Chronic irreducible posterolateral knee dislocation: two-stage surgical approach.

Posterolateral knee dislocation is a small subset of knee dislocations. Irreducible posterolateral dislocation has been reported and is caused by buttonholing of the medial femoral condyle into the anteromedial knee capsule, with interposition of the medial retinacular structures between the femoral and tibial condyles. Open reduction has been advocated to reduce the knee. We present a case of chronic irreducible posterolateral dislocation of the knee for 14 months associated with anterior and posterior cruciate ligament (ACL, PCL) and medial collateral ligament (MCL) rupture. The patient presented with continued instability. The classic dimple sign was absent in this case because of chronicity, but the limb was in valgus alignment compared with the other side. The magnetic resonance imaging (MRI) report commented only on the torn cruciates and the MCL, but missed the tissues preventing reduction. A 2-stage surgical procedure was performed. The first stage included arthroscopic debridement of the intervening tissues, which were thickened and resembled meniscal tissue, followed by reduction of the knee and open MCL repair to maintain the reduction. The second stage was done for ACL and PCL reconstruction. In conclusion we bring the attention of the surgeon to the clinical, radiographic, and MRI findings associated with this chronic irreducible posterolateral knee dislocation.

The Kingston Standardized Behavioural Assessment.

The Kingston Standardized Behavioural Assessment (KSBA), a behavioral screening tool that assesses the behavioral changes associated with dementia, particularly Alzheimer's disease (AD), is introduced. Designed to be user friendly for clinicians not trained in specialized behavioral assessment techniques, it addresses some of the problems of existing scales. A group of patients diagnosed with probable AD, vascular dementia, or mixed (AD and vascular) was assessed using the KSBA. A subgroup was also given the Neuropsychiatric Inventory (NPI). Behavioral profiles and scores were obtained for all subjects. Factor analysis revealed 2 factors described as neuropsychiatric and neuropsychological. The KSBA efficiently collects neuropsychological and neuropsychiatric behavioral symptoms of dementia, is easy to score and interpret, and yields a behavioral profile that helps identify target behaviors for intervention. It can be used to facilitate clinical decision making around level of care and can be easily incorporated into clinically based research.

Atraumatic haemarthrosis following total knee replacement treated with selective embolisation.

Spontaneous haemarthrosis in the absence of anticoagulant medication or a bleeding disorder is a very rare complication after total knee arthroplasty. A case of recurrent spontaneous haemarthrosis following total knee replacement in a 69-year-old patient is reported. Angiography was used to aid the diagnosis. It demonstrated an abnormal blush of vessels around the anterior aspect of the knee joint, that was fed by genicular branches and a recurrent branch of the anterior tibial artery. Selective embolisation of the bleeding vessels with coils led to immediate control of the bleeding. No further recurrence of haemarthrosis has been recorded.

Whole-body hyperthermia in the rat disrupts the blood-cerebrospinal fluid barrier and induces brain edema.

The present investigation was undertaken to find out whether whole-body hyperthermia (WBH) alters blood-cerebrospinal fluid barrier (BCSFB) permeability to exogenously-administered tracers and whether choroid plexus and ependymal cells exhibit morphological alterations in hyperthermia. Rats subjected to 4 hours of heat stress at 38 degrees C in a biological oxygen demand (BOD) incubator exhibited a profound increase in the BCSFB to Evans blue and radioiodine. Blue staining of the dorsal surface of the hippocampus and caudate nucleus and a significant increase in Evans blue and [131]Iodine in cisternal cerebrospinal fluid were seen following 4-hour heat stress compared to control. Degeneration of choroidal epithelial cells and underlying ependyma, a dilated ventricular space, and degenerative changes in the underlying neuropil were frequent. Hippocampus, caudate nucleus, thalamus, and hypothalamus exhibited profound increases in water content after 4 hours of heat stress. These observations suggest that hyperthermia induced by WBH is capable of breaking down the BCSFB and contributing to cell and tissue injury in the central nervous system.

Atrial natriuretic peptide: its putative role in modulating the choroid plexus-CSF system for intracranial pressure regulation.

Evidence continues to build for the role of atrial natriuretic peptide (ANP) in reducing cerebrospinal fluid (CSF) formation rate, and thus, intracranial pressure. ANP binds to choroid plexus (CP) epithelial cells. This generates cGMP, which leads to altered ion transport and the slowing of CSF production. Binding sites for ANP in CP are plentiful and demonstrate plasticity in fluid imbalance disorders; however, specific ANP receptors in epithelial cells need confirmation. Using antibodies directed against NPR-A and NPR-B, we now demonstrate immunostaining not only in the choroidal epithelium (including cytoplasm), but also in the ependyma and some endothelial cells of cerebral microvessels in adult rats (Sprague-Dawley). The choroidal and ependymal cells stained almost universally, thus substantiating the initial autoradiographic binding studies with 125I-ANP. Because ANP titers in human CSF have previously been shown to increase proportionally to increments in ICP, we propose a compensatory ANP modulation of CP function to down-regulate ICP in hydrocephalus. Further evidence for this notion comes from the current finding of increased frequency of "dark" epithelial cells in CP of hydrocephalic (HTx) rats, which fits our earlier observation that the "dark" choroidal cells, associated with states of reduced CSF formation, are increased by elevated ANP in CSF. Altogether, ANP neuroendocrine-like regulation at CSF transport interfaces and blood-brain barrier impacts brain fluid homeostasis.

Sex, haemoglobin and kidney disease: new perspectives.

Anaemia is recognized as a common complication of chronic kidney disease with significant associated morbidity and mortality. Published data document the negative impact of anaemia on cardiovascular disease outcomes, progression of chronic kidney disease (CKD), hospitalizations, rehabilitation and quality of life, among others. Gender differences have been identified in many of these areas as well as, and importantly, in cardiovascular and chronic kidney disease outcomes. Female gender is associated with lower risk of cardiovascular morbidity and mortality as well as slower progression of chronic kidney disease. Interestingly, there are some well-described physiological adaptations to anaemia in women, which include shifting of the haemoglobin oxygen dissociation curve to reduce oxygen affinity secondary to higher levels of 2,3-diphosphoglycerate. However, the complex physiology underlying the impact of anaemia or gender on patients with chronic kidney disease is not well-characterized to date. Furthermore, there has been little examination of the potential interaction between anaemia and gender on cardiac or kidney outcomes. In this paper, we review the documented impact of anaemia and gender on outcomes, and explore the interaction of anaemia and gender in patients with CKD. We also present data that describe the potential importance of considering gender when targeting specific levels of haemoglobin. The value of a new perspective on haemoglobin and gender in kidney disease is important from both a physiological and an economical perspective.

The brief Kingston Standardized Cognitive Assessment--revised.

OBJECTIVES: The Kingston Standardized Cognitive Assessment-Revised (KSCA-R) was designed to be a cognitive screening tool available to health professionals who were not trained in specialized cognitive assessment techniques. It was introduced to bridge the gap between brief, narrowly focused rating scales, and intensive, expensive, full neuropsychological assessments. We now present the Brief Kingston Standardized Cognitive Assessment-Revised (BriefKSCA-R). METHODS: Groups of Alzheimer's disease patients, patients suffering from other dementias, and a group of normal community dwelling elderly were assessed using the BriefKSCA-R. RESULTS: This shortened version of the full Kingston Standardized Cognitive Assessment-Revised can be given in half the time while retaining most of the full KSCA-R's effectiveness. CONCLUSIONS: Suitable for a quick screening, or follow-up of patients already more fully assessed.

Driving and dementia in Ontario: a quantitative assessment of the problem.

BACKGROUND: The population is becoming increasingly aged, and concomitantly, the prevalence of dementia is steadily rising. Persons aged 65 years and over are likely to continue driving for many years and often well into the dementia process. METHODS: Ontario Ministry of Transportation driving data, census data, and dementia prevalence data were combined to determine the number of persons with potential dementia who are driving, both now and in about 25 years' time. RESULTS: Actual and projected Ontario figures show that the number of senior drivers will increase markedly from just under 500,000 in 1986 to nearly 2,500,000 in 2028. Similarly, the number of drivers with dementia is also increasing. Although not all drivers with dementia are necessarily dangerous, most are estimated to continue driving well into the disease process. By combining the above-mentioned data sets, a best estimate of the number of drivers with dementia in Ontario was derived. It is estimated that this group has grown from just under 15,000 in 1986 to about 34,000 in 2000 and will number nearly 100,000 in 2028. INTERPRETATION: Increasingly, the responsibility for identifying drivers with dementia has fallen on the health care system, a role for which it was never designed nor equipped to handle. The risks associated with the dramatically increasing number of drivers with dementia demand a psychometrically sensitive and efficient screening procedure.

Reamer breakage in the femoral medulla during total knee arthroplasty: should reamers have a finite life?

We present a case of intraoperative breakage of an intramedullary reamer in the femoral canal during a total knee arthroplasty (TKA). The reamer snapped at the junction of its distal and middle thirds leaving the distal fragment of the reamer at the level of the femoral isthmus. The broken part was in the middle third of the femoral medulla invisible from the lower part of the femur. That was removed using a Küntscher intramedullary nail inserted proximally through the piriformis fossa. After removing it from the knee joint, the TKA was performed as initially planned. Our case highlights the rare however potential complication of intraoperative instrumentation failure and raises requests of metal fatigue and failure with repeated use. Further to that a technical note is made describing how to remove the broken instrument from the femoral medulla and complete the planned TKA.

The Revised Kingston Standardized Cognitive Assessment.

The original Kingston Standardized Cognitive Assessment (KSCA) was designed to assess cognitive functioning in the elderly with suspected organic brain damage (i.e. dementia). It was specifically designed to be a relatively quickly administered assessment tool available to mental health professionals who were not trained in specialized cognitive assessment techniques. It was introduced over a decade ago to bridge a gap between brief, narrowly focused rating scales, and intensive, expensive, full neuropsychological assessments. Recently, a revision of the KSCA was completed. This revision includes the addition of a word-list memory task with immediate recall, delayed recall and recognition formats, as well as new norms for patients with Alzheimer's disease (AD). The updated norms reflect the abilities of higher-functioning (community-dwelling) patients. In order to facilitate the Revised KSCAs use we have developed a new scoring and analysis form as well as a more comprehensive scoring and administration manual. These changes have resulted in better detection of earlier Alzheimer's disease and use of comparison groups that reflect the changing referral base. The structure of the revised scale and updated normative data are described. An illustrative clinical case example is also provided.

Early neutrophilic expression of vascular endothelial growth factor after traumatic brain injury.

The formation of edema after traumatic brain injury (TBI) is in part associated with the disruption of the blood-brain barrier. However, the molecular and cellular mechanisms underlying these phenomena have not been fully understood. One possible factor involved in edema formation is vascular endothelial growth factor (VEGF). This growth factor has previously been demonstrated to increase the blood-brain barrier permeability to the low molecular weight markers and macromolecules. In this study, we analyzed the temporal changes in VEGF expression after TBI in rats. In the intact brain, VEGF was expressed at relatively low levels and was found in the cells located close to the cerebrospinal fluid space. These were the astrocytes located under the ependyma and the pia-glial lining, as well as the epithelial cells of the choroid plexus. In addition, several groups of neurons, including those located in the frontoparietal cortex and in all hippocampal regions, were VEGF-positive. The pattern of VEGF-immunopositive staining of neurons and choroidal epithelium suggested that in these cells, VEGF binds to the cell membrane-associated heparan sulfate proteoglycans. Following TBI, there was an early (within 4 h post-injury) increase in VEGF expression in the traumatized parenchyma associated with neutrophilic invasion. The ipsilateral choroid plexus appeared to play a role in facilitating the migration of neutrophils from blood into the cerebrospinal fluid space, from where many of these cells infiltrated the brain parenchyma. VEGF-immunopositive staining of neutrophils resembled haloes and was found ipsilaterally within the frontoparietal cortex and around the velum interpositum, a part of the subarachnoid space. These haloes likely represent the deposition of neutrophil-derived VEGF within the extracellular matrix, from where this growth factor may be gradually released during an early post-traumatic period. The maximum number of VEGF-secreting neutrophils was observed between 8 h and 1 day after TBI. In addition, from 4 h post-TBI, there was a progressive increase in the number of VEGF-immunoreactive astrocytes in the ipsilateral frontoparietal cortex. The maximum number of astrocytes expressing VEGF was observed 4 days after TBI, and then the levels of astroglial VEGF expression declined gradually. Early invasion of brain parenchyma by VEGF-secreting neutrophils together with a delayed increase in astrocytic synthesis of this growth factor correlate with the biphasic opening of the blood-brain barrier and formation of edema previously observed after TBI. Therefore, these findings suggest that VEGF plays an important role in promoting the formation of post-traumatic brain edema.

Bilateral patellar component dissociation in a patient with total knee arthroplasties.

We present a case of bilateral patellar component dissociation 6 years after bilateral total knee arthroplasty. The patient had undergone arthroscopic lateral releases bilaterally for patellar maltracking. After repetitive trauma, the patient experienced patellar component dissociation, which was treated arthroscopically by removing the patellar components and leaving the patellae unresurfaced. The patient's symptoms improved substantially. Our case highlights certain features of the etiology as well as the management of patellar component dissociation in the total knee arthroplasty, showing the important role of arthroscopy.

Diffusion-weighted MR imaging of rim-enhancing brain masses: is markedly decreased water diffusion specific for brain abscess?

OBJECTIVE: This retrospective study investigated the specificity of restricted water diffusion for the diagnosis of brain abscess. Two of five rim-enhancing brain masses with restricted water diffusion (apparent diffusion coefficient of 0.79 [10(-3) mm(2)/sec] or less) were brain abscesses, but diagnoses in the other cases were metastatic squamous cell carcinoma (two cases) and radiation necrosis. CONCLUSION: Although an important diagnostic sign, restricted water diffusion is not specific for brain abscess.

Angiotensin II type 1 receptor gene polymorphisms in humans: physiology and pathophysiology of the genotypes.

Many studies have attempted to relate genetic variants of components of the renin-angiotensin system to complex diseases such as essential hypertension, cardiovascular disease and progressive renal failure. The angiotensin II type 1 receptor (AT1R) gene is an important example of this approach. Many polymorphisms of the AT1R gene have been identified, but the A1166-->C polymorphism has been the most extensively studied. The physiological significance of this polymorphism is uncertain because of its location in the 3'-untranslated region of the gene. The present review summarizes association studies of the AT1R gene, focusing on clinical end-points and physiological responses.

Effect of oral contraceptives on the renin angiotensin system and renal function.

We examined the effect of oral contraceptive (OC) usage on the renin angiotensin system (RAS) in two related experiments. In the first experiment, subjects were 34 healthy, normotensive, premenopausal women, 15 OC users and 19 OC nonusers, mean age 25 +/- 1 yr, ingesting a controlled sodium diet. We assessed arterial pressure, glomerular filtration rate, effective renal plasma flow, renal vascular resistance (RVR), and filtration fraction (FF) using inulin and p-aminohippurate clearance techniques, both at baseline and in response to the ANG II receptor blocker losartan. In the second experiment, in similar subjects, 10 OC users and 10 nonusers, we examined circulating RAS components [angiotensinogen, ANG II, aldosterone, plasma renin activity (PRA), and active renin] in response to incremental lower body negative pressure (LBNP), to determine whether renin secretion is suppressed by OC usage. OC users exhibited elevations in systolic blood pressure, RVR, and FF compared with nonusers, which were partially corrected by losartan. In the LBNP phase of the study, baseline measures of PRA, angiotensinogen, ANG II, and aldosterone were all increased in the OC group compared with the control group. Active renin levels did not differ between groups. Incremental LBNP resulted in increased circulating levels of RAS components in both groups. We conclude that the RAS is activated in women using OCs. There was no evidence that decreases in renin secretion result in normalization of the RAS as a whole.

Depalmitoylation of endothelial nitric-oxide synthase by acyl-protein thioesterase 1 is potentiated by Ca(2+)-calmodulin.

Protein palmitoylation represents an important mechanism governing the dynamic subcellular localization of many signaling proteins. Palmitoylation of endothelial nitric-oxide synthase (eNOS) promotes its targeting to plasmalemmal caveolae; agonist-promoted depalmitoylation leads to eNOS translocation. Depalmitoylation and translocation of eNOS modulate the agonist response, but the pathways that regulate eNOS palmitoylation and depalmitoylation are poorly understood. We now show that the newly characterized acyl-protein thioesterase 1 (APT1) regulates eNOS depalmitoylation. Immunoblot analyses indicate that APT1 is expressed in bovine aortic endothelial cells, which express eNOS. APT1 overexpression appears to accelerate the depalmitoylation of eNOS in COS-7 cells cotransfected with eNOS and APT1 cDNAs. Additionally, purified recombinant APT1 depalmitoylates eNOS assayed in biological membranes isolated from endothelial cells biosynthetically labeled with [(3)H]palmitate or COS-7 cells transfected with eNOS cDNA. More important, the APT1-catalyzed depalmitoylation of palmitoyl-eNOS is potentiated by Ca(2+)-calmodulin (CaM), a key allosteric activator of eNOS. In contrast, APT1-catalyzed depalmitoylation of the G protein Galpha(s) is unaffected by Ca(2+)-CaM. Furthermore, caveolin, a palmitoylated membrane protein, does not appear to be a substrate for APT1. Taken together, these results support a role for APT1 in the regulation of eNOS depalmitoylation and suggest that Ca(2+)-CaM activation of eNOS renders the enzyme more susceptible to APT1-catalyzed depalmitoylation.

Direct demonstration in synthetic oligonucleotides that N,N'-bis(2-chloroethyl)-nitrosourea cross links N1 of deoxyguanosine to N3 of deoxycytidine on opposite strands of duplex DNA.

The sequence specificity and covalent structure of the lesion caused by the DNA interstrand cross-linking reaction of N,N'-bis(2-chloroethyl)-nitrosourea (BCNU) were investigated using synthetic oligonucleotides. The efficiency of interstrand cross-linking was found to parallel the efficiency of monoadduct formation, preferring deoxyguanosine-deoxycytidine-rich duplexes and, particularly, runs of deoxyguanosine. No explicit sequence specificity was observed. Enzymatic digestion of purified, interstrand cross-linked DNA returned primarily the unmodified deoxynucleosides, along with 1-[N3-deoxycytidyl]-2-[N1-deoxyguanosyl]ethane. This substance was characterized by comparison of its mass spectrum, high-pressure liquid chromatography retention time, and UV spectrum to an authentic standard prepared by chemical synthesis. These studies provide the first direct evidence that BCNU has no strong sequence preference for interstrand cross-linking and that substance 4, which has been previously isolated from BCNU-treated DNA, derives from alkylation on opposite strands of DNA. The lack of sequence preference and lesion structure together suggest that one source of BCNU interstrand cross-links is linkage of deoxyguanosine and deoxycytidine partners from a single bp.