Use of a Parathyroid Hormone Peptide (PTH1−34)‐enriched Fibrin Hydrogel for the Treatment of a Subchondral Cystic Lesion in the Proximal Interphalangeal Joint of a Warmblood Filly

To describe the treatment of a subchondral bone cyst in the proximal phalanx with parathyroid hormone peptide‐enriched fibrin hydrogel in a warmblood filly. The cyst was localized with computer‐assisted orthopaedic surgery, then curetted and finally filled with parathyroid hormone fragment peptide 1–34 (PTH₁₋₃₄) covalently attached to a fibrin hydrogel. The cyst healed quickly without any complications. This result supports the hypothesis that PTH₁₋₃₄ delivered locally in a fibrin hydrogel may improve the postoperative prognosis of surgical management of subchondral bone cysts in horses. Subchondral bone cysts are fairly common in horses. Especially in older horses, the prognosis is poor, even after surgical curettage. Therefore, different management protocols have been investigated in conjunction with surgical curettage to improve prognosis. Locally delivered PTH₁₋₃₄ seems to be a new method in the treatment of subchondral bone cysts.     

Excitotoxic mechanisms, and age-related susceptibility to brain damage in ischemia, hypoglycemia and toxic mussel poisoning.

Initial research by Olney, investigating the toxicity of glutamate as a food additive, demonstrated that irreversible (necrotic) changes could be produced in the CNS by glutamate. Subsequently, it became clear that the release of excitatory amino acids into the extracellular space of nervous tissue may play a role in CNS ischemia, and, later hypoglycemia. Experiments utilizing excitatory amino acid antagonists at the N-methyl-d-aspartate and other subtypes of excitatory receptor have shown neuronal protection, in both ischemia and hypoglycemia. The protection is robust enough to produce a detectable improvement in neurologic deficit on neurobehavioral testing, in addition to significantly reducing the number of necrotic cells in the brain. A third condition where excitotoxicity plays a role is toxic mussel poisoning. In contrast to ischemia and hypoglycemia, an excitotoxin which is exogenous to the brain plays a role. Domoic acid is contained in mussels which have filter-fed large quantities of domoate-rich phytoplankton, and when contaminated mussels are ingested in large quantities, serious and irreversible CNS effects, accompanied by necrosis, may result. In contrast to ischemia and hypoglycemia, however, damage is mediated at a different excitatory CNS receptor, namely the kainate receptor. In all three conditions, a constant aspect of the excitotoxic pathology is an increased susceptibility to excitotoxic damage with increasing age. This may be due to the dendritic location of excitatory receptors, and the richer branching of neuronal dendritic trees in aged animals, leading to enhanced susceptibility of the neuron to excitotoxic necrosis with age.     

Anxiety and hippocampus volume in the rat.

In depressed patients as well as healthy controls, a positive relationship between hippocampal volume and trait anxiety has been reported. This study sought to explore the possible inter-relation between hippocampal volume and trait anxiety further. Magnetic resonance imaging at 7 T was used to measure hippocampal volumes in a rat model of extremes in trait anxiety (experiment 1) and in a Wistar population with normal anxiety-related behavior (experiment 2). In addition to anxiety-related behavior, potentially confounding factors (depression-like, exploratory, and locomotor behavior) were assessed. Experiment 1 globally supported the hypothesis of a positive relationship between hippocampus volume and trait anxiety but did not allow for ruling out possible confounds arising from cosegregation of other behavioral traits. Experiment 2 yielded strong evidence for a negative relationship which was specific for trait anxiety. Thus, the relationship between hippocampal volume and anxiety may be more complex than expected. Interestingly, anxiety-related behavior in experiment 2 had a stronger influence on hippocampal volume than depression-like behavior. In the light of hippocampal volume loss in anxiety disorder and frequent comorbidity of anxiety and depression, this finding suggests that further research into the relationship between anxiety and hippocampal volume may be critical for understanding hippocampal contributions to normal and pathological behavior.     

Diatoms and drowning

Summary An examination is made of the applicability of quantitative and qualitative diatom analysis to the diagnosis of death by drowning, definition of the environment in which drowning occurred, and delimitation of the area where it occurred. The material comprises 107 bodies of subjects known or suspected to have died by drowning together with a control series of 15 bodies of subjects over 30 years of age who had died of various diseases on land.Whenever diatoms were found in the greater circulatory organs they were also found in the lungs, and when none were present in the lungs none were found in the other organs either. No diatoms or fragments of diatoms were found in the samples from the control subjects. All the fresh, well-preserved bodies for which death by drowning could be regarded as certain from the macroscopic autopsy findings and police reports, the cases used to test the method, gave quantitative diatom results that supported a diagnosis of water aspiration.The diatoms identified in the qualitative analyses served well to describe the ecological properties of the environments in which death had taken place, and the site of drowning could be defined by means of comparative water samples provided that sufficient diatoms were present, the local environment was not too homogeneous or the diatoms were not of quite different species due to a completely unknown location of death.     

Disturbed cerebrospinal fluid circulation after subarachnoid hemorrhage and acute aneurysm surgery

In 138 patients with ruptured cerebral aneurysms operated on within 48 to 72 hours after subarachnoid hemorrhage, an external ventricular drainage catheter was inserted before craniotomy and was used intermittently during the first week after surgery. In 51 patients, intracranial pressure (ICP) was measured intraoperatively. The majority of patients showed increased ICP intraoperatively irrespective of the preoperative Hunt and Hess grade and the amount of subarachnoid blood accumulation or intraventricular blood clot. Intraoperative drainage of cerebrospinal fluid allowed easy access for aneurysm dissection by making the brain slack in more than 90% of patients. Postoperative ICP measurements revealed that significant brain swelling did not occur in the majority of patients. In 7 patients, persistently elevated ICP (greater than 20 mm Hg) was recorded. Nine patients (8%) developed shunt-dependent hydrocephalus; all of these patients had suffered an intraventricular hemorrhage. Measurements of the volumes of cerebrospinal fluid drained did not allow prediction of shunt-dependent hydrocephalus.     

Recombinant dissection of myosin heavy chain of Toxocara canis shows strong clustering of antigenic regions

Myosins from nematode parasites elicit strong humoral and cellular immune responses and have been investigated as vaccine candidates. In this study we cloned and sequenced a cDNA coding for myosin heavy chain from Toxocara canis, a nematode parasite of canids which may also infect humans and cause various unspecific symptoms. To determine the major antigenic regions the myosin heavy chain was systematically dissected into ten overlapping recombinant fusion polypeptides which were purified by metal chelate chromatography. Single fragments were then tested for their IgG reactivity in sera from toxocarosis patients and healthy probands. Two regions, one region at the mid to carboxy-terminal end of the head domain and one region in the rod domain, were identified as major antigens, which in combination were positive with 86% of the sera. The other domains were less reactive. This shows that the patients' IgG reactivity was not directed evenly against all parts of the molecule, but was rather clustered in few regions.     

Prognostic value of the combined assessment of proliferating cell nuclear antigen immunostaining and nuclear DNA content in invasive human mammary carcinomas

The expression of theS-phase associated, nuclear protein proliferating cell nuclear antigen (PCNA) was investigated in routinely paraffin-embedded surgical specimens from 209 breast cancer patients. Cytometric DNA assessments were performed on fine-needle aspirates, upon which the primary diagnosis of breast cancer had been based. The mean clinical follow-up was 16 years (range 13–20 years). The percentage of PCNA immunoreactive tumour cells ranged between less than 5 to 60% (mean value 13.34%). There was a direct association between PCNA expression, high histological tumour grade (p<0.01), and DNA aneuploidy (p=0.009). In a subgroup of 22 patients with near-diploid DNA distribution patterns the PCNA expression yielded additional prognostic information. Patients with tumours of near-diploid DNA histograms and more than 20% of PCNA immunoreactive neoplastic cells had a significantly worse clinical course, than patients with neardiploid tumours containing less than 20% PCNA immunoreactive cells (p=0.0001). In contrast, the PCNA immunoreactivity did not yield additional prognostic information for patients with distinctly diploid or highly aneuploid tumour variants. In a multivariate analysis comprising all 209 patients, nodal status (p<0.01), tumour size (p<0.01), and DNA ploidy (p<0.01) were found to have significant prognostic effect. The findings indicate that carcinomas characterised by high proliferative activity and near-diploid DNA distribution patterns can show rapid tumour progression. The combined assessment of the PCNA immunoreactivity and of the nuclear DNA content in routinely processed surgical specimens of breast cancer patients appears to be of prognostic value.     

Methodological aspects of DNA image cytometry in formalin-fixed paraffin-embedded material from pancreatic adenocarcinoma

Deparaffinized and disintegrated material from conventionally formalin-fixed and paraffin-embedded surgical specimens of 100 cases of ductal adenocarcinoma of the pancreas was Feulgen-stained, and the cytochemical DNA distribution patterns of at least 100 single tumour cells and 50 "control" cells (fibrocytes) were assessed by means of image cytometry (ICM). In 77 cases a sufficient number of neoplastic cells could be obtained for these DNA assessments. The fairly high number (23) of cases that had to be excluded due to too small amounts of disintegrated cells or cell nuclei may be explained by the high content of connective tissue stroma in these pancreatic adenocarcinomas. The tumour cell nuclei in 76 of these 77 cases showed cytochemically a clear-cut "non-diploid" DNA distribution pattern. This observation reflects the well-known highly malignant growth potential of this carcinoma. Despite the fact that about 1/4 of the tumours had to be excluded, the main result of our methodological study is, after all that conventionally formalin-fixed paraffin-embedded specimens of most pancreatic adenocarcinomas can be successfully used for the deparaffinization-disintegration procedure preceding the nuclear DNA assessments by means of ICM. Additional studies are, however, required to obtain the diagnostic and prognostic impact of the results of such cytochemical analyses of the DNA distribution pattern in adenocarcinomas of the pancreas.