An intra-articular vascular malformation with a ganglion in a knee

We report a case of an intra-articular vascular malformation occurring simultaneously with a ganglion in a knee joint. We believe this to be the first reported case of an intra-articular vascular malformation occurring simultaneously with a ganglion. The malformation was cauterized resulting in resolution of knee pain. We suggest that vascular malformations be considered in the differential diagnosis of knee pain.     

Fatal carbon monoxide poisoning at a motel

One man died and four other persons required hospitalization following accidental exposure to carbon monoxide at a motel. In spite of prompt diagnosis of the index cases, a search for the source of exposure and for other possible victims was delayed more than ten hours. Subsequent investigation revealed that air conditioning units drew carbon monoxide from the gas heaters for the motel's indoor swimming pools into three adjacent guest rooms through structural defects in the walls. Emergency care providers must remember that in environmental exposures, other persons may continue to be at risk, and efforts must be made to identify them.     

Equine cytomegalovirus: Cultural characteristics and properties of viral DNA

Equine cytomegalovirus (equine herpesvirus type 2; ECMV) exhibited cultural characteristics typical of the cytomegalovirus group. Ninety-six to one hundred twenty hours were required to reach a maximum titer of 1 × 10⁷ PFU/ml in infected cells, from which no more than 50% of infectious virus produced was released into the supernatant fluid. Only cells of equine or rabbit origin were permissive for virus replication. Ultrastructural investigation of ECMV-infected cells revealed the presence of three types of intranuclear nucleocapsids (empty capsidc, capsidc with a cross-shaped, electron-lucent core, and mature capsidc with an electron-dense core). The mature capsids appeared to acquire their envelope at the nuclear membrane. Infected cells were characterized by nuclei containing marginated chromatin in a large, electron-dense inclusion substance. Viral DNA extracted and purified from virions, nucleocapsids, or infected cells (Hirt fractionation) demonstrated an average density of 1.716 g/cm³ which corresponds to a G+C content of 57.7%. Sedimentation analyses of ECMV DNA in neutral sucrose gradients using phage T4 and equine herpesvirus type 1 (EHV-1) DNA as markers indicated a sedimentation coefficient of approximately 61 S. Sedimentation in alkaline sucrose suggested that the ECMV genome is a non-cross-linked, double-stranded DNA, possibly possessing nonligated areas either within the sugar phosphate backbone of the molecule or within specific alkali-labile regions. Sedimentation analyses of ECMV DNA yielded a molecular weight of approximately 121 × 10⁶ which was confirmed by restriction endonuclease analyses which indicated a value of 126 × 10⁶ Determination of the number, size, and molarity of ECMVDNA fragments generated by digestion with restriction enzymes revealed that ECMV DNA differs markedly in molecular structure from the genome of EHV-1.     

Atrial amyloid deposits in the failing human heart display both atrial and brain natriuretic peptide-like immunoreactivity

Atrial amyloid deposits are common in the ageing human heart and contain alpha-atrial natriuretic peptide (proANP99-126) immunoreactivity. However, atrial myocytes secrete both amino and carboxy terminal fragments of the ANP prohormone (proANP1-126) and also express an homologous, but separate brain natriuretic peptide (BNP). Characteristic amyloid deposits were identified in the atria of 9/22 patients (26-63 years of age) with end-stage heart failure. Amyloid fibrils displayed immunoreactivity for both amino and carboxy terminal fragments of proANP1-126 and for the distinct BNP sequence. As in other endocrine organs, both mature and precursor peptide sequences appear to be constituents of amyloid fibrils. Whilst immunoreactivity for cardiac peptide hormones is co-localized in atrial amyloid deposits, it is uncertain whether the increase in natriuretic peptide expression which accompanies cardiac failure contributes to the incidence of isolated atrial amyloidosis.     

Postnatal development of the innervation and paraganglia in the porcine pulmonary arterial bed

The innervation of the pulmonary trunk and pulmonary arterial bed was studied in 17 pigs from birth to 6 months of age. After birth, the pulmonary trunk and extra- and intra-pulmonary arteries contained neurofilament and protein gene-product-immunoreactive nerve fibres in both the adventitia and media. The density of nerve fibres increased from birth to 2 months, this being most marked during the first 2 weeks of life. Most of the fibres in the media were presumed to be sympathetic in origin as they contained both neuropeptide tyrosine and tyrosine hydroxylase immunoreactivity. Fibres were associated with the vasa-vasorum and vascular smooth muscle running around the vessel, between the elastic laminae and smooth muscle cells, in the outer two-thirds of the media. Vasoactive intestinal polypeptide and calcitonin gene-related peptide-immunoreactive nerve fibres were found to be associated with the pulmonary trunk and extra-pulmonary artery, but generally not with the intra-pulmonary arteries. Tyrosine hydroxylase immunoreactivity was detected in the glomus cells at birth, but peptide immunoreactivity (enkephalin) was not demonstrated in paraganglia until 14 days of age. Adaptation to extra-uterine life is associated with rapid development changes in the innervation of the pig pulmonary trunk, extra- and intra-pulmonary arteries and in the expression of peptide immunoreactivity in both nerve fibres and glomus cells. These changes may have a role in the postnatal adaptation of the pulmonary circulation.     

Effects of N-6 essential fatty acids on glioma invasion and growth: experimental studies with glioma spheroids in collagen gels

OBJECT: Intracranial infusions of gamma-linolenic acid (GLA), an essential fatty acid, have been used as an adjuvant therapy following malignant glioma resection; however, little is known about the dose response of glioma cells to this therapy. In this in vitro study the authors address this important pharmacological question. METHODS: Glioma spheroids derived from U87, U373, MOG-G-CCM, and C6 cell lines were grown in collagen gel and exposed to a range of GLA concentrations (0-1 mM) for 5 days. The diameter of glioma spheroids was measured, the apoptotic index was assessed using both the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling technique and cell morphological testing, and the levels of proliferating cell nuclear antigen were also measured. CONCLUSIONS: The dose-response patterns were similar for all four glioma spheroids. Low concentrations of GLA (<100 microM) increased both apoptosis and proliferation with a net increase in tumor growth and invasion, whereas high-dose GLA (>100 microM) significantly impaired spheroid cell growth. The proliferative effects of low-dose GLA could be a hazard in the clinical treatment of malignant glioma; however, because of the low toxicity of GLA against normal cells, local delivery of millimolar doses of GLA could significantly reduce tumor size.     

Superficially invasive squamous cell carcinoma of the cervix.

The microscopic pathologic features of early invasive squamous cell cervical carcinoma are used as determinants for the treatment of these lesions. This study is a retrospective review of 180 patients with squamous cell cervical carcinoma with invasion to a depth of 5 mm or less. Invasion of less than or equal to 1 mm, greater than 1 but less than or equal to 3 mm, greater than 3 but less than or equal to 5 mm was noted in 37, 84, and 59 patients, respectively. The median follow-up was 6.5 years. Four (2.2%) patients developed carcinoma in situ of the vagina and four (2.2%) patients progressed to invasive squamous carcinoma. Pelvic lymph node metastases were rare (1%). No patient has died from recurrent disease. Analysis of numerous clinical and pathological variables identified no risk factors for recurrence. Most (54/68) patients with tumor invading beyond 3 mm or with tumor demonstrating vascular invasion were treated by traditional "radical" methods. This limited a meaningful analysis of the risk of conservative treatment. The reliability of using the existing definitions of microinvasive disease for the guidance of treatment remains controversial. Further clarification may be rendered only with prospective clinical-pathologic studies performed by cooperative groups.     

Phase II trial of irinotecan in patients with metastatic epithelial ovarian cancer or peritoneal cancer.

PURPOSE: To evaluate the efficacy and toxicity of irinotecan in patients with metastatic platinum-resistant or platinum-refractory epithelial ovarian cancer or primary peritoneal cancer. PATIENTS AND METHODS: Thirty-one patients with measurable disease were enrolled in our study at The University of Texas M.D. Anderson Cancer Center. Twenty-five of these patients were treated with irinotecan at a dose of 300 mg/m2 intravenously for 90 minutes every 3 weeks; the remaining six patients were treated with 250 mg/m2 because their age was greater than 65 years. Median age was 57 years (range, 38 to 74 years). The majority (84%) had a Zubrod performance status of 0. All patients were evaluated for irinotecan toxicity, and 29 (94%) were evaluable for response. RESULTS: The overall response rate was 17.2%. One patient (3%) had a complete response, four (14%) had partial responses, 14 (48%) had stable disease, and 10 had (35%) disease progression. Median progression-free survival was 2.8 months (range, 1.1 to 16 months), median duration of response was 1.4 months (range, 0.7 to 10.1 months); median survival from primary diagnosis was 24.3 months (range, 6.5 to 85.7 months); and median survival from initiation of irinotecan was 10.1 months (range, 2.3 to 34 months). Major toxicities included fatigue (16 patients), neutropenia (11 patients), diarrhea (nine patients), nausea (10 patients), and anorexia (seven patients). Eleven patients required dose reductions because of these toxicities. No treatment-related deaths occurred. CONCLUSION: Irinotecan has moderate efficacy and substantial toxicity in patients with metastatic platinum-resistant or platinum-refractory epithelial ovarian or primary peritoneal cancer.     

Expression of poly(ADP-ribose) polymerase and distribution of poly(ADP-ribosyl)ation in glioblastoma and in a glioma multicellular tumour spheroid model

Development of necrosis is a characteristic feature of glioblastoma but its pathogenesis remains poorly understood. The process of poly(ADP-ribosyl)ation in response to DNA damage is mediated by poly(ADP-ribose) polymerase (PARP) and results in NAD+ depletion. The consequent ATP and energy depletion may result in cell necrosis. Therefore PARP activation is a potential candidate for a regulatory role in the pathogenesis of necrosis in glioblastoma. This study investigated whether there might be a relationship between both PARP expression and poly(ADP-ribosyl)ation, and necrosis in glioblastoma. The pattern of expression of PARP and of poly(ADP-ribose) groups in an archival series of glioblastoma was examined using immunohistochemistry. These parameters were also studied in multicellular tumour spheroids, derived from human glioma cell lines in which central necrosis develops with increasing spheroid diameter. Poly(ADP-ribose) groups were expressed in peri-necrotic tumour cells in glioblastoma. In the spheroid model poly(ADP-ribosyl)ation was seen centrally in pre-necrotic and necrotic cells with increasing spheroid diameter. PARP was widely expressed in viable tumour cells in the glioblastoma sections. In the spheroids, PARP expression, which was initially diffuse, became confined to the outer proliferative zone with increasing diameter. The pattern of expression of poly(ADP-ribose) groups in the spheroids and in glioblastoma raises the possibility that poly(ADP-ribosyl)ation may play a role in the development of necrosis in glioma. The high basal PARP expression in both glioblastoma and the spheroids suggests that this enzyme may have additional roles in glioma cell biology.     

Review: Astrocytes in Alzheimer's disease and other age‐associated dementias: a supporting player with a central role

Astrocytes have essential roles in the central nervous system and are also implicated in the pathogenesis of neurodegenerative disease. Forming non‐overlapping domains, astrocytes are highly complex cells. Immunohistochemistry to a variety of proteins can be used to study astrocytes in tissue, labelling different cellular components and sub‐populations, including glial fibrillary acidic protein, ALDH1L1, CD44, NDRG2 and amino acid transporters, but none of these labels the entire astrocyte population. Increasing heterogeneity is recognized in the astrocyte population, a complexity that is relevant both to their normal function and pathogenic roles. They are involved in neuronal support, as active components of the tripartite synapse and in cell interactions within the neurovascular unit (NVU), where they are essential for blood–brain barrier maintenance and neurovascular coupling. Astrocytes change with age, and their responses may modulate the cellular effects of neurodegenerative pathologies, which alone do not explain all of the variance in statistical models of neurodegenerative dementias. Astrocytes respond to both the neurofibrillary tangles and plaques of Alzheimer's disease, to hyperphosphorylated tau and Aβ, eliciting an effect which may be neuroprotective or deleterious. Not only astrocyte hypertrophy, in the form of gliosis, occurs, but also astrocyte injury and atrophy. Loss of normal astrocyte functions may contribute to reduced support for neurones and dysfunction of the NVU. Understanding how astrocytes contribute to dementia requires an understanding of the underlying heterogeneity of astrocyte populations, and the complexity of their responses to pathology. Enhancing the supportive and neuroprotective components of the astrocyte response has potential translational applications in therapeutic approaches to dementia.