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1.  Nicolau Syndrome after Intramuscular Injection: 3 Cases 
Archives of Plastic Surgery  2012;39(3):249-252.
Nicolau syndrome is a rare complication of intramuscular injection consisting of ischemic necrosis of skin, soft tissue, and muscular tissue that arises locoregionally. The characteristic pattern is pain around the injection site, developing into erythema, a livedoid dermatitis patch, and necrosis of the skin, subcutaneous fat, and muscle tissue. Three patients were injected with drugs (diclofenac sodium, ketoprofen, meperidine) for pain relief. Three patients complained of pain, and a skin lesion was observed, after which necrosis developed on their buttocks. Each patient underwent debridement and coverage. The wound healed uneventfully. We report three cases of Nicolau syndrome in the buttocks following diclofenac intramuscular injection.
PMCID: PMC3385328  PMID: 22783535
Necrosis; Nicolau syndrome; Injections; Intramuscular
2.  Nicolau Syndrome after Intramuscular Benzathine Penicillin Injection 
A 3-year-old boy was admitted to the emergency department with right lower limb pain, edema, and livedoid discoloration that occurred immediately after intramuscular injection of benzathine penicillin. The patient was diagnosed with Nicolau syndrome, a rare complication of intramuscular injection presumed to be related to the inadvertent intravascular injection. It was first reported following intramuscular injection of bismuth salt, but it can occur as a complication of various other drugs. Fasciotomy was carried out due to the resultant compartment syndrome and medical therapy with heparin, corticosteroid, and pentoxifyllin was initiated.
PMCID: PMC4242994  PMID: 25429182
Syndrome; Benzathine penicillin; Injection
3.  Nicolau Syndrome: An Iatrogenic Cutaneous Necrosis 
Nicolau syndrome is an uncommon complication of intramuscular injection leading to variable degrees of necrosis of skin and the underlying tissues. We report here two cases of this syndrome. Our first case was a 25 year-old male who developed intense pain and purplish discoloration of the skin in the right hip after intramuscular diclofenac injection. The second case was a 60 year-old male who developed intense pain and discoloration of skin, not only at the injection site, but also on the left scapular area and left elbow after receiving chlorpheniramine maleate injection intramuscularly. These cases highlight the need for awareness about this condition and the need to exercise utmost care during the administration of any parenteral injections by dermatologists.
PMCID: PMC2918347  PMID: 20808597
Avascular necrosis; intramuscular injection; Nicolau syndrome
4.  Minimally invasive procedures in severe acute pancreatitis treatment – assessment of benefits and possibilities of use 
Acute pancreatitis (AP) consists of an extremely varied complex of pathological symptoms and clinical conditions, ranging from mild gastric complaints to multi-organ failure resulting in death.
To present the authors’ own experience regarding surgical treatment for pancreatic necrosis complicated by infection using different methods, including classic and laparoscopic methods as well as those combined with percutaneous techniques.
Material and methods
In the period 2007–2010, 34 patients with the diagnosis of severe AP were treated at the Department of General, Gastroenterological and Oncological Surgery, Collegium Medicum, Nicolaus Copernicus University. In 7 patients classic necrosectomy with repeated peritoneal flushing was performed (type 1), in 5 patients laparotomy with active drainage (type 2), in 12 video-assisted retroperitoneal debridement (type 3), and in 10 only percutaneous drainage methods (type 4).
Total duration of hospitalisation was from 10 to 192 days. The highest death rate was observed for type 1 procedures. Significant differences with regard to the absolute number of postoperative complications between different groups were not observed; however, their quality varied. Classic methods were used in patients whose general and local condition was more severe.
When AP and its complications are diagnosed, a suitable method of surgical treatment has to be selected extremely precisely and in an individualised way. Minimally invasive methods used in selected patients provide better outcomes and higher safety superseding classic, open techniques of surgical treatment.
PMCID: PMC4105673  PMID: 25097683
acute pancreatitis; infected pancreatic necrosis; video-assisted retroperitoneal debridement
5.  Kaspar Schott’s “encyclopedia of all mathematical sciences” 
Poiesis & Praxis  2011;7(4):225-247.
In 1661, Kaspar Schott published his comprehensive textbook “Cursus mathematicus” in Würzburg for the first time, his “Encyclopedia of all mathematical sciences”. It was so successful that it was published again in 1674 and 1677. In its 28 books, Schott gave an introduction for beginners in 22 mathematical disciplines by means of 533 figures and numerous tables. He wanted to avoid the shortness and the unintelligibility of his predecessors Alsted and Hérigone. He cited or recommended far more than hundred authors, among them Protestants like Michael Stifel and Johannes Kepler, but also Catholics like Nicolaus Copernicus. The paper gives a survey of this work and explains especially interesting aspects: The dedication to the German emperor Leopold I., Athanasius Kircher’s letter of recommendation as well as Schott’s classification of sciences, explanations regarding geometry, astronomy, and algebra.
PMCID: PMC3106158  PMID: 21765821
6.  Laparoscopic surgery of esophageal hiatus hernia – single center experience 
Esophageal hiatal hernias are the most frequent types of internal hernias. This condition involves disturbance of normal functioning of the stomach cardiac mechanism and reflux of the gastric contents to the esophagus.
Aim: To evaluate postoperative results in our Clinic and the comparison of these results to data from the literature.
Material and methods
One hundred and seventy-eight patients underwent surgery due to esophageal hiatal hernia at the Clinic of General, Gastroenterological and Oncological Surgery, Collegium Medicum, Bydgoszcz, Nicolaus Copernicus University, Torun, Poland, from 2006 to 2011. All operations were performed using laparoscopy. Fundoplication by means of the Nissen-Rossetti method was carried out in 172 patients while Toupet's and Dor's methods were applied in 4 and 2 patients, respectively.
Average time of the surgery was 82 min (55–140 min). Conversion was performed in 4 cases. No serious intraoperative complications were noted. In the postoperative period, dysphagia was reported in 20 patients (11.2%). Postoperative wound infection was observed in 1 patient (0.56%). Hernias in the trocar insertion area were reported in 3 patients (1.68%). Ailments recurred in 6 patients. The recurrence of esophageal hiatal hernia was confirmed in 2 patients. Patients with recurrent hernia were re-operated using a laparoscopic approach.
Laparoscopic surgery is a simple and effective approach for patients with gastroesophageal reflux symptoms due to diaphragmatic esophageal hiatus hernia. The number of complications is lower after laparoscopic procedures than after “open” operations.
PMCID: PMC3983544  PMID: 24729804
laparoscopy; hiatal hernia; fundoplication
7.  Nicolau Syndrome in Patient Following Diclofenac Administration: A Case Report 
Annals of Dermatology  2011;23(4):501-503.
Nicolau syndrome is a rare adverse reaction to a variety of intra-muscular drug preparations. The typical presentation is pain around the injection site soon after injection, followed by erythema, livedoid patch, hemorrhagic patch, and finally, necrosis of skin, subcutaneous fat, and muscle tissue. The phenomenon has been related to the administration of a variety of drugs, including non-steroidal anti-inflammatory drugs, corticosteroids, and penicillin. We report a case with typical features associated with diclofenac injection for pain control in a patient who had undergone bilateral total knee arthroplasty.
PMCID: PMC3229946  PMID: 22148020
Diclofenac; Nicolau syndrome; Total knee arthroplasty
We are submitting this series of experiments as observed facts, realizing that there are so many uncertainties in this form of indirect observation that great caution must be exercised in drawing conclusions of any kind. The most serious of the possible errors involved is that the active substances which we have studied, the enzyme—the bacteriophage—and the several varieties of virus, may not be free in our suspensions, but are adsorbed to larger particles. The peculiar difficulties encountered in filtering herpes virus particularly suggest a source of error of this kind, and if we are right in assuming the intracellular position of this virus in the nervous tissue, it is more than likely that most of the virus obtained in suspension may be closely associated with protein particles derived from the cells. Keeping all this in mind, we may, nevertheless, derive a certain amount of information from our experiments as follows: 1. The order of magnitudes of the pure proteins with which we have worked,—namely, crystallized egg albumen, crystallized serum albumen and purified casein,—follows the order of molecular weights of these substances as determined by Cohn. As far as casein is concerned, the size indicated by filtration in comparison with collargol is far greater than it should be by calculations which take a molecular weight of 192,000 as the point of departure. While one cannot be sure of the reason for this, there are many possible explanations such as considerable swelling of the casein partides, aggregation of molecules and the fact that casein is not at its isoelectric point under the conditions of filtration and surely present as a salt. 2. Trypsin, even in the certainly very impure condition in which we employed it, is but very slightly larger than serum albumen and distinctly smaller than casein. In its pure form it may well be much smaller even than our filtrations indicate, but certainly not larger. This relatively small size of trypsin may have considerable bearing upon the question of whether or not the lytic agents spoken of as "bacteriophage" are substances of the nature of enzymes, or whether they are more comparable to the filtrable virus, as supposed by d'Hérelle. 3. Herpes virus, the Rous chicken sarcoma and a staphylococcus bacteriophage were all subjected to filtration at pH 7.2 and at hydrogen ion concentrations higher than 8, which is given by Olitsky and Boëz as the isoelectric point of foot-and-mouth disease, but failed to pass membranes which, at the same pressures, were permeable for casein and collargol. The bacteriophage and the Rous sarcoma with considerable regularity passed through membranes which held back colloidal arsenic trisulfide. We have cited only a few of the experiments which were actually done, every one of the tests tabulated being merely representative of a number of others that were omitted for economy of space. The herpes virus we have had greater difficulty in filtering. We cite one experiment with a 2 per cent acetic-collodion membrane and another with a 1.5 per cent membrane through which the herpes virus passed, the membrane being so controlled that gross leakage could be excluded. We believe that the difficulty here is very largely due to the fact that in preparing the herpes virus for filtration it cannot be separated from considerable amounts of brain material, from which, perhaps, it is not easily dissociated. This would be natural if the herpes virus were intracellularly located, as we believe it to be. This experiment and similar ones, however, incline us to believe that the herpes virus is not far different from the Rous sarcoma virus and the bacteriophage, as far as filtration through membranes is concerned. It certainly is not smaller than either of these substances and probably, as we judge from a few experiments carried out at higher pressures, is not much larger. It may be assumed, therefore, that in the form in which we were able to procure the bacteriophage and the two varieties of virus investigated by us, they were of a magnitude larger than casein and collargol and smaller than colloidal arsenic. The weak point in drawing our conclusions is the fact that we were not in a position to measure for ourselves with any accuracy the actual sizes of collargol and arsenic trisulfide particles. Accepting the general views of Bechhold and others, however, our experiments would define the sizes of the separticular substances as larger than 20 mµ and probably smaller than 100 mµ. The order of magnitudes of the substances measured by us would then be as follows: Crystallized egg albumen Crystallized serum albumen Trypsin Collargol Casein Bacteriophage, Rous sarcoma virus, herpes virus Arsenic trisulfide Our experiments show little agreement with the work of Levaditi and Nicolau and of Levaditi, Nicolau and Galloway. In their recent filtration tests of foot-and-mouth disease this virus is reported by them as passing through membranes that held back trypsin, indicating a size much smaller than any of the viruses measured by us. Our results, on the other hand, are in actual measurements comparable to those of Olitsky and Boëz, not only in the fact that the viruses with which we worked correspond approximately to the size determined by them for foot-and-mouth disease, but that the percentage of collodion in membranes permeable for virus and impermeable for colloidal arsenic corresponds almost exactly to our own. This gives us confidence that the technique developed may be more easily standardized than we at first believed and that the method of ultrafiltration, owing to the great ease with which membranes of relatively standard size may be made, may have valuable applications in the investigation of bacteriological and immunological problems.
PMCID: PMC2131172  PMID: 19869343
9.  An attachment-based model of complicated grief including the role of avoidance 
Complicated grief is a prolonged grief disorder with elements of a stress response syndrome. We have previously proposed a biobehavioral model showing the pathway to complicated grief. Avoidance is a component that can be difficult to assess and pivotal to treatment. Therefore we developed an avoidance questionnaire to characterize avoidance among patients with CG.
We further explain our complicated grief model and provide results of a study of 128 participants in a treatment study of CG who completed a 15-item Grief-related Avoidance Questionnaire (GRAQ).
Results of Avoidance Assessment
Mean (SD) GRAQ score was 25. 0 ± 12.5 with a range of 0–60. Cronbach's alpha was 0.87 and test re-test correlation was 0.88. Correlation analyses showed good convergent and discriminant validity. Avoidance of reminders of the loss contributed to functional impairment after controlling for other symptoms of complicated grief.
In this paper we extend our previously described attachment-based biobehavioral model of CG. We envision CG as a stress response syndrome that results from failure to integrate information about death of an attachment figure into an effectively functioning secure base schema and/or to effectively re-engage the exploratory system in a world without the deceased. Avoidance is a key element of the model.
PMCID: PMC2806638  PMID: 17629727
complicated grief; attachment; avoidance behaviour
10.  A systematic review of anterolateral thigh flap donor site morbidity 
The anterolateral thigh (ALT) flap, widely used in reconstructive procedures, has gained popularity and become an important option for many anatomical locations. Use of the ALT flap has many technical advantages and benefits and, furthermore, is associated with minimal donor site morbidity, which can impact outcome and patient postoperative quality of life. Although there have been many studies examining the ALT flap, sample sizes have been small, which have hindered the ability to objectively assess specific complications and complication rates. This literature review summarizes several types of complications and their incidence regarding the donor site of the ALT flap. The authors synthesize the data and discuss these complications and offer recommendations to avoid them.
The anterolateral thigh (ALT) flap is widely used in reconstruction. Its advantage over other flaps is its purported minimal donor site morbidity. The present systematic review summarizes the types of complications and their incidence with this flap. A secondary objective is to delineate factors that influence these complications and make recommendations to avoid them.
Two independent assessors undertook a systematic review of the literature using multiple databases. All patients with ALT flap reconstruction for any defect were included. Donor site complications including lateral thigh paresthesia, musculoskeletal dysfunction, hypertrophic scarring, wound breakdown, infection, donor site pain, seroma, hematoma, compartment syndrome and muscle necrosis were extracted from identified articles and tabulated. Based on the number of pooled events and the number of cases performed, an incidence rate was calculated.
Forty-two relevant articles were identified that included 2324 flaps. Of the 2324 flaps, the majority were fasciocutaneous (n=737), and 1303 of the flaps were used in head and neck reconstruction. The incidence of complications were: lateral thigh paresthesia (24.0%); musculoskeletal dysfunction (4.8%); hypertrophic scarring or wound dehiscence (4.8%); donor site pain (3.3%); seroma (2.4%); infection (2.2%); hematoma (0.7%); compartment syndrome (0.09%); and partial muscle necrosis (0.09%).
Lateral thigh paresthesia is the most common complication. Severe complications such as compartment syndrome and muscle necrosis can occur, but are rare. Preservation of the lateral cutaneous nerve of the thigh, femoral motor nerve branches and deep fascia decreases the risk of complications. The degree of vastus lateralis disruption did not show a significant impact on musculoskeletal dysfunction.
PMCID: PMC3307676  PMID: 23598761
Anterolateral thigh flap; Complications; Donor site
11.  Angiogenesis and lymphangiogenesis as prognostic factors after therapy in patients with cervical cancer 
Contemporary Oncology  2012;16(1):6-11.
Aim of the study
This retrospective study attempts to evaluate the influence of serum vascular endothelial growth factor C (VEGF-C), microvessel density (MVD) and lymphatic vessel density (LMVD) on the result of tumour treatment in women with cervical cancer.
Material and methods
The research was carried out in a group of 58 patients scheduled for brachytherapy for cervical cancer. All women were patients of the Department and University Hospital of Oncology and Brachytherapy, Collegium Medicum in Bydgoszcz of Nicolaus Copernicus University in Toruń. VEGF-C was determined by means of a quantitative sandwich enzyme immunoassay using a human antibody VEGF-C ELISA produced by Bender MedSystem, enzyme-linked immunosorbent detecting the activity of human VEGF-C in body fluids. The measure for the intensity of angiogenesis and lymphangiogenesis in immunohistochemical reactions is the number of blood vessels within the tumour. Statistical analysis was done using Statistica 6.0 software (StatSoft, Inc. 2001). The Cox proportional hazards model was used for univariate and multivariate analyses. Univariate analysis of overall survival was performed as outlined by Kaplan and Meier. In all statistical analyses p < 0.05 (marked red) was taken as significant.
In 51 patients who showed up for follow-up examination, the influence of the factors of angiogenesis, lymphangiogenesis, patients’ age and the level of haemoglobin at the end of treatment were assessed. Selected variables, such as patients’ age, lymph vessel density (LMVD), microvessel density (MVD) and the level of haemoglobin (Hb) before treatment were analysed by means of Cox logical regression as potential prognostic factors for lymph node invasion. The observed differences were statistically significant for haemoglobin level before treatment and the platelet number after treatment. The study revealed the following prognostic factors: lymph node status, FIGO stage, and kind of treatment. No statistically significant influence of angiogenic and lymphangiogenic factors on the prognosis was found.
Angiogenic and lymphangiogenic factors have no value in predicting response to radiotherapy in cervical cancer patients.
PMCID: PMC3687378  PMID: 23788848
cervical cancer; angiogenesis; lymphangiogenesis; VEGF-C
12.  Nicolaus A. Friedreich's description of peripheral facial nerve paralysis in 1798. 
In 1798, Nicolaus A. Friedreich of Wurzburg published a detailed clinical account of three patients with idopathic peripheral facial nerve paralysis. His astute observations of onset, physical findings, natural course, treatment, and recovery preceded those of Charles Bell by 23 years.
PMCID: PMC490158  PMID: 368292
In this paper we have sought to show that unequivocal strains of herpes virus exist in man, which, in the rabbit, exhibit a degree of encephalitogenic power not exceeded, and perhaps rarely equalled, by any strain of the so called encephalitis virus. The fact that such highly encephalitogenic strains of the herpes virus exist in nature has, at the moment, theoretical and practical importance. Until recently, the view has been accepted by certain workers in the field that two biologically distinct viruses of this class occur—one inducing epidemic encephalitis and the other febrile herpes in man. This view, is, indeed, being supplanted at the present time by the notion, advocated by Levaditi, Nicolau, and Poincloux, of a group of closely related virus organisms for which the name "herpetico-encephalitic" is proposed. Within this group they distinguish strains of virus displaying special affinities for the central nervous organs and others exhibiting equal affinities for skin and membrane (cornea) structures. The first mentioned strains are responsible, under suitable circumstances, for epidemics of encephalitis in man; the others give rise to ordinary attacks of febrile herpes. The H. F. virus described in this paper does not conform to the classification indicated. While being a true febrile herpes strain, it possesses, nevertheless) a high degree of power to attack the central nervous system as well as marked capacity to implant itself on the skin and the cornea of the rabbit. Not only does virus encephalitis follow invariably upon the intracranial injection of the H. F. virus, but as regularly upon corneal, skin, nasal, blood, and testicular modes of inoculation. The symptoms of virus encephalitis thus provoked and the character of the brain lesions induced are precisely those, in all their detail and variety, including the presence of intracellular inclusion bodies, which have been described for the so called virus of encephalitis. Moreover, the H. F. virus is durably glycerol-resistant, is filterable through Berkefeld candles, and behaves immunologically as do the usual strains of herpes and of encephalitis virus. On the basis of the experimental data presented, we conclude that any distinction made regarding, on the one hand, encephalitogenic power as a special property of a virus secured from cases of epidemic encephalitis, and, on the other hand, of ectotropic action as an equally special quality of a virus yielded by febrile herpes, is in its nature artificial and not in harmony with ascertained fact. What can, indeed, be distinguished are stronger and weaker strains of a virus) probably always herpetic in origin, as determined by the inoculation of rabbits. While a strong herpes virus is both dermatotropic and neurotropic, a weak virus tends, in its multiplication, to remain confined to the site of inoculation, to act chiefly on the tissues on which it is immediately implanted, and not to extend to distant parts. And this is equally true whether the strain of virus came originally from cases of epidemic encephalitis, or merely from cases of febrile herpes in man. Hence direct comparison cannot be made between the stronger encephalitogenic and weaker non-encephalitogenic strains, according to any specific etiological property. The viruses we are discussing do, indeed, compose one group but it is the group of febrile herpes with which epidemic encephalitis is associated accidentally, if at all. It happens, indeed, that the Levaditi strain (souche) C and the Doerr Basel strain, both supposedly originating in cases of encephalitis in man, are less encephalitogenic for the rabbit than the true herpes strains, H. F. and Goodpasture M.
PMCID: PMC2130935  PMID: 19868984
14.  Long-distance colonization and radiation in gekkonid lizards, Tarentola (Reptilia: Gekkonidae), revealed by mitochondrial DNA sequences. 
Morphological systematics makes it clear that many non-volant animal groups have undergone extensive transmarine dispersal with subsequent radiation in new, often island, areas. However, details of such events are often lacking. Here we use partial DNA sequences derived from the mitochondrial cytochrome b and 12S rRNA genes (up to 684 and 320 bp, respectively) to trace migration and speciation in Tarentola geckos, a primarily North African clade which has invaded many of the warmer islands in the North Atlantic Ocean. There were four main invasions of archipelagos presumably by rafting. (i) The subgenus Neotarentola reached Cuba up to 23 million years (Myr) ago, apparently via the North Equatorial current, a journey of at least 6000 km. (ii) The subgenus Tarentola invaded the eastern Canary Islands relatively recently covering a minimum of 120 km. (iii) The subgenus Makariogecko got to Gran Canaria and the western Canary Islands 7-17.5 Myr ago, either directly from the mainland or via the Selvages or the archipelago of Madeira, an excursion of 200-1200 km. (iv) A single species of Makariogecko from Gomera or Tenerife in the western Canaries made the 1400 km journey to the Cape Verde Islands tip to 7 Myr ago by way of the south-running Canary current. Many journeys have also occurred within archipelagos, a minimum of five taking place in the Canaries and perhaps 16 in the Cape Verde Islands. Occupation of the Cape Verde archipelago first involved an island in the northern group, perhaps São Nicolau, with subsequent spread to its close neighbours. The eastern and southern islands were colonized from these northern islands, at least two invasions widely separated in time being involved. While there are just three allopatric species of Makariogecko in the Canaries, the single invader of the Cape Verde Islands radiated into five, most of the islands being inhabited by two of these which differ in size. While size difference may possibly be a product of character displacement in the northern islands, taxa of different sizes reached the southern islands independently.
PMCID: PMC1690580  PMID: 10821607
15.  Parallel gigantism and complex colonization patterns in the Cape Verde scincid lizards Mabuya and Macroscincus (Reptilia: Scincidae) revealed by mitochondrial DNA sequences. 
The scincid lizards of the Cape Verde islands comprise the extinct endemic giant Macroscincus coctei and at least five species of Mabuya, one of which, Mabuya vaillanti, also had populations with large body size. Phylogenetic analysis based on DNA sequences derived from the mitochondrial cytochrome b, cytochrome oxidase I and 12S rRNA genes (711, 498 and 378 base pairs (bp), respectively) corroborates morphological evidence that these species constitute a clade and that Macroscincus is unrelated to very large skinks in other areas. The relationships are ((M. vaillanti and Mabuya delalandii) (Mabuya spinalis and Macroscincus coctei (Mabuya fogoensis nicolauensis (Mabuya fogoensis antaoensis and Mabuya stangeri)))). The Cape Verde archipelago was colonized from West Africa, probably in the Late Miocene or Early Pliocene period. The north-eastern islands were probably occupied first, after which the ancestor of M. vaillanti and M. delalandii may have originated on Boavista, the ancestor of the latter species arriving on Santiago or Fogo later. The M. fogoensis--M. stangeri clade colonized the islands of Branco, Razo, Santa Luzia and São Vicente from São Nicolau and reached Santo Antão after this. Colonization of these northeastern islands was slow, perhaps because the recipient islands had not developed earlier or because colonization cut across the path of the Canary Current and the Northeast Trade Winds, the main dispersing agents in the region. Rapid extension of range into the southwestern islands occurred later in M. spinalis and then in M. vaillanti and M. delalandii. The long apparent delay between the origin of these species and their southwestern dispersal may have been because there were earlier colonizations of the southern islands which excluded later ones until the earlier inhabitants were exterminated by volcanic or climatic events. The evolution of large size in Macroscincus occurred in the northwestern islands and was paralleled in the eastern and southern islands by populations of M. vaillanti. Both cases of size increase in Cape Verde skinks were accompanied by the development of herbivory.
PMCID: PMC1088783  PMID: 11487407
16.  Correlates of Quality of Life in Older Adults With Diabetes 
Diabetes Care  2011;34(8):1749-1753.
To evaluate associations between health-related quality of life (HRQL) and geriatric syndromes, diabetes complications, and hypoglycemia in older adults with diabetes.
A race-stratified random sample of 6,317 adults with type 2 or type 1 diabetes, aged 60 to 75 years, enrolled in Kaiser Permanente Northern California, who completed a survey that included a HRQL instrument based on the Short Form 8-item health survey. Administrative records were used to ascertain diagnoses of geriatric syndromes, diabetes complications, and hypoglycemia. Associations were estimated between HRQL and exposures in exposure-specific and combined exposure models (any syndrome, any complication, or hypoglycemia). Conservatively, differences of ≥3 points were considered the minimally important difference in HRQL scores.
HRQL was lower with nearly all exposures of interest. The lowest physical HRQL was associated with amputation. In combined exposure models, geriatric syndromes (−5.3 [95% CI −5.8 to −4.8], P < 0.001) and diabetes complications (−3.5 [−4.0 to −2.9], P < 0.001) were associated with lower physical HRQL. The lowest mental HRQL was associated with depression, underweight (BMI <18 kg/m2), amputation, and hypoglycemia. In combined exposure models, only hypoglycemia was associated with lower mental HRQL (−4.0 [−7.0 to −1.1], P = 0.008).
Geriatric syndromes and hypoglycemia are associated with lower HRQL to a comparable degree as diabetes complications. Addressing geriatric syndromes and avoiding hypoglycemia should be given as high a priority as preventing diabetes complications in older adults with diabetes.
PMCID: PMC3142040  PMID: 21636795
17.  Neuroacanthocytosis Syndromes 
Neuroacanthocytosis (NA) syndromes are a group of genetically defined diseases characterized by the association of red blood cell acanthocytosis and progressive degeneration of the basal ganglia. NA syndromes are exceptionally rare with an estimated prevalence of less than 1 to 5 per 1'000'000 inhabitants for each disorder. The core NA syndromes include autosomal recessive chorea-acanthocytosis and X-linked McLeod syndrome which have a Huntington´s disease-like phenotype consisting of a choreatic movement disorder, psychiatric manifestations and cognitive decline, and additional multi-system features including myopathy and axonal neuropathy. In addition, cardiomyopathy may occur in McLeod syndrome. Acanthocytes are also found in a proportion of patients with autosomal dominant Huntington's disease-like 2, autosomal recessive pantothenate kinase-associated neurodegeneration and several inherited disorders of lipoprotein metabolism, namely abetalipoproteinemia (Bassen-Kornzweig syndrome) and hypobetalipoproteinemia leading to vitamin E malabsorption. The latter disorders are characterized by a peripheral neuropathy and sensory ataxia due to dorsal column degeneration, but movement disorders and cognitive impairment are not present. NA syndromes are caused by disease-specific genetic mutations. The mechanism by which these mutations cause neurodegeneration is not known. The association of the acanthocytic membrane abnormality with selective degeneration of the basal ganglia, however, suggests a common pathogenetic pathway. Laboratory tests include blood smears to detect acanthocytosis and determination of serum creatine kinase. Cerebral magnetic resonance imaging may demonstrate striatal atrophy. Kell and Kx blood group antigens are reduced or absent in McLeod syndrome. Western blot for chorein demonstrates absence of this protein in red blood cells of chorea-acanthocytosis patients. Specific genetic testing is possible in all NA syndromes. Differential diagnoses include Huntington disease and other causes of progressive hyperkinetic movement disorders. There are no curative therapies for NA syndromes. Regular cardiologic studies and avoidance of transfusion complications are mandatory in McLeod syndrome. The hyperkinetic movement disorder may be treated as in Huntington disease. Other symptoms including psychiatric manifestations should be managed in a symptom-oriented manner. NA syndromes have a relentlessly progressive course usually over two to three decades.
PMCID: PMC3212896  PMID: 22027213
18.  Risks and complications in rhinoplasty 
Rhinoplasty is regarded to be associated with many risks as the expectations of patient and physician are not always corresponding. Besides of postoperative deformities many other risks and complications have to be considered.
Reduction-rhinoplasty e.g. can cause breathing disturbances which are reported in 70% of all revision-rhinoplasty-patients. One has to be aware however that scars and loss of mucosal-sensation can also give the feeling of a “blocked nose”.
The main risks of autogenous transplants are dislocation and resorption, while alloplasts can cause infection and extrusion. In this respect silicone implants can have a complication rate between 5-20%. Less complications are reported with other materials like Gore-Tex.
Complications of skin and soft tissues can be atrophy, fibrosis, numbness, cysts originating from displaced mucosa or subcutaneous granulomas caused by ointment material. Postoperative swelling depends mainly on the osteotomy technique. Percutaneous osteotomies cause less trauma, but may result in visible scars.
Infections are rare but sometimes life-threatening (toxic-shock-syndrome). The risk is higher, when sinus surgery and rhinoplasty are combined. Osteotomies can also cause injuries of the orbital region. Necrosis of eye-lids by infections and blindness by central artery occlusion are known. There are reports on various other risks like rhinoliquorrhea, brain damage, fistulas between sinus-cavernosus and carotid artery, aneurysms and thrombosis of the cavernous sinus. Discoloration of incisors are possible by damage of vessels and nerves. Rhinoplasty can also become a court-case in dissatisfied patients, a situation that may be called a “typical complication of rhinoplasty”. It can be avoided by proper patient selection and consideration of psychological disturbances.
Postoperative deformities are considered as main risks of rhinoplasty, causing revision surgery in 5% to 15% of the cases. The analysis of postoperative deformities allowes the identification of specific risks. The most frequent postoperative deformity is the “pollybeak” when a deep naso-frontal angle, cartilaginous hump and reduced tip projection are present preoperatively. The pollybeak is the indication in about 50% of all revision rhinoplasties. Other frequent postoperative deformities are a pendant and wide nasal tip, retractions of the columella base or irregularities of the nasal dorsum. These deformities are very often combined and caused by a loss of septal support. This is why the stability of the caudal septum in septorhinoplasty is the key for a predictable result. Maintaining the position of the tip and the columella is one of the main issues to avoid typical postoperative deformities.
The risks for rhinoplasty-complications can be reduced with increasing experience. A prerequisite is continuing education and an earnest distinction between complication and mistake.
PMCID: PMC3199839  PMID: 22073084
19.  Well leg compartment syndrome after pelvic and perineal surgery in the lithotomy position 
Postgraduate Medical Journal  2005;81(958):534-536.
Objective: Lower limb compartment syndrome after prolonged surgical procedures performed in the lithotomy position is a rare but potentially devastating complication. It is recognised after urological, colorectal, and gynaecological procedures. Sixteen cases of compartment syndrome after urological surgery have been reported. The objective of this study was to estimate the incidence of this complication in urological practice and identify risk factors for its development.
Design: A postal survey of UK consultant urologists was conducted.
Results: Replies were received from 261 consultants. In total there were 65 cases of compartment syndrome. Compartment syndrome occurred after radical cystectomy and urinary diversion in 51 cases and was rare in procedures lasting less than four hours. The incidence of compartment syndrome after cystectomy was estimated at around 1 in 500 cases. Risk factors for its development included perioperative blood loss, peripheral vascular disease, and obesity.
Conclusions: Compartment syndrome after use of the lithotomy position may be more common than is generally appreciated and has been underreported in the past. All staff should be aware of this serious complication and adopt strategies for its avoidance.
PMCID: PMC1743337  PMID: 16085748
20.  Spectrum of complicated migraine in children: A common profile in aid to clinical diagnosis 
Complicated migraine encompasses several individual clinical syndromes of migraine. Such a syndrome in children frequently presents with various neurological symptoms in the Emergency Department. An acute presentation in the absence of headache presents a diagnostic challenge. A delay in diagnosis and treatment may have medicolegal implication. To date, there are no reports of a common clinical profile proposed in making a clinical diagnosis for the complicated migraine. In this clinical review, we propose and describe: (1) A common clinical profile in aid to clinical diagnosis for spectrum of complicated migraine; (2) How it can be used in differentiating complicated migraine from migraine without aura, migraine with aura, and seizure; (3) We discuss the status of complicated migraine in the International Headache Society classification 2013; and (4) In addition, a common treatment strategy for the spectrum of migraine has been described. To diagnose complicated migraine clinically, it is imperative to adhere with the proposed profile. This will optimize the use of investigation and will also avoid a legal implication of delay in their management. The proposed common clinical profile is incongruent with the International Headache Society 2013. Future classification should minimize the dissociation from clinically encountered syndromes and coin a single word to address collectively this subtype of migraine with an acute presentation of a common clinical profile.
PMCID: PMC4318797  PMID: 25664241
Electroencephalography; Seizure; Seizure like activity; Complicated migraine; Stroke; Magnetic resonance imaging
21.  Complication avoidance in transcallosal transforaminal approach to colloid cysts of the anterior third ventriclen: An analysis of 80 cases 
Asian Journal of Neurosurgery  2014;9(2):51-57.
The objective of the present study is to analyze the complications and their avoidance in a series of 80 patients operated by transcallosal transforaminal approach to colloid cysts of the anterior third ventricle.
Materials and Methods:
The surgical outcome and complications of 80 patients operated by transcallosal transforaminal approach for colloid cysts in the anterior third ventricle was analyzed. A detailed pre- and post-operative neurological assessment was done in all patients. Neurocognitive assessment of corpus callosal function was done in the last 22 cases. CT scan of the brain was done in all patients, before and after surgery.
All patients underwent transcallosal transforaminal approach. Total excision of the lesion was achieved in 79 patients and subtotal in one. The complications encountered were postoperative seizures in six, acute hydrocephalus in four, venous cortical infarct in four, transient hemiparesis in four, transient memory impairment, especially for immediate recall in nine, mutism in one, subdural hematoma in one, meningitis in three, and tension pneumocephalus in one patient. There were two mortalities. There was no incidence of postoperative disconnection syndrome.
Colloid cyst is surgically curable. With good knowledge of the regional anatomy and meticulous microsurgical techniques, there is a low mortality and minimum morbidity, when compared to the natural history of the disease. With increasing experience, most of the complications are avoidable. The limited anterior callosotomy does not result in disconnection syndromes.
PMCID: PMC4129577  PMID: 25126118
Anterior third ventricle; colloid cyst; complications; disconnection syndrome; transcallosal; transforaminal
22.  Sotos syndrome and scoliosis surgical treatment: a 10-year follow-up 
European Spine Journal  2011;20(Suppl 2):271-277.
Sotos syndrome is caused by a gene deletion with an autosomal dominant pattern of inheritance. Cerebral gigantism, hypotonia and joint hyperextensibility are characteristic features of this syndrome. A percentage of these patients develop progressive scoliosis early in life. In the literature, few studies on the evolution of scoliosis in Sotos syndrome have been published. We retrospectively evaluated eight patients diagnosed with Sotos syndrome and scoliosis treated at the Garrahan Children Hospital between 1988 and March 2009. Clinical charts and imaging studies were assessed. Eight patients (19%) presented with scoliosis and seven of them (87.5%) required surgical treatment. The mean follow-up was 9.5 years (range 3–18). Mean age at first consultation was 5.2 years (range 1.1–11.2). Mean Cobb angle for scoliosis at first consultation was 34.3° (range 20°–42°) and the mean Cobb angle for kyphosis was 45.6° (range 30°–90°). Mean age at surgery was 11.2 years (range 3.7–18.10). The surgical procedures performed were instrumented posterior arthrodesis, alone or combined with anterior arthrodesis, instrumented anterior arthrodesis, while one patient is currently in treatment with growing rods. Preoperative mean Cobb angle for scoliosis was 72.3° (range 54°–130°) and for kyphosis was 59.8° (range 30°–108°); postoperative mean Cobb angle for scoliosis was 45.5° (range 6°–90°) and for kyphosis was 40.2° (range 30°–80°). There were three early complications (pleural effusion in two cases and death due to sepsis in one) and two late complications (kyphosis above the instrumentation area and dislodgement of the proximal hooks). Incidence of scoliosis in Sotos syndrome is high and thus close monitoring of patients with Sotos syndrome during growth is important for early detection of this entity. Joint hyperextensibility and hypotonia that are characteristic of the syndrome should be considered at the moment of surgery to avoid short fusions.
PMCID: PMC3111518  PMID: 21225435
Cerebral gigantism; Scoliosis deformity
23.  The HELLP syndrome: Clinical issues and management. A Review 
The HELLP syndrome is a serious complication in pregnancy characterized by haemolysis, elevated liver enzymes and low platelet count occurring in 0.5 to 0.9% of all pregnancies and in 10–20% of cases with severe preeclampsia. The present review highlights occurrence, diagnosis, complications, surveillance, corticosteroid treatment, mode of delivery and risk of recurrence.
Clinical reports and reviews published between 2000 and 2008 were screened using Pub Med and Cochrane databases.
Results and conclusion
About 70% of the cases develop before delivery, the majority between the 27th and 37th gestational weeks; the remainder within 48 hours after delivery. The HELLP syndrome may be complete or incomplete. In the Tennessee Classification System diagnostic criteria for HELLP are haemolysis with increased LDH (> 600 U/L), AST (≥ 70 U/L), and platelets < 100·109/L. The Mississippi Triple-class HELLP System further classifies the disorder by the nadir platelet counts. The syndrome is a progressive condition and serious complications are frequent. Conservative treatment (≥ 48 hours) is controversial but may be considered in selected cases < 34 weeks' gestation. Delivery is indicated if the HELLP syndrome occurs after the 34th gestational week or the foetal and/or maternal conditions deteriorate. Vaginal delivery is preferable. If the cervix is unfavourable, it is reasonable to induce cervical ripening and then labour. In gestational ages between 24 and 34 weeks most authors prefer a single course of corticosteroid therapy for foetal lung maturation, either 2 doses of 12 mg betamethasone 24 hours apart or 6 mg or dexamethasone 12 hours apart before delivery. Standard corticosteroid treatment is, however, of uncertain clinical value in the maternal HELLP syndrome. High-dose treatment and repeated doses should be avoided for fear of long-term adverse effects on the foetal brain. Before 34 weeks' gestation, delivery should be performed if the maternal condition worsens or signs of intrauterine foetal distress occur. Blood pressure should be kept below 155/105 mmHg. Close surveillance of the mother should be continued for at least 48 hours after delivery.
PMCID: PMC2654858  PMID: 19245695
24.  Design and rationale of the AngioSeal versus the Radial approach In acute coronary SyndromE (ARISE) trial: a randomized comparison of a vascular closure device versus the radial approach to prevent vascular access site complications in non-ST-segment elevation acute coronary syndrome patients 
Trials  2013;14:435.
Arterial access is a major site of bleeding complications after invasive coronary procedures. Among strategies to decrease vascular complications, the radial approach is an established one. Vascular closure devices provide more comfort to patients and decrease hemostasis and need for bed rest. However, the inconsistency of data proving their safety limits their routine adoption as a strategy to prevent vascular complications, requiring evidence through adequately designed randomized trials. The aim of this study is to compare the radial versus femoral approach using a vascular closure device for the incidence of arterial puncture site vascular complications among non-ST-segment elevation acute coronary syndrome patients submitted to an early invasive strategy.
ARISE is a national, multicenter, non-inferiority randomized clinical trial. Two hundred patients with non-ST-segment elevation acute coronary syndrome will be randomized to either radial or femoral access using a vascular closure device. The primary outcome is the occurrence of vascular complications at an arterial puncture site 30 days after the procedure, including major bleeding, retroperitoneal hematoma, compartment syndrome, hematoma ≥ 5 cm, pseudoaneurysm, arterio-venous fistula, infection, limb ischemia, arterial occlusion, adjacent nerve injury or the need for vascular surgical repair.
Enrollment was initiated in September 2012, and until October 2013 91 patients were included. The inclusion phase is expected to last until the second half of 2014.
The ARISE trial will help define the role of a vascular closure device as a bleeding avoidance strategy in patients with NSTEACS.
Trial registration identifier: NCT01653587
PMCID: PMC3878328  PMID: 24345099
Radial approach; Femoral approach; Vascular closure device; Angioplasty; Acute coronary syndrome; Access site complication
25.  Gluteal compartment syndrome after lumbar laminectomy 
BMJ Case Reports  2009;2009:bcr08.2009.2165.
Gluteal compartment syndrome may, in its severe form, have serious consequences. It may result in severe rhabdomyolysis, and if left untreated it can result in acute renal collapse, multiorgan failure and even death. The present report concerns a patient who developed a gluteal compartment syndrome after lumbar surgery. The syndrome was complicated by acute renal failure with high concentrations of serum creatinine kinase, myoglobin, and potassium, requiring acute haemodialysis before surgical release. The operation revealed increased intracompartmental pressure with weak or absent reaction of muscles to electric stimulation. To prevent the development of gluteal compartment syndrome during operative procedures, it is important to avoid harmful pressure to the gluteal regions on the operating table. It is also important to optimise muscle circulation by adequate hydration therapy and avoidance of nephrotoxic stimuli. If gluteal compartment syndrome develops, immediate diagnosis and surgical decompression are mandatory .
PMCID: PMC3029082  PMID: 22114624

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