity and mortality. This study was designed to address the question of long-term suitability of the technique of split-thickness skin grafting of the myelomeningocele patient. The incidence of late and/or severe skin ulceration and the presence of gibbus deformity were correlated with the method of skin closure. Long-term follow-up revealed a higher incidence of chronic skin ulceration in the split-thickness skin graft group as compared with the primary closure group. All skin breakdowns appeared in the presence of a gibbus deformity, and gibbus deformity was more prevalent in the split-thickness skin graft group. The incidence of skin ulceration and gibbus deformity was site-dependent. A thoracic or thoracolumbar myelomeningocele repair with split-thickness skin graft was significantly more likely to be complicated by skin problems than the defect in the lumbar, lumbosacral, or sacral region. This relationship was secondary to the frequency of gibbus deformity in the more cephalad defects than defects caudad. A treatment plan is outlined that is based on the primary variable of the location of the myelomeningocele and secondarily by defect size.

Seat belt injuries: radiologic findings and clinical correlation.

The seat belt syndrome consists of skeletal, soft-tissue, and visceral injuries associated with use of two- and three-point restraints in patients involved in motor vehicle accidents. Skin abrasions of the neck, chest, and abdomen--the classic seat belt sign--indicate internal injury in 30% of cases. Neck abrasions are associated with injuries to the carotid artery, larynx, and cervical spine; chest abrasions, with fractures of the sternum, ribs, and clavicles and injuries to the heart and thoracic aorta; and abdominal abrasions, with mesenteric tears, bowel perforation and hematoma, Chance fractures, and injuries to the abdominal aorta. The seat belt sign should prompt a diligent search for related injuries.

Alterations in SV40 DNA integration patterns are associated with acquisition of the invasive phenotype in hamster brain tumors.

A panel of cell lines that represents a reproducible, easily manipulated experimental system which discriminates between the minimally and diffusely invasive phenotypes of brain tumors has been developed. A population of SV40-transformed glial cells derived from newborn hamster cerebral cortex (Cx) has been sequentially passaged in newborn hamsters by intracerebral inoculation followed by in vitro culture, and after each passage progressively more invasive cell lines have been established. To study the molecular basis for the observed phenotypic characteristics associated with invasiveness, cloned cells were isolated from the first (Cx4T1-derived) and third Passage (Cx4T3-derived) cells lines. After injection into hamster brain, these cloned cells produce tumors that were either minimally invasive (Cx4T1-derived) or diffusely invasive (Cx4T3-derived) into normal brain tissue. In our initial attempt to identify and characterize the cellular and molecular factors that modulate the invasive phenotype, restriction endonuclease generated SV40 DNA-containing fragment patterns of DNA from each parental cell line and each of the clonal variants were determined by Southern transfer-hybridization. The results suggest the cell lines are composed of a limited number of tumorigenic subpopulations, each of which contain characteristic arrangements of integrated SV40 DNA with repeated in vivo/in vitro passage the avvangement of intecyvated SV40 changed. Analysis of DNA from minimally and diffusely invasive cloned cells indicated strong similarities of integrated SV40 DNA arrangement to their parental cells with the greatest similarities in cells exhibiting comparable invasive phenotypes. A striking difference was seen, however, in comparisons of SV40 DNA-containing fragment patterns of DNA extracted from clones which induced marginally versus diffusely invasive tumors. These differences suggest that the invasive cells were selected from a distinct minority subpopulation or that they may have arisen as a consequence of a more dynamic process of genetic rearrangement. This cell system appears to mimic the phenotypic and genetic heterogeneity observed in human tumors of glial origin and should prove valuable in defining the biochemical and molecular basis of tumor cell invasion.